Cosmetic formulations

Abstract

Cosmetic formulation supply [Solution] Cosmetic formulations and methods of using the same are described herein. In non-limiting examples, a cosmetic dermatological formulation comprises (i') a first composition containing glycerin and Lavandula angustifolia extract; (ii') a second composition containing (a) Vibrio alginolyticus fermentation filtrate; (b) a third composition containing acetyltyrosine, proline, and adenosine triphosphate; (c) cetyl hydroxyproline palmitamide; (d) N-succinyl-S-farnesyl-L-cysteine; (iii') one or more dermatologically acceptable carriers; and (iv') optionally one or more dermatologically acceptable additives.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 765,281, filed on 28 February 2025, the disclosure of which is incorporated herein by reference.

[0002] Field of Invention The present invention generally relates to cosmetic skin formulations and methods for using the same. [Background technology]

[0003] Background of the Invention To date, a wide variety of skin formulations have been developed. Such skin creams are topical formulations applied to the skin for a variety of purposes, including moisturizing, nourishing, protecting, treating, and / or preventing specific skin concerns or conditions. Such creams can be used, for example, as moisturizing creams, anti-aging creams, creams for sensitive skin, and barrier-repairing creams. These are just a few examples of the types of skin creams available on the market.

[0004] Despite the availability of numerous types of skin formulations, there is still a demand for improved skin formulations.

[0005] Therefore, the object of the present invention is to provide a cosmetic skin formulation that provides improved benefits to the skin.

[0006] A further object of the present invention is to provide a method for using such cosmetic skin formulations. [Overview of the project] [Means for solving the problem]

[0007] Summary of the Invention This specification describes various cosmetic formulations for skin use and their methods of use. In non-limiting examples, cosmetic dermatological formulations include: (i') A first composition containing glycerin and Lavandula angustifolia extract; (ii') (a) A second composition containing the fermentation filtrate of Vibrio alginolyticus; (b) A third composition containing acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii') One or more dermatologically acceptable carriers; and (iv') One or more dermatologically acceptable additives, as needed. It contains.

[0008] In another non-limiting example, cosmetic skin preparations are, (i'') A first composition containing glycerin and Lavandula angustifolia extract; (ii'')N-succinyl-S-farnesyl-L-cysteine; and (iii'') If necessary, (a) A second composition containing the fermentation filtrate of Vibrio alginolyticus; (b) A third composition containing acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'') One or more dermatologically acceptable carriers; and (v'') One or more dermatologically acceptable additives, as needed. It contains.

[0009] In yet another non-limiting example, cosmetic skin formulations are, (i''') A first composition containing glycerin and Lavandula angustifolia extract; (ii''') Cetyl hydroxyproline palmitamide; and (iii''') If necessary, (a) A second composition containing the fermentation filtrate of Vibrio alginolyticus; (b) A third composition containing acetyltyrosine, proline, and adenosine triphosphate; (c) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iv''') One or more dermatologically acceptable carriers; and (v''') One or more dermatologically acceptable additives, as needed. It contains.

[0010] In yet another non-limiting example, cosmetic skin formulations are, (i'''') A first composition containing glycerin and Lavandula angustifolia extract; (ii'''') A second composition containing the fermentation filtrate of Vibrio alginolyticus; and (iii'''') If necessary, (a) A third composition containing acetyltyrosine, proline, and adenosine triphosphate; (b) N-succinyl-S-farnesyl-L-cysteine; (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'''') One or more dermatologically acceptable carriers; and (v'''') One or more dermatologically acceptable additives, as needed. It contains.

[0011] In another non-limiting example, cosmetic skin preparations are, (i''''') A first composition containing acetyltyrosine, proline, and adenosine triphosphate; (ii''''') (a) A second composition containing the fermentation filtrate of Vibrio alginolyticus; (b) A third composition containing glycerin and Lavandula angustifolia extract; (c) Cetylhydroxyproline palmitamide; and / or (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii''''') One or more dermatologically acceptable carriers; and (iv) One or more dermatologically acceptable additives, as needed. It contains.

[0012] In yet another non-limiting example, cosmetic skin formulations are, (1') At least one activator of formula I (described below); and (2') A first composition comprising glycerin and Lavandula angustifolia extract; (3') one or more dermatologically acceptable additives as needed; and (4') One or more dermatologically acceptable carriers This is a scalp preparation containing [ingredient name].

[0013] In some specific cases, the active ingredient in scalp formulations is bis-aminopropyl diglycol dimaleate, with the following chemical structure: [ka] It can be expressed as follows.

[0014] The cosmetic dermatological formulations disclosed herein are applied to the skin of subjects such as mammals (typically humans). Cosmetic dermatological formulations typically comprise a combination of one or more agents, one or more compositions, and other optional components. Dermatological formulations are understood to be blends of these agents, compositions, and other optional components, typically forming a homogeneous composition. In some examples, cosmetic dermatological formulations are, A composition containing glycerin and Lavandula angustifolia extract; Compositions containing the fermentation filtrate of Vibrio alginolyticus; and / or It may contain different compositions, such as acetyltyrosine, proline, and adenosine triphosphate.

[0015] Cosmetic skin preparations may also contain other drugs / ingredients, such as cetylhydroxyproline palmitamide and / or N-succinyl-S-farnesyl-L-cysteine.

[0016] Cosmetic skin formulations typically contain one or more dermatologically acceptable carriers. Such carriers may be water, dermatologically acceptable organic solvents, or a combination thereof.

[0017] In some cases, cosmetic skin formulations contain one or more dermatologically acceptable additives. Dermatologically acceptable additives include, for example, abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based agents, plant extracts, buffering agents (such as lactic acid, sodium lactate, citric acid, trisodium citrate, sodium hydroxide, etc.), fillers, sedatives, chelating agents (such as EDTA or tetrasodium glutamate diacetate, etc.), cleansing agents, emulsifiers, colorants, conditioning agents, cooling agents, deodorants, depilators, detergents, disinfectants, and dispersants (hydroxyethyl acrylate / acrylohydrate). (e.g., sodium yldimethyltaurate copolymer), emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble agents, fibers, film-forming agents, fixatives, foaming accelerators, foaming stabilizers, foaming agents, fragrances, free radical scavengers, disinfectants, gelling agents, glossing agents, bleaching agents, conditioning agents, moisturizing agents, foaming agents, lubricants, makeup agents (for imparting color, tone, gloss, or matte finish to the formulation and / or the skin to which it is applied), moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbers Astringents, ointment bases, opacifiers, organosilicones, oxidizing agents, oxygen carriers, pearlescent agents, perfumes, perfume solvents, perfume stabilizers, peroxide stabilizers, photosensitizers, pigments, pigment colorants, pearlescent agents, plant extracts, plant-derived ingredients, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymers, polymer film-forming agents, preservatives, propellants, reducing agents, relipidating agents, resins, scalp agents, scrubs, metal ion chelating agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, skin bleaching agents, This may include solubilizers, suspending agents, sunscreens, mitigating agents (such as bisabolol), spreading agents, stabilizers, sunless tanning agents, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, accelerators, thickeners, thixotropes, tightening agents, lotions, tonics, vegetable oils, volatile agents, viscosity stabilizers, vitamins, waterproofing agents, waxes, wetting agents, whitening agents, or combinations thereof.

[0018] In some cases, cosmetic skin formulations may contain one or more additional additives. For example, additives may include cell differentiation regulators, cell proliferation regulators, dermal or epidermal polymer synthesis stimulants, dermal or epidermal polymer degradation inhibitors, microcirculatory agents, antimicrobial metal ion chelating agents, analgesics, anesthetics, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-seborrheic agents, anti-cracking agents, anti-cellulite agents, anti-stretch mark agents, anti-dandruff agents, antifungal agents, antihistamines, anti-inflammatory agents, anti-irritants, antimicrobial agents, antibiotics, antiviral agents, anti-skin cancer agents, anti-eczema agents, anti-psoriasis agents, antiperspirants, antipruritic agents, antipruritic agents, circulation promoters, collagen stimulants, elastin stimulants, extracellular matrix stimulants, and enzymes. These may be enzyme inhibitors, enzyme inducers, hormones, hormone-like agents, hyaluronic acid stimulants, keratolytic agents, mucosal adhesives, natural moisturizers, lipolytic agents, peptide agents (such as palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7), protein agents, rosacea inhibitors, scar preventive agents, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents (such as beta-glucan), skin penetration enhancers, skin penetration delayers, skin conditioning agents, skin exfoliants, skin peeling agents, skin healing agents, skin protectants, skin purifying agents, vasoconstrictors, wound healing agents, or combinations thereof.

[0019] In some cases, a cosmetic dermatological formulation is a serum, for example, a facial serum. In some other specific cases, a cosmetic dermatological formulation is a skin moisturizer formulation.

[0020] In some cases, cosmetic skin formulations are actually scalp formulations.

[0021] The cosmetic skin formulations described herein may be provided as part of a cosmetic kit. The cosmetic dermatological formulations described herein are used to treat the skin. In one non-limiting example, a method for treating the skin is: (1) The process of applying the cosmetic skin preparation described to the subject's skin. Includes.

[0022] Methods and processes for testing and evaluating the efficacy of cosmetic dermatological formulations are well known. For example, skin maintenance, prevention, amelioration and / or treatment of signs of skin aging, protection and / or improvement of skin conditions, and prevention and / or treatment of skin defects are functional characteristics that can be visualized, analyzed, measured and quantified using many techniques well known to experts in cosmetic dermatological treatments. In some cases, a described dermatological formulation may be evaluated for its ability to upregulate or downregulate one or more genes after one or more applications to the skin.

[0023] The skin treatment method using the above-described formulation can result in a skin rejuvenation effect and / or improvement in skin appearance, as measured by visual inspection after step (1), compared to the skin before step (1).

[0024] In some cases, the method may result in the maintenance of healthy skin, the recovery of damaged skin, enhanced skin recovery after cosmetic and dermatological procedures, enhanced wound healing, or a combination of these effects.

[0025] In other instances, the method may treat, alleviate, or improve one or more visual signs of skin aging. Signs of aging may include, but are not limited to, fine lines, wrinkles, enlarged pores, roughness, dryness, loss of elasticity, loss of volume, atrophic skin, stretch marks, puffy eyes, dark circles (under the eyes), and combinations thereof. [Brief explanation of the drawing]

[0026] [Figure 1] Figure 1 is a bar graph showing the results of the gene expression differences between placebo control and sample treatment studied in Example 1.

[0027] [Figure 2A] Figure 2A is a bar graph showing the results of the gene expression differences between the untreated control and the sample-treated control studied in Example 2.

[0028] [Figure 2B] Figure 2B is a bar graph showing the results of the gene expression differences between placebo control and sample treatment studied in Example 2.

[0029] [Figure 3A] Figure 3A shows a table of PCR clinical assessment scales for visual and tactile evaluation of the skin.

[0030] [Figure 3B] Figure 3B shows a table of PCR clinical evaluation scales for Vivascope assessment of collagen. [Modes for carrying out the invention]

[0031] Detailed description of the invention This specification describes cosmetic skin preparations and methods of use thereof. I. Definition

[0032] The numerical ranges disclosed herein disclose individually each possible numerical value within that range, as well as any subranges and combinations of subranges contained therein. For example, the carbon number range (i.e., C1 to C1). 10 ) is intended to individually disclose all possible carbon numbers and / or subranges included in that range. For example, C1~C 10 The carbon length range is C1, C2, C3, C4, C5, C6, C7, C8, C9, and C 10 The range is disclosed, along with subranges included within that range, such as C2-C9, C3-C8, and C1-C5. Similarly, for integer ranges from 1 to 10, the individual values ​​1, 2, 3, 4, 5, 6, 7, 8, and 10, and the subranges included within those ranges are disclosed. Furthermore, for concentration ranges or weight percentage ranges such as 1% to 2% by weight formulations, the individual values ​​and their decimal values, such as 1%, 1.1%, 1.2%, 1.32%, and 1.48%, as well as the subranges included within those ranges, are disclosed.

[0033] The term "approximately" is intended to indicate a value within approximately ±10% above or below the value it modifies, and in some cases, this value may be within approximately ±5% above or below the stated value. When the term "approximately" is used before a numerical range (i.e., approximately 1 to 5) or before a column of numbers (i.e., approximately 1, 2, 3, 4, etc.), it is intended to modify each number at either end of that numerical range or within that column of numbers, unless otherwise specified.

[0034] The term "skin" refers to the layer of tissue that forms the natural outer covering of the body of a subject (typically a human or animal).

[0035] "Effective amount" means the amount of one or more activators, compositions, and / or other components described herein that can form part of a cosmetic dermatological formulation. Such amount, when applied as part of a desired skin treatment, can achieve desired results or effects, such as skin rejuvenation, improvement of skin appearance, maintenance of healthy skin, recovery of damaged skin, enhancement of skin recovery after cosmetic and / or dermatological procedures, enhancement of wound healing, and / or treatment, mitigation, or improvement of one or more visual signs of skin aging, when the skin is compared before and after treatment with the cosmetic dermatological formulation described herein. Other methods for evaluating the effects of one or more activators, compositions, and / or other components on the skin are known, as described below.

[0036] The term "topical" means that the formulation described herein is applied to one or more areas of one or more surface layers of the subject's skin.

[0037] As used herein, the term "pH-adjusted" refers to a formulation having a pH of approximately 4 to approximately 7.

[0038] When used herein, the terms “apply,” “administer,” or “dosage” refer to applying a cosmetic dermatological formulation to an area of ​​skin by spreading, rubbing, or rubbing it in.

[0039] The terms “skin aging” or “signs of skin aging” include, but are not limited to, all perceptible visual and tactile symptoms resulting from skin aging, as well as any other macro or micro effects. These signs may be induced or caused by internal factors (manifesting as skin aging over time) and external factors (manifesting as environmental skin damage, including, but not limited to, photoaged skin). These signs may result from processes including, but are not limited to, discontinuities in texture such as wrinkles and rough, deep creases, fine or skin lines, grooves, bumps, large holes (e.g., related to the structure of appendages such as sweat ducts, sebaceous glands, hair follicles), or unevenness or roughness, loss of skin elasticity (loss and / or inactivation of functional skin elastin), sagging (including swelling of the eye area and chin), loss of skin firmness, loss of skin elasticity, loss of skin resilience to deformation, discoloration (including dark circles under the eyes), pigmentation of skin areas such as age spots, yellowing, freckles and age spots, keratosis, abnormal differentiation, hyperkeratosis, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, cutaneous vascular system (e.g., telangiectasia or capillaries) and underlying tissues, particularly near the skin.

[0040] "Cosmetic-acceptable" means a compound, material, or formulation suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, within the bounds of reasonable medical judgment that justifies the benefit / risk ratio. More specifically, "cosmetic-acceptable" means a material, compound, or formulation suitable for use in contact with skin, scalp, or hair. Cosmetic-acceptable materials are well known to those skilled in the art.

[0041] The terms "analog" and "derivative" are used interchangeably herein and refer to compounds that have the same core structure as the parent compound but differ from the parent compound in bond order, the presence or absence of one or more atoms and / or groups of atoms, and combinations thereof. A derivative may differ from the parent compound, for example, in the presence of one or more substituents on the core (which may include one or more atoms, functional groups, or substructures). In general, derivatives can be formed from the parent compound, at least theoretically, through chemical and / or physical processes.

[0042] The terms "electrophilic group" or "electrophilic moiety" are used interchangeably and refer to one or more functional groups or moies that have an affinity for or attract electrons.

[0043] As used herein, a "Michael acceptor" is a type of electrophilic group or moiety involved in a nucleophilic addition reaction. A Michael acceptor may be or may contain an α,β-unsaturated carbonyl-containing group or moiety (such as a ketone). Other Michael acceptors include π bonds such as double or triple bonds conjugated with other π-bond-containing electron-withdrawing groups such as nitro, nitrile, and carboxylic acid groups.

[0044] As used herein, "alkyl" refers to a saturated or unsaturated aliphatic radical, including a linear alkyl, alkenyl, or alkynyl group; a branched alkyl, alkenyl, or alkynyl group; a cycloalkyl, cycloalkenyl, or cycloalkynyl (alicyclic) group; an alkyl-substituted cycloalkyl, cycloalkenyl, or cycloalkynyl group; and a cycloalkyl-substituted alkyl, alkenyl, or alkynyl group. Unless otherwise specified, a linear or branched alkyl has 30 or fewer carbon atoms in its skeleton (for example, C1-C for a linear chain). 30 Regarding the branching chain, C3~C 30), or having 20 or fewer carbon atoms, or 12 or fewer carbon atoms, or 8 or fewer carbon atoms. In some examples, the chain has 1 to 6 carbon atoms. Similarly, cycloalkyls may have 3 to 10 carbon atoms in their ring structure, or 5, 6, or 7 carbon atoms in their ring structure. The ranges provided above include all values ​​between the minimum and maximum values.

[0045] The term "alkyl" includes both "unsubstituted alkyl" and "substituted alkyl," the latter referring to an alkyl moiety having one or more substituents that replace hydrogens on one or more carbons of a hydrocarbon skeleton. Such substituents include, but are not limited to, halogens, hydroxyls, carbonyls (such as carboxyls, alkoxycarbonyls, formyls, or acyls), thiocarbonyls (such as thioesters, thioacetates, or thioformates), alkoxyls, phosphoryls, phosphates, phosphonates, phosphinates, aminos, amides, amidines, imines, cyanos, nitros, azides, sulfhydryls, alkylthios, sulfates, sulfonates, sulfamoyls, sulfonamides, sulfonyls, heterocyclyls, aralkyls, or aromatic or heteroaromatic moieties.

[0046] Unless otherwise specified, "lower alkyl" as used herein means an alkyl group as defined above having 1 to 10 carbon atoms or 1 to 6 carbon atoms in its skeletal structure. Similarly, "lower alkenyl" and "lower alkynyl" have similar chain lengths.

[0047] Furthermore, alkyl groups may contain one or more heteroatoms within their carbon skeleton. Examples include oxygen, nitrogen, sulfur, and combinations thereof. In certain examples, alkyl groups contain between one and four heteroatoms.

[0048] "Alkenyl" and "alkynyl" as used herein refer to the alkyl group and the length (e.g., C2-C2) as described above. 30 ) and refers to unsaturated aliphatic groups containing one or more double or triple bonds, similar in possible substitutions.

[0049] As used herein, “aryl” refers to a five-membered, six-membered, and seven-membered aromatic ring. The ring may be a carbocyclic ring system, a heterocyclic ring system, a fused carbocyclic ring system, a fused heterocyclic ring system, a dicarbocyclic ring system, or a diheterocyclic ring system, and may be substituted with alkyl as described above, as necessary. In a broader sense, as used herein, “Ar” refers to a five-membered, six-membered, and seven-membered monocyclic aromatic group, optionally containing 0 to 4 heteroatoms. Examples include, but are not limited to, benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. Aryl groups having heteroatoms in their ring structure may also be called “heteroaryl,” “aryl heterocyclic,” or “heteroaromatic.” Aromatic rings may be substituted at one or more ring positions with the above substituents, e.g., halogens, azides, alkyls, aralkyls, alkenyls, alkynyls, cycloalkyls, hydroxyls, alkoxyls, aminos, nitros, sulfhydryls, iminos, amides, phosphonates, phosphinates, carbonyls, carboxyls, silyls, ethers, alkylthios, sulfonyls, sulfonamides, ketones, aldehydes, esters, heterocyclyls, aromatic or heteroaromatic moieties, -CF3, and -CN. The term "Ar" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are shared by two adjacent rings (the rings are "fused rings"), and at least one ring is aromatic (e.g., the other cyclic ring is cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, and / or heterocyclic, or both rings are aromatic).

[0050] As used herein, "alkylaryl" refers to an alkyl group substituted with an aryl group (e.g., an aromatic or heteroaromatic group).

[0051] As used herein, “heterocyclic” or “heterocyclic formula” refers to a cyclic radical linked via a ring carbon or ring nitrogen of a monocyclic or bicyclic ring containing 3 to 10 ring atoms, or 5 to 6 ring atoms, comprising carbon and 1 to 4 heteroatoms selected from non-peroxide oxygen, sulfur, and N(Y) (where Y is absent or H, O, (C1-4) alkyl, phenyl, or benzyl), optionally containing one or more double or triple bonds, and optionally substituted with one or more substituents. The term “heterocyclic” also includes substituted and unsubstituted heteroaryl rings.Examples of heterocyclic rings include benzimidazolyl, benzofuranil, benzothiofuranil, benzothiophenyl, benzoxazolyl, benzoxazolinil, benzothiazolyl, benzotriazolyl, benzotetrazolyl, benzoisoxazolyl, benzoisothiazolyl, benzimidazolinil, carbazolyl, 4aH-carbazolyl, carborinil, chromanil, chromenil, sinnolinil, decahydroquinolinil, 2H,6H-1,5,2-dithiadinyl, dihydroflo[2,3-b]tetrahydrofuranil, furanil, furazanil, imidazolyl Dinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolidinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranil, isochromanil, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthilidinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadi Azolyl, oxazolidinil, oxazolyl, oxindolyl, pyrimidinil, phenanthrolinil, phenanthrolinil, phenazinil, phenothiazinil, phenoxathinil, phenoxadinil, phthalazinil, piperadinil, piperidinil, piperidonil, 4-piperidonil, piperonil, pteridinil, prinil, pyranil, pyrazinil, pyrazolidinil, pyrazolinil, pyrazolyl, pyridazinil, pyridoxazole, pyridoimidazole, pyridothiazole, pyridinil, pyridyl, pyrimidinil, pyrrolidinil, pyrrolidinil, 2H-py Examples include, but are not limited to, loryl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolidinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranil, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienoxazolyl, thienoimidazolyl, thiophenyl, and xanthenyl.

[0052] "Heteroaryl," as used herein, refers to a monocyclic aromatic ring containing five or six ring atoms, each containing carbon and one, two, three, or four heteroatoms selected from non-peroxide oxygen, sulfur, and N(Y) (where Y is absent or H, O, (C1-C8) alkyl, phenyl, or benzyl). Non-limiting examples of heteroaryl groups include furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazolyl, pyrazolyl, pyrazinyl, tetrazolyl, pyridyl (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide), indolyl, isoquinolyl (or its N-oxide), quinolyl (or its N-oxide), and the like. The term "heteroaryl" may include radicals of ortho-condensed bicyclic heterocycles with approximately 8 to 10 ring atoms derived from them, particularly benz derivatives, or those derived by condensation with propylene, trimethylene, or tetramethylene diradicals. Examples of heteroaryls include, but are not limited to, furyl, imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isothiazolyl, pyraxazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl (or its N-oxide), thienyl, pyrimidinyl (or its N-oxide), indolyl, isoquinolyl (or its N-oxide), quinolyl (or its N-oxide), etc.

[0053] As used herein, "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0054] The term "substituted," as used herein, refers to all acceptable substituents of the compounds described herein. In its broadest sense, acceptable substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. Examples of substituents include, but are not limited to, halogens, hydroxyl groups, or other organic groups as needed containing as many carbon atoms as necessary, such as 1 to 14 carbon atoms, and those containing one or more heteroatoms, such as oxygen, sulfur, or nitrogen, in linear, branched, or cyclic structural forms as needed. Typical substituents include alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, alloxy, substituted alloxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amide, substituted amide, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, C3-C 20 Ring-shaped, substitution C3~C 20 This includes cyclic, heterocyclic, substituted heterocyclic, amino acid, peptide, and polypeptide groups.

[0055] Heteroatoms such as nitrogen may have hydrogen substituents that satisfy the valence of the heteroatom and / or any acceptable substituents of the organic compounds described herein. "Substituting" or "substituted" is understood to imply that such substitution conforms to the acceptable valences of the substituted atom and substituent, and that the substitution produces a stable compound (i.e., a compound that does not undergo spontaneous transformations such as rearrangement, cyclization, or elimination).

[0056] As used herein, "polymer" refers to a molecule containing more than 10 monomer units.

[0057] As used herein, "water-soluble" generally means that at least 50, 75, 100, 125, 150, 200, 225, or 250 g dissolves in 1 liter of water at 25°C. II. Cosmetic Dermatological Preparations

[0058] This specification describes cosmetic skin preparations. A. Exemplary cosmetic skin preparations

[0059] In non-specific examples, cosmetic dermatological formulations are, (i') A first composition comprising glycerin and Lavandula angustifolia extract; (ii') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; (d) N-succinyl-S-farnesyl-L-cysteine; At least one of the following: (iii') One or more dermatologically acceptable carriers; and (iv') One or more dermatologically acceptable additives, as needed. Includes.

[0060] In another non-limiting example, cosmetic skin preparations are, (i'') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'')N-succinyl-S-farnesyl-L-cysteine; and (iii'') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; At least one of the following: (iv'') One or more dermatologically acceptable carriers; and (v'') One or more dermatologically acceptable additives, as needed. Includes.

[0061] In yet another non-limiting example, cosmetic dermatological formulations are (i''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii''') Cetylhydroxyproline palmitamide; and (iii''') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) N-succinyl-S-farnesyl-L-cysteine; At least one of the following; (iv''') One or more dermatologically acceptable carriers; and (v''') One or more dermatologically acceptable additives, as needed. Includes.

[0062] In yet another non-limiting example, cosmetic skin formulations are, (i'''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'''') A second composition comprising a fermentation filtrate of Vibrio alginolyticus; and (iii'''') If necessary, (a) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (b) N-succinyl-S-farnesyl-L-cysteine; (c) Cetyl hydroxyproline palmitamide; At least one of the following: (iv'''') One or more dermatologically acceptable carriers; and (v'''') One or more dermatologically acceptable additives, as needed. Includes.

[0063] In another non-limiting example, cosmetic skin preparations are, (i''''') A first composition comprising acetyltyrosine, proline, and adenosine triphosphate; (ii''''') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising glycerin and Lavandula angustifolia extract; (c) Cetylhydroxyproline palmitamide; and / or (d) N-succinyl-S-farnesyl-L-cysteine; At least one of the following; (iii''''') One or more dermatologically acceptable carriers; and (iv''''') If necessary, one or more dermatologically acceptable additives, Includes.

[0064] In some examples, the cosmetic skin preparation containing at least one of components (a) to (d) contains at least two of components (a) to (d), or at least three of components (a) to (d). In yet other examples, the skin preparation contains each of components (a) to (d).

[0065] In all of the above examples, N-succinyl-S-farnesyl-L-cysteine ​​can exist in the form of a salt such as N-succinyl-S-farnesyl-L-cysteine ​​disodium.

[0066] In some examples, the above cosmetic skin preparation contains at least one of components (a) to (c), while in others it contains at least two of components (a) to (e). In yet other examples the skin preparation contains each of components (a) to (c).

[0067] The cosmetic skin formulations disclosed herein are applied to the skin of subjects such as mammals (typically humans). One or more dermatologically acceptable carriers and / or additives are considered safe for application to human skin and hair and can be applied to an individual's skin without causing undesirable biological side effects or similar adverse reactions at the application site, such as burning, irritation, itching, tingling, inflammation, and / or redness.

[0068] In yet another example, cosmetic skin preparations are, (1') At least one activator of formula I (as described below); and (2') A first composition comprising glycerin and Lavandula angustifolia extract; (3') one or more dermatologically acceptable additives as needed; and (4') One or more dermatologically acceptable carriers This is a scalp preparation containing:

[0069] One or more dermatologically acceptable additives and one or more dermatologically acceptable carriers may be selected from the list provided elsewhere in this specification.

[0070] In some cases, the active ingredient in scalp preparations is bis-aminopropyl diglycol dimaleate, with the following chemical structure:

[0071] [ka] It can be expressed as follows.

[0072] In some cases, scalp preparations are in the form of serums.

[0073] The cosmetic dermatological formulations described herein may have any pH suitable for application to the skin. In some examples, the cosmetic dermatological formulations include a pH in the range of about 4 to about 7, or a pH of 4.4 to 6, with individual pH values ​​or sub-ranges within the above range, or a pH of 5.5. In certain examples, the dermatological formulations are adjusted to provide a pH-adjusted dermatological formulation. a. Active agents (one or more), compositions (one or more), and other necessary ingredients (one or more) for cosmetic skin formulations.

[0074] The cosmetic dermatological formulations disclosed herein typically comprise a combination of one or more agents, one or more compositions, and one or more other components as needed. Dermatological formulations are understood to be blends of these agents, compositions, and other components as needed, typically forming a homogeneous composition. i. Drugs defined by formula I

[0075] In some cases, at least one activator of formula I is included in the skin formulation, and this activator contains a reactive moiety that can react with a nucleophile such as a thiol to form a bond. Such a reactive moiety can react with a thiol group to form a stable bond, for example, one that is resistant to hydrolysis. As used with respect to the bond formed between thiol groups, “stable” means that the bond remains intact for at least one week, two weeks, three weeks, four weeks, one month, or two months or longer when exposed to water at a temperature of about 5 to about 100°C, about 20°C to about 75°C, about 20°C to about 50°C, about 25°C to about 40°C, or about 25°C to about 30°C, or about 25°C at a pH of about 4 to about 6, or pH 4.4 to 6, or pH 5.5. In some cases, the temperature is about 25°C. The reaction between the reactive moiety and the thiol typically occurs around room temperature, for example, at around 15°C to 35°C, or around 20°C to 30°C, or around 22°C to 27°C.

[0076] As previously mentioned, the activator according to formula I can have the following structure: [ka] Here, A, B, C, and D are reactive parts with a charge of 1 or greater, R is a linker with a charge of 2 or greater, whose charge is opposite to that of the reactive part, where n = 1 to 100, preferably n = 1 to 10, more preferably n = 1. Each occurrence of p, q, r, and s is an independent integer between 0 and 25, preferably between 0 and 10, and more preferably between 0 and 2. The sum of p + q + r + s is equal to or greater than 2.

[0077] The reactive moieties can be located on any atom of the linker. In some cases, the reactive moieties are identical. In other cases, one or more of the reactive moieties differ.

[0078] In some examples, the reactive moiety is negatively charged, and the linker has a positively charged moiety. In other examples, the reactive moiety is positively charged, and the linker or spacer has a negatively charged moiety. Generally, the total charge on the active agent of Formula I is zero, but a stoichiometric imbalance may exist.

[0079] The reactive moieties on the active agent are typically linked via a linker R. As used herein, "linker R" refers to one or more polyfunctional molecules (e.g., difunctional molecules, trifunctional molecules, tetrafunctional molecules, etc.) that can be used to ionically bind two or more reactive moieties and do not interfere with the reactive properties of the reactive moieties. The reactive moiety can be bound to any portion of the linker R. 1. Linker R

[0080] In certain examples, for Formula I, n=1, and linker R is not a polymer. In some examples, linker R is a metal ion (e.g., Ca 2+ ) may be a single atom, or may be an atomic group of multiple atoms such as an alkyl, alkoxy, or alkenyl chain. Suitable linkers include, but are not limited to, oxygen, sulfur, carbon, boron, nitrogen, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, ether, amine, and polymers.

[0081] Linker R may be optionally independently substituted with one or more substituents, wherein the substituents include hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid (-COOH), -C(O)R 1 , -C(O)OR 1 , carboxylate (-COO - ), primary amide (e.g., -CONH2), secondary amide (e.g., -CONHR 1 ), -C(O)NR 1R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 , and -S(O)2NR 1 R 2 , sulfinyl group (e.g., -SOR 1 ), and sulfonyl groups (e.g., -SOOR 1 ) is included here R 1 and R 2 Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, R 1 and R 2 Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or "alkyl optionally substituted with hydroxyl", cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl.

[0082] In some cases, linker R may be based on alkoxy, ether, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, or amine. In yet other cases, the linker is a polyfunctional molecule that is an alkoxy or alkenyl molecule, and the linker may be hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, or -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 , and -S(O)2NR 1 R 2 It is substituted with one or more substituents selected from the group consisting of a sulfinyl group and a sulfonyl group, where R 1 and R 2 Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl, and R 1 and R 2Each of these is a halogen, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens or alkoxys or aryloxys, aryl optionally substituted with one or more halogens or alkoxys or alkyls or trihaloalkyls, aryl or heteroaryl or heterocycloalkyl optionally substituted with "=O or hydroxyl-substituted alkyl", cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens or alkoxys or alkyls or trihaloalkyls, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryl The linker may be a polyfunctional molecule that is independently substituted as needed with one or more substituents selected from the group consisting of hydroxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl, or the linker may be a substituted or unsubstituted alkyl molecule, and if substituted, the substituents of the alkyl molecule may be selected from the group consisting of halogen, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic, and heteroaromatic groups.

