A transdermally absorbed whitening supramolecular composition and use thereof

Abstract

The application relates to the technical field of skin care products, and particularly discloses a transdermal absorption whitening supermolecular composition and application thereof. The composition comprises a solvent, an external water-phase stabilizer dissolved in the solvent and whitening supermolecular particles dispersed in the solvent; the whitening supermolecular particles comprise an outer elastic liposome, the outer elastic liposome is wrapped with a water-soluble whitening agent, a water-soluble anti-glycation agent and small liposome particles; the outer elastic liposome is loaded with a penetration enhancer, a barrier repair agent and a cell autophagy activator, and the outer surface of the outer elastic liposome is also adsorbed with a keratinocyte target positioning agent; the small liposome particles comprise an inner elastic liposome, the inner elastic liposome is wrapped with a cyclodextrin-peptide amido supermolecular inclusion compound; the inner elastic liposome is loaded with an oil-soluble anti-glycation agent, and the inner elastic liposome is inlaid with a melanocyte target positioning agent. The application has the advantage of further improving the whitening effect.

Description

Technical Field

[0001] This invention relates to the field of skincare products, and in particular to a transdermal whitening supramolecular composition and its application. Background Technology

[0002] In today's beauty-conscious era, skin whitening has always been a topic of great interest to consumers. As people's living standards improve, the demand for whitening cosmetics continues to grow. However, while the market offers a wide variety of whitening cosmetics, many aspects fall short of expectations in practical application.

[0003] Many traditional skin-whitening cosmetics rely primarily on a single whitening ingredient, such as hydroquinone and kojic acid. While hydroquinone has a significant whitening effect, it has high cytotoxicity, and long-term use may pose potential threats to human health, such as causing skin irritation and uneven pigmentation loss. Its use has even been restricted in some countries. Kojic acid, on the other hand, is less stable and easily affected by factors such as light and temperature, causing discoloration and deterioration, thus reducing its whitening efficacy. Moreover, the skin whitening process involves multiple physiological steps, and a single ingredient often only acts on a specific step, making it difficult to achieve a comprehensive and effective whitening effect. For example, tyrosinase is a key enzyme in the melanin synthesis process; traditional single ingredients may only inhibit tyrosinase activity but cannot prevent the transfer of already synthesized melanin to keratinocytes, resulting in limited whitening effects.

[0004] While existing technologies include products that combine multiple whitening ingredients acting on different stages of the skin, the stratum corneum, acting as a natural barrier, hinders the penetration of many whitening ingredients. Simply mixing whitening ingredients from different stages often fails to effectively deliver them to the melanocytes deep within the skin during actual use. Without reaching their target sites, the whitening ingredients cannot fully exert their functions, such as inhibiting melanin synthesis and metabolizing existing melanin, significantly reducing their whitening effect and failing to meet consumer needs. Therefore, there is still room for improvement. Summary of the Invention

[0005] To further enhance the whitening effect, this application provides a transdermal whitening supramolecular composition and its application.

[0006] In a first aspect, this application provides a transdermal skin-whitening supramolecular composition, employing the following technical solution: A transdermal skin whitening supramolecular composition comprising a solvent, an external aqueous phase stabilizer dissolved in the solvent, and skin whitening supramolecular particles dispersed in the solvent; The whitening supramolecular particles include an outer elastic liposome with a bilayer structure, wherein the outer elastic liposome encapsulates a water-soluble whitening agent, a water-soluble anti-glycation agent, and small liposome particles. The outer elastic liposome has a bilayer structure loaded with a permeability enhancer, a barrier repair agent, and an autophagy activator. The outer surface of the outer elastic liposome also adsorbs a keratinocyte targeting agent. The small liposome particles include an inner elastic liposome with a bilayer structure, and the inner elastic liposome encapsulates a cyclodextrin-peptide ammonium supramolecular inclusion complex. The inner elastic liposome is loaded with an oil-soluble anti-glycation agent within its bilayer structure. The inner elastic liposome is embedded with a melanocyte-targeting agent, which includes a lipophilic end and a hydrophilic end. The lipophilic end of the melanocyte-targeting agent is embedded in the bilayer structure of the inner elastic liposome, while the hydrophilic end extends out of the inner elastic liposome.

