Preparation method of phenylethyl resorcinol / sodium alginate emulsion gel beads as well as product and application of phenylethyl resorcinol / sodium alginate emulsion gel beads

Abstract

The invention discloses a preparation method of phenylethyl resorcinol / sodium alginate emulsion gel beads as well as a product and application of the phenylethyl resorcinol / sodium alginate emulsion gel beads. The method comprises the following steps: firstly, dissolving phenethyl resorcinol in an oil phase, mixing with a water phase containing sodium alginate and a thickening agent, and homogenizing to form an oil-in-water emulsion; then, through an extrusion titration process, the emulsion is dropped into a calcium salt solution to be subjected to an ionic cross-linking reaction, and emulsion gel beads are formed through curing. According to the invention, the problems of poor water solubility, strong irritation and the like of phenylethyl resorcinol are effectively solved by utilizing an emulsion filled gel network structure, and meanwhile, the defect of unstable thermodynamics of the traditional emulsion is overcome. The prepared gel beads are high in sphericity degree, good in mechanical stability and good in mechanical property, can play a dual whitening effect by inhibiting tyrosinase activity and down-regulating protein expression of tyrosinase, and has a wide application prospect in the field of functional cosmetics.

Description

Technical Field

[0001] This invention relates to the field of functional skincare product preparation technology, specifically to a method for preparing phenylethyl resorcinol / sodium alginate emulsion gel beads, its products and applications, and a method for preparing phenylethyl resorcinol / sodium alginate emulsion gel beads with whitening properties, its products and applications. Background Technology

[0002] Phenethyl resorcinol, a derivative of resorcinol, is a new generation of highly effective tyrosinase inhibitors, exhibiting significantly superior whitening efficacy compared to traditional ingredients such as kojic acid and arbutin. It effectively blocks melanin synthesis by competitively occupying the active site of tyrosinase. However, phenylethyl resorcinol faces challenges in practical cosmetic formulations, including poor water solubility and strong irritation. Therefore, effective and simple technologies and materials are needed to load and sustain the release of this substance.

[0003] Compared to common nanocarrier technologies (liposomes, nanoparticles), emulsion technology is simple, efficient, has no upper limit on drug loading, is low-cost, and does not produce toxic intermediates, making it the most widely accepted loading strategy. However, emulsions are thermodynamically unstable systems, and under long-term storage or centrifugal force, they are prone to flocculation, stratification, or oil drift. Therefore, there is an urgent need to develop stable emulsion systems.

[0004] Sodium alginate is a natural linear anionic polysaccharide derived from brown algae. It is odorless, tasteless, and readily soluble in water. Its molecular structure contains many hydroxyl and carboxyl groups, allowing it to absorb large amounts of water to form a colloidal solution. Its most significant characteristic is its ability to undergo ionic cross-linking with metal cations (especially calcium ions) under mild conditions, forming a gel with a three-dimensional network structure.

[0005] Therefore, this invention utilizes phenylethyl resorcinol as the oil phase and sodium alginate as the aqueous phase to obtain an effectively loaded phenylethyl resorcinol / sodium alginate emulsion. The obtained emulsion is then dropped into a calcium chloride solution to prepare gel beads with good stability. These gel beads exhibit highly efficient loading and sustained release of the active substance phenylethyl resorcinol due to the presence of the emulsion, and also possess extremely strong mechanical stability due to the steric hindrance effect provided by the calcium alginate gel network. Summary of the Invention

[0006] In order to overcome the shortcomings of existing technologies, such as poor water solubility of phenylethyl resorcinol, strong irritation, and instability of emulsion carriers, the present invention aims to provide a method for preparing phenylethyl resorcinol / sodium alginate emulsion gel beads.

[0007] This method first dissolves phenylethyl resorcinol in an oil phase, mixes it with an aqueous phase containing sodium alginate and a thickener, and homogenizes it to form an oil-in-water emulsion. Then, through an extrusion titration process, the emulsion is dropped into a calcium salt solution to undergo an ionic cross-linking reaction, solidifying to form emulsion gel beads. This invention utilizes an "emulsion-filled gel" network structure, effectively solving the problems of poor water solubility and strong irritation of phenylethyl resorcinol, while overcoming the thermodynamic instability of traditional emulsions. The resulting gel beads have high sphericity, good mechanical stability, and excellent mechanical properties. They can also exert a dual whitening effect by inhibiting tyrosinase activity and downregulating its protein expression, showing broad application prospects in the field of functional cosmetics.