[0083] The reaction between the reactive moiety and the thiol group can begin at room temperature and atmospheric pressure when the thiol group and the reactive moiety come into contact, such as in the skin. In some other examples, the reaction may involve heat, a catalyst, basic conditions, and / or an initiator such as a free radical initiator. The reaction rate between the reactive moiety and the thiol can be increased by changes in temperature, pH, and / or the addition of one or more additives such as a catalyst, but this is generally not necessary.

[0084] In some cases, the reactive moiety can undergo conjugate addition reactions. The reactive moiety may independently be, or may contain, a Michael acceptor, a succinimidyl-containing group, a maleimide-containing group, an azulactone, a benzoxazinon derivative, a vinyl sulfone, a vinyl sulfoximine, a vinyl sulfonate, a vinyl phosphonate, a benzoxazinon, an isocyanate, an epoxide, an electrophilic moiety containing a leaving group, an electrophilic thiol acceptor, an acrylic or acrylate group, a methacrylic or methacrylate group, a styrene group, an acrylamide group, a methacrylamide group, a maleate group, a fumarate group, an itaconate group, a vinyl ether group, an allyl ether group, an allyl ester group, a vinyl ester group, a sulfonate group, a phosphonate group, a sulfoxide group, a sulfonamide group, a sulfinimide group, a sulfonimidate group, or a sulfonimidoamide group.

[0085] In certain examples, each of the reactive moieties A, B, C, and / or D (if present) independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, fumarate group, and itaconate group. Furthermore, in preferred examples, n=1 and linker R is not a polymer. If necessary, all reactive moieties are identical. For example, in some examples, all reactive moieties are maleate groups.

[0086] In some cases, the activator according to formula I has the following chemical structure: [ka] It can be represented by one of these.

[0087] In some specific cases, the activator according to formula I is bis-aminopropyl diglycol dimaleate, which can be expressed as shown below: [ka] .

[0088] The activator according to Formula I is further described in U.S. Patent Application Publication No. 2015 / 0034117 A1 by Pressly et al., which is incorporated herein by reference with respect to its disclosure of the activator.

[0089] The activators may typically be present in amounts ranging from about 0.001% to about 25% by weight of the total weight of the cosmetic dermatological formulation, from about 0.001% to about 15% by weight, from about 0.001% to about 10% by weight, or from about 0.001% to about 5% by weight of the total weight of the cosmetic dermatological formulation, as well as in amounts within the partial ranges or individual concentration values ​​disclosed within those ranges. Typically, the activators may be present in amounts ranging from about 0.001% to about 5% by weight, from about 0.001% to about 2.5% by weight, or from about 0.001% to about 1% by weight of the total weight of the cosmetic dermatological formulation, as well as in amounts within the partial ranges or individual concentration values ​​disclosed within those ranges. "Total weight of formulation" generally refers to the sum of the weights of all activators, compositions, other components, carriers, additives, and / or additives that may be present in a particular cosmetic dermatological formulation.

[0090] The activator is stable in the skin formulation for at least two, three, four, five, six, eight, nine, ten, eleven, or twelve months or longer at a pH of approximately 4 to approximately 7, or at pH 4.4 to 7 and individual pH values ​​or sub-ranges within the above range, or at pH 5.5, and at a temperature of approximately 25 to 30°C, for example, approximately 25°C. When used herein in relation to storage period, “stable” means that at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the compound remains unchanged over the specified period.

[0091] In one example, a cosmetic dermatological formulation is a moisturizing formulation comprising a compound of formula I (e.g., bis-aminopropyl diglycol dimaleate). The cosmetic dermatological formulation also comprises, as described above, a first composition comprising glycerin and lavandula angustifolia extract, a second composition comprising Vibrio alginolyticus fermentation filtrate, cetyl hydroxyproline palmitamide, one or more dermatologically acceptable carriers, and one or more dermatologically acceptable additives.

[0092] In some cases, cosmetic skin preparations are moisturizing preparations, and these moisturizing preparations include compounds of formula I (e.g., bis-aminopropyl diglycol dimaleate), water, sodium polyglutamate, hydroxyacetophenone, sclerotium gum, glycerin, 1,2-hexanediol, caprylyl glycol, cetearyl alcohol, cetearyl glucoside, glucose, polyglyceryl-4 oleate, polyglyceryl-3 polyricinoleate, glyceryl oleate citrate, C 10 ~C 18 Triglycerides, C 13 -C 15Alkane (hemisqualane), squalane, capryloyl glycerin / sebacate copolymer, VP / hexadecene copolymer, diisostearyl malate, caprylic / capric triglyceride, salicornia Herbacea extract, cetyl hydroxyproline palmitamide, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, sorbitan isostearate, polyacrylate crosspolymer-6, t-butyl alcohol, hydrogenated polydecene, glyceryl stearate, ceramide NP, hydrogenated lecithin, cholesterol, stearic acid, ceramide AP, phytosphingosine, tetraacetylphytosphingosine, xanthan gum, ceramide EOP, glycosphingolipid, beta-glucan, sodium benzoate, pentylene glycol, acetylated sodium hyaluronate, sodium hyaluronate, sodium hyaluronate crosspolymer, hydrolyzed sodium hyaluronate, ethylhexylglycerin, isomerized sugar, sodium citrate, citric acid, pentylene glycol, fructose, urea, sodium hydroxide, maltose, sodium PCA, sodium chloride, sodium lactate, trehalose, allantoin, Lavandula Contains angustifolia flower / leaf / stem extract, butylene glycol, Vibrio alginolyticus fermentation filtrate, and dilauramidoglutamidolynsin sodium.

[0093] In some cases, cosmetic skin formulations include a combination of carrier / vehicle and additives, such as humectants (glycerin, sodium hyaluronate, acetylated sodium hyaluronate, sodium hyaluronate crosspolymer, hydrolyzed sodium hyaluronate, sodium lactate, and / or beta-glucan); emollients / skin conditioning agents (hydrogenated ethylhexyl olive, Camellia japonica seed oil, isononyl isononanoate, caprylic / capric triglyceride, hydrogenated olive oil unsaponified, sesamum Indicum (sesame) seed oil, and / or hydrogenated polydecene, etc.); emulsifiers / surfactants (polyglyceryl-3 cetyl ether, polyglyceryl-4 caprate, sorbitan isostearate, hydrogenated lecithin, and / or glyceryl stearate, etc.); thickeners / viscosity modifiers (xanthan gum, cetearyl alcohol, sodium polyacryloyldimethyl taurate, stearic acid, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer, and / or polyacrylate crosspolymer-6, etc.); preservatives / Antibacterial agents (such as sodium benzoate, caprylyl glycol, ethylhexylglycerin, and / or hydroxyacetophenone); pH adjusters / buffers (such as lactic acid, sodium hydroxide, malic acid, citric acid, and / or trisodium citrate); chelating agents (such as tetrasodium glutamate diacetate); antioxidants (such as tocopherol and / or tocopheryl acetate); functional / natural ingredients (such as niacinamide (vitamin B3), hydrolyzed vegetable protein, lactococcus ferment lysate, hydroxyapatite, zingiber) Examples of such substances include: officinale (ginger) root extract, bisabolol, palmitoyl tripeptide-1, and / or palmitoyl tetrapeptide-7; ceramide / lipid barrier components (ceramide AP, ceramide EOP, ceramide NP, phytosphingosine, tetraacetylphytosphingosine, glycosphingolipids, and / or cholesterol); and / or solvents / carriers (water, propanediol, 1,2-hexanediol, pentylene glycol, and / or butylene glycol).These solvents / carriers and additives may be included in any suitable combination and concentration, for example, in the concentration values ​​and concentration ranges of carriers / vehicles and additives described elsewhere herein, to form part of a cosmetic dermatological formulation. It should also be understood that carriers / vehicles and additives may belong to one or more classes other than those listed above.

[0094] In another example, a cosmetic skin formulation is a scalp formulation comprising a compound of formula I (e.g., bis-aminopropyl diglycol dimaleate). The scalp formulation also comprises a first composition comprising glycerin and lavandula angustifolia extract, one or more dermatologically acceptable carriers (such as those described above), and optionally one or more dermatologically acceptable additives (such as those described above).

[0095] In some cases, cosmetic skin preparations are scalp preparations, and these include water, propanediol, glycerin, chlorphenesin, glycine soja (soybean) seed extract, sodium acrylate copolymer, lecithin, C9-C 12Alkanes, Caprylic / Capric Triglyceride, Oryza Sativa (Rice) Bran Oil, Octyldodecanol, Leptospermum Scoparium Branch / Leaf Oil, Magnolia Officinalis Bark Extract, Piper Nigrum (Black Pepper) Seed Extract, Menthoxypropanediol, Hydrogenated Polydecene, 1,2-Hexanediol, Ceramide NP, Cetearyl Alcohol, Glyceryl Stearate, Ceramide AP, Cholesterol, Hydrogenated Lecithin, Phytosphingosine, Stearic Acid, Tetraacetylphytosphingosine, Xanthan Gum, Ceramide EOP, Glycosphingolipids, Pogostemon Cablin Leaf / Stem Extract, Phenethyl Alcohol, Lavandula angustifolia (Lavender) Flower / Leaf / Stem Extract, Tasmannia Examples include lanceolata leaf extract, pentylene glycol, acetylated sodium hyaluronate, sodium hyaluronate, sodium hyaluronate crosspolymer, hydrolyzed sodium hyaluronate, ethylhexylglycerin, bis-aminopropyl diglycol dimaleate, phenoxyethanol, sodium benzoate, citric acid, and arginine.

[0096] In some cases, a scalp formulation contains a compound of formula I (e.g., bis-aminopropyl diglycol dimaleate) and a first composition comprising glycerin and lavandula angustifolia extract at concentrations effective in improving the scalp barrier function and reducing transepidermal water loss (TEWL) compared to before application of the scalp formulation to the scalp. b. Composition (one or more types) and other components (one or more types)

[0097] Cosmetic skin preparations include, for example, A composition containing glycerin and Lavandula angustifolia extract; Compositions containing the fermentation filtrate of Vibrio alginolyticus; and / or A composition comprising acetyltyrosine, proline, and adenosine triphosphate. This may include combinations of different compositions.

[0098] In some examples, compositions containing Vibrio alginolyticus fermentation filtrate further contain butylene glycol. In some examples, compositions containing acetyltyrosine, proline, and adenosine triphosphate further contain butylene glycol and / or hydrolyzed plant protein.

[0099] Furthermore, cosmetic skin preparations may contain other drugs / ingredients, for example, Cetylhydroxyproline palmitamide; N-succinyl-S-farnesyl-L-cysteine; Neuromide; It can also contain hydroxysomal calcium.

[0100] As described above, cosmetic dermatological formulations may also contain an activator of formula I (e.g., bis-aminopropyldiglycol dimaleate).

[0101] Each of the above compositions and other agents / components may be present independently in amounts ranging from about 0.001% to about 15% by weight of the total weight of the cosmetic dermatological preparation, from about 0.001% to about 10% by weight of the total weight of the cosmetic dermatological preparation, from about 0.001% to about 5% by weight of the total weight of the cosmetic dermatological preparation, from about 0.001% to about 2.5% by weight of the total weight of the cosmetic dermatological preparation, or from about 0.001% to about 1% by weight of the total weight of the cosmetic dermatological preparation, as well as in partial ranges or individual concentration values ​​disclosed within the above ranges.

[0102] In some other cases, each of the above compositions and other agents / components may be present independently in amounts based on the relative cytotoxicity of the compositions, agents, or components. In some cases, the dose of EXO-T® composition in a dermatological formulation does not exceed approximately 10,000 μg / mL. In some cases, the dose of WASTAR® lavender composition in a dermatological formulation does not exceed approximately 10,000 μg / mL. In some cases, the dose of UNIREPAIR® T-43 composition in a dermatological formulation does not exceed approximately 1,000 μg / mL. In some cases, the dose of SFC component in a dermatological formulation does not exceed approximately 0.1 μg / mL.

[0103] While not limited to these, cytotoxicity can be assessed using MTS cytotoxicity assays with reagents such as the Cell-Titer One-Solution MTS Assay and instruments such as the Envision plate reader (Perkin-Elmer). In an exemplary procedure, a) After incubating skin cells in plate wells with various concentrations of the test substance to be evaluated (i.e., composition, drug, or component), remove the treatment medium from the plate wells; b) Add 0.1 mL of 10% FBS-DMEM-phenol red-free-MTS medium to each well; c) Incubate the plate wells at 37°C and 5% CO2 for 30 minutes; d) Measure the absorbance at 490 nm using a plate reader; e) Calculate the survival rate (%) for each treatment concentration according to the following formula:

number

[0104] It is understood that the sum of the percentages of all possible compositions and other components, one or more dermatologically acceptable carriers, and one or more dermatologically acceptable additives as needed equals 100%. The foregoing may be present in any given skin formulation at any appropriate concentration and / or ratio among any two or more components, compositions, carriers, and additives that may be present.

[0105] Each of the composition and other components is stable in a skin formulation for a period of at least two, three, four, five, six, eight, nine, ten, eleven, or twelve months or longer at a pH of approximately 4 to approximately 6, or pH 4.4 to approximately 6, or pH 5.5, and at a temperature of approximately 25 to 30°C, or approximately 25°C. As used herein with respect to storage period, “stable” means that at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the compound remains unchanged over the specified period.

[0106] The various compositions and other components listed above can be obtained from commercially available sources as detailed below. 1. WASTAR (trademark) Lavender Composition

[0107] WASTAR® Lavender Composition contains glycerin and Lavandula angustifolia extract in water. WASTAR® Lavender Composition is commercially manufactured by Lucas Meyer Cosmetics as WASTAR® Lavender. WASTAR® Lavender is described as an upcycled lavender extract formed from by-products remaining after the production of natural essential oils, and is an anti-pollution, anti-stress, and protective agent. WASTAR® Lavender is an active ingredient that can provide protection to the skin against pollution.

[0108] Regarding lavandula angustifolia extract, the term "extract" can refer to an extract obtained from the flowers, leaves, fruits, seeds, roots, and / or stems of the lavender plant. Lavender belongs to the genus Lavandula, the family Lamiaceae, the order Lamiales, and the class Dicotyledonous plants. In certain cases, lavandula angustifolia extract may be an extract obtained from the flowers, leaves, and / or stems of lavender, and the extract has moderate to high water solubility (where moderate solubility is when the total amount of extract dissolved in water is about 10–1,000 mg / L, and high solubility is higher than 1,000 mg / L). In some other cases, lavandula angustifolia extract is an oil obtained from the seeds, flowers, leaves, and / or stems, and the extract is water-insoluble (total amount of extract dissolved in water is less than about 10 mg / L). In some cases, lavandula angustifolia extract is not an oil and does not contain any oil obtained from lavender. 2.EXO-T (trademark) composition

[0109] The EXO-T® composition contains the fermentation filtrate of Vibrio alginolyticus and contains water and butylene glycol as additives. The composition is commercially manufactured by Lucas Meyer Cosmetics as EXO-T®. EXO-T® is an exopolysaccharide derived from Kopara (microbial mat), which inhabits a unique ecosystem on the edge of atolls in French Polynesia.

[0110] EXO-T (trademark) improves skin smoothness, provides an even skin tone, and may also help reduce the appearance of stretch marks and blemishes. 3. UNIREPAIR® T-43 Composition

[0111] UNIREPAIR® T-43 composition contains acetyl tyrosine, proline, and adenosine triphosphate, with water, butylene glycol, and hydrolyzed vegetable protein as additives. The composition is commercially manufactured by Givaudan Active Beauty as UNIREPAIR® T-43. UNIREPAIR® T-43 is an amino acid-rich complex that can be used to reduce skin erythema. UNIREPAIR® T-43 is also said to act as a regenerative / repairing / reactivating, antioxidant, anti-redness, UV / sun protection, and SPF booster. 4. Ceramide Bio component

[0112] The CeramideBio component is formed from cetylhydroxyproline palmitamide. This component is commercially manufactured by Symrise as CeramideBio. CeramideBio is a pseudo-ceramide that is structurally and functionally similar to natural ceramide 2. Ceramides constitute one of the three main lipid components of the skin's permeable barrier (outer stratum corneum). CeramideBio is a preservative-free wax that can be used to maintain healthy skin and hair, as well as to support the repair of damaged skin and hair. 5.SFC components

[0113] The SFC component is formed from N-succinyl-S-farnesyl-L-cysteine ​​(SFC). This component is commercially manufactured by Signum Bioscience. SFC is an anti-inflammatory small molecule and the first farnesyl-cysteine ​​IPC to be shown to clinically improve appearance and signs of aging, and also has the potential to improve inflammatory skin conditions.

[0114] In addition to the ingredients listed above (at least one of which is present in this cosmetic skin preparation), the skin preparation may contain one or more of the following additional ingredients as needed. 6. Neuromide component

[0115] Neuromide® (Dr. Raymond Laboratories, Inc.) is an optional ingredient. Neuromide® is included in skincare formulations and contains N-palmitoylserinol. 7. Hydroxysomes® Calcium Components

[0116] As needed, Hydroxysomes® Calcium (Laboratory Skin Care, Inc.) is available as an ingredient. Hydroxysomes® Calcium is a microcarrier skin delivery platform containing nanoporous calcium phosphate particles (average particle size 2-4 mm). 8. HydroSal (registered trademark) moisturizing ingredient

[0117] As needed, Natural HydroSal® humectant (Salvona, LLC) is available. Natural HydroSal® humectant contains water, polyglyceryl-4 caprate, helianthus annuus (sunflower) seed oil, ceramide NP, ceramide AP, ceramide NG, phytosphingosine, phytosterol, lysolecithin, sclerotium gum, xanthan gum, pullulan, acacia senegal gum, bentonite, tragacanth gum, pentylene glycol, caprylyl glycol, propanediol, and ethylhexylglycerin. 9.Hymagic(TM)-4D component

[0118] The ingredients, as needed, include a formulation of sodium hyaluronate crosspolymer, sodium hyaluronate, acetylated sodium hyaluronate, hydrolyzed sodium hyaluronate, pentylene glycol, ethylhexylglycerin, and water. These ingredients, as needed, are commercially manufactured by Bloom Biotechnology Corporation, Ltd. as Hymagic®-4D. 10.MINIHA(TM) ingredients

[0119] The necessary components are formed from hydrolyzed sodium hyaluronate. These components are marketed as MINIHA (trademark) by Bloom Biotechnology Corporation, Ltd. 11.PRORENEW COMPLEX CLR(TM) Ingredients

[0120] The necessary components are formed from lactococcus fermentation lysates. These components are commercially available as PRORENEW COMPLEX CLR® by CLR Chemisches Laboratorium Dr. Kurt Richter GmbH. 12. DRAGOSANTOL (registered trademark) 100 ingredients

[0121] The necessary components include bisabolol, a monocyclic unsaturated sesquiterpene alcohol. This component is commercially available from Symrise as DRAGOSANTOL® 100.

[0122] As stated above, if any of the required ingredients described above are present, each required ingredient may be present in amounts ranging from approximately 0.001% to approximately 15% by weight of the total weight of the cosmetic dermatological preparation, from approximately 0.001% to approximately 10% by weight of the total weight of the cosmetic dermatological preparation, from approximately 0.001% to approximately 5% by weight of the total weight of the cosmetic dermatological preparation, from approximately 0.001% to approximately 2.5% by weight of the total weight of the cosmetic dermatological preparation, or from approximately 0.001% to approximately 1% by weight of the total weight of the cosmetic dermatological preparation, as well as in partial ranges or individual concentration values ​​disclosed within the above ranges.

[0123] Each of the components as needed is stable in a skin formulation for at least two, three, four, five, six, eight, nine, ten, eleven, or twelve months or longer at a pH of approximately 4 to approximately 6, or pH 4.4 to approximately 6, or pH 5.5, and a temperature of approximately 25 to 30°C, or approximately 25°C and 1 atm. As used herein with respect to storage period, “stable” means that at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the compound remains unchanged over the specified period. c. Carrier, additives as needed, and additives as needed

[0124] Additives The cosmetic skin formulations described herein typically contain one or more dermatologically acceptable carriers. Such carriers may be water, a dermatologically acceptable organic solvent, or a combination thereof.

[0125] The total weight of carriers, additives, and / or additives refers to the sum of the weights of each component in a particular category (e.g., carriers, additives, or additives) within the formulation. For example, if a skin formulation contains two or more dermatologically acceptable carriers, the total weight of dermatologically acceptable carriers refers to the sum of the weights of each dermatologically acceptable carrier in the formulation. To obtain the weight percentage of carriers, additives, and / or additives in a formulation, divide the total weight of the particular category (i.e., carriers, additives, or additives) by the total weight of all components in the skin formulation and multiply by 100.

[0126] The total weight of one or more dermatologically acceptable carriers may be in the range of about 0.01% to about 99% by weight, or 0.01% to about 95% by weight, of the total weight of the skin formulation, as well as a sub-range or individual concentration value within the above range. In some examples, the total weight of one or more dermatologically acceptable carriers may be in the range of about 0.1% to about 90% by weight, about 0.1% to about 80% by weight, about 0.1% to about 70% by weight, about 0.1% to about 60% by weight, about 0.1% to about 50% by weight, about 0.1% to about 40% by weight, about 0.1% to about 30% by weight, about 0.1% to about 20% by weight, or about 0.1% to about 10% by weight, of the total weight of the skin formulation, as well as a sub-range or individual concentration value within the above range. In some cases, cosmetic skin formulations may contain or substantially none of one or more of the dermatologically acceptable carriers described above, where "substantially absent" means formulations containing less than approximately 3% by weight, less than approximately 2% by weight, less than approximately 1% by weight, less than approximately 0.9% by weight, less than approximately 0.8% by weight, less than approximately 0.7% by weight, less than approximately 0.6% by weight, less than approximately 0.5% by weight, less than approximately 0.4% by weight, less than approximately 0.3% by weight, less than approximately 0.2% by weight, or less than approximately 0.1% by weight in the total weight of the skin formulation. The above ranges are understood to represent the sum of the concentrations of any one or a combination of dermatologically acceptable carriers that may be present.

[0127] In some cases, cosmetic skin formulations contain one or more dermatologically acceptable additives. Dermatologically acceptable additives include, for example, abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based agents, plant extracts, buffering agents (such as lactic acid, sodium lactate, citric acid, trisodium citrate, sodium hydroxide, etc.), fillers, sedatives, chelating agents (such as EDTA, tetrasodium glutamate diacetate, etc.), cleansing agents, emulsifiers, colorants, conditioning agents, cooling agents, deodorants, depilators, detergents, disinfectants, and dispersants (hydroxyethyl acrylate / acryloyl acrylate). (e.g., sodium dimethyltaurate copolymer), emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble agents, fibers, film-forming agents, fixatives, foaming accelerators, foaming stabilizers, foaming agents, fragrances, free radical scavengers, disinfectants, gelling agents, glossing agents, bleaching agents, conditioning agents, moisturizing agents, foaming agents, lubricants, makeup agents (for providing color, tone, gloss, or matte finish to the formulation and / or the skin to which it is applied), moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbers Agents, ointment bases, opacifying agents, organosilicones, oxidizing agents, oxygen carriers, pearlescent agents, perfumes, perfume solvents, perfume stabilizers, peroxide stabilizers, photosensitizers, pigments, pigment colorants, pearlescent agents, plant extracts, plant-derived ingredients, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymers, polymer film-forming agents, preservatives, propellants, reducing agents, relipidating agents, resins, scalp agents, scrubbing agents, metal ion chelating agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, skin bleaching agents, soluble These may be purifying agents, suspending agents, sunscreens, mitigating agents (such as bisabolol), spreading agents, stabilizers, sunless tanning agents, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, accelerators, thickeners, thixotropes, tightening agents, lotions, tonics, vegetable oils, volatile agents, viscosity stabilizers, vitamins, waterproofing agents, waxes, wetting agents, whitening agents, or combinations thereof.

[0128] The total weight of dermatologically acceptable additives (one or more) may be in the range of approximately 0.001% to approximately 99% by weight, 0.001% to approximately 95% by weight, or 0.001% to approximately 90% by weight of the total weight of the skin preparation, as well as individual concentration values ​​or sub-ranges within the above ranges. In some cases, the total weight of dermatologically acceptable additives (one or more) may be in the range of approximately 0.1% to approximately 95% by weight, approximately 0.1% to approximately 90% by weight, approximately 0.1% to approximately 80% by weight, approximately 0.1% to approximately 70% by weight, approximately 0.1% to approximately 60% by weight, approximately 0.1% to approximately 50% by weight, approximately 0.1% to approximately 40% by weight, approximately 0.1% to approximately 30% by weight, approximately 0.1% to approximately 20% by weight, or approximately 0.1% to approximately 10% by weight of the total weight of the skin preparation, as well as a subrange or individual concentration value within the above range. In some cases, cosmetic skin preparations may not contain, or substantially contain, one or more of the dermatologically acceptable additives listed above. "Substantially acceptable" means preparations containing less than approximately 3% by weight, less than approximately 2% by weight, less than approximately 1% by weight, less than approximately 0.9% by weight, less than approximately 0.8% by weight, less than approximately 0.7% by weight, less than approximately 0.6% by weight, less than approximately 0.5% by weight, less than approximately 0.4% by weight, less than approximately 0.3% by weight, less than approximately 0.2% by weight, or less than approximately 0.1% by weight of the dermatologically acceptable additives in any of the above ranges. It is understood that the values ​​within these ranges represent the sum of the concentrations of any one or more of the dermatologically acceptable additives that may be present.

[0129] In some cases, cosmetic skin formulations may further contain one or more additives. For example, additives include cell differentiation regulators, cell proliferation regulators, stimulants for the synthesis of dermal or epidermal polymers, inhibitors for the degradation of dermal or epidermal polymers, microcirculation stimulants, antimicrobial metal ion sequestering agents, analgesics, anesthetics, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-seborrheic agents, anti-cracking agents, anti-cellulite agents, anti-stretch mark agents, anti-dandruff agents, antifungal agents, antihistamines, anti-inflammatory agents, anti-irritants, antimicrobial agents, antibiotics, antiviral agents, anti-skin cancer agents, anti-eczema agents, anti-psoriasis agents, antiperspirants, antipruritic agents, antipruritic agents, circulatory stimulants, collagen stimulants, elastin stimulants, extracellular matrix stimulants, This may include enzymes, enzyme inhibitors, enzyme inducers, hormones, hormone-like agents, hyaluronic acid stimulants, keratolytic agents, mucosal adhesives, natural moisturizers, lipolytic agents, peptide agents (e.g., palmitoyl tripeptide-1, palmitoyl tetrapeptide-7), protein agents, rosacea inhibitors, scar preventive agents, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents (e.g., β-glucan), skin penetration enhancers, skin penetration delayers, skin conditioning agents, skin exfoliants, skin peeling agents, skin healing agents, skin protectants, skin purifying agents, vasoconstrictors, wound healing agents, or combinations thereof.

[0130] The total weight of the additive may be in the range of approximately 0.001% to approximately 99% by weight, 0.001% to approximately 95% by weight, or 0.001% to approximately 90% by weight of the total weight of the skin formulation, as well as individual concentration values ​​or sub-ranges within the above ranges. In some examples, the total weight of the additive may be in the range of approximately 0.1% to approximately 95% by weight, approximately 0.1% to approximately 90% by weight, approximately 0.1% to approximately 80% by weight, approximately 0.1% to approximately 70% by weight, approximately 0.1% to approximately 60% by weight, approximately 0.1% to approximately 50% by weight, approximately 0.1% to approximately 40% by weight, approximately 0.1% to approximately 30% by weight, approximately 0.1% to approximately 20% by weight, or approximately 0.1% to approximately 10% by weight of the total weight of the skin formulation, as well as individual concentration values ​​or sub-ranges within the above ranges. In some cases, cosmetic dermatological formulations may contain or substantially none of any of the above additives, with “substantially none” meaning formulations containing less than approximately 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1% of the total weight of the dermatological formulation.

[0131] As mentioned above, cosmetic dermatological formulations may contain a wide range of additives, carriers, and / or excipients. In addition to those listed above, "The 2012 International Cosmetic Ingredient Dictionary & Handbook, 14th Edition" and "The Cosmetic Bench Reference-Directory of Cosmetic Ingredients (published by Cosmetics & Toiletries)" describe a wide range of non-exclusive cosmetic and pharmaceutical ingredients commonly used in skincare, personal care, feminine care, and the dermatology and pharmaceutical industries, which may be used in the formulations of the present invention. Additional examples can be found in the United States Pharmacopeia (USP), the National Pharmaceutical Collection (NF), and other references on cosmetic and pharmaceutical ingredients known in the art. Each of these references is incorporated herein by reference in its entirety. This information is updated periodically with the addition of new ingredients.

[0132] The following are non-limiting examples of additives and / or additives that may form part of the cosmetic skin formulations described herein. 1. Vitamins

[0133] Cosmetic dermatological formulations may contain one or more vitamins, such as ascorbic acid (e.g., vitamin C, vitamin C derivatives, ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, tetrahexadecyl ascorbic acid, 3-aminopropyl ascorbyl phosphate), vitamin B, vitamin B derivatives, vitamins B1 to B12 and their derivatives, vitamin K, vitamin K derivatives, vitamin H, vitamin D, vitamin D3, vitamin D derivatives, vitamin E (tocopherol acetate), vitamin E derivatives, and their provitamins such as panthenol, as well as mixtures thereof. Vitamin compounds may be included as substantially pure substances or as extracts obtained by appropriate physical and / or chemical separation from natural (e.g., plant) sources. In one example, when a vitamin compound is included in a skin preparation, the preparation may contain the vitamin at a concentration of approximately 0.0001% to 25%, or approximately 0.001% to 10%, or approximately 0.01% to 5%, or approximately 0.1% to 1%, relative to the total weight of the preparation. 2. Sunscreen

[0134] Cosmetic skin formulations may contain sunscreen as needed. In this specification, “sunscreen” includes both sunscreen agents and physical sunscreens. Suitable sunscreen active ingredients may be organic or inorganic. A variety of conventional organic or inorganic sunscreen active ingredients are suitable for use in this specification. In one example, a formulation contains approximately 0.1% to 25%, more typically 0.5% to 10%, of the total weight of the formulation. The exact amount will vary depending on the selected sunscreen active ingredient and the desired sunscreen index (SPF). Organic UV-blocking agents include, but are not limited to, ethylhexyl salicylate, methoxydibenzoylmethanebutyl, ethylhexyl methoxycinnamate, octocrylene, phenylbenzimidazole sulfonic acid, terephthalilidene dicamphor sulfonic acid, benzophenone-3, benzophenone-4, benzophenone-5, 4-methylbenzylidene camphor, benzimidazolate, anisotriazine, ethylhexyl triazone, diethylhexylbutamide triazone, methylenebisbenzotriazolyltetramethylbutylphenol, drometrizole trisiloxane, or combinations or mixtures thereof. Exemplary inorganic sunscreen active ingredients that may be used in formulations include, but are not limited to, coated or uncoated metal oxide nanopigments (average primary particle size: generally between 5 nm and 100 nm, or between 10 nm and 50 nm; or aggregates thereof), such as titanium dioxide (amorphous or crystalline as rutile and / or anatase), iron oxide, zinc oxide, zirconium oxide, cerium oxide, and mixtures thereof. Suitable coating agents include, but are not limited to, alumina and / or aluminum stearate, as well as silicones. 3. Anti-wrinkle and anti-atrophy agents

[0135] Cosmetic skin formulations may contain one or more anti-wrinkle or anti-atrophy agents. Examples of anti-wrinkle / anti-atrophy agents suitable for use in formulations include amino acids, N-acetyl derivatives of amino acids (e.g., N-acetylcysteine), hydroxy acids (e.g., α-hydroxy acids such as lactic acid and glycolic acid, or β-hydroxy acids such as salicylic acid, octanoyl derivatives, etc., lactobionic acid), keto acids (e.g., pyruvic acid), phytic acid, ascorbic acid (vitamin C), retinoids (e.g., retinoic acid, tretinoin, isotretinoin, adapalene, retinol, retinyl aldehyde, retinoic acid, etc.) Nylpalmitate and other retinoid derivatives), kinetin (N6-furfuryladenine), zeatin and its derivatives (e.g., furfurylaminotetrahydropyranyladenine), niacinamide (nicotinamide); growth factors and cytokines (e.g., TGF-β1, 2, and 3, EGF, FGF-2, PDGF, IL-1, IL-6, IL-8, IGF-1, IGF-2, etc.), cell lysates (e.g., dermal fibroblast lysates, stem cell lysates, processed skin cell proteins (PSP®), etc.), prepared fine powders Cell culture media (e.g., modified cell culture media derived from dermal fibroblasts, modified cell culture media derived from stem cells (e.g., epidermal stem cells, adipose-derived stem cells, mesenchymal stem cells, etc.); cosmetic ingredients sold under the trademark names Nouricel-MD®, TNS®, or CCM® Complex; etc.); cell extracts, stem cell extracts, stem cell-derived ingredients; ingredients that stimulate epidermal or other human adult stem cells; skin conditioning agents, stilbene, cinnamate, sirtuin-1 activating ingredients (e.g., resveratrol); Ingredients that improve mitochondrial function include, but are not limited to, dimethylaminoethanol, synthetic anti-aging peptides, naturally derived peptides (e.g., soy peptides), and sugar salts (e.g., manganese gluconate, zinc gluconate), lipoic acid; lysophosphatidic acid, vitamin B3 (niacinamide) compounds, and other vitamin B compounds (e.g., thiamine (vitamin B1), pantothenic acid (vitamin B5), riboflavin (vitamin B2)), as well as their derivatives and salts (e.g., hydrochloride or calcium salts).

