Targeted energy metabolism composition for improving anti-aging effect of skin as well as preparation method and application of targeted energy metabolism composition

Abstract

The invention discloses a targeted energy metabolism composition for improving the anti-aging effect of skin as well as a preparation method and application of the targeted energy metabolism composition. The targeted energy metabolism composition is prepared from the following components in parts by mass: 0.1 to 5 parts of saccharomycetes rice fermentation filtrate, 0.1 to 5 parts of a tremella aurantialba sporocarp extract and 0.01 to 5 parts of nicotinamide mononucleotide NMN liposome. According to the targeted energy metabolism composition for improving the anti-aging effect of the skin and the preparation method and application of the targeted energy metabolism composition, effective permeation and precise delivery of functional components can be achieved, and the anti-aging, whitening and moisturizing effects of the skin are improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of cosmetic ingredients, and relates to a targeted energy metabolism composition, in particular to a targeted energy metabolism composition for improving skin anti-aging effect and a preparation method and application thereof. BACKGROUND

[0002] With the rapid development of society, people's living standards and quality of life have been greatly improved, and more and more people have begun to pursue and pay attention to their own maintenance. Among them, skin aging and anti-aging is one of the most discussed topics. According to relevant data, at present, anti-aging cosmetics and skin care products have accounted for more than 50% of the global cosmetic market share, and consumers are in urgent need of efficient and precise anti-aging solutions.

[0003] In recent years, scientific research in the relevant field has continued to deepen, and the secrets and mechanisms of skin aging have gradually become clear. At present, it has been reported that cell energy metabolism decline is the main cause of skin aging, which is manifested in three aspects:

[0004] (1) Mitochondrial dysfunction: with age, mitochondrial DNA damage accumulates, mitochondrial internal structure is damaged, leading to decreased ATP production efficiency, increased ROS (reactive oxygen species), accelerated collagen degradation and inflammatory response, and accelerated skin aging.

[0005] (2) Decreased NAD+ level: NAD+ is oxidized nicotinamide adenine dinucleotide, and external factors such as ultraviolet radiation reduce the NAD+ content of the skin, inhibit the activity of SIRTUIN protein, and trigger cell aging and pigment deposition.

[0006] (3) Decreased barrier repair capacity: energy deficiency leads to reduced synthesis of barrier proteins (such as filaggrin and AQP3) of keratinocytes, increased skin water loss, and skin susceptible to external stimuli, accelerating skin aging.

[0007] According to the molecular principle of skin aging, a large number of related products and technologies have been developed as an entry point to achieve the effects of anti-aging and whitening and skin repair through cell metabolism regulation. However, the existing technologies mostly adopt a single-dimensional solution, starting from a certain aspect of skin aging, such as using vitamin C as an antioxidant to inhibit the increase of ROS (reactive oxygen species) in cells, but this does not fully consider the multiple causes of skin aging, and can only improve the skin condition to a certain extent, and cannot solve the problem of skin cell energy metabolism decline from the root. In addition, some anti-aging products contain macromolecular active ingredients, which are difficult to enter the skin due to the lack of effective packaging and delivery technology, and have very limited improvement effect on the skin.

[0008] The existing research on skin care products ignores multiple causes and pathways of skin aging, and the effect of single-dimensional improvement is limited. Skin aging is the result of the combined action of multiple factors. The existing skin care products are designed to improve the skin condition by targeting a specific cause of skin aging. For example, vitamin C is used as an antioxidant to scavenge intracellular ROS (reactive oxygen species) and reduce the damage of ROS to organelles and cell structures. Although this method can improve the skin condition to some extent, the problem of energy metabolism decline in skin cells has not been effectively solved. Once the product is stopped, the skin condition is likely to deteriorate.

[0009] The efficacy ingredients of existing skin care products lack effective delivery means and are difficult to penetrate the skin barrier with low utilization efficiency. For the regulation of cellular energy metabolism, a considerable part of the efficacy ingredients used in existing technologies have substances with large molecular weight or are difficult to penetrate the skin barrier, such as polypeptides and nicotinamide mononucleotides. If these ingredients are not specially packaged or treated, they are likely to fail to penetrate the dermis and other internal structures of the skin, resulting in low skin penetration and absorption rate. In addition, long-term exposure of such ingredients on the skin surface is also likely to lose activity due to environmental factors, shorten the action time, and fail to continuously repair and improve the skin condition.

[0010] Therefore, there is an urgent need to design a new skin care ingredient to overcome at least some of the above-mentioned deficiencies of existing skin care ingredients. SUMMARY

[0011] The present application provides a targeted energy metabolism composition for improving skin anti-aging effect and a preparation method and application thereof, which can realize effective penetration and precise delivery of efficacy ingredients, and improve the effect of skin anti-aging, whitening and moisturizing.

[0012] To solve the above technical problems, according to one aspect of the present application, the following technical solution is adopted:

[0013] A targeted energy metabolism composition for improving skin anti-aging effect, comprising: a yeast rice fermentation filtrate with a mass fraction of 0.1-5, a gold ear fruiting body extract with a mass fraction of 0.1-5, and a nicotinamide mononucleotide NMN liposome with a mass fraction of 0.01-5.

[0014] As an embodiment of the present application, the mass ratio of the yeast rice fermentation filtrate, the gold ear fruiting body extract and the nicotinamide mononucleotide NMN liposome is (0.5-3):(0.1-3):(0.1-3).

[0015] As an embodiment of the present application, the nicotinamide mononucleotide NMN liposome is treated by liposome wrapping. The raw materials treated by liposome wrapping include membrane material components, solvents and buffers.

[0016] As an embodiment of the present application, the film material comprises phospholipids and sterols, the phospholipids are selected from at least one of hydrogenated soybean lecithin, soybean lecithin, egg yolk lecithin, hydrogenated egg yolk lecithin, and the sterols are selected from at least one of phytosterol oleate, cholesterol, stigmasterol, and sterylamine; the solvent is selected from at least one of anhydrous ethanol and methanol; and the buffer is selected from at least one of phosphate buffer and citrate buffer.

[0017] As an embodiment of the present application, the raw material treated by the liposome wrapping process further comprises a stabilizer / freeze-drying protective agent; the stabilizer / freeze-drying protective agent is selected from at least one of sucrose, trehalose, mannitol, vitamin E, and vitamin C palmitate.

[0018] As an embodiment of the present application, the preparation method of the nicotinamide mononucleotide NMN liposome comprises the following steps:

[0019] Lipid film preparation: transfer the above mixture to a rotary evaporator, rotate at 60-100 rpm under the condition of 35-45°C and a vacuum degree of ≤100 mbar, and completely evaporate the residual solvent until a uniform transparent lipid film is formed on the bottle wall.

[0020] Lipid film preparation: transfer the above mixture to a rotary evaporator, rotate at 60-100 rpm under the condition of 35-45°C and a vacuum degree of ≤100 mbar, and completely evaporate the residual solvent until a uniform transparent lipid film is formed on the bottle wall.

[0021] NMN aqueous solution preparation: weigh a certain amount of NMN (1-3% w / v according to the final liposome suspension concentration), add a 35-40°C preheated buffer (pH 5.5-6.0), and ultrasonically assist dissolution (power 150-250W) for 3-7 min until a clear solution is formed.

[0022] Liposome hydration wrapping: add the NMN aqueous solution to the flask containing the lipid film, with a lipid to water phase volume ratio of 1:8-1:12, a water bath temperature of 35-40°C, and magnetic stirring hydration for 40-80 min (rotation speed 80-120 rpm) until the lipid film is completely detached and an initial emulsion-like liposome suspension is formed.

