Permeation-promoting skin nano-composite sphere peptide, preparation method thereof and application of permeation-promoting skin nano-composite sphere peptide in preparation of scalp oil-control, anti-hair-loss and anti-aging products

Abstract

The invention relates to the technical field of transdermal delivery and cosmetics, in particular to a penetration-promoting skin nano-composite sphere peptide, a preparation method thereof and application of the penetration-promoting skin nano-composite sphere peptide in preparation of scalp oil-control, anti-alopecia and anti-aging products. The preparation method comprises the following steps: adding composite peptide into a first organic solvent, and heating and dissolving at a first temperature (35-45 DEG C) to obtain a first solution; adding tocoxolam into a second organic solvent, and heating and dissolving at a second temperature (40-60 DEG C) to obtain a second solution; adding poloxamer into water, and heating and dissolving at a third temperature (40-60 DEG C) to obtain a third solution; mixing the second solution and the third solution to obtain a fourth solution; adding the first solution into the fourth solution at a first rate (1mL / min to 3mL / min), and dispersing at a fourth temperature (40 DEG C to 50 DEG C); the penetration-promoting skin nano composite sphere peptide is high in stability, excellent in transdermal absorption performance and good in oil control, hair loss prevention and aging resistance effects on scalp.

Description

Technical Field

[0001] This application relates to the fields of transdermal delivery and cosmetic technology, and in particular to a transdermal nanocomposite spheropeptide, its preparation method, and its application in the preparation of scalp oil control, hair loss prevention, and anti-aging products. Background Technology

[0002] In the cosmetics and skincare industry, peptides have demonstrated great potential in skin care and drug therapy due to their highly efficient bioactivity. Lipid modification, such as palmitoylation, is a common method used in cosmetics to address the transdermal absorption of peptides. By linking fatty acid chains, water-soluble peptides are converted into lipid-soluble precursors, enhancing their affinity for the stratum corneum. Palmitoyl tripeptide-1, palmitoyl tripeptide-5, and palmitoyl tetrapeptide-7 are representative examples, proven to effectively promote collagen synthesis, inhibit inflammatory responses, and repair damaged skin barriers.

[0003] However, peptides modified with lipids such as palmitoylation become lipophilic peptides, making them difficult to apply in aqueous products. Existing application technologies are mainly designed for water-soluble peptides, which face bottlenecks in processing lipophilic peptides in water-based formulations, including poor solubility, low stability (easy hydrolysis and precipitation), and insufficient delivery efficiency. These limitations severely restrict their commercial development and the realization of their end-use efficacy.

[0004] In the field of active ingredient delivery technology, the self-assembly of amphiphilic polymers to form micelles is an effective strategy for solubilizing hydrophobic drugs. Currently, although there are reports of using poloxamer or tococelenum alone as peptide carriers to prepare peptide micelles, the stability of these micelles is not strong, and peptides may precipitate or degrade. In addition, the transdermal effect and dispersion performance of these micelles in aqueous solutions need to be improved. Summary of the Invention

[0005] This application, through extensive experiments, has discovered that a transdermal nanocomposite spheropeptide prepared using toxoxelam and poloxamer as carriers and through appropriate methods has small particle size, high stability, and excellent transdermal absorption performance. It also has good oil control, anti-hair loss, and anti-aging effects on the scalp.

[0006] The first aspect of this application provides a skin penetration-enhancing nanocomposite spheropeptide, the preparation method of which includes the following steps:

[0007] The complex peptide is added to a first organic solvent and mixed, and then ultrasonically dissolved at a first temperature to obtain a first solution; the complex peptide comprises components (i) to (iii): (i) palmitoyl tripeptide-1 or its derivative; (ii) palmitoyl tripeptide-5 or its derivative; (iii) palmitoyl tetrapeptide-7 or its derivative; the first organic solvent is an aliphatic polyol; the first temperature is 35℃-45℃;

[0008] Toxoxelane is added to a second organic solvent and mixed, then heated at a second temperature to dissolve, thus obtaining a second solution; wherein the toxoxelane is polyethylene glycol succinate; the second organic solvent is an aliphatic polyol; and the second temperature is 40℃-60℃.

[0009] Poloxamer is added to a first water and mixed, then heated to a third temperature to dissolve it, thus preparing a third solution; the third temperature is 40℃-60℃.

[0010] The second solution and the third solution are mixed to obtain the fourth solution;

[0011] The first solution is added to the fourth solution at a first rate and stirred and dispersed at a fourth temperature to obtain the aforementioned skin-penetrating nanocomposite spheroid peptide; the first rate is 1 mL / min-3 mL / min and the fourth temperature is 40℃-50℃.

[0012] This application discloses a skin-penetrating nanocomposite spheropeptide prepared using a specific method. The hydrophobic vitamin E group of tococelenum and the polyoxypropylene chain of poloxamer synergistically form a stable hydrophobic core, effectively encapsulating lipid-soluble peptides. Simultaneously, the hydrophilic polyethylene glycol chain of tococelenum and the polyoxyethylene chain of poloxamer intertwine to form a dense hydrophilic protective layer. This results in nanomicelles exhibiting excellent transdermal permeability and stability, along with small particle size and good dispersibility, effectively solving the problems of poor permeability, low solubility in aqueous solutions, and poor stability of lipid-soluble peptides. This skin-penetrating nanocomposite spheropeptide significantly enhances the retention and absorption of the complex peptide in the skin. The three components of the complex peptide synergistically promote the production of type I and III collagen, providing excellent oil control, anti-hair loss, and anti-aging effects for the scalp.

[0013] Furthermore, the first organic solvent and the second organic solvent each independently comprise one or more of the following: propylene glycol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, glycerol, dipropylene glycol, 1,2-hexanediol, 1,6-hexanediol, methylpropanediol (2-methyl-1,3-propanediol), trimethylolpropane, and pentaerythritol. These solvents exhibit good solubility and biocompatibility, making them suitable for cosmetic applications.

[0014] Furthermore, the polyethylene glycol structural units in the vitamin E succinate polyethylene glycol ester have a molecular weight of 500 Da-5000 Da. Different molecular weights of PEG chains affect the particle size and stability of the micelles; within the above molecular weight range, it is beneficial to maintain a uniform particle size distribution and system stability.