[0136] If a skin formulation contains anti-wrinkle / anti-atrophy agents, the formulation may contain approximately 0.0001% to 25%, or approximately 0.001% to 25%, or approximately 0.01% to 25%, or approximately 0.001% to 10%, or approximately 0.01% to 10%, or approximately 0.01% to 10%, or approximately 0.01% to 5%, or approximately 0.1% to 5%, or approximately 0.1% to 1% of the total weight of the formulation. The exact percentage of anti-wrinkle / anti-atrophy agents used in a formulation depends on the specific anti-wrinkle / anti-atrophy agent used, as their potency varies. 4. Moisturizing agents, humectants, and conditioning agents

[0137] Cosmetic skin formulations may contain safe and effective amounts of conditioning agents. Appropriate categories of conditioning agents include, for example, hydrates, moisturizers, and skin conditioners. Various materials of these may be used and may be present in amounts ranging from about 0.01% to about 80% by weight of the formulation, or about 0.1% to about 80% by weight, or about 0.1% to about 50% by weight, or about 0.1% to about 25% by weight, or about 0.5% to about 25% by weight, or about 0.5% to about 10% by weight. The exact percentage content of hydrates, moisturizers, and conditioning agents used in a formulation depends on the hydrates, moisturizers, and conditioning agents used, as their potency varies.

[0138] Moisturizing agents are ingredients that help maintain the skin's moisture level. Exemplary and suitable conditioning agents include, but are not limited to, glycerin, hydrolyzed sodium hyaluronate, hydrolyzed vegetable proteins, phytosphingosine, sodium hyaluronate crosslinked polymers, hydroxyacetophenone, polyhydric alcohols, water-soluble alkoxylated nonionic polymers, and mixtures thereof. Useful polyhydric alcohols for the formulations described herein include the aforementioned polyhydroxy alcohols and glycerin, hexylene glycol, ethoxylated glucose, 1,2-hexanediol, dipropylene glycol, trehalose, diglycerin, maltitol, maltose, glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate, sodium adenosine phosphate, sodium lactate, pyrrolidone carboxylic acid, glucosamine, cyclodextrin, and mixtures thereof. Examples of water-soluble alkoxylated nonionic polymers useful in the formulations described herein include polyethylene glycol and polypropylene glycol with molecular weights up to approximately 1000 daltons, such as CTFA names PEG-200, PEG-400, PEG-600, PEG-1000, and mixtures thereof. Additional suitable moisturizing agents include, but are not limited to, sodium hyaluronate, acetylated sodium hyaluronate, acetylarginine, algal extracts, aloe vera leaf extract, 2,3-butanediol, chitosan lauroyl glycinate, diglycerol-7 malate, diglycerin, diglycol guanidine succinate, erythritol, fructose, glucose, glycerin, honey, hydrolyzed proteins, hydroxypropyltrimonium hyaluronic acid, inositol, lactitol, maltitol, maltose, mannitol, mannose, methoxypolyethylene glycol, myristiadobutylguanidine acetate, polyglyceryl sorbitol, potassium pyrrolidone carboxylic acid (PCA), propylene glycol, butylene glycol, sodium pyrrolidone carboxylic acid (PCA), sorbitol, sucrose, dextran sulfate (i.e., of any molecular weight), natural moisturizing factors, and / or urea, as well as combinations thereof.

[0139] Suitable skin conditioners include guanidine, urea, glycolic acid, glycolates (e.g., ammonium and quaternary alkylammonium), salicylic acid, lactic acid, lactates (e.g., ammonium and quaternary alkylammonium), aloe vera in various forms (e.g., aloe vera gel), sorbitol, mannitol, xylitol, erythritol, hexanetriol, butanetriol, propylene glycol, butylene glycol, hexylene glycol, hydrogenated ethylhexyl olive, camellia japonica seed oil, hydroxyapatite, hydrogenated olive oil unsaponified, sesamum indicum (sesame) oil, caprylyl glycol, proline, polyhydroxy alcohols such as pentylene glycol, polyethylene glycol, propoxyglycerol, sugars (e.g., melibiose), starch, sugars and starch derivatives (e.g., alkoxylated glucose, fructose, glucosamine), C1-C 30 Examples of suitable skin conditioners include, but are not limited to, monoesters and polyesters of sugars and related substances, hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine, panthenol, dexpanthenol, allantoin, and mixtures thereof. Other suitable skin conditioners include fatty acids, fatty acid esters, lipids, ceramides, cholesterol, cholesterol esters, beeswax, petrolatum, and mineral oils. 5. Emulsifiers

[0140] The cosmetic skin formulations described herein may contain one or more emollients. Generally, emollients refer to ingredients that can help maintain a soft, smooth, and supple appearance of the skin. Generally, emollients remain on the skin surface or in the stratum corneum, acting as moisturizers or lubricants and reducing peeling.Some examples of emollients include hydrogenated ethylhexyl olive, isononyl isononanoate, caprylic / capric triglyceride, cetearyl alcohol, hydrogenated lecithin, stearic acid, cholesterol, polyglyceryl-4 caprylate, glycosphingolipid, hydrogenated polydecene, acetylarginine, acetylated lanolin, algal extract, apricot kernel oil polyethylene glycol-6 ester, avocado oil polyethylene glycol-11 ester, and bis-polyethylene glycol. -4 Dimethicone, Butoxyethyl Stearate, Glycol Ester, Alkyl Lactate, Caprylyl Glycol, Cetyl Ester, Cetyl Laurate, Coconut Oil, Polyethylene Glycol-10 Ester, Alkyl Tartrate, Diethyl Sebacate, Dihydrocholesteryl Butyrate, Dimethiconol, Dimyristyl Tartrate, Disteareth-5 Lauroyl Glutamate, Ethyl Avocadodate, Ethylhexyl Myristic Acid, Glyceryl Isostearate, Glyceryl Oleate, Hexyldecyl Therate, hexyl isostearate, hydrogenated palm glyceride, hydrogenated soybean glyceride, hydrogenated animal fat glyceride, isostearyl neopentanoic acid, isostearyl palmitate, isotridecyl isononanoate, laureth-2 acetate, lauryl polyglyceryl-6 cetearyl glycol ether, methyl gluceth-20 benzoate, mineral oil, palm oil, coconut oil, myreth-3 palmitate, octyldecanol, octyldodecanol, Odontella aurita oil, 2-oleamide Examples of these ingredients include, but are not limited to, -1,3-octadecanediol, palm glycerides, polyethylene glycol avocado glycerides, polyethylene glycol castor oil, polyethylene glycol-22 / dodecyl glycol copolymer, polyethylene glycol shea butter glycerides, phytol, raffinose, stearyl citrate, sunflower seed oil glycerides, petrolatum, silicone oils (including, but not limited to, caprylyl methicone), and / or tocopheryl glucosides. 6. Antioxidants and radical scavengers

[0141] Cosmetic dermatological formulations may contain antioxidants / radical scavengers as needed. In some cases, formulations contain approximately 0.001% to 25%, or approximately 0.01% to 10%, or approximately 0.1% to 5% of antioxidants / radical scavengers. The exact percentage of antioxidants / radical scavengers in a formulation depends on the specific antioxidant / radical scavenger used, as their potency varies.

[0142] Suitable antioxidants / radical scavengers include ascorbic acid (vitamin C) and its salts, fatty acid ascorbyl esters, and other ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate, ascorbyl palmitate, tetrahexyldecyl ascorbic acid, etc.), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other tocopherol esters, β-carotene, butylated hydroxybenzoic acid and its salts, ferulic acid, peroxides including hydrogen peroxide, perborates, thioglycolates, persulfates, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (marketed under the trade name Trolox®), gallic acid and its alkyl esters (especially propyl gallate), uric acid and its salts and alkyl esters, amines (e.g., N,N-diethyl hydroxybenzoate), Droxiamine (aminoguanidine), nordihydroguaiaretic acid, bioflavonoids, sulfhydryl compounds (e.g., glutathione), dihydroxyfumaric acid and its salts, lysine pyrate, arginine pyrate, amino acids, silymarin, lysine, 1-methionine, proline, superoxide dismutase, sorbic acid and its salts, lipoic acid, olive extract, tea extract, resveratrol, polyphenols such as proanthocyanidins derived from pine bark, carotenoids, curcumin compounds such as tetrahydrocurcumin, coenzyme Q10, OCTA (L-2-oxo-4-thiazolidinedic acid), selenium, creatine, glutathione, N-acetylcysteine, N-acetylcysteine ​​ester, dimethylmethoxychromanol, lipoic acid, melanin; coffee berry extract, green tea extract, rosemary extract, witch hazel extract, zingiber Polyphenol-containing plant extracts, including but not limited to officinale (ginger) root extract and grape skin / seed extract, may be used. 7. Antimicrobial peptide metal ion chelating agent

[0143] Antimicrobial peptide metal ion chelating agents can form part of cosmetic dermatological formulations. Suitable antimicrobial peptide metal ion chelating agents include, but are not limited to, sulfated or polysulfated monosaccharides and their salts and complexes; sulfated or polysulfated disaccharides and their salts and complexes; sulfated or polysulfated polysaccharides and their salts and complexes; dextran sulfate (e.g., sodium dextran sulfate) and its salts and complexes; chondroitin sulfate and its salts and complexes; pentosan polysulfate and its salts and complexes; sucrose sulfate (e.g., sucrose sulfate other than aluminum sucrose sulfate, such as octasulfate) and its salts and complexes; fucoidan and its salts and complexes; sulfated galactoane and its salts and complexes; carrageenan (e.g., Chondrus crispus) and its salts and complexes; sulfated starch and its salts and complexes; cellulose sulfate and its salts and complexes; sulfated glycosaminoglycans and their salts and complexes; heparin; heparan sulfate; sulfated glucans; or any combination thereof. The antimicrobial peptide metal ion chelating agent may be a plant extract, algae extract, aloe vera (barbadensis) extract, cactus extract, or shark or fish cartilage extract. The antimicrobial peptide metal ion chelating compound may also be a sulfated or polysulfated polymer (e.g., poly(vinyl sulfate), poly(anethole sulfonic acid)). Suitable polymeric sulfonic acids that can be used in the methods and formulations described herein are hydrophobic modified polymeric sulfonic acids, such as ARISTOFLEX® HMP or ARISTOFLEX® AVC (Clariant). Alternatively, the antimicrobial peptide metal ion chelating agent may be a phosphate or polyphosphate (e.g., monosaccharide phosphate, disaccharide phosphate, polysaccharide phosphate, glycerophosphate, or starch phosphate). Suitable examples of starch phosphates include, but are not limited to, hydroxypropyl starch phosphate (i.e., Structure XL (National Starch, LLC)).Antimicrobial peptide metal ion chelating agents can also be phospholipids such as phosphatidylcholine and lecithin. Furthermore, antimicrobial peptide metal ion chelating agents can be carboxylates, polyhydroxy acids, hyaluronic acid, alginates, and / or polylactic acid. In some examples, the amount of antimicrobial peptide metal ion chelating agent is 100 to 10,000 g per mole. 8. Rosacea inhibitors and alpha-adrenergic receptor agonists

[0144] Cosmetic skin preparations may contain rosacea inhibitors as needed. Suitable rosacea inhibitors include metronidazole, sulfacetamide, sodium sulfacetamide, sulfur, dapsone, doxycycline, minocycline, clindamycin, clindamycin phosphate, erythromycin, tetracycline, azelaic acid, calcium dobesylate, maleic acid, and compatible combinations thereof); alpha-adrenergic receptor agonists (e.g., clonidine, amphetamine, doxtroamphetamine, apraclonidine, dipivefrin, alpha-methyldopa, oxymetazoline, oxymetazoline hydrochloride, methoxamine, metalaminol, medetomidine, dexmedetomidine, ethylnorepinephrine, guanfacine, guanabenz, phenylephrine, phenylephrine hydrochloride, ephedrine, epinin, epinephrine, ethylnorepinephrine. , revatertenol, lofexidine, norepinephrine, norphenylephrine, norephedrine, phenylpropanolamine, pemoline, propylhexadrine, pseudoephedrine, methamphetamine, methylnorepinephrine, methylphenidate, mephentermine, midodrine, mibazerol, moxonidine, desglimidodrine, tetrahydrozoline, tetrahydrozoline hydrochloride, silazolin, amidoferrine, brimonidine, brimonidine tartrate, naphazoline, isoproterenol, xylazine, xylometazoline, and / or tizanidine); vasoconstrictive chemicals and plant extracts (including, but not limited to, corticosteroids, ephedrine, pseudoephedrine, caffeine, and / or esin); ephedra, Phedra Examples include, but are not limited to, sinica, Hamamelis viginiana, Hydrastis canadensis, Lycopus virginicus, Aspidosperma quebracho, Cytisus scoparius, Raphanus sativus linn (radish leaf extract), horse chestnut extract, and compatible combinations thereof. 9. Skin brightening agents and skin bleaching agents

[0145] Cosmetic skin preparations may contain skin brightening agents as needed. Suitable skin brightening agents include, but are not limited to, ascorbic acid and its derivatives, kojic acid and its derivatives, resorcinol and its derivatives (including, but not limited to, 4-ethyl resorcinol, 4-butyl resorcinol, 4-hexyl resorcinol, 4-octyl resorcinol, 4-decyl resorcinol, 6-methyl resorcinol, 6-ethyl resorcinol, 6-butyl resorcinol, 6-hexyl resorcinol, 6-octyl resorcinol, 6-decyl resorcinol, and 4-phenylethyl resorcinol), retinoic acid and its derivatives (e.g., retinol, retinyl palmitate), L-leucine and its derivatives (e.g., N-acyl derivatives of L-leucine, esters of L-leucine, etc.), glycine and its derivatives, disodium glycerophosphate and its derivatives, and Examples of these include, but are not limited to, dedecenoylphenylalanine, arbutin and its derivatives (e.g., dehydroxyarabutin), niacinamide and its derivatives, hydroquinone; mequinol, glabridin, aleosin, curcumin, genistein, ethyl linoleate, tranexamic acid, azelaic acid, resveratrol and its derivatives (e.g., oxyresveratrol), N-acetylglucosamine, 4-isopropyl ketochol, 4-ethoxybenzaldehyde, 2-ethoxybenzaldehyde, 4-propoxybenzaldehyde, α-hydroxy acids (e.g., glycolic acid, lactic acid, etc.), salicylic acid, polyphenols; and / or various plant extracts derived from licorice, grape seed, mulberry, soybean, green tea, and / or bearberry; and / or any combination thereof.

[0146] When used, cosmetic skin formulations may contain approximately 0.01% to 15% by weight, or approximately 0.1% to 10% by weight, or approximately 0.5% to 5% by weight of a skin brightening agent relative to the formulation. The exact percentage of skin brightening agent used in a formulation depends on the specific skin brightening agent used, as there are differences in the potency of these agents. 10. Skin protectants

[0147] Suitable skin protectants for use in cosmetic skin formulations described herein include, for example, compounds that protect damaged or exposed skin or mucous membrane surfaces from harmful or irritating external compounds. Typical examples include algal extracts, allantoin, Camellia sinensis leaf extract, cerebroside, dimethicone, glucuronolactone, glycerin, kaolin, lanolin, malt extract, mineral oil, petrolatum, white petrolatum, potassium gluconate, colloidal oatmeal, calamine, cocoa butter, starch, zinc oxide, zinc carbonate, zinc acetate, and / or talc. 11. Exfoliating agents, keratolytic agents, and peeling agents

[0148] Exfoliating / keratolytic agents may be included in cosmetic skin formulations described herein. In some examples, formulations contain exfoliating / keratolytic agents in amounts of about 0.01% to about 30%, or about 0.1% to about 10%, or about 0.5% to about 5%, relative to the total weight of the formulation. The exact percentage of exfoliating / keratolytic agent used in a formulation depends on the specific exfoliating / keratolytic agent used, as there are differences in the potency of these agents.

[0149] Examples of suitable keratolytic and / or exfoliating agents include, but are not limited to, urea, salicylic acid and its alkyl derivatives, saturated and unsaturated monocarboxylic acids, saturated and unsaturated dicarboxylic acids, tricarboxylic acids, α-hydroxy and β-hydroxy acids of monocarboxylic acids, α-hydroxy and β-hydroxy acids of dicarboxylic acids, α-hydroxy and β-hydroxy acids of tricarboxylic acids, keto acids of polycarboxylic acids, α-keto acids, β-keto acids, keto acids of polyhydroxymonocarboxylic acids, α-keto acids, β-keto acids, keto acids of polyhydroxydicarboxylic acids, α-keto acids, β-keto acids, and keto acids of polyhydroxytricarboxylic acids. Resorcinol and its low molecular weight derivatives are another example of a useful keratolytic and / or exfoliating agent.

[0150] In certain cases, keratolytic agents include, but are not limited to, glycolic acid, tartaric acid, salicylic acid, citric acid, lactic acid, pyruvic acid, gluconic acid, glucuronic acid, malic acid, mandelic acid, oxalic acid, malonic acid, succinic acid, acetic acid, phenol, resorcinol, retinoic acid, adapalene, trichloroacetic acid, 5-fluorouracil, or azelaic acid, or combinations thereof. Keratoplytic agents may also be salts, esters, possible cis or trans forms, racemic mixtures, and / or relative dextrorotatory or levorotatory forms of the compounds listed above. These substances may be used alone or in combination with each other. 12. Anti-inflammatory drugs

[0151] The cosmetic skin formulations described may contain anti-inflammatory agents. In some cases, the anti-inflammatory agent is included in the formulation at a concentration of approximately 0.01% to 10%, or approximately 0.5% to 5%, relative to the weight of the formulation. The exact percentage of anti-inflammatory agent used in the formulation depends on the specific anti-inflammatory agent used, as there are differences in the potency of those agents.

[0152] Steroidal anti-inflammatory agents include, but are not limited to, adrenocortical steroids such as hydrocortisone, hydroxyltriamcinolone, α-methyldexamethasone, dexamethasone phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoxymethasone, deoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butyl ester, fluocortolone, fluprednidene (fluprednilidene) acetate, fluradrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenolone, fludrocortisone, diflurosone diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone and remaining esters thereof, chlorprednisone, chlorprednisone acetate, clocortolone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluorometholone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, and triamcinolone, as well as mixtures thereof, and any of these can be used.

[0153] Furthermore, non-steroidal anti-inflammatory agents may be used. The types of compounds included in this group are known to those skilled in the art. Specific non-steroidal anti-inflammatory agents that may be useful in the formulation include, but are not limited to, diclofenac, indomethacin, oxicams such as piroxicam, salicylates such as aspirin; acetic acid derivatives such as felbinac, fenamates such as etofenamate, propionic acid derivatives such as flufenamic acid, mefenamic acid, meclofenamic acid, tolfenamic acid, ibuprofen, and naproxen, pyrazole, and mixtures thereof. Mixtures of these non-steroidal anti-inflammatory agents, as well as dermatologically acceptable salts and esters of these agents may also be used. For detailed disclosure of the chemical structure, synthesis methods, side effects and other details of non-steroidal anti-inflammatory agents, reference is made to standard literature including Anti-inflammatory and Anti-Rheumatic Drugs, K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985) and Anti-inflammatory Agents, Chemistry and Pharmacology, 1, R. A. Scherrer, et al., Academic Press, New York (1974).

[0154] Finally, "natural" anti-inflammatory agents may be useful in the described dermatological formulations. Such agents may suitably be obtained as extracts by appropriate physical and / or chemical isolation from natural sources (e.g., by-products of plants, fungi, microorganisms), or may be prepared synthetically. For example, candelilla wax, bisabolol (e.g., α-bisabolol), aloe vera, phytosterols (e.g., phytosterol), kola extract, chamomile, red clover extract, sea whip extract, licorice extract, and tea extract may be used.

[0155] Useful anti-inflammatory agents in this specification include allantoin, as well as compounds of licorice, including glycyrrhetinic acid, glycyrrhizic acid, and their derivatives (e.g., salts and suitable esters). Further anti-inflammatory agents include diosgenol, saponins, sapogenins, lignans, triterpene saponosides, and genins.

[0156] Additional examples of anti-inflammatory agents include tetraacetylphytosphingosine; anti-inflammatory interleukins (e.g., IL-1ra, IL-6, IL-8, IL-10); anti-inflammatory fatty acids (e.g., linoleic acid, linolenic acid) and their derivatives (e.g., esters); isoprenylcysteine ​​analogs (i.e., N-acetyl-S-farnesyl-L-cysteine); aromatic aldehydes with anti-inflammatory properties (e.g., 4-methoxybenzaldehyde, 4-ethoxybenzaldehyde, 4-butoxybenzaldehyde, 4-pentoxybenzaldehyde); and any interchangeable combination thereof. 13. Anti-acne drugs

[0157] Cosmetic dermatological formulations may contain one or more anti-acne agents. Examples of useful anti-acne active substances include, but are not limited to, resorcinol, sulfur, erythromycin, salicylic acid, benzoyl peroxide, retinoic acid, tretinoin, alpha-hydroxy acids (e.g., glycolic acid, lactic acid), dehydroacetic acid, and zinc. When anti-acne compounds are present in a formulation, the formulation may contain approximately 0.0001% to 50%, or approximately 0.001% to 20%, or approximately 0.01% to 10%, or approximately 0.1% to 5% of the total weight of the formulation. The exact percentage of anti-acne agents used in a formulation depends on the specific antimicrobial, antibacterial, and anti-acne active substances used, as there are differences in the potency of these agents. 14. Antimicrobial agents, antimicrobial agents, and antifungal agents

[0158] Cosmetic skin formulations may contain one or more antifungal or antimicrobial agents. Safe and effective amounts of antimicrobial or antifungal active substances may be added to the formulations of the present invention. For example, a formulation may contain about 0.001% to about 10%, or about 0.01% to about 5%, or about 0.05% to about 2% of the antimicrobial or antifungal agent based on the total weight of the formulation. The exact percentage content of antimicrobial, antimicrobial, and antifungal active substances used in a formulation depends on the specific antimicrobial, antimicrobial, and antifungal active substances used, as there are differences in the potency of these agents.

[0159] Suitable antimicrobial agents include coal tar, sulfur, aluminum chloride, gentian violet, octopirox (piroctone olamine), 3,4,4'-trichlorocarbanilide (triclosan), triclocarban, cyclopirox olamine, undecylenic acid and its metal salts, potassium permanganate, selenium sulfide, sodium thiosulfate, propylene glycol, bitter orange oil, urea preparations, griseofulvin, 8-hydroxyquinoline siloquinol, thiobendazole, thiocarbamate, haloprogin, polyene, hydroxypyridone, morpholine, benzylamine, allylamine (terbinafine, etc.), tea tree oil, clove leaf oil, coriander, palmarosa, berberine, thyme red, cinnamon oil, cinnamaldehyde, citronellic acid, hinokitol, and ichthyol. Examples include, but are not limited to, pale, iodopropynyl butylcarbamate, azelaic acid, isothiazolinones such as octylisothiazolinone, azoles, parabens (e.g., methylparaben, ethylparaben, etc.), glycols (e.g., hexylene glycol, ethylhexylglycerin), and combinations thereof.

[0160] For example, suitable agents with antifungal properties include ketoconazole, naphthifine hydrochloride, oxiconazole nitrate, sulconazole nitrate, urea, terbinafine hydrochloride, and selenium sulfide. 15. Anesthetics

[0161] Cosmetic dermatological formulations may also contain safe and effective amounts of local anesthetics. Examples of local anesthetics include benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, diclonin, hexylcaine, procaine, cocaine, ketamine, pramoxin, phenol, and their pharmaceutically acceptable salts; benzyl alcohol, camphor, menthol, resorcinol, and appropriate combinations thereof. 16. Plant extracts and botanical extracts

[0162] Skin formulations may also contain safe amounts of plant extracts and botanical extracts. Examples of plants or plant extracts include ivy (especially English ivy (Hedera Helix)), Bupleurum chinensis, barley, Bupleurum falcatum, arnica (Arnica montana L), rosemary (Rosmarinus officinalis N), marigold (Calendula officinalis), sage (Salvia officinalis L), soybean, ginseng (Panax ginseng), Ginko biloba, St. John's wort (Hyperycum perforatum), butcher's broom (Ruscus aculeatus L), European meadowsweet (Filipendula ulmaria L), large-flowered Java tea (Jarva tea) (Orthosiphon staminatus Bent), algae (Fucus vesiculosus), and birch (Betula alba), green tea, white tea, fermented tea, cola nut (Cola nipida), horse chestnut, bamboo, spade leaf (Centella asiatica), heather, fucus, willow, witch hazel, wild yam, mouse-ear, escine, cangzhu, chrysanthellum indicum, plants of the genus Armeniacea, Atractylodis platicodon, Sinnomenum, Pharbitidis, C. Forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C.Flemingia, Coleus, Coleus barbatus root, Ballote, Guioa, Davallia, Terminalia, Barringtonia, Trema, Antillia, Cecropia, Argania, Dioscoreae (Dioscorea opposita or Mexican, Ammi visnaga, Centella asiatica and Siegesbeckia (especially Siegesbeckia orientalis)), Ericaceae (especially bilberry extract (Vaccinium angustifolium) or Arctostaphylos uva ursi), Aloe vera, plant sterols (e.g., phytosterols), Manjistha (extracted from plants of the genus Rubia (especially Rubia Cordifolia)), and Guggal (extracted from plants of the genus Commiphora (especially Commiphora Mukul)), Cola extract, Chamomile, Red clover extract, Piper methysticum, Bacopa Monieri extract, sea whip, Glycyrrhiza glabra, mulberry, Melaleuca (tea tree), mushroom extract, Larrea divaricata, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa Hirudinea, Chaparral sorghum, sunflower extract, Enantia chlorantha, Spermacocea genus Mitracarpe, Buchu barosma, Lawsonia inermis L, Adiantium capillus-Veneris L, Chelidonium majus, Luffa cylindrical, Japanese mandarin (Citrus reticulata Blanco var.Examples of extracts obtained from unshiu (a type of citrus fruit), broccoli extract, Camelia sinensis, Imperata cylindrical, Glaucium flavum, Cupressus Sempervirens, Polygonatum multiflorum, loveyly hemsleya, Sambucus Nigra, Phaseolus lunatus, Centaurium, Macrocystis pyrifera, Turnera diffusa, Anemarrhena asphodeloides, Portulaca pilosa, Humulus lupulus, coffee arabica, coffee berry, blackberry, and Ilex Paraguariensis are also mentioned. 17. Oils and Lipids

[0163] Cosmetic skin preparations may contain any cosmetic or dermatological oil, or mixtures thereof. Examples of such oils include aliphatic hydrocarbons such as liquid paraffin, squalene, squalane, petrolatum, and ceresin; silicone oils such as dimethicone and cyclomethicone; vegetable oils such as avocado oil, apricot oil, almond oil, borage oil, borage seed oil, camellia oil, canola oil, castor oil, coconut oil, cocoa butter, corn oil, cottonseed oil, olive oil, evening primrose oil, linseed oil, palm oil, palm kernel oil, peanut oil, rapeseed oil, safflower oil, sesame oil, sweet almond oil, rosehip oil, calendula oil, chamomile oil, eucalyptus oil, juniper oil, safflower oil, sandalwood oil, tea tree oil, sunflower oil, soybean oil, and wheat germ oil; animal fats such as shark liver oil, cod liver oil, whale oil, beef tallow, and butterfat; beeswax, carnauba Examples of lipids include, but are not limited to, waxes such as coconut wax, whale wax, and lanolin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and behenic acid; omega-3 fatty acids such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid; omega-6 fatty acids such as linoleic acid and gamma-linolenic acid; aliphatic alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and oleyl alcohol; and aliphatic esters such as isopropyl myristate, isocetyl myristate or octadecyl myristate, butyl stearate, hexyl laurate, diisopropyl adipic acid, or diisopropyl sebacate; and / or mixtures thereof. Generally, oils are refined and / or hydrogenated. Lipids include monoglycerides, diglycerides, triglycerides, phospholipids, and ceramides. 18. Suspension

[0164] Cosmetic skin formulations may contain suspending agents at concentrations effective for suspending water-insoluble substances in a dispersed form within the formulation, or at concentrations effective for adjusting the viscosity of the formulation. Such concentrations may range from about 0.1% to about 10%, or from about 0.25% to about 5.0%. Useful suspending agents in this specification include anionic polymers and nonionic polymers. Useful materials in this specification include vinyl polymers such as crosslinked acrylic acid polymers having CTFA carbomers, cellulose derivatives and modified cellulose polymers such as methylcellulose, ethylcellulose, nitrocellulose, sodium carboxymethylcellulose, crystalline cellulose, and cellulose powder, microbial polymers such as polyvinylpyrrolidone, polyvinyl alcohol, guar gum, hydroxypropyl guar gum, gum arabic, galactan, carob gum, pectin, agar, starch (rice, corn, potato, wheat), algal colloids (algal extracts), dextran, succinoglucan, and pullulan, starch-based polymers such as carboxymethyl starch and methylhydroxypropyl starch, alginate-based polymers such as sodium alginate and propylene glycol alginate, acrylate polymers such as sodium polyacrylate, polyacrylate, and polyacrylamide, polyethyleneimine, and inorganic water-soluble substances such as bentonite, aluminum magnesium silicate, laponite, hectonite, and anhydrous silicic acid. The aforementioned thickeners may also be used as suspending agents in this specification.

[0165] Other necessary suspensions include crystalline suspensions which may be classified as acyl derivatives, long-chain amine oxides, long-chain acyl derivatives, and mixtures thereof. Exemplary suspending agents include ethylene glycol esters of fatty acids, alkanolamides of fatty acids, long-chain esters of long-chain fatty acids (e.g., stearyl stearate, cetyl palmitate, etc.), long-chain esters of long-chain alkanolamides (e.g., stearamide diethanolamide distearate, stearamide monoethanolamide stearate); and glyceryl esters (e.g., glyceryl distearate, trihydroxystearin, tribehenin). Other suitable suspending agents include primary amines having a fatty alkyl moiety with at least about 16 carbon atoms (examples include palmitamine or stearamine) and secondary amines having two fatty alkyl moieties, each having at least about 12 carbon atoms (examples include dipalmitoylamine or di(hydrogenated tallow)amine). Further other suitable suspending agents include di(hydrogenated tallow)phthalamides and crosslinked maleic anhydride-methyl vinyl ether copolymers. 19. Emulsifiers (surfactants)

[0166] The emulsifiers are known from the prior art and include a variety of nonionic, cationic, anionic, amphoteric, and amphoteric surfactants, which may be included in the cosmetic skin formulation described below.

[0167] In this specification, useful hydrophilic surfactants (cationic, anionic, amphoteric, and amphoteric surfactants) may include a single surfactant or any combination of suitable surfactants. The exact choice of one (or more) surfactant depends on the pH of the formulation and the other components present.

