A skin-penetrating preparation, its preparation method and use

Abstract

The application belongs to the field of new daily chemical materials, and discloses a skin introduction preparation containing trehalose, full-molecular-weight hyaluronate and hydroxytyrosol; the mass ratio of trehalose to full-molecular-weight hyaluronate is 1:99-99:1; and the mass ratio of hydroxytyrosol to full-molecular-weight hyaluronate is 20:1-200. The preparation introduces full-molecular-weight hyaluronate as one of core components, and improves the transdermal effect of trehalose and hydroxytyrosol through the full-molecular-weight hyaluronate. The active ingredient hydroxytyrosol in the preparation can effectively remove free radicals and decompose melanin to lighten and eliminate color spots. The trehalose and full-molecular-weight hyaluronate in the preparation can repair damaged skin, relieve inflammation and resist aging. The three components jointly act to achieve a synergistic skin repair effect. Meanwhile, the application also provides a preparation method and application of the transdermal introduction preparation.

Description

Technical Field

[0001] This invention relates to the field of new materials for daily chemical products, specifically to skin delivery preparations, their preparation methods, and applications. Background Technology

[0002] Nanoparticle-based skin delivery formulations can penetrate the stratum corneum of the human body, directly delivering the functional factors needed by the skin to the required layers of the skin, allowing the skin tissue to absorb them rapidly, thereby achieving effects such as improving skin texture.

[0003] CN116531376A and CN116440016A both disclose the same transdermal formulation:

[0004] It includes: a solid and a liquid; wherein the solid is composed of a co-crystal of hydroxytyrosol and nicotinamide and trehalose, wherein the molar ratio of hydroxytyrosol and nicotinamide in the co-crystal is 1:1;

[0005] The liquid comprises: oligopeptide-1, oligopeptide-2, oligopeptide-5, arginine / lysine polypeptide, acetyl octapeptide-3, dipeptide diaminobutyryl benzylamide diacetate, glyceryl glucoside, oat β-glucan, p-hydroxyacetophenone, 1,3-butanediol, 1,2-hexanediol, and water; the liquid optionally contains a soluble collagen cross-linking polymer, sodium hyaluronate or zinc hyaluronate, 1,2-pentanediol, glycerol, glycerophosphoinositol choline salt, phenoxyethanol, and / or ethylhexylglycerol; and the solid and liquid are physically separated before use.

[0006] According to the relevant patent CN113004198B cited, the method for preparing a co-crystal of hydroxytyrosol and nicotinamide is mainly used to improve the stability of hydroxytyrosol.

[0007] Table 1 in the two aforementioned documents verifies the functional differences of the different liquid components:

[0008] Formula 1: The eutectic has poor solubility with the product obtained from Formula 1, resulting in slow absorption and a sticky feel when applied topically to the back of the hand. Formula 2: The eutectic has good solubility with the product obtained from Formula 2, resulting in fast absorption when applied topically to the back of the hand, but the texture is thin and not moisturizing enough. Formula 3: The eutectic has good solubility with the product obtained from Formula 3, resulting in a light, smooth, and moisturizing feel when applied topically to the back of the hand. Based on the mixing with the eutectic and the user experience (including but not limited to stinging sensation, stickiness, and penetration speed), it is believed that liquid Formula 3 is more suitable for the eutectic.

[0009] In Formula 3, sodium hyaluronate has a molecular weight of 1.1 million Daltons and a content of 0.05%.

[0010] According to the formula in Table 3, the solid-liquid ratio is 20mg:1ml to 200mg:1ml;

[0011] Based on the conversion, the ratio of sodium hyaluronate to hydroxytyrosol is approximately in the range of 0.5mg:1 to 66mg.

[0012] The ratio of sodium hyaluronate to trehalose is approximately in the range of 0.5mg:18-66mg.

[0013] The instructions also state that sodium hyaluronate or zinc hyaluronate can provide the kit with a moisturizing effect, which is beneficial for hydration and improving dryness and roughness, and can also act as a thickener. In some embodiments, the liquid may contain sodium hyaluronate or zinc hyaluronate based on the total mass of the liquid, with a mass fraction of 0.01%-0.1%. In some embodiments, the liquid contains sodium hyaluronate with a mass fraction of 0.05%. The molecular weight of the sodium hyaluronate or zinc hyaluronate may be 1 million Daltons to 1.5 million Daltons.

