CN113559006A - A cosmetic composition for scavenging free radicals and resisting aging - Google Patents

Abstract

The invention discloses a cosmetic composition for removing free radicals and resisting aging, which can remove free radicals, reduce oxidative damage, resist cellular oxidative damage and cell aging and effectively play an antioxidant role through the synergistic action of an imidazo [1, 2-a ] pyridine compound and a pyrazine-oxazole biaryl compound. The components are matched with each other, so that the antioxidant capacity of skin tissues can be obviously enhanced, the free radical content of skin is reduced, and the skin aging is delayed.

Description

A cosmetic composition for scavenging free radicals and resisting aging

Technical Field

The invention relates to the technical field of skin care products, in particular to a cosmetic composition for removing free radicals and resisting aging.

Background

Aging is a complex process, which is caused by both internal and external causes. It is believed by the scholars that aging is a result of the production and elimination of free radicals being hindered. Normally, the production and elimination of oxygen radicals in an organism are in relative equilibrium, but certain pathological factors or irradiation with ultraviolet or blue light may increase the formation of oxygen radicals or hinder the capture of free radicals by lutein in human skin. Free radicals can attack, infiltrate, and damage skin cell structures to produce lipid peroxides, ultimately leading to accelerated skin aging.

Therefore, studies on the addition of a radical scavenging component or an antioxidant to a cosmetic composition have been increasing. For example, patent CN102008426A discloses a cosmetic composition with free radical scavenging effect, which comprises flavone extract extracted from apple pomace, yeast extract of reduced glutathione and natural alpha-hydroxy acid extract of alpha-hydroxy acid. Patent CN106727027A discloses a composition for resisting blue light, resisting oxidation and scavenging free radicals, which comprises the following components by mass percent: 0.1-5% of a composition of marigold flower extract and safflower seed oil, 1-10% of tea extract and 1-10% of edelweiss extract. Especially, substances extracted and separated from natural raw materials are added as additives. Patent CN103211729A discloses an anti-aging skin care composition, which comprises elderberry extract, ginkgo leaf extract, pepper extract, scutellaria extract and the like. The above patents all enhance the antioxidant capacity of skin tissues, reduce the free radical content of skin tissues and play a role in delaying skin aging by adding natural plant extracts.

Recent studies have found that imidazo [1, 2-a ] pyridine compounds and pyrazine-oxazole biaryl compounds exhibit excellent antioxidant properties and radical trapping properties. Zhang Ping et al synthesized a series of pyrazine-oxazole biaryl compounds, and tested the antioxidant activity and reducing ability of the compounds by inhibiting free radical-initiated DNA oxidation and quenching free radical reaction systems ("synthesis of pyrazine-oxazole biaryl compounds and their antioxidant properties", Zhang Ping et al, fine chemistry, Vol 37, No. 7, 7/2020). Mathe Gaili and the like are synthesized into imidazo [1, 2-a ] pyridine compounds by a solvent-free method, and the antioxidant activity of the compounds is tested by inhibiting a DNA oxidation reaction system initiated by HO and reduced glutathione free radicals (GS.), the solvent-free synthesis and the antioxidant performance of the imidazo [1, 2-a ] pyridine compounds, the Mathe Gaili and the like, the synthetic chemistry is 2020,28 (3)). However, the prior art does not report that the two are safely applied to skin care products to achieve the effects of resisting oxidation and removing free radicals.

Disclosure of Invention

Aiming at the defects of the prior art, the invention provides a cosmetic composition for removing free radicals and resisting aging.

The technical scheme of the invention is as follows:

a cosmetic composition for scavenging free radicals and resisting aging comprises 0.5-2% of imidazo [1, 2-a ] pyridine compound and 0.5-2% of pyrazine-oxazole biaryl compound in percentage by mass.

Preferably, the imidazo [1, 2-a ] pyridine compound is ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate (formula I). The pyrazine-oxazole biaryl compound is 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole (formula II).

Preferably, the content of ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate and 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole is 1%, the effect of scavenging free radicals is the best.

The preparation method of the imidazo [1, 2-a ] pyridine compound comprises the following steps: 2-aminopyridine, aromatic aldehyde, ethyl isocyanoacetate and LaCl3 were added to a round bottom flask and reacted for 2h (TLC detection) at 80 deg.C (bath temperature) with stirring. Cooling to room temperature, and purifying by silica gel column chromatography [ eluent: V (ethyl acetate)/V (petroleum ether) ═ 1/3 ].