[0023] Particle size optimization: transfer the suspension to an ultrasonic cell disruptor in an ice water bath, reduce the liposome particle size by probe sonication, power 250-350W, pulse mode: work for 2-4s, pause for 4-6s, total time 10-20min, until the suspension is translucent.

[0024] Free NMN removal: The obtained suspension was loaded into a dialysis bag with a molecular weight cutoff of 2000-4000 Da and placed in a buffer, dialyzed at 2-6°C for 8-16 hours, and the buffer was replaced every 4 hours to remove free NMN that was not encapsulated.

[0025] Stability treatment: ① Short-term storage: 0.05-0.2% stabilizer (such as vitamin E) was added to the NMN liposome solution, which was stored at 2-6°C in the dark (storage period ≤3 months). ② Long-term storage: 3-7% lyophilization protectant (such as sucrose) was added to the NMN liposome solution, which was freeze-dried (-35 to -45°C pre-freezing for 1-3 hours, vacuum degree ≤10 mTorr, temperature rising rate 0.5-1.5°C / min) to prepare a freeze-dried powder, which was reconstituted with a buffer before use.

[0026] According to another aspect of the present application, the following technical solution is adopted: a preparation method of the above-mentioned targeted energy metabolism composition for improving skin anti-aging effect, the preparation method comprising:

[0027] Preparation of nicotinamide mononucleotide NMN liposomes;

[0028] The mass fraction of 0.1-5 of the yeast rice fermentation filtrate, the mass fraction of 0.1-5 of the gold ear fruit body extract, and the mass fraction of 0.01-5 of the nicotinamide mononucleotide NMN liposomes are mixed to prepare a targeted energy metabolism composition.

[0029] As an embodiment of the present application, the step of preparing nicotinamide mononucleotide NMN liposomes comprises:

[0030] Lipid membrane material preparation: hydrogenated soybean lecithin and phytosteryl oleate were mixed in a mass ratio of (2-4):1, and the mixture was dissolved in a solvent (1 g of mixed lipids plus 8-12 mL of solvent). The mixture was stirred in a water bath at 45-55°C for 15-45 min until completely dissolved, forming a clear and transparent mixture with a concentration of 80-120 mg / mL.

[0031] Lipid film preparation: the above mixture was transferred to a rotary evaporator, and the residual solvent was completely evaporated under the conditions of 35-45°C and a vacuum degree of ≤100 mbar (rotation speed 60-100 rpm) until a uniform and transparent lipid film was formed on the bottle wall.

[0032] NMN aqueous solution preparation: a certain amount of NMN (1-3% w / v according to the final liposome suspension concentration) was weighed and added to a preheated buffer (pH 5.5-6.0) at 35-40°C, and ultrasonic assisted dissolution (power 150-250 W) was performed for 3-7 min until a clear solution was formed.

[0033] Liposome hydration package: add NMN aqueous solution to a flask containing a lipid film, wherein the volume ratio of lipid to aqueous phase is 1:8-1:12, the water bath temperature is 35-40℃, and the magnetic stirring hydration is 40-80min (rotation speed 80-120rpm) until the lipid film is completely removed and the initial emulsion liposome suspension is formed.

[0034] Particle size optimization: transfer the suspension to an ultrasonic cell disruptor in an ice water bath, reduce the particle size of the liposome by probe sonication, power 250-350W, pulse mode: work 2-4s, pause 4-6s, total time 10-20min, until the suspension is translucent.

[0035] Free NMN removal: the obtained suspension is loaded into a dialysis bag with a molecular weight cutoff of 2000-4000Da, and placed in a buffer, dialyzed at 2-6℃ for 8-16h, and the buffer is replaced every 4h to remove the unencapsulated free NMN.

[0036] Stability treatment: ① short-term storage: add 0.05-0.2% stabilizer (such as vitamin E) to the NMN liposome solution, store in the dark at 2-6℃ (storage period ≤3 months). ② long-term storage: add 3-7% lyophilization protectant (such as sucrose) to the NMN liposome solution, freeze-dry (-35- -45℃ pre-freeze 1-3h, vacuum degree ≤10mTorr, temperature rise rate 0.5-1.5℃ / min) to make lyophilized powder, and reconstitute with buffer before use.

[0037] According to another aspect of the present application, the following technical solution is adopted: the use of the above-mentioned targeted energy metabolism composition for improving skin anti-aging effect in the preparation of skin care products.

[0038] As an embodiment of the present application, the skin care product includes skin care water or serum or emulsion or cream.

[0039] The present application has the advantages that the targeted energy metabolism composition for improving skin anti-aging effect and its preparation method and application can realize effective penetration and precise delivery of active ingredients, and improve the effects of skin anti-aging, whitening and moisturizing.

[0040] The present application breaks through the single-dimensional anti-aging mode and constructs a metabolic regulation combination system taking yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide (NMN) as main components. The yeast rice fermentation filtrate has antioxidant and barrier repair effects. On the one hand, the antioxidant components in the yeast rice fermentation filtrate can scavenge intracellular ROS (reactive oxygen species), avoid damage to the structure of mitochondria, maintain the normal function of mitochondria, and promote the synthesis of ATP. On the other hand, the polysaccharide substances in the yeast rice fermentation filtrate can bind to the epidermal growth factor receptor (EGFR) to activate the cell signaling pathway and promote the proliferation and differentiation of keratinocytes. The gold ear fruiting body extract can reduce mitochondrial DNA damage, regulate mitochondrial energy metabolism-related enzyme activity, and enhance skin barrier function. Nicotinamide mononucleotide, as a direct precursor of NAD+, can accelerate cell energy metabolism cycle, increase NAD+ level, activate SIRTUIN pathway, delay cell aging, and inhibit melanin synthesis. At the same time, the nicotinamide mononucleotide is wrapped in liposomes, which can realize effective penetration and accurate delivery of the active ingredients. The synergistic use of these components forms a three-dimensional regulation network of mitochondrial structure protection-energy activation-barrier repair.

[0041] The present application uses liposome wrapping technology to improve penetration and delivery efficiency and uses multiple components to construct a three-dimensional regulation network of mitochondrial structure protection-energy activation-barrier repair.

[0042] The present application uses yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide as core components, and uses liposome technology to wrap nicotinamide mononucleotide into small particles, which overcomes the problem of low penetration and delivery efficiency of nicotinamide mononucleotide in traditional technology and greatly improves the absorbability. In addition, the synergistic use of yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide can regulate cell energy metabolism from multiple dimensions.

[0043] Dimension one: yeast rice fermentation filtrate has antioxidant and barrier repair effects. On the one hand, the antioxidant components in the yeast rice fermentation filtrate can scavenge intracellular ROS (reactive oxygen species), avoid damage to the structure of mitochondria, maintain the normal function of mitochondria, and promote the synthesis of ATP. On the other hand, the polysaccharide substances in the yeast rice fermentation filtrate can bind to the epidermal growth factor receptor (EGFR) to activate the cell signaling pathway and promote the proliferation and differentiation of keratinocytes.

[0044] Dimension two: gold ear fruiting body extract can act on cells from the dermis to the epidermis to achieve antioxidant, anti-aging and moisturizing effects.

[0045] Dimension three: nicotinamide mononucleotide liposome can supplement NAD+, promote ATP generation, double the cell energy metabolism with yeast rice fermentation filtrate, activate SIRTUIN pathway, inhibit melanin synthesis enzyme related gene expression, and achieve anti-aging and whitening effects.