[0008] This invention utilizes phenylethyl resorcinol as the oil phase and sodium alginate as the aqueous phase to obtain an effectively loaded phenylethyl resorcinol / sodium alginate emulsion. The obtained emulsion is then dropped into a calcium chloride solution to prepare gel beads with good stability. These gel beads exhibit highly efficient loading and slow release of the active substance phenylethyl resorcinol due to the presence of the emulsion, while also possessing extremely strong mechanical stability due to the steric hindrance effect provided by the calcium alginate gel network.

[0009] Another objective of this invention is to provide a phenylethyl resorcinol / sodium alginate emulsion gel bead product prepared according to the above method. This gel bead has whitening properties, effectively inhibits tyrosinase activity, and is characterized by simple and quick preparation, low cost, uniform size, and good mechanical properties.

[0010] Another object of the present invention is to provide an application of the product.

[0011] The objective of this invention is achieved through the following scheme: a method for preparing phenylethyl resorcinol / sodium alginate emulsion gel beads, characterized by comprising the following preparation steps: (1) Preparation of phenylethyl resorcinol oil phase: Phenethyl resorcinol, oily solute and oily solvent are mixed and dissolved to form a homogeneous oil phase; (2) Preparation of sodium alginate aqueous phase: Sodium alginate and aqueous solute are dissolved in water to form an aqueous phase; (3) Preparation of phenylethyl resorcinol / sodium alginate emulsion: The solutions obtained in steps (1) and (2) are mixed at a certain volume ratio, wherein the volume ratio of the oil phase to the water phase is any ratio between 1 / 20 and 1 / 5; the phenylethyl resorcinol / sodium alginate emulsion is obtained by heating and homogenizing emulsification step. (4) Preparation of phenylethyl resorcinol / sodium alginate emulsion gel beads: The emulsion obtained in step (3) is added dropwise to a 0.5-6wt% calcium chloride solution to crosslink and form gel beads.

[0012] Wherein, the oily solute in step (1) is any combination of jojoba oil, sunflower seed wax, C10-18 fatty acid triglyceride, glyceryl stearate, cetyl alcohol, stearyl alcohol, and polyacrylate crosspolymer-6.

[0013] The oily solvent in step (1) is at least one of butanediol, glycerol, caprylic / capric triglyceride, etc.; the mass concentration of the solute is 0.5, 1.0, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 or 6 wt.%.

[0014] The aqueous solute in step (2) is any combination of chitosan, trehalose, xanthan gum, cellulose gum, gum arabic, and sodium hyaluronate; the solution viscosity is any one of 500-1000 mPa·s; and the mass concentration of the solute is 0.5, 1.0, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, or 6 wt.%.

[0015] Step (3) includes heating and homogenizing emulsification, which involves high-speed shearing and ultrasound. The heating temperature is 80-100℃, the shearing rate is 600-1000 rpm, the emulsification time is 30-60 min, and the ultrasound time is 10-20 min.

[0016] The mass concentration of the calcium chloride solution in step (4) is 0.5, 1.0, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 or 6 wt%; the crosslinking time is 1-30 min.

[0017] This invention provides a phenylethyl resorcinol / sodium alginate emulsion gel bead, characterized in that it is prepared according to any of the methods described above, and the gel bead has whitening properties, effectively inhibits tyrosinase activity, and has the characteristics of simple and quick preparation, low cost, uniform size, and good mechanical properties.

[0018] This invention provides an application of phenylethyl resorcinol / sodium alginate emulsion gel beads in functional skin care products.

[0019] The efficacy includes at least one of whitening, moisturizing, and skin-nourishing.

[0020] Compared with the prior art, the present invention has the following advantages and beneficial effects: This invention achieves loading and sustained release of active ingredients through the dual physical barrier effect of emulsion encapsulation and gel network, avoiding skin irritation caused by high concentrations of phenylethyl resorcinol.

[0021] This invention utilizes a carrier system with a dual whitening mechanism, which can not only effectively deliver active ingredients to inhibit the catalytic activity of tyrosinase, but also significantly downregulate the expression level of tyrosinase at the protein level, thereby significantly reducing melanin production.

[0022] The gel beads obtained by this invention are uniform in size, have high sphericity, moderate hardness and elasticity, and have both good visual appearance and a refreshing and easy-to-spread skin feel. The preparation method is simple, the process is user-friendly, and it is easy to scale up for production, resulting in good economic benefits.