The preparation method of the pyrazine-oxazole biaryl compound comprises the following steps: 2, 5-dimethylpyrazine-N-oxide, an oxazole compound, anhydrous ferric chloride, 300-sand 400-mesh silica gel and anhydrous 1, 2-dichloroethane are sequentially added into a three-neck round-bottom flask provided with a thermometer and a reflux condenser, and are heated and refluxed for 8 hours at 100 ℃ under the protection of nitrogen (volume fraction is more than 98%). After the reaction is finished, cooling the reaction mixed liquid to room temperature, transferring the reaction mixed liquid to a single-neck flask, and performing rotary evaporation to obtain a powder solid; and using mixed solution of V (petroleum ether) and V (ethyl acetate) as eluent, adopting 300-400 mesh silica gel to carry out column chromatography separation, detecting effluent liquid through Thin Layer Chromatography (TLC), collecting eluent containing the target compound, carrying out rotary evaporation, and drying to obtain the pyrazine-oxazole biaryl compound.

The cosmetic composition of the present invention further comprises a humectant, an emulsifier, a thickener, vitamins, hydrolyzed protein, a plant extract, and deionized water.

Preferably, the cosmetic composition of the invention also comprises 2-10% of humectant, 10-20% of emulsifier, 0.1-0.2% of thickener, 1-3% of vitamin E1, and 5-10% of plant extract.

Wherein the humectant comprises one or more of sorbitol, propylene glycol, glycerol, lanolin, panthenol, cetyl alcohol, amino acid, and betaine;

wherein the emulsifier comprises one or more of polyoxyethylene monostearate, glyceryl monostearate, tween 60, tween 80 and polyoxyethylene monolaurate.

Wherein the thickener comprises one or more of hydroxyethyl cellulose, carboxymethyl cellulose, PMC, xanthan gum, hydroxypropyl cellulose and carrageenan.

Wherein the plant extract comprises one or more of Ginseng radix extract, Ganoderma extract, fructus Hippophae extract, cornu Cervi Pantotrichum extract, and herba Leontopodii Kaempferi extract.

Compared with the prior art, the cosmetic composition provided by the invention has the following beneficial effects:

(1) the composition disclosed by the invention is added with two compounds, through the synergistic effect of the imidazo [1, 2-a ] pyridine compound and the pyrazine-oxazole biaryl compound, free radicals can be removed, oxidative damage is reduced, cell oxidative damage and cell aging are prevented, the antioxidant effect is effectively exerted, and when the composition is applied to cosmetics, the composition can endow the cosmetics with a remarkable anti-aging effect, so that the skin is more delicate, white and moist.

(2) The moisturizing agent added in the components of the invention can lock skin moisture, maintain skin moisture, supplement skin collagen, delay skin aging, and is rich in various nutrition functions by adding the plant extracts, thus having the effects of preventing wrinkles, recovering elasticity, resisting aging and the like on skin. The extract of the alpine edelweiss is also included, so that the skin can be cleaned mildly and deeply, the grease on the epidermis and the dirt in pores can be removed, the skin tension state can be relieved, and the skin can be relieved, calmed, antioxidant, nourished and protected.

(3) The components are matched with each other, so that the antioxidant capacity of skin tissues can be obviously enhanced, the free radical content of skin is reduced, and the skin aging is delayed.

Detailed Description

The invention is further illustrated by the following examples.

Synthesis of Ethyl 12- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate (A) and pyrazine-oxazole Biarylate as 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole (B)

The two compounds, compound a and compound B, were synthesized by referring to the experimental methods described in "solvent-free synthesis of imidazo [1, 2-a ] pyridine compound and its antioxidant property" (sugao-leyi et al, synthetic chemistry, 2020,28(3)) and "synthesis of pyrazine-oxazole biaryl compound and its antioxidant property" (zhaoxiaping et al, fine chemical engineering, volume 37, phase 7, 2020, 7 months).

1.2 cosmetic compositions

Example 1, a cosmetic composition comprising a composition wherein 1.1 said compound a is synthesized 0.5%, compound B0.5%, sorbitol 2%, glycerin 2%, panthenol 1%, cetyl alcohol 1%, polyoxyethylene monostearate 2%, tween 803%, glyceryl monostearate 10%, hydroxyethyl cellulose 0.2%, sea buckthorn extract 1%, ganoderma lucidum extract 1%, edelweiss extract 5%, vitamin E1%, hydrolyzed protein 3%, the balance deionized water.