[0015] Furthermore, the poloxamer contains 70%-75% polyoxyethylene by mass and has an average molecular weight of 8000 Da-15000 Da. The above-mentioned polyoxyethylene content and average molecular weight of the poloxamer are within a suitable range, enabling the formation of a more stable micelle structure.

[0016] Furthermore, the aforementioned skin penetration-enhancing nanocomposite spheropeptide satisfies at least one of the following conditions:

[0017] (1) In the complex peptide, the mass ratio of components (i), (ii) and (iii) is 1:(0.8-1.2):(0.8-1.2);

[0018] (2) The mass ratio of the complex peptide to the tococelen is (0.0001-0.5):(1-20);

[0019] (3) The mass ratio of the tocosolvan and the poloxamer is (1-1.5):1.

[0020] Furthermore, the aforementioned skin penetration-enhancing nanocomposite spheropeptide satisfies at least one of the following conditions:

[0021] (1) The weight percentage of the complex peptide in the first solution is 0.0001%-0.5%;

[0022] (2) The toxoxelam in the second solution accounts for 20%-60% by weight;

[0023] (3) The weight percentage of poloxamer in the third solution is 0.1%-5%.

[0024] Furthermore, in the step of adding the first solution to the fourth solution at a first rate and dispersing it at a fourth temperature, the stirring speed is 100 rpm to 600 rpm. A suitable stirring speed helps to form uniform nanomicelles.

[0025] The second aspect of this application provides the application of the aforementioned transdermal-penetrating nanocomposite spheropeptide in the preparation of cosmetics. This application can effectively improve the stability and transdermal absorption efficiency of active ingredients in cosmetics, thereby enhancing the efficacy of the product.

[0026] Furthermore, the cosmetic product is an antioxidant. These nanomicelles can effectively scavenge free radicals, reduce oxidative stress damage to the skin and scalp, and slow down the aging process.

[0027] Furthermore, the cosmetic product is for scalp oil control, hair loss prevention, and anti-aging. Through the synergistic effect of the three peptides, it can regulate scalp sebum secretion, inhibit hair follicle miniaturization, promote hair growth, and improve the scalp microenvironment, achieving comprehensive scalp health care.

[0028] The technical solution of this application includes at least the following beneficial effects:

[0029] This application discloses a transdermal transdermal nanocomposite spheroid peptide prepared using toxoxalam and poloxamer as carriers through a suitable method. This transdermal transdermal transdermal nanocomposite spheroid peptide exhibits good stability, effectively preventing the degradation of palmitoyl tripeptide-1, palmitoyl tripeptide-5, and palmitoyl tetrapeptide-7. It also possesses excellent dispersibility, exhibiting no sedimentation or aggregation in solution. The aforementioned transdermal transdermal transdermal nanocomposite spheroid peptide demonstrates good transdermal absorption, high bioavailability, and high delivery efficiency in aqueous environments, showing broad application prospects in the cosmetics field.

[0030] The active ingredients in this transdermal-penetrating nanocomposite spheropeptide are stably and completely encapsulated in micelles. Based on the excellent transdermal effect of the micelles, it achieves comprehensive effects of oil control, hair loss prevention, and anti-aging, thereby improving scalp health at its root. In vitro cell experiments have demonstrated that this transdermal-penetrating nanocomposite spheropeptide, compared to unencapsulated composite peptides or single-encapsulated polypeptides, can better promote the production of type I and type III collagen and has a better antioxidant effect. Animal model experiments show that this transdermal-penetrating nanocomposite spheropeptide promotes hair growth in mice.

[0031] The present application discloses a transdermal nanocomposite spheroid peptide that is constructed based on self-assembly technology. Its preparation method is simple and suitable for large-scale industrial production. Attached Figure Description

[0032] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0033] Figure 1 This is a transmission electron microscope image of the nanomicelles of Example 1 of this application, with a scale bar of 50 nm.

[0034] Figure 2 This is a particle size distribution diagram of the nanomicelles in Example 1 and Comparative Example 1.

[0035] Figure 3 This is the antioxidant effect of 3-7 nanometer micelles in Example 1 and Comparative Example of this application.

[0036] Figure 4 This is the result of Example 1 and Comparative Example 3-7 nanometer micelles promoting the synthesis of type I and type III collagen and elastin in fibroblasts.

[0037] Figure 5 These are partial images of hair growth promotion in Example 1, the blank control group, and the positive control group. Detailed Implementation

[0038] The present application is further described below with reference to embodiments and examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the protection scope of the appended claims.

[0039] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0040] Unless otherwise stated or in case of contradiction, the terms or phrases used herein shall have the following meanings:

[0041] The term "and / or" as used herein includes any one of two or more related listed items, as well as any and all combinations of the related listed items. These arbitrary and all combinations encompass any two related listed items, any more related listed items, or a combination of all related listed items. It should be noted that when at least three items are connected using at least two conjunctions selected from "and / or," it should be understood that, in this application, the technical solution undoubtedly includes solutions connected by "logical AND," and also undoubtedly includes solutions connected by "logical OR." For example, "A and / or B" includes three parallel solutions: A, B, and A+B. For example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (that is, a technical solution that is connected by "logical OR"), as well as any and all combinations of A, B, C, and D, that is, combinations of any two or three of A, B, C, and D, and also combinations of all four of A, B, C, and D (that is, a technical solution that is connected by "logical AND").

[0042] In this application, terms such as "further" are used to describe purposes and indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0043] In this application, the terms "first aspect," "second aspect," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor should they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first," "second," "third," "fourth," etc., serve only as a non-exhaustive enumeration and should be understood not to constitute a closed limitation on quantity.

[0044] In this application, the technical features described in an open-ended manner include both closed technical solutions consisting of the listed features and open technical solutions that include the listed features.

[0045] In this application, numerical intervals (i.e., numerical ranges) are involved. Unless otherwise specified, optional numerical distributions within the aforementioned numerical intervals are considered continuous and include the two endpoints (i.e., the minimum and maximum values) of the numerical range, as well as every value between these two endpoints. Unless otherwise specified, when a numerical interval refers only to integers within that interval, it includes the two endpoint integers of the numerical range, as well as every integer between the two endpoints. Furthermore, when multiple ranges are provided to describe features or characteristics, these ranges can be merged. In other words, unless otherwise specified, the ranges disclosed herein should be understood to include any and all subranges to which they are included.