[0014] Through comprehensive analysis, we believe that in the above scheme, sodium hyaluronate only serves as a moisturizing and thickening agent, without realizing that sodium hyaluronate can act as a core component of the above ingredients to achieve functional effects on the skin.

[0015] The technical problem this solution aims to solve is: how to develop a transdermal delivery formulation with superior efficacy. Summary of the Invention

[0016] The purpose of this invention is to provide a transdermal delivery formulation that incorporates full molecular weight hyaluronic acid salt as one of its core components. The full molecular weight hyaluronic acid salt enhances the transdermal effects of trehalose and hydroxytyrosol. The active ingredient hydroxytyrosol can effectively remove free radicals, decompose melanin, and lighten and eliminate pigmentation. Trehalose and full molecular weight hyaluronic acid salt can repair damaged skin, relieve inflammation, and have anti-aging effects. The three components work together to achieve a synergistic skin repair effect.

[0017] In addition, the present invention also provides a method for preparing transdermal delivery formulations and their applications.

[0018] To achieve the above objectives, the present invention provides the following technical solution:

[0019] A skin delivery formulation containing trehalose, full molecular weight hyaluronic acid salt, and hydroxytyrosol;

[0020] The mass ratio of trehalose to full molecular weight hyaluronic acid salt is 1:99 to 99:1;

[0021] The mass ratio of hydroxytyrosol to full molecular weight hyaluronic acid salt is 20:1 to 200.

[0022] In some embodiments of the present invention, the mass ratio of trehalose to full molecular weight hyaluronic acid salt is 1:99, 5:95, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, 95:5 or 99:1;

[0023] In some embodiments of the present invention, the mass ratio of hydroxytyrosol to full molecular weight hyaluronic acid salt is: 20:1, 20:5, 20:10, 20:25, 20:30, 20:40, 20:50, 20:60, 20:70, 20:80, 20:90, 20:100, 20:110, 20:120, 20:130, 20:140, 20:150, 20:160, 20:170, 20:180, 20:190 or 20:200;

[0024] The principle of this invention is as follows:

[0025] The skin delivery formulation provided by this invention can penetrate into the dermis layer of the skin. The active ingredient hydroxytyrosol can effectively remove free radicals, decompose melanin, and lighten and eliminate age spots. The trehalose and full molecular weight hyaluronic acid salts can repair damaged skin, relieve inflammation, and fight aging.

[0026] When the amount of full molecular weight hyaluronic acid salt relative to trehalose is too small, it cannot synergistically repair damaged skin, relieve inflammation, and fight aging, thus further affecting the efficacy of hydroxytyrosol.

[0027] In summary, the combined use of full molecular weight hyaluronic acid salts, trehalose, and hydroxytyrosol can enhance the activity of hyaluronic acid and trehalose. The skin delivery formulation provided by this invention can penetrate into the dermis layer of the skin; this skin delivery formulation is safe to use and causes no damage to the skin. Therefore, this skin delivery formulation is effective and enriches the variety of nano-skin delivery formulations.

[0028] Preferably, the mass ratio of trehalose to full molecular weight hyaluronic acid salt is 10:90 to 90:10.

[0029] Preferably, the mass ratio of hydroxytyrosol to full molecular weight hyaluronic acid salt is 20:10 to 90:10.

[0030] Preferably, the weight-average molecular weight distribution range of the full molecular weight hyaluronic acid salt is 0.2 million to 1.5 million; the molecular weight dispersion coefficient Mw / Mn is above 5;

[0031] The full molecular weight hyaluronic acid salt of the present invention can be found in the applicant's patent application CN113512134A;

[0032] And / or, the full molecular weight hyaluronic acid salt is one or more of sodium hyaluronate, zinc hyaluronate, and potassium hyaluronate.

