KR101763933B1 - Phenolic acid derivative and cosmetic composition comprising the same - Google Patents

Abstract

The present invention relates to a phenolic acid derivative having an amino acid or peptide bonded thereto, a method for producing the same, and a cosmetic composition for skin whitening and antiaging agent containing the same.

Description

PHENOLIC ACID DERIVATIVE AND COSMETIC COMPOSITION COMPRISING THE SAME [0002]

The present invention relates to a phenolic acid derivative having an amino acid or peptide bonded thereto, a method for producing the same, and a cosmetic composition for skin whitening and antiaging agent containing the same.

Recently, cosmetic research has been focused on the development of functional cosmetics incorporating the concept of healing. Cosmeceutical is a combination of cosmetics and pharmaceuticals. It is called functional cosmetics. It focuses on research on active ingredients with high functionality, transdermal absorption of effective substances, formulation studies including them, and basic research on skin physiology.

The main areas of interest in functional cosmetics technology are delays in skin aging, skin protection from external sources such as ultraviolet and pollutants, whitening, as well as anti-wrinkle, smoothing stress, skin moisturizing We have been studying the development of functional materials and the methods for measuring the efficacy and skin stability of these substances. In the future, it will lead to the study of cells or genes that remove the cause in research on the factors involved in skin improvement.

Functional cosmetics can be defined as products that help to whiten skin, products that help to improve wrinkles on the skin, products that help to protect skin from burns or ultraviolet rays.

In general, human skin color depends on substances such as melanin, carotene and hemoglobin present in the skin. The most important effect is known as melanin. Melanin is synthesized by the melanocyte, a pigmented cell in the basal layer of the skin, and transformed into peripheral keratinocyte to show the color of human skin. The production of melanin is controlled by a complex mechanism depending on various factors.

The most widely used substances in whitening cosmetics are substances that inhibit the activity of tyrosinase, an enzyme important for the synthesis of melanin in pigment cells, and raw materials such as arbutin, licorice extract, mulberry extract and kojic acid have been developed and used . Vitamin C, glutathione and coenzyme Q10, which block melanin synthesis, are also used as raw materials for whitening cosmetics.

In order to develop functional cosmetics, it is necessary to develop functional ingredients that can physically demonstrate their efficacy in skin. However, the functional raw materials are used in cosmetics because of their poor efficacy, poor stability, skin side effects, and low skin absorption.

In order to synthesize a whitening agent that meets these criteria, in the art, a biocompatible substance is introduced into a substance known to have a whitening activity, so as to appropriately control whitening activity and biocompatibility, and to secure storage stability Has progressed.

Recent research has shown that polyphenols act as powerful scavengers to remove the harmful oxygen that accumulates in the body. In other words, polyphenols have been reported to neutralize unstable oxidizing substances in the skin and inhibit the formation of wrinkles. Furthermore, unlike vitamin C and E, polyphenol not only does not cause irritation to the skin, but also has a longer metabolism time than vitamins. Therefore, when used as a cream formulated cosmetic, It is a customary practice in the industry.

Protocatechuic acid (KR-0094635) and protocatechualaldehyde (KR-0025288) among phenolic acids not only can be safely used without side effects on skin, but also increase collagen synthesis and inhibit the activity of collagenase enzyme It is known that there are wrinkle improving effect, skin whitening effect, inflammation inhibiting effect, anti-obesity effect, hair loss and hair growth effect.

In addition, the gentic acid derivative has excellent melanogenesis inhibitory effect and is used as a skin-safe whitening cosmetic composition (KR-0046577).

In addition, hexyl gallate, methyl gallate, and stearyl gallate, which are plant extracts of gallic acid and gallic acid, have antioxidant activity by lowering the peroxide value compared to tocopherol, which is a natural antioxidant (KR-0056054).

The present inventors have found that an amino acid derivative of phenolic acid and its preparation, which can enhance biocompatibility and stability while enhancing whitening effect and antioxidant ability by binding phenolic acid derivative with amino acid or peptide for enhancing efficacy of the above- The present invention has been completed.

