Hyaluronic acid liposome with double anti-wrinkle and skin feeling improving functions, preparation method of hyaluronic acid liposome, essence, mask, toning lotion and application of hyaluronic acid liposome

Abstract

The invention provides a hyaluronic acid liposome with double anti-wrinkle and skin feeling improving functions, a preparation method thereof, essence, a mask, a toning lotion and application, and relates to the field of cosmetics. The hyaluronic acid liposome with the dual anti-wrinkle and skin feeling improving functions is prepared from the following raw materials in percentage by mass: 1 percent to 5 percent of hydrogenated lecithin, 0.5 percent to 1.5 percent of PEG-60 hydrogenated castor oil, 0.5 percent to 2 percent of Pellicer L-30, 2 percent to 10 percent of PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol, 2 percent to 50 percent of glycerol, 1 percent to 2 percent of hexanediol, 5 percent to 15 percent of polydimethylsiloxane, 0.05 percent to 0.5 percent of micromolecular hydrolyzed sodium hyaluronate, 0.05 percent to 0.1 percent of macromolecular sodium hyaluronate and the balance of water, wherein the total mass of the raw materials is 100 percent. Meanwhile, micromolecular hyaluronic acid and macromolecular hyaluronic acid are wrapped, so that the synergistic effect of the large and small molecular hyaluronic acid is realized.

Description

Technical Field

[0001] The present application relates to the field of cosmetics, and in particular to a hyaluronic acid liposome with dual anti-wrinkle and skin-improving properties, a preparation method thereof, an essence water, a facial mask, a lotion, and applications thereof. Background Art

[0002] Hyaluronic acid (sodium hyaluronate) is a highly effective moisturizing ingredient, widely used in various skincare products due to its unique molecular structure and excellent water-retention capacity. Hyaluronic acid of different molecular weights has varying penetration and efficacy within the skin. While small-molecule hyaluronic acid penetrates the skin quickly, its effect is relatively short-lived. Large-molecule hyaluronic acid, on the other hand, forms a protective film on the skin's surface but struggles to penetrate deeply. Therefore, a single molecular weight hyaluronic acid cannot simultaneously deliver both deep moisturizing and long-lasting anti-wrinkle benefits.

[0003] Water-based skincare products are water-based and possess the fluidity of water. These products include toners, essences, and facial masks. Their advantages are refreshing and easily absorbed, quickly replenishing moisture and regulating the skin's water-oil balance, making them suitable for all skin types. However, their disadvantages are their relatively weak moisturizing effect and rapid evaporation. Furthermore, the addition of other active ingredients such as sodium hyaluronate can make them sticky, affecting the user experience and making it difficult to achieve both skin feel and moisturizing and anti-wrinkle effects.

[0004] Based on this, how to combine the advantages of hyaluronic acid to develop an aqueous liposome that can both deeply moisturize and provide long-lasting anti-wrinkle effects has become a hot topic in the current field of skin care product research and development. Summary of the Invention

[0005] The purpose of this application is to provide a hyaluronic acid liposome with dual anti-wrinkle and skin feel improvement, as well as its preparation method, essence water, facial mask and lotion and application, to solve the above problems.

[0006] To achieve the above objectives, the present application provides a first aspect of a hyaluronic acid liposome with dual anti-wrinkle and skin-improving properties, wherein the raw materials thereof, calculated based on 100% total mass, include: 1%-5% hydrogenated lecithin, 0.5%-1.5% PEG-60 hydrogenated castor oil, 0.5%-2% Pellicer L-30, 2%-10% PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, 2%-50% glycerin, 1%-2% hexylene glycol, 5%-15% dimethicone, 0.05%-0.5% small molecule hydrolyzed sodium hyaluronate, 0.05%-0.1% large molecule sodium hyaluronate, the balance is water; The molecular weight of the small molecule sodium hyaluronate is 400Da-1600Da; The molecular weight of the macromolecular sodium hyaluronate is 1 million Da to 3 million Da.