[0046] The three components of the yeast rice fermentation filtrate, the gold ear fruiting body extract and the nicotinamide mononucleotide liposome have both parallel and cross functions, forming a three-dimensional regulation network of cell energy metabolism. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 The flow chart of the preparation method of the nicotinamide mononucleotide liposome in an embodiment of the present application. DETAILED DESCRIPTION

[0048] The preferred embodiments of the present application will be described in detail below with reference to the accompanying drawings.

[0049] In order to further understand the present application, the preferred embodiments of the present application will be described below in conjunction with the examples, but it should be understood that these descriptions are only for further illustrating the features and advantages of the present application, and are not limitations to the claims of the present application.

[0050] The description of this part is only for several typical embodiments, and the present application is not limited to the scope described in the embodiments. The same or similar prior art means and some technical features in the embodiments can be replaced with each other, which is also within the description and protection scope of the present application.

[0051] Unless otherwise indicated, implied from the context, or customary in the art, all parts and percentages in this application are based on weight, and the test and characterization methods used are synchronized with the filing date of this application. In applicable cases, the contents of any patents, patent applications or publications referred to in this application are incorporated herein by reference in their entirety, and their equivalent homologous patents are also introduced by reference, especially the definitions disclosed in these documents regarding the synthesis technology, product and processing design, polymer, comonomer, initiator or catalyst in the art. If the definition of a specific term disclosed in the prior art is inconsistent with any definition provided in this application, the definition of the term provided in this application shall prevail.

[0052] The numerical ranges in this application are approximate values ​​and therefore may include values ​​outside the range unless otherwise stated. A numerical range includes all values ​​from the lower limit to the upper limit, increasing by one unit, provided there is an interval of at least two units between any lower and any higher value. For example, if a component, physical, or other property (such as molecular weight, melt index, etc.) is described as 100 to 1000, this means that all individual values, such as 100, 101, 102, etc., are explicitly listed, as well as all subranges, such as 100 to 166, 155 to 170, 198 to 200, etc. For ranges containing values ​​less than 1 or fractions greater than 1 (e.g., 1.1, 1.5, etc.), one unit is appropriately considered as 0.0001, 0.001, 0.01, or 0.1. For ranges containing single digits less than 10 (e.g., 1 to 5), one unit is generally considered as 0.1. These are merely specific examples of what is intended to be expressed, and all possible combinations of values ​​between the listed minimum and maximum values ​​are considered to be clearly stated in this application. It should also be noted that the terms "first," "second," etc., used herein are not intended to specify a particular order, but are merely used to distinguish substances with different structures.

[0053] When referring to chemical compounds, unless explicitly stated otherwise, the singular includes all isomers and vice versa (e.g., "hexane" includes all isomers of hexane, individually or collectively). Additionally, unless explicitly stated otherwise, nouns described with "an," "a," or "the" also include their plural forms.

[0054] The terms “comprising,” “including,” “having,” and their derivatives do not exclude the presence of any other components, steps, or processes, regardless of whether such other components, steps, or processes are disclosed in this application. To eliminate any doubt, unless expressly stated otherwise, all compositions using the terms “comprising,” “including,” or “having” in this application may contain any additional additives, excipients, or compounds. Conversely, except for those necessary for operational performance, the term “substantially constitutes…” excludes any other components, steps, or processes described below with respect to that term. The term “consisting of…” does not include any components, steps, or processes not specifically described or listed. Unless expressly stated otherwise, the term “or” refers to the individual members listed or any combination thereof.

[0055] The steps described in the various embodiments in the specification are for illustrative purposes only, and the implementation of this application is not limited by the order of the steps.

[0056] The application discloses a targeted energy metabolism composition for improving skin anti-aging effect, which comprises: 0.1-5 mass parts of yeast rice fermentation filtrate, 0.1-5 mass parts of gold ear fruiting body extract, and 0.01-5 mass parts of nicotinamide mononucleotide NMN liposome.

[0057] In an embodiment, the mass ratio of the yeast rice fermentation filtrate, the gold ear fruiting body extract and the nicotinamide mononucleotide NMN liposome can be (0.5-3):(0.1-3):(0.1-3).

[0058] In an embodiment of the application, the nicotinamide mononucleotide NMN liposome is subjected to liposome encapsulation treatment, and the raw material for the liposome encapsulation treatment comprises a membrane material component, a solvent and a buffer solution. The membrane material comprises phospholipids and sterols, the phospholipids are selected from at least one of hydrogenated soybean lecithin, soybean lecithin, egg yolk lecithin and hydrogenated egg yolk lecithin, and the sterols are selected from at least one of phytosterol oleate, cholesterol, sitosterol and stigmasterol; the solvent is selected from at least one of anhydrous ethanol and methanol; and the buffer solution is selected from at least one of a phosphate buffer solution and a citrate buffer solution. The raw material for the liposome encapsulation treatment can further comprise a stabilizer / freeze-drying protective agent, and the stabilizer / freeze-drying protective agent is selected from at least one of sucrose, trehalose, mannitol, vitamin E and vitamin C palmitate.

[0059] In an embodiment, the nicotinamide mononucleotide NMN is subjected to liposome encapsulation treatment, and the raw material for the liposome encapsulation treatment comprises hydrogenated soybean lecithin, phytosterol oleate, anhydrous ethanol, a phosphate buffer solution, and sucrose or vitamin E.

[0060] Figure 1 The flow chart of the preparation method of the nicotinamide mononucleotide liposome in an embodiment of the application; please refer to Figure 1 In an embodiment of the application, the preparation method of the nicotinamide mononucleotide NMN liposome comprises the following steps:

[0061] Lipid membrane material preparation: hydrogenated soybean lecithin and phytosterol oleate are mixed at a mass ratio of (2-4):1, and the mixture is dissolved in a solvent (1g of mixed lipids plus 8-12mL of solvent), 45-55℃ water bath, magnetic stirring for 15-45min until complete dissolution, forming a clear and transparent mixture with a concentration of 80-120mg / mL.

[0062] Lipid thin film preparation: the above mixture is transferred to a rotary evaporator, 35-45℃, vacuum degree ≤100mbar, rotary evaporation (rotation speed 60-100rpm), and the residual solvent is completely volatilized until a uniform and transparent lipid thin film is formed on the bottle wall.

[0063] NMN aqueous solution preparation: weigh a certain amount of NMN (1-3% w / v final concentration of liposome suspension), add 35-40℃ preheated buffer (pH 5.5-6.0), and dissolve it with ultrasonic assistance (power 150-250W) for 3-7min until a clear solution is formed.

[0064] Liposome hydration encapsulation: add NMN aqueous solution to the flask containing the lipid film, with a volume ratio of lipid to aqueous phase of 1:8-1:12, 35-40℃ water bath, and magnetically stir for 40-80min (speed 80-120rpm) until the lipid film is completely detached and an initial emulsion-like liposome suspension is formed.

[0065] Particle size optimization: transfer the suspension to an ultrasonic cell disruptor in an ice water bath, reduce the liposome particle size by probe sonication, power 250-350W, pulse mode: work for 2-4s, pause for 4-6s, total time 10-20min, until the suspension is translucent.

[0066] Free NMN removal: load the resulting suspension into a dialysis bag with a molecular weight cutoff of 2000-4000Da, and place it in buffer, dialyze at 2-6℃ for 8-16h, and replace the buffer every 4h to remove unencapsulated free NMN.