[0033] CN113512134A provides a method for preparing full molecular weight sodium hyaluronate. The same method can be used to prepare full molecular weight zinc hyaluronate and full molecular weight potassium hyaluronate. The specific steps are as follows:

[0034] Step 1): Spray the solid raw material of zinc / potassium hyaluronic acid with hydrogen peroxide and irradiate it with ultraviolet light to obtain the degraded material of zinc / potassium hyaluronic acid;

[0035] Step 2): Dissolve the zinc / potassium hyaluronic acid degradation material in water, and adjust the pH to alkaline with NaOH solution to obtain an alkaline zinc / potassium hyaluronic acid solution;

[0036] Step 3): The zinc / potassium hyaluronic acid alkaline solution is subjected to ultrasonic treatment;

[0037] Step 4): Prepare a zinc / potassium hyaluronic acid solid raw material into a zinc / potassium hyaluronic acid solution with a concentration of 0.1% to 1% (w / v), and mix it evenly with the ultrasonically treated zinc / potassium hyaluronic acid alkaline solution obtained in Step 3) at an addition ratio of 20% to 60% (v / v).

[0038] Step 5): Adsorption treatment was performed using diatomaceous earth and activated carbon respectively, followed by filtration and concentration using a nanofiltration membrane. After drying, the zinc / potassium hyaluronic acid with the full molecular weight distribution was obtained.

[0039] For specific hyaluronic acid salts with corresponding molecular weight distributions, please refer to Examples 1-6 of CN113512134A.

[0040] Preferably, the formulation is contained in two separate packages, and the contents of the two packages are mixed before use.

[0041] One of the packages contained trehalose and full molecular weight hyaluronic acid.

[0042] The other package contained hydroxytyrosol.

[0043] Preferably, the trehalose and full molecular weight hyaluronic acid salt are mixed in the form of nanoparticles and placed in one package; the hydroxytyrosol and solvent are mixed and placed in another package; before mixing the contents of the two packages, the trehalose and full molecular weight hyaluronic acid salt are first dispersed in the solvent, and then mixed with the hydroxytyrosol and solvent to form a mixture.

[0044] Preferably, the solvent is one of deionized water and physiological saline.

[0045] Of course, the above-mentioned skin delivery preparations can also be prepared as a mixed solution by mixing trehalose, full molecular weight hyaluronic acid salt in the form of nanoparticles with hydroxytyrosol and solvent and sealing or storing under inert gas.

[0046] Preferably, in the mixture formed by trehalose, full molecular weight hyaluronic acid salt, and solvent, the total mass ratio of trehalose and full molecular weight hyaluronic acid salt powder to the volume ratio of solvent is 2:10 to 1:99 (w / v, g / mL).

[0047] In the mixture formed by the hydroxytyrosol and the solvent, the mass ratio of hydroxytyrosol to the volume ratio of the solvent is 1:3 to 1:99 (w / v, g / mL).

[0048] Meanwhile, the formulation of the present invention does not exclude the addition of its functional components to the formulation of the present invention, and the functional components include, but are not limited to: plant extracts, polysaccharides, polypeptides, amino acids, and chemical agents;

[0049] The plant extracts may be selected from Rhodiola rosea extract, rose extract, Angelica sinensis extract, Coptis chinensis extract, chamomile extract, etc.

[0050] Polysaccharides can be selected from chitosan, hydrolyzed chitosan, tremella polysaccharide, chondroitin sulfate, etc.

[0051] The polypeptides can be selected from polyglutamic acid, ascorbic acid polypeptides, yeast polypeptides, soybean polypeptides, etc.

[0052] Amino acids can be selected from collagen amino acids, keratin amino acids, yeast amino acids, plant amino acids, etc.

[0053] Chemical agents that can be selected include γ-aminobutyric acid, ectoine, nicotinamide, ergothioneine, bosine, etc.

[0054] Furthermore, this invention also discloses a method for preparing any of the above-described skin-delivery formulations, comprising the following steps:

[0055] Trehalose and full molecular weight hyaluronic acid salts were mixed evenly and then subjected to nano-homogenization to obtain nano powder.

[0056] The hydroxytyrosol was mixed evenly with a solvent to obtain an active solution;

[0057] Before use, the nanopowder is dissolved in the active solution, or the nanopowder is dissolved in a solvent and mixed with the active solution.

[0058] Finally, the present invention also discloses a use of a skin-infusion formulation as described above in the preparation of daily chemical products.

[0059] Compared with the prior art, the beneficial effects of the present invention are:

[0060] The skin delivery formulation provided by this invention can penetrate into the dermis layer of the skin. The active ingredient hydroxytyrosol can effectively remove free radicals, decompose melanin, and lighten and eliminate age spots. The trehalose and full molecular weight hyaluronic acid salts can repair damaged skin, relieve inflammation, and fight aging.