[0168] Useful nonionic surfactants include condensation products of alkylene oxides and fatty acids (i.e., alkylene oxide esters of fatty acids), condensation products of alkylene oxides and 2 moles of fatty acids (i.e., alkylene oxide diesters of fatty acids), condensation products of alkylene oxides and fatty alcohols (i.e., alkylene oxide ethers of fatty alcohols), and condensation products of alkylene oxides and both fatty acids and fatty alcohols [i.e., the polyalkylene oxide moiety is esterified with the fatty acid at one end and etherified with the fatty alcohol at the other end (i.e., linked via an ether bond)]. Non-limiting examples of these alkylene oxide-derived nonionic surfactants include ceteth-6, ceteth-10, ceteth-12, ceteareth-6, ceteareth-10, ceteareth-12, steareth-6, steareth-10, steareth-12, steareth-21, PEG-6 stearate, PEG-10 stearate, PEG-100 stearate, PEG-12 stearate, PEG-20 glyceryl stearate, PEG-80 tallow glyceryl, PEG-10 glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80 glyceryl cocoate, PEG-200 tallow glyceryl, PEG-8 dilaurate, PEG-10 distearate, and mixtures thereof. Other useful nonionic surfactants include polyhydroxy fatty acid amide surfactants. Suitable nonionic surfactants include, but are not limited to, Steareth-21, Ceteareth-20, Ceteareth-12, sucrose cocoate, Steareth-100, PEG-100 stearate, and mixtures thereof. Other nonionic surfactants suitable for use in the formulations disclosed herein include sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C 30 C1-C of aliphatic alcohols 30 Fatty acid esters, C1-C 30 C1-C of aliphatic alcohols 30 Alkoxylated derivatives of fatty acid esters, C1-C 30 Alkoxylated ethers of aliphatic alcohols, C1-C 30Polyglyceryl esters of fatty acids, C1-C polyols 30 Esters, polyols C1-C 30 Examples include ethers, alkyl phosphates, polyoxyalkylene fatty acid ether phosphates, fatty acid amides, acyl lactylates, and mixtures thereof. Non-limiting examples of these emulsifiers include glyceryl stearate, sodium polyacryloyldimethyl taurate, polyglyceryl-3 cetyl ether, polyethylene glycol 20 sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soyasterol, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, polysorbate 60, glyceryl stearate, polyoxyethylene 20 sorbitan triolate (polysorbate 85), sorbitan monolaurate, sorbitan isostearate, sodium polyoxyethylene 4 lauryl ether stearate, polyglyceryl-4 isostearate, hexyl laurate, PPG-2 methyl glucose ether distearate, PEG-100 stearate, and mixtures thereof. Another group of nonionic surfactants useful herein are fatty acid ester blends based on a mixture of sorbitan or sorbitol fatty acid esters and sucrose fatty acid esters, where in each example the fatty acids are C8-C8. 24 or C 10 ~C 20 That is the case.

[0169] Furthermore, cationic surfactants such as dialkyl quaternary ammonium compounds are useful in this specification. Non-limiting examples of these cationic emulsifiers include stearamidopropyl PG-dimonium chloride phosphate, behenamidopropyl PG-dimonium chloride, stearamidopropyl ethyldimonium ethosulfate, stearamidopropyl dimethyl(myristyl acetate)ammonium chloride, stearamidopropyl dimethylcetearylammonium tosylate, stearamidopropyl dimethylammonium chloride, stearamidopropyl dimethylammonium lactate, and mixtures thereof. Non-limiting examples of quaternary ammonium salt cationic surfactants include cetylammonium chloride, cetylammonium bromide, laurylammonium chloride, laurylammonium bromide, stearylammonium chloride, stearylammonium bromide, cetyldimethylammonium chloride, cetyldimethylammonium bromide, lauryldimethylammonium chloride, lauryldimethylammonium bromide, stearyldimethylammonium chloride, stearyldimethylammonium bromide, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, lauryltrimethylammonium chloride, lauryltrimethylammonium bromide, and stearyl Examples include trimethylammonium, stearyltrimethylammonium bromide, lauryldimethylammonium chloride, stearyldimethylcetyldihydroxydimethylammonium chloride, dicetylammonium chloride, dicetylammonium bromide, dilaurylammonium chloride, dilaurylammonium bromide, distearylammonium chloride, distearylammonium bromide, dicetylmethylammonium chloride, dicetylmethylammonium bromide, dilaurylmethylammonium chloride, dilaurylmethylammonium bromide, distearylmethylammonium chloride, distearylmethylammonium bromide, and mixtures thereof. Additional quaternary ammonium salts include C 12 ~C 30 Examples include alkyl carbon chains derived from animal fat fatty acids or coconut fatty acids. The term "animal fat" refers to alkyl groups derived from animal fat fatty acids (usually hydrogenated animal fat fatty acids), and generally C 16 ~C18 It has a mixture of alkyl chains in the range of C. The term "coconut" refers to alkyl groups derived from coconut fatty acids, and is generally C 12 ~C 14 They have mixtures of alkyl chains in the range of . Examples of these quaternary ammonium salts derived from fat and coconut sources include difatdimethylammonium chloride, difatdimethylammonium methylsulfate, di(hydrogenated fat)dimethylammonium chloride, di(hydrogenated fat)dimethylammonium acetate, difatdipropylammonium phosphate, difatdimethylammonium nitrate, di(coconut alkyl)dimethylammonium chloride, di(coconut alkyl)dimethylammonium bromide, fat ammonium chloride, coconut ammonium chloride, and mixtures thereof. An example of a quaternary ammonium compound having alkyl groups with ester bonds is ditaloyloxyethyldimethylammonium chloride. Additional cationic surfactants are selected from behenamidopropyl PG-dimonium chloride, dilauryldimethylammonium chloride, distearyldimethylammonium chloride, dimyristyldimethylammonium chloride, dipalmityldimethylammonium chloride, distearyldimethylammonium chloride, stamidopropyl PG-dimonium chloride phosphate, stearamidopropyl ethyldiamonium ethosulfate, stearamidopropyl dimethyl(myristylacetate)ammonium chloride, stearamidopropyl dimethylcetearylammonium tosylate, stearamidopropyl dimethylammonium chloride, stearamidopropyl dimethylammonium lactate, and mixtures thereof. In some examples, the cationic surfactant is selected from behenamidopropyl PG-dimonium chloride, dilauryldimethylammonium chloride, distearyldimethylammonium chloride, dimyristyldimethylammonium chloride, dipalmityldimethylammonium chloride, and mixtures thereof.

[0170] Various anionic surfactants can also be used. Non-limiting examples of anionic surfactants include alcoyl isethionates, as well as alkyl and alkyl ether sulfates. Alcoyl isethionates, reaction products obtained by esterifying and neutralizing fatty acids with isethionic acid, typically have the formula RCOOCH2CH2SO3M (wherein R is an alkyl or alkenyl with approximately 10 to 30 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, and triethanolamine). For example, the fatty acid can be derived from coconut or palm kernel oil. Non-limiting examples of these isethionates include alcoyl isethionates selected from ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearoyl isethionate, and mixtures thereof. Salts of fatty acids and methyl taurine amides are also suitable. Alkyl and alkyl ether sulfates typically have the formulas ROSO3M and RO(C2H4O), respectively. xSO3M, where R is an alkyl or alkenyl having about 10 to about 30 carbon atoms, x is about 1 to about 10, and M is a water-soluble cation such as ammonium, an alkanolamine such as triethanolamine, a monovalent metal such as sodium and potassium, and a polyvalent metal cation such as magnesium and calcium. In some examples, in both alkyl and alkyl ether sulfates, R has about 8 to about 18 carbon atoms, or about 10 to about 16 carbon atoms, or about 12 to about 14 carbon atoms. Alkyl ether sulfates are typically produced as condensation products of ethylene oxide and a monohydric alcohol having about 8 to about 24 carbon atoms. The alcohol may be a synthetic product or may be derived from fats (e.g., coconut oil, palm kernel oil, animal fat). These alcohols react with ethylene oxide in a molar ratio of about 0 to about 10, or about 2 to about 5, or about 3 molars, and the resulting mixture, for example having an average of 3 moles of ethylene oxide per mole of alcohol, is sulfated and neutralized. Another suitable class of anionic surfactants is the sulfuric acid reaction product of the general formula R1-SO3-M, where R1 is selected from the group comprising linear or branched saturated aliphatic hydrocarbon radicals having about 8 to about 24 or about 10 to about 16 carbon atoms, and M is the aforementioned cation. Further other anionic synthetic surfactants include those classified as succinates, olefin sulfons having about 12 to about 24 carbon atoms, and β-alkyloxyalkane sulfons. Examples of these materials are sodium lauryl sulfate and ammonium lauryl sulfate. Other anionic surfactants suitable for use in formulations are succinates, examples of which include disodium N-octadecyl sulfosuccinate, disodium lauryl sulfosuccinate, diammonium lauryl sulfosuccinate, tetrasodium N-(1,2-dicarboxyethyl)-N-octadecyl sulfosuccinate, diamyl ester of sodium sulfosuccinate, dihexyl ester of sodium sulfosuccinate, and dioctyl ester of sodium sulfosuccinate. Other suitable anionic surfactants include olefin sulfonates having about 10 to about 24 carbon atoms.In addition to true alkenesulfonates and certain proportions of hydroxyalkanesulfonates, olefin sulfonates may contain trace amounts of other substances, such as alkendisulfonates, depending on the reaction conditions, the proportion of reactants, the nature of impurities in the starting olefins and olefin stocks, and side reactions during the sulfonation process. Another class of anionic surfactants suitable for use in formulations is the β-alkyloxyalkanesulfonate group. Other anionic substances useful herein are soaps of fatty acids (i.e., alkali metal salts, e.g., sodium or potassium salts) typically having about 8 to about 24 carbon atoms, or about 10 to about 20 carbon atoms. Fatty acids used in soap production can be obtained from natural resources such as glycerides of plant or animal origin (e.g., palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc.). Fatty acids can also be prepared synthetically.

[0171] Amphoteric and zwitterionic surfactants may also be included herein. Examples of amphoteric and zwitterionic surfactants that may be used in formulations are those in which the aliphatic radical can be linear or branched, and one of the aliphatic substituents contains about 8 to about 22 carbon atoms (or C8 to C8). 18 ), and one of them is broadly described as a derivative of aliphatic secondary and tertiary amines, comprising an anionic water-soluble group, such as a carboxyl, sulfonate, sulfate, phosphate, or phosphonate. Examples include alkyliminoacetates, as well as those of the formula RN[(CH2) m CO2M]2 and RNH(CH2) m These are iminodialkanoates and aminoalkanoates of CO2M, where m is 1 to 4 and R is C8 to C 22The surfactant is alkyl or alkenyl, where M is H, alkali metal, alkaline earth metal ammonium, or alkanol ammonium. Exemplary amphoteric surfactants for use in formulations may include cocoamphoacetate, cocoamphodiaacetate, lauroamphoacetate, lauroamphodiaacetate, and mixtures thereof. Also included are imidazolinium derivatives and ammonium derivatives. Specific examples of suitable amphoteric surfactants include sodium 3-dodecylaminopropionate, sodium 3-dodecylaminopropanesulfonate, N-alkyltaurines such as those prepared by reacting dodecylamine with sodium isethionate, N-higher alkylaspartates, and products marketed under the "Miranol" trademark. Other examples of useful amphoteric substances include phosphates such as coamidopropyl PG-dimonium chloride phosphate (marketed as Monaquat PTC by Mona Corp.).

[0172] Zwitterionic surfactants suitable for use in formulations are well known in the art and include surfactants broadly described as derivatives of aliphatic quaternary ammonium compounds, phosphonium compounds, and sulfonium compounds, where the aliphatic radical can be linear or branched, one of the aliphatic substituents contains about 8 to about 18 carbon atoms, and one contains an anionic group such as a carboxy, sulfonate, sulfate, phosphate, or phosphonate. Examples of betaines include cocodimethylcarboxymethyl betaine, lauryldimethylcarboxymethyl betaine, lauryldimethyl α-carboxyethyl betaine, cetyldimethylcarboxymethyl betaine, cetyldimethyl betaine (available from Lonza Corp. as Lonzaine 16SP), laurylbis-(2-hydroxyethyl)carboxymethyl betaine, stearylbis-(2-hydroxypropyl)carboxymethyl betaine, oleyldimethylγ-carboxypropyl betaine, laurylbis-(2-hydroxypropyl)α-carboxyethyl betaine, cocodimethylsulfopropyl betaine, stearyldimethylsulfopropyl betaine, lauryldimethylsulfoethyl betaine, laurylbis-(2-hydroxyethyl)sulfopropyl betaine, as well as amide betaine and amide sulfobetaine (in which the RCONH(CH2)3 radical is bonded to the nitrogen atom of the betaine), oleyl betaine (from Henkel as amphoteric Velvetex). Examples include higher alkyl betaines such as cocamidopropyl betaine (available from Henkel as Velvetex BK-35 and BA-35), as well as cocamidopropyl betaine.Other useful amphoteric and zwitterionic surfactants include sultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine (available as Mirataine CBS from Rhone-Poulenc), and alkanoyl sarcosinates corresponding to the formula RCON(CH3)CH2CH2CO2M, wherein R is alkyl or alkenyl of from about 10 to about 20 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, and trialkanolamine (e.g., triethanolamine). 20. Thickeners

[0173] Suitable thickeners for inclusion in the cosmetic dermatological formulations described herein include agents commonly used as additives or carriers for topical application to increase the viscosity of the formulation. Thickeners may also be used to improve the stability of the formulation.

[0174] More specifically, such examples include, but are not limited to, xanthan gum, acrylamide copolymers, agarose, amylopectin, bentonite, calcium alginate, calcium carboxymethyl cellulose, carbomer, carboxymethyl chitin, cellulose gum, dextrin, gelatin, hydrogenated tallow, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl starch, magnesium alginate, methyl cellulose, microcrystalline cellulose, pectin, various polyethylene glycols, polyacrylic acid, polyacrylate crosspolymer-6, poly-methacrylic acid, polyvinyl alcohol, various polypropylene glycols, sodium acrylate copolymers, sodium carrageenan, xanthan gum, and / or yeast β-glucan.

[0175] Furthermore, carboxylic acid polymers can be useful thickeners. Carboxylic acid polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acid, and salts and esters of these acrylic and substituted acrylic acid, where the crosslinker contains two or more carbon-carbon double bonds and is derived from polyhydric alcohols. Examples of commercially available carboxylic acid polymers that are useful thickeners for use in the formulations described herein include carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerythritol. Carbomers are available from BFGoodrich as the CARBOPOL® 900 series (e.g., CARBOPOL® 954). Furthermore, other suitable carboxylic acid polymer agents include acrylic acid C 10~30 Alkyl compounds and acrylic acid, methacrylic acid, or their short chains (i.e., C 1~4 Examples include copolymers with one or more monomers of alcohol esters, where the crosslinking agent is the allyl ether of sucrose or pentaerythritol. These copolymers are acrylate / acrylic acid C 10~30 Alkyl crosspolymers are well known and are commercially available from BFGoodrich as CARBOPOL® 1342, CARBOPOL® 1382, Pemulen TR-1, and Pemulen TR-2. Examples of useful carboxylic acid polymer thickeners used herein include carbomers and acrylates / C acrylates. 10~30 Examples include alkyl crosspolymers and mixtures thereof.

[0176] Further suitable thickeners may include ammonium acryloyldimethyltaurate / VP copolymer, SEPIMAX ZEN (polyacrylate crosspolymer-6), and / or SEPINOV WEO (hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer).

[0177] Furthermore, a wide variety of polysaccharides are useful as thickeners in this specification. Non-limiting examples of polysaccharide gelling agents include cellulose, carboxymethyl hydroxyethyl cellulose, cellulose propionate acetate carboxylate, hydroxyethyl cellulose, hydroxyethyl ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl hydroxyethyl cellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof. Alkyl-substituted celluloses are also useful in this specification. In these polymers, the hydroxyl groups of the cellulose polymer are hydroxyalkylated (e.g., hydroxyethylated or hydroxypropylated) to form hydroxyalkylated cellulose, which is then C via ether bonds. 10~30 They are further modified with linear or branched alkyl groups. Typically, these polymers are C 10~30These are ethers of linear or branched-chain alcohols and hydroxyalkylcellulose. Examples of useful alkyl groups used herein include those selected from stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (e.g., alkyl groups derived from coconut oil alcohols), palmityl, oleyl, linoleyl, linolenyl, ricinoleyl, behenyl, and mixtures thereof. Of particular interest among alkylhydroxyalkylcellulose ethers is the material having the CTFA designation cetylhydroxyethylcellulose, which is an ether of cetyl alcohol and hydroxyethylcellulose. This material is marketed by Aqualon Corporation (Wilmington, Del.) under the trademark name NATROSOL® CS Plus. Further examples can be found in The International Cosmetic Ingredient Dictionary and Handbook, the Cosmetic Bench Reference-Directory of Cosmetic Ingredients, publications provided by the United States Pharmacopeia (USP) and the National Pharmaceutical Collection (NF), and other references on cosmetic and pharmaceutical ingredients known in the art. Other useful polysaccharides include scleroglucan, a linear chain of (1-3) linked glucose units, with (1-6) linked glucose units every three units. A commercially available example is Clearogel® CS11 from Michel Mercier Products Inc. (Mountainside, NJ).

[0178] Other thickeners and gelling agents useful herein include materials primarily derived from natural sources. Non-limiting examples of these gelling gums include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran, dextran sulfate, potassium carrageenan, tragacanth gum, xanthan gum, and / or mixtures thereof. Furthermore, these formulations may also optionally contain polyacrylamide polymers, particularly nonionic polyacrylamide polymers including substituted branched or unbranched polymers. Among these polyacrylamide polymers, particularly those with the CTFA designation polyacrylamide and nonionic polymers having isoparaffin and laureth-7, are available from Seppic Corporation (Fairfield, NJ) under the trade name Sepigel 305. Other polyacrylamide polymers useful herein include multiblock copolymers of acrylamide and substituted acrylamide with acrylic acid and substituted acrylic acid. 21. Penetration enhancer

[0179] Penetration enhancers that may be included in cosmetic skin formulations are substances that promote the absorption of penetrating agents through the skin film by temporarily reducing the impermeability of the skin. Ideally, these materials should be pharmacologically inert, non-toxic, non-irritating, non-allergenic, odorless, tasteless, and colorless, and should have good solvent properties. Enhancers should not cause significant loss of body fluids, electrolytes, and other endogenous substances, and the skin should recover its barrier properties upon removal within an acceptable time. It is impossible for a single penetration enhancer to possess all the required properties. However, many enhancers exhibit many of these attributes, and these are described (for example, as outlined in Drug Development and Industrial Pharmacy 2000, 26, 1131-1140). 22. Antihistamines

[0180] Cosmetic skin preparations may contain antihistamines (also called histamine antagonists) as needed. These are substances that inhibit the action of histamine by blocking histamine from binding to histamine receptors, by inhibiting the enzymatic activity of histidine decarboxylase, which catalyzes the reaction that converts histidine to histamine, or by similar means. Examples of appropriate antihistamines include acribastine, azelastine, brompheniramine, buclidine, bromodifenhydramine, carbinoxamine, cetirizine, chlorpromazine, cyclidine, chlorpheniramine, chlorodiphenhydramine, cimetidine, clemastine, cyproheptadine, desloratadine, dexbrompheniramine, deschlorpheniramine, dexchlorpheniramine, dimenhydrinate, dimeth These include lenden, diphenhydramine, doxylamine, ebastine, embramin, famotidine, fexofenadine, lafutidine, levocetirizine, loratadine, meclozine, mirtazapine, nizatidine, olopatadine, orphenadrine, phenindamine, pheniramine, phenyltroxamine, promethazine, pyrilamine, quetiapine, ranitidine, roxatidine, rupatadine, triperenamine, and triprolidine.

[0181] Antihistamines may be included in cosmetic skin formulations described herein. In one example, the antihistamine may be included at a level of about 0.01% to about 10%, or about 0.5% to about 5%, relative to the weight of the formulation. The exact percentage of antihistamine to be used in the formulation depends on the specific anti-inflammatory agent used, because such agents may have different potencies. 23. Preservatives

[0182] Cosmetic dermatological formulations contain one or more preservatives as necessary to prevent the growth of microorganisms in the formulation. Suitable preservatives include, but are not limited to, glycerin-containing compounds (e.g., glycerin or ethylhexylglycerin or phenoxyethanol), 1,2-hexanediol, propanediol, benzyl alcohol, parabens (methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, etc.), sodium benzoate, ethylenediaminetetraacetic acid (EDTA), potassium sorbate, and / or grapefruit seed extract, or combinations thereof. More than one preservative may be contained in the formulation. Other preservatives are well known in the cosmetics industry and include sodium chloride, salicylic acid, DMDM ​​hydantoin, formaldehyde, chlorphenisine, triclosan, imidazolidinyl urea, diazolidinyl urea, sorbic acid, methylisothiazolinone, sodium dehydroacetate, dehydroacetic acid, quaternium-15, stearalkonium chloride, zinc pyrithione, sodium metabisulfite, 2-bromo-2-nitropropane, chlorhexidine digluconate, polyaminopropyl biguanide, benzalkonium chloride, sodium sulfite, sodium salicylate, citric acid, neem oil, various essential oils, lactic acid, and vitamin E (tocopherol).

[0183] Preservatives may be added to the cosmetic skin formulations described. In one example, the preservative is added at a level of about 0.01% to about 10%, or about 0.5% to about 5%, relative to the weight of the formulation. The exact percentage of preservative to be used in the formulation depends on the specific preservative used, because such agents may have different potencies. In some examples, the preservative(s) may be included in amounts ranging from about 0.1% to about 5%, preferably from about 0.3% to about 3%, relative to the weight of the formulation, as needed. Preferably, the formulation does not contain parabens. 24. Ceramide

[0184] Cosmetic skin formulations may contain one or more ceramides as needed. Suitable ceramides include, but are not limited to, ceramide AP, ceramide EOP, ceramide NS, ceramide NP, ceramide NG, and combinations thereof. In one example, ceramides are added at levels of approximately 0.01% to 10%, or approximately 0.5% to 5%, relative to the weight of the formulation. The exact percentage of ceramide to be used in a formulation depends on the specific ceramide being used, because such formulations may have different potencies. 25. Exfoliating agent

[0185] Cosmetic skin formulations may contain, as needed, one or more ceramides, selected from, but not limited to, alpha hydroxy acids such as lactic acid, glycolic acid, mandelic acid, tartaric acid, and malic acid, to promote the removal of dead cells and stimulate the formation of collagen and elastin. In some cases, exfoliants are added at levels of approximately 0.01% to 10%, or approximately 0.5% to 5%, relative to the weight of the formulation. The exact percentage of exfoliant to be used in a formulation depends on the specific exfoliant being used, as such agents may have different potencies.

[0186] Skin formulations may contain, as necessary, one or more additional substances (additives, carriers, or excipients), such as those described herein, which should provide some benefit to the purpose of the formulation. In some cases, the selected additional substance may result in enhanced potency of the formulation compared to a formulation that does not contain this additional substance. This enhanced potency may be additive (the sum of the potencies of the individual agents alone) or greater than additive (greater than the sum of the potencies of the individual agents alone). The decision of whether to include additional components or substances, and the selection of specific components or substances, depends on the specific use of the formulation. d. Forms of cosmetic skin preparations

[0187] The cosmetic dermatological formulations described may be any suitable physical form. Suitable forms include, but are not limited to, liquids, lotions, emulsions, gels, emulsions (i.e., macroemulsions, microemulsions, nanoemulsions, oil-in-water, silicone-in-water, water-in-oil, water-in-silicone, water-in-oil, water-in-water oil, and oil-in-water-in-oil emulsions), ointments, creams, serums, colloids, solutions, suspensions, dispersions, pastes, ointments, and oils. In some examples, cosmetic dermatological formulations may be present in at least part of a patch, a microneedle device, or form at least part of any other cosmetic or dermatologically acceptable formulation or device. In some examples, cosmetic dermatological formulations may be skin rejuvenation products, skin conditioners, or skin moisturizers. In some cases, cosmetic skin formulations exist in or form part of skin patches (i.e., iontophoresis patches, microprojection patches, microneedle patches), skin masks, tissue wipes, foundations, lip liners, lip glosses, lip balms, sunscreens, sunblocks, soaps, body scrubs, exfoliants (such as malic acid), cold creams, cleansers, rinses, and / or any other forms readily apparent to those skilled in the art.

[0188] In some specific cases, cosmetic dermatological formulations are serums, such as face serums. In some other specific cases, cosmetic dermatological formulations are skin moisturizer formulations. In yet another case, cosmetic dermatological formulations are scalp formulations, such as scalp serums.

[0189] The cosmetic skin formulations described may have any appropriate viscosity, depending on the form of the formulation. In some cases, the viscosity may be in the range of approximately 100 cps to approximately 1,000,000 cps, approximately 100 cps to approximately 500,000 cps, approximately 100 cps to approximately 100,000 cps, approximately 100 cps to approximately 75,000 cps, or approximately 1,000 cps to approximately 50,000 cps, as well as sub-ranges and individual viscosity values ​​that fall within the aforementioned ranges. III. Kit

[0190] The cosmetic skin formulations described herein may be provided as part of a cosmetic kit. The kit may include instructions for use, if necessary.

[0191] The kit may further include one or more different cosmetic dermatological formulations that may serve different purposes, such as providing different effects and / or improvements in the appearance of the skin. The kit may, as necessary, include one or more other dermatological formulations that are commercially available and not included in the scope of the cosmetic dermatological formulations described herein. Each of the cosmetic dermatological formulations and, as necessary, the dermatological formulations are typically provided in separate, suitable containers and / or compartments forming the kit.

[0192] In some examples, the kit may include at least one cosmetic skin formulation, which is in the form of a serum, and at least one other cosmetic skin formulation, which is a moisturizer. Such a kit may further include one or more other skin formulations, such as a skin cleanser. In certain examples, the serum is a facial serum. In some other examples, the kit may also include a scalp formulation (which may be in the form of a serum, if necessary).

[0193] In one example, the kit includes at least one cosmetic skin formulation in the form of a serum. In another example, the kit includes one cosmetic skin formulation in the form of a serum and one cosmetic skin formulation in the form of a moisturizer. In yet another example, the kit includes one cosmetic skin formulation in the form of a serum, one cosmetic skin formulation in the form of a moisturizer, and another skin formulation which is a skin cleanser. IV.How to use

[0194] The cosmetic dermatological formulations described herein are used to treat the skin. In one non-limiting example, a method for treating the skin is: (1) The process of applying the cosmetic skin preparation described to the subject's skin. Includes.

[0195] The subjects are typically mammals, such as humans.

[0196] In some cases, the cosmetic dermatological formulation is applied topically to any area of ​​the subject's face, neck, neckline, décolleté, scalp, hands, palms, arms, legs, feet, soles of feet, chest, breasts, back, abdomen, buttocks, and / or any other skin area. In some cases, the cosmetic dermatological formulation is applied to the face. In some specific cases, the cosmetic dermatological formulation is in a form suitable for application to the skin of the subject's face and / or scalp, and the formulation is in the form of a serum, if necessary.

[0197] In some cases, cosmetic skin formulations, once applied, remain on the skin for a period of up to 24 hours, up to 20 hours, up to 15 hours, up to 10 hours, up to 8 hours, up to 7 hours, up to 6 hours, up to 5 hours, up to 4 hours, up to 3 hours, up to 2 hours, or up to 1 hour.

[0198] In some other cases, skin formulations remain on the skin for approximately 1 to 30 minutes, 1 to 20 minutes, 1 to 15 minutes, 1 to 10 minutes, 5 to 30 minutes, 5 to 20 minutes, 5 to 15 minutes, or 5 to 10 minutes.

[0199] In further examples, cosmetic skin formulations may be removed from the skin after step (1) if necessary, for example, by rinsing the skin with water or washing the skin with a cleansing agent and water. In certain other examples, the formulation is completely absorbed by the skin, so it is not necessary to remove the formulation from the skin during application.

[0200] In some cases, cosmetic dermatological formulations may also be applied (i.e., before, after, or simultaneously) in combination with the use of dermatological devices to alter the penetration properties of the skin, such as lasers, light, infrared, radiofrequency, ultrasound, electroporation, sonophoresis, thermal, plasma, and / or high-pressure devices, and / or any combination thereof (including combined devices). Any other commonly used means of administration may also be available.

[0201] In some cases, cosmetic skin formulations are supplied with instructions for use / application. In one non-limiting example, the instructions may include guidance such as applying a certain amount of the skin formulation product to the skin (e.g., face and / or body) at least once a day (morning or evening) or twice a day (morning and evening) after using a cleanser and / or lotion, before applying any other skin care formulation, and / or after a typical skin regimen used by the user.

[0202] In some cases, cosmetic skin formulations are, for example, scalp formulations applied daily in the form of a serum. Scalp formulations are applied to dry or damp hair, rubbed into the scalp, and the formulation can be dispersed and absorbed into the subject's scalp skin. In some cases, scalp formulations are applied to the subject's natural parting and / or along the hairline. a. Evaluating the efficacy of cosmetic skin preparations.

[0203] Methods and processes for testing and evaluating the efficacy of cosmetic dermatological formulations are well known. For example, skin maintenance, prevention, amelioration and / or treatment of signs of skin aging, protection and / or improvement of skin conditions, and prevention and / or treatment of skin defects are functional characteristics that can be visualized, analyzed, measured and quantified using many techniques well known to experts in cosmetic dermatological treatments.

[0204] In some cases, the described skin formulations may be evaluated for their ability to reduce fine lines, wrinkles, skin folds, and skin roughness, either by direct, non-contact quantification of a person using fringe projection (FOITS = High-Speed ​​Optical In vivo Topometry System; DERMATOP® or PRIMOS® system), or by silicone replication of skin areas subsequently analyzed by a technique called “drop shadowing,” or by a FIOTS system, or by a Canfield VISIA® instrument. Changes in facial volume and shape may be quantified using a non-contact surface texture acquisition system with fringe projection FIOTS systems. Changes in the skin barrier may be quantified by measuring transepidermal water loss (TEWL) using TEWAMETER®, VAPOMETER®, DERMALAB®, and / or AQUAFLUX® instruments. Loss of skin firmness and / or elasticity and / or tone, as well as fatigue, can be quantified using CUTOMETER®, REVISCOMETER®, AEROFLEXMETER®, DYNASKIN®, BALLISTOMETER®, TWISTOMETER®, and / or DERMALAB® instruments. Dull skin color, loss of skin tone uniformity, changes in pigmentation (hypopigmentation and hyperpigmentation), localized redness, loss of skin color clarity and radiance, pigmented spots, rosacea, and dark circles can be directly measured using MEXAMETER®, CHROMAMETER®, COLORMETER®, Canfield VISIA®, Canfield VISIA-CR®, SIASCOPE®, GONIOLUX®, or confocal laser microscopes, and / or by specific color analysis on photographs (possible by imaging techniques using polarized crossed and parallel light). The number and size of facial pores can be quantified by the silicone replication techniques described above, or by specific analysis on photographs (which can be performed using a video microscope or macroscopic imaging system).Atrophy and thinning of the skin, epidermis, dermis, or subcutaneous tissue (e.g., in the study of slimming agents) can be measured by measuring TEWL (e.g., in the study of the epidermis) or by ultrasound and / or confocal laser microscopy. Skin fiber density can be quantified by ultrasound and then by image analysis. Cellulite is quantified either directly by a non-contact surface texture acquisition system using fringe projection (FOITS) or indirectly by measuring the length of the dermal-subcutaneous tissue junction with ultrasound. Stretch marks are quantified either directly using a non-contact surface texture acquisition system using fringe projection (FOITS) or directly by silicone replication techniques. Skin softness can be measured directly by friction research techniques using friction measuring devices or indirectly by silicone replication techniques. Changes in collagen, extracellular matrix components, and / or connective tissue fibers can be quantified by histology, confocal laser microscopy, UV spectroscopy, SIASCOPE®, and / or multiphoton spectroscopy. All visible changes (including, but not limited to, fine lines, wrinkles, folds, texture, sagging, loss of elasticity, discoloration, tone, pigmentation, and redness) can be quantified directly or photographically, with or without a visual scoring system (e.g., a four-level severity scale), with or without a trained examiner (or panel of examiners).

