Nanoemulsion composition, nanometer skin care product, preparation method and application

Abstract

The invention provides a nano-emulsion composition, a nano skin care product, a preparation method and application, the nano-emulsion composition comprises a nano-emulsion and nucleic acid loaded on the surface of the nano-emulsion, and the nano-emulsion comprises a functional component, an emulsifier, an emollient, an antioxidant, a humectant and water; the functional component comprises a barrier repair lipid, the barrier repair lipid comprises sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid and cholesterol; the mass ratio of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%. The nanoemulsion composition has excellent permeability, so that the skin permeability of the nucleic acid is improved, and the bioavailability of the nucleic acid is improved; meanwhile, the nucleic acid can be specifically bound with adenosine A2A receptors distributed on keratinocytes, so that the binding speed of the nano-emulsion and the cells can be increased, the absorption and action effects of the nano-emulsion are specifically promoted, and the resistance of the skin to light aging is improved.

Description

Technical Field

[0001] The present application relates to the field of cosmetic technology, and in particular to a nanoemulsion composition, a nano skin care product, a preparation method and an application. Background Art

[0002] Photoaging is a complex physiological process involving multiple layers of skin structure, different cell types, diverse signaling pathways, and numerous skin molecules and substances. Photoaging has a wide range of effects on skin function, including but not limited to skin barrier function, skin tone changes, wrinkle formation, and skin resistance.

[0003] The solar spectrum is composed of radiation of various wavelengths. The full spectrum of sunlight comprises 5% ultraviolet (UV), 45% visible light (VL), and 50% infrared (IR). Visible light primarily affects the skin by causing oxidative damage, while IR induces thermal damage and alters the integrity of skin cell mitochondria, leading to the production of reactive oxygen species (ROS). UVA and UVB are the most significant wavelengths of UV radiation that cause skin damage. UV damages the skin barrier, weakening the skin's ability to resist photoaging, making it more susceptible to damage from UV rays and other factors, leading to photoaging. Summary of the Invention

[0004] Based on this, the present application provides a nanoemulsion composition, a nano skin care product, a preparation method and an application. The nanoemulsion composition electrostatically self-assembles positively charged nanoemulsions with negatively charged nucleic acids, and utilizes the specific binding of nucleic acids to the A2A receptors of keratinocytes to achieve precise targeted delivery; its nanoscale particle size characteristics can enhance the skin permeability of active ingredients, and the composition can efficiently load barrier repair lipids and promote their absorption by cells, thereby enhancing lipid metabolism, repairing barrier structure, and improving the skin's ability to resist photoaging.

[0005] The first aspect of the present application provides a nanoemulsion composition, comprising a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, wherein the nanoemulsion contains an effective ingredient, an emulsifier, an emollient, an antioxidant, a moisturizer and water; the effective ingredient includes a barrier repair lipid, the barrier repair lipid includes a sphingolipid, the sphingolipid includes phytosphingosine, and the barrier repair lipid further includes one or more of ceramide, free fatty acid and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0006] In some embodiments, the mass proportion of the phytosphingosine in the barrier-repair lipid is 15%-50%.

[0007] In some embodiments, the barrier repair lipid comprises phytosphingosine and one or more of ceramide EOS, ceramide NS, ceramide NP, ceramide AS, ceramide AP, linoleic acid, palmitic acid, and cholesterol.

[0008] In some embodiments, the active ingredients further include one or more of glabridin, salicylic acid, astaxanthin, phenethylresorcinol and hydroxypinacolone retinoate.

[0009] In some embodiments, the molecular weight of the nucleic acid is 5 wDa-150 wDa; and / or

[0010] The mass percentage content of DNA in the nucleic acid is ≥70%, and can be optionally ≥90%.

[0011] In some embodiments, the emulsifier includes one or more of alkyl glycoside emulsifiers, polyol ester emulsifiers, Span emulsifiers, Tween emulsifiers, phosphate emulsifiers, fatty alcohol polyether emulsifiers, polyglycerol emulsifiers and high molecular weight polymer emulsifiers.

[0012] In some embodiments, the emulsifier includes one or more of C14-22 alkyl alcohol / C12-20 alkyl glucoside, eicosyl behenyl alcohol / eicosyl glucoside, cetyl alcohol / cetearyl glucoside / sucrose stearate, steareth-21, lecithin, Span 20, Span 40, Span 60, Span 80, Tween 80, Tween 120, polyglyceryl-10 stearate, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters.

[0013] In some embodiments, the emollient comprises one or more of a high molecular weight polymer, plant oil, animal oil, mineral oil, and synthetic oil.

[0014] In some embodiments, the emollient includes one or more of caprylic / capric triglyceride, caprylic / capric / myristic / stearic triglyceride, bis-PEG-18 methyl ether dimethyl silane, isononyl isononanoate, cetearyl alcohol, squalane, shea butter, candelilla wax, dipentaerythrityl hexahydroxystearate / hexastearate / hexarosinate, phytosteryl / octyldodecanol lauroyl glutamate, pentaerythrityl tetraethylhexanoate, dimethicone, ethylhexyl palmitate, coconut oil, olive oil, palm oil, beeswax, jojoba oil, mineral oil, and petrolatum.

[0015] In some embodiments, the antioxidant includes one or more of tocopheryl acetate, butylated hydroxytoluene, and pentaerythritol tetrakis-di-tert-butylhydroxyhydrocinnamate.

[0016] In some embodiments, the moisturizing agent includes one or more of a polyol moisturizing agent, a natural moisturizing factor, a polymer biochemical moisturizing agent, and an amino acid moisturizing agent.

[0017] In some embodiments, the humectant includes one or more of glycerin, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, glycereth-26, and trehalose.

[0018] In some embodiments, the nanoemulsion composition comprises, by weight:

[0019] 0.05-0.3 parts of nucleic acids, 0.05-2 parts of barrier repair lipids, 1-10 parts of emulsifiers, 1-10 parts of emollients, 0.01-0.2 parts of antioxidants, 1-8 parts of moisturizers and 20-50 parts of water.

[0020] In some embodiments, the nanoemulsion composition comprises, by weight:

[0021] 0.05-0.25 parts of nucleic acids, 0.1-1.5 parts of barrier repair lipids, 1-5 parts of emulsifiers, 2-8 parts of emollients, 0.05-0.2 parts of antioxidants, 1-7 parts of moisturizers and 20-40 parts of water.

[0022] In some embodiments, the nanoemulsion composition has a particle size of 100 nm to 500 nm and a polydispersity index of 0.05 to 0.55.

[0023] In some embodiments, the nanoemulsion composition has a particle size of 100 nm to 300 nm and a polydispersity index of 0.05 to 0.35.

[0024] The second aspect of the present application provides a method for preparing a nanoemulsion composition, comprising the following steps:

[0025] Prepare phase A, which includes an effective ingredient, a portion of an emollient, an antioxidant, and a portion of an emulsifier;

[0026] Prepare phase B, which includes humectant, part of water, remaining emollient and remaining emulsifier;

[0027] Mixing the phase A and the phase B to prepare a nanoemulsion;

[0028] mixing the nucleic acid with the remaining water to prepare an aqueous nucleic acid solution;

[0029] mixing the nanoemulsion with the nucleic acid aqueous solution to prepare a nanoemulsion composition;

[0030] Wherein, the effective ingredients include barrier repair lipids, the barrier repair lipids include sphingolipids, the sphingolipids include phytosphingosine, and the barrier repair lipids also include one or more of ceramides, free fatty acids and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0031] In some embodiments, the preparation method of phase A comprises:

[0032] The phase A is prepared by dissolving the phytosphingosine in a portion of the emollient, and then adding the antioxidant, a portion of the emulsifier, and the components of the barrier repair lipid except the phytosphingosine.

[0033] In some embodiments, the phytosphingosine is dissolved in a portion of the emollient under heating conditions of 90°C-100°C.

[0034] In some embodiments, the antioxidant, part of the emulsifier, and the components of the barrier repair lipid except the phytosphingosine are added to the emollient under heating conditions of 80° C. to 90° C.

[0035] In some embodiments, the preparation method of the phase B comprises: adding the moisturizer, the remaining emollient, and the remaining emulsifier to a portion of water, and stirring uniformly to prepare the phase B.

[0036] In some embodiments, the step of mixing the phase A and the phase B comprises:

[0037] After the phase A and the phase B are mixed, a first homogenization treatment and a second homogenization treatment are sequentially performed; the first homogenization treatment has a rate of 2000 rpm-12000 rpm and a time of 2 min-60 min; the second homogenization treatment has a pressure of 100 bar-2000 bar and a number of times of 2 times-20 times.