[0061] When the amount of full molecular weight hyaluronic acid salt relative to trehalose is too small, it cannot synergistically repair damaged skin, relieve inflammation, and fight aging, thus further affecting the efficacy of hydroxytyrosol.

[0062] In summary, the combined use of full molecular weight hyaluronic acid salts, trehalose, and hydroxytyrosol can enhance the activity of hyaluronic acid and trehalose. The skin delivery formulation provided by this invention can penetrate into the dermis layer of the skin; this skin delivery formulation is safe to use and causes no damage to the skin. Therefore, this skin delivery formulation is effective and enriches the variety of nano-skin delivery formulations. Detailed Implementation

[0063] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0064] Example 1

[0065] (1) Thoroughly mix trehalose and sodium hyaluronate of full molecular weight in an appropriate weight ratio, disperse them using a nano-disperser at a speed of 1000 rpm for 1.5 h to obtain nano powder with a particle size of 80 nm.

[0066] (2) Dissolve the nanopowder in physiological saline at a concentration of 5% (w / v) and sonicate it at 60W for 130 min to obtain solution 1;

[0067] (3) The hydroxytyrosol was mixed with physiological saline at 50% (w / v) and stirred continuously at 4°C in the dark for 0.5 h. The mixture was then sonicated at 30-200 W for 30 min to obtain solution 2.

[0068] (4) After solution 1 and solution 2 are separately sealed, they are subjected to high temperature and high pressure sterilization at 115℃ for 30 minutes.

[0069] (5) Before using the skin delivery preparation, mix the solution 1 and the solution 2 thoroughly.

[0070] The sodium hyaluronate of the present invention refers to Examples 1-6 of CN113512134A, and yields sodium hyaluronate 1 (Mw / Mn = 5.2), sodium hyaluronate 2 (Mw / Mn = 5.6), sodium hyaluronate 3 (Mw / Mn = 6.1), sodium hyaluronate 4 (Mw / Mn = 6.5), sodium hyaluronate 5 (Mw / Mn = 6.9), and sodium hyaluronate 6 (Mw / Mn = 7.1).

[0071] In addition, the present invention also purchased commercially available sodium hyaluronate with a molecular weight of 6 kDa (sodium hyaluronate 7), sodium hyaluronate with a molecular weight of 200 kDa (sodium hyaluronate 8), and sodium hyaluronate with a molecular weight of 1200 kDa (sodium hyaluronate 9).

[0072] The preparation methods of the various embodiments and comparative examples of the present invention are as described in Example 1 above, and their formulations are as described in Table 1.

[0073] Table 1 Formula Table

[0074]

[0075]

[0076] Taking Example 1 as an example, in the preparation process, 1g of trehalose and 99g of sodium hyaluronate were first prepared into nanoparticles, and then mixed with physiological saline at a concentration of 5% (w / v) and sonicated to obtain solution 1; then 20g of hydroxytyrosol was mixed with physiological hydrochloric acid at a concentration of 50% (w / v) and sonicated in the dark to obtain solution 2; then solution 1 and solution 2 were combined for use.

[0077] Other embodiments and comparative examples refer to the preparation method described above.

[0078] Volunteer Experiment

[0079] 156 female volunteers, aged between 30 and 50, were recruited and randomly divided into 26 groups: saline group, Examples 1-15, and Comparative Examples 1-10, with 6 volunteers in each group.

[0080] The mixed solution was prepared according to the formula in Table 1 and the method in Example 1. The weight ratio of each substance in the mixed solution is shown in Table 1.

[0081] After cleaning the volunteers' faces and allowing them to air dry naturally, volunteers in the saline group had saline solution continuously applied to their entire face. Then, a nano-microcrystalline infusion device (manufacturer: Suzhou Naton Bio-Nano Technology Co., Ltd., model SPE18CYT) was used to vertically contact the skin surface and electrically prick each point one by one, for 1 second at each point, and then moved 1 mm to the side to prick the next point. This method was used to complete the infusion of the entire face, and was repeated 3 times. Volunteers in Examples 1-15 and Comparative Examples 1-10 used the nano-microcrystalline infusion device (manufacturer: Suzhou Naton Bio-Nano Technology Co., Ltd., model SPE18CYT) to infuse the entire face. Volunteers in Examples 1-15 and Comparative Examples 1-10 received the infusion once a week for a total of 2 months. During this period, volunteers could use regular moisturizing skin care products and sunscreen, but did not receive any other facial beauty interventions or take any beauty-related drugs or health products. Every week, before and after the intervention, each group of volunteers had photos taken with a digital camera and their transepidermal water loss (TEWL), stratum corneum moisture content, erythema, melanin, and skin elasticity were measured. Volunteer satisfaction and adverse reactions were investigated through a skin condition questionnaire.

