A liposome-encapsulated whitening composition, its preparation and use

Abstract

The present application provides a liposome-encapsulated whitening composition, a preparation method and an application thereof, and belongs to the field of medical, dental or cosmetic preparations. The components of the present application are 4-butyl resorcinol, tranexamic acid, alpha-arbutin, coenzyme Q10, Ceylon cinnamon oil, sweep leaf Australian tea branch / leaf oil, hydrogenated soybean lecithin and a humectant. The present application is compounded with a variety of different whitening components, covering the three major pathways of "inhibiting tyrosinase activity, inhibiting melanin transfer and accelerating melanin metabolism" for melanin production; in line with the modern multi-target whitening trend. At the same time, the additional plant essential oil has the effect of promoting penetration and strengthening the inhibition of tyrosinase; at the same time, the liposome-encapsulated preparation solves the problem of mutual incompatibility between raw materials and increases the transdermal absorption rate and reduces the irritation. It can be added to a variety of different specific products, such as serums, creams, lotions, etc.

Description

Technical Field

[0001] This invention belongs to the field of formulations for medical, dental or cosmetic use, and particularly relates to a liposome-encapsulated whitening composition, its preparation method and its application. Background Technology

[0002] In the field of skin aesthetics and cosmetic science, skin whitening has become an important research direction. Achieving skin whitening requires a deep understanding of its mechanisms of action, combined with scientifically effective active ingredients and formulation technologies. The whitening effect of skincare products is mainly achieved through three core pathways: inhibiting melanin production, blocking melanin transport, and accelerating melanin metabolism. Inhibiting melanin production: Melanin biosynthesis begins within melanocytes. Catalyzed by tyrosinase, tyrosine undergoes a series of oxidation reactions to gradually transform into dopa and dopaquinone, ultimately polymerizing to form melanin. By targeting and inhibiting tyrosinase activity, key steps in melanin production can be effectively blocked, reducing melanin production at its source, thereby preventing skin pigmentation and age spots, and achieving a whitening effect.

[0003] Blocking melanin transport: After melanin is produced, it needs to be transported from melanocytes to keratinocytes via intercellular communication mechanisms, and finally distributed on the skin surface. By interfering with the signal transduction pathways or related carrier protein functions in the melanin transport process, melanin deposition in keratinocytes can be prevented, thereby maintaining an even skin tone and improving dull skin.

[0004] Accelerating melanin metabolism: Keratinocytes containing melanin gradually migrate to the epidermis as the skin metabolizes and are eventually expelled from the body as dead skin cells. By promoting the normal turnover rate of keratinocytes and accelerating the shedding of melanin-containing keratinocytes, the time melanin stays in the skin can be effectively shortened, prompting newly formed keratinocytes with lower melanin content to appear on the skin surface more quickly, thus achieving the goal of brightening the skin tone.

[0005] Currently, commonly used skin-whitening ingredients include: Niacinamide, a derivative of vitamin B3, is widely used in the skin whitening field. Its mechanism of action includes inhibiting the transport of melanin from melanocytes to keratinocytes, while simultaneously accelerating the shedding of melanin-containing stratum corneum by regulating keratinocyte metabolism. Research data shows that when the concentration of niacinamide in skincare products reaches 5%, it can significantly enhance the whitening effect. In addition, niacinamide also has multiple benefits such as strengthening the skin barrier function, regulating sebum secretion, and delaying skin aging, making it suitable for various skin types.

[0006] However, some people may experience skin intolerance after use, such as stinging, redness, and itching, especially those with weak skin barrier function or those using high-concentration niacinamide products for the first time. These irritation reactions are more pronounced in these cases. Furthermore, niacinamide is most stable at a pH of around 6. If the pH of the skincare product formula is not properly controlled, niacinamide can easily hydrolyze to form nicotinic acid, which can actually worsen skin irritation.

[0007] Tranexamic acid is a protease inhibitor that reduces melanin production by inhibiting the indirect activation of tyrosinase by plasminogen activator. Due to its good safety and gentleness, it is especially suitable for whitening skincare for sensitive skin. In cosmetic formulations, it is often added to products such as masks and serums to achieve a gentle brightening effect and improve dull skin tone.

[0008] However, tranexamic acid's whitening effect is relatively slow, requiring continuous use over a longer period to observe noticeable changes. Furthermore, the amount of tranexamic acid added to skincare products is limited; excessively high concentrations may affect the product's formula stability. Additionally, its mechanism of action is relatively simple, primarily targeting the melanin production process, and its effect on improving existing melanin is weak.

