CN115957160A - A product that effectively inhibits AGEs from generating anti-wrinkle, firming and brightening skin and its application - Google Patents

Abstract

The invention relates to the field of A61K, in particular to a product for effectively inhibiting AGEs from generating wrinkles, tightening skin and brightening skin and application thereof, and the preparation raw materials of the product at least comprise 0.01-15% of an effect composition, 2-15% of a cosolvent, 2-15% of a humectant, 0.01-0.2% of a chelating agent, 0.1-5% of a thickening agent, 0.2-20% of an emollient, 0.01-10% of a skin conditioner, 1-10% of an emulsifier and the balance of a solvent. Through the synergistic effect of the raw materials of the efficacy composition, the emollient, the skin conditioner and the like in the system, the weight ratio of the efficacy composition, the emollient and the skin conditioner is especially controlled to be (0.1-8): (2-6): (0.1-5), the provided product can effectively prevent, avoid and even treat skin aging caused by external factors, delay and even avoid damage of skin tissues, reduce aging phenomena such as wrinkles of the skin and the like, and has higher safety.

Description

A product that effectively inhibits the generation of AGEs, resists wrinkles, tightens the skin, and brightens the skin, and its application

Technical Field

The present invention relates to the field of A61K, and in particular to a product and its application that effectively inhibits the generation of AGEs and resists wrinkles, tightens the skin and brightens the skin.

Background Art

The skin includes the epidermis, dermis, subcutaneous tissue and skin microcirculation, and is the body's first line of immune defense against ultraviolet radiation. The epidermis contains melanocytes that produce melanin, and the dermis contains collagen and elastic fibers. If the skin is overexposed to ultraviolet radiation, melanin is produced in the epidermis, and collagen and elastin cellulose in the dermis are damaged, which in turn leads to skin pigmentation, darkening, reduced skin elasticity, skin aging and wrinkles. The skin around the eyes is the most sensitive and fragile.

Studies have shown that advanced glycation end products (AGEs) are important factors that lead to various accelerated aging. The production and accumulation of AGEs lead to skin pigmentation, thinning, loss of elasticity, dryness, spot formation, stiffness, and the formation of fine lines and wrinkles. The anti-glycation products currently on the market, including some preparations including active ingredients such as aminoguanidine and mogroside, can play a certain degree of anti-glycation effect, but the efficacy is insufficient and there are certain side effects. For example, Chinese invention patent application CN110664868A discloses a composition with anti-glycation effect and its application, which specifically enhances the anti-glycation ability of the skin by using osmanthus extract, pomegranate extract, and olive fruit extract. Chinese invention patent application CN102462650B discloses an anti-glycation composition derived from Podocarpus plants and its preparation method and application, which mainly uses Podocarpus plants as raw materials, and extracts the anti-glycation composition from the Podocarpus plant raw materials through specific ultrasonic extraction and solid-liquid separation processes. However, the anti-glycosylation effect of the composition needs to be further improved. Therefore, it is of great practical research and application significance to provide a product that can effectively inhibit the generation of AGEs, resist wrinkles, tighten and brighten the skin, so as to prevent, avoid or even treat exogenous skin aging, delay or even avoid damage to skin tissue, reduce skin wrinkles and other aging phenomena, and has high safety.

Summary of the invention

In order to solve the above problems, the present invention provides, on one hand, a product for effectively inhibiting the generation of AGEs, anti-wrinkle, firming and skin-lightening, which comprises at least the following raw materials by weight percentage: 0.01-15% of an effective composition, 2-15% of a cosolvent, 2-15% of a moisturizer, 0.01-0.2% of a chelating agent, 0.1-5% of a thickener, 0.2-20% of an emollient, 0.01-10% of a skin conditioner, 1-10% of an emulsifier, and the remainder of solvent replenishment.