[0023] This invention forms a dense gel cross-linked network using calcium alginate, which generates a steric hindrance effect, effectively freezing the movement of internal oil droplets and blocking the aggregation and migration of emulsion droplets. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art are briefly introduced.

[0025] Figure 1 Flowchart of the preparation process of phenylethyl resorcinol / sodium alginate emulsion gel beads; Figure 2 Macroscopic morphology of phenylethyl resorcinol / sodium alginate emulsion and gel beads; Figure 3 Optical microscope images and particle size distribution diagrams of phenylethyl resorcinol / sodium alginate emulsion gel beads; Figure 4 Scanning electron microscope image of sodium phenylethyl resorcinol alginate / emulsion gel beads; Figure 5 Mechanical properties of sodium alginate / emulsion gel beads prepared with different calcium chloride concentrations; Figure 6 Comparison of centrifugal stability between emulsion and gel beads. Detailed Implementation

[0026] The present invention will be further described below with reference to specific embodiments, so that the present invention can be more completely and thoroughly understood by those skilled in the art. It is not limited to the preferred embodiments described, and does not constitute a limitation on the content and scope of protection of the present invention.

[0027] Example 1: Preparation of sodium alginate / phenylethyl resorcinol emulsion gel beads Formula composition: Aqueous phase: Sodium alginate 0.5 g, xanthan gum 0.5 g, trehalose 0.2 g, sodium hyaluronate 0.05 g, deionized water 90 g.

[0028] Oil phase: 1 g phenylethyl resorcinol, 0.2 g glyceryl stearate, 0.2 g jojoba ester, 0.2 g C10-18 fatty acid triglyceride, 3 g caprylic / capric triglyceride, 3 g butanediol.

[0029] Curing solution: 4% (w / v) calcium chloride aqueous solution.

[0030] A phenylethyl resorcinol / sodium alginate emulsion gel bead, the preparation process is as follows: Figure 1 As shown, the preparation steps are as follows: (1) Preparation of phenylethyl resorcinol oil phase: 1 g of phenylethyl resorcinol, 0.2 g of glyceryl stearate, 0.2 g of jojoba ester, 0.2 g of C10-18 fatty acid triglyceride, 3 g of caprylic / capric triglyceride, and 3 g of butanediol were mixed and stirred to dissolve, resulting in a homogeneous oil phase; (2) Preparation of sodium alginate aqueous phase: Dissolve 0.5 g of sodium alginate, 0.5 g of xanthan gum, 0.2 g of trehalose and 0.05 g of sodium hyaluronate in 90 g of deionized water and allow them to swell fully to form an aqueous phase; (3) Preparation of phenylethyl resorcinol / sodium alginate emulsion: The solutions obtained in steps (1) and (2) are mixed, magnetically stirred at 800 rpm for 60 min at 90℃, and ultrasonically treated for 20 min to obtain phenylethyl resorcinol / sodium alginate emulsion. (4) Preparation of phenylethyl resorcinol / sodium alginate emulsion gel beads: The emulsion obtained in step (3) is drawn into a syringe. A disposable syringe with an inner diameter of 0.6 mm is selected. The height of the needle tip from the surface of the curing liquid is controlled to be 5 cm. The emulsion is added drop by drop into a 4% (w / v) calcium chloride solution. After curing and crosslinking for 5 min, the solution is filtered and washed 3 times with deionized water to obtain phenylethyl resorcinol / sodium alginate emulsion gel beads.

[0031] like Figure 2 As shown, the phenylethyl resorcinol / sodium alginate emulsion is light pink to dark brown, and the gel beads are light brown.

[0032] like Figure 3 As shown, the gel beads exhibit a normally distributed particle size and 98.58% sphericity under a microscope, with an average particle size of 2725.95 μm.

[0033] Example 2: Performance Characterization of Gel Beads Comparative Example 1 Following the formulation of Example 1, with other conditions unchanged, the amount of phenylethyl resorcinol added was changed to 0, and unloaded blank emulsion and gel beads were prepared.

[0034] 1. Macroscopic morphological characterization was performed on the emulsions and gel beads prepared in Example 1 and Comparative Example 1, respectively: like Figure 2 As shown, the blank emulsion and gel beads are milky white; the phenylethyl resorcinol / sodium alginate emulsion is light pink to dark brown, and the gel beads are light brown. Figure 3 As shown, the gel beads exhibit a normally distributed particle size and high sphericity under a microscope, with an average particle size of 2725.95 μm and a sphericity of 98.58%.