[0009] Vitamin C (ascorbic acid) is a powerful antioxidant that can reduce dopaquinone to dopa, interrupting the oxidation process of melanin synthesis. However, due to its unstable chemical properties, it is easily oxidized and degraded by light and oxygen, losing its whitening activity and potentially causing product discoloration, thus affecting the user experience. To address this, researchers have developed various vitamin C derivatives, such as tetraisopalmitate ascorbate and 3-O-ethyl ascorbic acid. These derivatives maintain their whitening activity while significantly improving chemical stability and skin permeability, and also possess additional functions such as promoting collagen synthesis and enhancing skin elasticity. However, some vitamin C derivatives have large molecular weights, and their transdermal absorption efficiency still needs improvement. Furthermore, their production costs are high, resulting in relatively expensive skincare products containing these ingredients. In addition, the efficiency with which some derivatives are converted into active vitamin C in the body varies among individuals, potentially affecting the final whitening effect.

[0010] Arbutin achieves its whitening effect by competitively inhibiting tyrosinase activity, reducing the oxidation of melanin precursors. Alpha-arbutin exhibits approximately 10 times the tyrosinase inhibitory activity of β-arbutin and has lower skin irritation, effectively fading dark spots and promoting overall skin brightening. However, arbutin is relatively unstable under high temperature and high pH conditions, easily decomposing, which places high demands on the manufacturing process and storage conditions of skincare products. Furthermore, the whitening effect of arbutin depends to some extent on continuous use; once discontinued, as tyrosinase activity recovers, melanin may regenerate, leading to a rebound effect in skin tone.

[0011] Addressing the shortcomings of each of the aforementioned skin-whitening ingredients, liposome encapsulation technology, as an advanced drug delivery system, effectively solves these problems.

[0012] Liposomes, with their closed vesicle structure composed of a phospholipid bilayer, share a highly similar lipid composition and molecular arrangement with human cell membranes, thus exhibiting excellent biocompatibility. From a component stability perspective, the bilayer membrane structure of liposomes forms a physical barrier, effectively isolating whitening ingredients from external factors such as oxygen and light, significantly extending their active shelf life. Regarding skin penetration, based on the similarity and compatibility between liposomes and cell membranes, they can fuse with stratum corneum cells, directly delivering encapsulated whitening ingredients to deep skin tissues, significantly improving the transdermal absorption rate of active ingredients and enhancing whitening efficacy. Furthermore, liposomes can control the release rate of whitening ingredients to achieve a sustained-release effect, avoiding irritation from high local concentrations of ingredients, improving product safety and comfort, and broadening the range of suitable skin types. Summary of the Invention

[0013] The purpose of this invention is to provide a liposome-encapsulated whitening composition, its preparation method, and its application. This composition achieves a superior whitening effect through multiple synergistic effects. The liposome-encapsulated whitening composition comprises the following components by weight: 4-Butylresorcinol 0.1-0.3 Tranexamic acid 0.8-1.5 α-Arbutin 1-2 Coenzyme Q10 0.05-0.15 Ceylon cinnamon oil 0.1-0.2 Broom-leaf Australian tea twigs / leaf oil 0.2-0.4 Hydrogenated soybean lecithin 5-7 Moisturizer 2-8 The preparation method of the liposome-encapsulated whitening composition is as follows: the components are divided into lipid-soluble and water-soluble components; the lipid-soluble components are mixed and dissolved in an organic solvent, and then rotary evaporated to obtain a lipid phase; the water-soluble components are dissolved in water to obtain an aqueous phase; the aqueous phase is added to the lipid phase, stirred evenly and homogenized; and then freeze-dried.

[0014] Preferably, the method for preparing the liposome-encapsulated whitening composition includes the following steps: S1: The components are classified into fat-soluble and water-soluble types; S2: Prepare an organic solvent and heat it in a water bath to at least 55°C, then add hydrogenated soybean lecithin and 4-butylresorcinol; then add coenzyme Q10 when the temperature drops to 50°C; continue cooling to 45°C and add Ceylon cinnamon oil and broomcorn apple branch / leaf oil; rotary evaporate at a temperature not exceeding 55°C and a vacuum degree not exceeding -0.09 MPa to obtain the lipid phase; S3: Dissolve tranexamic acid, α-arbutin, and humectant in water, adjust the pH to 5.8-6.0, and then heat to 60℃ for preheating to obtain the aqueous phase; S4: Add the aqueous phase to the lipid phase for hydration, control the temperature at 55±2℃, and stir until homogeneous; then homogenize under high pressure at a pressure of at least 100MPa; after homogenization, cool to a maximum of 30℃ to obtain the hydrated body. S5: The hydrated body was freeze-dried to obtain a liposome-encapsulated whitening composition.