[0007] By adopting the above technical solution, the keratinocyte targeting agent targets keratinocytes. Since keratinocytes are adjacent to melanocytes, the first-level targeting is achieved, so that the transdermal whitening supramolecular composition can better target melanocytes after penetrating into the skin. When the transdermal whitening supramolecular composition targets and positions keratinocytes, it releases the permeation enhancer, barrier repair agent, and autophagy activator within the bilayer structure of the outer elastic liposome. This allows the water-soluble whitening agent, water-soluble anti-glycation agent, and small liposome particles to penetrate the skin barrier effectively. At the same time, it promotes the repair of the skin barrier, making the skin less prone to allergic reactions. Furthermore, it activates keratinocyte autophagy, promoting the degradation of lysosomes that have already engulfed melanin, thus achieving the first layer of whitening effect. When water-soluble whitening agents, water-soluble anti-glycation agents, and small liposome particles penetrate the skin barrier, the water-soluble whitening agents and water-soluble anti-glycation agents can block the transfer of melanosomes from melanocytes to keratinocytes and inhibit the production of AGEs to reduce glycation, thus achieving a second whitening effect. Meanwhile, small liposome particles competitively bind to the MC1R receptor through melanocyte targeting agents, enabling small liposome particles to actively recognize melanocytes and complete the targeted localization of melanocytes. After the small liposome particles target and locate melanocytes, they release oil-soluble anti-glycation agents on the surface of melanocytes and competitively bind to RAGE receptors on the cell membrane surface, inhibiting the production of AGEs from the source, thereby achieving anti-glycation and whitening effects, and realizing a third whitening effect. At the same time, the cyclodextrin-peptido supramolecular inclusion complex released by the small liposome particles enters the melanocytes. Peptido is released from the cyclodextrin cavity and inhibits tyrosinase activity in the melanocytes, blocking melanin production from the source and achieving the fourth whitening effect. Through the combined effect of the above multiple whitening effects, the whitening ingredients acting on different whitening stages can better exert their whitening effects on the corresponding areas of the skin. With the superposition of multiple whitening effects, the overall whitening effect is significantly improved, making the whitening effect faster and better meeting the needs of consumers.

[0008] Preferably, the water-soluble whitening agent is niacinamide; the water-soluble anti-glycation agent is carnosine; the penetration enhancer is oleic acid; the barrier repair agent is ceramide; the autophagy activator is resveratrol; the keratinocyte targeting agent is acetyl tetrapeptide-9; the oil-soluble anti-glycation agent is naringin; and the melanocyte targeting agent is palmitoyl hexapeptide-8.

[0009] By adopting the above technical solution and specifically selecting niacinamide, carnosine, oleic acid, ceramide, resveratrol, acetyl tetrapeptide-9, naringin, and palmitoyl hexapeptide-8, the effects of inhibiting melanin transfer, inhibiting AGEs production, promoting the penetration of active ingredients into the skin barrier, promoting skin barrier repair, promoting the degradation of lysosomes that have already engulfed melanin, and targeting keratinocytes and melanocytes are improved, resulting in a more significant overall whitening effect.

[0010] Preferably, the outer elastic liposome is formed by a compound of hydrogenated lecithin, cholesterol, and Tween-80; the inner elastic liposome is formed by a compound of hydrogenated lecithin, cholesterol, and Tween-80.

[0011] By adopting the above technical solution, the outer elastic liposomes, through the combination of hydrogenated lecithin, cholesterol, and Tween-80, combined with the permeation-enhancing effect of oleic acid, endow the liposomes with a high deformability, allowing them to be squeezed through the stratum corneum channels to achieve deep delivery of intact vesicles; the inner elastic liposomes, through the combination of hydrogenated lecithin, cholesterol, and Tween-80, make the small liposome particles more stable, and after targeting melanocytes, they release the cyclodextrin-peptide supramolecular inclusion complex, allowing peptide-amida to better enter the melanocytes and achieve a better effect in blocking melanin production at the source.

[0012] Preferably, the solvent is deionized water and the external aqueous phase stabilizer is PVA.

[0013] By adopting the above technical solution and adding PVA, the stability of the whitening supramolecular particles is improved, and the quality of the transdermal whitening supramolecular composition is more stable.

