Composition and use thereof

Abstract

The present application provides a composition containing a hyaluronic acid-glutamic acid grafted compound and palmitoyl tetrapeptide-7, wherein the mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1. The composition can significantly enhance the anti-inflammatory efficacy of a hyaluronic acid-glutamic acid graft with a high grafting degree, thereby achieving both long-lasting anti-inflammatory and effective anti-inflammatory effects.

Description

Technical Field

[0001] The present application belongs to the field of cosmetic technology, and specifically relates to a composition and its use. Background Art

[0002] In skincare formulations, grafted compounds are often used as active ingredients. It is known that grafted compounds with high grafting degrees can achieve longer-lasting effects in the skin compared to those with low grafting degrees. However, this longer-lasting effect does not necessarily translate into more effective skincare benefits. Enabling active ingredients to more effectively deliver skincare benefits remains a pressing issue in this field. Summary of the Invention

[0003] Previous research by the inventors of this application has shown that high-grafting hyaluronic acid-glutamic acid grafts can exert anti-inflammatory effects, but their anti-inflammatory effects need to be improved compared to hyaluronic acid-glutamic acid grafts with other grafting degrees. Therefore, this application aims to develop a composition formula to enhance the anti-inflammatory efficacy of high-grafting hyaluronic acid-glutamic acid grafts.

[0004] The technical solution of this application is as follows:

[0005] 1. A cosmetic composition comprising palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, and in the grafted compound, at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are linked to the amino groups of the glutamic acid or a salt thereof in the form of an amide bond.

[0006] 2. The composition according to item 1, wherein

[0007] The mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1, preferably in the range of 1:4 to 4:1.

[0008] 3. The composition according to item 1, wherein

[0009] The general formula of the grafted compound is shown in formula (I):

[0010]

[0011] Wherein, in formula (I), R is a metal ion or H, 0≤x<1, 0<y≤1, x+y=1, and n is a positive integer from 1 to 2000.

[0012] 4. The composition according to item 1, wherein

[0013] The grafting rate of the grafted compound is 20% or more, preferably 50% or more, and more preferably 70% to 100%.

[0014] 5. The composition according to item 1, wherein

[0015] The molecular weight of the grafted compound is 3k-500kDa.

[0016] 6. Use of the composition according to any one of Items 1 to 5 for preventing and / or alleviating skin discomfort caused by inflammation.

[0017] 7. Use of the composition according to any one of items 1 to 5 for anti-inflammatory purposes.

[0018] Compared with the prior art, the present invention has the following advantages:

[0019] In the composition of the present application, the hyaluronic acid-glutamic acid graft with a high grafting degree can produce a synergistic effect with palmitoyl tetrapeptide-7, thereby significantly enhancing the anti-inflammatory effect of the hyaluronic acid-glutamic acid graft with a high grafting degree. As a result, the composition of the present application can take into account both long-term anti-inflammatory and effective anti-inflammatory effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 HA-GLU(1) is shown 1 H NMR spectrum. DETAILED DESCRIPTION

[0021] The present application is further described below with reference to examples. It should be understood that the examples are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0022] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as those commonly understood by those skilled in the art. Although methods and materials similar or identical to those described herein may be used in experiments or practical applications, the materials and methods are described herein below. In the event of a conflict, the present specification, including definitions, will prevail. In addition, the materials, methods, and examples are provided for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific examples, which are not intended to limit the scope of this application.

[0023] Composition

[0024] One subject matter of this application relates to a composition. A "composition" is sufficient as long as it can achieve the effects described herein. This includes, but is not limited to, using the components simultaneously or sequentially. "Simultaneous use" includes using the components together in the same formulation or separately in different formulations. "Sequential use" includes using the components sequentially in different formulations, and there is no limitation on the order of sequential use.

[0025] The present application provides a cosmetic composition comprising palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, and in the grafted compound, at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof is connected to the amino group of the glutamic acid or a salt thereof in the form of an amide bond.

[0026] The degree of substitution refers to the molar ratio of glutamic acid or its salt connected to the disaccharide structure of hyaluronic acid or its salt through an amide bond to the disaccharide structure of hyaluronic acid or its salt.

[0027] The hyaluronate includes unmodified hyaluronate or modified hyaluronate (e.g., acetylated hyaluronate), for example, sodium salt, zinc salt, calcium salt, magnesium salt, etc. of hyaluronic acid, or any combination of these salts.

[0028] Glutamate includes unmodified glutamate or modified glutamate, such as hydrochloride, acetate, sulfonate, etc. of glutamic acid, or any combination of these salts.