[0007] The second aspect of the present application provides a method for preparing the dual anti-wrinkle and skin-improving hyaluronic acid liposomes, comprising: The hydrogenated lecithin, the hexylene glycol, the PEG-60 hydrogenated castor oil, the glycerin, the PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin and the polydimethylsiloxane are first mixed and first heated to obtain a first mixture; performing a second mixing and a second heating of the Pellicer L-30, the small molecule hydrolyzed sodium hyaluronate, the large molecule sodium hyaluronate, and the water to obtain a second mixture; performing a third mixing of the first mixture and the second mixture to obtain the third mixture; The third mixture is stirred and homogenized to obtain the hyaluronic acid liposomes with dual anti-wrinkle and skin feel improvement properties.

[0008] Optionally, the first heating temperature is 60°C-80°C.

[0009] Optionally, the second heating temperature is 60°C-80°C.

[0010] Optionally, the preparation method of the dual anti-wrinkle and skin-improving hyaluronic acid liposomes satisfies at least one of the following conditions: A. The stirring speed is 2000rpm-5000rpm, and the time is 2min-4min; B. Using high-pressure microfluidization to carry out the homogenization process.

[0011] Optionally, the pressure of the high-pressure microjet is 800-1200 bar, and the number of cycles is 3-4 times.

[0012] The third aspect of the present application provides an essence water, comprising the hyaluronic acid liposomes for dual anti-wrinkle and skin-improving effects.

[0013] The fourth aspect of the present application provides a facial mask comprising the aforementioned dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes.

[0014] The fifth aspect of the present application provides a lotion comprising the aforementioned dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes.

[0015] The sixth aspect of the present application provides a use of the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes in the preparation of external preparations and cosmetics.

[0016] Compared with the prior art, the advantages of this application include: The present application provides a dual anti-wrinkle and skin-feel improving hyaluronic acid liposome. The aqueous phase in the liposome simultaneously encapsulates hydrolyzed hyaluronic acid (small molecule hyaluronic acid) and sodium hyaluronate (large molecule hyaluronic acid), achieving the synergistic effect of large and small molecule hyaluronic acid. It can not only slowly release small molecule hyaluronic acid and prolong its action time, but also nano-encapsulation promotes the penetration of large molecule hyaluronic acid and protects it from rapid degradation by hyaluronidase. After release, the large molecule hyaluronic acid can fill the gaps in collagen fibers and achieve long-lasting moisturizing and anti-wrinkle dual effects together with the small molecule hyaluronic acid. At the same time, polydimethylsiloxane (silicone oil) is loaded in the non-polar region of the liposome, supplemented with PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol, so that the liposome can be added in any ratio in the aqueous formulation to significantly improve the skin feel of the aqueous skin care product.

[0017] The present application provides a method for preparing hyaluronic acid liposomes with dual anti-wrinkle and skin feel improvement. The product is stable and easy to obtain, which is conducive to large-scale mechanized production.

[0018] The essence water, facial mask and lotion provided in this application are deeply moisturizing and have long-lasting anti-wrinkle effects.

[0019] The application provided by this application has a wide range of applications and is applicable to a variety of aqueous formulation skin care products. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following is a brief introduction to the drawings required for use in the embodiments. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope of the present application.

[0021] Figure 1 A graph showing the stability of a dilution prepared from the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes provided in Example 1; Figure 2 This is a photo showing the stability test of the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes provided in Example 1; Figure 3 This is a graph showing the cytotoxicity test results of the dual anti-wrinkle and skin-improving hyaluronic acid liposomes provided in Example 1; Figure 4 This is a diagram showing the cytotoxicity test results of the liposomes provided in Comparative Example 1; Figure 5 This is a graph showing the cytotoxicity test results of hyaluronic acid containing large and small molecules provided in Comparative Example 2; Figure 6 This is the result of the test for type I collagen content; Figure 7 The results of the transdermal absorption test performed on Example 1 and Comparative Example 2 are shown; Figure 8 This is the actual picture of the essence water; Figure 9 This is the skin feel test result of the essence water; Figure 10 This is a real picture of the mask; Figure 11 This is the skin feel test result of the mask. DETAILED DESCRIPTION

[0022] As used herein: "Prepared from" is synonymous with "comprising." As used herein, the terms "comprising," "including," "having," "containing," or any other variations thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0023] The conjunction "consisting of" excludes any unspecified element, step, or component. If used in a claim, this phrase renders the claim closed, excluding materials other than those described, except for conventional impurities associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately following the subject matter, it limits only the elements described in that clause; other elements are not excluded from the claim as a whole.