[0015] Preferably, in step S5, a freeze-drying protectant is added, and the amount of the freeze-drying protectant is 2-3 parts; the freeze-drying protectant is a sugar or a polyol.

[0016] Preferably, it also includes polyquaternium-10, in an amount of 0.1-0.3 parts.

[0017] Preferably, it also includes an antioxidant; the antioxidant is rosmarinic acid and / or vitamin E, in an amount of 0.15-0.3 parts.

[0018] Preferably, it also includes cholesterol, wherein the amount of cholesterol used is 0.5-1.5 parts.

[0019] Preferably, the moisturizer is at least one selected from glycerin, 1,3-butanediol, trehalose, and sorbitol.

[0020] The present invention also provides the application of the aforementioned liposome-encapsulated whitening composition in the preparation of cosmetics; including but not limited to dosage forms such as serums, creams, lotions, and lyophilized powders.

[0021] This invention achieves a whitening effect by synergistically targeting different whitening pathways, specifically: 4-Butylresorcinol: It inhibits the catalytic function of tyrosinase by competitively binding to the active site of tyrosinase; at the same time, it blocks tyrosinase-associated protein (TRP-1), interfering with the entire melanin synthesis chain.

[0022] Tranexamic acid: It blocks the conversion of plasminogen to plasmin, reduces arachidonic acid metabolism, and decreases the release of inflammatory factors (such as prostaglandins), thereby inhibiting inflammatory pigmentation. Its structure is similar to tyrosine, partially competing for the active site of tyrosinase; it also interferes with the transfer of melanocytes to keratinocytes.

[0023] α-Arbutin: As a competitive inhibitor of tyrosinase, it reversibly occupies its active site, blocking the conversion of tyrosine to dopaquinone. It can also scavenge free radicals and promote the breakdown of existing melanin.

[0024] Coenzyme Q10: Reduces UV-induced reactive oxygen species (ROS), inhibits the synthesis of α-melanocyte-stimulating hormone (α-MSH) in keratinocytes; enhances skin antioxidant enzymes (such as SOD and glutathione peroxidase), and reduces UV-induced pigmentation.

[0025] Ceylon cinnamon oil: It has the ability to scavenge free radicals, inhibit inflammatory factors and reduce oxidative stress damage; and this invention has found that Ceylon cinnamon oil can enhance the inhibitory effect of arbutin and 4-butylresorcinol on tyrosinase.

[0026] Australian tea leaf / branch oil: Australian tea leaf, also known as pine bud, has the effects of scavenging free radicals, reducing oxidative stress damage, and enhancing skin hydration. This invention also reveals that Australian tea leaf / branch oil can enhance the inhibitory effects of arbutin and 4-butylresorcinol on tyrosinase; and its effect is even stronger when combined with Ceylon cinnamon oil. Furthermore, both Ceylon cinnamon oil and Australian tea leaf / branch oil also promote skin penetration and reduce potential irritation from whitening ingredients.

[0027] Hydrogenated soybean lecithin: As a core component of the liposome bilayer framework, it encapsulates water-soluble / lipid-soluble active ingredients, enhancing transdermal absorption.

[0028] Moisturizers: Maintain the hydration environment of liposomes, reduce damage to vesicle structure during freeze-drying, and improve the skin feel of the product.

[0029] The following are optional components of the present invention; Cholesterol: As an auxiliary component of the liposome bilayer framework, it fills the gaps between phospholipid molecules, enhances the density of the lipid membrane, and prevents leakage of encapsulated components.

[0030] Polyquaternium-10: Imparts a positive charge to liposomes, enhancing their adsorption to the negatively charged stratum corneum of the skin and prolonging their duration of action.

[0031] Antioxidants: protect easily oxidized components such as coenzyme Q10 and essential oils, extending shelf life.

[0032] In terms of process, the present invention uses a method of liposome and aqueous phase distribution treatment followed by hydration and freeze-drying to prepare its lipid encapsulation; this avoids the use of organic solvents and eliminates the risk of residue.

[0033] This invention combines multiple whitening ingredients to cover the three major pathways of melanin production: "inhibition of tyrosinase activity, inhibition of melanin transfer, and acceleration of melanin metabolism," aligning with the modern trend of multi-target whitening. The added plant essential oils enhance penetration and strengthen the inhibition of tyrosinase. Furthermore, the liposome encapsulation method solves the problem of incompatibility between raw materials, increases transdermal absorption, and reduces irritation. It can be added to various specific products, such as serums, creams, and lotions. Detailed Implementation

[0034] To better understand the present invention, the present invention will be further described below with reference to specific serial numbers. The terminology used in the serial numbers is for describing specific embodiments and does not constitute a limitation on the scope of protection of the present invention.