[0205] Some of the benefits and effects associated with the use of the dermatological formulations described herein may be evaluated by trained individuals or panels of trained individuals using scoring systems or scales. It is possible to determine the increase / decrease in scores attributable to the application of the cosmetic dermatological formulation by comparing the scores of skin condition (e.g., fine lines, wrinkles, folds, texture, sagging, loss of elasticity, color, tone, pigmentation, redness, etc.) before and after treatment with the cosmetic dermatological formulation. It is also possible to determine the increase / decrease in scores over time attributable to the application of the cosmetic dermatological formulation by comparing the scores of skin condition (e.g., fine lines, wrinkles, folds, texture, sagging, loss of elasticity, color, tone, pigmentation, redness, etc.) at two different time points between the application of the cosmetic dermatological formulation (e.g., after one or two applications of the formulation daily, and at weeks 2 and 5). In some cases, where a higher score indicates an improvement in skin characteristics or condition, the score after treatment with the cosmetic dermatological formulation increases by at least 1 point or more. In some cases, if a lower score indicates improvement in skin characteristics or condition, the score after treatment with a cosmetic dermatological formulation decreases by at least 1 point or more. In some cases, if a higher score indicates improvement, the score after treatment with a cosmetic dermatological formulation increases by at least approximately 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% or more compared to the score before treatment with the cosmetic dermatological formulation. In some cases, if a lower score indicates improvement, the score after treatment with a cosmetic dermatological formulation decreases by at least approximately 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% or more compared to the score before treatment with the cosmetic dermatological formulation.

[0206] In some cases, the effect on one or more skin properties is assessed on a given number of point-based ordinal scales, such as 0-5 scales (0 = no effect, 1 = very slight effect, 2 = mild effect, 3 = moderate effect, 4 = large effect), and this effect is assessed by looking at the change in score between two time points (e.g., before and after the initial treatment, or between two time points, e.g., before the initial treatment and at time points ranging from 1 week, 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 1 year after the treatment). For example, rank scores may be assigned to skin characteristics before application of a skin formulation (including, but not limited to, facial erythema, fine lines, wrinkles, brightness / radiance, tactile skin roughness, visual skin roughness, and / or overall appearance) and may be compared to scores at a second (subsequent) time point after one or more treatments with the skin formulation. In some cases, the comparison is between scores at two time points after application of the formulation to the skin (e.g., in the case of repeated applications over time). Scores may change between two given time points during treatment with the cosmetic skin formulation (e.g., between week 1 and week 4). In some cases, scores increase between two given time points if an increase is considered desirable. In some cases, scores decrease between two given time points if a decrease is considered desirable. In some cases, if possible on the selected ordinal scale, the score increases or decreases by at least 1 point, which indicates improvement of desired effects on the skin (e.g., brightness / radiance, overall appearance) and / or amelioration of undesirable effects (e.g., facial erythema, wrinkles, skin roughness) as a result of using the skin formulation.

[0207] In some cases, a skin formulation may have an effect on one or more skin properties compared to untreated skin or a control skincare formulation. This effect may be an improvement in one or more desirable skin properties and / or a reduction / decreasation of one or more undesirable skin properties. For example, one or more properties may include, but are not limited to: improved skin texture, improved skin elasticity when pinched or pressed, improved skin firmness, reduced skin redness, reduced skin inflammation, increased smoothness of lines and / or wrinkles, reduced fine lines and / or wrinkles, reduced visibility and / or prominence of fine lines and / or wrinkles, improved skin smoothness, improved skin softness, improved skin hydration, improved skin plumpness, reduced skin dryness, reduced skin peeling, improved skin brightness, improved skin radiance, improved skin appearance, or improved skin redness, or any combination thereof. Improvements in one or more properties of the skin can be evaluated using various methods known in the art, including the methods described herein.

[0208] In some cases, the skin formulation is a serum, and after a certain period of time, the skin's barrier function, luster, hydration, smoothness, firmness, elasticity, texture, and / or brightness are improved compared to the skin before the serum was applied to the subject's skin, and / or redness, lines, and / or wrinkles are reduced compared to the skin before the serum was applied to the subject's skin. Such improvements or reductions may be evaluated, for example, by visual and / or tactile grading, or by other appropriate methods described herein, after a certain period of time, compared to the skin before the serum was applied to the subject's skin. 1. Gene expression analysis

[0209] In some cases, skin formulations may be evaluated for their ability to upregulate or downregulate the expression of one or more genes after one or more applications to the skin.

[0210] Gene expression may be assessed using standard methods known in the field, which may include determining target mRNA levels in a cell sample. RNA may be extracted from cells using RNA extraction techniques, including, for example, acid phenol / guanidine isothiocyanate extraction (RNAzol B; Biogenesis), RNeasy RNA preparation kits (Qiagen), or PAXgene (PreAnalytix, Switzerland). Typical assay forms utilizing ribonucleic acid hybridization include nuclear run-on assays, reverse transcription PCR (RT-PCR), quantitative PCR analysis, RNase protection assays, Northern blotting, in situ hybridization, sequential gene expression analysis (SAGE), differential or incremental hybridization, microarrays, and sequencing techniques such as next-generation sequencing (NGS) and / or RNA-Seq. The analysis may involve the analysis of one, two, three, four, five or more individual targets, and / or the analysis of the entire transcriptome. The transcriptome refers to the set of all RNA-coding transcripts, and optionally all non-coding transcripts, in a single cell or a population of cells.

[0211] Gene expression analysis can be a comparative analysis of gene expression under two or more different conditions and / or between two or more different cell types. For example, in some forms, the gene expression of one or more targets or the whole transcriptome before treatment with a cutaneous formulation is compared to the gene expression of one or more targets or the whole transcriptome after one or more treatments with a cutaneous formulation. In some forms, the gene expression of one or more targets or the whole transcriptome after one or more treatments with a cutaneous formulation is compared to the gene expression of one or more targets or the whole transcriptome after one or more additional subsequent treatments with a cutaneous formulation.

[0212] For example, skin formulations can be evaluated in vitro at the gene level based on changes in the human transcriptome from cultured human 3D skin tissue models such as EPIDERM-FT®. Based on this, differential gene expression can be quantified using microarray methods such as the CLARIOM® S microarray method. Such a test method allows whole gene expression profiling from 21,448 well-annotated genes analyzable with the Affymetrix Human CLARIOM® S array, and significant expression changes can be filtered / identified using a multiplier change threshold: <-2 or >2 relative to placebo or no treatment. Typically, the genes evaluated affect or regulate (i.e., upregulate or downregulate) enhancement of skin barrier function, development of the outer stratum corneum, and / or outer stratum corneum lipid synthesis. Examples of such gene expression tests are described below and in the Examples section.

[0213] In some cases, when tested for gene expression, skin formulations may upcontrol or downcontrol one or more of the following genes: involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), filaggrin (FLG), loricrin (LOR), and any combination thereof, as needed.

[0214] In some cases, when tested for gene expression, skin formulations may upcontrol or downcontrol one or more of the following genes: TNF-α, interleukin-6, and interleukin-8, and all of them as needed.

[0215] In other examples, when tested for gene expression, the skin formulation upregulates one or more of the following genes: involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), filaggrin (FLG), loricrin (LOR), and combinations thereof, and all of them as appropriate. The skin formulation downregulates one or more of the following genes: TNF-α, interleukin-6, and interleukin-8, and, as appropriate, one or more of kappa light chain polypeptide gene enhancer nuclear factor 1 (NFKB1) in B cells, and all of them as appropriate.

[0216] In some cases, skin formulations modulate (i.e., upregulate or downregulate) genes associated with enhancing skin barrier function, including ceramide synthase 1 (CERS1), ceramide synthase 2 (CERS2), ceramide synthase 3 (CERS3), ceramide synthase 4 (CERS4), ceramide synthase 5 (CERS5), ceramide synthase 6 (CERS6), tight junction protein 1 (TJP1), occludin (OCLN), filaggrin (FLG), prostaglandin-endoperoxidase synthase 2 (PTGS2), and one or more of the following in B cells: kappa light chain polypeptide gene enhancer nuclear factor 1 (NFKB1), involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), loricrin (LOR), and combinations thereof.

[0217] In other examples, when tested for gene expression, skin formulations upregulate or downregulate one or more of the following genes of outer stratum corneum development: loricrin (LOR), small proline-rich protein 1A (SPRR1A), small proline-rich protein 1B (SPRR1B), small proline-rich protein 2A (SPRR2A), small proline-rich protein 2B (SPRR2B), small proline-rich protein 2D (SPRR2D), small proline-rich protein 2E (SPRR2E), small proline-rich protein 2F (SPRR2F), small proline-rich protein 2G (SPRR2G), small proline-rich protein 3 (SPRR3), and small proline-rich protein 4 (SPRR4), as well as combinations thereof.

[0218] In other examples, when testing gene expression, skin formulations may target the following genes that regulate outer stratum corneum lipid synthesis: UDP-glucose ceramide glucosyltransferase (UGCG), fatty acid synthase (FASN), late stratum corneum 1A (LCE1A), late stratum corneum 1B (LCE1B), late stratum corneum 1C (LCE1C), late stratum corneum 1D (LCE1D), late Upregulating or downregulating one or more of the following: late keratinized membrane 1E (LCE1E), late keratinized membrane 1F (LCE1F), late keratinized membrane 2A (LCE2A), late keratinized membrane 2B (LCE2B), late keratinized membrane 2C (LCE2C), late keratinized membrane 2D (LCE2D), late keratinized membrane 3A (LCE3A), late keratinized membrane 3B (LCE3B), late keratinized membrane 3C (LCE3C), late keratinized membrane 3D (LCE3D), late keratinized membrane 3E (LCE3E), late keratinized membrane 4A (LCE4A), late keratinized membrane 5A (LCE5A), and late keratinized membrane 6A (LCE6A), or any combination thereof. 2. Clinical research on skin formulations

[0219] Skin formulations can be evaluated using clinical studies. In one non-limiting example, if a group of subjects is studied using a skin formulation once or twice daily, according to the instructions provided to the study participants, over a period of time, for example, over approximately three months or 90 days of use at home, the clinical study may rely on any combination of expert visual / tactile grading, corneometer measurements, TEWL measurements, cutometer measurements, vivaScope measurements, SkiCon measurements, and self-report questionnaires.

[0220] The efficacy of skin formulations for improving skin elasticity and firmness can be evaluated by aspiration, for example, using a Cutometer®. The efficacy of formulations for maintaining healthy skin, or skin conditioning efficacy, can be evaluated by transepidermal water loss (TEWL) measurement, for example, using a Tewameter®.

[0221] Exemplary parameters for clinical research are provided below. However, clinical research in the field of skincare can be diverse and can be designed in any appropriate manner. Exemplary research methods:

[0222] A rinse-off product may be used by the research subject before the first application of the skin formulation being evaluated. Skin formulations are supplied to subjects along with instructions for use, to be followed accordingly. Illustrative instructions for use are as follows:

[0223] After cleansing / toning, apply a generous amount (1-2 pumps) of the formulation to the face and forearms twice daily (morning and evening) before applying the research participant's regular regimen. No other serums / moisturizers should be used. Each research participant should indicate whether they used the product each day. Exemplary research procedure: First visit - rinsing period (-5 days):

[0224] A rinse-off product is provided to the subjects and used on their face and forearms for five consecutive days prior to their second study visit, in place of their usual facial cleanser. Subjects use a usage log to track the progress of rinsing.

[0225] Participants who met the registration criteria were provided with a rinse-off product, which they used on their face and forearms for five consecutive days prior to their second study visit, in place of their usual facial cleanser. Participants were given a usage log to track the progress of the rinse-off. Participants were instructed not to apply any creams or moisturizers to their face or forearms starting two days before their second visit and throughout the entire study period. Participants were also instructed to come to all study visits without makeup. At their next visit, participants brought their log and the rinse-off product and washed their face 2.5 hours before their appointment. Visit 2 - Baseline (Day 1 of the study):

[0226] Subjects visit the testing facility where their eligibility is verified, their record sheets are checked, and rinse products are collected. If accepted into the study, subjects acclimate to indoor environmental conditions (temperature 20-22°C and relative humidity 30-50%) for at least 30 minutes prior to evaluation. Baseline measurements are then taken, and the subject's face is visually and tactilely evaluated by a professional scorer. Corneometer, SkiCon, and TEWL assessments are also performed using the forearm, and Vivascope and Cutometer assessments are conducted on the face.

[0227] After the baseline assessment is complete, the skin formulation will be applied to the face and forearm, followed by a visual assessment of the face by a specialist, as well as a reassessment of the forearm using a corneometer, SkiCon, and TEWL. The subject will also complete a Self-Report Questionnaire (SPQ). The subject will then be given the skin formulation and instructions for use, to be used as directed over the next three months upon returning home. The subject will also thoroughly wash their face at least 2.5 hours prior to each visit. Day 3 of hospital visit - Day 7 of study:

[0228] After using the product at home for 7 days (as directed), the subject returns to the testing facility. The test item is weighed, and a record sheet is checked for compliance with regulations. The subject also acclimates to indoor environmental conditions (temperature 20-22°C and relative humidity 30-50%) for at least 30 minutes prior to evaluation. Subsequently, a professional evaluator visually and tactilely assesses the subject's face, performing Corneometer, SkiCon, and TEWL assessments on the forearm, and Cutometer assessments on the face. The subject also completes a self-awareness questionnaire. Day 4 of hospital visit - Day 30 of study:

[0229] After using the product at home for 30 days (as directed), the subject returns to the testing facility. The test item is weighed, and a record sheet is checked for compliance with regulations. The subject also acclimates to indoor environmental conditions (temperature 20-22°C and relative humidity 30-50%) for at least 30 minutes prior to evaluation. The subject's face is visually and tactilely evaluated by a professional scorer, and the forearm is used to assess the Corneometer, SkiCon, and TEWL scores. The subject also completes a self-awareness questionnaire. Day 5 of hospital visit - Day 60 of study:

[0230] After using the product at home for 60 days (as directed), the subject returns to the testing facility. The test item is weighed, and a record sheet is checked for compliance with regulations. The subject also acclimates to indoor environmental conditions (temperature 20-22°C and relative humidity 30-50%) for at least 30 minutes prior to evaluation. A professional scorer visually and tactilely evaluates the subject's face, assesses the Corneometer, SkiCon, and TEWL using the forearm, and performs a VivaScope assessment on the face. The subject also completes a self-awareness questionnaire. Day 6 of hospital visits - Day 90 of the study (final visit):

[0231] After using the product at home for 90 days (as directed), the subjects return to the testing facility.

[0232] The same measurements and tests as those performed during visit 5 were carried out.

[0233] Each subject's participation is considered complete once all evaluations are finished and all record sheets and test materials have been received. Exemplary visual evaluation: Expert visual and tactile grading:

[0234] Visual assessments were performed on the face at baseline, immediately after use (1 hour), and on days 7, 30, 60, and 90. Tactile assessments were also performed on the face at baseline, and on days 7, 30, 60, and 90. The same professional evaluator assessed all subjects throughout the study period according to the following grading scale. The subjects' faces were illuminated by a 60-watt pearl bulb approximately 30 cm from the site. The PCR clinical grading scale that may be used in the study is shown in Figure 3A. Instrumental evaluation: Corneometer

[0235] Moisture measurement is performed using a Corneometer CM825 (Courage and Khazaka, Germany). This instrument relies on the dielectric constant, a physical property of water (which is relatively high and therefore affects the capacitance of a capacitor). Any change in dielectric constant due to fluctuations in skin moisture content changes the capacitance of a precision capacitor within the instrument. These fluctuations are electronically detected by the Corneometer and converted into numerical values.

[0236] Three readings are taken at the test site on the forearm using the corneometer probe attachment, with the corneometer probe attachment pressed against a dry tissue between each evaluation. The subject is in a controlled environment (temperature 20-22°C and relative humidity 30-50%) for at least 15 minutes before any evaluation is performed. If one measurement is greater than ±10 units from the other measurements (outlier), a fourth measurement is taken.

[0237] Measurements are taken at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. SkiCon

[0238] Skin conductivity is an alternative method for measuring skin moisture, derived from changes in the electrical properties of the stratum corneum (SC). This device can overcome the problems of erroneous or inaccurate readings that occur in capacitance and impedance measurements due to external influences. SkiCon can mitigate these influences by applying a higher frequency of 3.5 MHz to closely spaced electrodes within a probe that maintain an electric field within the skin surface.

[0239] The SkiCon 200EX (IBS co., Hamamatsu, Japan) measures skin conductivity using a fixed high-frequency current of 3.5 MHz. The device displays conductivity readings in microsiemens (μS) in the range of 0 to 1999. All conductivity measurements are displayed after a 3-second reading interval.

[0240] Measurements are taken on the forearm at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. Transepidermal water loss (TEWL) using Tewameter® probe

[0241] Water evaporation from the skin is a normal part of skin metabolism. However, even a slight impairment of the skin's barrier function increases water loss. Transepidermal water loss can be measured using the Tewameter™300 probe (Courage and Khazaka, Cologne, Germany). This method is an effective way to measure skin barrier function. The amount of water evaporation, i.e., TEWL, is measured in g / m³ based on the diffusion principle in an open chamber. 2 The density gradient is measured as / h. The density gradient is measured indirectly by two sets of sensors in the probe attachment (one set for temperature and the other set for relative humidity). This density gradient is then analyzed by a microprocessor in the instrument.

[0242] Measurements are taken on the forearm at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. Evaluation of VIVASCOPE(registered trademark) 1500-Collagen:

[0243] The structure and appearance of collagen, as observed using a confocal laser scanning microscope, are determined by the relationships between reticular, coarse, aggregated, and curled collagen fibers, and these change with age. Youthful, healthy skin primarily exhibits fine reticular fibers. With age, the proportion of fine reticular fibers gradually decreases, and in older adults, coarse, aggregated, and curled collagen fibers become dominant. These structural changes are recognizable in confocal images. As skin ages, the collagen network in the dermis becomes increasingly fragmented, characterized by short, less organized fibers that accumulate as degraded collagen fragments. The younger and healthier the skin, the larger, more diffuse, and less fragmented the collagen structure is.

[0244] In Vivascope® evaluations, subjects are placed in a controlled environment (temperature 20-24°C, relative humidity 35-50%) for 30 minutes prior to any evaluation. Measurements are taken at baseline, at day 60, and at day 90 from the crow's feet area at the outer corner of the right eye.

[0245] The test area is captured using VivaCam, allowing for correlation between confocal images and photographic images.

[0246] Collagen structure (i.e., the fragmentation and density of collagen in the papillary layer and superficial dermis) is visualized in vivo using a confocal laser scanning microscope (VIVASCOPE® 1500, VivaScope GmbH, Munich, Germany). This allows visualization of the cellular ultrastructure as optical cross-sections with a horizontal resolution of up to 1.25 μm and a vertical resolution of 3–5 μm, at a maximum depth of 200 μm down to the superficial dermis. Collagen fibers appear as white structures.

[0247] Approximately 40 individual images (500 μm × 500 μm) are acquired using a 5 μm scanning process, and an image stack is created. Only images targeting the collagen network (in the papillary layer and superficial dermis) are analyzed. Baseline images are compared with images acquired on day 60 and separately with images acquired on day 90. Each image is graded by a specialist on a visual analog scale for collagen fragmentation and density. The PCR clinical grading scale used for Vivascope® evaluation of collagen is shown in Figure 3B. Cutometer® measures firmness (R0) / elasticity (R2):

[0248] The viscoelastic properties (elasticity and firmness) of the skin can be measured at baseline, on day 7, and on day 90 using the Cutometer® MPA 580 (Courage and Khazaka, Germany). The measurement principle is based on suction. Negative pressure is created inside the device, and the skin is drawn into the opening of the probe.

[0249] Inside the probe, the penetration depth is measured by a non-contact optical measurement system. This optical measurement system includes a light source and a receiver, as well as two opposing prisms that project light from the transmitter to the receiver. The light intensity changes due to the penetration depth into the skin. Passive stretch measurements are recorded. These measurements can be displayed as a curve at the end of each measurement using Windows®-based software. Measurement mode 1 involves constant suction of 400 mbar for 5 seconds, followed by a 3-second relaxation period, repeated three times. The elastic parameters measured are R2 and R0, which are indicators of firmness, and the average value of the repetitions (e.g., 3 repetitions) is reported. The following R parameters can be calculated using the Cutometer® MPA 580:

[0250] R0: This parameter represents the passive behavior of the skin in response to force.

[0251] R1: The ability of skin to return to its original state.

[0252] R2: Total modulus of elasticity. The closer the value is to 1 (100%), the higher the elasticity of the curve, making it a very important parameter.

[0253] R3: The maximum amplitude of the final suction curve after repeated suction. Since the amplitude increases with each new suction, the "fatigue effect" on the skin is visible.

[0254] R4: The final minimum amplitude compared to the initial curve; the skin's "fatigue effect" is visible because the ability to re-deform decreases with each new suction.

[0255] R5: Net modulus of elasticity; the higher the value, the more elastic the skin.

[0256] R6: The proportion of viscoelasticity in the elastic portion of the curve. A smaller value indicates higher elasticity.

[0257] R7: The ratio of the elastic modulus to a perfect curve; the closer the value is to 1 (100%), the more elastic the skin is.

[0258] R8: Skin recovery. The closer the value is to R0, the greater the skin's ability to return to its original state.

[0259] R9: Represents the fatigue effect on the skin after repeated suction and release. A smaller R9 indicates less fatigue.

[0260] Cutometer® can also be used to calculate other skin parameters, including the F and Q parameters. The F parameters are regional parameters that can only be measured in Mode 1, and some require 10 repetitions in Mode 1. The Q parameter can be measured to evaluate the correlation between skin age and skin viscoelastic recovery. Self-awareness questionnaire:

[0261] Research subjects can be instructed to complete a self-report questionnaire several days after the procedure, for example, on day 1 (immediately after use, up to 1 hour), day 7, day 30, day 60, and day 90. b. Effects of skin preparations on the skin

[0262] A method of treating the skin using the above-described formulation can provide a skin rejuvenation effect and / or improvement of skin condition compared to the skin before step (1), as evaluated by visual inspection after step (1).

[0263] In some cases, this method provides effects such as maintaining healthy skin, repairing damaged skin, enhancing skin repair after cosmetic and / or dermatological procedures, enhancing wound healing, or a combination thereof.

[0264] In yet another example, this method can treat, alleviate, or improve one or more visible signs of skin aging, which may include, but are not limited to, fine lines, wrinkles, enlarged pores, roughness, dryness, redness, loss of elasticity, loss of volume, atrophic skin, stretch marks, puffy eyes, dark circles (under the eyes), and combinations thereof.

[0265] Treating, mitigating, or improving signs of skin aging can include delaying, minimizing, and / or preventing visible and / or tactile discontinuities in the skin (e.g., unevenness in skin texture that can be detected visually or tactilely), or improving discontinuities in the skin, for example, reducing, minimizing, and / or eliminating them.

[0266] Certain benefits of using cosmetic skin formulations by the method described (e.g., moisturizing, soothing, calming, firming, smoothing, etc.) may be observed within a few hours (i.e., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 hours) to a few days (i.e., about 1, 2, 3, 4, 5, 6, or 7 days) after topical application of the formulation according to this method. In some cases, it may take several weeks (i.e., about 1, 2, 3, or 4 weeks) or at least several months (i.e., about 1, 2, 3, 4, 5, or 6 months) to observe the benefits (e.g., anti-aging, wrinkle reduction, skin brightening, anti-redness, improvement of atrophy, wound healing, etc.). In certain cases, the skin formulation is applied to the skin at least once or twice a day. However, determining the effective dose of any formulation to achieve the desired effect is within the ordinary state of the art in this field.

[0267] The aforementioned effects can be evaluated using appropriate techniques / methods that are generally known in the field of skincare, as described above.

[0268] In some cases, the method improves the brightness, gloss, and / or lightness of the skin by visual grading compared to the skin before step (1'). In some cases, the brightness, gloss, and / or lightness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from about 1% to 100% of the brightness, gloss, and / or lightness of the skin. In some other cases, the brightness, gloss, and / or lightness of the skin is improved by at least about 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from about 75% to 100% of the brightness, gloss, and / or lightness of the skin. In other examples, skin brightness, gloss, and / or lightness are improved by at least approximately 90%, 95%, or 100%, or by an amount ranging from approximately 90% to 100%.

[0269] In some cases, this method reduces or eliminates skin redness by visual grading compared to the skin before step (1'). In some cases, skin redness is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from approximately 1% to 100% of skin redness. In some other cases, skin redness is reduced by at least approximately 60%, 65%, 70%, 75%, or 80%, or by an amount ranging from approximately 60% to 80% of skin redness. In other cases, skin redness is reduced by at least approximately 70%, 75%, or 80%, or by an amount ranging from approximately 70% to 80%.

[0270] In some cases, the method improves the visible or tactile texture and / or smoothness of the skin compared to the skin before step (1') by visual and / or tactile grading. In some cases, the visible or tactile texture and / or smoothness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from about 1% to 100% of the visible or tactile texture and / or smoothness of the skin. In some other cases, the visible or tactile texture and / or smoothness of the skin is improved by at least approximately 30%, 35%, 40%, 45%, or 50%, or by an amount ranging from approximately 30% to 50%. In yet another case, the visible or tactile texture and / or smoothness of the skin is improved by at least approximately 40%, 45%, or 50%, or by an amount ranging from approximately 40% to 50%.

[0271] In some cases, this method improves skin hydration and / or moisturization compared to the skin before step (1'), as measured by a corneometer and / or SkiCon value. In some cases, SkiCon is used to assess skin hydration. In some cases, skin hydration and / or moisturizing improve by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or by an amount ranging from approximately 1% to 200% of skin hydration and / or moisturizing. In some other cases, skin hydration and / or moisturizing improves by at least approximately 90%, 95%, 100%, 105%, 110%, 115%, 120%, or 125%, or by an amount ranging from approximately 90% to 125%. In yet another case, skin hydration and / or moisturizing improves by at least approximately 100%, 105%, 110%, or 115%, or by an amount ranging from approximately 100% to 115%.

[0272] In some cases, this method reduces transepidermal water loss by the skin and improves the skin's barrier function compared to the skin before step (1'), as measured by Tewameter® values. In some cases, transepidermal water loss by the skin is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or by an amount ranging from about 1% to 50%. In some other cases, transepidermal water loss by the skin is reduced by at least about 20%, 25%, 30%, 35%, or 40%, or by an amount ranging from about 20% to 40%.

[0273] In other examples, transepidermal water loss by the skin is reduced by at least approximately 30%, 35%, or 40%, or by an amount ranging from approximately 30% to 40%.

[0274] In some cases, the skin barrier function is improved by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from approximately 1% to 35%. In some other cases, the skin barrier function is improved by at least approximately 20%, 25%, 30%, or 35%, or by an amount ranging from approximately 20% to 35%. In yet another case, the skin barrier function is improved by at least approximately 25%, 30%, or 35%, or by an amount ranging from approximately 25% to 35%.

[0275] In some cases, this method improves skin firmness and / or elasticity compared to the skin before step (1'), as measured by cutometer® R2 and R0 values. In some cases, skin firmness and / or elasticity is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, or 30%, or by an amount in the range of about 1% to 30% of skin firmness and / or elasticity. In some other cases, skin firmness and / or elasticity is improved by at least about 15%, 20%, 25%, or 30%, or by an amount in the range of about 15% to 30% of skin firmness and / or elasticity. In yet another case, skin firmness and / or elasticity is improved by at least about 20%, 25%, or 30%, or by an amount in the range of about 20% to 30% of skin firmness and / or elasticity.

[0276] In some cases, the appearance of collagen in the skin is improved compared to the skin before process (1'), as measured by Vivascope® image visual grading.

[0277] In some cases, the method reduces lines and / or wrinkles on the skin by visual grading compared to the skin before step (1'). In some cases, lines and / or wrinkles on the skin are reduced by at least approximately 1%, 5%, 10%, 15%, 20%, or 25%, or by an amount ranging from approximately 1% to 25%. In some other cases, lines and / or wrinkles on the skin are reduced by at least approximately 5%, 10%, 15%, or 20%, or by an amount ranging from approximately 5% to 20%. In yet another case, lines and / or wrinkles on the skin are reduced by at least approximately 5%, 10%, or 15%, or by an amount ranging from approximately 5% to 15%.

[0278] It is understood that the individual values ​​and subranges within the aforementioned ranges are also disclosed.

[0279] The disclosed skin formulations, as well as their manufacturing methods and methods of use, can be further understood by referring to the numbered embodiments below.

[0280] Paragraph 1. A skin preparation, (i') A first composition comprising glycerin and Lavandula angustifolia extract; (ii') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii') One or more dermatologically acceptable carriers; and (iv') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0281] Paragraph 2. A skin preparation, (i'') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'')N-succinyl-S-farnesyl-L-cysteine; (iii'') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'') One or more dermatologically acceptable carriers; and (v'') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0282] Paragraph 3. A skin preparation, (i''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii''') Cetyl hydroxyproline palmitamide; (iii''') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iv''') One or more dermatologically acceptable carriers; and (v''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0283] Paragraph 4. A skin preparation, (i'''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'''') A second composition containing the fermentation filtrate of Vibrio alginolyticus; (iii'''') If necessary, (a) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (b) N-succinyl-S-farnesyl-L-cysteine; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'''') One or more dermatologically acceptable carriers; and (v'''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0284] Paragraph 5. A skin preparation, (i''''') A first composition comprising acetyltyrosine, proline, and adenosine triphosphate; (ii''''') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising glycerin and Lavandula angustifolia extract; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii''''') One or more dermatologically acceptable carriers; and (iv) One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0285] Paragraph 6. A skin formulation according to any one of paragraphs 1 to 5, wherein the second composition further comprises butylene glycol.

[0286] Paragraph 7. A skin formulation according to any one of paragraphs 1 to 4, wherein the third composition further comprises butylene glycol and / or hydrolyzed plant protein.

[0287] Paragraph 8. The skin formulation of paragraph 5, wherein the first composition further comprises butylene glycol and / or hydrolyzed plant protein.

[0288] Paragraph 9. A skin formulation comprising at least two of (a) to (d) as described in either paragraph 1 or 5.

[0289] Paragraph 10. A skin formulation comprising at least three of (a) to (d) as described in either paragraph 1 or 5.

[0290] Paragraph 11. A skin formulation comprising (a) to (d) of either paragraph 1 or 5.

[0291] Paragraph 12. A skin formulation comprising at least two of (a) to (c), one of the skin formulations described in paragraphs 2 to 4.

[0292] Paragraph 13. A skin formulation is one of the skin formulations described in paragraphs 2 to 4, including (a) to (c).

[0293] Paragraph 14. One or more dermatologically acceptable additives are present, including abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based ingredients, plant extracts, buffers, fillers, sedatives, chelating agents, cleansing agents, emulsifiers, colorants, conditioning agents, coolants, deodorants, depilators, detergents, disinfectants, dispersants, emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble ingredients, fibers, film-forming agents, and fixatives. Foaming accelerators, foaming stabilizers, foaming agents, fragrances, free radical scavengers, disinfectants, gelling agents, glossing agents, bleaching agents, conditioning agents, water-retaining agents, foaming agents, lubricants, makeup agents, moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbents, ointment bases, opacifying agents, organosilicones, oxidizing agents, oxygen carriers, pearlescent agents, perfumes, perfume solvents, perfume stabilizers, peroxide stabilizers, photosensitizers, pigments, pigment colorants, pearlescent agents, plants A skin formulation selected from the group consisting of extracts, plant-derived ingredients, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymers, polymer film-forming agents, preservatives, propellants, reducing agents, relipidating agents, resins, scalp preparations, scrubs, metal ion sequestering agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, skin bleaching agents, solubilizers, suspending agents, sunscreens, mitigating agents, spreading agents, stabilizers, sunless tanning agents, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, accelerators, thickeners, thixotropes, tightening agents, lotions, tonics, vegetable oils, volatile agents, viscosity stabilizers, vitamins, waterproofing agents, waxes, wetting agents, and whitening agents, as well as combinations thereof, any one of the skin formulations described in paragraphs 1 to 13.

[0294] Paragraph 15. A skin preparation according to paragraph 14, wherein the total weight of one or more dermatologically acceptable additives in the skin preparation is in the range of approximately 0.001% to approximately 99% by weight of the total weight of the skin preparation.

[0295] Paragraph 16. Skin preparations include cell differentiation regulators, cell proliferation regulators, dermal or epidermal polymer synthesis stimulants, dermal or epidermal polymer degradation inhibitors, microcirculation stimulants, antimicrobial metal ion chelating agents, analgesics, anesthetics, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-seborrheic agents, anti-cracking agents, anti-cellulite agents, anti-stretch mark agents, anti-dandruff agents, antifungal agents, antihistamines, anti-inflammatory agents, anti-irritants, antimicrobial agents, antibiotics, antiviral agents, anti-skin cancer agents, anti-eczema agents, anti-psoriasis agents, antiperspirants, antipruritic agents, antipruritic agents, circulation promoters, collagen stimulants, elastin stimulants, extracellular matrix stimulants, enzymes, enzyme inhibitors A skin formulation according to any one of paragraphs 1 to 15, further comprising one or more additives selected from the group consisting of harmful agents, enzyme inducers, hormones, hormone-like agents, hyaluronic acid stimulants, keratolytic agents, mucosal adhesives, natural moisturizers, lipolytic agents, peptide agents, protein agents, rosacea inhibitors, scar preventive agents, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents, skin penetration enhancers, skin penetration delayers, skin conditioning agents, skin exfoliants, skin peeling agents, skin healing agents, skin protective agents, skin purifying agents, vasoconstrictors, wound healing agents, and combinations thereof.