[0038] In some embodiments, the first homogenization process is performed at a rate of 3000 rpm to 10000 rpm, and for a time of 3 min to 30 min.

[0039] In some embodiments, the second homogenization process is performed at a pressure of 300 bar to 1000 bar and is repeated 2 to 10 times.

[0040] The third aspect of the present application provides a nano skin care product, comprising a nanoemulsion composition, the nanoemulsion composition comprising a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, the nanoemulsion comprising an effective ingredient, an emulsifier, an emollient, an antioxidant, a moisturizer and water; the effective ingredient comprises a barrier repair lipid, the barrier repair lipid comprises a sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0041] In some embodiments, the nano skin care product further comprises an active ingredient, a skin conditioning agent, a preservative, a chelating agent, a thickener and water.

[0042] In some embodiments, the active ingredient comprises one or more of saccharide derivatives, natural plant extracts, nucleosides, metal oxides, and amide compounds.

[0043] In some embodiments, the active ingredients include one or more of cerium oxide, glyceryl glucoside, madecassoside, adenosine, niacinamide, β-glucan, sodium hyaluronate, tranexamic acid, retinol, vitamin C, ferulic acid, green tea extract, arbutin, soy isoflavones, and hydrolyzed oat protein.

[0044] In some embodiments, the thickener includes one or more of polyacrylic acids, fatty alcohols, fatty acids, celluloses, natural gums and modifications thereof, esters, inorganic polymers and modifications thereof.

[0045] In some embodiments, the thickening agent includes one or more of sodium polyacrylate, carbomer, sodium polyacryloyldimethyl taurate, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, starch, gum arabic, pectin, agar, gelatin, alginate, carrageenan, and dextrin.

[0046] In some embodiments, the preservative includes one or more of an alcohol preservative, a paraben preservative, an isothiazolinone preservative, a formaldehyde-releasing preservative, and an acid preservative.

[0047] In some embodiments, the preservative includes one or more of 1,2-pentanediol, 1,2-hexanediol, phenoxyethanol / ethylhexylglycerin, methylparaben, ethylparaben, propylparaben, sorbic acid, benzoic acid, dehydroacetic acid, methylchloroisothiazolinone, and methylisothiazolinone.

[0048] In some embodiments, the chelating agent comprises one or more of a hydroxyhydroxy acid chelating agent and an amino acid derivative chelating agent.

[0049] In some embodiments, the chelating agent includes one or more of disodium EDTA, ethylenediaminetetraacetic acid, tetrasodium ethylenediaminetetraacetic acid, and disodium nitrilotriacetate.

[0050] In some embodiments, the active ingredient accounts for 1%-10% by weight of the nano skin care product, optionally 1%-6% by weight; and / or

[0051] The mass proportion of the skin conditioning agent in the nano skin care product is 0.1%-4%, optionally 0.5%-3%; and / or

[0052] The mass proportion of the preservative in the nano skin care product is 1%-10%, optionally 1%-6%; and / or

[0053] The mass proportion of the cerium oxide in the nano skin care product is 0.1%-2%, optionally 0.1%-1%; and / or

[0054] The mass proportion of the chelating agent in the nano skin care product is 0.01%-0.06%, and can be optionally 0.01%-0.05%;

[0055] The mass proportion of the thickener in the nano skin care product is 0.05%-4%, optionally 0.5%-3%; and / or

[0056] The barrier repair lipid accounts for 0.05%-2% by weight in the nano skin care product, and can be optionally 0.1%-1.5% by weight; and / or

[0057] The mass proportion of the emulsifier in the nano skin care product is 1%-10%, optionally 1%-5%; and / or

[0058] The emollient accounts for 1%-10% by weight of the nano skin care product, and can be optionally 2%-8% by weight; and / or

[0059] The antioxidant accounts for 0.01%-0.2% by weight in the nano skin care product, and can be optionally 0.05%-0.2%; and / or

[0060] The mass proportion of the moisturizing agent in the nano skin care product is 1%-8%, optionally 1%-7%; and / or

[0061] The mass proportion of the nucleic acid in the nano skin care product is 0.05%-0.3%, and can be optionally 0.05%-0.25%.

[0062] In some embodiments, the pH value of the nano skin care product is 4.0-8.0, and can be optionally 4.5-7.5.

[0063] In some embodiments, the types of the nano skin care products include one or more of lotions, emulsion creams, facial masks, and essence creams.

[0064] The fourth aspect of the present application provides a use of the nanoemulsion composition of the first aspect of the present application in preparing a skin care product with a targeted effect.

[0065] In some embodiments, the targeting is to keratinocytes.

[0066] The above-mentioned nanoemulsion composition forms a positively charged nanoemulsion through the regulation of specific components, and the linear nucleic acid is adsorbed on the nanoemulsion through electrostatic self-assembly with the negatively charged nucleic acid. Since the nanoemulsion composition reaches a nanometer particle size, it has excellent permeability, thereby improving the skin permeability of the nucleic acid and increasing the bioavailability of the nucleic acid. At the same time, since the nucleic acid can specifically bind to the adenosine A2A receptor distributed on keratinocytes, the targeting of the nucleic acid is used to accurately locate the nanoemulsion on the keratinocytes, which can accelerate the binding speed of the nanoemulsion to the cells, achieve targeted promotion of the absorption and effect of the barrier repair lipids, improve the bioavailability of the barrier repair lipids, accurately and scientifically repair the skin barrier, and enhance the skin's resistance to photoaging. In addition, by regulating the mass proportion of nucleic acids in the nanoemulsion composition within an appropriate range, it is beneficial to obtain a nanoemulsion composition with excellent stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] In order to more clearly illustrate the technical solutions in the embodiments of the present application and to more fully understand the present application and its beneficial effects, the following is a brief introduction to the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present application. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0068] Figure 1 TEM images of the nanoemulsion composition and nano essence cream in Example 2.

[0069] Figure 2 These are the test results of the phagocytic ability of the essence cream in Example 2 and Comparative Example 8 on keratinocytes. DETAILED DESCRIPTION

[0070] To facilitate understanding of the present invention, the present application will be described more fully below with reference to the relevant embodiments. The following provides preferred embodiments of the present application. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present application more thorough and comprehensive.

[0071] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0072] The terms "and / or", "or / and", and "and / or" used herein include any one of two or more related listed items, and also include any and all combinations of the related listed items, wherein the any and all combinations include any combination of two related listed items, any more related listed items, or all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in this application, the technical solution undoubtedly includes technical solutions connected by "logical AND" and technical solutions connected by "logical OR".

[0073] In this application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0074] In this application, when referring to numerical ranges, unless otherwise specified, the numerical ranges are considered continuous and include the minimum and maximum values ​​of the range, as well as every value between such minimum and maximum values. Further, when a range refers to an integer, every integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe a feature or characteristic, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges subsumed therein.

[0075] Only certain numerical ranges are specifically disclosed herein. However, any lower limit may be combined with any upper limit to form an unspecified range; and any lower limit may be combined with other lower limits to form an unspecified range, and similarly, any upper limit may be combined with any other upper limit to form an unspecified range. In addition, each individually disclosed point or single value may itself serve as a lower limit or upper limit and be combined with any other point or single value, or with other lower limits or upper limits, to form an unspecified range.

[0076] The temperature parameters in this application, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows for temperature fluctuations within the precision range of instrument control. Fluctuations within the ranges of ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are permitted.

[0077] Herein, the “suitable” mentioned in “suitable combination”, “suitable method”, “any suitable method”, etc. shall be based on the ability to implement the technical solution of this application, solve the technical problems of this application, and achieve the expected technical effects of this application.

[0078] In this application, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be understood as limiting the scope of protection of this application.

[0079] In this application, the terms "optionally," "optional," and "optional" mean optional or dispensable, i.e., they refer to either option being selected from two parallel options: "with" or "without." If a technical solution contains multiple "optional" clauses, each "optional" clause is independent unless otherwise specified and there are no contradictions or constraints.

[0080] In the description of the application, "multiple" means at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0081] Unless otherwise stated, all formulations and tests herein took place at 25°C.

[0082] As used herein, the terms "comprise," "include," "contain," "have," "have," or other variations thereof are intended to encompass non-exclusive inclusions, and no distinction is made between these terms. The term "comprising" means that other steps and ingredients that do not affect the end result may be added. The compositions and methods / processes of the present invention comprise, consist of, and consist essentially of the essential elements and limitations described herein, as well as any additional or optional ingredients, components, steps, or limitations described herein. As used herein, no distinction is made between the terms "efficacy," "performance," "effect," and "efficacy."