[0014] Preferably, the preparation method of the transdermal skin-whitening supramolecular composition includes the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 9-11 parts of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 9-11%. Steps 1-2): Mix 0.9-1.1 parts of Peptidone with anhydrous ethanol to obtain a Peptidone ethanol solution; Steps 1-3): Continuously stir the cyclodextrin solution and add peptide ammonium ethanol solution dropwise to the cyclodextrin solution. Then, after ultrasonic homogenization, stirring, and drying, the cyclodextrin-peptide ammonium supramolecular inclusion complex is obtained. Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.4-0.6 parts hydrogenated lecithin, 0.04-0.06 parts Tween-80, 0.09-0.11 parts cholesterol, 0.09-0.11 parts naringin, and 49-51 parts anhydrous ethanol to obtain an intraliposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): 0.1-0.2 parts of palmitoyl hexapeptide-8 solution were added to the liposome premix, and the mixture was subjected to ultrasonic vibration and rotary evaporation under reduced pressure to obtain a lipid film. Steps 2-4): Mix 0.9-1.1 parts of cyclodextrin-peptide ammonium supramolecular inclusion complex with 4.9-5.1 parts of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, and after ultrasonic vibration, hydration and homogenization, obtain a small liposome particle solution; Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.4-1.6 parts hydrogenated lecithin, 0.09-0.11 parts cholesterol, 0.28-0.32 parts oleic acid, 0.19-0.21 parts ceramide, 0.09-0.11 parts resveratrol, 0.19-0.21 parts Tween-80, and 9.5-10.5 parts 1,3-propanediol / glycerol mixture to obtain the exoliposome premix. Step 3-2): Mix 0.9-1.1 parts niacinamide, 0.45-0.55 parts carnosine, and 4.9-5.1 parts deionized water to obtain a whitening solution. Step 3-3): Add the whitening solution to the external liposome premix, stir and homogenize by sonication to obtain the colostrum; Steps 3-4): Mix 0.28-0.32 parts of PVA and 49-51 parts of deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir to obtain external liposome solution; Step 4): Add the small liposome particle solution to the external liposome solution, stir and homogenize, then add 0.004-0.006 parts of acetyl tetrapeptide-9, stir, and obtain a transdermal whitening supramolecular composition.

[0015] By adopting the above technical solution and through special process steps, the transdermal whitening supramolecular composition is of relatively stable quality and can form a special multi-layer inclusion structure, which enables the transdermal whitening supramolecular composition to release the corresponding whitening active ingredients in the skin step by step to achieve a better full-chain whitening effect.

[0016] Preferably, in step 1-1), the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0017] By adopting the above technical solution and specifically selecting hydroxypropyl-β-cyclodextrin, the effect of inclusion peptide Anmido is better. Peptide Anmido can be delivered to melanocytes more stably, resulting in a better whitening effect.

[0018] Preferably, in step 3-1), the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 1.9-2.1:1. By specifically selecting the mass ratio of 1,3-propanediol and glycerol, the solubility of each component is high, and the resulting exoliposome premix system is more stable.

[0019] By adopting the above technical solution Secondly, this application provides an application of a transdermal skin-whitening supramolecular composition, employing the following technical solution: The above-mentioned transdermal whitening supramolecular composition can be used directly as a standalone skincare product or added to a skincare formula for the preparation of whitening skincare products.

[0020] By adopting the above technical solution, the transdermal whitening supramolecular composition can achieve step-by-step release and can target keratinocytes and melanocytes, with corresponding whitening effects on the entire chain of melanin "generation-transfer-accumulation", resulting in a significant improvement in the overall whitening effect and faster results.

[0021] In summary, this application has the following beneficial effects: 1. Because this application has a multi-layered structure, it can achieve step-by-step release. Through the combined effect of multiple whitening effects, the whitening ingredients that act on different whitening stages can better exert their whitening effects in the corresponding areas of the skin. With the superposition of multiple whitening effects, the overall whitening effect is significantly improved, making the whitening effect faster and better meeting the needs of consumers.

[0022] 2. In this application, PVA is preferably added to make the whitening supramolecular particles more stable and the quality of the transdermal whitening supramolecular composition more stable. Detailed Implementation

[0023] The present application will be further described in detail below with reference to the embodiments.

