Phospholipid nanoparticle emulsions, preparation thereof, and use in cosmetics as carriers for active ingredients

Abstract

Provided in the present invention are an emulsion composition, a preparation method therefor and the use thereof. The emulsion composition comprises the following components in percentage by mass: 1-20% of ceramide, 1-20% of cholesterol, 0.1-5% of a nucleotide, 1-10% of squalene, 0.1-1% of vitamin E, 5-50% of phospholipid, 0.2-2% of a PEGylated lipid, 0.1-10% of a plant extract, 1-40% of a peptide and 1-15% of hyaluronic acid, with the balance being a phosphate buffer solution. The emulsion composition of the present invention organically combines the lipid nanoparticle technology with active ingredients, so that the lipid nanoparticles can be utilized for targeted delivery of the active ingredients, thereby enhancing the permeability of skin care ingredients, exerting the beneficial effects of the active ingredients to the maximum extent, and improving skin elasticity and firmness; furthermore, by integrating hydration, anti-aging and skin repair functions in one product, a deep skin care effect can be achieved, thereby revitalizing youthful skin from the basal layer.

Description

[0001] The present application relates to the technical field of skin care, in particular to an emulsion composition and a preparation method and application thereof.

[0002] The safety and transdermal absorption of skin care products have been a worldwide problem. Various nutrients only stay on the surface of the skin and cannot penetrate into the skin. With further research, liposomes are no longer the exclusive pet of the medical and scientific communities, but have become the ceiling of the cosmetics industry, a trusted cosmetic ingredient transporter and a skin care ambassador. However, how to organically combine liposome technology with active ingredients has always been a difficult point and direction of development. It should be noted that the information disclosed in the foregoing background section is only used to strengthen the understanding of the background of the present application, and therefore it can include information that does not constitute prior art known to those of ordinary skill in the art. The present application aims to overcome the shortcomings of the prior art and provide an emulsion composition that organically combines liposome technology with active ingredients, which can effectively enhance the skin care effect and become a valuable supplement to the cosmetics industry. In order to achieve the above-mentioned purpose, the present application provides an emulsion composition comprising the following components by mass percentage:

[0003] 1-20% ceramide, 1-20% cholesterol, 0.1-5% nicotinic acid, 1-10% squalene, 0.1-1% vitamin E, 5-50% phospholipid, 0.2-2% pegylated lipid, 0.1-10% plant extract, 1-40% peptide, 1-15% hyaluronic acid, and the rest of phosphate buffer. In some embodiments, the phospholipid is selected from one or more of distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE). In some embodiments, the pegylated lipid has a molecular weight of 2000-200000, and the hyaluronic acid has a molecular weight of 10000-1000000. In some embodiments, the plant extract is selected from one or more of stevia extract, aloe extract, green tea extract, lavender extract, licorice extract, chamomile extract. In some embodiments, the peptide is selected from one or more of collagen peptide, keratin peptide, elastin peptide, glycine peptide. In some embodiments, the emulsion composition comprises 2.5-10% ceramide, 5-10% cholesterol, 1-2.5% nicotinic acid, 1-10% squalene, 0.1-1% vitamin E, 10-25% phospholipid, 1-2% pegylated lipid, 2.5-5% plant extract, 5-10% peptide, 1-15% hyaluronic acid, and the rest of phosphate buffer, by mass percentage. In some embodiments, the pH value of the phosphate buffer is 7.4. In some embodiments, the emulsion composition further comprises one or more of preservative, pH adjuster, and stabilizer, the preservative is selected from one or more of phenoxyethanol, benzoate, and benzalkonium chloride, and the content of the preservative is 0.5-2%, the pH adjuster is selected from one or more of citric acid, lactic acid, and sodium bicarbonate, and the content of the pH adjuster is 0.1-3%, the stabilizer is selected from one or more of glycerol, stearic acid, and glyceryl behenate, and the content of the stabilizer is 1-3%. In another aspect, the present application also provides a preparation method of the above emulsion composition, comprising the following steps: dissolving ceramide, cholesterol, nicotinic acid, squalene, vitamin E, peptide, phospholipid, and pegylated lipid in ethanol to obtain an ethanol phase solution; adding hyaluronic acid and plant extract to phosphate buffer to obtain an aqueous phase solution; rapidly mixing the ethanol phase solution and the aqueous phase solution, and then removing ethanol by filtration to obtain the emulsion composition.In another aspect, the present application also provides use of the emulsion composition as described above in the preparation of a cosmetic product. The emulsion composition of the present application combines the lipid nanoparticle technology with active ingredients, can utilize the lipid nanoparticle to target delivery of the active ingredients, enhance the penetration of skin care ingredients, maximize the beneficial effects of the active ingredients, increase the elasticity and firmness of the skin, and combine hydration, anti-aging and skin repair in one product, thereby can have a deep care effect on the skin, and activate the new skin from the skin base. BRIEF DESCRIPTION OF DRAWINGS FIG. 1 is the particle size measurement result of the emulsion composition prepared in Preparation Example 1; FIG. 2 is the ZETA potential test result of the emulsion composition prepared in Preparation Example 1; FIG. 3 is the electron microscope photograph of the emulsion composition prepared in Preparation Example 1. DETAILED DESCRIPTION The technical solutions of the present application are further described below according to specific examples. The protection scope of the present application is not limited to the following examples, and these examples are listed only for exemplary purposes and do not limit the present application in any way. All publications, patent applications, patents and other references mentioned in the specification are hereby incorporated by reference. Unless otherwise defined, all technical and scientific terms used in the specification have the meanings commonly understood by one of ordinary skill in the art. In case of conflict, the definitions in the specification prevail. When the specification derives materials, substances, methods, steps, devices or components, etc. with the word head “known to those skilled in the art”, “prior art” or its synonyms, the objects derived by the word head cover those commonly used in the art at the time of filing the present application, but also include those not commonly used at present, but will be recognized as suitable for similar purposes in the art. In the context of the specification, except for the explicitly stated content, any unmentioned matters or matters are directly applicable to those known in the art without any change. Moreover, any embodiment described herein can be freely combined with one or more other embodiments described herein, and the technical solutions or technical ideas formed thereby are considered as part of the original disclosure or original description of the present application, and should not be considered as new content not disclosed or anticipated herein, unless the combination is considered by those skilled in the art to be obviously unreasonable. All features disclosed by the present application can be combined arbitrarily, and these combinations should be understood as disclosed or described by the present application, unless the combination is considered by those skilled in the art to be obviously unreasonable. The endpoints and any values of the ranges disclosed herein are not limited to the exact ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical value ranges, the endpoint values of each range, the endpoint values of each range and the individual point values, and the individual point values can be combined with each other to obtain one or more new numerical value ranges, which should be considered as specifically disclosed herein.All percentages, parts, ratios, etc. stated in this specification are based on weight unless otherwise indicated. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, suitable methods and materials are described herein. The emulsion composition of the present application comprises the following mass percentage of components: 1-20% of ceramide, 1-20% of cholesterols, 0.1-5% of nucleic acid, 1-10% of squalene, 0.1-1% of vitamin E, 5-50% of phospholipids, 0.2-2% of polyethylene glycolated lipids, 0.1-10% of plant extracts, 1-40% of peptides, 1-15% of hyaluronic acid, and the balance of phosphate buffer. In a preferred embodiment, the emulsion composition comprises 2.5-10% of ceramide, 5-10% of cholesterols, 1-2.5% of nucleic acid, 1-10% of squalene, 0.1-1% of vitamin E, 10-25% of phospholipids, 1-2% of polyethylene glycolated lipids, 2.5-5% of plant extracts, 5-10% of peptides, 1-15% of hyaluronic acid, and the balance of phosphate buffer. Ceramides are a class of lipid molecules with various skin protection effects, which play an important role in maintaining the integrity of the skin barrier. The decrease of ceramide level in the stratum corneum caused by various reasons will further lead to the impairment of the skin barrier, thus forming a vicious cycle. Ceramides can protect the skin through moisturizing, repairing, anti-inflammatory, protective, anti-aging, etc. The ceramide used in the present application is selected from one or more of ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6, which is essential for enhancing the natural barrier of the skin and retaining moisture. Among them, ceramide 3 can effectively improve the water retention capacity of the skin, reduce water loss, repair dry and damaged skin, and also help the renewal of the natural protective layer of the skin; ceramide 6 can promote the rapid metabolism of the stratum corneum of the skin, inhibit the secretion of active sebaceous glands while perfecting the sebaceous membrane, normalize the natural peeling process of the skin through skin scaling, balance the water and oil of the skin, enhance the self-protection function of the skin, enhance the skin barrier, and form an effective barrier to prevent water loss and reduce the influence of the external environment. The content of ceramide in the emulsion composition is 1-20%, preferably 2.5-10%. Cholesterol is a derivative of cyclopentane polyhydrogenophenanthrene.The chemical formula is C27H46O, which is applied to the emulsion composition of the application, can help to improve the moisture retention capacity of the skin, repair damaged cell membranes, protect the skin from environmental stress, etc., and also helps to improve the stability and texture of the skin care product, and cholesterol can enhance the stability of LNP, enhance the uptake capacity of cells, and thus enhance the drug loading capacity and therapeutic effect of lipid nanoparticles. The content of cholesterol in the emulsion composition is 1-20%, preferably 5-10%. Nucleosides are a class of compounds composed of three substances: folic acid or ribose or deoxyribose and phosphate, which mainly play the role of promoting the synthesis of skin proteins, regulating skin metabolism, anti-aging and promoting cell growth, and have the effect of moisturizing the skin. The content of nucleosides in the emulsion composition is 0.1-5%, preferably 1-2.5%. Squalene is a common mushroom compound in shark liver, also known as triacontahexaene, which is a natural antioxidant that can strengthen metabolism, update cells and promote tissue growth, protect cells from DNA oxidative damage, and is applied to the emulsion composition of the application. It helps to protect the skin from free radical damage. The content of squalene in the emulsion composition is 1-10% 0 Vitamin E is a fat-soluble vitamin, also known as tocopherol, which is one of the essential nutrients for the human body, known for its nourishing and protective properties against environmental stress, and when applied to the emulsion composition of the application, it can reduce oxidative stress damage to the skin, promote skin repair and regeneration, delay skin aging, and promote skin damage repair, thereby improving skin texture. The content of vitamin E in the emulsion composition is 0.1-l%o Lipid nanoparticles (LNP) are currently the most advanced non-viral gene delivery system in clinical practice, which usually contains four lipid components: first, ionizable lipids that produce positive charges in a specific environment, which can bind tightly to negatively charged mRNA; second, a class of pegylated lipids responsible for stabilizing the structure of nanoparticles; the last two are phospholipids and cholesterol molecules, responsible for filling the structure of nanoparticles. These four simple ingredients wrap mRNA to prevent their degradation and deliver them into cells. From transdermal administration to functional cosmetics, the microparticles of liposomes are refined to the nanometer level, truly recreating a nanometer component skincare world, and liposomes are composed of phospholipids similar to human skin structure. Each nanometer liposome star can find its own place in the vast universe of the skin, and then penetrate the skin to provide skin repair, and has a sustained-release function to continuously deliver nutrients to the skin.In the emulsion composition of the present application, ceramide, cholestanol, cholecalciferol, squalene and vitamin E together constitute the core of the lipid nanoparticle, and phospholipid and pegylated lipid together constitute the shell of the lipid nanoparticle. The phospholipid can enhance the stability and delivery efficiency of the lipid nanoparticle, effectively encapsulate various hydrophobic active ingredients, and promote the penetration ability of other active ingredients. The pegylated lipid helps to improve the lifespan and circulation time of the nanoparticles in the emulsion composition. The phospholipid used in the present application is selected from synthetic neutral phospholipids with high safety, for example, one or more selected from distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE). The content of phospholipid in the emulsion composition is 5-50%, preferably 10-25%. oThe polyethylene glycolized lipid used in the present application has a molecular weight of 2000-200000, and the content of the polyethylene glycolized lipid in the emulsion composition is 0.2-2%. The plant extract used in the present application is a natural plant extract, for example, one or more selected from the group consisting of stevia extract, aloe extract, green tea extract, lavender extract, licorice extract, and chamomile extract. The active ingredients extracted from various plants can be used to increase the efficacy or adjust the properties of the product, such as moisturizing, fragrance, and antioxidant. The content of the plant extract in the emulsion composition is 0.1-10%, preferably 2.5-5%. The peptide is mostly a short-chain polypeptide composed of amino acids. It can promote collagen regeneration, moisturizing, whitening, and the like on the surface or deep layer of the skin. The peptide used in the present application is selected from one or more of collagen peptide, keratin peptide, elastin peptide, and glutamic acid peptide. The content of the peptide in the emulsion composition is 1-40%, preferably 5-10%. Hyaluronic acid is a polysaccharide