[0024] When an amount, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper preferred values ​​and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value with any range lower limit or preferred value, regardless of whether the range is disclosed alone. For example, when a range of "1 to 5" is disclosed, the described range should be interpreted as including the range "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5", etc. When a numerical range is described herein, unless otherwise stated, the range is intended to include its end values ​​and all integers and fractions within the range.

[0025] In these examples, parts and percentages are by mass unless otherwise indicated.

[0026] "Parts by mass" refers to the basic unit of measurement used to express the mass ratio of multiple components. One part can represent any unit of mass, such as 1g or 2.689g. For example, if we say that the parts by mass of component A are a parts and the parts by mass of component B are b parts, this means the ratio of the mass of component A to the mass of component B is a:b. Alternatively, we could say that the mass of component A is aK and the mass of component B is bK (K is an arbitrary number representing a multiplication factor). It's important to note that, unlike parts by mass, the sum of the parts by mass of all components is not limited to 100 parts.

[0027] "And / or" is used to indicate that one or both of the stated situations may occur, for example, A and / or B includes (A and B) and (A or B).

[0028] In a first aspect, the present application provides a hyaluronic acid liposome with dual anti-wrinkle and skin-improving properties, wherein the raw materials thereof, calculated based on 100% by total mass, include: 1%-5% hydrogenated lecithin, 0.5%-1.5% PEG-60 hydrogenated castor oil, 0.5%-2% Pellicer L-30, 2%-10% PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, 2%-50% glycerin, 1%-2% hexylene glycol, 5%-15% dimethicone, 0.05%-0.5% small molecule hydrolyzed sodium hyaluronate, 0.05%-0.1% large molecule sodium hyaluronate, the balance is water; Optionally, the raw materials of the dual anti-wrinkle and skin-improving hyaluronic acid liposomes are calculated based on the total mass of 100%, hydrogenated lecithin can be 1%, 2%, 3%, 4%, 5% or any value between 1% and 5%, PEG-60 hydrogenated castor oil can be 0.5%, 1%, 1.5% or any value between 0.5% and 1.5%, Pellicer L-30 can be 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or any value between 2% and 10%, glycerin can be 2%, 10%, 20%, 30%, 40%, 50% or any value between 2% and 50%, hexylene glycol can be 1%, 1.5%, 2% or any value between 1% and 2%, polydimethylsiloxane can be 5%, 10%, 15% or any value between 5% and 15%, small molecule hydrolyzed sodium hyaluronate can be 0.05%, 0.1%, 0.2%, 0.5% or any value between 0.05% and 0.5%, and large molecule sodium hyaluronate can be 0.05%, 0.08%, 0.1% or any value between 0.05% and 0.1%; It should be noted that Pellicer L-30 is also known as sodium di(laurylamide glutamine) lysine; The molecular weight of the small molecule sodium hyaluronate is 400Da-1600Da; Optionally, the molecular weight of the small molecule sodium hyaluronate can be 400Da, 800Da, 1200Da, 1600Da, or any value between 400Da and 1600Da; The molecular weight of the macromolecular sodium hyaluronate is 1 million Da to 3 million Da.

[0029] Optionally, the molecular weight of the macromolecular sodium hyaluronate can be 1 million Da, 2 million Da, 3 million Da, or any value between 1 million Da and 3 million Da.

[0030] It should be noted that the hydrogenated lecithin and sodium di(laurylamide glutamine) lysine provided in this application The phospholipid bilayer vesicles are composed of PEG-60 hydrogenated castor oil and PEG-30 hydrogenated castor oil. The amphiphilic nature of the phospholipid bilayer vesicles allows the encapsulation of large and small molecular weight hyaluronic acid within the phospholipid layer. Sodium di(laurylamide glutamine) lysine is a bimolecular peptide anionic surfactant with a phospholipid-like structure and multiple functional properties. It can be inserted into the phospholipid bilayer through hydrophobic interactions to participate in liposome formation. Its hydrophilic head group forms a hydrogen bond network with the phosphate groups of hydrogenated lecithin, enhancing the mechanical strength of the membrane. Its anionic properties also form an electrostatic repulsion layer on the liposome surface, inhibiting liposome aggregation. PEG-60 hydrogenated castor oil, through its long-chain PEG structure, adsorbs on the liposome surface to form a dense steric barrier, further preventing liposome aggregation and enhancing liposome stability. Glycerin and PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol are then added to modulate liposome membrane fluidity, achieve nanoparticle size (<150 nm), and enhance liposome permeability.