Example 2 a cosmetic composition comprising a composition wherein 1.1 said compound a, compound B1, propylene glycol 1, glycerin 2, lanolin 1, betaine 1, polyoxyethylene monolaurate 5, glyceryl monostearate 10, hydroxyethyl cellulose 0.1, xanthan gum 0.05, ginseng extract 1, ganoderma lucidum extract 1, leontopodium alpinum extract 5, vitamin E1.5, hydrolyzed protein 2%, balance deionized water, was synthesized.

Example 3 a cosmetic composition comprising a composition wherein 1.1 said compound a is synthesized 1%, compound B2%, propylene glycol 3%, panthenol 4%, cetyl alcohol 1.5%, lanolin 1.5%, polyoxyethylene monolaurate 10%, glyceryl monostearate 10%, hydroxyethyl cellulose 0.1%, xanthan gum 0.1%, ginseng extract 3%, ganoderma lucidum extract 2%, edelweiss extract 5%, vitamin E2%, hydrolyzed protein 3%, and balance deionized water.

Comparative example 1, which differs from example 2 in that compound a and compound B are not present, made up with deionized water.

Comparative example 2, which differs from example 2 in that it contains only 2% of compound a.

Comparative example 3 differs from example 2 in that it contains only 2% of compound B.

Safety test

The skin irritation test was carried out by dividing 18 healthy rabbits into 3 groups, each group having half male and female, depilating one side of the spinal column of the animal 24 hours before administration with Na2S, applying the compositions of examples 1-3, respectively, and administering for 24 hours, and then removing the composition from the skin with warm water, and no significant skin irritation was observed.

The patch test is mainly used for detecting the irritation of the final cosmetic product or raw material. In examples 1 to 3 of the present invention, a closed patch test of a human body was performed to evaluate the potential skin irritation.

Suitable volunteers were selected 40, and randomly selected in the age range of 18-60 years. 1mL of the liquid sample was added dropwise to the filter paper sheet, which was then placed in a plaque tester. A blank control is set and an equal amount of sample solvent, such as deionized water, is added to the control cuvette well. The test part is selected as the back of a human body, and the spot tester is fixedly attached to the back of the testee by using a non-irritant adhesive tape. The test period lasted 24 h. In order to ensure the accuracy, credibility and scientificity of test results, the volunteers cannot remove the spot tester or make the tested part contact water according to the requirements during the test. And removing the spot tester after 24h, standing for 30min, waiting for the indentation to disappear, and observing the reaction of the skin. If the test result is negative, the test needs to be observed once more at 24h and 48h after the patch test.

The results of the spotting test are shown in Table 1

TABLE 1 Patch test results

"-" ═ negative reactions;

"±" ═ suspicious reaction: only faint erythema;

"+" ═ weak positive reaction (erythema reaction): erythema, infiltration, edema, and possibly pimples;

"+ +", strong positive reaction (herpes response); erythema, infiltration, edema, pimples, herpes; the reaction may be beyond the test area;

"+ + + +" -very strong positive reaction (fusogenic herpes response); obvious erythema, severe infiltration, edema, and fusional herpes; the reaction goes beyond the test area.

As can be seen from table 1, the cosmetic compositions provided in examples 1-3 all produced only 1 suspected reaction in the test. The cosmetic composition provided by the invention is safe and does not bring adverse reactions to human bodies.

Second, anti-aging experiment

Free radicals are intermediates of biochemical reactions during vital activities and can cause skin aging. The anti-aging effect of the compositions of examples 1 to 3 and comparative examples 1 to 3 according to the present invention was evaluated on the effect on DPPH radicals. The detection method comprises the following steps: 3.0mL (0.02mg/mL) of an absolute ethyl alcohol solution of DPPH and 3.0mL (3mg/mL) of an absolute ethyl alcohol diluent of each sample are sequentially added into a 10mL colorimetric tube, absolute ethyl alcohol is added to the mixture to a scale, the mixture is immediately mixed, a 1cm cuvette is used for measuring the light absorption value at the wavelength of 517nm and marking the value as Ai, the mixture is stored in a greenhouse in a dark place for 30min and then the light absorption value is measured and marked as Aj, and a control test is an ethanol solution only added with DPPH, and the light absorption value is marked as Ac. The radical clearance (K) was calculated as follows:

K(％)＝[1-(Ai-Aj)/Ac]*100％

the average value of three measurements was taken and the results are shown in Table 2

TABLE 2

Sample (I)	Clearance rate%
		Example 1	80.5
Example 2	89.2
		Example 3	81.3
Comparative example 1	37.8
		Comparative example 2	76.6
Comparative example 3	75.3

As can be seen from the experimental results of Table 1, the cosmetic composition provided by the present invention can effectively remove free radicals and prevent skin aging. It was surprisingly found that the comparison of example 2 with comparative examples 1 to 3 concluded that the clearance was 89.2% maximum and that the two were synergistic when the content of compound a and compound B was 1%.

