CN107822916A - A kind of whitening active ingredients - Google Patents

Abstract

The invention discloses a whitening active ingredient, which comprises 3-(3-(substituted aryl) carbamoyl) methyl benzoacrylate and vitamin P. The weight ratio of 3-(3-(substituted aryl)carbamoyl)methyl benzoacrylate to vitamin P is 1:30-30:1. The present invention has a certain inhibitory effect on tyrosinase through the compatibility of 3-(3-(substituted aryl) carbamoyl) methyl phenylacrylate and vitamin P, especially in a certain proportion range, it has a very significant synergistic effect, Can be used as a whitening active agent.

Description

A whitening active ingredient

technical field

The invention relates to a whitening active ingredient, which belongs to the field of cosmetic and skin care products.

Background technique

Skin hyperpigmentation is considered a common dermatological reaction that causes discomfort to individuals suffering from it, as it significantly affects psychological well-being, promoting productivity, social activity and lowered self-esteem. Its basic feature is: increased production and accumulation of melamine on the skin. As the main factors causing this change, we can mention endocrine dysfunction, exposure to solar radiation, pregnancy, genetic factors, aging and skin inflammation caused by acne or contact dermatitis.

The formation of skin melanin is a very complicated process. In the process of skin melanin formation, due to the influence of ultraviolet rays, genetics, endocrine, inflammatory mediators, improper diet and other factors, the pigment metabolism is abnormal, and the skin melanin grows too fast and does not distribute well. Even, it will cause local skin hyperdarkness and pigmentation, manifested as chloasma, freckles and post-inflammatory pigmentation. Tyrosinase is an oxidase containing Cu ions. It is commonly found in mammals, plants and microorganisms. It is mainly involved in the formation of melanin and other polyphenols in organisms. It is the key enzyme for the synthesis of melanin in organisms. Tyrosinase Acidase inhibitors inhibit melanin production by inhibiting tyrosinase activity, so they can be used to prevent and treat pigmentation. Research on tyrosinase inhibitors has been ongoing.

Contents of the invention

Aiming at the above-mentioned problems in the prior art, the present invention provides a whitening active ingredient, which has a good effect of inhibiting tyrosinase and is suitable as a whitening active agent.

In order to achieve the above object, the technical solution adopted by the present invention is: a whitening active ingredient, including 3-(3-(substituted aryl)carbamoyl)methyl benzoacrylate and vitamin P.

The weight ratio of methyl 3-(3-(substituted aryl)carbamoyl)benzoacrylate to vitamin P is 1:30-30:1.

Through the compatibility of 3-(3-(substituted aryl)carbamoyl)methyl phenylacrylate and vitamin P, the present invention has a certain inhibitory effect on tyrosinase, especially in a certain proportion range, it has a very significant synergistic effect, Can be used as a whitening active agent.

Detailed ways

The present invention will be further described below.

Vitamin P of the present invention, another name: rutin, molecular formula: C27H30O16, molecular weight: 610.51, CAS number: 153-18-4.

3-(3-(substituted aryl) carbamoyl) synthetic general method of methyl phenylacrylate of the present invention:

Using m-bromobenzoic acid (1) as raw material, react with methyl acrylate (2) to synthesize 3-(2-(methoxyformyl) vinyl) benzoic acid (3) through Heck reaction, and then react with thionyl chloride to obtain 3-(2-(methoxyformyl)vinyl)benzoyl chloride (4), acid chloride (4) reacts with substituted arylamine (5) to obtain 3-(3-(substituted aryl)carbamoyl)benzene Methyl acrylate.

Synthesis of 3-(2-(methoxyformyl)vinyl)benzoic acid (3)

Dissolve m-bromobenzoic acid (3.0 g, 15 mmol) and methyl acrylate (6.45 g, 75 mmol) in N,N-dimethylformamide (50 mL), add triethylamine (202 mg, 2 mmol ), palladium acetate (67 mg, 0.3 mmol) and tris(o-methylphenyl)phosphine (92 mg, 0.3 mmol). Under nitrogen, the temperature of the reaction solution was raised to 110° C. for 5 hours. Then cool to room temperature, adjust the pH value to about 2 with dilute hydrochloric acid, filter the precipitated solid, and recrystallize with acetone to obtain 2.15 g of white solid, with a yield of 70%. ¹ HNMR (400 MHz, DMSO- d ₆ ) δ 8.20 (d, J = 1.8 Hz, 1H), 8.02-7.95 (m, 2H), 7.74(d, J = 16.1 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 6.72 (d, J = 16.1 Hz, 1H),3.74 (s, 3H).