molecule naturally present in human skin tissue. Hyaluronic acid with different molecular weights has different functions in the field of cosmetics. Low-molecular-weight hyaluronic acid has good permeability and can promote the synthesis of collagen and elastin, thereby playing a role in anti-aging and moisturizing. High-molecular-weight hyaluronic acid can lock water and moisturize, thereby increasing the water content of the skin. The molecular weight of the hyaluronic acid used in the present application is 10000-1000000, wherein high-molecular-weight hyaluronic acid (1000000 MW, 1 / 1000 to 1 / 100 concentration) provides a high level of surface hydration and visible fullness, and low-molecular-weight hyaluronic acid (10000 MW, 1 / 1000 to 1 / 100 concentration) can penetrate deep into the skin, thereby achieving long-lasting hydration and elasticity. The content of the hyaluronic acid in the emulsion composition is 1-15%. Phosphate-buffered saline (PBS) is the most widely used balanced salt solution in biochemical research. The main components are Na2HPO4, KH2PO4, NaCl, and KCL. PBS buffer is commonly used for rinsing tissue blocks, washing cells, transporting cells or tissues, preparing other reagents, and diluting cell counting, and has the functions of salt balance and buffering to adjust the appropriate pH value. In the emulsion composition of the present application, the pH value of the phosphate buffer is 7.2-7.4, preferably 7.4, which is conducive to improving the safety of the emulsion composition. The emulsion composition of the present application also includes one or more of preservatives, pH adjusters, and stabilizers. As a preservative, it can prolong the shelf life of the product. The preservative used in the present application is selected from one or more of phenoxyethanol, benzoate, and chlorobenzene, and the content of the preservative in the emulsion composition is 0.5-2%.As a pH stabilizer, it can ensure the pH value of the product to be at an appropriate level, maintain the healthy state of the skin and improve the use experience. The pH regulator used in the present application is selected from one or more of citric acid, lactic acid and sodium bicarbonate, and the content of the pH regulator in the emulsion composition is 0.1-3%. As a stabilizer, it can be used to maintain the stability of the product and prevent problems such as delamination and solidification. The stabilizer used in the present application is selected from one or more of glycerol, stearic acid and glyceryl behenate, and the content of the stabilizer in the emulsion composition is 1-3%. O The emulsion composition of the present application can be prepared by the following steps: dissolving ceramide, cholestanol, nucleic acid, squalene, vitamin E, peptide, phospholipid and pegylated lipid in ethanol to obtain an ethanol phase solution; adding hyaluronic acid and plant extract into phosphate buffer to obtain an aqueous phase solution; rapidly mixing the ethanol phase solution and the aqueous phase solution, and then filtering to remove ethanol to obtain the emulsion composition. The ethanol phase solution is obtained by dissolving ceramide, cholestanol, nucleic acid, squalene, vitamin E, peptide, phospholipid and pegylated lipid in ethanol, and stirring until fully dissolved. The aqueous phase solution is obtained by adding hyaluronic acid and plant extract into phosphate buffer, and stirring until fully transparent. The rapid mixing of the ethanol phase solution and the aqueous phase solution can be by rapidly injecting the ethanol phase solution into the aqueous phase solution, or by simultaneously injecting the ethanol phase solution and the aqueous phase solution into a new container. The filtration to remove ethanol can be by membrane filtration, such as a 0.22 micron membrane. When the ethanol phase solution and the aqueous phase solution are rapidly mixed, the ethanol gradually mixes and dilutes with water due to the mutual solubility between ethanol and water, thereby causing the lipids to gradually contact with water. When the lipids gradually mix with water, the lipid molecules spontaneously form a double-layer liposome structure, in which the hydrophobic lipid part faces the inside and the hydrophilic head group faces the outside, forming one or more closed vesicles. The emulsion composition of the present application can be applied in the field of cosmetics as an emulsion or cream. The present application is further illustrated by specific examples, which describe preferred embodiments, but do not constitute a limitation on the present application, and any skilled person in the art can modify the above-mentioned related content of the application to obtain equivalent examples with equivalent changes. In the examples, the reagents used in the present application are all analytical pure, and the reagents used are commercially available, such as from Sigma-Aldrich oPreparation Example 1: 1 g ceramide, 1 g cholesterol, 1 g nucleic acid, 1 g squalene, 0.2 g vitamin E, 5 g peptide, 5 g phospholipid and 1 g polyethylene glycol lipid are dissolved in ethanol, stirred uniformly to obtain an ethanol phase solution; 1 g hyaluronic acid and 1 g plant extract are added to a proper amount of phosphate buffer, stirred until completely transparent to obtain an aqueous phase solution; the ethanol phase solution and the aqueous phase solution are quickly mixed, and then filtered through a 0.22 micron filter membrane to remove ethanol to obtain a emulsion composition. The obtained emulsion composition is detected, and the particle size measurement result is shown in FIG. 1, which is suitable for in vivo application. The ZETA potential test result is shown in FIG. 2, and the electron microscope photo is shown in FIG. 3, which shows that the prepared emulsion is a round particle with uniform particle size, the particle size is about 100 nm, the potential is neutral, and it is suitable for human application.Moreover, any combination of the various embodiments of the present application can be made, as long as it does not deviate from the idea of the present application, which should also be considered as disclosed by the present application. Of course, the present application can have other various embodiments, and those skilled in the art can make various corresponding changes and modifications according to the present application without departing from the spirit and essence of the present application, and these corresponding changes and modifications should all fall within the protection scope of the claims of the present application.