[0024] Example 1

[0025] A transdermal skin-brightening supramolecular composition, prepared by the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 9g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 9%. Steps 1-2): Mix 0.9g of Peptido with anhydrous ethanol to prepare a 9% Peptido ethanol solution. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0026] Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.4g hydrogenated lecithin, 0.04g Tween-80, 0.09g cholesterol, 0.09g naringin, and 49g anhydrous ethanol to obtain an endoplasmic liposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): 0.1g palmitoyl hexapeptide-8 solution was added to the liposome premix, and the mixture was sonicated at 200W and 30℃ for 20 minutes. The lipid film was then formed by rotary evaporation under reduced pressure at 45℃ using the thin film rotary evaporation method. Steps 2-4): Mix 0.9g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 4.9g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, sonicate at 200W and 40℃ for 5 minutes, let stand for hydration for 30 minutes, and then use an ultrasonic homogenizer in an ice bath at 200W for 5 seconds on and 5 seconds off for 5 minutes to homogenize for 5 minutes. Repeat this cycle 3 times to obtain a small liposome particle solution.

[0027] Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.4g hydrogenated lecithin, 0.09g cholesterol, 0.28g oleic acid, 0.19g ceramide, 0.09g resveratrol, 0.19g Tween-80, and 9.5g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 1.9:1), and stir at 70°C under nitrogen protection to dissolve and obtain the external liposome premix. Step 3-2): Mix 0.9g niacinamide, 0.45g carnosine, and 4.9g deionized water to obtain a whitening solution. Step 3-3): The external liposome premix is ​​kept at 70℃ and stirred continuously at 300rpm. Then, the whitening effect solution is added dropwise to the external liposome premix. After the addition is complete, the mixture is stirred continuously at 70℃ for 15 minutes under nitrogen protection. Then, it is cooled to room temperature and homogenized by sonication at 200W for 5 seconds on and 5 seconds off under ice bath conditions for 3 minutes to obtain the initial emulsion. Steps 3-4): Mix 0.28g PVA and 49g deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir continuously at 800 rpm for 2 hours at room temperature to obtain the external liposome solution.

[0028] Step 4) Add the small liposome particle solution to the external liposome solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.004 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain a transdermal whitening supramolecular composition.

[0029] Example 2

[0030] A transdermal skin-brightening supramolecular composition, prepared by the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 10g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 10%. Steps 1-2): Mix 1g of Peptido with anhydrous ethanol to prepare a 10% Peptido ethanol solution. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0031] Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.5g hydrogenated lecithin, 0.05g Tween-80, 0.1g cholesterol, 0.1g naringin, and 50g anhydrous ethanol to obtain an endoplasmic liposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): 0.15g palmitoyl hexapeptide-8 solution was added to the liposome premix, and the mixture was sonicated at 200W and 30℃ for 20 minutes. The lipid film was then formed by rotary evaporation under reduced pressure at 45℃ using the thin-film rotary evaporation method. Steps 2-4): Mix 1g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 5g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, sonicate at 200W and 40℃ for 5 minutes, let stand for hydration for 30 minutes, and then use an ultrasonic homogenizer in an ice bath at 200W for 5 seconds on and 5 seconds off for 5 minutes to homogenize for 5 minutes. Repeat this cycle 3 times to obtain a small liposome particle solution.

[0032] Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.5g hydrogenated lecithin, 0.1g cholesterol, 0.3g oleic acid, 0.2g ceramide, 0.1g resveratrol, 0.2g Tween-80, and 10g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 2:1), and stir at 70°C under nitrogen protection to dissolve and obtain the external liposome premix. Step 3-2): Mix 1g niacinamide, 0.5g carnosine, and 5g deionized water to obtain a whitening solution. Step 3-3): The external liposome premix is ​​kept at 70℃ and stirred continuously at 300rpm. Then, the whitening effect solution is added dropwise to the external liposome premix. After the addition is complete, the mixture is stirred continuously at 70℃ for 15 minutes under nitrogen protection. Then, it is cooled to room temperature and homogenized by sonication at 200W for 5 seconds on and 5 seconds off under ice bath conditions for 3 minutes to obtain the initial emulsion. Steps 3-4): Mix 0.3g PVA and 50g deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir continuously at 800 rpm for 2 hours at room temperature to obtain the external liposome solution.

[0033] Step 4) Add the small liposome particle solution to the external liposome solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.005 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain a transdermal whitening supramolecular composition.