[0083] Unless otherwise specified, all embodiments and optional embodiments of the present application can be combined with each other to form a new technical solution. Unless otherwise specified, all technical features and optional technical features of the present application can be combined with each other to form a new technical solution.

[0084] Unless otherwise specified, all steps of the present application can be performed sequentially or randomly, preferably sequentially.

[0085] The solar spectrum is composed of radiation of various wavelengths. The full spectrum of sunlight comprises 5% ultraviolet (UV), 45% visible light (VL), and 50% infrared (IR). Visible light primarily affects the skin by causing oxidative damage, while IR induces thermal damage and alters the integrity of skin cell mitochondria, leading to the production of reactive oxygen species (ROS). UVA and UVB are the wavelengths most responsible for skin damage.

[0086] Ultraviolet radiation affects keratinocyte proliferation, differentiation, and the expression of permeability-related proteins on the cell membrane. It also influences the content and ratio of intercellular lipids in the epidermis and the expression of enzymes and proteins involved in corneal mantle differentiation. Therefore, UV damages the skin barrier. UVA-induced immediate pigmentation occurs primarily through photooxidation of existing melanin rather than the synthesis of new pigments, while UVB leads to persistent pigmentation. Therefore, UV radiation can cause hyperpigmentation. UV radiation penetrates the surface layers of the skin, reaching the lower layers of the epidermis, generating harmful reactive oxygen and nitrogen species (ROS and RNS), which cause inflammation and sunburn, and accelerate skin aging. Increased ROS production leads to increased expression of matrix metalloproteinases (MMPs). MMPs (MMP-1, MMP-3, and MMP-9) are responsible for destroying collagen and degrading dermal matrix proteins, leading to damage to collagen, glycosaminoglycans, and elastin, further accelerating skin aging. UV radiation can also induce angiogenesis or dilation, and can contribute to the development of skin cancer.

[0087] When ultraviolet rays damage the skin barrier, the skin's ability to resist photoaging will be weakened, making the skin more susceptible to damage from ultraviolet rays and other factors, resulting in photoaging.

[0088] Nucleic acids are an important class of biomolecules in living organisms, playing a key role in storing and transmitting genetic information within cells. Nucleic acids are divided into two main types: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). PDRN, a growth factor-like bioactive molecule, is one of the building blocks of DNA within cells and possesses natural biocompatibility. Nucleic acids exert powerful anti-inflammatory and repairing effects in wound healing, scar repair, and joint damage, and they also promote angiogenesis, collagen synthesis, and the activity of fibroblasts and osteoblasts. However, PDRN has a short half-life of only approximately three hours, and its inherent negative charge makes it difficult to be internalized by receptor cells. Due to their negative charge, high molecular weight, and hydrophilic nature, nucleic acids have a poor ability to penetrate cell membranes, significantly limiting their application in cosmetics.

[0089] Based on the above problems, the present application non-covalently modifies nucleic acids on a nanoemulsion containing barrier-repairing lipids. The nanoemulsion penetrates the barrier-repairing lipids into the skin and precisely locates them on keratinocytes through the action of nucleic acid molecules, thereby accelerating the binding speed of the nanoemulsion to the cells, achieving targeted promotion of the absorption and effect of the barrier-repairing lipids, and achieving the effect of resisting photoaging.

[0090] One or more embodiments of the present application provide a nanoemulsion composition, comprising a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, the nanoemulsion comprising an effective ingredient, an emulsifier, an emollient, an antioxidant, a moisturizer, and water; the effective ingredient comprises a barrier repair lipid, the barrier repair lipid comprises a sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid, and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0091] It should be noted that the nanoemulsion is positively charged and the nucleic acid is negatively charged, and the nanoemulsion and the nucleic acid form a nanoemulsion composition through electrostatic self-assembly.

[0092] As a non-limiting example, the mass percentage of nucleic acid in the nanoemulsion composition can be, but is not limited to, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, or a range between any two of the above mass percentages.

[0093] The use of phytosphingosine helps the nanoemulsion to carry a positive charge and can also increase the level of ceramide in the stratum corneum and the barrier function.

[0094] As we age or develop skin problems, the ceramide content in the intercellular lipids of the stratum corneum decreases. The ceramides, free fatty acids, and cholesterol added to the nanoemulsion can replace stratum corneum lipids, improve skin condition, and accelerate the repair of the skin barrier. Ceramides can also increase skin hydration, strengthen the skin barrier, protect against external stimuli, and repair the skin. They can also enhance the resistance of stratum corneum cells, improve the skin's adaptability and resistance to light exposure, protect against ultraviolet radiation, and enhance the skin's inherent resistance to photoaging.

[0095] Nucleic acids can bind to the A2A receptors expressed by keratinocytes. The A2A receptors are involved in the proliferation response of keratinocytes. Activation of the A2A receptors can promote the proliferation of keratinocytes. Activation of the A2A receptors can reduce the production and secretion of inflammatory cytokines by keratinocytes under inflammatory stimulation.

[0096] Understandably, the nanoemulsion composition of the present application forms a positively charged nanoemulsion through the regulation of specific components, and the linear nucleic acid is adsorbed on the nanoemulsion through electrostatic self-assembly with the negatively charged nucleic acid; because the nanoemulsion composition reaches a nanometer particle size, it has excellent permeability, thereby improving the skin permeability of the nucleic acid and increasing the bioavailability of the nucleic acid; at the same time, because the nucleic acid can specifically bind to the adenosine A2A receptor distributed on the keratinocytes, the targeting of the nucleic acid is used to accurately locate the nanoemulsion on the keratinocytes, which can accelerate the binding speed of the nanoemulsion to the cells, achieve targeted promotion of the absorption and effect of the barrier repair lipids, improve the bioavailability of the barrier repair lipids, accurately and scientifically repair the skin barrier, and enhance the skin's resistance to photoaging. In addition, by regulating the mass proportion of nucleic acids in the nanoemulsion composition within an appropriate range, it is beneficial to obtain a nanoemulsion composition with excellent stability.

[0097] In some embodiments, the mass proportion of phytosphingosine in the barrier-repairing lipids is 15%-50%; for example, it can be, but is not limited to, 15%, 17%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46%, 48%, 50%, or a range between any two of the above values. When the mass proportion of phytosphingosine in the barrier-repairing lipids is within the above range, it is beneficial to further improve the stability of the nanoemulsion composition.

[0098] In some embodiments, the barrier-repairing lipids include phytosphingosine and one or more of ceramide EOS, ceramide NS, ceramide NP, ceramide AS, ceramide AP, linoleic acid, palmitic acid, and cholesterol. It should be noted that the barrier-repairing lipids include phytosphingosine and one or more of ceramide EOS, ceramide NS, ceramide NP, ceramide AS, ceramide AP, linoleic acid, palmitic acid, and cholesterol.

[0099] In some embodiments, the active ingredient further comprises one or more of glabridin, salicylic acid, astaxanthin, phenethylresorcinol, and hydroxypinacolone retinoate.

[0100] As one possible embodiment, the molecular weight of the nucleic acid is 5 wDa-150 wDa; for example, but not limited to, 5 wDa, 10 wDa, 20 wDa, 30 wDa, 40 wDa, 50 wDa, 60 wDa, 70 wDa, 80 wDa, 90 wDa, 100 wDa, 110 wDa, 120 wDa, 130 wDa, 140 wDa, 150 wDa, or a range between any two of the foregoing molecular weights. When the molecular weight of the nucleic acid is within the above range, its negative charge density forms a strong electrostatic interaction with the positive charge on the surface of the cationic nanoemulsion, significantly enhancing adsorption efficiency and delivery stability.

[0101] In some optional embodiments, the mass percentage of DNA in the nucleic acid is ≥70%. Thus, the stability of its double-stranded structure is significantly improved, which can enhance the electrostatic binding efficiency with the cationic nanoemulsion.

[0102] In some exemplary embodiments, the mass percentage of DNA in the nucleic acid is ≥90%.

[0103] As a possible embodiment, the emulsifier includes one or more of alkyl glycoside emulsifiers, polyol ester emulsifiers, Span emulsifiers, Tween emulsifiers, phosphate emulsifiers, fatty alcohol polyether emulsifiers, polyglycerol emulsifiers and high molecular polymer emulsifiers.