[0035] 2. Microstructure characterization of the gel beads prepared in Example 1: like Figure 4 Scanning electron microscopy revealed that the surface of the gel beads had a dense white wavy structure, confirming the formation of micron-sized oil droplets and a dense calcium alginate gel network inside.

[0036] Comparative Example 2 Following the formulation of Example 1, with other conditions unchanged, the concentration of calcium chloride was varied from 2 to 6 wt.% to obtain gel beads prepared at different crosslinking agent concentrations.

[0037] 3. The gel beads obtained in Comparative Example 2 were subjected to full textural analysis using a texture analyzer to test their mechanical properties, including hardness and elasticity: like Figure 5 As shown, the optimal performance was achieved at a calcium chloride concentration of 4 wt.%, with a hardness of 0.846 ± 0.035 N and an elasticity of 1.236 ± 0.056 mm. The gel beads obtained at this concentration can be applied to the skin, exhibiting a pleasant tactile feel with easy spreadability and strong elasticity.

[0038] Example 3: Stability Comparison Test The emulsion and gel beads prepared in Example 1 were subjected to accelerated aging tests by centrifugation at 3000 rpm for 60 min at 25°C.

[0039] result: like Figure 6 As shown, the emulsion completely separated into layers after centrifugation for 40 minutes, with an oil phase precipitating on top and a polymer precipitate on the bottom. Its natural settling stability period was calculated to be only about 14 days. Under the same centrifugation conditions, the gel beads maintained their structural integrity without rupture, deformation, or leakage of contents, and the supernatant was clear.

[0040] in conclusion: The calcium alginate gel beads in this embodiment form a stable gel network through ionic cross-linking. The resulting steric hindrance significantly improves the kinetic stability of the emulsion system and solves the problem of easy stratification in traditional emulsions.

[0041] Example 4: Evaluation of biosafety and whitening efficacy 1. Test Item: Stimulation Test The chicken embryo chorioallantoic membrane test was used. A certain amount of the test substance was directly exposed to the blood vessels of the mid-stage chorioallantoic membrane of 9-day-old fertilized chicken embryos. After a period of time, vascular damage was observed, and different degrees of vascular damage were scored, with higher scores for more severe damage. Each sample consisted of 6 fertilized chicken embryos, and the stimulation score was obtained based on the sum of the damage scores.

[0042] Sample preparation: Example 1 Negative control group sample preparation: Comparative Example 1 Preparation of positive control group samples: 1 mM NaOH solution The samples from Example 1, Comparative Example 1, and the positive control were each coated evenly onto the chorioallantoic membrane of chicken embryos at a coating volume of 3 mL. After 5 min of treatment, vascular damage was observed and scored.

[0043] The evaluation criteria are shown in Table 1: The irritant classification is shown in Table 2: The test results are shown in Table 3: in conclusion: As can be seen from the results in the table above, the irritation score of the phenylethyl resorcinol / sodium alginate emulsion in this application embodiment is 5.00, which falls into the category of "non-irritating / mildly irritating", far lower than the irritation score of the positive control; and the irritation score of the blank emulsion in the comparative example of this application is 0.00, close to non-irritating, indicating that the carrier system has good biocompatibility.

[0044] 2. Test item: Whitening effect The B16-F10 mouse melanoma cell model was used for testing. The emulsion sample from Example 1 was diluted to a cell-safe concentration of 30 μg / mL. The sample loading volume was 100 μL, corresponding to 10 cells per cell. 4 The samples were cultured for 72 hours at 37°C with 5% CO2. After treatment, the supernatant was collected by centrifugation.

[0045] Tyrosinase activity and melanin content were detected by ELISA, and tyrosinase expression was detected by Western blotting.

[0046] result: ELISA analysis showed that the phenylethyl resorcinol / sodium alginate emulsion inhibited intracellular tyrosinase activity by approximately 40%, and reduced melanin content to 58%. Western blot analysis revealed that the expression level of tyrosinase protein in the treated cells was significantly reduced to 24%.

[0047] Conclusion: The emulsion in this application not only reduces the irritation of phenylethyl resorcinol through physical encapsulation, but also achieves highly effective whitening through a dual mechanism of inhibiting enzyme activity and reducing enzyme synthesis.