Synthesis of 3-(2-(methoxyformyl)vinyl)benzoyl chloride (4)

3-(2-(Methoxyformyl)vinyl)benzoic acid 3 (1.03 g, 5 mmol) was dissolved in an appropriate amount of toluene, added thionyl chloride (1.1 mL, 15 mmol) and 1 drop of N,N-di Methylformamide. After reacting at 90°C for 1 hour, toluene and excess thionyl chloride were distilled off under reduced pressure to obtain acid chloride 4. The crude product was used directly in the next step without purification.

General Synthesis of Methyl 3-(3-(Substituted Aryl)carbamoyl)Benzacrylate (6)

Substituted arylamines 5a-o (5 mmol) were dissolved in dichloromethane (20 mL), cooled in an ice-water bath to 0°C, triethylamine (7 mmol) was added, and then a solution of compound 4 in dichloromethane was slowly added dropwise. The reaction solution was slowly raised to room temperature and stirred for 1-2 hours until compound 4 disappeared (monitored by TLC). After the reaction, the pH value was adjusted to about 2 with dilute hydrochloric acid. The organic layer was separated, the aqueous layer was extracted with dichloromethane, the organic layers were combined, washed with water, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. Separation by column chromatography (petroleum ether: ethyl acetate = 3:1) gave the compound 3-(3-(substituted aryl) carbamoyl) methyl benzoacrylate.

White solid, yield 35%. 1H NMR (400 MHz, DMSO-d6) δ 9.97 (s, 1H), 8.34 (d,J = 1.7 Hz, 1H), 8.02-7.95 (m, 2H), 7.77 (d , J = 16.1 Hz, 1H), 7.59 (t, J =7.7 Hz, 1H), 7.41-7.13 (m, 4H), 6.80 (d, J = 16.1 Hz, 1H), 3.78 (s, 3H), 2.26 (s, 3H).

Tyrosinase inhibition test:

Experiments were carried out using the mushroom tyrosinase dopa rate oxidation method. 2 mL of reaction mixture in different administration groups: 0.1 MPBS, pH 6.7-6.8, 0.9 mL of PBS plus 1 mL of different concentrations of medicinal solutions, plus 0.1 mL of 0.03% tyrosine. Incubate in an incubator at 37°C for 10min, add 0.1mL of tyrosinase (350u/mL) aqueous solution, mix the solution evenly, place it in an incubator at 37°C for 25min, and determine the absorbance value at 475mmN with a spectrophotometer (A); The blank group is treated with an equal volume of PBS instead of the tyrosinase solution, and the absorbance value is determined at 475mmN with a spectrophotometer (B); the control group is replaced with an equal volume of distilled water, and is measured at 475mm with a spectrophotometer Absorbance value (C); in the total blank group, an equal volume of distilled water was used instead of the drug solution, and an equal volume of PBS was used instead of the tyrosinase solution, and the absorbance value (D) was determined at 475mmN with a spectrophotometer. 0.1M PBS, pH6.7-6.8 was prepared according to the 2005 edition of "Chinese Pharmacopoeia". The concentration of the drug solution in each group was 10%.

A is 3-(3-(substituted aryl) carbamoyl) methyl benzoacrylate, B is vitamin P, the results are as follows,

Experimental observation of the inhibitory effect of 3-(3-(substituted aryl) carbamoyl) methyl phenylacrylate, vitamin P and their different ratios on tyrosinase activity, the results show that different ratios of whitening active liquid have The tyrosinase activity has a certain inhibitory effect, but the effect is not very significant. Compared with the single active ingredient, the mixed synergy has an inhibition rate of about 5-10%, but the applicant found that the ratio is 8-10:1 The inhibition rate in this interval has reached a very high level, and it can be seen that the synergistic effect of the two in the interval on the inhibition of tyrosinase is obvious, and it can be seen that it has a very good whitening effect.

Claims (2)

1. A whitening active ingredient, characterized in that it comprises: Methyl 3-(3-(substituted aryl)carbamoyl)benzoacrylate and vitamin P. 2. A whitening active ingredient according to claim 1, wherein the weight ratio of 3-(3-(substituted aryl)carbamoyl)methyl phenylacrylate to vitamin P is 1:30-30:1 .