[0104] In some optional embodiments, the emulsifier includes one or more of C14-22 alkyl alcohol / C12-20 alkyl glucoside, eicosyl behenyl alcohol / eicosyl glucoside, cetyl alcohol / cetearyl glucoside / sucrose stearate, steareth-21, lecithin, Span 20, Span 40, Span 60, Span 80, Tween 80, Tween 120, polyglyceryl-10 stearate, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters.

[0105] In some embodiments, the emollient includes one or more of a high molecular weight polymer, a plant oil, an animal oil, a mineral oil, and a synthetic oil.

[0106] In some optional embodiments, the emollient includes one or more of caprylic / capric triglyceride, caprylic / capric / myristic / stearic triglyceride, bis-PEG-18 methyl ether dimethyl silane, isononyl isononanoate, cetearyl alcohol, squalane, shea butter, candelilla wax, dipentaerythrityl hexahydroxystearate / hexastearate / hexarosinate, phytosteryl / octyldodecanol lauroyl glutamate, pentaerythrityl tetra(ethylhexanoate), polydimethylsiloxane, ethylhexyl palmitate, coconut oil, olive oil, palm oil, beeswax, jojoba oil, mineral oil and petrolatum.

[0107] In some embodiments, the antioxidant includes one or more of tocopheryl acetate, butylated hydroxytoluene, and pentaerythritol tetrakis-di-tert-butylhydroxyhydrocinnamate.

[0108] In a possible embodiment, the moisturizing agent includes one or more of a polyol moisturizing agent, a natural moisturizing factor, a polymer biochemical moisturizing agent, and an amino acid moisturizing agent.

[0109] In some exemplary embodiments, the humectant includes one or more of glycerin, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, glycereth-26, and trehalose.

[0110] As a possible embodiment, the nanoemulsion composition includes, by mass, 0.05-0.3 parts of nucleic acid, 0.05-2 parts of barrier repair lipids, 1-10 parts of emulsifiers, 1-10 parts of emollients, 0.01-0.2 parts of antioxidants, 1-8 parts of moisturizers and 20-50 parts of water.

[0111] As a non-limiting example, the mass fraction of the nucleic acid in the nanoemulsion composition can be, but is not limited to, 0.05, 0.08, 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, 0.3, or a range between any two of the foregoing mass fractions.

[0112] The mass fraction of the barrier repair lipid in the nanoemulsion composition can be, but is not limited to, 0.05 parts, 0.1 parts, 0.2 parts, 0.4 parts, 0.6 parts, 0.8 parts, 1 part, 1.2 parts, 1.4 parts, 1.6 parts, 1.8 parts, 2 parts, or a range between any two of the above mass fractions.

[0113] The mass fraction of the emulsifier in the nanoemulsion composition can be, but is not limited to, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, or a range between any two of the above mass fractions.

[0114] The mass fraction of the emollient in the nanoemulsion composition can be, but is not limited to, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, or a range between any two of the above mass fractions.

[0115] The amount of the antioxidant in the nanoemulsion composition may be, but is not limited to, 0.01, 0.02, 0.04, 0.06, 0.08, 0.1, 0.12, 0.14, 0.16, 0.18, 0.2, or a range between any two of the foregoing amounts.

[0116] The mass fraction of the moisturizing agent in the nanoemulsion composition can be, but is not limited to, 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, or a range between any two of the above mass fractions.

[0117] The mass fraction of water in the nanoemulsion composition can be, but is not limited to, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 45 parts, 50 parts, or a range between any two of the above mass fractions.

[0118] When the mass fractions of the components in the nanoemulsion composition are respectively within the above ranges, the particle size of the nanoemulsion can be synergistically optimized to form a more stable nanoscale dispersion system, while reducing particle aggregation and Ostwald ripening, thereby improving the physical stability and loading efficiency of the nanoemulsion composition.

[0119] In some optional embodiments, the nanoemulsion composition includes, by mass, 0.05-0.25 parts of nucleic acid, 0.1-1.5 parts of barrier repair lipids, 1-5 parts of emulsifiers, 2-8 parts of emollients, 0.05-0.2 parts of antioxidants, 1-7 parts of moisturizers, and 20-40 parts of water.

[0120] In some embodiments, the particle size of the nanoemulsion is 100 nm to 500 nm; for example, it can be, but is not limited to, 100 nm, 120 nm, 140 nm, 160 nm, 180 nm, 200 nm, 220 nm, 240 nm, 260 nm, 280 nm, 300 nm, 320 nm, 340 nm, 360 nm, 380 nm, 400 nm, 420 nm, 440 nm, 460 nm, 480 nm, 500 nm, or a range between any two of the above particle sizes. When the particle size of the nanoemulsion composition is within the above range, it is beneficial to further improve the skin permeability of the nanoemulsion.

[0121] In some optional embodiments, the particle size of the nanoemulsion is 100 nm-300 nm.

[0122] As a possible embodiment, the polydispersity index of the nanoemulsion is 0.05-0.55; for example, it can be, but is not limited to, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, or a range between any two of the above polydispersity indices. When the polydispersity index of the nanoemulsion composition is within the above range, the dispersion of the system can be improved and the particle / molecule size distribution can be more uniform.

[0123] In some alternative embodiments, the polydispersity index of the nanoemulsion is 0.05-0.35.

[0124] One or more embodiments of the present application provide a method for preparing a nanoemulsion composition, which can be used to prepare the above-mentioned nanoemulsion composition. The preparation method comprises the following steps:

[0125] Phase A is prepared, and phase A includes an effective ingredient, a portion of an emollient, an antioxidant, and a portion of an emulsifier; phase B is prepared, and phase B includes a moisturizer, a portion of water, the remaining emollient, and the remaining emulsifier; phase A and phase B are mixed to prepare a nanoemulsion; nucleic acid is mixed with the remaining water to prepare a nucleic acid aqueous solution; the nanoemulsion is mixed with the nucleic acid aqueous solution to prepare a nanoemulsion composition; wherein the effective ingredient includes barrier repair lipids, the barrier repair lipids include sphingolipids, the sphingolipids include phytosphingosine, and the barrier repair lipids further include one or more of ceramides, free fatty acids, and cholesterol; the mass proportion of nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0126] As a non-limiting example, the mass percentage of nucleic acid in the nanoemulsion composition can be, but is not limited to, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, or a range between any two of the above mass percentages, etc. By regulating the mass percentage of nucleic acid in the nanoemulsion composition within the above range, it is beneficial to obtain a nanoemulsion composition with excellent stability.

[0127] It can be understood that the nanoemulsion composition prepared by this preparation method has similar technical solutions and advantages to the aforementioned nanoemulsion composition, which will not be described in detail here.

[0128] In some embodiments, the preparation method of phase A comprises: dissolving phytosphingosine in a portion of an emollient, and then adding antioxidants, a portion of emulsifiers, and components of the barrier repair lipids other than phytosphingosine to prepare phase A. When preparing phase A, first dissolving phytosphingosine in the emollient can ensure that it is fully dissolved and forms a uniform oil phase, thereby avoiding crystallization during the subsequent cooling process. In some optional embodiments, phytosphingosine is dissolved in a portion of the emollient under heating conditions of 90°C-100°C. As an example, the heating temperature when dissolving phytosphingosine in a portion of the emollient can be, but is not limited to, 90°C, 92°C, 94°C, 96°C, 98°C, 100°C, or a range between any two of the above temperatures.

[0129] In some exemplary embodiments, the antioxidant, part of the emulsifier, and the components of the barrier repair lipid other than phytosphingosine are added to the emollient under heating conditions of 80°C to 90°C.

[0130] As a non-limiting example, the effective ingredients further include one or more of glycyrrhizin, salicylic acid, astaxanthin, phenylethylresorcinol and hydroxypinacolone retinoate; the preparation method of phase A comprises: dissolving phytosphingosine in part of the emollient, and then adding an antioxidant, part of the emulsifier, the components of the barrier repair lipid other than phytosphingosine, and the components of the effective ingredients other than the barrier repair lipid to prepare phase A.

[0131] In some optional embodiments, the preparation method of phase A includes: dissolving phytosphingosine in a portion of the emollient under heating conditions of 90°C-100°C; adding antioxidants, part of the emulsifier, components of the barrier repair lipid other than phytosphingosine, and other effective ingredients (one or more of salicylic acid, phenylethyl resorcinol and hydroxypinacolone retinoate) to the lotion under heating conditions of 80°C-90°C, or adding glycyrrhizin and astaxanthin after the temperature is reduced to about 50°C to prepare phase A.

[0132] As a possible embodiment, the preparation method of phase B includes: adding the moisturizer, the remaining emollient and the remaining emulsifier to a portion of water, and stirring to prepare phase B.