Amino acids are molecules with biological activity, which have amino groups, carboxyl groups and various residues as basic constituent units of proteins. The residues of amino acids can be divided into hydrophobic and hydrophilic ones, and amino acids having a hydrocarbon chain or a ring are hydrophobic. Typically, there are 20 types - phenylalanine (F), tyrosine (Y), tryptophan (W), serine (S), threonine (T), aspartic acid (D), asparagine (N), glutamic acid (A), valine (V), glutamine (Q), lysine (K), arginine (R), histidine (H), cysteine (C), methionine ), Leucine (L), and isoleucine (I)), and three-dimensionally, L- and D- structures, respectively. Further exemplary 20 amino acids in addition to beta-alanine, sarcosine, norvaline, norleucine, ornithine thin, alpha-amino adipic acid, N-methyl-leucine, N-methyl-phenylalanine, phenylglycine, l kolrik acid, 4-keto-l kolrik acid There are many kinds of amino acids not found in proteins such as beta-hydroxy-leucine, beta-methyl aspartic acid, beta-mercaptolin, lan cyanine, dihydroalanine and dihydrobutyrin.

Peptides are polymeric molecules of amino acids and polymers of more than 100 amino acids are generally classified as proteins. Peptide bonds are bonds between water molecules (-CONH-) and water molecules escaping between the carboxyl group (-COOH) and the amine group (-NH ₂ ). That is, the peptide refers to a compound in which two or more amino acids, which are basic units of a protein, are linked by an amide bond. The peptide is a polymer formed by bonding 2 to 50 amino acids, and has a molecular weight of 100,000 or less. The number of peptides with 2, 3, 4, etc. constituent amino acids is referred to as a dipeptide, a tripeptide, a tetrapeptide or the like depending on the number of peptides. About 10 or fewer amino acid polymers are referred to as oligopeptides, and more than one amino acid is linked by an amide bond is referred to as a polypeptide.

In the present invention, an amino acid or a peptide is introduced into a carboxy group of phenolic acid to synthesize a phenolic acid-peptide derivative, and the effect of inhibiting tyrosinase activity and the antioxidative effect are promoted.

A basic object of the present invention is to provide a phenolic acid derivative to which an amino acid or peptide of formula (I) is bonded.

(I)

R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH.

Yet another object of the present invention is to provide a method for preparing a solid support comprising: (i) introducing one to five amino acids (R < ⁶ >) on a solid support resin; (ii) binding a phenolic acid derivative to the peptide comprising the amino acid of (i) or 2 to 5 amino acids to form a peptide-bound phenolic acid derivative represented by the following formula (I); And (iii) separating the peptide-bound phenolics acid derivative obtained in the step (ii) from the solid support resin, wherein the amino acid or peptide-linked phenolics acid derivative is represented by formula .

It is still another object of the present invention to provide a skin whitening cosmetic composition comprising a phenolic acid derivative having an amino acid or a peptide of the above formula (I) and a physiologically acceptable cosmetic base.

It is still another object of the present invention to provide a cosmetic composition for preventing skin aging comprising a phenolic acid derivative having an amino acid or peptide of formula (I) and a physiologically acceptable cosmetic base.

The above-described basic object of the present invention can be achieved by providing a phenolic acid derivative to which an amino acid or a peptide of the following formula (I) is bonded.

(I)

R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH.

Phenolic acid is an aromatic carboxylic acid having -OH and -COOH bonded to the benzene nucleus and is an aromatic carboxylic acid having at least one of salicylic acid, protocatechuic acid, gallic acid, syringic acid, Gentisic acid, vanillic acid, and the like. However, in the present invention, the phenolic acid does not contain resorcillic acid.