[0067] Stability treatment: ①Short-term storage: add 0.05-0.2% stabilizer (such as vitamin E) to the NMN liposome solution, store in the dark at 2-6℃ (storage period ≤3 months). ②Long-term storage: add 3-7% lyophilization protectant (such as sucrose) to the NMN liposome solution, freeze-dry it (-35- -45℃ pre-freeze for 1-3h, vacuum degree ≤10mTorr, temperature rise rate 0.5-1.5℃ / min) to make a lyophilized powder, and reconstitute it with buffer before use.

[0068] In an embodiment of the present application, the preparation method of the nicotinamide mononucleotide NMN liposome comprises the following steps:

[0069]

Step S1

[0070]

Step S2

[0071]

Step S3

[0072]

Step S4

[0073]

Step S5

[0074]

Step S6

[0075]

Step S7

[0076] The yeast rice fermentation filtrate contains various active ingredients, which have antioxidant and barrier repair effects. Among them, polypeptide components such as glutathione and antioxidant peptides can scavenge intracellular ROS (reactive oxygen species), avoid damage to mitochondrial structure, thereby maintaining the normal function of mitochondria and promoting ATP synthesis. In addition, polysaccharide substances in the yeast rice fermentation filtrate can bind to epidermal growth factor receptor (EGFR), activate cell signaling pathways, and promote the proliferation and differentiation of keratinocytes.

[0077] The fruiting body extract of Tremella aurantialba has the effects of antioxidation, anti-aging and moisture retention. Specifically, (1) the molecular structure of Tremella aurantialba polysaccharide has the ability to capture free radicals, reduces the damage of ROS to mitochondrial DNA, and at the same time, the polysaccharide can also activate the expression of related genes and regulate the enzyme activity related to mitochondrial energy metabolism. (2) The fruiting body extract of Tremella aurantialba can improve the activity of hyaluronic acid synthase and promote the synthesis of endogenous hyaluronic acid in the dermal layer cells. In addition, the fruiting body extract of Tremella aurantialba can also activate the PI3K / Akt pathway, promote the expression and localization of aquaporin 3 (AQP3) in the basement membrane of keratinocytes, and realize the whole layer repair from the dermal layer to the epidermal layer. (3) The fruiting body extract of Tremella aurantialba can enhance the activity of SIRT1, deacetylate related proteins, and then inhibit the release of cell aging-related factors and inflammatory factors.

[0078] Nicotinamide mononucleotide (NMN) is a direct precursor of oxidized nicotinamide adenine dinucleotide (NAD+). NAD+ acts as a hydrogen acceptor in the mitochondrial electron transport chain, accepts electrons and is reduced to NADH, and promotes ATP synthesis. In skin cells, processes such as collagen synthesis and barrier repair are highly dependent on ATP supply. When nicotinamide mononucleotide (NMN) liposomes and yeast rice fermentation filtrate are used together, they can promote ATP synthesis from two aspects, enhance the efficiency of cell energy metabolism, and promote barrier repair. In addition, NAD+ can also combine with SIRTUIN family deacetylases to exert activity, regulate the acetylation and deacetylation process of related proteins, on the one hand, reduce the release of aging-related secretory phenotype inflammatory factors, and on the other hand, inhibit the expression of melanin synthase-related genes, and have anti-aging and whitening effects.

[0079] The effects of the three components of yeast rice fermentation filtrate, Tremella aurantialba fruiting body extract and nicotinamide mononucleotide (NMN) liposomes are both parallel and have overlapping parts, forming a three-dimensional regulatory network of cell energy metabolism.

[0080] The present application also discloses a preparation method of the above-mentioned targeted energy metabolism composition for improving skin anti-aging effect, which comprises the following steps:

[0081] Preparation of nicotinamide mononucleotide NMN liposomes;

[0082] Mixing 0.1-5 parts by mass of yeast rice fermentation filtrate, 0.1-5 parts by mass of Tremella aurantialba fruiting body extract and 0.01-5 parts by mass of nicotinamide mononucleotide NMN liposomes to prepare a targeted energy metabolism composition.

[0083] Figure 1 It is a flow chart of the preparation method of nicotinamide mononucleotide liposomes in an embodiment of the present application; please refer to Figure 1In one embodiment of the present invention, the method for preparing the nicotinamide mononucleotide (NMN) liposomes includes the following steps:

[0084] Lipid membrane preparation: Mix hydrogenated soybean lecithin and phytosterol oleate at a mass ratio of (2-4):1, and dissolve the mixture in a solvent (1g of mixed lipids plus 8-12mL of solvent). Heat in a water bath at 45-55℃ and stir magnetically for 15-45min until completely dissolved to form a clear and transparent mixture with a concentration of 80-120mg / mL.

[0085] Lipid film preparation: Transfer the above mixture to a rotary evaporator and rotary evaporate at 35-45°C and a vacuum of ≤100 mbar (60-100 rpm) until the residual solvent is completely evaporated and a uniform and transparent lipid film is formed on the bottle wall.

[0086] Preparation of NMN aqueous solution: Weigh a certain amount of NMN (1-3% w / v according to the final liposome suspension concentration), add a buffer solution preheated at 35-40℃ (pH 5.5-6.0), and sonicate to dissolve (power 150-250W) for 3-7 minutes until a clear solution is formed.

[0087] Liposome hydration and encapsulation: Add NMN aqueous solution to a flask containing a lipid film, wherein the volume ratio of lipid to water phase is 1:8 to 1:12. Hydrate at 35 to 40°C with magnetic stirring for 40 to 80 minutes (80 to 120 rpm) until the lipid film is completely detached, forming an initial emulsified liposome suspension.

[0088] Particle size optimization: The suspension was transferred to an ultrasonic cell disruptor in an ice-water bath. The probe ultrasonic method was used to reduce the size of the liposomes. The power was 250-350W, and the pulse mode was used: 2-4 seconds of operation followed by 4-6 seconds of pause, with a total time of 10-20 minutes, until the suspension became semi-transparent.

[0089] Free NMN removal: The obtained suspension was placed in a dialysis bag with a molecular weight cutoff of 2000-4000 Da and then placed in a buffer solution. Dialysis was performed at 2-6°C for 8-16 hours, with the buffer solution being changed every 4 hours to remove unencapsulated free NMN.

[0090] Stability treatment: ① Short-term storage: Add 0.05-0.2% stabilizer (such as vitamin E) to the NMN liposome solution and refrigerate at 2-6℃ protected from light (shelf life ≤ 3 months). ② Long-term storage: Add 3-7% lyophilization protectant (such as sucrose) to the NMN liposome solution, and freeze-dry (pre-freeze at -35 to -45℃ for 1-3 hours, vacuum degree ≤ 10 mTorr, heating rate 0.5-1.5℃ / min) to prepare lyophilized powder. Reconstitute with buffer solution before use.

[0091] In an embodiment of the present application, the preparation method of the nicotinamide mononucleotide NMN liposome comprises the following steps:

[0092] [Step S1] Lipid membrane material preparation: Take hydrogenated soybean lecithin and phytosterol oleate at a mass ratio of 3:1, and take a certain amount of the mixture and dissolve it in anhydrous ethanol (1 g of mixed lipid plus 10 mL of anhydrous ethanol), 50°C water bath, magnetic stirring for 30 min to completely dissolve, forming a clear and transparent mixture with a concentration of 100 mg / mL.

[0093] [Step S2] Lipid film preparation: Transfer the above 100 mg / mL mixture to a rotary evaporator, 40°C, vacuum degree ≤100 mbar, rotary evaporation (rotation speed 80 rpm), and the residual ethanol is completely volatilized until a uniform transparent lipid film is formed on the bottle wall.