Preferably, the raw materials for preparing the product include the following raw materials by weight percentage: 0.1-10% of the functional composition, 5-10% of the cosolvent, 5-10% of the moisturizer, 0.01-0.1% of the chelating agent, 0.3-0.5% of the thickener, 1-10% of the emollient, 0.1-8% of the skin conditioner, 3-8% of the emulsifier, and the remainder of the solvent supplement.

As a preferred technical solution, the efficacy composition comprises at least 8.0-18 parts of hymenium yeast extract, 0.2-4 parts of Paliurusspina-christi Mill. extract, 0.05-5 parts of Acmella oleracea extract, 0.3-3 parts of Medicago Sativa Linn extract, 2-10 parts of decaboxy carnosine HCL, and 1-10 parts of Momordica grosvenorii Swingle extract.

Based on the system of the present invention, by introducing the efficacy composition including hymenine yeast extract, jujube extract, millet extract, soybean alfalfa extract, decarboxylated carnosine, and monk fruit extract, various active ingredients effectively reverse the degradation of matrix and collagen elastin through different mechanisms, thereby promoting angiogenesis, restoring microvascular elasticity, and enhancing vascular dilation of the skin microcirculation to fully perfuse the dermis tissue and supporting structure with oxygen and nutrients. The inventor analyzed that the reason may be that jujube extract, millet extract, and monk fruit extract can produce effective synergistic effects, effectively prevent or even reverse skin glycation to reduce wrinkles, restore collagen capacity and skin elasticity, eradicate skin melanin production and pigmentation caused by glycation, inhibit the expression of AGEs receptors and the splitting of formed AGEs, effectively treat premature aging, and especially reduce the generation of eye wrinkles after use. The inventors unexpectedly discovered that the simultaneous introduction of 2-10 parts by weight of decarboxylated carnosine enables the provided product to be highly resistant to hydrolysis by skin enzymes. This may be because decarboxylated carnosine, in conjunction with soybean alfalfa extract and hymenium yeast extract, can synergistically remove carbonyl compounds, protect skin proteins from cross-linking, and compete with glucose to effectively inhibit protein glycosylation, thereby effectively inhibiting hydrolysis by skin enzymes and inhibiting and reducing skin aging.

As a preferred technical solution, the mass ratio of the functional composition, the emollient and the skin conditioner is (0.1-8):(2-6):(0.1-5).

As a preferred technical solution, the emollient is selected from at least one of squalane, tocopherol acetate, and octyldodecanol; preferably, the emollient is a combination of squalane and tocopherol acetate; preferably, the mass ratio of squalane to tocopherol acetate is 1:(0.2-0.6).

As a preferred technical solution, the skin conditioning agent is selected from at least one of hydrogenated lecithin, sodium hyaluronate, trehalose, dipalmitoyl hydroxyproline, panthenol and arginine; preferably, the skin conditioning agent is a combination of sodium hyaluronate, trehalose and panthenol; preferably, the mass ratio of sodium hyaluronate, trehalose and panthenol is (2-4):(3-5):1.

Based on the system of the present invention, through the synergistic effect of the raw materials in the system, especially controlling the mass ratio of the functional composition, emollient, and skin conditioner introduced into the system to (0.1-8): (2-6): (0.1-5), the provided product can effectively prevent, avoid, or even treat exogenous skin aging, delay or even avoid damage to skin tissue, reduce skin wrinkles and other aging phenomena, and has high safety.

During the research, the inventors found that there were large differences in the effects of the synergistic promotion of the compounding effect of the introduction of different emollients and skin conditioners and the functional composition. Based on the functional composition in the system, squalane and tocopherol acetate with a mass ratio of 1: (0.2-0.6) were introduced as emollients, and sodium hyaluronate, trehalose, and panthenol with a mass ratio of (2-4): (3-5): 1 were introduced as skin conditioners to effectively ensure the skin condition after use. The inventors analyzed that the reason may be that under the joint action of the emollients squalane and tocopherol acetate and the skin conditioners sodium hyaluronate, trehalose, and panthenol, the chronic contraction of the facial, especially the fragile subcutaneous muscles of the eyes, was effectively blocked, promoting muscle relaxation, increasing muscle tension, promoting the stimulation and sufficiency of the collagen network, improving vascular elasticity, accelerating the repair of functional wrinkles on the skin, and restoring the vitality of the skin structure.