The amino acid or peptide-linked phenolic acid derivative of the formula (I) of the present invention is a compound having a biocompatible and safe amino acid or peptide introduced into phenolic acid. As a result, the phenolic acid derivative of the above formula (I) is more suitable as a raw material for functional cosmetic, because the free radical scavenging ability and thyrosinase inhibiting ability are remarkably increased, and the biocompatibility and stability are improved as compared with phenolic acid.

Preferably, R ¹ , R ² , R ³ , R ⁴ and R ⁵ of the phenolic acid derivative of the above formula (I) are represented by R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH , Derivatives of protocatechuic acid); R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH (ie derivatives of gentic acid); ^{R 3 = R 4 = R 5} = H and R ¹ = R ² = OH (i.e., o - derivatives of Pyro category cue acid (o -pyrocatechuic acid)); R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH (ie, derivatives of gallic acid); R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ (ie derivatives of vanillyric acid); Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH (ie derivatives of cyclic acid).

Preferably, R < ⁶ > of the compound of formula (I) may be phenylalanine, tryptophan or tyrosine.

Still another object of the present invention is to provide a method for preparing a solid support comprising: (i) introducing one to five amino acids (R < ⁶ >) on a solid support resin; (ii) binding a phenolic acid derivative to the peptide comprising the amino acid of (i) or 2 to 5 amino acids to form a peptide-bound phenolic acid derivative represented by the following formula (I); And (iii) separating the peptide-bound phenolics acid derivative obtained in the step (ii) from the solid support resin, wherein the amino acid or peptide-linked phenolics acid derivative is represented by the formula (I) ≪ / RTI >

Step (i) of the method for producing a phenolic acid derivative of the present invention can be carried out according to a conventional solid phase peptide synthesis. In step (i), the same or different amino acids may be introduced into the solid support resin. Preferably, the introduced amino acid may be phenylalanine, tryptophan or tyrosine.

For example, in step (i), two equivalents of Fmoc-amino acid may be added to a polystyrene resin to which a linker is introduced, such as benzotriazole-1-yloxy-tris (dimethylamino) -phosphonium hexafluoro-phosphate (BOP) (1-hydroxybenzotriazole), DIEA (diisopropylethylamine) and N-methylpyrrolidone (NMP) for about 2 hours to introduce an amino acid or peptide.

In step (ii) of the method of the present invention, R ¹ , R ² , R ³ , R ⁴ and R ⁵ of the phenolic acid bonded to the amino acid or peptide introduced into the solid support resin in step (i) H, an OH or OCH _3. Preferably, R ¹ , R ² , R ³ , R ⁴ and R ⁵ are selected from the group consisting of R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH (ie protocatechuic acid); R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH (ie, gentic acid); R ³ = R ⁴ = R ⁵ = H and R ¹ = R ² = OH (ie, o -pyrocatechuic acid); R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH (i.e., gallic acid); R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ (ie, vanillylic acid); Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH (ie, cyclic acid).

In one embodiment of the present invention, in the step (ii), the phenolic acid is introduced in the same manner as the Fmoc-amino acid. The reaction of step (ii) is carried out at room temperature for 20 minutes to 12 hours, more preferably for 30 minutes to 5 hours. As the coupling agent for introducing phenolic acid, HBTU, BOP, DCC, DIC, HOBt, HOAt or HOOBT, or a mixture thereof may be used.

In particular, the end groups (R ⁷ ) differ depending on the type of the solid phase and the type of the linker. For example, when aminomethylresin with a link amide linker is used, R ⁷ is obtained as an amide (-NH ₂ ) form and when synthesized on a 2-CTC resin with a hydroxyamine linker, R ⁷ is hydroxyamine (NHOH) If the form is obtained, the synthesis on the 2-CTC resin is R ⁷ is obtained with a carboxylic acid (-COOH) form.

In step (iii) of the method of the present invention, trifluoroacetic acid (TFA) / dichloromethane (DCM) is added to separate the amino acid or peptide-bound phenolic acid derivative from the solid support resin. The reaction of step (iii) is carried out at room temperature for 10 minutes to 1 hour.