[0029] In some embodiments of the present application, the general formula of the grafted compound is as shown in formula (I):

[0030]

[0031] Wherein, in formula (I), R is a metal ion or H, 0≤x<1, 0<y≤1, x+y=1, and n is a positive integer from 1 to 2000.

[0032] For example, x can be 0, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 0.99, or any value therebetween;

[0033] y can be 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 or any value therebetween;

[0034] n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560 , 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000 or a positive integer therebetween.

[0035] In some embodiments of the present application, the grafting ratio can be expressed as y / x+y.

[0036] In some embodiments of the present application, the grafting rate is determined by nuclear magnetic resonance spectroscopy. 1 H NMR determination; wherein the grafting rate is obtained by nuclear magnetic resonance detection 1 The calculation is performed by integrating the peak area of ​​the methine (-CH- proton) of glutamic acid or its salt in the grafted compound at a shift to 4.05-4.12 ppm in the H NMR spectrum, or by 1 The calculation is performed by integrating the proton peak areas of the two methylene groups (-CH2-) of glutamic acid or its salt and the methyl group (-CH3-) of hyaluronic acid or its salt in the grafted compound in the H NMR spectrum.

[0037] In some embodiments of the present application, the grafting rate of the grafted compound is 20% or more, preferably 50% or more, and more preferably 70% to 100%. For example, it can be 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or any range therebetween.

[0038] In some embodiments of the present application, the molecular weight of the grafted compound is 3k-500kDa; for example, the molecular weight of the grafted compound can be 3kDa, 5kDa, 10kDa, 15kDa, 20kDa, 25kDa, 30kDa, 35kDa, 40kDa, 45kDa, 50kDa, 55kDa, 60kDa, 65kDa, 70kDa, 75kDa, 80kDa, 85kDa, 90kDa, 95kDa, 100kDa, 110kDa, 120kDa, 130kDa, 140kDa, 150kDa, 160kDa, 170kDa, 180kDa, 190kDa, 200kDa, 210kDa, 220kDa, 230kDa, 240kDa, 250kDa, 260kDa, 270kDa, 280kDa, 290kDa, 300kDa, 310kDa, 320kDa, 330kDa, 340kDa, 350kDa, 360kDa, 370kDa, 380kDa, 390kDa, 400kDa, 410kDa, 420kDa, 430kDa, 440kDa kDa, 410 kDa, 420 kDa, 430 kDa, 440 kDa, 450 kDa, 460 kDa, 470 kDa, 480 kDa, 490 kDa, 500 kDa, or any range therebetween.

[0039] In some embodiments of the present application, the grafted compound is detected by nuclear magnetic resonance. 1 In the HNMR spectrum, the grafted compound has a characteristic peak at a chemical shift δ of 4.00-4.15 ppm; preferably, the grafted compound is detected by nuclear magnetic resonance. 1 In the H NMR spectrum, the grafted compound has characteristic peaks at chemical shifts δ of 2.10-2.25 ppm and 1.71-2.10 ppm.

[0040] In some embodiments of the present application, the mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1, preferably in the range of 1:4 to 4:1; for example, the mass ratio of the grafted compound to palmitoyl tetrapeptide-7 can be 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1 or any range therebetween.

[0041] In a specific embodiment of the present application, the composition includes palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, in which at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino groups of the glutamic acid or a salt thereof in the form of an amide bond, the grafting rate of the grafted compound is greater than 20%, and the general formula of the grafted compound is shown in formula (I):

[0042]

[0043] Wherein, in formula (I), R is a metal ion or H, 0≤x<1, 0<y≤1, x+y=1, and n is a positive integer from 1 to 2000.

[0044] In a specific embodiment of the present application, the composition includes palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, in which at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino group of glutamic acid or a salt thereof in the form of an amide bond, the grafting rate of the grafted compound is greater than 20%, and the molecular weight of the grafted compound is 3k-500kDa.

[0045] In a specific embodiment of the present application, the composition includes palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, in which at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino group of glutamic acid or a salt thereof in the form of an amide bond, the grafting rate of the grafted compound is greater than 20%, the molecular weight of the grafted compound is 3k-500kDa, and the mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1.

[0046] In a specific embodiment of the present application, the composition includes palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, in which at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino group of glutamic acid or a salt thereof in the form of an amide bond, the grafting rate of the grafted compound is greater than 20%, the molecular weight of the grafted compound is 3k-500kDa, the mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1, and the grafted compound is detected by nuclear magnetic resonance. 1 In the H NMR spectrum, the grafted compound has a characteristic peak at a chemical shift δ of 4.00-4.15 ppm.