[0046] Unless otherwise specified, the temperature parameters in this application are permitted to be either constant-temperature treatment or variations within a certain temperature range. It should be understood that the constant-temperature treatment allows temperature fluctuations within the precision range of the instrument control, such as ±5°C, ±4°C, ±3°C, ±2°C, or ±1°C.

[0047] In this application, weight can be a well-known unit of mass in the cosmetics or materials field, such as μg, mg, g, or kg.

[0048] In this application, unless otherwise specified, the terms "size", "particle size", and "diameter" generally refer to average values.

[0049] In this application, unless otherwise specified, molecular weight refers to average molecular weight, and further, unless otherwise specified, refers to weight-average molecular weight.

[0050] In this application, "at least one" means one, two, or more.

[0051] In this application, the polypeptide palmitoyl tripeptide-1 is "palmitoyl-glycine-histidine-lysine", the palmitoyl tripeptide-5 is "palmitoyl-lysine-valine-lysine", and the palmitoyl tetrapeptide-7 is "palmitoyl-glycine-glutamine-proline-arginine".

[0052] In this article, peptide derivatives, such as those described in "palmitoyl tripeptide-1 or its derivatives," "palmitoyl tripeptide-5 or its derivatives," and "palmitoyl tetrapeptide-7 or its derivatives," include chemical structural analogs of the corresponding peptides or higher peptides, such as palmitoyl hexapeptide-12 and palmitamide pentapeptide-4. These derivatives can maintain or enhance the biological activity of the original peptides while improving their physicochemical properties, such as solubility, stability, and transdermal absorption performance, providing more options for product development.

[0053] Human fibroblasts (HSFs) are one of the main cell types in the skin, playing a crucial role in skin repair and regeneration. Researchers have investigated how HSFs respond to skin damage and how they participate in the skin healing process. For example, researchers have found that HSFs can produce substances such as collagen and fibronectin, which are essential for the formation of new skin structures and promoting wound healing. In some embodiments of this application, HSFs were used to evaluate the antioxidant efficacy of skin-penetrating nanocomposite globulins.

[0054] Type I and Type III collagen and elastin are among the most important markers of human fibroblasts, synthesized and secreted by dermal fibroblasts. They play a crucial role in maintaining skin elasticity and firmness. With age, collagen synthesis gradually decreases, leading to skin laxity and wrinkles. Therefore, promoting the synthesis of type I and Type III collagen and elastin is one of the core efficacy features of many anti-aging cosmetics. In some embodiments of this application, the anti-aging efficacy of the skin-penetrating nanocomposite globulin was evaluated by measuring the content of type I and Type III collagen in fibroblasts before and after treatment.

[0055] The first aspect of this application provides a skin penetration-enhancing nanocomposite spheropeptide, and a method for preparing the skin penetration-enhancing nanocomposite spheropeptide includes the following steps:

[0056] S1. The complex peptide is added to a first organic solvent and mixed, and then ultrasonically dissolved at a first temperature to obtain a first solution; the complex peptide comprises components (i) to (iii): (i) palmitoyl tripeptide-1 or its derivative; (ii) palmitoyl tripeptide-5 or its derivative; (iii) palmitoyl tetrapeptide-7 or its derivative; the first organic solvent is an aliphatic polyol; the first temperature is 35℃-45℃;

[0057] S2. Toxoxelam is added to the second organic solvent and mixed, then heated at the second temperature to dissolve it, thus obtaining the second solution; toxoxelam is polyethylene glycol succinate; the second organic solvent is an aliphatic polyol; the second temperature is 40℃-60℃.

[0058] S3. Add poloxamer to the first water and mix. Heat the mixture at a third temperature to dissolve the solution and obtain a third solution. The third temperature is 40℃-60℃.

[0059] S4. Mix the second solution and the third solution to obtain the fourth solution;

[0060] S5. The first solution is added to the fourth solution at a first rate and stirred and dispersed under a fourth temperature condition to obtain a skin-penetrating nanocomposite spheroid peptide; the first rate is 1 mL / min-3 mL / min and the fourth temperature is 40℃-50℃.

[0061] In the above-mentioned method for preparing a transdermal nanocomposite peptide, in step S1, the composite peptide is added to a first organic solvent and mixed, and then ultrasonically dissolved at a first temperature (35℃-45℃). This allows the composite peptide to dissolve fully at a temperature that will not denature, resulting in a homogeneous solution (first solution) of appropriate concentration. In step S2, tococelen is added to a second organic solvent and mixed, and then heated to a second temperature (40℃-60℃). This allows both the hydrophilic portion (polyethylene glycol chain) and the hydrophobic portion (vitamin E succinate) of tococelen to be in a relatively relaxed state, which is beneficial for the peptide molecules to fully interact with the hydrophobic portion. In step S3, poloxamer is added to the first water and mixed, then heated at a third temperature (40℃-60℃) to dissolve it, which allows the hydrophilic part (PEO chain) of poloxamer to fully extend and dissolve the molecule, thus obtaining the third solution. In step S4, the second and third solutions are mixed to obtain a homogeneous fourth solution. In step S5, the first solution is added to the fourth solution at a first rate (1mL / min-3mL / min), and stirred and dispersed at a fourth temperature (40℃-50℃). During this process, the complex peptide changes from its original single organic solvent environment (the solvent environment of the first solution) to a more stable organic solvent environment. The peptide undergoes a dramatic transformation into a complex solvent environment (the solvent environment of the fourth solution), and self-assemblies are driven by hydrophobic interactions. During this self-assembly, toxoxelam and poloxamer together form the outer phase of the complex peptide. Toxoxelam exhibits high lipophilicity and a higher affinity for lipophilic peptide molecules. Its lipophilic vitamin E end can insert into or tightly encapsulate lipophilic peptide molecules, while the PEG chain extends into the water, providing water solubility. Simultaneously, poloxamer forms various intermolecular forces with toxoxelam to more firmly encapsulate the peptide molecule. On one hand, the hydrophobic PPO chain of poloxamer can insert into the hydrophobic portion (vitamin E) of toxoxelam. The core expands and stabilizes the inner core; on the other hand, the hydrophilic polyoxyethylene (PEO) of poloxamer can interweave with the hydrophilic polyethylene glycol (PEG) chain shell of toxoxelam to form a dense and stable hydrophilic protective layer, preventing micelle aggregation or disintegration; the skin-penetrating nanocomposite spheroid peptide prepared by the above method has a specific carrier structure and a small particle size (e.g., the particle size can be ≤20nm), thereby obtaining excellent skin permeability, which can significantly enhance the retention and absorption of the composite peptide in the skin; in addition, the skin-penetrating nanocomposite spheroid peptide has good dispersibility and can exist stably in aqueous solution without sedimentation or aggregation.