[0034] Example 3

[0035] A transdermal skin-brightening supramolecular composition, prepared by the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 11g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 11%. Steps 1-2): Mix 1.1g of Peptido with anhydrous ethanol to prepare a Peptido ethanol solution with a mass concentration of 11%. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0036] Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.6g hydrogenated lecithin, 0.06g Tween-80, 0.11g cholesterol, 0.11g naringin, and 51g anhydrous ethanol to obtain an intraliposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): 0.2g palmitoyl hexapeptide-8 solution was added to the liposome premix and sonicated at 200W and 30℃ for 20 minutes. The lipid film was then formed by rotary evaporation under reduced pressure at 45℃ using the thin film rotary evaporation method. Steps 2-4): Mix 1.1g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 5.1g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, sonicate at 200W and 40℃ for 5 minutes, let stand for hydration for 30 minutes, and then use an ultrasonic homogenizer in an ice bath at 200W for 5 seconds on and 5 seconds off for 5 minutes to homogenize for 5 minutes. Repeat this cycle 3 times to obtain a small liposome particle solution.

[0037] Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.6g hydrogenated lecithin, 0.11g cholesterol, 0.32g oleic acid, 0.21g ceramide, 0.11g resveratrol, 0.21g Tween-80, and 10.5g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 2.1:1), and stir at 70°C under nitrogen protection to dissolve and obtain the external liposome premix. Step 3-2): Mix 1.1g niacinamide, 0.55g carnosine, and 5.1g deionized water to obtain a whitening solution. Step 3-3): The external liposome premix is ​​kept at 70℃ and stirred continuously at 300rpm. Then, the whitening effect solution is added dropwise to the external liposome premix. After the addition is complete, the mixture is stirred continuously at 70℃ for 15 minutes under nitrogen protection. Then, it is cooled to room temperature and homogenized by sonication at 200W for 5 seconds on and 5 seconds off under ice bath conditions for 3 minutes to obtain the initial emulsion. Steps 3-4): Mix 0.32g PVA and 51g deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir continuously at 800 rpm for 2 hours at room temperature to obtain the external liposome solution.

[0038] Step 4) Add the small liposome particle solution to the external liposome solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.006 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain a transdermal whitening supramolecular composition.

[0039] The source information for each raw material in Examples 1-3 is as follows: The cyclodextrin was hydroxypropyl-β-cyclodextrin, purchased from Maclean's.

[0040] Peptide Amide was purchased from Hangzhou Chuangtai Biotechnology.

[0041] Hydrogenated lecithin was purchased from Suzhou Nacon Biotechnology.

[0042] Cholesterol was purchased from Aladdin.

[0043] Twain-80 was purchased from Aladdin.

[0044] Naringin was purchased from Sinopharm Group.

[0045] Palmitoyl hexapeptide-8 was purchased from Hangzhou Chuangtai Biotechnology.

[0046] Oleic acid was purchased from Maclean's.

[0047] Ceramides were purchased from McLean.

[0048] Resveratrol was purchased from Hangzhou Chuangtai Biotechnology.

[0049] Niacinamide was purchased from McLean.

[0050] Carnosine was purchased from Hangzhou Chuangtai Biotechnology.

[0051] 1,3-Propanediol was purchased from Aladdin.

[0052] Glycerin was purchased from Aladdin.

[0053] PVA was purchased from Aladdin.

[0054] Acetyl tetrapeptide-9 was purchased from Hangzhou Chuangtai Biotechnology.

[0055] Comparative Example 1 A whitening composition, the preparation method of which includes the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 10g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 10%. Steps 1-2): Mix 1g of Peptido with anhydrous ethanol to prepare a 10% Peptido ethanol solution. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0056] Step 2), preparing the mixed solution, specifically includes: Step 2-1): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Step 2-2): Mix 1g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 5g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. (Steps 2-3) Add 0.15g palmitoyl hexapeptide-8 solution to cyclodextrin-peptide supramolecular inclusion complex solution, sonicate and hydrate at 40℃ for 30min, then homogenize using an ultrasonic homogenizer in an ice bath at 200W for 5s on and 5s off for 5min, repeat 3 times to obtain a mixed solution.