[0094] [Step S3] Preparation of NMN aqueous solution: Weigh a certain amount of NMN (2% w / v final liposome suspension concentration, 100 mL suspension plus 2 g NMN), then add 37°C preheated phosphate buffer (pH 5.5-6.0), and ultrasonic assisted dissolution (power 200W) for 5 min until a clear solution is formed.

[0095] [Step S4] Liposome hydration and encapsulation: Add NMN aqueous solution to the flask containing the lipid film, with a lipid to water phase volume ratio of 1:10, a 37°C water bath, and magnetic stirring for 60 min (100 rpm) until the lipid film is completely removed and an initial emulsion-like liposome suspension is formed.

[0096] [Step S5] Particle size optimization: Transfer the suspension to an ultrasonic cell disruptor in an ice water bath, and use probe sonication to reduce the size of the liposome particles, power 300W, pulse mode: work for 3s, pause for 5s, total time 15min, until the suspension is translucent.

[0097] [Step S6] Free NMN removal: The resulting suspension is placed in a dialysis bag with a molecular weight cutoff of 3000 Da and placed in a phosphate buffer, dialyzed at 4°C for 12h, and the buffer is replaced every 4h to remove the unencapsulated free NMN.

[0098] [Step S7] Stability treatment: ① Short-term storage: Add 0.1% vitamin E to the NMN liposome solution, store at 4°C in the dark (storage period ≤3 months). ② Long-term storage: Add 5% sucrose (lyophilization protectant) to the NMN liposome solution, freeze-dry (-40°C pre-freezing for 2 hours, vacuum degree ≤10 mTorr, temperature rise rate 1°C / min) to obtain a freeze-dried powder, which is reconstituted with phosphate buffer before use.

[0099] The application also discloses application of the targeted energy metabolism composition for improving skin anti-aging effect in preparation of skin care products.

[0100] In order to further explain the role and effect of each component in the application, the following examples and comparative examples are used to carry out tests:

[0101] Example 1

[0102] The composition of the application is composed of the following components: 0.5 parts of yeast rice fermentation filtrate, 0.1 parts of tremella fuciformis fruiting body extract, and 0.1 parts of nicotinamide mononucleotide liposome.

[0103] Example 2

[0104] The composition of the application is composed of the following components: 1.5 parts of yeast rice fermentation filtrate, 1.3 parts of tremella fuciformis fruiting body extract, and 1.5 parts of nicotinamide mononucleotide liposome.

[0105] Example 3

[0106] The composition of the application is composed of the following components: 3 parts of yeast rice fermentation filtrate, 3 parts of tremella fuciformis fruiting body extract, and 3 parts of nicotinamide mononucleotide liposome.

[0107] Comparative Example 1

[0108] The composition of the application is composed of the following components: 0 parts of yeast rice fermentation filtrate, 0.4 parts of tremella fuciformis fruiting body extract, and 0.3 parts of nicotinamide mononucleotide liposome.

[0109] Comparative Example 2

[0110] The composition of the application is composed of the following components: 0.5 parts of yeast rice fermentation filtrate, 0 parts of tremella fuciformis fruiting body extract, and 0.2 parts of nicotinamide mononucleotide liposome.

[0111] Comparative Example 3

[0112] The composition of the application is composed of the following components: 0.5 parts of yeast rice fermentation filtrate, 0.2 parts of tremella fuciformis fruiting body extract, and 0 parts of nicotinamide mononucleotide liposome.

[0113] Comparative Example 4

[0114] The composition of the application is composed of the following components: 0 parts of yeast rice fermentation filtrate, 0 parts of tremella fuciformis fruiting body extract, and 0.7 parts of nicotinamide mononucleotide liposome.

[0115] Comparative Example 5

[0116] The composition of the application is composed of the following components: 0 parts of yeast rice fermentation filtrate, 0.7 parts of tremella fuciformis fruiting body extract, and 0 parts of nicotinamide mononucleotide liposome.

[0117] Comparative Example 6

[0118] The composition of the present application consists of: 0.7 parts of yeast-rice fermentation filtrate, 0 parts of gold ear fruiting body extract, and 0 parts of nicotinamide mononucleotide liposome.

[0119] Blank Comparative Example 7

[0120] The composition of the present application consists of: 0 parts of yeast-rice fermentation filtrate, 0 parts of gold ear fruiting body extract, and 0 parts of nicotinamide mononucleotide liposome.

[0121] The compositions prepared in the above examples and comparative examples can be used in skin care products. The types of skin care products include, but are not limited to, skin care water, serum, emulsion, cream, etc. In preparation, in addition to the above-mentioned composition, the skin care product also includes the base ingredients necessary for the preparation of various skin care products. The base ingredients can be selected from conventional base ingredients of various products in the prior art, and the skin care product preparation method is prepared according to the conventional method in the prior art.

[0122] In order to verify the excellent effect of a composition targeting energy metabolism, the compositions prepared in the above examples and comparative examples were prepared into serums.

[0123] A skin care product containing yeast-rice fermentation filtrate, gold ear fruiting body extract, and nicotinamide mononucleotide (NMN) liposome, specifically a serum, has the following component contents:

[0124] Table 1: Serum formulation ratio table

[0125]

[0126] Table 2: Composition content table in serum

[0127]

[0128] Note: The amount of each component in the above table is the mass percentage content, and can be obtained through commercial channels.

[0129] The difference between Examples 1-3 is the content of each functional ingredient. The difference between Comparative Examples 1-3 and Example 1 is that only one key functional ingredient is missing. The difference between Comparative Examples 4-6 and Example 1 is that only two key functional ingredients are missing. The difference between Blank Comparative Example 7 and Example 1 is that Blank Comparative Example 7 lacks all functional ingredients.

[0130] The preparation method of the serum is as follows:

[0131] (1) Water phase preparation: Take a certain amount of deionized water in the reactor, then take hyaluronic acid, beta-glucan, glycerol, panthenol according to the formula proportion, slowly add into the reactor, 70-80℃ water bath heating, and constant stirring, make each component fully dissolved.

[0132] (2) Oil phase preparation: Take phytosphingosine, carbomer, squalane, vitamin E according to the formula proportion in the reactor, 70-80℃ water bath heating, and constant stirring until a transparent and uniform system is formed.

[0133] (3) Water phase-oil phase mixing: Slowly pour the prepared oil phase into the water phase reactor, stir while pouring, the speed is 150-200rpm, last for 20 minutes, ensure that the system is emulsified uniformly (no stratification, no oil droplets).

[0134] (4) When the liquid is cooled to about 40℃, add the corresponding mass of yeast rice fermentation filtrate, auricularia auricula fruiting body extract and nicotinamide mononucleotide liposome in turn, stir while pouring, until all ingredients are mixed uniformly.

[0135] (5) Add phenoxyethanol, octisalate, EDTA-2Na and essence to the mixture, and adjust the pH to 5.5-6.0 with triethanolamine, and finally homogenize to obtain the essence.

[0136] The present application introduces the technical scheme of the present application by taking some examples and comparative examples as examples; each example and comparative example discloses corresponding product characterization data and effect data. The experimental means is in vitro cell experiment; in one scenario of the present application, the mitochondrial energy metabolism activity of HaCaT human keratinocyte is tested.

[0137] Table 3 Cell experiment raw material component allocation ratio table (μg / mL)

[0138]

[0139]

[0140] (1) Materials and reagents

[0141] ① HaCaT human keratinocyte

[0142] ② The samples prepared according to the above experimental examples 1-3, experimental comparative examples 1-6 and experimental blank example 7

[0143] ③ ATP detection kit (containing luciferase, luciferin, reaction buffer, cell lysis solution, ATP standard, etc.)