[0062] In this embodiment, the first temperature is 35℃-45℃, for example 35℃, 38℃, 40℃, 42℃, 45℃, etc.; further, the second temperature is 40℃-60℃, for example 40℃, 45℃, 50℃, 55℃, 60℃, etc.; further, the third temperature is 40℃-60℃, for example 40℃, 45℃, 50℃, 55℃, 60℃, etc.; further, the fourth temperature is 40℃-50℃, for example 40℃, 42℃, 45℃, 48℃, 50℃, etc.

[0063] In some embodiments, a skin-penetrating nanocomposite spheroid peptide is a spherical nanomicelle with a certain particle size.

[0064] Furthermore, the average particle size of this skin-penetrating nanocomposite spheropeptide is 14.79±0.05nm, and the polydispersity index is 0.1472±0.02.

[0065] Furthermore, the zeta potential of this skin-penetrating nanocomposite spheropeptide is -5.711±1.30mV.

[0066] In some embodiments, the first and second organic solvents are aliphatic polyols. Aliphatic polyols refer to organic compounds with an open-chain (non-cyclic or non-aromatic ring) molecular structure and containing two or more hydroxyl groups (-OH). Aliphatic polyols have good solubility for complex peptides, good biocompatibility, and are suitable for cosmetic applications.

[0067] Optionally, the first organic solvent and the second organic solvent independently comprise one or more of the following: propylene glycol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, glycerol, dipropylene glycol, 1,2-hexanediol, 1,6-hexanediol, methylpropanediol (2-methyl-1,3-propanediol), trimethylolpropane, and pentaerythritol.

[0068] In some embodiments, the molecular weight of the polyethylene glycol (PEG) structural units in vitamin E succinate is 500 Da to 5000 Da. Different molecular weights of PEG chains affect the particle size and stability of the micelles; within the above molecular weight range, it is beneficial to maintain a uniform particle size distribution and system stability. For example, the molecular weight of the PEG structural units can be 500 Da, 1000 Da, 2000 Da, 3000 Da, 4000 Da, 5000 Da, etc.

[0069] In some embodiments, the polyoxyethylene content of poloxamer is 70%-75%, and the average molecular weight is 8000 Da-15000 Da. When the above-mentioned polyoxyethylene content and the average molecular weight of poloxamer are within a suitable range, a more stable micelle structure can be formed. For example, the polyoxyethylene content can be 70%, 72%, 75%, etc.; the average molecular weight can be 8000 Da, 9000 Da, 10000 Da, 11000 Da, 12000 Da, 13000 Da, 14000 Da, 15000 Da, etc. Further, the poloxamer can be poloxamer 407.

[0070] In some embodiments, the mass ratio of components (i), (ii), and (iii) in the complex peptide is 1:(0.8-1.2):(0.8-1.2), which can better exert a synergistic effect and play a role in controlling oil, preventing hair loss, and anti-aging of the scalp. For example, the mass ratio of components (i), (ii), and (iii) can be 1:0.8:0.8, 1:1:0.8, 1:0.8:1, 1:1:1, 1:0.8:1.2, 1:1:1.2, etc.

[0071] In some embodiments, the mass ratio of the complex peptide to tococelen is (0.0001-0.5):(1-20). Within this range, it is beneficial for the peptide molecule to interact more fully with the hydrophobic portion (vitamin E succinate) of tococelen. For example, the mass ratio of the complex peptide to tococelen can be 0.0001:1, 0.001:1, 0.01:1, 0.1:1, 0.05:1, 0.5:1, 0.5:10, 0.5:20, etc.

[0072] In some embodiments, the mass ratio of toxoxexron to poloxamer is (1-1.5):1. The hydrophobic PPO chain of poloxamer can insert into the hydrophobic core of the hydrophobic portion (vitamin E) of toxoxexron, expanding and stabilizing the core. This also allows the hydrophilic polyethylene oxide (PEO) chain of poloxamer to better interweave with the hydrophilic polyethylene glycol (PEG) chain shell of toxoxexron, resulting in the peptide molecule being stably encapsulated within the micelles, forming a denser and more stable hydrophilic protective layer. For example, the mass ratio of toxoxexron to poloxamer can be 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, etc.

[0073] In some embodiments, the weight percentage of the complex peptide in the first solution is 0.0001%-0.5%; preferably 0.001%-0.2%. For example, the weight percentage of the palmitoylated polypeptide compound can be selected from any value among 0.001%, 0.005%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%.

[0074] In some embodiments, the weight percentage of tococelen in the second solution is 20%-60%; preferably 25%-40%. For example, the weight percentage of tococelen can be selected from any value among 20%, 25%, 30%, 37%, 38%, 40%, 42%, 45%, 50%, 60%, etc.

[0075] In some embodiments, the weight percentage of poloxamer in the third solution is 0.1%-5%, preferably 0.1%-1%. For example, the weight percentage of poloxamer can be selected from any value among 0.1%, 0.5%, 1%, 2.5%, and 5%.

[0076] In some embodiments, in the step of adding the first solution to the fourth solution at a first rate and dispersing by stirring at a fourth temperature, the stirring speed is 100 rpm to 600 rpm. A suitable stirring speed helps to form uniform nanomicelles. For example, the stirring speed can be 100 rpm, 200 rpm, 300 rpm, 400 rpm, 500 rpm, 600 rpm, etc.