Still another object of the present invention can be attained by providing a cosmetic composition for skin whitening comprising a phenolic acid derivative and a physiologically acceptable cosmetic base to which the amino acid or peptide of formula (I) is bonded.

Preferably, R ¹ , R ² , R ³ , R ⁴ and R ⁵ of the phenolic acid derivative (formula (I)) contained in the cosmetic composition for skin whitening of the present invention are represented by R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH (i.e., derivatives of protocatechuic acid); R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH (ie derivatives of gentisic acid); ^{R 3 = R 4 = R 5} = H and R ¹ = R ² = OH (i.e., o - derivatives of Pyro category cue acid (o -pyrocatechuic acid)); R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH (ie a derivative of gallic acid); R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ (ie, a derivative of vanillic acid); Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH (ie derivatives of syringic acid).

Also preferably, R ⁶ of the compound of formula (I) may be phenylalanine, tryptophan or tyrosine.

The skin whitening cosmetic composition may be in the form of a lotion, an emulsion, a cream, a pack or a serum, and may further contain an ultraviolet screening agent or a light scattering agent.

Still another object of the present invention can be attained by providing a cosmetic composition for preventing skin aging comprising a phenolic acid derivative having an amino acid or peptide of formula (I) and a physiologically acceptable cosmetic base.

Preferably, R ¹ , R ² , R ³ , R ⁴ and R ⁵ of the phenolic acid derivative (formula (I)) contained in the cosmetic composition for preventing skin aging according to the present invention are represented by R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH (i.e., derivatives of protocatechuic acid); R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH (ie derivatives of gentisic acid); ^{R 3 = R 4 = R 5} = H and R ¹ = R ² = OH (i.e., o - derivatives of Pyro category cue acid (o -pyrocatechuic acid)); R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH (ie a derivative of gallic acid); R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ (ie, a derivative of vanillic acid); Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH (ie derivatives of syringic acid).

Also preferably, R ⁶ of the compound of formula (I) may be phenylalanine, tryptophan or tyrosine.

The cosmetic composition for preventing skin aging may be a lotion, a milky lotion, a cream, a pack or a cosmetic formulation, and may further comprise a sunscreen agent or a light scattering agent.

The phenolic acid derivative of the present invention is a compound in which a biocompatible amino acid or peptide is introduced into phenolic acid, which is a conventional antioxidant and whitening agent, and has the stability of improving the free radical scavenging ability and simultaneously enhancing the whitening effect by the action of inhibiting melanin production High skin whitening and anti-aging substances.

1 is a graph comparing the free radical scavenging activity of antioxidants comprising the phenolic acid according to the prior art and the phenolic acid derivative of the present invention.
2 is a graph comparing the inhibitory activity of tyrosinase activity of the phenolic acid according to the prior art with the phenolic acid derivative of the present invention.
3 is a graph comparing the inhibitory effect of phenolic acid according to the prior art on the intracellular melanin synthesis of the phenolic acid derivative of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, it should be understood that the following examples are intended to illustrate specific embodiments of the present invention and are not intended to limit or limit the scope of the present invention.

Example  1. Solid-state antioxidant using polystyrene resin Peptides  synthesis

1-yl-oxy-tris (dimethylamino) -phosphonium hexafluorophosphate (BOP), HOBt (1-hydroxybenzotriazole), and the like were reacted with 2 equivalents of Fmoc-amino acid on the polystyrene resin into which the peptide was linked by solid- And DIEA (diisopropylethylamine) and N - methylpyrrolidone (NMP) for 2 hours to synthesize the peptide. Conditions for removing Fmoc were treated with 20% piperidine / NMP (piperidine / NMP) for 2 min each for 3 min and 7 min.