[0057] Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.5g hydrogenated lecithin, 0.1g cholesterol, 0.3g oleic acid, 0.2g ceramide, 0.1g resveratrol, 0.2g Tween-80, and 10g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 2:1), and stir at 70°C under nitrogen protection to dissolve and obtain the external liposome premix. Step 3-2): Mix 1g niacinamide, 0.5g carnosine, and 5g deionized water to obtain a whitening solution. Step 3-3): The external liposome premix is ​​kept at 70℃ and stirred continuously at 300rpm. Then, the whitening effect solution is added dropwise to the external liposome premix. After the addition is complete, the mixture is stirred continuously at 70℃ for 15 minutes under nitrogen protection. Then, it is cooled to room temperature and homogenized by sonication at 200W for 5 seconds on and 5 seconds off under ice bath conditions for 3 minutes to obtain the initial emulsion. Steps 3-4): Mix 0.3g PVA and 50g deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir continuously at 800 rpm for 2 hours at room temperature to obtain the external liposome solution.

[0058] Step 4) Add the mixed solution to the external liposome solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.005 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain the whitening composition.

[0059] Comparative Example 2 A whitening composition, the preparation method of which includes the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 10g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 10%. Steps 1-2): Mix 1g of Peptido with anhydrous ethanol to prepare a 10% Peptido ethanol solution. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0060] Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.5g hydrogenated lecithin, 0.05g Tween-80, 0.1g cholesterol, 0.1g naringin, and 50g anhydrous ethanol to obtain an endoplasmic liposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): 0.15g palmitoyl hexapeptide-8 solution was added to the liposome premix, and after sonication until dissolved, lipid films were formed by rotary evaporation at 45°C under reduced pressure. Steps 2-4): Mix 1g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 5g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, sonicate and hydrate at 40°C for 30 min, then homogenize using an ultrasonic homogenizer in an ice bath at 200W for 5 seconds on and 5 seconds off for 5 min, repeating the cycle 3 times to obtain a small liposome particle solution.

[0061] Step 3), preparing the composite solution, specifically includes: Step 3-1): Mix 0.3g oleic acid, 0.2g ceramide, 0.1g resveratrol, and 10g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 2:1), and stir at 70°C under nitrogen protection to dissolve and obtain the premix. Step 3-2): Mix 1g niacinamide, 0.5g carnosine, and 5g deionized water to obtain a whitening solution. Step 3-3): Keep the premix at a constant temperature of 70℃ and stir continuously at 300rpm. Then, add the whitening solution dropwise into the premix. After the addition is complete, stir continuously at 70℃ for 15 minutes under nitrogen protection. Then, cool down to room temperature and sonicate for 3 minutes at 200W under ice bath conditions, turning on for 5 seconds and turning off for 5 seconds to obtain the initial mixture. Steps 3-4): Mix 0.3g PVA and 50g deionized water to obtain a PVA solution; Steps 3-5): Add the PVA solution to the initial mixture, stir continuously at 800 rpm for 2 hours at room temperature to obtain the composite solution.

[0062] Step 4) Add the small liposome particle solution to the composite solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.005 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain the whitening composition.

[0063] Comparative Example 3 A whitening composition, the preparation method of which includes the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 10g of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 10%. Steps 1-2): Mix 1g of Peptido with anhydrous ethanol to prepare a 10% Peptido ethanol solution. (Steps 1-3) The cyclodextrin solution was kept at a constant temperature of 45℃ and stirred continuously at 300rpm. Then, the peptide amide ethanol solution was added dropwise to the cyclodextrin solution. After the addition was complete, the solution was homogenized using an ultrasonic homogenizer at 25℃ and 200W for 10 minutes with the on end for 5 seconds and the off end for 5 seconds. After that, the solution was kept at room temperature and protected from light, and stirred continuously at 300rpm for 6 hours under sealed conditions. After the process was completed, the solution was freeze-dried to obtain the cyclodextrin-peptide amide supramolecular inclusion complex.

[0064] Step 2), preparing the mixed solution, specifically includes: Step 2-1): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Step 2-2): Mix 1g of cyclodextrin-peptide ammonium supramolecular inclusion complex with 5g of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. (Steps 2-3) Add 0.15g palmitoyl hexapeptide-8 solution to cyclodextrin-peptide supramolecular inclusion complex solution, sonicate and hydrate at 40℃ for 30min, then homogenize using an ultrasonic homogenizer in an ice bath at 200W for 5s on and 5s off for 5min, repeat 3 times to obtain a mixed solution.