[0077] The second aspect of this application provides the application of the aforementioned skin-penetrating nanocomposite spheropeptide in the preparation of cosmetics. This skin-penetrating nanocomposite spheropeptide, when used in cosmetics, offers advantages such as high safety, no skin irritation, and good antioxidant, oil-controlling, anti-hair loss, and anti-aging effects. Furthermore, it possesses excellent skin permeability and can be used to prepare functional skincare products with one or more of these functions.

[0078] Furthermore, the cosmetics mentioned above are antioxidant products. The skin-penetrating nanocomposite spheropeptide of this application can effectively scavenge free radicals, reduce oxidative stress damage to the skin and scalp, and delay the aging process.

[0079] Furthermore, the cosmetics mentioned above are used in products for controlling scalp oil, preventing hair loss, and anti-aging.

[0080] There are two main reasons for scalp health problems. One is excessive sebum secretion. Excessive sebum oxidation can lead to abnormal keratinization of the hair follicle opening and the production of inflammatory factors, which in turn can cause hair follicle miniaturization and accelerate the hair loss process. The other is scalp aging. Continuous oxidative stress and chronic inflammation are important factors that cause scalp aging. The aging scalp microenvironment will further weaken hair follicle function and aggravate sebum secretion imbalance and hair loss problems.

[0081] This application presents a scalp-penetrating nanocomposite spheropeptide that comprehensively achieves oil control, hair loss prevention, and anti-aging. It effectively regulates scalp sebum secretion, inhibits hair follicle miniaturization, promotes hair growth, and improves the scalp microenvironment, thus achieving comprehensive scalp health care and fully solving scalp health problems.

[0082] In some embodiments, the cosmetic dosage form is an essence, ointment, cream, mask, powder, or microneedle.

[0083] The following are some specific examples.

[0084] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0085] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0086] Palmitoyl tripeptide-1 was purchased from Guangzhou Tongjun Pharmaceutical Technology Co., Ltd., under the trade name CG Pal-GHK, with an HPLC purity of ≥95%.

[0087] Palmitoyl tripeptide-5 was purchased from Guangzhou Tongjun Pharmaceutical Technology Co., Ltd., under the trade name CG Pal-KVK, with an HPLC purity of ≥95%.

[0088] Palmitoyl tetrapeptide-7 was purchased from Guangzhou Tongjun Pharmaceutical Technology Co., Ltd., under the trade name CG Pal-GQPR, with an HPLC purity of ≥95%.

[0089] I. Preparation of skin penetration-enhancing nanocomposite spheropeptides

[0090] Example 1

[0091] This embodiment provides a method for preparing a skin penetration-enhancing nanocomposite spheropeptide according to this application. The prepared skin penetration-enhancing nanocomposite spheropeptide exists in the form of nanomicelles, and is therefore referred to as nanomicelles below. The specific preparation method includes the following steps:

[0092] (1) Add 0.1g palmitoyl tripeptide-1, 0.1g palmitoyl tripeptide-5 and 0.1g palmitoyl tetrapeptide-7 to 80mL pentanediol and mix. Dissolve by ultrasonic heating at 40℃ to obtain the first solution.

[0093] (2) Add 12.0g tococelen (1000 Da) to 20mL pentanediol and mix. Dissolve by ultrasonic heating at 50℃ to obtain the second solution.

[0094] (3) Add 10.0g of poloxamer 407 (12600 Da) to 1.878L of deionized water and heat at 50℃ to dissolve it, thus preparing the third solution.

[0095] (4) Mix the second solution with the third solution to obtain the fourth solution (the temperature of the mixed solution is about 45°C).

[0096] (5) The first solution is added to the fourth solution at a rate of 2 mL / min and mixed. During the addition process, the mixture is kept at 45°C and stirred to disperse, forming nano micelles.

[0097] Example 2

[0098] This embodiment provides a method for preparing a skin-penetrating nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (1), the dissolution temperature of the composite peptide is 35°C.

[0099] Example 3

[0100] This embodiment provides a method for preparing a transdermal nanocomposite peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (1), the dissolution temperature of the composite peptide is 45°C.

[0101] Example 4

[0102] This embodiment provides a method for preparing a skin-penetrating nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (2), the dissolution temperature of tococelen in the first solution is 40°C.

[0103] Example 5

[0104] This embodiment provides a method for preparing a transdermal nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (2), the dissolution temperature of tococelen in the first solution is 60°C.

[0105] Example 6

[0106] This embodiment provides a method for preparing a permeation-enhancing nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (3), the dissolution temperature of poloxamer in the first water is 40°C.

[0107] Example 7

[0108] This embodiment provides a method for preparing a permeation-enhancing nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (3), the dissolution temperature of poloxamer in the first water is 60°C.

[0109] Example 8

[0110] This embodiment provides a method for preparing a transdermal nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (5), the addition rate is 1 mL / min and the fourth temperature is 40 °C.

[0111] Example 9

[0112] This embodiment provides a method for preparing a skin-penetrating nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that in step (5), the addition rate is 3 mL / min and the fourth temperature is 50 °C.

[0113] Example 10

[0114] This embodiment provides a method for preparing a transdermal nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that the first organic solvent and the second organic solvent are 1,3-propanediol.

[0115] Example 11

[0116] This embodiment provides a method for preparing a skin-penetrating nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that the mass ratio of tococelen and poloxamer is 1:1.

[0117] Example 12

[0118] This embodiment provides a method for preparing a skin-penetrating nanocomposite spheroid peptide according to this application. The preparation method is basically the same as that in Example 1, except that the mass ratio of tococelen and poloxamer is 1.5:1.

[0119] Comparative Example 1

[0120] This comparative example provides another method for preparing permeation-enhancing skin nanocomposite sphere peptides, which is prepared using a method that is basically the same as that in Example 1. The difference is that in step (3), poloxamer 407 is not added, and in step (4), the first water and the third solution are directly mixed to obtain the fourth solution.

[0121] Comparative Example 2

[0122] This comparative example provides another method for preparing permeation-enhancing skin nanocomposite globulins, which is prepared using a method that is basically the same as that in Example 1. The difference is that in step (2), toxoxelam is not added, and in step (4), the second organic solvent and the third solution are directly mixed to obtain the fourth solution.