[0133] In some embodiments, the step of mixing phase A and phase B includes: after mixing phase A and phase B, performing a first homogenization treatment and a second homogenization treatment in sequence; the rate of the first homogenization treatment is 2000 rpm-12000 rpm, and the time is 2 min-60 min; the pressure of the second homogenization treatment is 100 bar-2000 bar, and the number of times is 2 times to 20 times.

[0134] It should be noted that, in this document, the terms "first" and "second," etc., such as "first homogenization treatment" and "second homogenization treatment," are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor as implicitly indicating the importance or quantity of the technical features being referred to. Furthermore, "first," "second," etc., serve only as non-exhaustive enumeration and description and should not constitute a closed-ended limitation on quantity.

[0135] As a non-limiting example, the speed of the first homogenization process may be, but is not limited to, 2000 rpm, 4000 rpm, 6000 rpm, 8000 rpm, 10000 rpm, 12000 rpm, or a range between any two of the above speeds. Alternatively, the speed of the first homogenization process is 3000 rpm-10000 rpm. The time of the first homogenization process may be, but is not limited to, 2 min, 5 min, 10 min, 15 min, 20 min, 25 min, 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min, or a range between any two of the above time periods. Alternatively, the time of the first homogenization process is 3 min-30 min.

[0136] It should be noted that the rate and time of the first homogenization process can be combined in any suitable manner, and both can be selected from any of the rates and times of the first homogenization process described herein.

[0137] As a non-limiting example, the pressure of the second averaging process may be, but is not limited to, 100 bar, 200 bar, 400 bar, 600 bar, 800 bar, 1000 bar, 1200 bar, 1400 bar, 1600 bar, 1800 bar, 2000 bar, or a range between any two of the above pressures. Optionally, the pressure of the second averaging process is 300 bar-1000 bar. The number of times of the second homogenization process may be, but is not limited to, 2 times, 4 times, 6 times, 8 times, 10 times, 12 times, 14 times, 16 times, 18 times, 20 times, or a range between any two of the above numbers. Optionally, the number of times of the second homogenization process is 2 times-10 times.

[0138] In some embodiments, the stirring time when the nucleic acid is mixed with the remaining water is 0.5 hours to 24 hours, for example, but not limited to 0.5 hours, 1 hour, 5 hours, 10 hours, 15 hours, 20 hours, 24 hours, or a range between any two of the above times. Alternatively, the stirring time when the nucleic acid is mixed with the remaining water is 0.5 hours to 12 hours.

[0139] As a possible embodiment, the stirring time when the nanoemulsion and the nucleic acid aqueous solution are mixed is 0.5 h to 4 h; for example, it can be, but is not limited to, 0.5 h, 1 h, 2 h, 3 h, 4 h, or a range between any two of the above times. Optionally, the stirring time when the nanoemulsion and the nucleic acid aqueous solution are mixed is 0.5 h to 3 h.

[0140] One or more embodiments of the present application provide a nano skin care product, comprising a nanoemulsion composition, the nanoemulsion composition comprising a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, the nanoemulsion comprising an effective ingredient, an emulsifier, an emollient, an antioxidant, a moisturizer and water; the effective ingredient comprises a barrier repair lipid, the barrier repair lipid comprises a sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

[0141] The nanoemulsion composition contained in this nano skin care product has a nanometer-scale particle size and excellent permeability, thereby improving the skin permeability of nucleic acids and increasing the bioavailability of nucleic acids. At the same time, because nucleic acids can specifically bind to adenosine A2A receptors distributed on keratinocytes, the targeting of nucleic acids is used to accurately locate the nanoemulsion on keratinocytes, which can accelerate the binding speed of the nanoemulsion to the cells, achieve targeted promotion of the absorption and effect of barrier repair lipids, improve the bioavailability of barrier repair lipids, accurately and scientifically repair the skin barrier, and enhance the skin's resistance to photoaging. In addition, by regulating the mass proportion of nucleic acids in the nanoemulsion composition within an appropriate range, it is beneficial to obtain a nanoemulsion skin care product with excellent stability.

[0142] It is understandable that the nanoemulsion composition contained in the nano skin care product has similar technical solutions and advantages to the aforementioned nanoemulsion composition, which will not be described in detail here.

[0143] In some embodiments, the nano skin care product further comprises an active ingredient, a skin conditioning agent, a preservative, a chelating agent, a thickener and water.

[0144] As a possible embodiment, the active ingredient includes one or more of sugar derivatives, natural plant extracts, nucleosides, metal oxides and amide compounds.

[0145] In some optional embodiments, the active ingredient includes one or more of cerium oxide, glyceryl glucoside, madecassoside, adenosine, niacinamide, β-glucan, sodium hyaluronate, tranexamic acid, retinol, vitamin C, ferulic acid, green tea extract, arbutin, soy isoflavones and hydrolyzed oat protein.

[0146] As a possible implementation, the thickener includes one or more of polyacrylic acid, fatty alcohols, fatty acids, cellulose, natural rubber and its modifications, esters, inorganic polymers and their modifications.

[0147] In some exemplary embodiments, the thickener includes one or more of sodium polyacrylate, carbomer, sodium polyacryloyldimethyl taurate, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, starch, gum arabic, pectin, agar, gelatin, alginate, carrageenan, and dextrin.

[0148] In some embodiments, the preservative includes one or more of an alcohol preservative, a paraben preservative, an isothiazolinone preservative, a formaldehyde-releasing preservative, and an acid preservative.

[0149] In some embodiments, the preservative includes one or more of 1,2-pentanediol, 1,2-hexanediol, phenoxyethanol / ethylhexylglycerin, methylparaben, ethylparaben, propylparaben, sorbic acid, benzoic acid, dehydroacetic acid, methylchloroisothiazolinone, and methylisothiazolinone.

[0150] As a possible embodiment, the chelating agent includes one or more of hydroxy acid chelating agents and amino acid derivative chelating agents.

[0151] In some optional embodiments, the chelating agent includes one or more of disodium EDTA, ethylenediaminetetraacetic acid, tetrasodium ethylenediaminetetraacetic acid, and disodium nitrilotriacetate.

[0152] In some embodiments, the nano skin care product is composed of the following components, in percentage by mass: active ingredient 1%-10%, skin conditioner 0.1%-4%, preservative 1%-10%, chelating agent 0.01%-0.06%, thickener 0.05%-4%, barrier repair lipid 0.05%-2%, emulsifier 1%-10%, emollient 1%-10%, antioxidant 0.01%-0.2%, moisturizer 1%-8%, nucleic acid 0.05%-0.3%, and the balance is water.

[0153] In some embodiments, the active ingredient accounts for 1% to 10% by weight of the nano skin care product; for example, it can be, but is not limited to, 1%, 2%, 4%, 6%, 8%, 10%, or a range between any two of the above values. In some optional embodiments, the active ingredient accounts for 1% to 6% by weight of the nano skin care product.

[0154] As a possible embodiment, the mass proportion of the skin conditioning agent in the nano skin care product is 0.1%-4%; for example, it can be but not limited to 0.1%, 0.5%, 1%, 2%, 3%, 4%, or a range between any two of the above values. Optionally, the mass proportion of the skin conditioning agent in the nano skin care product is 0.5%-3%.

[0155] In some embodiments, the preservative accounts for 1% to 10% by weight of the nano skin care product; for example, it can be, but is not limited to, 1%, 2%, 4%, 6%, 8%, 10%, or a range between any two of the above values. Optionally, the preservative accounts for 1% to 6% by weight of the nano skin care product.

[0156] In some embodiments, the weight percentage of the chelating agent in the nano skin care product is 0.01%-0.06%, for example, but not limited to 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, or a range between any two of the above values. Optionally, the weight percentage of the chelating agent in the nano skin care product is 0.01%-0.05%.

[0157] As a possible embodiment, the mass proportion of the thickener in the nano skin care product is 0.05%-4%; for example, it can be but not limited to 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, or a range between any two of the above values. Optionally, the mass proportion of the thickener in the nano skin care product is 0.5%-3%.

[0158] In some optional embodiments, the weight percentage of barrier-repairing lipids in the nano-skin care product is 0.05%-2%, for example, but not limited to 0.05%, 0.1%, 0.5%, 1%, 2%, or a range between any two of the above values. Alternatively, the weight percentage of barrier-repairing lipids in the nano-skin care product is 0.1%-1.5%.