[0048] It should be noted that when numerical ranges are mentioned in the claims of this invention, it should be understood that any value between the two endpoints of each numerical range can be used. The above description is only a preferred embodiment of this invention. It should be pointed out that any modifications or equivalent substitutions to the technical solution of this invention without departing from the spirit and scope of the technical solution of this invention should be covered within the protection scope of this invention.

Claims

1. A method for preparing phenylethyl resorcinol / sodium alginate emulsion gel beads, characterized in that: The preparation steps include the following: (1) Preparation of phenylethyl resorcinol oil phase: Mix phenylethyl resorcinol, oily solute and oily solvent to form a homogeneous oil phase; (2) Preparation of sodium alginate aqueous phase: Sodium alginate and aqueous solute are dissolved in water to form an aqueous phase; (3) Preparation of phenylethyl resorcinol / sodium alginate emulsion: The solutions obtained in steps (1) and (2) are mixed in any ratio of oil phase to water phase of 1 / 20-1 / 5, and the phenylethyl resorcinol / sodium alginate emulsion is obtained by heating and homogenizing emulsification step. (4) Preparation of phenylethyl resorcinol / sodium alginate emulsion gel beads: The emulsion obtained in step (3) is added dropwise to a calcium chloride solution with a concentration of 0.5-5 wt% to crosslink and form gel beads.

2. The preparation method according to claim 1, characterized in that: In step (1), the oily solute is any combination of jojoba oil, sunflower seed wax, C10-18 fatty acid triglyceride, glyceryl stearate, cetyl alcohol, stearyl alcohol, and polyacrylate crosspolymer-6; the oily solvent is at least one of butanediol, glycerol, caprylic / capric triglyceride, etc., and the mass concentration of the solute is 0.5-5 wt%.

3. The preparation method according to claim 1, characterized in that: In step (2), the aqueous solute is any combination of chitosan, trehalose, xanthan gum, cellulose gum, gum arabic, and sodium hyaluronate; the solution viscosity is any one of 500-1000 mPa·s; and the mass concentration of the solute is 0.5-5 wt.%.

4. The preparation method according to claim 1, characterized in that: In step (3), the heating homogenization emulsification step includes high-speed shearing and ultrasound; the heating temperature is 80-100℃; the shearing rate is 600-1000 rpm; the emulsification time is 30-60 min; and the ultrasound time is 10-20 min.

5. The preparation method according to claim 1, characterized in that: In step (4), the mass concentration of the calcium chloride solution is 0.5-5 wt%; the crosslinking time is 1-30 min.

6. The preparation method according to any one of claims 1 to 5, characterized in that, Prepare according to the following steps: (1) Preparation of phenylethyl resorcinol oil phase: 1 g of phenylethyl resorcinol, 0.2 g of glyceryl stearate, 0.2 g of jojoba ester, 0.2 g of C10-18 fatty acid triglyceride, 3 g of caprylic / capric triglyceride, and 3 g of butanediol were mixed and stirred to dissolve, resulting in a homogeneous oil phase; (2) Preparation of sodium alginate aqueous phase: Dissolve 0.5 g of sodium alginate, 0.5 g of xanthan gum, 0.2 g of trehalose and 0.05 g of sodium hyaluronate in 90 g of deionized water and allow them to swell fully to form an aqueous phase; (3) Preparation of phenylethyl resorcinol / sodium alginate emulsion: The solutions obtained in steps (1) and (2) are mixed, magnetically stirred at 800 rpm for 60 min at 90℃, and ultrasonically treated for 20 min to obtain phenylethyl resorcinol / sodium alginate emulsion. (4) Preparation of phenylethyl resorcinol / sodium alginate emulsion gel beads: The emulsion obtained in step (3) is drawn into a syringe. A disposable syringe with an inner diameter of 0.6 mm is selected. The height of the needle tip from the surface of the curing liquid is controlled to be 5 cm. The emulsion is added drop by drop into a 4% (w / v) calcium chloride solution. After curing and crosslinking for 5 min, the solution is filtered and washed 3 times with deionized water to obtain phenylethyl resorcinol / sodium alginate emulsion gel beads.

7. A phenylethyl resorcinol / sodium alginate emulsion gel bead, characterized in that... Prepared by the method according to any one of claims 1-6.

8. The application of the phenylethyl resorcinol / sodium alginate emulsion gel beads according to claim 7 in functional skin care products.

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