[0123] Comparative Example 3

[0124] This comparative example provides a method for preparing single-peptide nanospheres, which is prepared using a method that is basically the same as that in Example 1, except that in step (1), only 0.3g of palmitoyl tripeptide-1 is added.

[0125] Comparative Example 4

[0126] This comparative example provides a method for preparing single-peptide nanospheres, which is prepared using a method that is basically the same as that in Example 1, except that in step (1), only 0.3g of palmitoyl tripeptide-5 is added.

[0127] Comparative Example 5

[0128] This comparative example provides a method for preparing single-peptide nanospheres, which is prepared using a method that is basically the same as that in Example 1. The difference is that in step (1), only 0.3g of palmitoyl tetrapeptide-7 is added.

[0129] Comparative Example 6

[0130] This comparative example provides another method for preparing permeation-enhancing skin nanocomposite sphere peptides, which is prepared using a method that is basically the same as that in Example 1. The difference is that in step (1), only 0.15g of palmitoyl tripeptide-1 and 0.15g of palmitoyl tetrapeptide-7 are added.

[0131] Comparative Example 7

[0132] This comparative example provides a method for preparing a blank vector, which is prepared using a method that is basically the same as that in Example 1. The difference is that no peptide is added in step (1), and in step (4), the first organic solvent is directly used to replace the first solution and added to the fourth solution for mixing to obtain a blank vector.

[0133] Comparative Example 8

[0134] This comparative example provides another method for preparing skin-penetrating nanocomposite spheroids, using essentially the same raw materials as in Example 1. The steps are as follows: directly mix appropriate amounts of palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, a first organic solvent, a second organic solvent, a first water, tococelen, and poloxamer, and stir to dissolve at 45°C.

[0135] Comparative Example 9

[0136] This comparative example provides another method for preparing skin-penetrating nanocomposite spheroids, the difference being that the second temperature is 80℃.

[0137] Comparative Example 10

[0138] This comparative example provides another method for preparing skin-penetrating nanocomposite spheroids, the difference being that the third temperature is 80℃.

[0139] Comparative Example 11

[0140] This comparative example provides another method for preparing transdermal nanocomposite spheroids, the difference being that the first rate is 0.5 mL / min.

[0141] Comparative Example 12

[0142] This comparative example provides another method for preparing transdermal nanocomposite spheroids, the difference being that the first rate is 8 mL / min.

[0143] Comparative Example 13

[0144] This comparative example provides another method for preparing transdermal nanocomposite spheroids, the difference being that the fourth temperature is 25℃.

[0145] Comparative Example 14

[0146] This comparative example provides another method for preparing skin-penetrating nanocomposite spheroids, the difference being that the fourth temperature is 80℃.

[0147] II. Morphology and Particle Size Characterization

[0148] The nanomicelle solution from Example 1 was drop-cast onto a copper mesh. After the copper mesh was air-dried at room temperature, its morphology was observed using a transmission electron microscope (TEM). The TEM image is shown below. Figure 1 As shown. Figure 1 As shown, the nanomicelles of Example 1 exhibit a transparent, uniform, and spherical morphology.

[0149] The nanomicelle solutions of Example 1, Comparative Example 1, and Comparative Example 7 were injected into the PS particle size cell or the U-shaped capillary sample cell (DTS0012). Dynamic light scattering was used to test the particle size and determine the particle size and zeta potential. The results are shown in Table 1.

[0150] Table 1. Measurement results of nanomicelle size and Zeta potential in Comparative Examples 1 and 7 of Example 1

[0151]

[0152] According to Table 1, the average particle size of the nanomicelles in Example 1 was 14.79 ± 0.05 nm, and the zeta potential was -5.711 ± 2.0 mV. The average particle size of the nanomicelles in Comparative Example 7 was 13.92 ± 0.50 nm, and the zeta potential was -8.15 ± 5.0 mV. This indicates that the nanomicelles in Example 1 had a negative surface charge. This negative surface charge promoted electrostatic repulsion between nanoparticles, thereby enhancing their dispersibility and contributing to the stability of the system.

[0153] The polydispersity index of the nanomicelles in Example 1 was 0.1369 ± 0.02, which was significantly lower than the polydispersity index of the nanomicelles in Comparative Example 1 (0.4386 ± 0.02), indicating that the molecular distribution uniformity of the nanomicelles in Example 1 was significantly improved. Furthermore, according to... Figure 2 The particle size distribution of the nanomicelles in Example 1 shows a single peak, while the particle size distribution of the nanomicelles in Comparative Example 1 shows multiple heterogeneous peaks, indicating that tocoxexyl in combination with poloxamer helps to improve the stability and dispersibility of the encapsulated peptides.

[0154] III. Performance Testing

[0155] (1) Light stability test

[0156] Following the light stability test conditions described in the 2020 edition of the Chinese Pharmacopoeia, "Guidelines for Stability Testing of Raw Materials and Preparations (9001)," the light stability of each example and comparative example was investigated. The state of each system after being placed in a light chamber for 0 and 14 days was observed and recorded. The test results of each example and comparative example are statistically summarized in Tables 2-1 and 2-2.

[0157] Table 2-1 Stability test results of Examples 1-12

[0158]

[0159] Table 2-2 Stability test results of Comparative Examples 1-14

[0160]

[0161] According to Tables 2-1 and 2-2, the nanomicelles of each embodiment showed no significant changes after 14 days of storage, with no crystallization or stratification, exhibiting good surface stability and no other stability issues, indicating that the embodiments have relatively good photostability. In contrast, most comparative examples (such as Comparative Examples 1-2 and 8-14) showed crystallization or significant color changes after 14 days of storage, indicating that the nanomicelles prepared in the comparative examples had poor stability.