Example  2. Amino acids or The peptide  Introduced new Phenolic acid - Peptides  derivative beauty Manufacture of Baekje

Amino acids such as protocatechuic acid, gentic acid, resorcillic acid, gallic acid, vanillyric acid, cyclic acid or quinic acid were synthesized in the same manner as Fmoc-amino acid on the polystyrene resin on which the peptide prepared in Example 1 was synthesized And the reaction time was 30 minutes to 5 hours to prepare a novel phenolic acid-peptide derivative. The target substance was then removed from the resin by treatment with 25% trifluoroacetic acid (TFA) / dichloromethane (DCM) and then precipitated with ether to finally obtain the phenolic acid-peptide derivative .

Example  3. Hydroxy Cinnamic acid - Peptides  Identification of derivatives

Phenolic acid-peptide derivatives were confirmed to be the desired product by ESI-MS after confirming purity by HPLC. The formula of the synthesized compound is as follows. As a result of HPLC analysis, it was confirmed that this substance was a pure substance, and mass analysis by ESI-MS confirmed that it was a phenolic acid-peptide derivative. The results in Table 1 below are higher than the original molecular weight because they are cationized.

Determination of yield, purity and mass of phenolic acid-peptide derivatives
Yield
(%) water
(%) ESI-MS Calculated value Actual value Protocateque Iksan (PA) 95 154.2 ([M + H] < + >) [ 154.3 PA-phenylalanine 70 86 301.3 ([M + H] < + >) [ 301.7 PA-tryptophan 65 84 340.4 ([M + H] < + >) [ 340.7 PA-tyrosine 84 90 317.4 ([M + H] < + >) [ 317.9

Example  4. The Phenolic acid - Peptides  Freedom of derivative Radical Scatters  Test

The substance obtained in Example 2 was added to a DPPH radical solution (0.1 M) dissolved in methanol, reacted at 25 ° C for 10 minutes, and the absorbance at 516 nm was measured. The free radical scavenging activity was measured by the following equation.

% DPPH radical scavenging ability = (A-B) / A x 100

Where A is the absorbance of the material without the material of Example 2 and B is the absorbance of the absorbed material. The free radical scavenging activity of each of the peptides and phenolic acids introduced by this equation was measured and compared. The results are shown in FIG. In the above figures, there was an increase or decrease in free radical scavenging ability when an amino acid having a ring structure at the residue was introduced into phenolic acid.

Example  5. The Phenolic acid - Peptides  Derivative Tyrosinase  activation Inhibition  Test

Phosphate buffer (pH 6.8, 0.1 M) was added with tyrosinase and tyrosine

And the substance obtained in Example 4 were added and reacted at 37 ° C for 10 minutes,

The pack was transferred to stop the reaction. The absorbance was then measured at 475 nm,

The activity inhibition degree of tyrosinase was measured by the formula.

% Active inhibition = (A-B) / A x 100

Where A is the absorbance of the material without addition of the material from Example 4 and B is the absorbance of the material added.

The degree of inhibition of each tyrosinase activity was compared according to the type of amino acid introduced by this formula, and the results are shown in FIG. The concentration of the whitening substance in the reaction solution was 20 μM.

Example  6. The Phenolic acid - Peptides  Test for inhibition of intracellular melanin synthesis of derivatives

By measuring the intracellular melanin content using B16 cells, the whitening effect was enhanced and the possibility of cell permeation was confirmed. The results are shown in Fig. In the above figure, among the phenolic acid derivatives having an amino acid bond, the protocatechium itself promotes melanin synthesis but inhibits melanin synthesis by binding of amino acids. From these results, it was confirmed that the phenolic acid peptides penetrate the cells and participate in the synthesis of melanin and show inhibitory activity.