[0159] As a possible embodiment, the mass proportion of the emulsifier in the nano skin care product is 1%-10%, for example, but not limited to 1%, 2%, 4%, 6%, 8%, 10%, or a range between any two of the above values. Optionally, the mass proportion of the emulsifier in the nano skin care product is 1%-5%.

[0160] In some embodiments, the emollient accounts for 1% to 10% by weight of the nano-skin care product; for example, but not limited to, 1%, 2%, 4%, 6%, 8%, 10%, or a range between any two of the above values. Optionally, the emollient accounts for 2% to 8% by weight of the nano-skin care product.

[0161] As a possible embodiment, the weight percentage of the antioxidant in the nano skin care product is 0.01%-0.2%; for example, it can be but not limited to 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, or a range between any two of the above values. Optionally, the weight percentage of the antioxidant in the nano skin care product is 0.05%-0.2%.

[0162] In some embodiments, the mass proportion of the moisturizer in the nano skin care product is 1%-8%, for example, but not limited to 1%, 2%, 4%, 6%, 8%, or a range between any two of the above values. Optionally, the mass proportion of the moisturizer in the nano skin care product is 1%-7%.

[0163] In some embodiments, the mass proportion of nucleic acid in the nano skin care product is 0.05%-0.3%, for example, but not limited to 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, or a range between any two of the above values. Optionally, the mass proportion of nucleic acid in the nano skin care product is 0.05%-0.25%.

[0164] In some embodiments, the pH value of the nano skin care product is 4.0-8.0, for example, but not limited to 4.0, 5.0, 6.0, 7.0, 8.0, or a range between any two of the above pH values. Optionally, the pH value of the nano skin care product is 4.5-7.5.

[0165] As a possible implementation manner, the types of nano skin care products include one or more of lotions, emulsion creams, facial masks and essence creams.

[0166] One or more embodiments of the present application provide a use of the above-mentioned nanoemulsion composition in preparing a skin care product with a targeted effect.

[0167] Optionally, targeting refers to targeting keratinocytes.

[0168] The following is a detailed description of the technical solutions of the present application in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. For experimental methods in the following examples where specific conditions are not specified, reference should be made to the instructions given in this application, or to experimental manuals or conventional conditions in the field, or to conditions recommended by the manufacturer, or to experimental methods known in the art.

[0169] In the following specific examples, the measured parameters of raw material components may have slight deviations within the range of weighing accuracy unless otherwise specified. For temperature and time parameters, acceptable deviations caused by instrument testing accuracy or operational accuracy are allowed.

[0170] It should be noted that the raw materials used in the following examples and comparative examples can all be purchased from the market.

[0171] 1. Preparation of Nanoemulsion Composition and Nano Essence Cream

[0172] Example 1

[0173] 1. Formula composition of nanoemulsion composition

[0174] Taking water as the solvent, the composition, calculated by mass percentage in the essence cream, includes: lecithin (emulsifier) ​​0.25%, caprylic / capric triglyceride (emollient) 1.5%, isononyl isononanoate (emollient) 3%, phytosphingosine (barrier repair lipid) 0.075%, ceramide NP (barrier repair lipid) 0.1%, cholesterol (barrier repair lipid) 0.0665%, linoleic acid (barrier repair lipid) 0.0485%, tocopheryl acetate (antioxidant) 0.05%, pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) ester (antioxidant) 0.015%, emulsifying base 1.8%, bis-PEG-18 methyl ether dimethyl silane (emollient) 2%, glycerin (humectant) 4%, nucleic acid 0.1%, and the balance is water. Among them, the emulsifying matrix includes C14-22 alkyl alcohol / C12-20 alkyl glucoside 0.5%, eicosyl behenyl alcohol / eicosyl glucoside 0.5% and steareth-21 0.8%.

[0175] 2. Preparation of Nanoemulsion Compositions

[0176] Dissolve phytosphingosine in caprylic / capric triglyceride and isononyl isononanoate at 90°C. After dissolution, cool to 85°C, then add lecithin, ceramide NP, cholesterol, linoleic acid, tocopheryl acetate, pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate), C14-22 alkyl alcohol / C12-20 alkyl glucoside, and eicosyl behenyl alcohol / eicosyl glucoside, and stir to dissolve to obtain Phase A components.

[0177] Heat and stir Steareth-21, Bis-PEG-18 Methyl Ether Dimethyl Silane, glycerin, and water at 85°C to obtain Phase B.

[0178] The phase A and phase B were mixed, homogenized at 8000 rpm for 5 min, and then subjected to high-pressure homogenization at 700 bar for 5 cycles to prepare a ceramide-loaded nanoemulsion.

[0179] The raw nucleic acid and water were stirred and mixed for 30 minutes to obtain a nucleic acid aqueous solution; the nucleic acid aqueous solution and the ceramide-encapsulated nanoemulsion were stirred to obtain a nanoemulsion composition.

[0180] Example 2

[0181] The preparation methods of Example 2 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of nucleic acid added is 0.3%, the amount of water used is 36.745%, and the other conditions are the same.

[0182] Example 3

[0183] The preparation methods of Example 3 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of nucleic acid added is 0.05%, the amount of water used is 36.995%, and the other conditions are the same.

[0184] Example 4

[0185] The preparation methods of Example 4 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of ceramide NP added is 0.05%, the amount of water used is 36.745%, and the other conditions are the same.

[0186] Example 5

[0187] The preparation methods of Example 5 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of ceramide NP added is 0.3%, the amount of water used is 36.045%, and the other conditions are the same.

[0188] Example 6

[0189] The preparation methods of Example 6 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of phytosphingosine added is 0.05%, the amount of water used is 36.77%, and the other conditions are the same.

[0190] Example 7

[0191] The preparation methods of Example 7 are similar to those of Example 1, except that when preparing the nanoemulsion composition, the amount of phytosphingosine added is 0.15%, the amount of water used is 36.87%, and the other conditions are the same.

[0192] Example 8

[0193] 1. The composition of nano essence cream

[0194] Taking water as solvent, the ingredients, calculated by mass percentage, include: β-glucan (active ingredient) 0.1%, niacinamide (active ingredient) 2%, adenosine (active ingredient) 1%, glyceryl glucoside (active ingredient) 0.1%, madecassoside (active ingredient) 0.2%, cerium oxide (active ingredient) 0.3%, 1,2-hexanediol (preservative) 1%, 1,2-pentanediol (preservative) 2%, disodium EDTA (chelating agent) 0.03%, sodium polyacrylate (thickener) 1%, lecithin (emulsifier) 0.25%, Caprylic / Capric Triglyceride (Emollient) 1.5%, Isononyl Isononanoate (Emollient) 3%, Phytosphingosine (Barrier-Repairing Lipid) 0.075%, Ceramide NP (Barrier-Repairing Lipid) 0.1%, Cholesterol (Barrier-Repairing Lipid) 0.0665%, Linoleic Acid (Barrier-Repairing Lipid) 0.0485%, Tocopheryl Acetate (Antioxidant) 0.05%, Pentaerythrityl Tetra-(Di-t-Butyl Hydroxyhydrocinnamate) (Antioxidant) 0.015%, Emulsifying Base 1.8%, Bis-PEG-18 Methyl Ether Dimethyl Silane (Emollient) 2%, Glycerin (Humectant) 4%, Nucleic Acids 0.1%, Balance Water. The emulsifying base includes 0.5% C14-22 Alkyl Alcohol / C12-20 Alkyl Glucoside, 0.5% Eicosyl Behenyl Alcohol / Eicosyl Glucoside, and 0.8% Steareth-21.

[0195] Among them, lecithin, caprylic / capric triglyceride, isononyl isononanoate, phytosphingosine, ceramide NP, cholesterol, linoleic acid, tocopheryl acetate, pentaerythritol tetra(bis-tert-butyl hydroxyhydrocinnamate), emulsifying base, bis-PEG-18 methyl ether dimethyl silane, glycerol, nucleic acid and 36.945% water are used to prepare the nanoemulsion composition.

[0196] 2. Preparation process

[0197] 2.1 Preparation of nanoemulsion composition: same as in Example 1

[0198] 2.2 Preparation of Nano Essence Cream

[0199] FlexiGiu, niacinamide, adenosine, glyceryl glucoside, madecassoside, 1,2-hexanediol, and 1,2-pentanediol are added to the above-mentioned nanoemulsion composition and stirred to dissolve. The cerium oxide, chelating agent, and water that have been dispersed in advance are also added to the targeted nanoemulsion composition and stirred evenly. The thickener and the remaining water are added to the above-mentioned composition and stirred to dissolve to obtain the light-repairing nano essence cream.