[0035] In the specific implementation methods, unless otherwise specified, the experimental methods used are all conventional methods, and the materials and reagents used are all commercially available unless otherwise specified.

[0036] Unless otherwise specified, percentages, % and so on in the specific implementation method are assumed to be mass percentages.

[0037] The sources of some of the raw materials used in this invention are shown in Table 1 below: Table 1 Example 1 The preparation of lipid encapsulations includes the following steps: S1: Weigh each raw material according to Table 2 and classify the raw materials into fat-soluble and water-soluble types; S2: Prepare anhydrous ethanol and heat it in a water bath to 55°C, then add hydrogenated soybean lecithin and 4-butylresorcinol; then add coenzyme Q10 when the temperature drops to 50°C; continue cooling to 45°C and add essential oil components; rotary evaporate at a vacuum degree not greater than -0.09 MPa below 55°C to obtain the lipid phase; S3: Dissolve tranexamic acid, α-arbutin, and humectant in water, adjust the pH to 5.8-6.0, and then heat to 60℃ for preheating to obtain the aqueous phase; The amount of water used should be at least nine times the volume of the solute; S4: Slowly add the aqueous phase to the lipid phase for hydration, controlling the temperature at 55±2℃ and stirring until homogeneous; then homogenize under high pressure at a pressure of at least 100MPa; cycle the homogenization 3 times; after homogenization, cool to 30℃ to obtain the hydrated body. S5: Add a freeze-drying protectant to the hydrated body, then pre-freeze at -50°C, freeze-dry to convert it into liposome powder, and then seal and store it to obtain a liposome-encapsulated whitening composition.

[0038] Table 2. Composition ratio of lipid inclusions Table 2 (continued) Composition of lipid inclusions Table 2 (continued) Composition of lipid inclusions Example 2 Safety tests were conducted on the lipid encapsulations prepared in Example 1, specifically as follows: Human skin patch test After reconstituted and diluted with water to 50 wt% of the 13 samples obtained in Example 1, the human skin patch test was performed in accordance with the "2022 Cosmetic Safety Technical Specifications".

[0039] Skin reactions were observed according to standard at 30 min (after the indentation disappeared), 24 h and 48 h, and the results were recorded. The experimental results showed that no discomfort, redness, swelling or itching or other adverse reactions occurred.

[0040] Example 3 The antioxidant properties of the lipid encapsulations prepared in Example 1 were tested, specifically including: DPPH methanol solution is violet in color and has a strong absorbance at 517 nm. If it binds to the sample, it will reduce the absorbance at 517 nm, thus determining the sample's ability to scavenge DPPH free radicals.

[0041] The specific method is as follows: (1) Take the sample from Example 1, mix it with sterile water, and prepare an equal volume (2 mL) of the test solution with a concentration of 5% and 2 × 10 4 Mix the mol / L DPPH solution thoroughly (Al); (2) Take equal volumes of anhydrous ethanol (the solvent for the analyte) and 2×10 4 Mix the mol / L DPPH solution thoroughly (A2); (3) Take an equal volume of anhydrous ethanol and mix it with the test solution (A3); (4) After reacting for 40 min, the absorbance values ​​of tubes A1, A2 and A3 were measured at 517 nm.

[0042] The formula for calculating the clearance rate is: Clearance rate (%) = [1 - (A1 - A3) / A2] × 100% The test results are shown in Table 3.

[0043] Table 3. Antioxidant Test Results According to the experimental data in Table 3, the antioxidant properties of the four different essential oils are as follows: Pine Blossom > Ceylon Cinnamon > Cinnamon > Tea Tree; among them, Tea Tree has the lowest antioxidant properties; Pine Blossom essential oil has the best antioxidant properties. Cinnamon (CINNAMOMUM CASSIA) is weaker than Ceylon cinnamon (CINNAMOMUM ZEYLANICUM).

[0044] Example 4 To examine the whitening ability of each sample, a tyrosinase inhibition experiment was conducted for comparison; the specific method is as follows: The corresponding reagents and different volumes of the sample to be tested were added sequentially to the 96-well microplates corresponding to the 13 samples prepared in Example 1. After adding tyrosinase, the microplates were incubated at 37°C for 10 min, followed by the addition of L-tyrosine substrate solution, and the reaction was allowed to proceed for another 10 min. The absorbance (OD value) was then measured at a wavelength of 475 nm using a microplate reader.