[0082] Skin testing: The testing room was kept away from direct sunlight and wind, with the room temperature controlled at approximately 22℃ and humidity at 50%–60%. Before the test, each volunteer cleansed their face without applying any cosmetics and entered the testing room 30 minutes prior to the test, sitting quietly. First, photos were taken with a digital camera. Then, the moisture loss test probe, moisture test probe, melanin and hemoglobin test probe, and elastic fiber tissue test probe of a multi-functional skin analyzer were used to measure TEWL, stratum corneum water content, erythema amount, melanin, and skin elasticity, respectively. During the test, four fixed locations were selected on the face for measurement. Readings were taken after each measurement stabilized, and the average value was used for statistical analysis. The same tests were performed on volunteers 72 hours after the last intervention. Specific results are shown in Tables 2 to 6.

[0083] Table 2 compares the TWEL and stratum corneum moisture content measured in volunteers before and after the last intervention.

[0084]

[0085]

[0086] In Table 2, * indicates a significant difference compared to before the intervention (P<0.05).

[0087] As shown in Table 2, the TWEL and stratum corneum moisture content of Examples 1-15 of the present invention are significantly better than those of Comparative Examples 1-10 and the saline group.

[0088] Table 3 compares the erythema index and elasticity index measured in volunteers before and after the last intervention.

[0089]

[0090]

[0091] In Table 3, * indicates a significant difference compared to before the intervention (P<0.05).

[0092] Table 4 shows the melanin values ​​measured in volunteers before and after the last intervention.

[0093]

[0094]

[0095] *In Table 4, * indicates a statistically significant difference compared to before the intervention (P<0.05). Meanwhile, there were no statistically significant differences in melanin levels in the skin of the volunteers in each group before the intervention, making them comparable. In the saline group, there were no statistically significant differences in melanin levels measured after each intervention compared to the initial intervention values.

[0096] As shown in Table 4, the melanin values ​​in the embodiment group of the present invention decreased to a greater extent after intervention.

[0097] Adverse reactions: No adverse reactions such as infection, erythema, or edema were observed in any of the volunteers participating in the study.

[0098] Results analysis:

[0099] 1. As can be seen from Tables 2, 3, and 4, the performance of Examples 1 to 15 is generally better than that of Comparative Examples 1 to 10; this shows that sodium hyaluronate, trehalose, and hydroxytyrosol are all indispensable; it also proves that ordinary hyaluronic acid is almost ineffective; as can be seen from Comparative Example 10, ordinary hyaluronic acid can also achieve certain effects when compounded with different molecular weights, but its overall performance is still far inferior to that of Example 8 in this case.

[0100] 2. As can be seen from Tables 2, 3 and 4, the optimal performance range is when the ratio of trehalose to full molecular weight hyaluronic acid is in the range of 10:90-90:10, and more preferably in the range of 30:70-50:50.

[0101] 3. As can be seen from Tables 2, 3, and 4, the sodium hyaluronate of the present invention, when used with trehalose or hydroxytyrosol, or when used alone, has a slight effect. This demonstrates the superior performance of the sodium hyaluronate of the present invention. Furthermore, relevant cases also prove that the performance of the sodium hyaluronate of the present invention can be synergistically improved in the presence of trehalose and hydroxytyrosol. This synergistic improvement was not observed in Comparative Examples 7-9; its synergistic effectiveness is also significantly better than that of Comparative Example 10.

[0102] In summary, full molecular weight sodium hyaluronate in skin-delivery formulations regulates water balance and maintains cell structure through its high water retention and viscosity. Topical application of full molecular weight sodium hyaluronate can enhance the skin's natural defense function, accelerate wound healing, improve skin physiological properties, increase skin firmness, alleviate skin inflammation and wrinkle formation, stimulate dermal fibroblasts, and promote collagen synthesis. Full molecular weight sodium hyaluronate delivered to the dermis can provide long-term improvement in facial wrinkles and strengthen facial soft tissue, with few side effects and good tolerability.