[0144] ④ Phosphate buffer (PBS, pH 6.5-7.5), deionized water

[0145] (2) Instruments and equipment

[0146] 96-well plate, chemiluminescence detector, pipette, centrifuge, clean bench, constant temperature incubator (37℃)

[0147] (3) Experimental principle

[0148] In the presence of Mg 2+ and oxygen, luciferase can catalyze the oxidation of luciferin to produce oxidized luciferin, while ATP is hydrolyzed to AMP and pyrophosphate (PPi), and the released energy is released in the form of light (wavelength about 560 nm). Within a certain range, the light intensity is linearly related to the ATP concentration. The energy metabolism of cell mitochondria is more active, producing more ATP, and the enzymatic reaction is more intense, resulting in a larger RLU value.

[0149] (4) Experimental method

[0150] ① Prepare a cell suspension from logarithmic phase cells, evenly inoculate into a 96-well plate, and ensure that the number of cells in each well is basically consistent, with 3 replicates per group. Incubate in a 37℃, 5% CO2 incubator for 24 hours, and select wells with 70%-80% confluence for subsequent processing.

[0151] ② Add 20μL of sample to each well of experimental examples 1-3, experimental comparative examples 1-6 and experimental blank example 7, and incubate in the incubator for 24 hours.

[0152] ③ Discard the culture medium in the wells, and gently wash the cells with pre-cooled PBS twice (avoiding vigorous washing that causes cell shedding).

[0153] Add an appropriate amount of cell lysis solution to each well, and let it stand at room temperature for 5-10 minutes to ensure complete lysis of the cells (you can gently shake or blow to promote lysis).

[0154] ④ Place the above-mentioned lysed liquid in a centrifuge tube, centrifuge at 4℃, 12000rpm for 5 minutes, and take the supernatant for detection (to avoid interference with the luminescence signal by debris).

[0155] ⑤ According to the instructions of the kit, mix the luciferase-luciferin reaction solution (freshly prepared, avoid light) with the sample / standard (1:1 volume mixing, i.e. add 50μL of sample supernatant + 50μL of reaction solution per well). Mix quickly and immediately place in the chemiluminescence detector to detect the luminescence intensity (RLU, relative light unit).

[0156] ⑥ Take experimental blank example 7 as a reference to calculate the mitochondrial energy metabolism difference of experimental examples 1-3 and experimental comparative examples 1-6. Mitochondrial energy metabolism difference (%) = (experimental group luminescence intensity - experimental blank example 7 luminescence intensity) / experimental blank example 7 luminescence intensity * 100%. Take the average value of each group of data, and take the absolute value of the calculation result.

[0157] (5) Experimental results

[0158] According to the above experimental procedures, the differences in mitochondrial energy metabolism of different experimental groups were measured as shown in the following table:

[0159] Table 4: Differences in mitochondrial energy metabolism

[0160] Sample Difference (%) Experimental Example 1 21.78 Experimental Example 2 34.53 Experimental Example 3 42.25 Experimental Comparative Example 1 15.87 Experimental Comparative Example 2 17.46 Experimental Comparative Example 3 14.84 Experimental Comparative Example 4 8.32 Experimental Comparative Example 5 5.13 Experimental Comparative Example 6 7.41

[0161] As shown in Table 4, the compositions of Experimental Examples 1-3 all showed significant promotion effects on the mitochondrial energy metabolism of human keratinocytes, and the promotion effect increased with the increase of the concentration of each active ingredient. Comparing Experimental Example 1 and Comparative Experimental Examples 1-3, when the nicotinamide mononucleotide liposome was absent, the difference in cell energy metabolism was the lowest, indicating that the nicotinamide mononucleotide liposome played a leading role in promoting cell energy metabolism. Comparing Comparative Experimental Examples 1-3, the difference degree was: Comparative Experimental Example 2 > Comparative Experimental Example 1 > Comparative Experimental Example 3, which indicated that the nicotinamide mononucleotide liposome had the strongest effect on promoting cell energy metabolism, followed by the yeast rice fermentation filtrate, and the tremella fruiting body extract was relatively weak. In addition, comparing Experimental Example 1 and Comparative Experimental Examples 4-6, the difference degree of Comparative Experimental Example 5, which only added the tremella fruiting body extract, was the lowest, which again indicated that the promotion effect of cell energy metabolism was: nicotinamide mononucleotide liposome > yeast rice fermentation filtrate > tremella fruiting body extract. When the three components were used synergistically, the promotion effect on cell energy metabolism was much greater than that when the three components were used alone.

[0162] Human efficacy evaluation experiment.

[0163] (1) Test sample: serum prepared from the components of Examples 1-3, Comparative Examples 1-6, and Blank Comparative Example 7 described in Table 1

[0164] (2) Test subjects: 100 healthy individuals aged 30 to 60 years old, with forehead wrinkles of 3-6 levels, nasolabial folds of 1-3 levels, and corner wrinkles of 2-4 levels, with F4 mean values of both left and right cheeks > 6 or R2 mean values < 0.65, all of whom had sensitive skin. Before testing, they signed a written informed consent form, and then were randomly divided into 10 groups, each using the same product.

[0165] (3) Test method:

[0166] ① The subjects complete facial cleansing at the test center, sit for 30 minutes in a constant temperature and humidity environment, and then use a skin color tester (Colorimeter CL 400) to test the cheek skin color L value, a skin elasticity tester (Cutometer MPA580) to test the skin tightness F4 value, and a stratum corneum moisture content tester (Corneometer CM 825) to test the skin water content.

[0167] ② Subsequently, each group member uses the corresponding test serum, and immediately uses a skin color tester (Colorimeter CL 400) to test the cheek skin color L value, a skin elasticity tester (Cutometer MPA 580) to test the skin tightness F4 value, and a stratum corneum moisture content tester (Corneometer CM 825) to test the skin water content.

[0168] ③ In addition, after using the serum for 7 days and 28 days, a skin color tester (Colorimeter CL 400) is used again to test the cheek skin color L value, a skin elasticity tester (Cutometer MPA 580) is used to test the skin tightness F4 value, and a stratum corneum moisture content tester (Corneometer CM 825) is used to test the skin water content.

[0169] (4) Test instructions

[0170] ① Test environment: temperature 20-22°C, humidity 40-60% RH.

[0171] ② The skin color tester (Colorimeter CL 400) can measure the brightness of the skin, and the L value ranges from 0 to 100. The larger the value, the brighter the skin (closer to white).

[0172] ③ The skin elasticity tester (Cutometer MPA 580) measures the maximum stretch of the skin under negative pressure and the immediate retraction after removing the negative pressure to calculate the F4 value. The smaller the F4 value, the better the skin elasticity and the higher the skin tightness.

[0173] ④ The stratum corneum moisture content tester (Corneometer CM 825) reflects the water state in the skin by detecting the conductivity of the uppermost layer of the skin.

[0174] ⑤ The test results can be calculated using the following formula: change rate = (analysis value after using the product - analysis value before using the product) ÷ analysis value before using the product x 100%, and the absolute value of the calculation result is taken. The change rate of the same group is averaged.