Claims (20)

A phenolic acid derivative having an amino acid or peptide bonded thereto represented by the following formula (I):

(I)
R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH, except that the salicylic acid derivative in which one of R ¹ or R ⁵ is OH is excluded and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH; R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH; R ³ = R ⁴ = R ⁵ = H and R ¹ = R ² = OH; R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH; R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ ; Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH. delete The amino acid or peptide-linked phenolic acid derivative according to claim 1, wherein the R ⁶ is selected from the group consisting of phenylalanine, tryptophan and tyrosine. (i) introducing one to five amino acids (R < ⁶ >) onto a solid support resin;
(ii) binding a phenolic acid derivative to the peptide comprising the amino acid of (i) or 2 to 5 amino acids to form a peptide-bound phenolic acid derivative represented by the following formula (I); And
(iii) separating the peptide-bound phenolic acid derivative obtained in the step (ii) from the solid support resin, wherein the peptide-bound phenolic acid derivative has the formula (I)

(I)
R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH, except that the salicylic acid derivative in which one of R ¹ or R ⁵ is OH is excluded and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH; R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH; R ³ = R ⁴ = R ⁵ = H and R ¹ = R ² = OH; R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH; R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ ; Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH. delete 5. The method according to claim 4, wherein the R ⁶ is selected from the group consisting of phenylalanine, tryptophan, and tyrosine. 5. The method according to claim 4, wherein at least one coupling agent selected from the group consisting of HBTU, BOP, DCC, DIC, HOBt, HOAt and HOOBT is added in step (ii) ≪ / RTI > 5. The method according to claim 4, wherein the reaction of step (ii) is carried out at room temperature for 20 minutes to 12 hours. 5. The method according to claim 4, wherein trifluoroacetic acid (TFA) / dichloromethane (DCM) is added in step (iii). 5. The method according to claim 4, wherein the reaction of step (iii) is carried out at room temperature for 10 minutes to 1 hour. WHAT IS CLAIMED IS: 1. A cosmetic composition for skin whitening comprising a phenolic acid derivative and a physiologically acceptable cosmetic base to which an amino acid or peptide of formula (I)

(I)
R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH, except that the salicylic acid derivative in which one of R ¹ or R ⁵ is OH is excluded and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH; R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH; R ³ = R ⁴ = R ⁵ = H and R ¹ = R ² = OH; R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH; R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ ; Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH. delete The method of claim 11, wherein the cosmetic composition for skin whitening according to the features that R ⁶ is selected from the group consisting of phenylalanine, tryptophan and tyrosine. 12. The cosmetic composition for skin whitening according to claim 11, wherein the composition is a formulation selected from the group consisting of lotion, milky lotion, cream, pack, and serum. 12. The cosmetic composition for whitening skin according to claim 11, further comprising an ultraviolet screening agent or a light scattering agent. A cosmetic composition for inhibiting senescence by free radical scavenging comprising a phenolic acid derivative having an amino acid or peptide bonded to the following formula (I) and a physiologically acceptable cosmetic base:

(I)
R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently H, OH or OCH ₃ ; R ⁶ is an amino acid or a peptide consisting of 2 to 5 amino acids; R ⁷ is NH ₂ , OH or NHOH, except that the salicylic acid derivative in which one of R ¹ or R ⁵ is OH is excluded and R ¹ , R ² , R ³ , R ⁴ and R ⁵ are R ¹ = R ² = R ⁵ = H and R ³ = R ⁴ = OH; R ² = R ³ = R ⁵ = H and R ¹ = R ⁴ = OH; R ³ = R ⁴ = R ⁵ = H and R ¹ = R ² = OH; R ¹ = R ⁵ = H and R ² = R ³ = R ⁴ = OH; R ¹ = R ² = R ⁵ = H, R ³ = OH and R ⁴ = OCH ₃ ; Or R ¹ = R ⁵ = H, R ² = R ⁴ = OCH ₃ and R ³ = OH. delete The cosmetic composition according to claim 16, wherein the R ⁶ is selected from the group consisting of phenylalanine, tryptophan and tyrosine. 17. The cosmetic composition according to claim 16, wherein the composition is a formulation selected from the group consisting of lotion, milky lotion, cream, pack, and serum. 17. The cosmetic composition according to claim 16, which further comprises a UV-blocking agent or a light-scattering agent.

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