[0031] It should also be noted that the dual anti-wrinkle and skin-improving hyaluronic acid liposomes provided in this application can achieve the coordinated delivery of two molecules of hyaluronic acid, breaking through the functional limitations of the traditional single-molecular-weight hyaluronic acid delivery system; the liposomes delay the release of small-molecule sodium hyaluronate and protect it from degradation by hyaluronidase, continuously penetrate into the dermis, stimulate collagen synthesis, and repair the basement structure; and, while the liposomes encapsulate high-molecular-weight sodium hyaluronate to protect it from degradation by hyaluronidase, they also enhance the transdermal efficiency with the help of the membrane fusion properties of sodium di(laurylamide glutamine) lysine, physically fill the gaps between collagen fibers after release, and instantly reduce wrinkles; through the formation of a "double anti-wrinkle network" by small-molecule hyaluronic acid (dynamic repair) + large-molecule hyaluronic acid (static support), the superimposed effect of instant filling + long-term anti-aging is achieved.

[0032] In addition, the present application loads polydimethylsiloxane in the double-layer membrane of the liposome, and cooperates with PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol to optimize the skin feel of the liposome. Polydimethylsiloxane can spread on the skin surface to form a highly breathable membrane, reducing water evaporation, while avoiding the risk of acne caused by traditional occlusive oils, and maintaining the stability of the liposome system; PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol absorbs and locks moisture through polyol groups, forming a hydration film on the surface of the liposome, and enhancing the skin barrier function. The two work together to achieve a balance between refreshing and hydrating skin feel and silky extension, significantly reducing the sticky feeling and the risk of acne, and providing skin care products with the dual guarantee of long-lasting moisturizing and light skin feel.

[0033] In summary, this application achieves a breakthrough in the trinity of "anti-wrinkle-moisturizing-skin feel" for the first time through the design of a hydrogenated lecithin / sodium di(laurylamide glutamine) lysine / PEG-60 hydrogenated castor oil composite phospholipid bilayer structure, combined with dual-molecular weight hyaluronic acid co-loading technology and a silicone oil-polyol synergistic skin feel optimization system. Nano-liposomes are used to simultaneously deliver large and small molecular weight hyaluronic acid, and the dual anti-wrinkle mechanisms of dynamic repair + static filling are used to extend the efficacy. At the same time, relying on silicone oil film-forming and polyol water-locking technology, while maintaining high system stability, the water-based product is given a revolutionary skin feel experience of long-lasting moisturizing, lightness, breathability, and zero stickiness.

[0034] The second aspect of the present application provides a method for preparing the dual anti-wrinkle and skin-improving hyaluronic acid liposomes, comprising: The hydrogenated lecithin, the hexylene glycol, the PEG-60 hydrogenated castor oil, the glycerin, the PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin and the polydimethylsiloxane are first mixed and first heated to obtain a first mixture; performing a second mixing and a second heating of the Pellicer L-30, the small molecule hydrolyzed sodium hyaluronate, the large molecule sodium hyaluronate, and the water to obtain a second mixture; performing a third mixing of the first mixture and the second mixture to obtain the third mixture; The third mixture is stirred and homogenized to obtain the hyaluronic acid liposomes with dual anti-wrinkle and skin feel improvement properties.

[0035] In some embodiments, the first heating temperature is 60°C-80°C.

[0036] Optionally, the first heating temperature may be 60°C, 70°C, 80°C or any value between 60°C and 80°C.

[0037] In some embodiments, the second heating temperature is 60°C-80°C.