[0296] Paragraph 17. A skin formulation according to paragraph 16, wherein the total weight of one or more additives in the skin formulation is in the range of approximately 0.001% to approximately 99% by weight of the total weight of the skin formulation.

[0297] Paragraph 18. A skin formulation according to any one of paragraphs 1 to 17, comprising one or more dermatologically acceptable carriers, and selected from the group consisting of water, dermatologically acceptable organic solvents, and combinations thereof.

[0298] Paragraph 19. The skin formulation of paragraph 18, wherein one or more dermatologically acceptable carriers are present in an amount ranging from about 0.01% to about 95% by weight of the total weight of the skin formulation.

[0299] Paragraph 20. If (a) to (d) are present, each independently present in a concentration ranging from approximately 0.001% to approximately 5% by weight, or from approximately 0.001% to approximately 1% by weight, of the total weight of the skin preparation, one of the skin preparations from paragraphs 1 or 5.

[0300] Paragraph 21. If (a) to (c) are present, each independently present in a concentration ranging from approximately 0.001% to approximately 5% by weight, or from approximately 0.001% to approximately 1% by weight, of the total weight of the skin preparation, one of the skin preparations described in paragraphs 2 to 4.

[0301] Paragraph 22. A skin formulation further containing hydroxysomal calcium, one of the skin formulations described in paragraphs 1-21.

[0302] Paragraph 23. The skin preparation of paragraph 22, wherein hydroxysomal calcium is present in an amount ranging from approximately 0.001% to approximately 5% by weight of the total weight of the skin preparation.

[0303] Paragraph 24. The skin preparation of paragraph 22, wherein hydroxysomal calcium is present in an amount ranging from approximately 0.001% to approximately 1% by weight of the total weight of the skin preparation.

[0304] Paragraph 25. Skin preparations, Formula I: [ka] It further contains the activator, In formula I, A, B, C, and D are reactive moieties each having a charge of 1 or greater, where each of the reactive moieties A, B, C, and D independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, and itaconate group; R is a linker having a charge of 2 or greater, wherein the charge is opposite to the charge of the reactive moiety, n is 1 to 10, and R is not a polymer, and the total charge is zero, and the reactive moiety is ionically bound to the linker; each occurrence of p, q, r and s is independently an integer of 0 to 25, wherein the sum of p+q+r+s is equal to or greater than 2, the dermatological preparation according to any one of paragraphs 1 to 24.

[0305] Paragraph 26. the linker is a polyfunctional molecule, wherein the linker is optionally independently substituted with one or more substituents selected from the group consisting of hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid, -C(O)R 1 , -C(O)OR 1 , carboxylate, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 , -S(O)2R 2 , -SR 1 , -S(O)2NR 1 R 2 , sulfinyl groups, and sulfonyl groups; wherein R 1 and R 2 may each independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl; wherein R 1 and R 2Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl. The skin formulation described in paragraph 25.

[0306] Paragraph 27. The linker is a polyfunctional molecule that is an alkoxy or alkenyl molecule, and the linker is hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 -S(O)2NR 1 R 2 Substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R 1 and R 2Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; Here R 1 and R 2 Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl; or The linker is a polyfunctional molecule which is an alkyl molecule, and the alkyl molecule may be substituted or unsubstituted, and if substituted, the substituents of the alkyl molecule are selected from the group consisting of halogens, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic group, and heteroaromatic group. The skin formulation described in paragraph 25.

[0307] Paragraph 28. The activator, [ka] This is the skin preparation described in paragraph 25.

[0308] Paragraph 29. A skin preparation according to any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from 0.001% to 25% by weight of the total weight of the skin preparation.

[0309] Paragraph 30. A skin preparation according to any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 15% by weight of the total weight of the skin preparation.

[0310] Paragraph 31. A skin preparation described in any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 10% by weight of the total weight of the skin preparation.

[0311] Paragraph 32. A skin formulation according to any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 5% by weight of the skin formulation.

[0312] Paragraph 33. A skin preparation described in any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 2.5% by weight of the total weight of the skin preparation.

[0313] Paragraph 34. A skin preparation described in any one of paragraphs 25 to 28, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 1% by weight of the total weight of the skin preparation.

[0314] Paragraph 35. A method of treating the skin, (1') A method comprising applying one of the skin formulations described in paragraphs 1 to 34 to the skin of a subject.

[0315] Paragraph 36. The method of paragraph 35, wherein during step (1'), the skin formulation is topically applied to any area of ​​the subject's face, neck, neckline, décolleté, scalp, hands, palms, arms, legs, feet, soles of feet, chest, breasts, back, abdomen, buttocks, and / or any other skin area.

[0316] Paragraph 37. One of the methods described in paragraphs 35-36, wherein, after step (1'), the skin formulation remains on the skin for a period of up to 24 hours, up to 20 hours, up to 15 hours, up to 10 hours, up to 8 hours, up to 7 hours, up to 6 hours, up to 5 hours, up to 4 hours, up to 3 hours, up to 2 hours, or up to 1 hour.

[0317] Paragraph 38. One of the methods described in paragraphs 35-37, wherein, after step (1'), the skin formulation remains on the skin for approximately 1 to 30 minutes, 1 to 20 minutes, 1 to 15 minutes, 1 to 10 minutes, 5 to 30 minutes, 5 to 20 minutes, 5 to 15 minutes, or 5 to 10 minutes.

[0318] Paragraph 39. (2') After step (1'), further comprising removing the skin preparation from the skin, wherein step (2') is performed by rinsing the skin with water or washing the skin, in any way described in paragraphs 35-38.

[0319] Paragraph 40. The method further comprises repeating step (1'), and if necessary, then repeating step (2') once a day, so that the formulation is applied twice each day over a period of 1 day to 6 months, and if necessary, the period is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, one of the methods of paragraphs 35-39.

[0320] Paragraph 41. The method of paragraph 40, in which, when evaluated by visual examination after the period, a rejuvenating effect on the skin and / or improvement in the appearance of the skin is observed compared to the skin before step (1').

[0321] Paragraph 42. The method of paragraph 40, when evaluated by visual examination after a period of time, shows an effect of maintaining healthy skin, an effect of repairing damaged skin, an effect of promoting skin repair after cosmetic and / or dermatological procedures, an effect of promoting wound healing, or a combination thereof, in the skin compared to the skin before procedure (1').

[0322] Paragraph 43. When evaluated by visual inspection after the period, one or more visible signs of skin aging are reduced compared to the skin before process (1'). Paragraph 40 methods, in which signs of aging are selected from the group consisting of fine lines, moderate lines, deep lines, wrinkles, enlarged pores, roughness, dryness, redness, loss of elasticity, loss of volume, atrophic skin, stretch marks, puffy eyes, dark circles (under the eyes), and combinations thereof.

[0323] Paragraph 44. As shown by gene expression analysis, skin barrier function, development of the outer stratum corneum, and / or skin outer stratum corneum lipid synthesis are improved after the period compared to the skin before step (1') by the method of paragraph 40.

[0324] Paragraph 45. The method of paragraph 40, in which, when evaluated by visual grading after the period, the skin's brightness, gloss, and / or lightness are improved compared to the skin before step (1').

[0325] Paragraph 46. The method of paragraph 45, wherein the brightness, gloss, and / or lightness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from about 1% to 100% of the brightness, gloss, and / or lightness of the skin.

[0326] Paragraph 47. The method of paragraph 40, in which skin redness is reduced compared to the skin before process (1') when evaluated by visual grading after the period.

[0327] Paragraph 48. The method of paragraph 47, wherein skin redness is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from approximately 1% to 100% of skin redness.

[0328] Paragraph 49. The method of paragraph 40, in which, when evaluated by visual and / or tactile grading after the period, the visual texture, tactile texture, and / or smoothness of the skin are improved compared to the skin before step (1').

[0329] Paragraph 50. The method of paragraph 49, wherein the visual or tactile texture and / or smoothness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from about 1% to 100% of the visual or tactile texture and / or smoothness of the skin.

[0330] Paragraph 51. The method of paragraph 40, wherein skin hydration and / or moisturization is improved after the period compared to the skin before step (1').

[0331] Paragraph 52. The method of paragraph 51, wherein skin hydration and / or moisturizing is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or an amount of skin hydration and / or moisturizing is improved in the range of about 1% to 200%.

[0332] Paragraph 53. The method of paragraph 40, wherein, compared to the skin before step (1'), transepidermal water loss from the skin is reduced and / or the skin's barrier function is improved after the period.

[0333] Paragraph 54. The method of paragraph 53, wherein transepidermal water loss by the skin is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or by an amount ranging from approximately 1% to 50%.

[0334] Paragraph 55. The method of paragraph 53, which improves the skin barrier function by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from approximately 1% to 35% of the skin barrier function.

[0335] Paragraph 56. The method of paragraph 40, wherein the firmness and / or elasticity of the skin is improved after a period of time compared to the skin before step (1').

[0336] Paragraph 57. The method of paragraph 56, wherein skin firmness and / or elasticity is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, or 30%, or by an amount ranging from about 1% to 30%.

[0337] Paragraph 58. The method of paragraph 40, wherein the appearance of collagen in the skin is improved after a period of time compared to the skin before step (1').

[0338] Paragraph 59. The method of paragraph 40, in which lines and / or wrinkles on the skin are reduced after the period compared to the skin before step (1') when measured by visual grading.

[0339] Paragraph 60. The method of paragraph 59, wherein lines and / or wrinkles on the skin are reduced by at least about 1%, 5%, 10%, 15%, 20%, or 25%, or the amount of lines and / or wrinkles on the skin is reduced by about 1% to 25%.

[0340] Paragraph 61. The method of paragraph 40, wherein a skin formulation upregulates the expression of one or more of the following genes after a period of time, as shown by gene expression analysis, when compared to skin before step (1'): ceramide synthase 1 (CERS1), ceramide synthase 2 (CERS2), ceramide synthase 3 (CERS3), ceramide synthase 4 (CERS4), ceramide synthase 5 (CERS5), ceramide synthase 6 (CERS6), tight junction protein 1 (TJP1), occludin (OCLN), filaggrin (FLG), prostaglandin endoperoxide synthase 2 (PTGS2), or kappa light chain polypeptide gene enhancer nuclear factor 1 (NFKB1) in B cells, or a combination thereof.

[0341] Paragraph 62. The method of paragraph 40, in which, when a skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, one or more of the following genes: involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), filaggrin (FLG), and / or loricrin (LOR), and all of them as necessary, are upregulated.

[0342] Paragraph 63. The method of paragraph 40, which, when comparing the skin formulation to the skin before step (1') as shown by gene expression analysis, downregulates one or more of the following genes: TNF-α, interleukin 6, and / or interleukin 8, and all of them as necessary, after the period.

[0343] Paragraph 64. The method of paragraph 40, in which a skin formulation, when compared to the skin before step (1') as shown by gene expression analysis, upregulates one or more genes that upregulate the development of the outer stratum corneum after the period, such as loricrin (LOR), small proline-rich protein 1A (SPRR1A), small proline-rich protein 1B (SPRR1B), small proline-rich protein 2A (SPRR2A), small proline-rich protein 2B (SPRR2B), small proline-rich protein 2D (SPRR2D), small proline-rich protein 2E (SPRR2E), small proline-rich protein 2F (SPRR2F), small proline-rich protein 2G (SPRR2G), small proline-rich protein 3 (SPRR3), and small proline-rich protein 4 (SPRR4), as well as combinations thereof.

[0344] Paragraph 65. When a skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, for example, UDP-glucose ceramide glucosyltransferase (UGCG), fatty acid synthase (FASN), late keratin membrane 1A (LCE1A), late keratin membrane 1B (LCE1B), late keratin membrane 1C (LCE1C), late keratin membrane 1D (LCE1D), late keratin membrane 1E (LCE1E), late keratin membrane 1F (LCE1F), late keratin membrane 2A (LCE2A), late keratin membrane 2B (LCE2B) The method of paragraph 40, which upregulates one or more genes that upregulate extracorporeal membrane lipid synthesis, such as late extracorporeal membrane 2C (LCE2C), late extracorporeal membrane 2D (LCE2D), late extracorporeal membrane 3A (LCE3A), late extracorporeal membrane 3B (LCE3B), late extracorporeal membrane 3C (LCE3C), late extracorporeal membrane 3D (LCE3D), late extracorporeal membrane 3E (LCE3E), late extracorporeal membrane 4A (LCE4A), late extracorporeal membrane 5A (LCE5A), or late extracorporeal membrane 6A (LCE6A), or a combination thereof.

[0345] Paragraph 66. The skin preparation is a moisturizer, one of the skin preparations described in paragraphs 1-34.

[0346] Paragraph 67. A skin preparation, (1') Equation I: [ka] At least one activator of, In formula I, A, B, C, and D are reactive moieties each having a charge of 1 or greater, where each of the reactive moieties A, B, C, and D independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, and itaconate group; R is a linker with a charge of 2 or greater, where the charge is opposite to that of the reactive part, where n=1 to 10, and R is not a polymer, and The total charge is zero, and The reactive part is ionically bonded to the linker; Each occurrence of p, q, r, and s is an integer between 0 and 25, where the sum of p + q + r + s is equal to or greater than 2, and there is at least one activator; (2') A first composition comprising glycerin and Lavandula angustifolia extract; (3') one or more dermatologically acceptable additives as needed; and (4') One or more dermatologically acceptable carriers A skin preparation containing [this ingredient].

[0347] Paragraph 68. A linker is a polyfunctional molecule, where the linker is composed of hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid, -C(O)R 1 , -C(O)OR 1 carboxylate, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 -S(O)2NR 1 R 2 They are optionally independently substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R 1 and R 2Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; where R 1 and R 2 Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl. The skin formulation described in paragraph 67.

[0348] Paragraph 69. The linker is a polyfunctional molecule that is an alkoxy molecule or an alkenyl molecule, and the linker is a hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 -S(O)2NR 1 R 2Substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R 1 and R 2 Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; Here R 1 and R 2 Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl; or The linker is a polyfunctional molecule which is an alkyl molecule, and the alkyl molecule may be substituted or unsubstituted, and if substituted, the substituents of the alkyl molecule are selected from the group consisting of halogens, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic group, and heteroaromatic group. The skin formulation described in paragraph 67.

[0349] Paragraph 70. The activator, [ka] This is the skin preparation described in paragraph 67.

[0350] Paragraph 71. A skin formulation according to any one of paragraphs 67 to 70, wherein the first composition is concentrated in a range of about 0.001% to about 5% by weight, or about 0.001% to about 1% by weight, of the total weight of the skin formulation.

[0351] Paragraph 72. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from 0.001% to 25% by weight of the total weight of the skin preparation.

[0352] Paragraph 73. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 15% by weight of the total weight of the skin preparation.

[0353] Paragraph 74. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 10% by weight of the total weight of the skin preparation.

[0354] Paragraph 75. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 5% by weight of the total weight of the skin preparation.

[0355] Paragraph 76. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 2.5% by weight of the total weight of the skin preparation.

[0356] Paragraph 77. A skin preparation described in any one of paragraphs 67 to 71, wherein the activator is present in an amount ranging from approximately 0.001% to approximately 1% by weight of the total weight of the skin preparation.

[0357] Paragraph 78. A skin preparation that is a scalp preparation, one of the skin preparations described in paragraphs 67-77.

[0358] Paragraph 79. A method for treating the scalp and skin, (a') A method comprising applying one of the skin formulations described in paragraphs 67-78 to the scalp of a subject.

[0359] Paragraph 80. The method of paragraph 79, wherein scalp hydration and / or moisturization is improved after the period compared to the skin before step (a').

[0360] Paragraph 81. The method of paragraph 80, wherein scalp hydration and / or moisturizing is improved by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or by an amount ranging from approximately 1% to 200% of scalp hydration and / or moisturizing.

[0361] Paragraph 82. The method of paragraph 79, wherein, compared to the skin before step (a'), transepidermal water loss from the scalp is reduced and / or the barrier function of the scalp is improved after the period.

[0362] Paragraph 83. The method of paragraph 82, wherein transepidermal water loss by the scalp is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or by an amount ranging from approximately 1% to 50% of the transepidermal water loss by the scalp.

[0363] Paragraph 84. The method of paragraph 79, which improves the scalp barrier function by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from approximately 1% to 35% of the scalp barrier function.

[0364] Paragraph 85. The method of paragraph 79, wherein scalp redness is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount ranging from approximately 1% to 100% of the skin redness.

[0365] Paragraph 86. During step (a'), the skin formulation is first applied to dry or damp hair and rubbed into the scalp, in any one of the methods described in paragraphs 79-85.

[0366] Paragraph 87. A skin preparation, (i) [ka] Activating agent; (ii) A first composition comprising glycerin and Lavandula angustifolia extract; (iii) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (iv) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (v) Cetyl hydroxyproline palmitamide; (vi) N-succinyl-S-farnesyl-L-cysteine; (vii) one or more dermatologically acceptable carriers; and (viii) one or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

[0367] Paragraph 88. The dermatological formulation of paragraph 87, wherein the second composition further comprises butylene glycol.

[0368] Paragraph 89. A skin formulation according to any one of paragraphs 87-88, wherein the third composition further comprises butylene glycol and hydrolyzed plant protein.

[0369] Paragraph 90. A skin preparation described in any one of paragraphs 87 to 89, wherein the activator is present in an amount ranging from 0.001% to 10% by weight of the total weight of the skin preparation.

[0370] Paragraph 91. A skin preparation described in any one of paragraphs 87 to 89, wherein the activator is present in an amount ranging from 0.001% to 5% by weight of the total weight of the skin preparation.

[0371] Paragraph 92. A skin preparation comprising any one of paragraphs 87 to 91, wherein the first composition, the second composition, the third composition, cetylhydroxyproline palmitamide, and N-succinyl-S-farnesyl-L-cysteine ​​are each independently present in an amount ranging from 0.001% to 5% by weight of the total weight of the skin preparation.

[0372] Paragraph 93. A skin preparation comprising any one of paragraphs 87 to 91, wherein the first composition, the second composition, the third composition, and cetyl hydroxyproline palmitamide are each independently present in an amount ranging from 0.001% to 5% by weight of the total weight of the skin preparation.

[0373] Paragraph 94. One or more dermatologically acceptable additives are present, and include abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based agents, buffers, fillers, sedatives, chelating agents, cleansing agents, emulsifiers, colorants, conditioning agents, coolants, deodorants, depilators, detergents, disinfectants, dispersants, emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble agents, fibers, film-forming agents, fixatives, foam promoters, foam stabilizers, foaming agents, fragrances, free radical scavengers, gelling agents, glossing agents, hair growth agents, conditioning agents, moisturizers, lubricants, makeup agents, moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbents, opacifiers, oxidizing agents, perfumes, perfume solvents, perfume stabilizers, and pigments. A skin preparation selected from the group consisting of plant extracts, plant-derived ingredients, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymer film-forming agents, preservatives, propellants, relipidants, metal ion chelating agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, solubilizers, suspending agents, sunscreens, mitigating agents, stabilizers, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, thickeners, tightening agents, lotions, tonics, viscosity stabilizers, vitamins, waterproofing agents, waxes, humectants, and combinations thereof, any one of the skin preparations described in paragraphs 87-93.

[0374] Paragraph 95. A skin preparation according to paragraph 94, wherein the total weight of one or more dermatologically acceptable additives in the skin preparation is in the range of approximately 0.001% by weight to approximately 99% by weight of the total weight of the skin preparation.

[0375] Paragraph 96. A skin formulation according to any one of paragraphs 87 to 95, wherein the skin composition further comprises one or more additives selected from the group consisting of cell differentiation regulators, cell proliferation regulators, dermal or epidermal polymer synthesis stimulants, dermal or epidermal polymer degradation inhibitors, microcirculation stimulants, antimicrobial metal ion chelating agents, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-inflammatory agents, anti-inflammatory agents, antimicrobial agents, collagen stimulants, elastin stimulants, extracellular matrix stimulants, enzymes, enzyme inhibitors, enzyme inducers, hyaluronic acid stimulants, keratolytic agents, natural moisturizers, peptide agents, protein agents, rosacea inhibitors, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents, skin penetration enhancers, skin penetration delayers, skin conditioning agents, skin exfoliating agents, skin peeling agents, skin healing agents, skin protective agents, skin purifying agents, wound healing agents, and combinations thereof.

[0376] Paragraph 97. Any one of the skin formulations described in paragraphs 87 to 96, wherein the skin formulation further contains one or more additives, and the total weight percentage of the one or more additives in the skin formulation is in the range of approximately 0.001% to approximately 99% by weight of the total weight of the skin formulation.

[0377] Paragraph 98. A skin formulation according to any one of paragraphs 87-97, wherein one or more dermatologically acceptable carriers are selected from the group consisting of water, dermatologically acceptable organic solvents, and combinations thereof.

[0378] Paragraph 99. A skin formulation according to paragraph 98, wherein the total weight percentage of one or more dermatologically acceptable carriers in the skin formulation is in the range of approximately 0.01% to approximately 95% by weight of the total weight of the skin formulation.

[0379] Paragraph 100. The skin preparation is a serum, as described in paragraph 87.

[0380] Paragraph 101. The skin preparation is a moisturizer, as described in paragraph 87.

[0381] Paragraph 102. A method of treating the skin, the method is (i) A method comprising topically applying one of the skin formulations described in paragraphs 87 to 1011 to the skin of a subject.

[0382] Paragraph 103. The method of paragraph 102, wherein, after step (i), the skin formulation remains on the subject's skin for a period of up to 24 hours, up to 20 hours, up to 15 hours, up to 10 hours, up to 8 hours, up to 7 hours, up to 6 hours, up to 5 hours, up to 4 hours, up to 3 hours, up to 2 hours, or up to 1 hour.

[0383] Paragraph 104. The method of any one of paragraphs 102-103, further comprising repeating step (i) once a day, with the formulation being applied twice each day over a period of 1 day to 6 months, and optionally, the skin formulation being applied to the skin of the subject over a period of at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months.

[0384] Paragraph 105. If evaluated by visual examination after the period, a rejuvenating effect on the skin and / or improvement in the appearance of the skin is observed compared to the skin before process (i), one of the methods described in paragraphs 102-104.

[0385] Paragraph 106. As evaluated by visual examination after the period, any one of the methods in paragraphs 102-105 is observed in the skin, compared to the skin before procedure (i), including the effect of maintaining healthy skin, the effect of repairing damaged skin, the effect of promoting skin repair after cosmetic and / or dermatological procedures, the effect of promoting wound healing, or a combination thereof.

[0386] Paragraph 107. When evaluated by visual inspection after the period, one or more visible signs of skin aging are reduced compared to the skin before process (i). Signs of aging are selected from the group consisting of fine lines, moderate lines, deep lines, wrinkles, enlarged pores, roughness, dryness, redness, loss of elasticity, loss of volume, atrophic skin, stretch marks, puffy eyes, dark circles under the eyes, and any combination thereof, in any one of the methods described in paragraphs 102–106.

[0387] Paragraph 108. As shown by gene expression analysis, skin barrier function, development of the outer stratum corneum, and / or outer stratum corneum lipid synthesis are improved after the period compared to the skin before step (i), by any one of the methods described in paragraphs 102-107.

[0388] Paragraph 109. Any one of the methods described in paragraphs 102–108, wherein the brightness, luster, and / or lightness of the skin are improved compared to the skin before step (i), as assessed by visual grading after the period.

[0389] Paragraph 110. Any one of the methods described in paragraphs 102–109, wherein the visual texture, tactile texture, and / or smoothness of the skin are improved compared to the skin before step (i), as assessed by visual and / or tactile grading after the period.

[0390] Paragraph 111. One of the methods described in paragraphs 102–110, wherein skin hydration and / or moisturization is improved after the period compared to the skin before step (i).

[0391] Paragraph 112. One of the methods described in paragraphs 102–111, wherein the skin's firmness and / or elasticity is improved compared to the skin before step (i), as measured by cutometer® R0 and R2 values ​​after application to the skin for a period of at least about one hour.

[0392] Paragraph 113. One of the methods described in paragraphs 102–112, wherein the appearance of collagen in the skin is improved compared to the skin before step (i), as measured by Vivascope® image visual grading after application to the skin for a period of at least about one hour.

[0393] Paragraph 114. If lines and / or wrinkles on the skin are measured by visual grading, then any one of the methods in paragraphs 102–113, which reduces them after the period compared to the skin before step (i).

[0394] Paragraph 115. The skin formulation is a serum, and after step (i), the skin barrier function is improved compared to the skin before step (i), as indicated by a decrease in transepidermal water loss measured by Tewameter® values, in any one of the methods described in paragraphs 102-114.

[0395] Paragraph 116. The method of paragraph 115, wherein transepidermal water loss by the skin is reduced by at least approximately 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%.

[0396] Paragraph 117. A skin formulation, when applied to the skin, improves the skin's barrier function, as measured by a reduction in transepidermal water loss by the skin, as described in paragraphs 102-114, for a period of at least about one hour after application to the skin.

[0397] Paragraph 118. A skin formulation, when applied to the skin, improves skin firmness and / or elasticity as measured by Cutometer® R0 and R2 values ​​after being applied to the skin for a period of at least about one hour, one of the skin formulations described in paragraphs 102-114.

[0398] Paragraph 119. A skin formulation, when applied to the skin, improves the appearance of collagen in the skin as measured by Vivascope® image visual grading after being applied to the skin for a period of at least about one hour, one of the skin formulations described in paragraphs 102-114. [Examples]

[0399] Examples Example 1: Study I - RNA microarray analysis of skin formulations in a reconstituted human skin model EPIDERM-FT™ -material and method: - Experimental design Gene expression testing in the EPIDERM-FT (trademark) skin model:

[0400] Human 3D full-thickness skin model EPIDERM-FT® was obtained from MatTek Corp. and acclimatized in vitro in a 6-well plate using standard cell culture conditions (37°C, 5% CO2) on day 1. The tissue was acclimatized for 24 hours and randomly divided into 8 groups (n=3 wells). Each treatment group was tested with either one of the test substances, designated as Samples 1-7, or a placebo test substance (Sample 8). Each test substance (Samples 1-7 and placebo (Sample 8)) was stored at room temperature and handled by a qualified research scientist. The vials were sealed and the preparations were used immediately for treatment.

[0401] The compositions of samples 1 to 8 are listed in Table 1 below. [Table 1]

[0402] WASTAR® Lavender, EXO-T®, UNIREPAIR® T-43, CeramideBio, and SFC were purchased commercially. "Bis-amino" refers to an aqueous formulation containing approximately 20% (by weight / by weight) bis-aminodiglycol dimaleate.

[0403] A placebo was also prepared as a control formulation. The placebo contained deionized water, glycerin, distarch phosphate, ammonium dimethyltaurate acrylate / VP copolymer, SEPIMAX ZEN, SEPINOV WEO, Sesamuls OW, sesame seed oil, malic acid, isononyl isononanoate, caprylic / capric triglyceride, tocopheryl acetate, Fision EcoSoil, and MIKROKILL COS. The placebo did not contain any active ingredients.

[0404] All samples contained the same components as the placebo, and each sample also contained specific activators listed in Table 1 above. For example, sample number 3 contained water, glycerin, distarch phosphate, ammonium dimethyltaurate acrylate / VP copolymer, SEPIMAX ZEN, SEPINOV WEO, Sesamuls OW, sesame seed oil, malic acid, isononyl isononanoate, caprylic / capric triglyceride, tocopheryl acetate, Fision EcoSoil, and MIKROKILL COS, and further contained the active ingredients: WASTAR® lavender, EXO-T®, UNIREPAIR® T-43, SFC, and Gelest XG-2820.

[0405] 200 μL of the test substance was administered topically to the tissue and incubated for 24 hours. After treatment incubation, the test substance was removed and the tissue was washed with PBS. Subsequently, total RNA was extracted from 6 mm biopsy samples and sent to an RNA microarray facility for CLARIOM® S assay for transcriptome analysis. Differential gene expression was compared with that of an untreated control group.

[0406] The conditions for the tissue assay are described in detail below in the research protocol (RNA microarray gene cluster analysis). organization

[0407] EPIDERM-FT® skin tissue was sourced from human neonatal (EFT-400) cells and purchased as a stock insert from MatTek Corp. MatTek's EPIDERM-FT® system consists of normal human-derived epidermal keratinocytes (NHEKs) and dermal fibroblasts (HDFs) cultured to form a highly differentiated model of the multilayer structure of the human epidermis / dermis. These “ready-to-use” tissues were cultured in serum-free medium on specially prepared cell culture inserts. The tissues were cultured for 24 hours prior to the treatment and administration procedures, then acclimatized, and the tissue populations were identified using appropriate 6-well cell culture plates. All cell culture procedures were performed in a Signum Biosciences laboratory meeting the standards of a Biosafety Level 2 (BL-2) cell culture room. environmental conditions

[0408] The tissue culture incubator was set to a constant flow rate of 5% CO2 by volume, and the temperature and humidity were monitored and controlled to be within the range of 36°C to 38°C and 50% to 65%, respectively. Dosage and frequency of test substance

[0409] The test substance was administered as a single local dose using an appropriately sized plastic dispensing pipette. A fixed dose volume of 200 μL / well was added to each cell culture well and incubated at 37°C and 5% CO2 for 24 hours. After 24 hours, the tissue was washed and total RNA was isolated. Expression analysis parameters

[0410] Differential gene expression was analyzed using Thermo-Fisher Scientific Inc.'s Transcriptome Analysis Console (TAC) software (v4.0.1). Data normalization was performed using a placebo control group and the parameters shown in Table 2. [Table 2]

[0411] result:

[0412] The whole RNA samples submitted for gene arrays passed quality control (QC) evaluation for microarray analysis. Whole gene expression profiling was performed on 21,448 well-annotated human genes using the Affymetrix Human Clariom® S array, and the data were visualized using Transcriptome Analysis Console (TAC) software (Thermo-Fisher Scientific, Inc.). Significant expression changes between the effective treatment group and the placebo group were filtered using empirical Bayesian ANOVA with a magnification change of ≥2 (upward control) or ≤-2 (downward control) and a p-value <0.05.

[0413] Table 3 and Figure 1 below summarize the differential gene expression results between each treatment group compared to the placebo control group. Sample number 3 had the highest total number of regulatory genes (multiplier change ≥2 or ≤-2) (736), showing a generally downward regulatory effect (465 genes). Sample number 1 had the second highest number of regulatory genes (309), showing the second highest level of regulation. [Table 3]

[0414] Strengthening the skin barrier function

[0415] In both sample numbers 3 and 4, CERS4 (ceramide synthase 4) was significantly upregulated by 42–67% compared to placebo, suggesting a positive benefit in ceramide production for skin barrier protection. Sample number 1 was the only treatment group to significantly upregulate TJP1 (tight junction protein 1, occlusion zone 1; 108%) and OCLN (occludin; 227%), suggesting a benefit in the formation of tight junctions between cells that restrict the movement of substances across intercellular spaces, efficient epithelial polarization, and / or barrier formation. Although not statistically significant, samples number 1, 3, and 4 upregulated FLG (filaggrin) by 103–171%, suggesting a positive support in epidermal differentiation. Sample number 2 was the only substance that downregulated both PTGS2 (prostaglandin endoperoxide synthase 2; 231%) and NFKB1 (kappa light chain polypeptide gene enhancer nuclear factor 1 in B cells; 110%), which are key regulators of common inflammatory mechanisms activated by intracellular and extracellular stimuli that degrade the epidermal barrier. Development of the outer stratum corneum

[0416] Sample 1 significantly upregulated small proline-rich proteins (SPRR2G=631%, SPRR3=726%), which contribute to the formation of the late-differentiated keratinocyte outer membrane beneath the cell membrane. Sample 3 upregulated SPRR4 (small proline-rich protein 4), a cross-linked outer membrane protein of keratinocytes involved in UV-induced keratinization. Although not statistically significant, sample 1 also upregulated LOR (loricrin, 250%), a major protein component of the keratinized cell outer membrane. Outer corneal membrane lipid synthesis

[0417] Sample 3 significantly downregulated UGCG (UDP-glucose ceramide glucosyltransferase; -163%) and FASN (fatty acid synthase; -33%), respectively, which are involved in the de novo biosynthesis of glycosphingolipids and long-chain saturated fatty acids, which are part of the outer keratin membrane in terminal keratinocytes. Samples 1 and 3 were the best materials for upregulating (40-128%) genes of the late outer keratin membrane lipid mechanism (LCE1A, LCE1B, LCE1D, LCE1F, LCE2C, LCE2D, LCE6A). In contrast, samples 5-7 downregulated some of these late outer keratin membrane lipid genes (LCE3E, LCE5A) and therefore had a negative effect on this mechanism. Example 2: Study II - RNA microarray analysis of skin formulations in a reconstituted human skin model EPIDERM-FT™

[0418] material and method: Research details

[0419] Signum Biosciences, Inc. conducted a second study using the same procedure as described in Example 1 and the study protocol below, but with different sample formulations tested. In addition to testing the same placebo as in Example 1, untreated tissue was also tested as a control. RNA samples were sent for microarray assay (see details of the study protocol below). Transcriptome profiling results were obtained one week later.