As a preferred technical solution, the moisturizing agent is selected from at least one of glycerol, glycerol polyether-26, isopentyl glycol, and 1,2-hexanediol; preferably, the moisturizing agent is glycerol, glycerol polyether-26 and 1,2-hexanediol; the mass ratio of glycerol, glycerol polyether-26 and 1,2-hexanediol is (6-10):(4-6):1.

As a preferred technical solution, the cosolvent is a combination of pentamethylene glycol and triglyceride. Preferably, the mass ratio of pentamethylene glycol to triglyceride is (3-5): (2-4).

Based on the system of the present invention, a combination of pentamethylene glycol and triglyceride in a mass ratio of (3-5): (2-4) is introduced as a cosolvent to promote effective dissolution of the active ingredients in the system and ensure the stability of the formulation system.

As a preferred technical solution, the emulsifier is a combination of cetearyl olivate and cetearyl alcohol; preferably, the mass ratio of cetearyl olivate and cetearyl alcohol is (2-4): 1. Based on the raw materials in the system of the present invention, cetearyl olivate and cetearyl alcohol in a mass ratio of (2-4): 1 are selected as emulsifiers to homogenize the raw materials in the system to form a stable system, thereby improving the long-term effectiveness and safety of the product.

As a preferred technical solution, the thickener is carbomer; preferably, the carbomer is carbomer 940.

As a preferred technical solution, the chelating agent is EDTA-2Na.

As a preferred technical solution, the solvent is deionized water.

As a preferred technical solution, the method for preparing the product that effectively inhibits the generation of AGEs and has anti-wrinkle, skin-tightening and skin-lightening effects comprises at least the following steps:

(1) Add a chelating agent, a cosolvent and a solvent into a container and homogenize for 15-20 minutes, then add a thickener and homogenize for 10-20 minutes to obtain a mixture A.

(2) Controlling the temperature to 60-80° C., adding an emollient and a humectant to the mixture A, stirring and mixing for 2-10 minutes, then adding an emulsifier, and homogenizing for 5-10 minutes to obtain a mixture B.

(3) Cooling the mixture B to 40-45° C., adding the functional composition and the skin conditioning agent, stirring for 20-30 minutes, and then detecting the material to obtain the mixture.

Another aspect of the present invention provides an application of a product that effectively inhibits the generation of AGEs and resists wrinkles, tightens the skin and brightens the skin, and is applied to anti-aging prevention and treatment.

Beneficial effects:

1. The present invention uses the synergistic effect of the functional composition, emollient, skin conditioner and other raw materials in the system, especially controlling the mass ratio of the functional composition, emollient and skin conditioner introduced into the system to (0.1-8): (2-6): (0.1-5), so that the provided product can effectively prevent, avoid, or even treat externalized skin aging, delay or even avoid damage to skin tissue, reduce skin wrinkles and other aging phenomena, and has high safety.

2. Based on the system of the present invention, by introducing a functional composition including hyaluronic acid yeast extract, jujube extract, millet chrysanthemum extract, soybean alfalfa extract, decarboxylated carnosine, and monk fruit extract, various active ingredients effectively reverse the degradation of matrix, collagen and elastin through different mechanisms, thereby promoting angiogenesis and restoring microvascular elasticity, thereby enhancing vasodilation of the skin microcirculation to fully perfuse the dermis tissue and supporting structure with oxygen and nutrients.

3. Based on the functional composition in the system, squalane and tocopherol acetate are introduced in a mass ratio of 1:(0.2-0.6) as emollients, and sodium hyaluronate, trehalose and panthenol are introduced in a mass ratio of (2-4):(3-5):1 as skin conditioners to effectively ensure the skin condition after use.