[0038] Optionally, the second heating temperature may be 60°C, 70°C, 80°C or any value between 60°C and 80°C.

[0039] In some embodiments, the method for preparing the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes satisfies at least one of the following conditions: A. The stirring speed is 2000rpm-5000rpm, and the time is 2min-4min; Optionally, the stirring speed may be 2000 rpm, 3000 rpm, 4000 rpm, 5000 rpm or any value between 2000 rpm and 5000 rpm, and the stirring time may be 2 min, 3 min, 4 min or any value between 2 min and 4 min; B. Using high-pressure microfluidization to carry out the homogenization process.

[0040] In some embodiments, the pressure of the high-pressure microjet is 800 bar-1200 bar, and the number of cycles is 3-4 times.

[0041] Optionally, the pressure of the high-pressure microjet may be 800 bar, 900 bar, 1000 bar, 1100 bar, 1200 bar or any value between 800 bar and 1200 bar, and the number of cycles may be 3 or 4 times.

[0042] The third aspect of the present application provides an essence water, comprising the hyaluronic acid liposomes for dual anti-wrinkle and skin-improving effects.

[0043] The fourth aspect of the present application provides a facial mask comprising the aforementioned dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes.

[0044] The fifth aspect of the present application provides a lotion comprising the aforementioned dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes.

[0045] The sixth aspect of the present application provides a use of the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes in the preparation of external preparations and cosmetics.

[0046] The embodiments of the present application will be described in detail below in conjunction with specific examples, but it will be understood by those skilled in the art that the following examples are merely illustrative of the present application and should not be considered as limiting the scope of the present application. In the examples, if specific conditions are not specified, the conditions are carried out according to conventional conditions or manufacturer recommendations. The reagents or instruments used are not specified by the manufacturer and are conventional products that can be purchased commercially.

[0047] Example 1 In a first aspect, this embodiment provides a hyaluronic acid liposome with dual anti-wrinkle and skin feel improvement properties. The raw materials are calculated based on the total mass as 100%, as shown in Table 1.

[0048] Table 1 Raw material composition

[0049] The molecular weight of small-molecule sodium hyaluronate is 400-1000 Da, and the molecular weight of large-molecule sodium hyaluronate is 1 million-1.6 million Da. Pellicer L-30 was purchased from Asahi Kasei, Japan, and PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol was purchased from Guangzhou Kosifa.

[0050] The second aspect of the present application provides a method for preparing hyaluronic acid liposomes with dual anti-wrinkle and skin feel improvement, as follows: S1: Weigh the raw materials of Phase A in the weight proportions shown in Table 1, and place them in a constant temperature water bath at 65°C, heating and stirring until uniformly dissolved, to serve as the oil phase; S2: Weigh the raw materials of Phase B in the proportions shown in Table 1 and heat them in a constant temperature water bath at 60°C until the sodium hyaluronate is completely dissolved, as the aqueous phase; S3: While stirring, slowly pour the aqueous phase into the oil phase, stir evenly, and then homogenize at 3000 rpm for 2 minutes to obtain crude liposomes; then homogenize the obtained crude liposomes three times by high-pressure microjetting at 1000 bar to obtain hyaluronic acid liposomes with dual anti-wrinkle and improved skin feel.

[0051] Examples 2-4 Examples 2-4 respectively provide a dual anti-wrinkle and skin-feel improving hyaluronic acid liposome. The preparation method is the same as that of Example 1. The difference from Example 1 is that the amount of raw materials used is different, as shown in Table 2.

[0052] Table 2 Raw materials

[0053] Comparative Example 1 The difference from Example 1 is that small molecule sodium hyaluronate and large molecule sodium hyaluronate are not added.

[0054] Comparative Example 2 The difference from Example 1 is that 0.2 wt % of small molecule sodium hyaluronate, 0.05 wt % of large molecule sodium hyaluronate and 99.75 wt % of water are mixed and stirred until completely dissolved.

[0055] Comparative Example 3 The difference from Example 1 is that small molecule sodium hyaluronate is not added.

[0056] Comparative Example 4 The difference from Example 1 is that no macromolecular sodium hyaluronate is added.

[0057] Comparative Example 5 The difference from Example 1 is that Pellicer L-30 is not added.