[0420] Each treatment group was either tested with one of the test substances, designated as sample numbers 1-6, or a placebo test substance, or left untreated. Each test substance (sample numbers 1-6 and placebo) was stored at room temperature and handled by a qualified research scientist. The vials were sealed, and the formulations were used immediately for treatment.

[0421] The compositions of samples 1 through 6 are listed in Table 4 below. [Table 4]

[0422] In addition to samples 1-6 mentioned above, the "untreated" group and the "placebo" group were also evaluated. Samples 1-6 were prepared in the same manner as sample 3 in Example 1 above. A "placebo" sample identical to that described in Example 1 above was also prepared. -result:

[0423] All RNA samples submitted for gene array analysis passed the quality control (QC) evaluation for microarray analysis.

[0424] Table 5 and Figures 2A and 2B below summarize the differential gene expression results between each treatment group compared to the untreated group or the placebo control group. Treatment in sample number 4 showed the highest total number of regulatory genes (multiplier change ≥2 or ≤-2) (822), and was generally an upregulatory substance (457 genes). Sample number 2 regulated the second highest number of total regulatory genes, with 564 genes being regulated. [Table 5]

[0425] Strengthening the skin barrier function

[0426] The placebo group significantly downregulated ceramide synthases 2 and 3 (CERS2 and CERS3) compared to the untreated group. Samples 4, 5, and 6 significantly upregulated CERS5 (ceramide synthase 5) by 74–102% compared to the placebo group. Sample 4 showed the strongest effect (97%), suggesting a positive benefit to ceramide production for skin barrier protection. The placebo group also significantly downregulated TJP1 (tight junction protein 1, occluding zone 1) and occludin (OCLN) compared to the untreated group, but none of the treatments significantly upregulated these genes compared to the placebo group. Although there was no significant difference compared to the placebo group, samples 1, 3, 5, and 6 significantly upregulated FLG (filaggrin) by 32–636%, suggesting a positive support in epidermal differentiation. Compared to the untreated group, placebo upregulated both PTGS2 (prostaglandin endoperoxide synthase 2) and NFKB1 (kappa light chain polypeptide gene enhancer nuclear factor 1 in B cells). Sample number 2 downregulated PTGS2 (-20%), a key regulator of common inflammatory mechanisms activated by intracellular and extracellular stimuli that degrade the epidermal barrier, compared to placebo, but NFKB1 was the only substance that did not downregulate it. Development of the outer stratum corneum

[0427] The placebo significantly downregulated small proline-rich protein genes (SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, SPRR4) compared to the untreated group. None of the treatments significantly upregulated small proline-rich proteins compared to placebo, however, sample 1 upregulated SPRR2A, SPRR2B, SPRR2D, SPRR2E, SPRR2F, SPRR2G, and SPRR4 by 19–219%, resulting in the formation of the late-differentiated keratinocyte outer membrane beneath the cell membrane. The placebo also significantly downregulated LOR (loricrin) compared to the untreated group. Although not statistically significant, samples 1, 3, 5, and 6 also upregulated LOR by 35–563% compared to placebo, which is a positive effect as loricrin is a major protein component of the keratinized outer membrane. Outer corneal membrane lipid synthesis

[0428] Placebo did not significantly upregulate UGCG (UDP-glucose ceramide glucosyltransferase) or FASN (fatty acid synthase), which are involved in the de novo biosynthesis of glycosphingolipids and long-chain saturated fatty acids, respectively, which are part of the outer keratin membrane in terminal keratinocytes. However, samples 3 and 5 significantly upregulated UGCG by 66–67% compared to placebo. Placebo significantly downregulated all genes in the late outer keratin membrane (LCE) mechanism compared to the untreated group, and none of the sample treatments significantly upregulated LCE mechanism genes compared to placebo, although samples 1–4 showed upregulation of some of these genes (LCE3B, LCE5A). All treatments significantly downregulated some of these late outer keratin membrane genes compared to placebo, thus producing a negative effect on this mechanism.

[0429] Study protocols for Examples 1 and 2: RNA microarray gene cluster analysis Tissue: A fully reconstructed human skin (EPIDERM-FT®) model was purchased from MatTek Corp (catalog number EFT-400, lot number 34296, kits P and Q).

[0430] Tissue culture: The EpiDerm-FT® model was cultured in serum-free medium from MatTek Corp (catalog number EFT-400-ASY, lot number 101722GSA) at 37°C and 5% CO2. Skin tissue from neonatal donors was collected in a 6-well plate format and acclimatized for 24 hours.

[0431] Route of administration / frequency of administration: Single local administration at 37°C and 5% CO2 for 24 hours. GLP compliant: Not GLP compliant

[0432] protocol: Day 1: Tissue equilibration

[0433] a) EPIDERM-FT® tissue inserts were obtained from MatTek Corp., and the manufacturer's tissue equilibration protocol was followed.

[0434] b) The tissue inserts were transferred to a 6-well plate pre-filled with 2.5 mL of culture medium per well.

[0435] c) Incubated at 37°C and 5% CO2 for 24 hours. Day 2: Treatment

[0436] a) After the tissue equilibration period, the tissue inserts were transferred to a new 6-well plate pre-filled with 2.5 mL of culture medium per well.

[0437] b) For each procedure, 200 μL was administered topically to the tissue within the basal compartment using a positive displacement pipette (n=3).

[0438] c) The tissue was incubated at 37°C and 5% CO2 for 24 hours. Day 3: RNA extraction Reagent: RNAQUEOUS® kit (ThermoFisher, catalog number AM1912)

[0439] a) After incubation with the test material for 24 hours, the tissue was washed with sterile 1× DPBS to remove any remaining wash solution. Excess DPBS was removed from the tissue by gently shaking the insert and blotting on sterile blotting paper.

[0440] b) Using forceps, tissue was removed from the insert, and 6 mm punch biopsies were taken from each tissue sample. 450 μL of lysis / binding solution was added to a 1 mL homogenizing container (Kontes Duall ground-glass tissue grinder).

[0441] c) The tissue was added dropwise to the dissolution / binding solution and homogenized until a uniform lysate was formed (approximately 10 strokes).

[0442] d) The lysate was transferred to a new, labeled, RNase-free microcentrifuge tube and incubated on ice.

[0443] e) A 2.5 mL aliquot of the elution solution in a microcentrifuge tube free of RNase was heated on a heat block set to 70-80°C.

[0444] f) In a new, labeled, RNase-free microcentrifuge tube, 350 μL of 64% ethanol and 350 μL of tissue lysate were mixed and gently but thoroughly mixed by vortexing.

[0445] g) The lysate / ethanol mixture (from the previous step) was added to a filter cartridge assembled in a collection tube (included) and centrifuged at 10,000-14,000 rcf for 1 minute.

[0446] h) The flow-through was discarded, and the collection tube was reused in the cleaning process.

[0447] i) 700 μL of washing solution number 1 was added to the filter cartridge. As in the previous step, the washing solution was added through the filter. The flow-through was discarded, and the tube was reused for the next wash.

[0448] j) 500 μL of washing solution number 2 / 3 was added. The washing solution was added through the filter, as in the previous step.

[0449] k) Repeat with a second 500 μL aliquot of washing solution number 2 / 3.

[0450] l) After discarding the washing solution, centrifugation was continued to completely remove the washing solution.

[0451] m) I placed the filter cartridge into a new collection tube.

[0452] n) 50 μL of the elution solution, preheated to approximately 70-80°C, was pipettered to the center of the filter. The tube cap was closed. The eluate was collected by centrifugation at room temperature for approximately 30 seconds (RCF 10,000-14,000 × g). RNA microarray analysis

[0453] RNA samples were submitted to an expression profiling service using the Affymetrix Human CLARIOM® S array (21,448 coding genes). Human gene cluster analysis was performed focusing on well-annotated genes to perform gene-level expression profiling and evaluate changes in major genes and pathways. Differential gene expression was quantified using the CLARIOM® S microarray method after 24-hour incubation with the test material.

[0454] Whole-gene expression profiling from 21,448 well-annotated human genes was analyzed using the Affymetrix Human CLARIOM® S array. Significant expression changes were filtered using a magnification change (>2 (upward control) or <-2 (downward control)) relative to the untreated group. Example 3: Clinical trial of a skin formulation

[0455] This study evaluated the efficacy of a skin formulation, hereafter referred to as "Face Serum," in 40 healthy subjects with all skin types, including very dry / very damaged skin. The subjects' skin was assessed over a 3-month / 90-day period of home use, following the instructions provided to the study participants, using expert visual / tactile grading, a corneometer, TEWL, cutometer, VivaScope, SkiCon, and self-assessment questionnaires. This was a single-center, home-use study. Selection of research subjects: screening:

[0456] Thirty-two women and eight men were enrolled as subjects in this study, and it was expected that at least 30 subjects would complete the study. Subjects met the following inclusion and exclusion criteria, were willing to accept the prohibitions and restrictions, and were given written informed consent.

[0457] The eligibility of each participant was confirmed before acceptance into the study through the completion and review of a study-specific pre-study questionnaire. method:

[0458] The study participants were supplied with ivory soap rinse-off products. The face serum products were certified to be manufactured / formulated using safe and appropriate ingredients for the intended purpose of the product.

[0459] The face serum product contained the following active ingredients: bis-aminopropyl diglycol dimaleate, lavandula angustifolia extract, acetyl tyrosine, proline, adenosine triphosphate, cetyl hydroxyproline palmitamide, and N-succinyl-S-farnesyl-L-cysteine. The face serum product also contained additional carriers / additives, including hydrating agents, emollients / skin conditioning agents, emulsifiers / surfactants, thickeners / viscosity modifiers, preservatives / antimicrobial agents, pH adjusters / buffers, chelating agents, natural ingredients, ceramides / lipid barrier components, and solvents / carriers.

[0460] The facial serum product (or test item) was used as supplied, according to the following instructions: After cleansing / toning, apply a generous amount (1-2 pumps) of the product to the face and forearms twice daily (morning and night), before the application of the regular regimen. No other serums / moisturizers should be used. Indicates whether the product was used each day. The product should be used twice daily for 5 consecutive days prior to visit 2, and for 90 days after visit. Research procedure: -Visit to the clinic 1-Rinsing (-5 days):

[0461] Participants who met the registration criteria were provided with a rinse-off product, which they used daily on their face and forearms for five consecutive days prior to their second study visit, in place of their usual facial cleanser. Participants were given a usage log to track their rinsing progress. Participants were instructed not to apply any creams or moisturizers to their face or forearms starting two days before their second visit and throughout the entire study period. They were also instructed to come to each study visit without makeup. Participants were also required to bring their log and rinse-off product to their next visit and to wash their face 2.5 hours prior to their appointment. -Visit 2-Baseline (Day 1 of the study):

[0462] Subjects visited the testing facility, underwent qualification verification, checked their record sheets, and collected rinsed products. Upon acceptance into the study, subjects acclimatized to indoor environmental conditions (temperature 20–22°C and relative humidity 30–50%) for at least 30 minutes prior to evaluation. Baseline measurements were then taken, and expert evaluators visually and tactilely assessed the subjects' faces. Corneometer, SkiCon, and TEWL assessments were performed on the forearm, and VivaScope and Cutometer assessments were conducted on the face.

[0463] After baseline assessment was completed, the test product was applied to the face and forearm, followed by a visual assessment of the face by a specialist, as well as reassessment of the forearm using a corneometer, SkiCon, and TEWL. Participants also completed a Self-Report Questionnaire (SPQ). Subsequently, participants were provided with the product and instructions for use, which they took home and used as directed for the next three months. In addition, participants thoroughly washed their face at least 2.5 hours before each visit. -3rd visit to the hospital-7th day of the study:

[0464] After using the product at home (as instructed) for 7 days, the subjects returned to the testing facility. The weight of the test item was measured, and a record sheet was checked for compliance with the rules. In addition, the subjects also adapted to the indoor environmental conditions as described above during the baseline test (Day 1 of the study), and then a professional evaluator visually and tactilely assessed the subjects' faces, performing Corneometer, SkiCon, and TEWL assessments on the forearms, and Cutometer assessments on the faces. The subjects also completed a self-awareness questionnaire. -4th visit to the hospital-30th day of the study:

[0465] The subjects used the product at home as instructed for 30 days, and then returned to the testing facility. The same measurements and tests were performed as in Visit 3. -5th visit to the hospital-60th day of the study:

[0466] The subjects used the product at home as instructed for 60 days, and then returned to the testing facility.

[0467] The same measurements and tests were performed as in the third visit.

[0468] Furthermore, VivaScope evaluation was performed on the face. -6th visit - 90th day of study (final visit):

[0469] The subjects used the product at home as instructed for 90 days, and then returned to the testing facility.

[0470] The same measurements and tests were performed as in the fifth visit.

[0471] Subject participation was considered complete when all evaluations were finished and all record sheets and test materials were received. Visual evaluation using visual and tactile grading.

[0472] Visual assessments were performed on the face at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. Tactile assessments were also performed on the face at baseline, on day 7, day 30, day 60, and day 90. The same professional scorer evaluated all subjects throughout the study period according to the following grading scale. The subjects' faces were illuminated by a 60-watt pearl light bulb approximately 30 cm from the area. The PCR clinical grading scale used in this study is shown in Figure 3A. Evaluation using equipment Corneometer

[0473] Moisture content was measured using a Corneometer CM825 (Courage and Khazaka, Germany). This instrument relies on the dielectric constant, a physical property of water (which is relatively high and therefore affects the capacitance of a capacitor). Any change in dielectric constant due to fluctuations in skin moisture content changes the capacitance of a precision capacitor within the instrument. These fluctuations are electronically detected by the Corneometer and converted into numerical values.

[0474] Three readings were taken at the test site on the forearm using the corneometer probe attachment. Between each evaluation, the corneometer probe attachment was pressed against a dry tissue. Subjects were in a controlled environment (temperature 20–22°C and relative humidity 30–50%) for at least 15 minutes before any evaluation was performed. If one measurement was greater than ±10 units from the others (outlier), a fourth measurement was taken. Measurements were taken at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. SkiCon

[0475] Skin conductivity can be used to measure skin moisture levels, which are derived from changes in the electrical properties of the stratum corneum.

[0476] The SkiCon 200EX (IBS co., Hamamatsu, Japan) measures skin conductivity through the stratum corneum using a fixed high-frequency current of 3.5 MHz. The device displays conductivity readings in microsiemens (μS) in the range of 0 to 1999. All conductivity measurements are displayed after a 3-second reading. Measurements were taken from the forearm at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. Transepidermal water loss (TEWL) measured by the Tewameter® probe.

[0477] Transepidermal water loss was measured using the Tewameter™300 probe (Courage and Khazaka, Cologne, Germany). Water evaporation, i.e., TEWL, was measured in g / m³ based on the diffusion principle within an open chamber. 2 The density gradient is measured as / h. The density gradient is measured indirectly by two sets of sensors in the probe attachment (one set for temperature and the other set for relative humidity). This density gradient was then analyzed by a microprocessor in the instrument. Measurements were taken from the forearm at baseline, immediately after use (1 hour), on day 7, day 30, day 60, and day 90. Evaluation of VIVASCOPE(registered trademark) 1500-Collagen:

[0478] In Vivascope evaluations, subjects were in a controlled environment (temperature 20–24°C and relative humidity 35–50%) for 30 minutes prior to any evaluation performed. Measurements were taken from the fine wrinkle area of ​​the right outer corner of the eye at baseline, day 60, and day 90.

[0479] The test area was captured using VivaCam, making it possible to correlate confocal images with photographic images.

[0480] Collagen structure (i.e., fragmentation and density of collagen in the papillary layer and superficial dermis) was visualized in vivo using a confocal laser scanning microscope (VIVASCOPE® 1500, VivaScope GmbH, Munich, Germany). This allowed visualization of cellular ultrastructure as optical sections with a maximum horizontal resolution of 1.25 μm and a vertical resolution of 3–5 μm, down to the maximum depth of the superficial dermis (200 μm). Collagen fibers appeared as white structures.

[0481] Individual images (500 μm × 500 μm) were acquired in a 5 μm scanning process (approximately 40 images), and stacked images were created. Only images targeting the collagen network (in the papillary layer and superficial dermis) were analyzed. Images acquired at baseline were compared with images acquired at day 60, and separately with images acquired at day 90. Each image was graded by a professional grader on a visual analog scale for collagen fragmentation and density. The PCR clinical grading scale used for collagen evaluation with Vivascope® is provided in Figure 3B. Cutometer® measures firmness (R0) / elasticity (R2):

[0482] The viscoelastic properties (elasticity and firmness) of the skin were measured at baseline, day 7, and day 90 using a Cutometer® MPA 580 (Courage and Khazaka, Germany).

[0483] Passive stretch measurements were recorded. These measurements were displayed as a curve at the end of each measurement using Windows®-based software.

[0484] Measurement mode 1 involved applying a constant suction of 400 mbar for 5 seconds, followed by a 3-second relaxation period, repeated three times. The measured elastic parameters were R2 and R0, an indicator of tension, and the average value of the three repetitions was reported. Self-awareness questionnaire:

[0485] The study subjects also completed self-awareness questionnaires on day 1 (immediately after use, up to 1 hour), day 7, day 30, day 60, and day 90. Research results:

[0486] Forty subjects participated in the study, and 38 completed it. Two subjects withdrew from the study for personal reasons. The table below provides details of the study subjects. [Table 6]

[0487] No side effects were reported. Although there were some minor differences in the statistical characteristics of the subjects, the study protocol was followed and this did not affect the integrity of the study.

[0488] Conclusion: Visual and tactile grading:

[0489] For all visual grading assessments, a decrease in the average score indicates an improvement in that assessment. Under the conditions of this study, the test items used statistically significantly reduced the average score for all visual grading assessments.

[0490] In an in-treatment analysis of the visual grading scores for moderate / deep facial wrinkles, the mean score showed a statistically significant decrease compared to baseline by day 90 after application. Furthermore, sustained reductions from baseline were observed at 1 hour, 7 days, 30 days, and 60 days, and the mean reduction in wrinkle appearance was statistically significant after using the test product twice daily for 90 days. Therefore, the test product contributed to a reduction in the appearance of moderate / deep wrinkles after 90 days of use.

[0491] Intratreatment analysis of the visual grading scores for facial skin brightness / luminosity showed a statistically significant decrease in the mean score after application compared to baseline. The mean baseline score decreased at 1 hour, 7 days, 30 days, 60 days, and 90 days after application, respectively. Therefore, a statistically significant mean rate of change (improvement in overall brightness and radiance of the skin's appearance) was observed at all time points after 90 days of use, twice daily.

[0492] Intratreatment analysis of the visual grading of facial skin redness also showed a statistically significant decrease in the mean score after application compared to baseline. The mean baseline score decreased at 1 hour, 7 days, 30 days, 60 days, and 90 days after application, respectively. Therefore, after 90 days of use twice daily, a statistically significant mean rate of change (from reduction in skin redness to complete disappearance of redness) was observed at all time points.

[0493] In an intratreatment analysis of visual grading scores for facial skin texture / smoothness, the mean score after application showed a statistically significant decrease compared to baseline. The mean baseline score decreased at 1 hour, 7 days, 30 days, 60 days, and 90 days after application, respectively. Therefore, after 90 days of use twice daily, a statistically significant mean rate of change (improvement in skin texture / smoothness appearance to a smoother, softer, and more uniform-looking skin texture) was observed at all time points.

[0494] Intra-treatment analysis of tactile grading for facial skin texture / smoothness also showed a statistically significant decrease in the mean score after application compared to baseline. The mean baseline score decreased at 1 hour, 7 days, 30 days, 60 days, and 90 days after application, respectively. Therefore, after 90 days of use twice daily, a statistically significant mean rate of change (improvement in skin texture / smoothness to smoother, softer, and more uniform skin texture) was observed at all time points. Corneometer and SkiCon for hydration / moisturizing:

[0495] Under the conditions of this study, the test product statistically significantly improved skin hydration / moisture at all time points, as measured by a corneometer and SkiCon. Intra-treatment analysis showed significant improvements in data from 1 hour, day 7, day 30, day 60, and day 90 compared to baseline readings. In particular, corneometer measurements showed an increase in skin hydration at 1 hour and a change from baseline after 90 days of twice-daily use of the test product. This is consistent with the increase in SkiCon measurements at 1 hour and the change from baseline after 90 days of twice-daily use of the test product. Tewameter for transepidermal water loss (TEWL):

[0496] Under the conditions of this study, the test product also statistically significantly reduced transepidermal water loss at all time points, as measured by Tewameter® (p<0.01). In intratreatment analysis, data from 1 hour, day 7, day 30, day 60, and day 90 were significantly reduced compared to baseline readings. After using the test product twice daily for 90 days, transepidermal water loss gradually decreased (improved barrier function). Cutometer® R0 / R2 for firmness and elasticity:

[0497] Under the conditions of this study, the test product showed statistically significant improvement in skin elasticity as measured by the R2 value using a Cutometer® (p<0.01). Intra-treatment analysis showed significant improvement in data from 1 hour, 7 days, 30 days, 60 days, and 90 days compared to baseline readings. After using the test product twice daily for 90 days, skin elasticity gradually increased.

[0498] Under the conditions of this study, the test product showed a statistically significant effect in improving skin firmness, as measured by the R0 value using a Cutometer®. Intratreatment analysis showed significant improvement in data from 1 hour, 7 days, 30 days, 60 days, and 90 days compared to baseline readings. After using the test product twice daily for 90 days, skin firmness gradually increased. Vivascope (registered trademark) (Visual) - Collagen:

[0499] Data from the visual grading of collagen were obtained from the fine wrinkle area at the outer corner of the right eye. Vivascope® images showed that the test product statistically significantly improved the appearance of collagen, as measured by the visual grading of Vivascope® images (p<0.05). Intra-treatment analysis under the conditions of this study showed that the mean data from days 60 and 90 were statistically significantly reduced compared to baseline reads (p<0.05).

[0500] Self-awareness questionnaire: Subjects completed self-perception questionnaires immediately after the first application of the test product and after 7, 30, 60, and 90 days of use, using the product twice daily. Subjects indicated their degree of agreement or disagreement with descriptions of the test product and their experiences with the test product using a 5-point Likert scale. Based on data from the self-perception questionnaires, the test product elicited either a favorable (>50%) or very favorable (≧80%) response for all questions at all time points.

[0501] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art in the field to which the disclosed invention pertains. Publications cited herein and materials from which they are cited are incorporated herein by special reference.

[0502] Those skilled in the art will recognize, or can verify by ordinary experiment alone, numerous specific examples and equivalents of the present invention described herein. Such equivalents are intended to be encompassed by the following claims. The present invention provides, for example, the following items: (Item 1) A skin preparation, (i') A first composition comprising glycerin and Lavandula angustifolia extract; (ii') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii') One or more dermatologically acceptable carriers; and (iv') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient]. (Item 2) A skin preparation, (i'') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'')N-succinyl-S-farnesyl-L-cysteine; (iii'') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'') One or more dermatologically acceptable carriers; and (v'') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient]. (Item 3) A skin preparation, (i''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii''') Cetyl hydroxyproline palmitamide; (iii''') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iv''') One or more dermatologically acceptable carriers; and (v''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient]. (Item 4) A skin preparation, (i'''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'''') A second composition containing the fermentation filtrate of Vibrio alginolyticus; (iii'''') If necessary, (a) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (b) N-succinyl-S-farnesyl-L-cysteine; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'''') One or more dermatologically acceptable carriers; and (v'''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient]. (Item 5) A skin preparation, (i''''') A first composition comprising acetyltyrosine, proline, and adenosine triphosphate; (ii''''') (a) A second composition comprising the fermentation filtrate of Vibrio alginolyticus; (b) A third composition comprising glycerin and Lavandula angustifolia extract; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii''''') One or more dermatologically acceptable carriers; and (iv) One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient]. (Item 6) The skin formulation according to any one of the above items, wherein the second composition further comprises butylene glycol. (Item 7) A skin formulation according to any one of the above items, wherein the third composition further comprises butylene glycol and / or hydrolyzed plant protein. (Item 8) A skin formulation according to any one of the above items, wherein the first composition further comprises butylene glycol and / or hydrolyzed plant protein. (Item 9) The skin preparation according to any one of the above items, wherein the skin preparation comprises at least two of (a) to (d). (Item 10) The skin preparation according to any one of the above items, wherein the skin preparation comprises at least three of (a) to (d). (Item 11) The skin preparation described above is a skin preparation according to any one of the above items, comprising (a) to (d). (Item 12) The skin preparation according to any one of the above items, wherein the skin preparation comprises at least two of (a) to (c). (Item 13) The skin preparation described above is a skin preparation according to any one of the above items, comprising (a) to (c). (Item 14) The following dermatologically acceptable additives are present, and the following are also present: abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based agents, plant extracts, buffers, fillers, sedatives, chelating agents, cleansing agents, emulsifiers, colorants, conditioning agents, coolants, deodorants, depilators, detergents, disinfectants, dispersants, emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble agents, fibers, film-forming agents, solids Fixatives, foaming accelerators, foaming stabilizers, foaming agents, fragrances, free radical scavengers, disinfectants, gelling agents, glossing agents, bleaching agents, conditioning agents, water-retaining agents, foaming agents, lubricants, makeup agents, moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbents, ointment bases, opacifying agents, organosilicones, oxidizing agents, oxygen carriers, pearlescent agents, perfumes, perfume solvents, perfume stabilizers, peroxide stabilizers, photosensitizers, pigments, pigment colorants, pearlescent agents, Skin preparations according to any one of the above items, selected from the group consisting of plant extracts, plant-derived ingredients, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymers, polymer film-forming agents, preservatives, propellants, reducing agents, relipidating agents, resins, scalp preparations, scrubs, metal ion sequestering agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, skin bleaching agents, solubilizers, suspending agents, sunscreens, mitigating agents, spreading agents, stabilizers, sunless tanning agents, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, accelerators, thickeners, thixotropes, tightening agents, lotions, tonics, vegetable oils, volatile agents, viscosity stabilizers, vitamins, waterproofing agents, waxes, wetting agents, and whitening agents, and combinations thereof. (Item 15) A skin preparation according to any one of the above items, wherein the total weight of the one or more dermatologically acceptable additives in the skin preparation is in the range of about 0.001% by weight to about 99% by weight of the total weight of the skin preparation. (Item 16) The aforementioned skin preparations include cell differentiation regulators, cell proliferation regulators, dermal or epidermal polymer synthesis stimulants, dermal or epidermal polymer degradation inhibitors, microcirculation stimulants, antimicrobial metal ion sequestering agents, analgesics, anesthetics, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-seborrheic agents, anti-cracking agents, anti-cellulite agents, anti-stretch mark agents, anti-dandruff agents, antifungal agents, antihistamines, anti-inflammatory agents, anti-irritants, antimicrobial agents, antibiotics, antiviral agents, anti-skin cancer agents, anti-eczema agents, anti-psoriasis agents, antiperspirants, antipruritic agents, antipruritic agents, circulation promoters, collagen stimulants, elastin stimulants, extracellular matrix stimulants, enzymes, yeasts. A skin preparation according to any one of the above items, further comprising one or more additives selected from the group consisting of enzyme inhibitors, enzyme inducers, hormones, hormone-like agents, hyaluronic acid stimulants, keratolytic agents, mucosal adhesives, natural moisturizers, lipolytic agents, peptide agents, protein agents, rosacea inhibitors, scar preventive agents, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents, skin penetration enhancers, skin penetration delayors, skin conditioning agents, skin exfoliants, skin peeling agents, skin healing agents, skin protective agents, skin purifying agents, vasoconstrictors, wound healing agents, and combinations thereof. (Item 17) A skin preparation according to any one of the above items, wherein the total weight of the one or more additives in the skin preparation is in the range of about 0.001% by weight to about 99% by weight of the total weight of the skin preparation. (Item 18) A skin formulation according to any one of the above items, comprising one or more dermatologically acceptable carriers, and selected from the group consisting of water, dermatologically acceptable organic solvents, and combinations thereof. (Item 19) A skin preparation according to any one of the above items, wherein one or more of the aforementioned dermatologically acceptable carriers are present in an amount ranging from about 0.01% to about 95% by weight of the total weight of the skin preparation. (Item 20) The skin preparation according to any one of the above items, wherein if (a) to (d) are present, each is independently concentrated in a range of approximately 0.001% to approximately 5% by weight, or approximately 0.001% to approximately 1% by weight, of the total weight of the skin preparation. (Item 21) The skin preparation according to any one of the above items, wherein if (a) to (c) are present, each is independently concentrated in a range of approximately 0.001% to approximately 5% by weight, or approximately 0.001% to approximately 1% by weight, of the total weight of the skin preparation. (Item 22) The skin preparation according to any one of the above items, wherein the skin preparation further comprises hydroxysome calcium. (Item 23) The skin preparation according to any one of the above items, wherein the hydroxysome calcium is present in an amount ranging from about 0.001% by weight to about 5% by weight of the total weight of the skin preparation. (Item 24) The skin preparation according to any one of the above items, wherein the hydroxysome calcium is present in an amount ranging from about 0.001% by weight to about 1% by weight of the total weight of the skin preparation. (Item 25) The dermatological formulation has formula I: [ka] It further contains the activator, In formula I, A, B, C, and D are reactive moieties each having a charge of 1 or greater, wherein each of the reactive moieties A, B, C, and D independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, and itaconate group; R is a linker with a charge of 2 or greater, where the charge is opposite to the charge of the reactive portion, where n=1 to 10, and R is not a polymer, and The sum of the aforementioned charges is zero, and The reactive portion is ionically bonded to the linker; Each occurrence of p, q, r, and s is an integer between 0 and 25, where the sum of p+q+r+s is equal to or greater than 2. A skin preparation described in any one of the above items. (Item 26) The linker is a polyfunctional molecule, where the linker is hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid, -C(O)R 1 , -C(O)OR 1 carboxylate, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 -S(O)2NR 1 R 2 They are optionally independently substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R 1 and R 2 Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; where R 1 and R 2Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl. A skin preparation described in any one of the above items. (Item 27) The linker is a polyfunctional molecule that is an alkoxy molecule or an alkenyl molecule, and the linker is hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, -C(O)NR 1 R 2 , -NR 1 R 2 , -NR 1 S(O)2R 2 , -NR 1 C(O)R 2 -S(O)2R 2 , -SR 1 -S(O)2NR 1 R 2 Substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R 1 and R 2Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; Here R 1 and R 2 Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl; or The linker is a polyfunctional molecule which is an alkyl molecule, and the alkyl molecule is substituted or unsubstituted, and if substituted, the substituent of the alkyl molecule is selected from the group consisting of halogen, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic group, and heteroaromatic group. A skin preparation described in any one of the above items. (Item 28) The aforementioned activator, [ka] A skin preparation described in any one of the above items. (Item 29) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from 0.001% to 25% by weight of the total weight of the skin preparation. (Item 30) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from about 0.001% by weight to about 15% by weight of the total weight of the skin preparation. (Item 31) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from about 0.001% by weight to about 10% by weight of the total weight of the skin preparation. (Item 32) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from about 0.001% by weight to about 5% by weight of the total weight of the skin preparation. (Item 33) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from about 0.001% by weight to about 2.5% by weight of the total weight of the skin preparation. (Item 34) The skin preparation according to any one of the above items, wherein the activator is present in an amount ranging from about 0.001% by weight to about 1% by weight of the total weight of the skin preparation. (Item 35) A method of treating the skin, (1') A method comprising applying a skin preparation described in any one of the above items to the skin of a subject. (Item 36) The method according to any one of the above items, wherein during step (1'), the skin formulation is topically applied to any area of ​​the subject's face, neck, neckline, décolleté, scalp, hands, palms, arms, legs, feet, soles of feet, chest, breasts, back, abdomen, buttocks, and / or any other skin area. (Item 37) The method according to any one of the above items, wherein, after step (1'), the skin preparation remains on the skin for a period of up to 24 hours, up to 20 hours, up to 15 hours, up to 10 hours, up to 8 hours, up to 7 hours, up to 6 hours, up to 5 hours, up to 4 hours, up to 3 hours, up to 2 hours, or up to 1 hour. (Item 38) The method according to any one of the above items, wherein, after step (1'), the skin preparation remains on the skin for approximately 1 minute to approximately 30 minutes, approximately 1 minute to approximately 20 minutes, approximately 1 minute to approximately 15 minutes, approximately 1 minute to approximately 10 minutes, approximately 5 minutes to approximately 30 minutes, approximately 5 minutes to approximately 20 minutes, approximately 5 minutes to approximately 15 minutes, or approximately 5 minutes to approximately 10 minutes. (Item 39) (2') The method according to any one of the above items, further comprising removing the skin preparation from the skin after step (1'), wherein step (2') is performed by rinsing the skin with water or washing the skin, if necessary. (Item 40) The method according to any one of the above items, further comprising repeating step (1'), and if necessary, subsequently repeating step (2') once a day, so that the formulation is applied twice each day over a period of 1 day to 6 months, wherein the period is, if necessary, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months. (Item 41) The method according to any one of the above items, wherein, when evaluated by visual inspection after the aforementioned period, a rejuvenating effect on the skin and / or improvement in the appearance of the skin is observed compared to the skin before step (1'). (Item 42) The method according to any one of the above items, wherein, when evaluated by visual inspection after the aforementioned period, the following effects are observed in the skin compared to the skin before step (1'): an effect of maintaining healthy skin, an effect of repairing damaged skin, an effect of promoting the repair of the skin after cosmetic and / or dermatological procedures, an effect of promoting wound healing, or a combination thereof. (Item 43) When evaluated by visual inspection after the aforementioned period, one or more visible signs of skin aging are reduced compared to the skin before step (1'). The method according to any one of the above items, wherein the aforementioned signs of aging are selected from the group consisting of fine lines, moderate lines, deep lines, wrinkles, enlarged pores, roughness, dryness, redness, loss of elasticity, loss of volume, atrophic skin, stretch marks, eye puffiness, dark circles (under the eyes), and combinations thereof. (Item 44) The method according to any one of the above items, wherein, as shown by gene expression analysis, the barrier function of the skin, the development of the outer stratum corneum, and / or the outer stratum corneum lipid synthesis of the skin are improved after the period compared to the skin before step (1'). (Item 45) The method according to any one of the above items, wherein, when evaluated by visual grading after the aforementioned period, the brightness, gloss, and / or lightness of the skin is improved compared to the skin before step (1'). (Item 46) The method according to any one of the above items, wherein the brightness, gloss, and / or lightness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the brightness, gloss, and / or lightness of the skin is improved by an amount ranging from about 1% to 100%. (Item 47) The method according to any one of the above items, wherein, when evaluated by visual grading after the aforementioned period, the redness of the skin is reduced compared to the skin before step (1'). (Item 48) The method according to any one of the above items, wherein the redness of the skin is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the amount of the redness of the skin is reduced by about 1% to 100%. (Item 49) The method according to any one of the above items, wherein, when evaluated by visual and / or tactile grading after the aforementioned period, the visual texture, tactile texture, and / or smoothness of the skin are improved compared to the skin before step (1'). (Item 50) The method according to any one of the above items, wherein the visual or tactile texture and / or smoothness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the amount of the visual or tactile texture and / or smoothness of the skin is improved by about 1% to 100%. (Item 51) The method according to any one of the above items, wherein the hydration and / or moisturizing of the skin is improved after the period compared to the skin before step (1'). (Item 52) The method according to any one of the above items, wherein the hydration and / or moisturizing of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or the amount of the hydration and / or moisturizing of the skin is improved by about 1% to 200%. (Item 53) The method according to any one of the above items, wherein, after the period, the amount of transepidermal water loss from the skin is reduced and / or the barrier function of the skin is improved compared to the skin before step (1'). (Item 54) The method according to any one of the above items, wherein the transepidermal water loss by the skin is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or the amount of transepidermal water loss by the skin is reduced by about 1% to 50%. (Item 55) The method according to any one of the above items, wherein the barrier function of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from about 1% to 35% of the barrier function of the skin. (Item 56) The method according to any one of the above items, wherein the firmness and / or elasticity of the skin is improved after the period compared to the skin before step (1'). (Item 57) The method according to any one of the above items, wherein the firmness and / or elasticity of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, or 30%, or by an amount ranging from about 1% to 30% of the firmness and / or elasticity of the skin. (Item 58) The method according to any one of the above items, wherein the appearance of collagen in the skin is improved after the period compared to the skin before step (1'). (Item 59) The method according to any one of the above items, wherein lines and / or wrinkles on the skin are reduced after the period compared to the skin before step (1'), if measured by visual grading. (Item 60) The method according to any one of the above items, wherein the lines and / or wrinkles on the skin are reduced by at least about 1%, 5%, 10%, 15%, 20%, or 25%, or the amount of the lines and / or wrinkles on the skin is reduced by about 1% to 25%. (Item 61) The method according to any one of the above items, wherein the skin formulation, when compared to the skin before step (1') as shown by gene expression analysis, upregulates the gene expression of one or more of the following after the period: ceramide synthase 1 (CERS1), ceramide synthase 2 (CERS2), ceramide synthase 3 (CERS3), ceramide synthase 4 (CERS4), ceramide synthase 5 (CERS5), ceramide synthase 6 (CERS6), tight junction protein 1 (TJP1), occludin (OCLN), filaggrin (FLG), prostaglandin endoperoxide synthase 2 (PTGS2), or kappa light chain polypeptide gene enhancer nuclear factor 1 (NFKB1) in B cells, or a combination thereof. (Item 62) The method according to any one of the above items, wherein, when the skin formulation is compared to the skin prior to step (1') as shown by gene expression analysis, after the period, one or more of the following genes: involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), filaggrin (FLG), and / or loricrin (LOR), and all of them as necessary. (Item 63) The method according to any one of the above items, wherein, when the skin formulation is compared to the skin prior to step (1') as shown by gene expression analysis, after the period, one or more of the following genes: TNF-α, interleukin 6, and / or interleukin 8, and all of them as necessary. (Item 64) The method according to any one of the above items, wherein, when the skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, one or more genes that upregulate the development of the outer stratum corneum, such as loricrin (LOR), small proline-rich protein 1A (SPRR1A), small proline-rich protein 1B (SPRR1B), small proline-rich protein 2A (SPRR2A), small proline-rich protein 2B (SPRR2B), small proline-rich protein 2D (SPRR2D), small proline-rich protein 2E (SPRR2E), small proline-rich protein 2F (SPRR2F), small proline-rich protein 2G (SPRR2G), small proline-rich protein 3 (SPRR3), and small proline-rich protein 4 (SPRR4), and combinations thereof. (Item 65) When the skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, for example, UDP-glucose ceramide glucosyltransferase (UGCG), fatty acid synthase (FASN), late keratin membrane 1A (LCE1A), late keratin membrane 1B (LCE1B), late keratin membrane 1C (LCE1C), late keratin membrane 1D (LCE1D), late keratin membrane 1E (LCE1E), late keratin membrane 1F (LCE1F), late keratin membrane 2A (LCE2A), late keratin membrane 2B (LCE2B) The method according to any one of the above items, which upregulates one or more genes that upregulate outer keratin membrane lipid synthesis, such as late outer keratin membrane 2C (LCE2C), late outer keratin membrane 2D (LCE2D), late outer keratin membrane 3A (LCE3A), late outer keratin membrane 3B (LCE3B), late outer keratin membrane 3C (LCE3C), late outer keratin membrane 3D (LCE3D), late outer keratin membrane 3E (LCE3E), late outer kerati...