[0047] In a specific embodiment of the present application, the composition includes palmitoyl tetrapeptide-7 and a grafted compound, wherein the grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, in which at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino group of glutamic acid or a salt thereof in the form of an amide bond, the grafting rate of the grafted compound is greater than 20%, the molecular weight of the grafted compound is 3k-500kDa, the mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:5 to 5:1, and the grafted compound is detected by nuclear magnetic resonance.1 In the H NMR spectrum, the grafted compound has characteristic peaks at chemical shifts δ of 4.00-4.15 ppm, 2.10-2.25 ppm, and 1.71-2.10 ppm.

[0048] In the application, there is no restriction on the source of the grafted compound of hyaluronic acid or its salt and glutamic acid or its salt, and the grafted compound can be purchased commercially or prepared by itself.

[0049] In the present application, the preparation method of the grafted compound of hyaluronic acid or its salt and glutamic acid or its salt is not particularly limited. For example, it can be prepared by the following method: mixing hyaluronic acid or its salt and a quaternary ammonium base, reacting to obtain a quaternary ammonium salt of hyaluronic acid or its salt; dissolving the quaternary ammonium salt of hyaluronic acid or its salt, then adding glutamic acid or its salt, an activator, and a catalyst to react, hydrolyzing under an alkaline environment, and adjusting the pH to obtain a grafted compound of hyaluronic acid or its salt and glutamic acid or its salt (HA-GLU).

[0050] In a specific embodiment of the present application, the quaternary ammonium base includes tetrabutylammonium hydroxide.

[0051] In a specific embodiment of the present application, glutamic acid or a salt thereof includes L-glutamic acid diethyl ester hydrochloride.

[0052] In a specific embodiment of the present application, the activating agent includes 2-chloro-1-methylpyridinium iodide.

[0053] In one embodiment of the present application, the catalyst comprises triethylamine.

[0054] In a specific embodiment of the present application, the quaternary ammonium base salt of hyaluronic acid or its salt is dissolved in an organic solvent, and the organic solvent includes N,N-dimethylformamide (DMF).

[0055] In some embodiments of the present application, the mass ratio of the quaternary ammonium base salt of hyaluronic acid or its salt to glutamic acid or its salt is 1:(0.01-1); for example, it can be 1:0.01, 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1 or any range therebetween.

[0056] In some embodiments of the present application, the mass ratio of glutamic acid or its salt, activator, and catalyst is 1: (0.1-10): (0.1-5); for example, it can be 1:0.1:0.1, 1:0.1:0.2, 1:0.1:0.3, 1:0.1:0.4, 1:0.1:0.5, 1:0.1:0.6, 1:0.1:0.7, 1:0.1:0.8, 1:0.1:0.9, 1:0.1:1.0, 1:0.1:2.0, 1:0.1:3.0, 1:0.1:4.0, 1:0.1:5.0, 1:0.2:0.1, 1:0.2:0.2, 1:0.2:0.3, 1:0.2:0.4, 1:0.1:0.5, 1:0.1:0.6, 1:0.1:0.7, 1:0.1:0.8, 1:0.1:0.9, 1:0.1:1.0, 1:0.1:2.0, 1:0.1:3.0, 1:0.1:4.0, 1:0.1:5.0, 1:0.2:0.1, 1:0.2:0.2, 1:0.2:0.3, 1:0.2:0.4, 1:0.2:0.5, 1 :0.2:0.6、1:0.2:0.7、1:0.2:0.8、1:0.2:0.9、1:0.2:1.0、1:0.2:2.0、1:0.2:3.0、1:0.2:4.0、1:0.2:5.0、1:0.5:0.1、1:0.5:0.2、1:0.5:0.3、1:0.5 :0.4、1:0.5:0.5、1:0.5:0.6、1:0.5:0.7、1:0.5:0.8、1:0.5:0.9、1:0.5:1.0、1:0.5:2.0、1:0.5:3.0、1:0.5:4.0、1:0.5:5.0、1:1.0:0.1、1:1.0:0.2、 1:1.0:0.3, 1:1.0:0.4, 1:1.0:0.5, 1:1.0:0.6, 1:1.0:0.7, 1:1.0:0.8, 1:1.0:0.9, 1:1.0:1.0, 1:1.0:2.0, 1:1.0:3.0, 1:1.0:4.0, 1:1.0:5.0, 1:2. 0:0.1, 1:2.0:0.2, 1:2.0:0.3, 1:2.0:0.4, 1:2.0:0.5, 1:2.0:0.6, 1:2.0:0.7, 1:2.0:0.8, 1:2.0:0.9, 1:2.0:1.0, 1:2.0:2.0, 1:2.0:3.0, 1:2.0:4. 0, 1:2.0:5.0, 1:5.0:0.1, 1:5.0:0.2, 1:5.0:0.3, 1:5.0:0.4, 1:5.0:0.5, 1:5.0:0.6, 1:5.0:0.7, 1:5.0:0.8, 1:5.0:0.9, 1:5.0:1.0, 1:5.0:2.0, 1: 5.0:3.0, 1:5.0:4.0, 1:5.0:5.0, 1:10:0.1, 1:10:0.2, 1:10:0.3, 1:10:0.4, 1:10:0.5, 1:10:0.6, 1:10:0.7, 1:10:0.8, 1:10:0.9, 1:10:1.0, 1:10:2.0, 1:10:3.0, 1:10:4.0, 1:10:5.0 or any range in between.