[0162] The nanomicelle solution of Example 1 was transparent and clear, and the Tyndall effect could be observed when irradiated with a laser beam, confirming the formation of colloids. The results on day 14 showed that the nanomicelle solution of Example 1 remained transparent and clear, and the Tyndall effect could be observed when irradiated with a laser beam, indicating good photostability. This demonstrates the feasibility of this encapsulation scheme. Compared to Example 1, the results on day 0 of Comparative Examples 1 and 2 showed a small amount of suspended particles and partial precipitation in the nanomicelle solution, proving that the carrier in the system has limitations on the encapsulation of peptides. This indicates that only when both tococelenol and poloxamer are present as carriers can they synergistically enhance the solubility and stability of poorly soluble peptides. The nanomicelle solution of Comparative Example 8 was prepared using a completely different method, and a large number of suspended particles and partial precipitation were present from day 0. Comparative Example 9 used excessively high temperatures when preparing the tococelenol solution, causing partial oxidation of vitamin E in the tococelenol. The compound exhibited degradation (yellowing) of poloxamer. Although it was transparent and yellow on day 0, with the Tyndall effect observed, it turned yellow and turbid on day 14. This indicates that excessively high temperatures affect its micellization ability and synergistic stabilization with poloxamer, and micelles tend to aggregate after prolonged storage. In contrast, Comparative Example 10 used excessively high temperatures when preparing the poloxamer solution, leading to degradation and conformational changes in poloxamer. Although it was white and transparent on day 0, with the Tyndall effect observed, it turned white and turbid on day 14. This indicates that excessively high temperatures affect its micellization ability and synergistic stabilization with toxoxexron, and micelles tend to aggregate after prolonged storage. Comparative Example 11 showed that the complex peptide was added to the carrier solution at too slow a rate. The solution was semi-transparent on day 0 but turned white and turbid on day 14. This indicates that a slow addition rate is not conducive to the formation of uniform and dense nano-assembly nuclei, thus affecting the structural compactness of the aggregates. The system had high initial turbidity and was prone to sedimentation and stratification after long-term standing. Comparative Example 12 showed that the complex peptide was added to the carrier solution at too fast a rate. The solution was white and turbid on day 0. This may be because when the local peptide concentration was instantaneously too high, the self-assembly process driven by hydrophobic interactions was too violent and disordered, easily forming large flocs or precipitates, thus failing to form stable nanoparticles. Micelle dispersions; Comparative Example 13: The temperature at which the complex peptide was added to the carrier solution was too low, far below the suitable dissolution and unfolding temperatures of tococelen and poloxamer. The molecular chains of both were coiled up and could not effectively participate in and stabilize the self-assembly process of the peptide, so it was white and turbid on day 0. Comparative Example 14: The temperature at which the complex peptide was added to the carrier solution was too high. Although it may have accelerated molecular motion, it was far above the upper limit of the peptide's stability temperature, resulting in partial denaturation or degradation of the peptide. Therefore, it was yellow and transparent on day 0. At the same time, the micelles formed at high temperature may have aggregated, resulting in a yellow and turbid state on day 14, indicating poor long-term stability.

[0163] The above photostability test results show that Example 1 has the best stability. Therefore, the nanomicelle solution of Example 1 was selected for further testing of antioxidant properties, fibroblast type I and type III collagen synthesis / content, and hair growth.

[0164] (2) Evaluation of antioxidant efficacy

[0165] This experiment investigated the protective effect of skin-penetrating nanocomposite globulins against oxidative damage in human dermal papillary cells.

[0166] The DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) probe was used to assess the ROS scavenging capacity of the samples. HSF cells were seeded into 96-well and 24-well plates and cultured at 37°C for 12 hours. Blank, control, and experimental groups were set up. The experimental groups were co-cultured with the permeation-enhancing nanocomposite globulins (10× degradation products) from Examples 1 and Comparative Examples 3-7 for 4-6 hours. After culture, an equal volume of 50 μM H2O2 aqueous solution was added to the experimental and control groups; an equal volume of water was added to the blank group. After H2O2 treatment for 20-30 minutes, the old culture medium was discarded, and the cells were lightly washed twice with basal medium. Serum-free medium containing DCFH-DA (1 μL / mL) was added to each well, and the cells were cultured for another 20 minutes. The 24-well plates were imaged using an inverted fluorescence microscope, and the 96-well plates were quantitatively detected using a fluorescence and chemiluminescence microplate reader (excitation wavelength: 488 nm, emission wavelength: 525 nm). Light should be avoided during the experiment.

[0167] The results are as follows Figure 3 As shown, according to Figure 3 The smallest green fluorescence signal in the untreated blank group confirmed the healthy cell state with low basal ROS levels and no apoptosis trend. Treatment with 50 μM H2O2 significantly increased fluorescence intensity in the control group. Toxoxexole in the blank carrier of Comparative Example 7 showed some antioxidant capacity, but its fluorescence intensity was also reduced. The experimental groups treated with the composite globulin (Comparative Examples 3, 4, 5, 6, and Example 1) showed varying degrees of reduced fluorescence intensity, with Example 1 exhibiting the weakest fluorescence intensity among all treatment groups. This indicates that the nanomicelles of the composite peptide consisting of palmitoyl tripeptide-1, palmitoyl tripeptide-5, and palmitoyl tetrapeptide-7 have a better ability to scavenge intracellular reactive oxygen species (ROS) than nanomicelles of any single peptide or a composite peptide consisting of two peptides. This suggests that the composite globulin containing palmitoyl tripeptide-1, palmitoyl tripeptide-5, and palmitoyl tetrapeptide-7 can synergistically enhance the scavenging capacity of intracellular ROS.

[0168] (3) Evaluation of anti-aging efficacy

[0169] This experiment investigated the promoting effect of the skin-penetrating nanocomposite globulin on the synthesis of type I and type III collagen and elastin in fibroblasts.

[0170] HSF cells were seeded in 24-well plates and cultured until the cell density reached 80%-90%. A control group and an experimental group were set up. The experimental groups were treated with the permeation-enhancing nanocomposite globulin (10× degradation product) from Examples 1 and Comparative Examples 3-7, respectively. The control group was treated with an equal volume of TGF-β working solution. Cells were co-cultured for 24 h ± 2 h. After culture, the cell supernatant was collected, and the content of type I and type III collagen and elastin in the cell supernatant of each group was detected using an ELISA kit, following the kit instructions.