4. Based on the raw materials in the system of the present invention, a mass ratio of (2-4): 1 cetearyl olivate and cetearyl alcohol is selected as an emulsifier to homogenize the raw materials in the system to form a stable system, thereby improving the long-term effectiveness and safety of the product.

5. Based on the system of the present invention, a combination of pentamethylene glycol and triglyceride in a mass ratio of (3-5): (2-4) is introduced as a cosolvent to promote effective dissolution of the active ingredients in the system and ensure the stability of the formulation system.

DETAILED DESCRIPTION

Example 1

Example 1 of the present invention provides a product that effectively inhibits the generation of AGEs and has anti-wrinkle, firming and skin-lightening effects, which comprises the following raw materials, by weight percentage: 6% of an effective composition, 8% of a cosolvent, 10% of a moisturizer, 0.03% of a chelating agent, 0.4% of a thickener, 6% of an emollient, 4% of a skin conditioner, 5% of an emulsifier, and the remainder of solvent replenishment.

The effective composition comprises, by weight, 8 parts of hyssop yeast extract, 2 parts of Paliurusspina-christi Mill. extract, 3 parts of Acmella oleracea extract, 1.5 parts of Medicago Sativa Linn extract, 5 parts of Decaboxy Carnosine HCL, and 5 parts of Momordicagrosvenorii Swingle extract.

The hymosin yeast extract is from Qingdao Qingyao Bioengineering Co., Ltd. The jujube extract is from Guangzhou Fuyulong Biotechnology Co., Ltd. The spatholobi extract is from Lanzhou Waterless Biotechnology Co., Ltd.; the soybean alfalfa extract is from Shandong Tengwang Chemical Co., Ltd.; the decarboxylated carnosine is from Guorun Biotechnology (Shenzhen) Co., Ltd.; and the monk fruit extract is from Guilin Rhine Biotechnology Co., Ltd.

The emollient is a combination of squalane and tocopherol acetate; the mass ratio of squalane to tocopherol acetate is 1:0.5.

The skin conditioning agent is a combination of sodium hyaluronate, trehalose and panthenol; the mass ratio of the sodium hyaluronate, trehalose and panthenol is 3:4:1.

The moisturizing agent is glycerol, glycerol polyether-26 and 1,2-hexanediol; the mass ratio of glycerol, glycerol polyether-26 and 1,2-hexanediol is 8:5:1.

The cosolvent is a combination of pentamethylene glycol and triglyceride, and the mass ratio of pentamethylene glycol to triglyceride is 4:3.

The emulsifier is a combination of cetearyl olivate and cetearyl alcohol; the mass ratio of cetearyl olivate and cetearyl alcohol is 3:1.

The thickener is carbomer; the carbomer is carbomer 940.

The chelating agent is EDTA-2Na.

The solvent is deionized water.

The method for preparing the product that effectively inhibits the generation of AGEs and resists wrinkles, tightens the skin and brightens the skin comprises the following steps:

(1) Add a chelating agent, a cosolvent and a solvent into a container and homogenize for 15 minutes, then add a thickener and homogenize for 15 minutes to obtain a mixture A.

(2) The temperature was controlled at 70° C., an emollient and a humectant were added to the mixture A, and the mixture was stirred for 5 minutes. Then, an emulsifier was added, and the mixture was homogenized for 8 minutes to obtain a mixture B.

(3) Cooling the mixture B to 40° C., adding the functional composition and the skin conditioning agent, stirring for 30 minutes, and then detecting the material to obtain the mixture.

Example 2

Example 2 of the present invention provides a product that effectively inhibits the generation of AGEs and has anti-wrinkle, firming and skin-lightening effects. The specific implementation method is the same as that of Example 1, except that the product comprises the following raw materials by weight percentage: 8% of the functional composition, 8% of the cosolvent, 10% of the moisturizer, 0.03% of the chelating agent, 0.4% of the thickener, 5% of the emollient, 3% of the skin conditioner, 5% of the emulsifier, and the remainder of the solvent supplement.