[0058] Comparative Example 6 The difference from Example 1 is that PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerol is not added.

[0059] Comparative Example 7 The difference from Example 1 is that no hydrogenated lecithin is added.

[0060] Comparative Example 8 The difference from Example 1 is that PEG-60 hydrogenated castor oil is not added.

[0061] Comparative Example 9 The difference from Example 1 is that no polydimethylsiloxane is added.

[0062] Stability testing Examples 1-4 and Comparative Examples 1-6 and 8 are all transparent solutions. The active ingredients and skin feel regulating ingredients are removed from Comparative Examples 1, 3, 4 and 6, which are not expected to affect the stability and are therefore not discussed here.

[0063] Comparative Examples 7 and 9 failed to prepare liposomes. Comparative Example 7 lacked an emulsifier and the preparation system was unstable. In the preparation of Comparative Example 9, the system was very thick and gelled. No further experimental verification was performed.

[0064] In order to further verify the stability of the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes prepared in Example 1, the following tests were performed: The sample solutions prepared in Examples 1-4 and Comparative Examples 5 and 8 were mixed with deionized water to prepare 5 wt % dilutions. The dilutions and stock solutions were placed at 4° C. and 45° C., respectively, for a 3-month stability test.

[0065] Examples 1-4, the experimental results showed similar performance, Figure 1 The following are the stability test results of 5% dilutions of Example 1, Comparative Example 5, and Comparative Example 8 for three consecutive months. Figure 2 The figures are the actual pictures of the 5% dilution and original solution of Example 1 after 3 months. The results show that the particle size of the 5% dilutions of Examples 1-4 did not change significantly, the original solution was transparent in appearance and slightly yellowed at high temperature, which may be caused by the oxidation of hydrogenated lecithin. The particle size of the 5% dilutions of Comparative Examples 5 and 8 showed a significant trend of increasing, indicating that the small molecule hyaluronic acid of the present invention has the characteristics of small particle size and high stability.

[0066] Cell experiments Cytotoxicity test experiment: The products of Example 1, Comparative Example 1, and Comparative Example 2 were diluted with culture medium solution to seven mass concentrations of 5%, 3%, 1%, 0.2%, 0.04%, 0.08%, and 0.0016%, respectively. Cytotoxicity test experiments were carried out on fibroblasts, wherein the seven concentrations selected by the samples were used as the horizontal axis and the relative cell viability values ​​were used as the vertical axis to draw a cell relative viability graph; the cytotoxicity test results of Example 1 are shown in FIG. Figure 3 As shown, the cytotoxicity test results of Comparative Example 1 are as follows Figure 4 As shown, the cytotoxicity test results of Comparative Example 2 are as follows Figure 5 shown.

[0067] Test results: The dual-anti-wrinkle, skin-feeling-improving hyaluronic acid liposomes provided in Example 1 and Comparative Example 1 showed no significant cytotoxicity at concentrations below 1% on immortalized keratinocytes, while Comparative Example 2 showed no significant cytotoxicity at concentrations below 5%. Comparative Examples 3-4 differ from Example 1 in the addition of large and small molecule sodium hyaluronate, so the cytotoxic concentrations of Example 1 were used as a reference for subsequent efficacy experiments. Type I collagen content detection experiment: HFF-1 cells were seeded at 10,000 cells / well in a 96-well plate and cultured in a 37°C, 5% CO2 incubator for 24 h. The test substance working solution was prepared according to the experimental design. The specific data are shown in Table 3. Seven test sample groups were set up, including a blank group, a positive control group, and sample groups 1-5. According to the test protocol, drug administration was performed after the cell growth rate reached 80%-90%. After drug administration, the 96-well plate was placed in an incubator (37°C, 5% CO2) and cultured for 24 h. The cell supernatant was collected and the type I collagen content was detected using a kit. GraphPad Prism 8.0 software was used for statistical analysis and graphing. Quantitative data are expressed as x ± s. Differences between groups were analyzed by one-way ANOVA. P < 0.05 was considered statistically significant, P < 0.05 was considered significantly different, and P < 0.01 was considered extremely significant.