[0065] Step 3), preparing the composite solution, specifically includes: Step 3-1): Mix 0.3g oleic acid, 0.2g ceramide, 0.1g resveratrol, and 10g 1,3-propanediol / glycerol mixture (the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 2:1), and stir at 70°C under nitrogen protection to dissolve and obtain the premix. Step 3-2): Mix 1g niacinamide, 0.5g carnosine, and 5g deionized water to obtain a whitening solution. Step 3-3): Keep the premix at a constant temperature of 70℃ and stir continuously at 300rpm. Then, add the whitening solution dropwise into the premix. After the addition is complete, stir continuously at 70℃ for 15 minutes under nitrogen protection. Then, cool down to room temperature and sonicate for 3 minutes at 200W under ice bath conditions, turning on for 5 seconds and turning off for 5 seconds to obtain the initial mixture. Steps 3-4): Mix 0.3g PVA and 50g deionized water to obtain a PVA solution; Steps 3-5): Add the PVA solution to the initial mixture, stir continuously at 800 rpm for 2 hours at room temperature to obtain the composite solution.

[0066] Step 4) Add the mixed solution to the composite solution, stir continuously at 800 rpm for 1 hour at room temperature, homogenize at 20 MPa using a high-pressure homogenizer, cycle 3 times, then add 0.005 g of acetyl tetrapeptide-9, stir at 800 rpm for 30 minutes at room temperature to obtain the whitening composition.

[0067] Experiment 1 Sixty volunteers were recruited and divided into groups of 10. The groups used the compositions prepared in the various examples and comparative examples.

[0068] Volunteers cleansed their faces with water and a disposable face towel before bed each day, then applied 5ml of the mixture evenly to their faces until fully absorbed, and continued using it for 30 days.

[0069] Before using the composition, volunteers cleansed their faces with water and disposable face towels and dried them with a clean towel. Then, the melanin content was measured using the MX18 melanin tester from CK (Germany). The test point was the middle of the forehead, and this was recorded as the initial melanin content.

[0070] After using the composition for 30 days, volunteers first cleansed their faces with water and disposable face towels and then dried them with a clean towel. Then, the melanin content was measured using the MX18 melanin tester from CK Company in Germany. The test point was the middle of the forehead, and the melanin content was recorded as 30 days after the whitening treatment.

[0071] Calculate the melanin reduction value after 30 days of skin whitening using the following formula: Melanin reduction value after 30 days of whitening = initial melanin content - melanin content after 30 days of whitening.

[0072] The experimental data are detailed in Table 1.

[0073] Table 1

[0074] According to the data in Table 1, the melanin reduction value of the embodiment after 30 days of whitening was significantly higher than that of the comparative example. This shows that the whitening effect of the embodiment is more significant than that of the comparative example. This proves that, under the premise of using the same whitening ingredients, the transdermal absorption supramolecular composition with a multi-layer structure made by special process can significantly improve the efficiency of whitening ingredients being absorbed by the skin. By controlling the release of different whitening ingredients in different areas of the skin, the efficacy of the whitening ingredients is more targeted, the overall whitening effect is significantly improved, and the whitening effect is seen faster.

[0075] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A transdermal skin-brightening supramolecular composition, characterized in that: This includes solvents, external aqueous phase stabilizers dissolved in the solvent, and whitening supramolecular particles dispersed in the solvent; The whitening supramolecular particles include an outer elastic liposome with a bilayer structure, wherein the outer elastic liposome encapsulates a water-soluble whitening agent, a water-soluble anti-glycation agent, and small liposome particles. The outer elastic liposome has a bilayer structure loaded with a permeability enhancer, a barrier repair agent, and an autophagy activator. The outer surface of the outer elastic liposome also adsorbs a keratinocyte targeting agent. The small liposome particles include an inner elastic liposome with a bilayer structure, and the inner elastic liposome encapsulates a cyclodextrin-peptide ammonium supramolecular inclusion complex. The inner elastic liposome is loaded with an oil-soluble anti-glycation agent within its bilayer structure. The inner elastic liposome is embedded with a melanocyte-targeting agent, which includes a lipophilic end and a hydrophilic end. The lipophilic end of the melanocyte-targeting agent is embedded in the bilayer structure of the inner elastic liposome, while the hydrophilic end extends out of the inner elastic liposome.

2. The transdermal whitening supramolecular composition according to claim 1, characterized in that: The water-soluble whitening agent is niacinamide; the water-soluble anti-glycation agent is carnosine; the penetration enhancer is oleic acid; the barrier repair agent is ceramide; the autophagy activator is resveratrol; the keratinocyte targeting agent is acetyl tetrapeptide-9; the oil-soluble anti-glycation agent is naringin; and the melanocyte targeting agent is palmitoyl hexapeptide-8.