[0175] (5) Test results

[0176] ① whitening effect

[0177] According to the above experimental procedure, the cheek skin color of the subjects was tested at different times using a skin color tester (Colorimeter CL 400), and the facial skin brightness was reflected by the specific numerical value (L value) size. The data of each group was statistically calculated to obtain the following results:

[0178] Table 5 Change in facial skin brightness of subjects in each group at different times

[0179]

[0180]

[0181] As can be seen from Table 5, the compositions of Examples 1-3 have better whitening effects, and as the concentration of the effective ingredients increases, the whitening effect is more obvious. By observing Example 1 and Comparative Examples 1-3, it can be found that the change in facial skin brightness of the subjects in the group lacking the yeast rice fermentation filtrate and the group lacking the Tremella fuciformis fruiting body extract is close to that of Example 1, while the change in facial skin brightness of the subjects in the group lacking the nicotinamide mononucleotide liposome is quite different from that of Example 1, which indicates that the nicotinamide mononucleotide liposome is the main whitening component among the three. By observing Comparative Examples 3 and 5, 6, and Comparative Examples 3 and 6, it can be found that there is little difference in the change in facial skin brightness of the subjects between the two groups, while there is a larger difference between Comparative Examples 3 and 5, which indicates that the whitening effect of the Tremella fuciformis fruiting body extract is the smallest, followed by the yeast rice fermentation filtrate. Since the blank Comparative Example 7 does not contain effective ingredients, the change in facial skin brightness of the subjects in this group remains in a very low range.

[0182] ② Anti-wrinkle firming effect

[0183] According to the above experimental procedure, the skin firmness of the subjects was tested at different times using a skin elasticity tester (Cutometer MPA580), and the facial skin firmness was reflected by the specific numerical value (F4 value) size. The data of each group was statistically calculated to obtain the following results:

[0184] Table 6 Change in facial skin firmness of subjects in each group at different times

[0185]

[0186] From Table 6, it can be seen that the compositions of Examples 1-3 have better anti-wrinkle firming effects after use for a period of time, and the higher the concentration of the effective components, the higher the degree of skin firming. Observing the data of the degree of skin firming immediately after use of the serum samples in each group of Table 6, except for the blank comparative example 7, the differences between the other groups are not large, which may be because the serum has a short action time and the effective components cannot immediately play a role. After use of the serum for 4 weeks, the data of the examples and comparative examples become significantly different, which to some extent reflects that the repair of skin anti-wrinkle is a relatively long process. By comparing the data after use for 4 weeks of Example 1 and Comparative Examples 1-3, it can be found that the yeast rice fermentation filtrate, the golden ear fruiting body extract and the nicotinamide mononucleotide liposome all have the effects of anti-wrinkle firming and skin repair, but the effect of the golden ear fruiting body extract is slightly lower. By comparing the data after use for 4 weeks of Example 1 and Comparative Examples 4-6, it can be known that the synergistic use of the three effective components is better than the use of one effective component alone.

[0187] ③Moisturizing and water-locking effects

[0188] According to the above experimental procedures, the skin water content of the subjects was tested at different times using a corneometer (Corneometer CM 825), and compared with the skin water content before use. The data of each group were statistically calculated to obtain the following results:

[0189] Table 7 Changes in the skin water content of the subjects in each group at different times

[0190]

[0191] From Table 7, it can be seen that the compositions of Examples 1-3 have better moisturizing and water-locking effects, and the higher the concentration of the effective components, the better the moisturizing and water-locking effects. By observing Example 1 and Comparative Examples 1-3, it can be found that the changes in the skin water content of the subjects in the group lacking the golden ear fruiting body extract are most different from those in Example 1, followed by the group lacking the yeast rice fermentation filtrate, and the group lacking the nicotinamide mononucleotide liposome has the least difference, which indicates that the moisturizing and water-locking effects of the three effective components are: golden ear fruiting body extract > yeast rice fermentation filtrate > nicotinamide mononucleotide liposome. By comparing Example 1 and Comparative Examples 4-6, since Comparative Example 4 lacks the golden ear fruiting body extract and the yeast rice fermentation filtrate, its moisturizing effect is the worst among all the comparative examples, which is consistent with the foregoing conclusion. The blank comparative example still has a low degree of moisturizing effect, which may be because of the action of other matrix components in the serum.

[0192] In summary, the targeted energy metabolism composition for improving the anti-aging effect of skin and the preparation method and application thereof can realize effective penetration and precise delivery of the effective components, and improve the effects of skin anti-aging, whitening and moisturizing.

[0193] The present application breaks through the single-dimensional anti-aging mode and constructs a metabolic regulation combination system taking yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide (NMN) as main components. The antioxidant and barrier repair properties of yeast rice fermentation filtrate are used to scavenge intracellular ROS (reactive oxygen species), protect the structure and function of mitochondria, and promote the expression of barrier repair-related protein genes. The gold ear fruiting body extract can reduce mitochondrial DNA damage, regulate mitochondrial energy metabolism-related enzyme activity, and enhance skin barrier function. Nicotinamide mononucleotide, as a direct precursor of NAD+, accelerates cell energy metabolism cycle, increases NAD+ level, activates SIRTUIN pathway, delays cell aging, and inhibits melanin synthesis. At the same time, the use of liposome-encapsulated nicotinamide mononucleotide can achieve effective penetration and precise delivery of active ingredients. The synergistic use of these components forms a three-dimensional regulation network of mitochondrial structure protection-energy activation-barrier repair.

[0194] The present application uses liposome encapsulation technology to improve penetration and delivery efficiency and uses multiple components to construct a three-dimensional regulation network of mitochondrial structure protection-energy activation-barrier repair.

[0195] Taking yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide as core components, the use of liposome technology to encapsulate nicotinamide mononucleotide into small particles overcomes the problem of low penetration and delivery efficiency of traditional technology, greatly improving the absorbability. In addition, the synergistic use of yeast rice fermentation filtrate, gold ear fruiting body extract and nicotinamide mononucleotide can regulate cell energy metabolism from multiple dimensions:

[0196] Dimension one: yeast rice fermentation filtrate has antioxidant and barrier repair effects. On the one hand, the antioxidant components in it can scavenge intracellular ROS (reactive oxygen species) to avoid damage to mitochondrial structure, thereby maintaining the normal function of mitochondria and promoting ATP synthesis; on the other hand, the polysaccharide substances in it can bind to epidermal growth factor receptor (EGFR), activate cell signaling pathways, and promote the proliferation and differentiation of keratinocytes.

[0197] Dimension two: gold ear fruiting body extract can act on cells from the dermis to the epidermis to achieve antioxidant, anti-aging and moisturizing effects.

[0198] Dimension three: nicotinamide mononucleotide liposome can supplement NAD+, promote ATP generation, double the cell energy metabolism with yeast rice fermentation filtrate, activate SIRTUIN pathway, inhibit melanin synthesis enzyme-related gene expression, and achieve anti-aging and whitening effects.

[0199] The three components of the yeast rice fermentation filtrate, the gold ear fruiting body extract and the nicotinamide mononucleotide liposome have both parallel and cross effects, forming a three-dimensional regulation network of cell energy metabolism.

[0200] The technical features of the above-described embodiments can be combined in any manner. To make the description concise, all possible combinations of the technical features in the above-described embodiments are not described, but it should be considered that any combination of the technical features is within the scope of the present disclosure, as long as the combination does not result in a contradiction.

[0201] The description and application of the present disclosure are illustrative, and are not intended to limit the scope of the present disclosure to the above-described embodiments. The effects or advantages involved in the embodiments can not be embodied in the embodiments due to various factors, and the description of the effects or advantages is not intended to limit the embodiments. Variations and modifications of the disclosed embodiments are possible, and various components of the embodiments are known to those of ordinary skill in the art. It should be clear to those skilled in the art that the present disclosure can be implemented in other forms, structures, arrangements, proportions, and with other components, materials, and parts without departing from the spirit or essential characteristics of the present disclosure. Other variations and modifications of the disclosed embodiments can be made without departing from the scope and spirit of the present disclosure.