Third, stability test

Sample preparation: examples 1 to 3 products

The test method comprises the following steps: internal control standard (illumination for 1 month, high and low temperature test for 3 months); the method comprises the following steps: is higher than the national standard and the industry standard. The test results show that examples 1 to 3 have very good stability.

Fourthly, 60 people try out the composition prepared by the compositions of the embodiments 1 to 3 for 28 days, each group has 20 people, and 95 percent of results show that the composition can obviously improve the skin luster, moisten the face, and has no allergy or stimulation.

The foregoing examples are illustrative of embodiments of the present invention only and are not intended to be limiting in any way; those skilled in the art can make various changes and modifications to the disclosed technology, which are equivalent to those of the embodiments of the present invention, and it is within the scope of the present invention to make various changes and modifications of the invention based on the technical spirit of the present invention.

Claims (9)

1. A cosmetic composition for scavenging free radicals and resisting aging comprises 0.5-2% of imidazo [1, 2-a ] pyridine compound and 0.5-2% of pyrazine-oxazole biaryl compound in percentage by mass.

2. The composition of claim 1, wherein the imidazo [1, 2-a ] pyridine compound is ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate (formula I) and the pyrazine-oxazole biaryl compound is 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole (formula II).

3. The composition of claim 2, wherein the composition comprises 1% ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate and 1% 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole.

4. The composition of any one of claims 1-3, further comprising a humectant, an emulsifier, a thickener, a vitamin, a hydrolyzed protein, a plant extract, and deionized water.

5. The composition of claim 4, further comprising 2-10% of a humectant, 10-20% of an emulsifier, 0.1-0.2% of a thickener, 2-2% of vitamin E1, 1-3% of a hydrolyzed protein, 5-10% of a plant extract, and the balance deionized water.

6. The composition of claim 5, wherein the humectant comprises one or more of sorbitol, propylene glycol, glycerin, lanolin, panthenol, cetyl alcohol, amino acids, and betaine; the emulsifier comprises one or more of polyoxyethylene monostearate, glyceryl monostearate, tween 60, tween 80 and polyoxyethylene monolaurate; the thickening agent comprises one or more of hydroxyethyl cellulose, carboxymethyl cellulose, PMC, xanthan gum, hydroxypropyl cellulose and carrageenan; the plant extract comprises one or more of Ginseng radix extract, Ganoderma extract, fructus Hippophae extract, cornu Cervi Pantotrichum extract, and herba Leontopodii Kaempferi extract.

7. The composition of claim 6, wherein the composition consists of: 0.5% of ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate, 0.5% of 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole, 2% of sorbitol, 2% of glycerol, 1% of panthenol, 1% of cetyl alcohol, 2% of polyoxyethylene monostearate, tween 803, 10% of glyceryl monostearate, 0.2% of hydroxyethyl cellulose, 1% of sea buckthorn extract, 1% of ganoderma lucidum extract, 5% of leontopodium alpinum extract, vitamin E1%, 3% of hydrolyzed protein and the balance of deionized water.

8. The composition of claim 6, wherein the composition consists of ethyl 2- { (2-phenylimidazo [1, 2-a ] pyridin-3-yl) amino } acetate 1%, 2- (3, 6-dimethylpyrazin-2-yl) benzoxazole 1%, propylene glycol 1%, glycerol 2%, lanolin 1%, betaine 1%, polyoxyethylene monolaurate 5%, glyceryl monostearate 10%, hydroxyethyl cellulose 0.1%, xanthan gum 0.05%, ginseng extract 1%, ganoderma extract 1%, edelweiss extract 5%, vitamin E1.5%, hydrolyzed protein 2%, and the balance deionized water.

9. Use of a composition according to any one of claims 1 to 8 for the preparation of a cosmetic for scavenging free radicals and anti-ageing.