Claims

CLAIM 1. An emulsion composition, characterized in that, comprises the following components by mass percentage: 1-20% of ceramide, 1-20% of cholesterol, 0.1-5% of nicotinic acid, 1-10% of squalene, 0.1-1% of vitamin E, 5-50% of phospholipid, 0.2-2% of pegylated lipid, 0.1-10% of plant extract, 1-40% of peptide, 1-15% of hyaluronic acid, and the balance of phosphate buffer.

2. The emulsion composition according to claim 1, characterized by, The phospholipid is selected from one or more of distearoylphosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), and dioleoylphosphatidylethanolamine (DOPE).

3. The emulsion composition according to claim 1, characterized by, The molecular weight of the pegylated lipid is 2000-200000, and the molecular weight of the hyaluronic acid is 10000-1000000 o 4. The emulsion composition according to claim 1, characterized by, The plant extract is selected from one or more of stevia extract, aloe extract, green tea extract, lavender extract, licorice extract, and chamomile extract.

5. The emulsion composition according to claim 1, characterized by, The peptide is selected from one or more of collagen peptide, keratin peptide, elastin peptide, and glutamic acid peptide.

6. The emulsion composition according to claim 1, characterized by, The emulsion composition comprises, by mass percentage, 2.5-10% of ceramide, 5-10% of cholesterol, 1-2.5% of nicotinic acid, 1-10% of squalene, 0.1-1% of vitamin E, 10-25% of phospholipid, 1-2% of pegylated lipid, 2.5-5% of plant extract, 5-10% of peptide, 1-15% of hyaluronic acid, and the balance of phosphate buffer.

7. The emulsion composition according to claim 1, characterized by, The pH value of the phosphate buffer is 7.

4.

8. The emulsion composition according to any one of claims 1 to 7, characterized by, The emulsion composition further comprises one or more of preservative, pH adjuster, and stabilizer, the preservative is selected from one or more of phenoxyethanol, benzoate, and benzalkonium chloride, and the content of the preservative is 0.5-2%, the pH adjuster is selected from one or more of citric acid, lactic acid, and sodium bicarbonate, and the content of the pH adjuster is 0.1-3%, and the stabilizer is selected from one or more of glycerol, stearic acid, and glyceryl behenate, and the content of the stabilizer is 1-3%.

9. The method of producing an emulsion composition according to any one of claims 1 to 8, characterized by, The method comprises the following steps: dissolving ceramide, cholesterol, nicotinic acid, squalene, vitamin E, peptide, phospholipid, and pegylated lipid in ethanol to obtain an ethanol phase solution; adding hyaluronic acid and plant extract to a phosphate buffer to obtain an aqueous phase solution; 9 The ethanol phase solution and the aqueous phase solution are rapidly mixed, and then filtered to remove ethanol to obtain the emulsion composition.

10. Use of the emulsion composition according to any one of claims 1 to 8 in the preparation of a cosmetic product.

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