[0171] according to Figure 4 The blank vector in Comparative Example 7 could not promote protein synthesis. The single peptides or complex globular peptides in Comparative Examples 3, 4, 5, 6, and Example 1 promoted the synthesis of the three proteins to varying degrees. Among them, Example 1 had the strongest promoting effect on the synthesis of type II and III collagen and elastin in all treatment groups, indicating that the complex globular peptide containing palmitoyl tripeptide-1, palmitoyl tripeptide-5, and palmitoyl tetrapeptide-7 can synergistically enhance the synthesis capacity of type I and III collagen and elastin in fibroblasts.

[0172] (4) Evaluation of hair growth efficacy

[0173] Healthy male C57BL / 6 mice (6 weeks old) were selected and treated after acclimatizing to the laboratory environment for 7 days. Before the animal experiment, the hair on the back of the selected mice was evenly shaved (2cm × 2cm) using a power shaver, and then depilatory cream was applied to remove the remaining hair. The mice were randomly divided into 7 groups (n = 3): model group; minoxidil group (3% minoxidil, solvent: propylene glycol / ethanol / water = 3 / 3 / 4, v / v / v); experimental group (10ppm, 20ppm, 30ppm of the skin penetration-enhancing nanocomposite globulin of Example 1, solvent: propylene glycol / ethanol / water = 3 / 3 / 4, v / v / v).

[0174] Dihydrotestosterone (DHT) (0.2%, w / v) was dissolved in an ethanol solution (50%, v / v). Except for the blank control group, all other groups received topical application of DHT solution (0.1 mL / cm²) daily for 28 days to establish an androgenetic alopecia model. On day 1, the corresponding treatment drugs were applied topically to the backs of mice treated with 0.2% DHT solution (0.1 mL / cm² at intervals of several hours). 2 (This is a continuous treatment for 13 days. Throughout the treatment period, changes in the skin on the back of the mice were monitored by taking local images on days 1, 6, 10, and 14.)

[0175] See results Figure 5 .according to Figure 5 It is evident that the skin-penetrating nanocomposite globulin prepared in the 10-day model group significantly promoted hair growth in mice compared to the blank control group, indicating that this skin-penetrating nanocomposite globulin has a good promoting effect on hair growth. The skin-penetrating nanocomposite globulin prepared in the 14-day model group showed hair growth comparable to or even better than the 3% minoxidil group (positive control treatment group), demonstrating that this skin-penetrating nanocomposite globulin has excellent oil-controlling, hair loss-preventing, and anti-aging effects on the scalp.

[0176] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity, not all possible combinations of the technical features in the above-described embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0177] The embodiments described above merely illustrate several implementation methods of this application and should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Furthermore, it should be understood that after reading the above teachings, those skilled in the art can make various alterations or modifications to this application, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the protection scope of the appended claims. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. A skin-penetrating nanocomposite peptide, characterized in that, The preparation method of the skin penetration-enhancing nanocomposite spheropeptide includes the following steps: The complex peptide is added to a first organic solvent and mixed, and then ultrasonically dissolved at a first temperature to obtain a first solution; the complex peptide comprises components (i) to (iii): (i) palmitoyl tripeptide-1 or its derivative; (ii) palmitoyl tripeptide-5 or its derivative; (iii) palmitoyl tetrapeptide-7 or its derivative; the first organic solvent is an aliphatic polyol; the first temperature is 35℃-45℃; Toxoxelane is added to a second organic solvent and mixed, then heated at a second temperature to dissolve, thus obtaining a second solution; wherein the toxoxelane is polyethylene glycol succinate; the second organic solvent is an aliphatic polyol; and the second temperature is 40℃-60℃. Poloxamer is added to a first water and mixed, then heated to a third temperature to dissolve it, thus preparing a third solution; the third temperature is 40℃-60℃. The second solution and the third solution are mixed to obtain the fourth solution; The first solution is added to the fourth solution at a first rate and stirred and dispersed at a fourth temperature to obtain the aforementioned skin-penetrating nanocomposite spheroid peptide; the first rate is 1 mL / min-3 mL / min and the fourth temperature is 40℃-50℃.

2. The skin penetration-enhancing nanocomposite spheroid peptide according to claim 1, characterized in that, The first organic solvent and the second organic solvent each independently comprise one or more of the following: propylene glycol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, glycerol, dipropylene glycol, 1,2-hexanediol, 1,6-hexanediol, methylpropanediol (2-methyl-1,3-propanediol), trimethylolpropane, and pentaerythritol.

3. The skin penetration-enhancing nanocomposite spheroid peptide according to claim 1, characterized in that, The polyethylene glycol structural unit in the vitamin E succinate polyethylene glycol ester has a molecular weight of 500 Da-5000 Da.

4. The skin penetration-enhancing nanocomposite spheroid peptide according to claim 1, characterized in that, The polyoxyethylene content in the poloxamer is 70%-75% by mass, and the average molecular weight is 8000Da-15000Da.

5. A skin-penetration-enhancing nanocomposite peptide according to any one of claims 1-4, characterized in that, At least one of the following conditions must be met: (1) In the complex peptide, the mass ratio of components (i), (ii) and (iii) is 1:(0.8-1.2):(0.8-1.2); (2) The mass ratio of the complex peptide to the tococelen is (0.0001-0.5):(1-20); (3) The mass ratio of the tocosolvan and the poloxamer is (1-1.5):

1.

6. The skin penetration-enhancing nanocomposite spheroid peptide according to any one of claims 1-4, characterized in that, At least one of the following conditions must be met: (1) The weight percentage of the complex peptide in the first solution is 0.0001%-0.5%; (2) The toxoxelam in the second solution accounts for 20%-60% by weight; (3) The weight percentage of poloxamer in the third solution is 0.1%-5%.

7. The skin penetration-enhancing nanocomposite peptide according to any one of claims 1-4, characterized in that, In the step of adding the first solution to the fourth solution at a first rate and stirring and dispersing at a fourth temperature, the stirring and dispersing speed is 100 rpm to 600 rpm.

8. The application of the skin penetration-enhancing nanocomposite spheropeptide according to any one of claims 1-7 in the preparation of cosmetics.

9. The application according to claim 8, characterized in that, The cosmetic product in question is an antioxidant product.

10. The application according to claim 8, characterized in that, The cosmetics mentioned are products used for scalp oil control, hair loss prevention, and anti-aging.

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