[0068] Table 3 Type I collagen content test sample information

[0069] Type I collagen content test results Figure 6As shown, at a concentration of 0.02%, by comparing Example 1 with Comparative Examples 1 and 2, it can be seen that the double-molecular-weight hyaluronic acid liposomes encapsulated in Example 1 have a significant up-regulating effect on COL I in human HFF cells, with a significance level of <0.01, and the effect is equivalent to that of the double-molecular-weight hyaluronic acid not encapsulated in Comparative Example 2, while the blank liposomes of Comparative Example 1 have no effect, indicating that the liposomes of the present invention do not affect the efficacy of the active ingredient after encapsulating the double-molecular-weight hyaluronic acid, and have the effect of promoting the regeneration of type I collagen; by comparing Example 1 with Comparative Examples 3 and 4, it can be seen that the single-molecular-weight sodium hyaluronate encapsulated in Comparative Examples 3 and 4 has a lower effect on up-regulating COL I than the double-molecular-weight sodium hyaluronate encapsulated in Example 1, and the double-molecular-weight hyaluronic acid in the present invention has a synergistic effect of promoting the regeneration of type I collagen.

[0070] Pigskin penetration test Take the samples of Example 1 and Comparative Example 2, add 0.02% sulforhodamine salt respectively, and prepare a 50% fluorescent solution with deionized water as the test sample; use 0.8-1 cm ex vivo Bama Xiang pig skin as the in vitro transdermal test material, use PBS as the receiving medium, and measure the permeation absorption by Franz diffusion cell; set the parameters to 37.5°C and 600rpm, and after 30 minutes of penetration, clean the pig skin surface with PBS and slice it; observe the distribution of fluorescence signals in the pig skin under a fluorescence microscope, use Image J software to analyze the fluorescence penetration depth, and evaluate the transdermal absorption effect of the encapsulated small molecule hyaluronic acid liposomes and the unencapsulated composite hyaluronic acid. The test results are as follows: Figure 7 As shown, by comparing the fluorescence penetration depths of Example 1 and Comparative Example 2, Example 1 penetrates significantly deeper than Comparative Example 2, indicating that the encapsulated liposomes have a better penetration effect.

[0071] Skin feel test To further verify the application and effect of the liposomes prepared in Example 1 and Comparative Examples 2 and 6 in essence water, the liposomes provided in Example 1 and Comparative Examples 2 and 6 were used as raw materials to prepare essence water. The raw material composition and dosage of the essence water are shown in Table 4.

[0072] Table 4 Essence Water Raw Materials

[0073] The preparation method of essence water is: (1) Weigh the raw materials of phase C in Table 5 in parts by weight, heat and stir in a constant temperature water bath at 80°C to disperse evenly, keep warm for 30 minutes, and then cool to 40°C-45°C; (2) Weigh the raw materials of phase D in the mass fractions in Table 5 in sequence, add them to the cooled phase C mixture, and continue stirring until the system is homogeneous to obtain the essence water.

[0074] In order to further verify the application and effect of Example 1 in a facial mask, the products provided in Example 1 and Comparative Example 1 were used as raw materials to prepare a facial mask. The raw material composition and dosage of the facial mask are shown in Table 5.

[0075] Table 5 Mask raw materials

[0076] A questionnaire was set up and 30 subjects were invited to rate the two groups of essence water and two groups of facial masks in terms of appearance, refreshing feeling, absorption feeling, moisturizing feeling, softness feeling, stickiness feeling and other skin feel dimensions, and the analysis results were recorded.

[0077] The essence water prepared in Example 1 and Comparative Example 2 is as follows: Figure 8 (The left picture uses Example 1 as the raw material, and the right picture uses Comparative Example 2 as the raw material) As shown in the skin feel test results of the essence water Figure 9 As shown, the appearance of the raw materials of Comparative Example 6 is the same as that of Comparative Example 2.

[0078] The facial masks prepared in Example 1 and Comparative Example 2 are as follows: Figure 10 (The left picture uses Example 1 as the raw material, and the right picture uses Comparative Example 1 as the raw material) As shown in the skin feel test results of the mask, Figure 11 As shown, the appearance of the raw materials of Comparative Example 6 is the same as that of Comparative Example 2.