The effective composition comprises, by weight, 6 parts of hyssop yeast extract, 2 parts of Paliurusspina-christi Mill. extract, 3 parts of Acmella oleracea extract, 1.5 parts of Medicago Sativa Linn extract, 6 parts of decaboxy carnosine HCL, and 6 parts of Momordicagrosvenorii Swingle extract.

Example 3

Example 3 of the present invention provides a product that effectively inhibits the generation of AGEs, resists wrinkles, tightens the skin and brightens the skin. The specific implementation method is the same as that of Example 1, except that the product comprises the following raw materials by weight percentage: 5% of the efficacy composition, 8% of the cosolvent, 10% of the moisturizer, 0.03% of the chelating agent, 0.4% of the thickener, 4% of the emollient, 5% of the skin conditioner, 5% of the emulsifier, and the solvent supplement balance. By weight, the efficacy composition comprises: 10 parts of hymenium yeast extract, 1 part of Paliusspina-christi Mill. extract, 2 parts of Acmella oleracea extract, 1.5 parts of Medicago Sativa Linn extract, 6 parts of Decaboxy Carnosine HCL, and 6 parts of Momordicagrosvenorii Swingle extract.

Comparative Example 1

Comparative Example 1 of the present invention provides a product that effectively inhibits the generation of AGEs and resists wrinkles, tightens the skin and brightens the skin. The specific implementation method is the same as that of Example 1, except that the co-solvent is dibutylene glycol.

Comparative Example 2

Comparative Example 2 of the present invention provides a product that effectively inhibits the generation of AGEs and resists wrinkles, tightens the skin and brightens the skin. The specific implementation method is the same as that of Example 1, except that the emulsifier is Tween 80.

Performance Testing Methods

1. Test to verify the anti-glycation effect of the product provided in Example 1.

1. Experimental steps

1.1 Preparation of AGEs solution: Dissolve BSA (50 mg/mL) and D-Glu (0.1 mol/L) in PB, mix well and incubate (50°C, 102 h).

1.2 Reaction: Add different concentrations of the aqueous solution of the product prepared in Example 1 to be tested into the AGEs solution, set up positive and negative controls, and incubate at 50° C. for 3 h.

1.3 Fluorescence value determination: Take 200 μL into a 96-well plate and measure the fluorescence value at λex/λem=360nm/446nm.

1.4 Result analysis: Calculate the inhibition rate according to the following formula

AGEs inhibition rate (%) = [1-(A-B)/(C-D)] × 100

Where: A—fluorescence intensity of AGEs solution with test substance or positive substance added;

B—fluorescence intensity of PB solution with test substance or positive substance added;

C—fluorescence intensity of AGEs solution without test substance or positive substance;

D—fluorescence intensity of PB solution without test substance or positive substance; GraphPrism was used for fitting and IC ₅₀ was calculated, ie, the concentration of the test solution when the inhibition rate was 50%.

Table 1 Experimental results

Under the conditions of this experiment, the IC ₅₀ of the positive group was 11.63 mg/mL (95% CI: 0.1771, 764.2), and the IC ₅₀ of the preparation prepared in Example 1 was 2.812% (95% CI: 1.624, 4.867).

2. Conclusion

Under the conditions of this test, the smaller the concentration required for the test substance to achieve a half inhibition rate, that is, the smaller the IC ₅₀ , the stronger the ability of the test substance to inhibit the production of glycosylated proteins. At a concentration of 2.812%, the inhibition rate of the preparation prepared in Example 1 on the production of glycosylated proteins was 50%. This shows that the preparation prepared in Example 1 has an inhibitory effect on the production of glycosylated proteins and has an anti-glycation effect.

2. Human Clinical Research

A total of 60 subjects were included, with an average age of 52.1 years old, including 30 test group subjects and 30 control group subjects. The test period was 6 weeks, and the subjects applied the product prepared in Example 1 (18 wt % aqueous solution) to the area around the eyes twice a day, while the control group did not apply it. DERMASCAN and DERMAFLEX were used to measure the increase in skin elasticity (%) and smoothness (%) of the subjects. The results are shown in Tables 2 and 3.