3. The transdermal whitening supramolecular composition according to claim 2, characterized in that: The outer elastic liposome is formed by combining hydrogenated lecithin, cholesterol, and Tween-80; the inner elastic liposome is formed by combining hydrogenated lecithin, cholesterol, and Tween-80.

4. The transdermal whitening supramolecular composition according to claim 3, characterized in that: The solvent is deionized water, and the external aqueous phase stabilizer is PVA.

5. The transdermal whitening supramolecular composition according to claim 4, characterized in that: The preparation method of the transdermal skin-whitening supramolecular composition includes the following steps: Step 1), preparation of cyclodextrin-peptide supramolecular inclusion complex, specifically includes: Step 1-1): Mix 9-11 parts of cyclodextrin with deionized water to prepare a cyclodextrin solution with a mass concentration of 9-11%. Steps 1-2): Mix 0.9-1.1 parts of Peptidone with anhydrous ethanol to obtain Peptidone ethanol solution; Steps 1-3): Continuously stir the cyclodextrin solution and add peptide amido ethanol solution dropwise to the cyclodextrin solution. Then, after ultrasonic homogenization, stirring, and drying, the cyclodextrin-peptide amido supramolecular inclusion complex is obtained. Step 2), preparing a small liposome particle solution, specifically includes: Step 2-1): Mix 0.4-0.6 parts hydrogenated lecithin, 0.04-0.06 parts Tween-80, 0.09-0.11 parts cholesterol, 0.09-0.11 parts naringin, and 49-51 parts anhydrous ethanol to obtain an intraliposome premix. Step 2-2): Mix palmitoyl hexapeptide-8 with deionized water to prepare a 5 mg / mL palmitoyl hexapeptide-8 solution; Steps 2-3): Add 0.1-0.2 parts of palmitoyl hexapeptide-8 solution to the endoliposome premix, and obtain a lipid film by ultrasonic vibration and vacuum rotary evaporation. Steps 2-4): Mix 0.9-1.1 parts of cyclodextrin-peptide ammonium supramolecular inclusion complex with 4.9-5.1 parts of deionized water to obtain a cyclodextrin-peptide ammonium supramolecular inclusion complex solution. Steps 2-5): Add the cyclodextrin-peptide supramolecular inclusion complex solution to the lipid film, and after ultrasonic vibration, hydration and homogenization, obtain a small liposome particle solution; Step 3), preparing the exoliposome solution, specifically includes: Step 3-1): Mix 1.4-1.6 parts hydrogenated lecithin, 0.09-0.11 parts cholesterol, 0.28-0.32 parts oleic acid, 0.19-0.21 parts ceramide, 0.09-0.11 parts resveratrol, 0.19-0.21 parts Tween-80, and 9.5-10.5 parts 1,3-propanediol / glycerol mixture to obtain the exoliposome premix. Step 3-2): Mix 0.9-1.1 parts niacinamide, 0.45-0.55 parts carnosine, and 4.9-5.1 parts deionized water to obtain a whitening solution. Step 3-3): Add the whitening solution to the external liposome premix, stir and sonicate to obtain the colostrum; Steps 3-4): Mix 0.28-0.32 parts of PVA and 49-51 parts of deionized water to obtain a PVA solution; Steps 3-5): Add PVA solution to the primary emulsion and stir to obtain external liposome solution; Step 4): Add the small liposome particle solution to the external liposome solution, stir and homogenize, then add 0.004-0.006 parts of acetyl tetrapeptide-9, stir, and obtain a transdermal whitening supramolecular composition.

6. The transdermal whitening supramolecular composition according to claim 5, characterized in that: In step 1-1), the cyclodextrin is hydroxypropyl-β-cyclodextrin.

7. A transdermal whitening supramolecular composition according to claim 5 or 6, characterized in that: In step 3-1), the 1,3-propanediol / glycerol mixture is prepared by compounding 1,3-propanediol and glycerol in a mass ratio of 1.9-2.1:

1.

8. The application of a transdermal whitening supramolecular composition according to any one of claims 1-7, characterized in that: The transdermal whitening supramolecular composition can be used directly as a standalone skincare product or added to skincare formulations for the preparation of whitening skincare products.

Images