Claims

1. A targeted energy metabolism composition for enhancing skin anti-aging effects, characterized in that, The targeted energy metabolism composition comprises: 0.1-5 parts by weight of yeast rice fermentation filtrate, 0.1-5 parts by weight of Auricularia auricula-judae fruiting body extract, and 0.01-5 parts by weight of nicotinamide mononucleotide (NMN) liposomes.

2. The targeted energy metabolism composition for improving skin anti-aging effects according to claim 1, characterized in that: The mass ratio of the yeast rice fermentation filtrate, the extract of Auricularia auricula-judae fruiting body, and the nicotinamide mononucleotide (NMN) liposomes is (0.5-3):(0.1-3):(0.1-3).

3. The targeted energy metabolism composition for improving skin anti-aging effects according to claim 1, characterized in that: The nicotinamide mononucleotide (NMN) liposomes are encapsulated using liposome encapsulation. The raw materials used for liposome encapsulation include membrane material components, solvents, and buffer solutions.

4. The targeted energy metabolism composition for improving skin anti-aging effects according to claim 3, characterized in that: The membrane material contains phospholipids and sterols. The phospholipids are selected from at least one of hydrogenated soybean lecithin, soybean lecithin, egg yolk lecithin, and hydrogenated egg yolk lecithin. The sterols are selected from at least one of phytosterol oleate, cholesterol, sitosterol, and stigmasterol. The solvent is selected from at least one of anhydrous ethanol and methanol. The buffer solution is selected from at least one of phosphate buffer and citrate buffer.

5. The targeted energy metabolism composition for improving skin anti-aging effects according to claim 4, characterized in that: The raw material treated with liposome encapsulation further includes a stabilizer / lyophilization protectant; the stabilizer / lyophilization protectant is selected from at least one of sucrose, trehalose, mannitol, vitamin E, and vitamin C palmitate.

6. The targeted energy metabolism composition for improving skin anti-aging effects according to claim 3, characterized in that: The method for preparing the nicotinamide mononucleotide (NMN) liposomes includes the following steps: Lipid membrane preparation steps: Mix hydrogenated soybean lecithin and phytosterol oleate at a mass ratio of (2-4):1, and dissolve the mixture in a solvent. Add 8-12 mL of solvent to each 1 g of mixed lipids, and stir magnetically in a water bath at 45-55℃ for 15-45 min until completely dissolved to form a clear and transparent mixture with a concentration of 80-120 mg / mL. Lipid film preparation steps: Transfer the above mixture to a rotary evaporator and rotary evaporate at 35-45°C and a vacuum degree ≤100mbar at a speed of 60-100rpm to completely evaporate the residual solvent until a uniform and transparent lipid film is formed on the bottle wall. NMN aqueous solution preparation steps: Weigh the set amount of NMN, add a buffer solution with pH 5.5-6.0 preheated at 35-40℃ according to the final liposome suspension concentration of 1-3% w / v, and sonicate for 3-7 minutes until a clear solution is formed. Liposome hydration and encapsulation steps: Add NMN aqueous solution to a flask containing a lipid film, wherein the volume ratio of lipid to water phase is 1:8 to 1:12, hydrate by magnetic stirring at a water bath temperature of 35 to 40°C for 40 to 80 minutes until the lipid film is completely detached, forming an initial emulsified liposome suspension. Particle size optimization steps: Transfer the suspension to an ultrasonic cell disruptor in an ice-water bath, and use probe ultrasound to reduce the size of liposomes. Power 250-350W, pulse mode: work for 2-4 seconds, pause for 4-6 seconds, total time 10-20 minutes, until the suspension is semi-transparent. Free NMN removal steps: The obtained suspension is placed in a dialysis bag with a molecular weight cutoff of 2000-4000 Da and placed in a buffer solution. Dialyze at 2-6℃ for 8-16 hours, changing the buffer solution every 4 hours to remove unencapsulated free NMN. Stability treatment steps: ① Short-term storage: Add 0.05-0.2% stabilizer to the NMN liposome solution and store at 2-6℃ in the dark; ② Long-term storage: Add 3-7% lyophilization protectant to the NMN liposome solution and freeze-dry to make lyophilized powder; freeze-drying temperature -35 to -45℃, pre-freeze for 1-3 hours, vacuum degree ≤10mTorr, heating rate 0.5-1.5℃ / min, and reconstitute with buffer solution before use.

7. A method for preparing a targeted energy metabolism composition for improving skin anti-aging effects as described in any one of claims 1 to 6, characterized in that, The preparation method includes: Preparation of nicotinamide mononucleotide (NMN) liposomes; A targeted energy metabolism composition was prepared by mixing 0.1–5 parts by weight of yeast rice fermentation filtrate, 0.1–5 parts by weight of Auricularia auricula-judae fruiting body extract, and 0.01–5 parts by weight of nicotinamide mononucleotide (NMN) liposomes.

8. The preparation method according to claim 7, characterized in that: The preparation of nicotinamide mononucleotide (NMN) liposomes includes the following steps: Lipid membrane preparation steps: Mix hydrogenated soybean lecithin and phytosterol oleate at a mass ratio of (2-4):1, and dissolve the mixture in a solvent. Add 8-12 mL of solvent to each 1 g of mixed lipids, and stir magnetically in a water bath at 45-55℃ for 15-45 min until completely dissolved to form a clear and transparent mixture with a concentration of 80-120 mg / mL. Lipid film preparation steps: Transfer the above mixture to a rotary evaporator and rotary evaporate at 35-45°C and a vacuum degree ≤100mbar at a speed of 60-100rpm to completely evaporate the residual solvent until a uniform and transparent lipid film is formed on the bottle wall. NMN aqueous solution preparation steps: Weigh the set amount of NMN, add a buffer solution preheated to 35-40℃ with a pH of 5.5-6.0 according to the final liposome suspension concentration of 1-3% w / v, and sonicate for 3-7 minutes until a clear solution is formed. Liposome hydration and encapsulation steps: Add NMN aqueous solution to a flask containing a lipid film, wherein the volume ratio of lipid to water phase is 1:8 to 1:12, hydrate at a water bath temperature of 35 to 40°C, and magnetically stir for 40 to 80 minutes at a speed of 80 to 120 rpm until the lipid film is completely detached, forming an initial emulsified liposome suspension. Particle size optimization steps: Transfer the suspension to an ultrasonic cell disruptor in an ice-water bath, and use probe ultrasound to reduce the size of liposomes. Power 250-350W, pulse mode: work for 2-4 seconds, pause for 4-6 seconds, total time 10-20 minutes, until the suspension is semi-transparent. Free NMN removal steps: The obtained suspension is placed in a dialysis bag with a molecular weight cutoff of 2000-4000 Da and placed in a buffer solution. Dialyze at 2-6℃ for 8-16 hours, changing the buffer solution every 4 hours to remove unencapsulated free NMN. Stability treatment steps: ① Short-term storage: Add 0.05-0.2% stabilizer to the NMN liposome solution and store at 2-6℃ in the dark; ② Long-term storage: Add 3-7% lyophilization protectant to the NMN liposome solution, freeze-dry to make lyophilized powder, freeze-drying temperature is -35 to -45℃, pre-freeze for 1-3 hours, vacuum degree ≤10mTorr, heating rate 0.5-1.5℃ / min 1℃ / min; reconstitute with buffer solution before use.

9. The use of the targeted energy metabolism composition for improving skin anti-aging effects as described in any one of claims 1 to 6 in the preparation of skin care products.

10. The application according to claim 9, characterized in that: The skincare products include toners, serums, lotions, or creams.

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