Table 2

initial 6 weeks later Increased skin elasticity (%) Test Group 48 65 35 Control group 47 46 -0.02

Table 3

initial 6 weeks later Smoothness increase (%) Test Group 0.92 1.31 42 Control group 0.95 0.93 -0.02

3. Stability Test

The products prepared in the examples and comparative examples were placed in a thermostat at 50°C, 25°C and 0°C for 14 days, and taken out for observation after 14 days to observe the state of the hair growth essence product at 50°C, 25°C and 0°C. If the product did not delaminate, the physical and chemical stability was recorded as "qualified"; if the product delaminated, the physical and chemical stability was recorded as "unqualified"; the results are shown in Table 4.

Table 4

Claims (10)

1. A product that effectively inhibits the generation of AGEs and has anti-wrinkle, firming and skin-lightening effects, characterized in that it comprises at least the following raw materials, by weight percentage: 0.01-15% of an effective composition, 2-15% of a cosolvent, 2-15% of a moisturizer, 0.01-0.2% of a chelating agent, 0.1-5% of a thickener, 0.2-20% of an emollient, 0.01-10% of a skin conditioner, 1-10% of an emulsifier, and the remainder of solvent supplementation. 2. The product for effectively inhibiting AGEs generation, anti-wrinkle, firming and brightening skin according to claim 1 is characterized in that the raw materials for preparing the product include the following raw materials by weight percentage: 0.1-10% of the functional composition, 5-10% of the cosolvent, 5-10% of the moisturizer, 0.01-0.1% of the chelating agent, 0.3-0.5% of the thickener, 1-10% of the emollient, 0.1-8% of the skin conditioner, 3-8% of the emulsifier, and the remainder of the solvent supplement. 3. The product for effectively inhibiting AGEs generation, anti-wrinkle, firming and brightening skin according to claim 1 or 2, characterized in that, in parts by weight, the functional composition comprises at least: 8.0-18 parts of hyssop yeast extract, 0.2-4 parts of jujube extract, 0.05-5 parts of schizonepeta extract, 0.3-3 parts of soybean alfalfa extract, 2-10 parts of decarboxylated carnosine, and 1-10 parts of monk fruit extract. 4. The product for effectively inhibiting AGEs generation, anti-wrinkle, firming and brightening skin according to claim 3, characterized in that the mass ratio of the functional composition, the emollient and the skin conditioner is (0.1-8):(2-6):(0.1-5). 5. The product for effectively inhibiting the generation of AGEs and preventing wrinkles, tightening and brightening the skin according to claim 4, characterized in that the emollient is selected from at least one of squalane, tocopherol acetate and octyldodecanol. 6. The product for effectively inhibiting the generation of AGEs and preventing wrinkles, tightening and brightening the skin according to claim 5, characterized in that the skin conditioning agent is selected from at least one of hydrogenated lecithin, sodium hyaluronate, trehalose, dipalmitoyl hydroxyproline, panthenol and arginine. 7. The product for effectively inhibiting the generation of AGEs and preventing wrinkles, tightening and brightening the skin according to claim 3, characterized in that the moisturizing agent is selected from at least one of glycerol, glyceryl polyether-26, isopentyl glycol and 1,2-hexanediol. 8. The product for effectively inhibiting the generation of AGEs and preventing wrinkles, tightening and brightening the skin according to claim 3, characterized in that the co-solvent is a combination of pentamethylene glycol and triglyceride. 9. The product for effectively inhibiting the generation of AGEs and preventing wrinkles, tightening and brightening the skin according to claim 3, characterized in that the emulsifier is a combination of cetearyl olivetate and cetearyl alcohol. 10. Use of the product according to any one of claims 1 to 8 for effectively inhibiting the generation of AGEs and for anti-wrinkle, skin tightening and skin lightening, for anti-aging prevention and treatment.