[0079] Skin feel analysis: Comparing Example 1 with Comparative Example 2, the essence water with 3% of Example 1 (hyaluronic acid liposomes for dual anti-wrinkle and improved skin feel) significantly improved smoothness, softness, moisturizing, and smoothness. The mask liquid also showed significant improvements in absorption, moisturizing, softness, and moisturizing. After adding liposomes, the appearance of both products exhibited a bluish glow. Comparing Example 1 with Comparative Example 6, Example 1 performed better in terms of skin feel for both the essence water and the mask liquid, indicating that the liposome composition of the present invention can provide a unique appearance and significantly improved skin feel for aqueous formulations.

[0080] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some or all of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present application.

[0081] Furthermore, those skilled in the art will appreciate that although some embodiments herein include certain features included in other embodiments but not others, combinations of features from different embodiments are intended to be within the scope of this application and to form distinct embodiments. For example, in the claims above, any of the claimed embodiments may be used in any combination. The information disclosed in this background section is intended solely to enhance understanding of the overall background of this application and should not be construed as an admission or any implication that such information constitutes prior art known to those skilled in the art.

Claims

1. A hyaluronic acid liposome with dual anti-wrinkle and skin feel improvement, characterized in that: The raw materials, calculated based on the total mass as 100%, include: 1%-5% hydrogenated lecithin, 0.5%-1.5% PEG-60 hydrogenated castor oil, 0.5%-2% Pellicer L-30, 2%-10% PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, 2%-50% glycerin, 1%-2% hexylene glycol, 5%-15% dimethicone, 0.05%-0.5% small molecule hydrolyzed sodium hyaluronate, 0.05%-0.1% large molecule sodium hyaluronate, the balance is water; The molecular weight of the small molecule sodium hyaluronate is 400Da-1600Da; The molecular weight of the macromolecular sodium hyaluronate is 1 million Da to 3 million Da.

2. A method for preparing the dual anti-wrinkle and skin-improving hyaluronic acid liposomes according to claim 1, characterized in that: include: The hydrogenated lecithin, the hexylene glycol, the PEG-60 hydrogenated castor oil, the glycerin, the PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin and the polydimethylsiloxane are first mixed and first heated to obtain a first mixture; performing a second mixing and a second heating of the Pellicer L-30, the small molecule hydrolyzed sodium hyaluronate, the large molecule sodium hyaluronate, and the water to obtain a second mixture; performing a third mixing of the first mixture and the second mixture to obtain the third mixture; The third mixture is stirred and homogenized to obtain the hyaluronic acid liposomes with dual anti-wrinkle and skin feel improvement properties.

3. The method for preparing the dual anti-wrinkle and skin-improving hyaluronic acid liposomes according to claim 2, characterized in that: The first heating temperature is 60°C-80°C.

4. The method for preparing the dual anti-wrinkle and skin-improving hyaluronic acid liposomes according to claim 2, characterized in that: The second heating temperature is 60°C-80°C.

5. The method for preparing the dual anti-wrinkle and skin-feel improving hyaluronic acid liposome according to any one of claims 2 to 4, characterized in that: At least one of the following conditions is met: A. The stirring speed is 2000rpm-5000rpm, and the time is 2min-4min; B. Using high-pressure microfluidization to carry out the homogenization process.

6. The method for preparing the dual anti-wrinkle and skin-feel improving hyaluronic acid liposomes according to claim 5, characterized in that: The pressure of the high-pressure micro jet is 800 bar-1200 bar, and the number of cycles is 3-4 times.

7. An essence water, characterized in that: The invention comprises the hyaluronic acid liposomes for dual anti-wrinkle and skin feel improvement as claimed in claim 1.

8. A facial mask, characterized in that: The invention comprises the hyaluronic acid liposomes for dual anti-wrinkle and skin feel improvement as claimed in claim 1.

9. A lotion, characterized in that: The invention comprises the hyaluronic acid liposomes for dual anti-wrinkle and skin feel improvement as claimed in claim 1.

10. Use of the dual anti-wrinkle and skin feel improving hyaluronic acid liposomes according to claim 1 in the preparation of external preparations and cosmetics.

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