Claims

1. A skin preparation, (i') A first composition comprising glycerin and Lavandula angustifolia extract; (ii') (a) A second composition comprising the fermentation filtrate of Vibrio alginoleticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii') One or more dermatologically acceptable carriers; and (iv') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

2. A skin preparation, (i'') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'') N-succinyl-S-farnesyl-L-cysteine; (iii'') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginoleticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'') one or more dermatologically acceptable carriers; and (v'') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

3. A skin preparation, (i''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii''') Cetyl hydroxyproline palmitamide; (iii'') If necessary, (a) A second composition comprising the fermentation filtrate of Vibrio alginoleticus; (b) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; and (c) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iv''') one or more dermatologically acceptable carriers; and (v''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

4. A skin preparation, (i'''') A first composition comprising glycerin and Lavandula angustifolia extract; (ii'''') A second composition comprising the fermentation filtrate of Vibrio alginoleticus; (iii'''') If necessary, (a) A third composition comprising acetyltyrosine, proline, and adenosine triphosphate; (b) N-succinyl-S-farnesyl-L-cysteine; and (c) Cetyl hydroxyproline palmitamide; at least one of the following; (iv'''') one or more dermatologically acceptable carriers; and (v'''') One or more dermatologically acceptable additives, as needed. A skin preparation containing [this ingredient].

5. A skin preparation, (i'''') A first composition comprising acetyltyrosine, proline, and adenosine triphosphate; (ii'''') (a) A second composition comprising the fermentation filtrate of Vibrio alginoleticus; (b) A third composition comprising glycerin and Lavandula angustifolia extract; (c) Cetyl hydroxyproline palmitamide; and (d) N-succinyl-S-farnesyl-L-cysteine; at least one of the following; (iii'''') One or more dermatologically acceptable carriers; and (iv''''') one or more dermatologically acceptable additives, as needed A skin preparation containing [this ingredient].

6. The skin formulation according to any one of claims 1 to 5, wherein the second composition further comprises butylene glycol.

7. The skin formulation according to any one of claims 1 to 4, wherein the third composition further comprises butylene glycol and / or hydrolyzed plant protein.

8. The skin formulation according to claim 5, wherein the first composition further comprises butylene glycol and / or hydrolyzed plant protein.

9. The skin preparation according to any one of claims 1 or 5, wherein the skin preparation comprises at least two of (a) to (d).

10. The skin preparation according to any one of claims 1 or 5, wherein the skin preparation comprises at least three of (a) to (d).

11. The skin preparation according to any one of claims 1 or 5, wherein the skin preparation comprises (a) to (d).

12. The skin preparation according to any one of claims 2 to 4, wherein the skin preparation comprises at least two of (a) to (c).

13. The skin preparation according to any one of claims 2 to 4, wherein the skin preparation comprises (a) to (c).

14. The following dermatologically acceptable additives are present, and include abrasives, acidulants, adhesion promoters, antioxidants, preservatives, astringents, barrier agents, bioadhesion agents, plant-based agents, plant extracts, buffers, fillers, sedatives, chelating agents, cleansing agents, emulsifiers, colorants, conditioning agents, coolants, deodorants, depilators, detergents, disinfectants, dispersants, emollients, emulsifiers, emulsifying stabilizers, essential oils, exfoliants, lipid-soluble agents, fibers, and film-forming agents. Fixatives, foaming accelerators, foaming stabilizers, foaming agents, fragrances, free radical scavengers, disinfectants, gelling agents, glossing agents, bleaching agents, conditioning agents, water-retaining agents, foaming agents, lubricants, makeup agents, moisture barrier agents, humectants, neutralizing agents, odor masking agents, oils, oil absorbents, ointment bases, opacifying agents, organosilicones, oxidizing agents, oxygen carriers, pearlescent agents, perfumes, perfume solvents, perfume stabilizers, peroxide stabilizers, photosensitizers, pigments, pigment colorants, pearlescent A skin preparation according to claim 1, selected from the group consisting of auxiliary agents, plant extracts, plant-derived components, plant tissue extracts, plant root extracts, plant seed extracts, vegetable oils, plasticizers, polymers, polymer film-forming agents, preservatives, propellants, reducing agents, relipidating agents, resins, scalp preparations, scrubbing agents, metal ion chelating agents, silicone agents, skin clearing agents, skin cleansing agents, skin lipids, skin brightening agents, skin bleaching agents, solubilizers, suspending agents, sunscreens, mitigating agents, spreading agents, stabilizers, sunless tanning agents, sunscreens, UVA sunscreens, UVB sunscreens, broadband sunscreens, surfactants, amphoteric surfactants, anionic surfactants, cationic surfactants, nonionic surfactants, silicone surfactants, accelerators, thickeners, thixotropes, tightening agents, lotions, tonics, vegetable oils, volatile agents, viscosity stabilizers, vitamins, waterproofing agents, waxes, wetting agents, and whitening agents, as well as combinations thereof.

15. The skin preparation according to claim 14, wherein the total weight of the one or more dermatologically acceptable additives in the skin preparation is in the range of about 0.001% by weight to about 99% by weight of the total weight of the skin preparation.

16. The aforementioned skin preparations include cell differentiation regulators, cell proliferation regulators, dermal or epidermal polymer synthesis stimulants, dermal or epidermal polymer degradation inhibitors, microcirculation stimulants, antimicrobial metal ion sequestering agents, analgesics, anesthetics, anti-acne agents, anti-aging agents, anti-wrinkle agents, anti-atrophy agents, antibacterial agents, anti-scarring agents, anti-seborrheic agents, anti-cracking agents, anti-cellulite agents, anti-stretch mark agents, anti-dandruff agents, antifungal agents, antihistamines, anti-inflammatory agents, anti-irritants, antimicrobial agents, antibiotics, antiviral agents, anti-skin cancer agents, anti-eczema agents, anti-psoriasis agents, antiperspirants, antipruritic agents, antipruritic agents, circulation promoters, collagen stimulants, elastin stimulants, extracellular matrix stimulants, yeast A skin preparation according to claim 1, further comprising one or more additives selected from the group consisting of: ions, enzyme inhibitors, enzyme inducers, hormones, hormone-like agents, hyaluronic acid stimulants, keratolytic agents, mucosal adhesives, natural moisturizers, lipolytic agents, peptide agents, protein agents, rosacea inhibitors, scar preventive agents, skin barrier agents, skin barrier repair agents, skin sedatives, skin smoothing agents, skin sedatives, skin soothing agents, skin penetration enhancers, skin penetration delayants, skin conditioning agents, skin exfoliants, skin peeling agents, skin healing agents, skin protective agents, skin purifying agents, vasoconstrictors, wound healing agents, and combinations thereof.

17. The skin preparation according to claim 16, wherein the total weight of the one or more additives in the skin preparation is in the range of about 0.001% by weight to about 99% by weight of the total weight of the skin preparation.

18. The skin formulation according to claim 1, wherein one or more dermatologically acceptable carriers are present, and the carrier is selected from the group consisting of water, dermatologically acceptable organic solvents, and combinations thereof.

19. The skin formulation according to claim 18, wherein the one or more dermatologically acceptable carriers are present in an amount ranging from about 0.01% to about 95% by weight of the total weight of the skin formulation.

20. The skin preparation according to any one of claims 1 or 5, wherein if (a) to (d) are present, each is independently concentrated in a range of about 0.001% to about 5% by weight, or about 0.001% to about 1% by weight, of the total weight of the skin preparation.

21. The skin preparation according to any one of claims 2 to 4, wherein if (a) to (c) are present, each is independently concentrated in a range of about 0.001% to about 5% by weight or about 0.001% to about 1% by weight of the total weight of the skin preparation.

22. The skin preparation according to claim 1, wherein the skin preparation further comprises hydroxysome calcium.

23. The skin preparation according to claim 22, wherein the hydroxysome calcium is present in an amount ranging from about 0.001% by weight to about 5% by weight of the total weight of the skin preparation.

24. The skin preparation according to claim 22, wherein the hydroxysome calcium is present in an amount ranging from about 0.001% by weight to about 1% by weight of the total weight of the skin preparation.

25. The dermatological formulation has formula I: 【Chemistry 15】 It further contains the activator, In formula I, A, B, C, and D are reactive moieties having a charge of 1 or greater, wherein each of the reactive moieties A, B, C, and D independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, and itaconate group; R is a linker having a charge of 2 or greater, where the charge is opposite to the charge of the reactive portion, where n = 1 to 10, and R is not a polymer, and The sum of the aforementioned charges is zero, and The reactive portion is ionically bonded to the linker; Each occurrence of p, q, r, and s is an integer between 0 and 25, where the sum of p + q + r + s is equal to or greater than 2. The skin preparation according to claim 1.

26. Said linker is a multifunctional molecule, wherein said linker is optionally independently substituted with one or more substituents selected from the group consisting of hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid, -C(O)R １ , -C(O)OR １ , carboxylate, primary amide, secondary amide, -C(O)NR １ R ２ , -NR １ R ２ , -NR １ S(O) ２ R ２ , -NR １ C(O)R ２ , -S(O) ２ R ２ , -SR １ , -S(O) ２ NR １ R ２ , a sulfinyl group, and a sulfonyl group, as needed; Here R １ and R ２ Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; where R １ and R ２ Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl. The skin preparation according to claim 25.

27. The linker is a polyfunctional molecule which is an alkoxy molecule or an alkenyl molecule, and the linker is a hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, -C(O)NR １ R ２ , -NR １ R ２ , -NR １ S(O) ２ R ２ , -NR １ C(O)R ２ , -S(O) ２ R ２ , -SR １ , -S(O) ２ NR １ R ２ Substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R １ and R ２ Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; Here R １ and R ２ Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl; or The linker is a polyfunctional molecule which is an alkyl molecule, and the alkyl molecule is substituted or unsubstituted, and if substituted, the substituent of the alkyl molecule is selected from the group consisting of halogen, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic group, and heteroaromatic group. The skin preparation according to claim 25.

28. The aforementioned activator, 【Chemistry 16】 【Chemistry 17】 The skin preparation according to claim 25.

29. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from 0.001% to 25% by weight of the total weight of the skin preparation.

30. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from about 0.001% by weight to about 15% by weight of the total weight of the skin preparation.

31. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from about 0.001% by weight to about 10% by weight of the total weight of the skin preparation.

32. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from about 0.001% by weight to about 5% by weight of the total weight of the skin preparation.

33. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from about 0.001% by weight to about 2.5% by weight of the total weight of the skin preparation.

34. The skin preparation according to any one of claims 25 to 28, wherein the activator is present in an amount ranging from about 0.001% by weight to about 1% by weight of the total weight of the skin preparation.

35. A skin preparation according to any one of claims 1 to 5 for use in a method of treating the skin, wherein the method is (1') A skin preparation comprising applying the skin preparation to the skin of a subject.

36. The skin formulation according to claim 35, characterized in that during step (1'), the skin formulation is topically applied to any area of ​​the subject's face, neck, neckline, décolleté, scalp, hands, palms, arms, legs, feet, soles of feet, chest, breasts, back, abdomen, buttocks, and / or any other skin area.

37. The skin formulation according to claim 35, wherein, after step (1'), the skin formulation remains on the skin for a period of up to 24 hours, up to 20 hours, up to 15 hours, up to 10 hours, up to 8 hours, up to 7 hours, up to 6 hours, up to 5 hours, up to 4 hours, up to 3 hours, up to 2 hours, or up to 1 hour.

38. The skin preparation according to claim 35, wherein, after step (1'), the skin preparation remains on the skin for approximately 1 minute to approximately 30 minutes, approximately 1 minute to approximately 20 minutes, approximately 1 minute to approximately 15 minutes, approximately 1 minute to approximately 10 minutes, approximately 5 minutes to approximately 30 minutes, approximately 5 minutes to approximately 20 minutes, approximately 5 minutes to approximately 15 minutes, or approximately 5 minutes to approximately 10 minutes.

39. The skin preparation according to claim 35, wherein the method further comprises (2') removing the skin preparation from the skin after step (1'), and if necessary, step (2') is achieved by rinsing the skin with water or washing the skin.

40. The skin formulation according to claim 35, wherein the method further comprises repeating step (1'), and if necessary, subsequently repeating step (2') once a day, so that the formulation is applied twice each day over a period of 1 day to 6 months, wherein the period is, if necessary, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months.

41. The skin formulation according to claim 40, wherein, when evaluated by visual inspection after the aforementioned period, a rejuvenating effect on the skin and / or improvement in the appearance of the skin is observed compared to the skin before step (1').

42. The skin formulation according to claim 40, wherein, when evaluated by visual inspection after the aforementioned period, an effect of maintaining healthy skin, an effect of repairing damaged skin, an effect of promoting the repair of skin after cosmetic and / or dermatological procedures, an effect of promoting wound healing, or a combination thereof is observed in the skin compared to the skin before step (1').

43. When evaluated by visual inspection after the aforementioned period, one or more visible signs of skin aging are reduced compared to the skin before step (1'). The skin formulation according to claim 40, wherein the aforementioned signs of aging are selected from the group consisting of fine lines, moderate lines, deep lines, wrinkles, enlarged pores, roughness, dryness, redness, loss of elasticity, loss of volume, atrophic skin, stretch marks, eye puffiness, dark circles (under the eyes), and combinations thereof.

44. The skin formulation according to claim 40, wherein, as shown by gene expression analysis, the barrier function of the skin, the development of the outer stratum corneum, and / or the outer stratum corneum lipid synthesis of the skin are improved after the period compared to the skin before step (1').

45. The skin formulation according to claim 40, wherein, when evaluated by visual grading after the aforementioned period, the brightness, gloss, and / or lightness of the skin are improved compared to the skin before step (1').

46. The skin formulation according to claim 45, wherein the brightness, gloss, and / or lightness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or by an amount in the range of about 1% to 100% of the brightness, gloss, and / or lightness of the skin.

47. The skin formulation according to claim 40, wherein, when evaluated by visual grading after the aforementioned period, the redness of the skin is reduced compared to the skin before step (1').

48. The skin formulation according to claim 47, wherein the redness of the skin is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the amount of the redness of the skin is reduced in the range of about 1% to 100%.

49. The skin formulation according to claim 40, wherein, when evaluated by visual and / or tactile grading after the aforementioned period, the visual texture, tactile texture, and / or smoothness of the skin are improved compared to the skin before step (1').

50. The skin formulation according to claim 49, wherein the visual or tactile texture and / or smoothness of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the visual or tactile texture and / or smoothness of the skin is improved by an amount ranging from about 1% to 100%.

51. The skin formulation according to claim 40, wherein the hydration and / or moisturizing of the skin is improved after the period compared to the skin before step (1').

52. The skin formulation according to claim 51, wherein the hydration and / or moisturizing of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or the amount of the hydration and / or moisturizing of the skin is improved by about 1% to 200%.

53. The skin formulation according to claim 40, wherein, compared to the skin before step (1'), the amount of transepidermal water loss from the skin is reduced and / or the barrier function of the skin is improved after the period.

54. The skin formulation according to claim 53, wherein the amount of transepidermal water loss by the skin is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or by an amount in the range of about 1% to 50% of the amount of transepidermal water loss by the skin.

55. The skin formulation according to claim 53, wherein the barrier function of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from about 1% to 35% of the barrier function of the skin.

56. The skin formulation according to claim 40, wherein the firmness and / or elasticity of the skin is improved after the period compared to the skin before step (1').

57. The skin formulation according to claim 56, wherein the firmness and / or elasticity of the skin is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, or 30%, or by an amount ranging from about 1% to 30% of the firmness and / or elasticity of the skin.

58. The skin formulation according to claim 40, wherein the appearance of collagen in the skin is improved after the period compared to the skin before step (1').

59. The skin formulation according to claim 40, wherein, when measured by visual grading, the lines and / or wrinkles on the skin are reduced after the period compared to the skin before step (1').

60. The skin formulation according to claim 59, wherein the lines and / or wrinkles on the skin are reduced by at least about 1%, 5%, 10%, 15%, 20%, or 25%, or the amount of the lines and / or wrinkles on the skin is reduced by about 1% to 25%.

61. The skin formulation according to claim 40, wherein, when the skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, the expression of one or more genes selected from ceramide synthase 1 (CERS1), ceramide synthase 2 (CERS2), ceramide synthase 3 (CERS3), ceramide synthase 4 (CERS4), ceramide synthase 5 (CERS5), ceramide synthase 6 (CERS6), tight junction protein 1 (TJP1), occludin (OCLN), filaggrin (FLG), prostaglandin endoperoxide synthase 2 (PTGS2), or kappa light chain polypeptide gene enhancer nuclear factor 1 (NFKB1) in B cells, or a combination thereof.

62. The skin formulation according to claim 40, wherein, when the skin formulation is compared to the skin prior to step (1') as shown by gene expression analysis, after the period, one or more of the following genes: involucrin (IVL), keratin 1 (KRT1), transglutaminase 1 (TGM1), filaggrin (FLG), and / or loricrin (LOR), and optionally all of them, are upregulated.

63. The skin formulation according to claim 40, wherein, when the skin formulation is compared to the skin prior to step (1') as shown by gene expression analysis, after the period, one or more of the following genes: TNF-α, interleukin 6, and / or interleukin 8, and optionally all of them, are downregulated.

64. The skin formulation according to claim 40, wherein, when the skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, one or more genes that upregulate the development of the outer stratum corneum, such as loricrin (LOR), small proline-rich protein 1A (SPRR1A), small proline-rich protein 1B (SPRR1B), small proline-rich protein 2A (SPRR2A), small proline-rich protein 2B (SPRR2B), small proline-rich protein 2D (SPRR2D), small proline-rich protein 2E (SPRR2E), small proline-rich protein 2F (SPRR2F), small proline-rich protein 2G (SPRR2G), small proline-rich protein 3 (SPRR3), and small proline-rich protein 4 (SPRR4), and combinations thereof.

65. When the skin formulation is compared to the skin before step (1') as shown by gene expression analysis, after the period, for example, UDP-glucose ceramide glucosyltransferase (UGCG), fatty acid synthase (FASN), late keratin membrane 1A (LCE1A), late keratin membrane 1B (LCE1B), late keratin membrane 1C (LCE1C), late keratin membrane 1D (LCE1D), late keratin membrane 1E (LCE1E), late keratin membrane 1F (LCE1F), late keratin membrane 2A (LCE2A), late keratin membrane 2B (LCE2B) A skin formulation according to claim 40, which upregulates one or more genes that upregulate outer stratum corneum lipid synthesis, such as late outer stratum corneum 2C (LCE2C), late outer stratum corneum 2D (LCE2D), late outer stratum corneum 3A (LCE3A), late outer stratum corneum 3B (LCE3B), late outer stratum corneum 3C (LCE3C), late outer stratum corneum 3D (LCE3D), late outer stratum corneum 3E (LCE3E), late outer stratum corneum 4A (LCE4A), late outer stratum corneum 5A (LCE5A), or late outer stratum corneum 6A (LCE6A), or a combination thereof.

66. The skin preparation according to any one of claims 1 to 5, wherein the skin preparation is a moisturizer.

67. A skin preparation, (1') Equation I: [Chemistry 18] At least one activator of, In formula I, A, B, C, and D are reactive moieties each having a charge of 1 or greater, wherein each of the reactive moieties A, B, C, and D independently contains a moiety selected from the group consisting of vinyl sulfone, acrylate group, methacrylate group, styrene group, acrylamide group, methacrylamide group, maleate group, and itaconate group; R is a linker having a charge of 2 or greater, where the charge is opposite to the charge of the reactive portion, where n = 1 to 10, and R is not a polymer, and The sum of the aforementioned charges is zero, and The reactive portion is ionically bonded to the linker; Each occurrence of p, q, r, and s is an integer between 0 and 25, where the sum of p + q + r + s is equal to or greater than 2, and there is at least one activator; (2') A first composition comprising glycerin and Lavandula angustifolia extract; (3') one or more dermatologically acceptable additives as needed; and (4') One or more dermatologically acceptable carriers A skin preparation containing [this ingredient].

68. The linker is a polyfunctional molecule, where the linker is a hydrogen, halogen, cyano, alkoxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocycloalkyl, heteroaryl, amine, hydroxy, formyl, acyl, carboxylic acid, -C(O)R １ , -C(O)OR １ carboxylate, primary amide, secondary amide, -C(O)NR １ R ２ , -NR １ R ２ , -NR １ S(O) ２ R ２ , -NR １ C(O)R ２ , -S(O) ２ R ２ , -SR １ , -S(O) ２ NR １ R ２ They are optionally independently substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R １ and R ２ Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; where R １ and R ２ Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with aryl or heteroaryl or =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl. The skin preparation according to claim 67.

69. The linker is a polyfunctional molecule which is an alkoxy molecule or an alkenyl molecule, and the linker is a hydrogen, halogen, cyano, alkenyl, cycloalkyl, cycloalkenyl, amine, hydroxy, formyl, acyl, primary amide, secondary amide, -C(O)NR １ R ２ , -NR １ R ２ , -NR １ S(O) ２ R ２ , -NR １ C(O)R ２ , -S(O) ２ R ２ , -SR １ , -S(O) ２ NR １ R ２ Substituted with one or more substituents selected from the group consisting of sulfinyl groups and sulfonyl groups; Here R １ and R ２ Each of these can independently be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl; Here R １ and R ２ Each of these is optionally independently substituted with one or more substituents selected from the group consisting of halogens, hydroxyl, cyano, nitro, amino, alkylamino, dialkylamino, alkyl optionally substituted with one or more halogens, alkoxy or aryloxy, aryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, heterocycloalkyl optionally substituted with =O or alkyl (optionally substituted with hydroxyl), cycloalkyl optionally substituted with hydroxyl, heteroaryl optionally substituted with one or more halogens, alkoxy or alkyl or trihaloalkyl, haloalkyl, hydroxyalkyl, carboxy, alkoxy, aryloxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, and dialkylaminocarbonyl; or The linker is a polyfunctional molecule which is an alkyl molecule, and the alkyl molecule is substituted or unsubstituted, and if substituted, the substituent of the alkyl molecule is selected from the group consisting of halogen, hydroxyl, thiocarbonyl, alkoxyl, phosphoryl, phosphate, phosphonate, phosphine, amino, amide, amidine, imine, cyano, nitro, azide, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamide, sulfonyl, heterocyclyl, aralkyl, aromatic group, and heteroaromatic group. The skin preparation according to claim 67.

70. The aforementioned activator, 【Chemistry 19】 The skin preparation according to claim 67.

71. The skin preparation according to any one of claims 67 to 70, wherein the first composition is concentrated in an amount of about 0.001% to about 5% by weight, or about 0.001% to about 1% by weight, of the total weight of the skin preparation.

72. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from 0.001% to 25% by weight of the total weight of the skin preparation.

73. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from about 0.001% by weight to about 15% by weight of the total weight of the skin preparation.

74. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from about 0.001% by weight to about 10% by weight of the total weight of the skin preparation.

75. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from about 0.001% by weight to about 5% by weight of the total weight of the skin preparation.

76. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from about 0.001% by weight to about 2.5% by weight of the total weight of the skin preparation.

77. The skin preparation according to any one of claims 67 to 70, wherein the activator is present in an amount ranging from about 0.001% by weight to about 1% by weight of the total weight of the skin preparation.

78. The skin preparation according to any one of claims 67 to 70, wherein the skin preparation is a scalp preparation.

79. A skin preparation according to claim 67 for use in a method of treating the scalp, wherein the method is (a') A skin preparation comprising applying the skin preparation to the scalp of a subject.

80. The skin formulation according to claim 79, wherein the hydration and / or moisturizing of the scalp is improved after the period compared to the skin before step (a').

81. The skin formulation according to claim 80, wherein the hydration and / or moisturizing of the scalp is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or the amount of the hydration and / or moisturizing of the scalp is improved by about 1% to 200%.

82. The skin formulation according to claim 79, wherein, compared to the skin before step (a'), after the period, the amount of transepidermal water loss from the scalp is reduced and / or the barrier function of the scalp is improved.

83. The skin formulation according to claim 82, wherein the amount of transepidermal water loss by the scalp is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or by an amount in the range of about 1% to 50% of the amount of transepidermal water loss by the scalp.

84. The skin formulation according to claim 79, wherein the barrier function of the scalp is improved by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, or 35%, or by an amount ranging from about 1% to 35% of the barrier function of the scalp.

85. The skin formulation according to claim 79, wherein the redness of the scalp is reduced by at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%, or the amount of the redness of the skin is reduced by about 1% to 100%.

86. The skin preparation according to any one of claims 79 to 85, characterized in that during step (a'), the skin preparation is first applied to dry or wet hair and rubbed into the scalp.

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