[0045] Each sample was diluted and reconstituted with PBS solution to a concentration of 10%, and the results are shown in Table 4 below.

[0046] The formula for calculating the inhibition rate of tyrosinase activity is as follows: Tyrosinase inhibition rate (%) = The control group consisted of a mixture of tyrosinase and substrate. The blank group consisted of PBS solution.

[0047] Table 4. Results of tyrosinase inhibition According to the experimental results in Table 4, Ceylon cinnamon oil and pine berry oil have a strong inhibitory effect on tyrosinase, and the combination of Ceylon cinnamon oil and pine berry oil further enhances the inhibitory effect on tyrosinase. However, tea tree oil and cinnamon oil do not have this effect; the addition of cinnamon oil and tea tree oil did not increase the tyrosinase inhibition rate. On the contrary, the dilution of other whitening ingredients actually led to a decrease in the tyrosinase inhibition rate.

[0048] The above detailed description is a specific description of one of the feasible embodiments of the present invention. This embodiment is not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included within the scope of the technical solution of the present invention.

Claims

1. A liposome-encapsulated whitening composition, characterized in that, The following components are included in parts by weight: 4-Butylresorcinol 0.1-0.3 Tranexamic acid 0.8-1.5 α-Arbutin 1-2 Coenzyme Q10 0.05-0.15 Ceylon cinnamon oil 0.1-0.2 Broom-leaf Australian tea twigs / leaf oil 0.2-0.4 Hydrogenated soybean lecithin 5-7 Moisturizer 2-8 The preparation method of the liposome-encapsulated whitening composition is as follows: the components are divided into lipid-soluble and water-soluble components; the lipid-soluble components are mixed and dissolved in an organic solvent, and then rotary evaporated to obtain a lipid phase; the water-soluble components are dissolved in water to obtain an aqueous phase; the aqueous phase is added to the lipid phase, stirred evenly and homogenized; and then freeze-dried.

2. The liposome-encapsulated whitening composition according to claim 1, characterized in that, The preparation method of the liposome-encapsulated whitening composition includes the following steps: S1: The components are classified into fat-soluble and water-soluble types; S2: Prepare an organic solvent and heat it in a water bath to at least 55°C, then add hydrogenated soybean lecithin and 4-butylresorcinol; then add coenzyme Q10 when the temperature drops to 50°C; continue cooling to 45°C and add Ceylon cinnamon oil and broomcorn apple branch / leaf oil; rotary evaporate at a temperature not exceeding 55°C and a vacuum degree not exceeding -0.09 MPa to obtain the lipid phase; S3: Dissolve tranexamic acid, α-arbutin, and humectant in water, adjust the pH to 5.8-6.0, and then heat to 60℃ for preheating to obtain the aqueous phase; S4: Add the aqueous phase to the lipid phase for hydration, control the temperature at 55±2℃, and stir until homogeneous; then homogenize under high pressure at a pressure of at least 100MPa; after homogenization, cool to a maximum of 30℃ to obtain the hydrated body. S5: The hydrated body was freeze-dried to obtain a liposome-encapsulated whitening composition.

3. The liposome-encapsulated whitening composition according to claim 2, characterized in that, In step S5, a freeze-drying protectant is added, and the amount of the freeze-drying protectant is 2-3 parts; the freeze-drying protectant is a sugar or a polyol.

4. The liposome-encapsulated whitening composition according to claim 1, characterized in that, It also includes polyquaternium-10, used in amounts of 0.1-0.3 parts.

5. The liposome-encapsulated whitening composition according to claim 1, characterized in that, It also includes antioxidants; the dosage is 0.15-0.3 parts.

6. The liposome-encapsulated whitening composition according to claim 5, characterized in that, The antioxidant is rosmarinic acid and / or vitamin E.

7. The liposome-encapsulated whitening composition according to claim 1, characterized in that, It also includes cholesterol, in an amount of 0.5-1.5 parts.

8. The liposome-encapsulated whitening composition according to claim 1, characterized in that, The moisturizer is at least one of glycerin, 1,3-butanediol, trehalose, and sorbitol.

9. The use of the liposome-encapsulated whitening composition according to any one of claims 1-8 in the preparation of cosmetics.

10. The application of the liposome-encapsulated whitening composition according to claim 9 in the preparation of cosmetics, characterized in that, The cosmetic product is at least one of the following: serum, face cream, lotion, skin lotion, essential oil, and freeze-dried agent.

Images