[0103] Trehalose is a non-reducing disaccharide composed of two glucose molecules. It is a stress molecule produced by organisms under harsh environments and has a strong protective effect on biological macromolecules and cells.

[0104] Hydroxytyrosol is a small molecule compound with excellent antioxidant and free radical scavenging capabilities. It also has a strong ability to capture free radicals such as reactive oxygen species, effectively eliminating intrinsic oxygen free radicals and reducing the damage to various cellular physiological functions caused by free radicals stealing electrons from cells or gene protein molecules. This slows down skin aging and has a powerful function in repairing oxidative damage to the skin. Simultaneously, hydroxytyrosol can inhibit oxidative damage to cellular DNA, reduce DNA damage caused by oxides, restore the normal physiological functions of glutathione and other peptides, stabilize the activity of free radicals, and reduce their aggressiveness. Hydroxytyrosol itself has activating or revitalizing effects on various receptors and signaling pathways. The physiological activities of sodium hyaluronate and trehalose (such as promoting wound healing, inhibiting inflammatory responses, and protecting cells) are achieved by activating downstream signaling pathways within the cell after acting on receptors on the cell surface and undergoing signal transduction. The active solution and nanoparticles can have a synergistic effect on skin repair. Therefore, the combined use of sodium hyaluronate, trehalose, and hydroxytyrosol can, to a certain extent, promote the better activity of sodium hyaluronate and trehalose.

[0105] The skin-delivery formulation provided by this invention can penetrate into the dermis layer of the skin. Its active ingredient, hydroxytyrosol, effectively removes free radicals, breaks down melanin, and lightens and eliminates age spots. The trehalose and full-molecular-weight sodium hyaluronate it contains can repair damaged skin, relieve inflammation, and have anti-aging effects. This skin-delivery formulation is safe to use and causes no damage to the skin.

[0106] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, it is intended that all variations falling within the meaning and scope of equivalents of the claims be included within the present invention.

Claims

1. A dermal introduction preparation, characterized by comprising, trehalose, a full molecular weight hyaluronic acid salt, hydroxytyrosol; The mass ratio of trehalose to the full molecular weight hyaluronic acid salt is 10:90~90:10; The mass ratio of hydroxytyrosol to the full molecular weight hyaluronic acid salt is 20:10~90; The weight average molecular weight distribution range of the full molecular weight hyaluronic acid salt is 0.2~1.5 million; the molecular weight dispersion coefficient Mw / Mn is 5.2~7.1; The full molecular weight hyaluronic acid salt is one or more mixtures of full molecular weight sodium hyaluronate, full molecular weight zinc hyaluronate, and full molecular weight potassium hyaluronate; The trehalose and the full molecular weight hyaluronic acid salt form a mixture with a solvent, and in the mixture, the total mass of the powders of trehalose and the full molecular weight hyaluronic acid salt and the mass volume ratio of the solvent are 5% w / v; The mixture of the hydroxytyrosol and the solvent, and in the mixture, the mass of the hydroxytyrosol and the mass volume ratio of the solvent are 50% w / v; The solvent is one of deionized water and physiological saline.

2. The dermal introduction preparation according to claim 1, characterized by The trehalose and the full molecular weight hyaluronic acid salt are mixed in the form of nano-powder and placed in one package; the hydroxytyrosol and the solvent are mixed and placed in another package; before mixing the contents of the two packages, the trehalose and the full molecular weight hyaluronic acid salt are dispersed in the solvent, and then mixed with the mixture of the hydroxytyrosol and the solvent.

3. The method for preparing a skin-penetrating preparation according to claim 1, wherein The method comprises the following steps: The trehalose and the full molecular weight hyaluronic acid salt are mixed uniformly and nano-homogenized to obtain nano-powder; The hydroxytyrosol is mixed uniformly with the solvent to obtain an active solution; Before use, the nano-powder is dissolved in the solvent and mixed with the active solution.

4. Use of the skin introduction preparation according to any one of claims 1~3 in the preparation of a daily-use cosmetic.

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