[0200] Example 9

[0201] The preparation methods of Example 9 are similar to those of Example 8, except that when preparing the nano essence cream, the amount of sodium polyacrylate added is 3%, and all other aspects are the same.

[0202] Example 10

[0203] The preparation methods of Example 10 are similar to those of Example 8, except that when preparing the nano essence cream, the amount of sodium polyacrylate added is 0.3%, and all other aspects are the same.

[0204] Comparative Example 1

[0205] The preparation methods of Comparative Example 1 and Example 1 are similar, except that when preparing the nanoemulsion composition, the amount of nucleic acid added is 0.025%, the amount of water used is 37.02%, and the other conditions are the same.

[0206] Comparative Example 2

[0207] The preparation methods of Comparative Example 2 and Example 1 are similar, except that when preparing the nanoemulsion composition in Comparative Example 2, the amount of nucleic acid added is 0.35%, the amount of water used is 36.695%, and the other conditions are the same.

[0208] Comparative Example 3

[0209] The preparation methods of Comparative Example 3 and Example 2 are similar, except that caprylic / capric triglyceride is not added when preparing the nanoemulsion composition in Comparative Example 3, the amount of water used is 38.445%, and all other conditions are the same.

[0210] Comparative Example 4

[0211] The preparation methods of Comparative Example 4 and Example 1 are similar, except that when preparing the nanoemulsion composition in Comparative Example 4, the amount of ceramide NP added is 0.35%, the amount of water used is 36.445%, and the other conditions are the same.

[0212] Comparative Example 5

[0213] The preparation methods of Comparative Example 5 and Example 1 are similar, except that in Comparative Example 5, no phytosphingosine was added when preparing the nanoemulsion composition, the amount of water used was 37.02%, and all other conditions were the same.

[0214] Comparative Example 6

[0215] The preparation methods of Comparative Example 6 and Example 1 are similar, except that in Comparative Example 6, the amount of phytosphingosine added when preparing the nanoemulsion composition is 0.2%, and the amount of water used is 36.82%. Other details are the same.

[0216] Comparative Example 7

[0217] The preparation methods of Comparative Example 7 are similar to those of Example 1, except that in the preparation of the nanoemulsion composition in Comparative Example 7, polyglyceryl-10 laurate is used instead of steareth-21.

[0218] Comparative Example 8

[0219] The preparation methods of Comparative Example 8 are similar to those of Example 1, except that in the preparation of the nanoemulsion composition in Comparative Example 8, sucrose stearate SE121 is used instead of steareth-21.

[0220] Comparative Example 9

[0221] The preparation methods of Comparative Example 9 are similar to those of Example 8, except that in Comparative Example 9, the nucleic acid is not combined with the nanoemulsion to form a nanoemulsion composition, but is added to a thickener system and stirred into a cream. Other aspects are the same.

[0222] Comparative Example 10

[0223] The preparation methods of Comparative Example 10 and Example 8 are similar, except that when preparing the nano essence cream, the added amount of sodium polyacrylate is 5%, and the other aspects are the same.

[0224] 2. Performance Testing

[0225] 1. The nano essence creams prepared in the above embodiments and comparative examples were tested for usage experience and storage stability. The results are shown in Table 1.

[0226] Table 1

[0227]

[0228] The nano essence cream described in Example 8 was tested for effectiveness on 40 women aged 20-60 over five days. The subjects used the nano essence cream twice daily, as per their usual usage habits. After use, the subjects evaluated the product's immediate redness-reducing effect, moisturizing effect, skin feel, and mildness. The results are shown in Table 2.

[0229] Table 2

[0230]

[0231] As can be seen from the results in Table 2, the nano essence cream of the present application has better redness-removing and moisturizing effects. The product is mild and non-irritating, has a better skin feel, and has a certain effect of improving facial sensitivity problems.

[0232] 2. TEM Observation

[0233] The nanoemulsion composition and nano essence cream prepared in Example 8 were subjected to TEM testing. The testing method was as follows: the nanoemulsion composition and nano essence cream were diluted 10 times with water to obtain test samples. The test sample was dropped onto a copper mesh. After a few seconds, the copper mesh sample was gently picked up with tweezers and excess liquid was absorbed along one side with filter paper. After it was slightly dry, the copper mesh was placed on a drop of 2% phosphotungstic acid dye solution and stained for 60 seconds. After it was picked up with tweezers, excess liquid was also absorbed along one side with filter paper. The membrane was placed on the filter paper with the membrane facing up to dry. The sample was observed and photographed using a transmission electron microscope. The results are shown in FIG. Figure 1 As shown. Among them, Figure 1 (a) is a TEM image of the nanoemulsion composition, Figure 1 Middle (b) is the TEM image of the nano essence cream.

[0234] Depend on Figure 1 It can be seen that the nanoemulsion composition is spherical. Figure 1 As shown in (a), the nanoemulsion is surrounded by layers of nucleic acid molecules. According to the scale, the particle size of the nanoemulsion can be measured to be approximately 100 nm. Figure 1 As shown in (b), after the nanoemulsion composition is prepared into an essence cream, the structure of the nanoemulsion is not destroyed, indicating that the nanoemulsion can exist well in the cream.

[0235] 3. Testing of keratinocyte phagocytic ability

[0236] Fluorescein free acid was used to label the essence creams in Example 8 and Comparative Example 9. Human immortal keratinocyte cell line (HaCaT) cells were placed in a 25 cm 2 The cells were cultured in DMEM supplemented with fetal bovine serum (10%), penicillin (100 units / ml) and streptomycin (50 units / ml) at 37°C in a carbon dioxide incubator (relative humidity 95%, carbon dioxide 5%).

[0237] HaCaT cells were plated at 2 × 10 5 Cells were cultured at a density of 100 μg / mL in glass-bottomed culture dishes overnight. 1 mL of sample (0.03%) was added and incubated at 37°C for another 30 minutes. The cell culture medium was discarded and the cells were rinsed three times with PBS. The nuclei were then stained with DAPI for 20 minutes. Finally, the cells were rinsed three times with cold PBS and observed using a laser confocal scanning microscope. Figure 2 shown.

[0238] like Figure 2As shown, in the comparative example 9 group, a small number of HaCaT cells showed weak fluorescence, while the fluorescence in the cells of the example 8 group was significantly stronger and more widely distributed, indicating that more cells successfully engulfed the fluorescently labeled Royal Light Repair Essence Cream of the example 8 group, and that the binding rate of the example 8 to the cells was faster. This shows that the nanoemulsion composition prepared in this application can effectively promote the binding ability of keratinocytes to the nanoemulsion composition.

[0239] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0240] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A nanoemulsion composition, characterized in that The invention comprises a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, wherein the nanoemulsion contains an effective ingredient, an emulsifier, an emollient, an antioxidant, a moisturizer and water; the effective ingredient includes a barrier repair lipid, the barrier repair lipid includes a sphingolipid, the sphingolipid includes phytosphingosine, and the barrier repair lipid further includes one or more of ceramide, free fatty acid and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

2. The nanoemulsion composition according to claim 1, wherein The mass proportion of the phytosphingosine in the barrier repair lipids is 15%-50%.

3. The nanoemulsion composition according to claim 1, wherein The barrier repair lipids include phytosphingosine and one or more of ceramide EOS, ceramide NS, ceramide NP, ceramide AS, ceramide AP, linoleic acid, palmitic acid and cholesterol; and / or The effective ingredients further include one or more of glabridin, salicylic acid, astaxanthin, phenethyl resorcinol and hydroxypinacolone retinoic acid ester.

4. The nanoemulsion composition according to claim 1, wherein The molecular weight of the nucleic acid is 5wDa-150wDa; and / or The mass percentage content of DNA in the nucleic acid is ≥70%, and can be optionally ≥90%.

5. The nanoemulsion composition according to claim 1, wherein The emulsifier includes one or more of an alkyl glycoside emulsifier, a polyol ester emulsifier, a Span emulsifier, a Tween emulsifier, a phosphate emulsifier, a fatty alcohol polyether emulsifier, a polyglycerol emulsifier and a high molecular polymer emulsifier; optionally, the emulsifier includes one or more of C14-22 alkyl alcohol / C12-20 alkyl glucoside, eicosyl behenyl alcohol / eicosyl glucoside, cetyl alcohol / cetearyl glucoside / sucrose stearate, steareth-21, lecithin, Span 20, Span 40, Span 60, Span 80, Tween 80, Tween 120, polyglyceryl-10 stearate, sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester; and / or The emollient includes one or more of a high molecular weight polymer, a vegetable oil, an animal oil, a mineral oil and a synthetic oil; optionally, the emollient includes one or more of caprylic / capric triglyceride, caprylic / capric / myristic / stearic triglyceride, bis-PEG-18 methyl ether dimethyl silane, isononyl isononanoate, cetearyl alcohol, squalane, shea butter, candelilla wax, dipentaerythritol hexahydroxystearate / hexastearate / hexarosinate, phytosterol / octyldodecanol lauroyl glutamate, pentaerythritol tetraethylhexanoate, polydimethylsiloxane, ethylhexyl palmitate, coconut oil, olive oil, palm oil, beeswax, jojoba oil, mineral oil and petrolatum; and / or The antioxidant comprises one or more of tocopheryl acetate, butylated hydroxytoluene and pentaerythritol tetrakis (di-tert-butyl hydroxyhydrocinnamate); and / or The moisturizing agent includes one or more of a polyol moisturizing agent, a natural moisturizing factor, a high molecular biochemical moisturizing agent and an amino acid moisturizing agent; optionally, the moisturizing agent includes one or more of glycerol, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexanediol, glycerol polyether-26 and trehalose.

6. The nanoemulsion composition according to any one of claims 1 to 5, wherein In parts by mass, the nanoemulsion composition comprises: 0.05-0.3 parts of nucleic acid, 0.05-2 parts of barrier repair lipid, 1-10 parts of emulsifier, 1-10 parts of emollient, 0.01-0.2 parts of antioxidant, 1-8 parts of moisturizer and 20-50 parts of water; Optionally, the nanoemulsion composition comprises, in parts by mass: 0.05-0.25 parts of nucleic acids, 0.1-1.5 parts of barrier repair lipids, 1-5 parts of emulsifiers, 2-8 parts of emollients, 0.05-0.2 parts of antioxidants, 1-7 parts of moisturizers and 20-40 parts of water.

7. The nanoemulsion composition according to any one of claims 1 to 5, wherein The nanoemulsion composition has a particle size of 100 nm to 500 nm and a polydispersity index of 0.05 to 0.55; Optionally, the nanoemulsion composition has a particle size of 100 nm to 300 nm and a polydispersity index of 0.05 to 0.

35.

8. A method for preparing a nanoemulsion composition, characterized in that: The steps include: Prepare phase A, which includes an effective ingredient, a portion of an emollient, an antioxidant, and a portion of an emulsifier; Prepare phase B, which includes humectant, part of water, remaining emollient and remaining emulsifier; Mixing the phase A and the phase B to prepare a nanoemulsion; mixing the nucleic acid with the remaining water to prepare an aqueous nucleic acid solution; mixing the nanoemulsion with the nucleic acid aqueous solution to prepare a nanoemulsion composition; Wherein, the effective ingredients include barrier repair lipids, the barrier repair lipids include sphingolipids, the sphingolipids include phytosphingosine, and the barrier repair lipids also include one or more of ceramides, free fatty acids and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

9. The preparation method according to claim 8, wherein The preparation method of the phase A comprises: Dissolving the phytosphingosine in a portion of the emollient, and then adding the antioxidant, a portion of the emulsifier, and the components of the barrier repair lipid except the phytosphingosine to prepare the phase A; Optionally, dissolving the phytosphingosine in a portion of the emollient under heating conditions of 90° C. to 100° C.; Optionally, the antioxidant, part of the emulsifier and the components of the barrier repair lipid except the phytosphingosine are added to the emollient under heating conditions of 80° C. to 90° C.; and / or, The preparation method of the phase B comprises: The moisturizing agent, the remaining emollient and the remaining emulsifier are added to a portion of the water and stirred to prepare the phase B.

10. The preparation method according to any one of claims 8 to 9, characterized in that: The step of mixing the phase A and the phase B comprises: After mixing the phase A and the phase B, a first homogenization treatment and a second homogenization treatment are sequentially performed; the first homogenization treatment rate is 2000 rpm-12000 rpm, and the time is 2 min-60 min; the second homogenization treatment pressure is 100 bar-2000 bar, and the number of times is 2 times-20 times; Optionally, the first homogenization process is performed at a rate of 3000 rpm to 10000 rpm and for a time of 3 min to 30 min; Optionally, the pressure of the second homogenization treatment is 300 bar-1000 bar, and the number of times is 2 times-10 times.

11. A nano skin care product, characterized in that: The invention comprises a nanoemulsion composition, which comprises a nanoemulsion and a nucleic acid loaded on the surface of the nanoemulsion, wherein the nanoemulsion contains an effective ingredient of an emulsifier, a moisturizer, an antioxidant, a moisturizer and water; the effective ingredient comprises a barrier repair lipid, the barrier repair lipid comprises a sphingolipid, the sphingolipid comprises phytosphingosine, and the barrier repair lipid further comprises one or more of ceramide, free fatty acid and cholesterol; the mass proportion of the nucleic acid in the nanoemulsion composition is 0.1%-0.6%.

12. The nano skin care product according to claim 11, characterized in that: The nano skin care product further comprises an active ingredient, a skin conditioning agent, a preservative, a chelating agent, a thickener and water; Optionally, the active ingredient includes one or more of saccharide derivatives, natural plant extracts, nucleosides, metal oxides and amide compounds; further optionally, the active ingredient includes one or more of cerium oxide, glyceryl glucoside, madecassoside, adenosine, niacinamide, β-glucan, sodium hyaluronate, tranexamic acid, retinol, vitamin C, ferulic acid, green tea extract, arbutin, soy isoflavones and hydrolyzed oat protein; Optionally, the thickener includes one or more of polyacrylic acids, fatty alcohols, fatty acids, celluloses, natural gums and modifications thereof, esters, inorganic polymers and modifications thereof; optionally, the thickener includes one or more of sodium polyacrylate, carbomer, sodium polyacryloyldimethyl taurate, ammonium acryloyldimethyl taurate / beheneth-25 methacrylate crosspolymer, starch, gum arabic, pectin, agar, gelatin, alginate, carrageenan and dextrin; Optionally, the preservative includes one or more of an alcohol preservative, a paraben preservative, an isothiazolinone preservative, a formaldehyde-releasing preservative, and an acid preservative; further optionally, the preservative includes one or more of phenoxyethanol / ethylhexylglycerin, methylparaben, ethylparaben, propylparaben, sorbic acid, benzoic acid, dehydroacetic acid, methylchloroisothiazolinone, and methylisothiazolinone; Optionally, the chelating agent includes one or more of hydroxyhydroxy acid chelating agents and amino acid derivative chelating agents; further optionally, the chelating agent includes one or more of disodium EDTA, ethylenediaminetetraacetic acid, tetrasodium ethylenediaminetetraacetic acid and disodium nitrilotriacetate.

13. The nano skin care product according to claim 12, characterized in that: The active ingredient accounts for 1%-10% by weight of the nano skin care product, and can be optionally 1%-6% by weight; and / or The mass proportion of the skin conditioning agent in the nano skin care product is 0.1%-4%, optionally 0.5%-3%; and / or The mass proportion of the preservative in the nano skin care product is 1%-10%, optionally 1%-6%; and / or The mass proportion of the chelating agent in the nano skin care product is 0.01%-0.06%, and can be optionally 0.01%-0.05%; The mass proportion of the thickener in the nano skin care product is 0.05%-4%, optionally 0.5%-3%; and / or The barrier repair lipid accounts for 0.05%-2% by weight in the nano skin care product, and can be optionally 0.1%-1.5% by weight; and / or The mass proportion of the emulsifier in the nano skin care product is 1%-10%, optionally 1%-5%; and / or The emollient accounts for 1%-10% by weight of the nano skin care product, and can be optionally 2%-8% by weight; and / or The antioxidant accounts for 0.01%-0.2% by weight in the nano skin care product, and can be optionally 0.05%-0.2%; and / or The mass proportion of the moisturizing agent in the nano skin care product is 1%-8%, optionally 1%-7%; and / or The mass proportion of the nucleic acid in the nano skin care product is 0.05%-0.3%, and can be optionally 0.05%-0.25%.

14. The nano skin care product according to claim 11, characterized in that: The pH value of the nano skin care product is 4.0-8.0, and can be optionally 4.5-7.

5.

15. The nano skin care product according to any one of claims 11 to 14, characterized in that: The types of the nano skin care products include one or more of lotions, emulsion creams, facial masks and essence creams.

16. Use of the nanoemulsion composition according to any one of claims 1 to 7 in preparing a skin care product with a targeted effect; optionally, the targeting effect refers to targeting keratinocytes.

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