[0057] In a specific embodiment of the present application, hyaluronic acid or a salt thereof and tetrabutylammonium hydroxide are mixed and reacted to obtain a TBA salt of hyaluronic acid or a salt thereof (HA-TBA); the TBA salt of hyaluronic acid or a salt thereof is dissolved in N,N-dimethylformamide (DMF), and then 2-chloro-1-methylpyridinium iodide, L-glutamic acid diethyl ester hydrochloride, and triethylamine are added to react, and the mixture is hydrolyzed under an alkaline environment and the pH is adjusted to obtain a graft copolymer of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof (HA-GLU).

[0058] In one embodiment of the present application, hyaluronic acid or a salt thereof and tetrabutylammonium hydroxide are mixed to react to obtain a TBA salt of hyaluronic acid or a salt thereof (HA-TBA); the TBA salt of hyaluronic acid or a salt thereof is dissolved in N,N-dimethylformamide (DMF), and then 2-chloro-1-methylpyridinium iodide, L-glutamic acid diethyl ester hydrochloride, and triethylamine are added to react, and hydrolyzed in an alkaline environment, and the pH is adjusted to obtain a graft copolymer of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof (HA-GLU). The mass ratio of the quaternary ammonium base salt of hyaluronic acid or a salt thereof to glutamic acid or a salt thereof is 1:(0.01-1), and the molar ratio of L-glutamic acid diethyl ester hydrochloride, 2-chloro-1-methylpyridinium iodide, and triethylamine is 1:(0.1-10):(0.1-5).

[0059] The cosmetic composition described herein may be, for example, a composition for preventing and / or alleviating skin discomfort, a composition for preventing and / or alleviating skin discomfort caused by inflammation, an anti-inflammatory composition, and the like.

[0060] Another aspect of the present application relates to use. The term "article" may cover products in various forms, such as cosmetics, medicines, etc.

[0061] The present application provides use of the above composition in preventing and / or alleviating skin discomfort caused by inflammation.

[0062] The present application provides use of the above composition in anti-inflammatory treatment.

[0063] The present application provides use of the above composition in preparing a product for preventing and / or alleviating skin discomfort caused by inflammation.

[0064] The present application provides use of the above composition in preparing anti-inflammatory products.

[0065] The present application provides use of the above composition for non-therapeutic purposes in preventing and / or alleviating skin discomfort caused by inflammation.

[0066] The present application provides the use of the above composition in anti-inflammatory for non-therapeutic purposes.

[0067] In a specific embodiment, the skin discomfort caused by inflammation (such as IL-6) includes dermatitis, eczema, acne, vitiligo, sebum secretion, scars, skin aging, etc.

[0068] Example

[0069] The raw materials and equipment used in this application are shown in Table 1.

[0070] Table 1

[0071]

[0072] Preparation Example

[0073] Preparation Example 1 Preparation of HA-GLU (1)

[0074] Low molecular weight hyaluronic acid (denoted as LMW-HA) was swollen in ethanol and then acidified. After washing with anhydrous ethanol, the mixture was filtered. The filter cake was dissolved in water and the pH was adjusted to neutral using tetrabutylammonium hydroxide. The mixture was filtered and dried to obtain solid hyaluronic acid TBA salt (denoted as HA-TBA). The molecular weight of the low molecular weight hyaluronic acid was 4.7 wDa.

[0075] 2.0 g of HA-TBA was dissolved in N,N-dimethylformamide (DMF). After dissolution, 0.79 g of 2-chloro-1-methylpyridinium iodide (CMPI), 1.0 g of L-glutamic acid diethyl ester hydrochloride, and 0.81 g of triethylamine were added to the system and stirred at room temperature overnight. After the reaction was completed, purified water and alkali were added to the reaction system for hydrolysis, and then the pH was adjusted to weak acidity with acid. The mixture was precipitated and purified with an organic solvent, and the filter cake was obtained by filtration. After drying, the sample was recorded as HA-GLU (1). The molecular weight of HA-GLU (1) was 4.88 w Da, and it was determined by nuclear magnetic resonance spectroscopy. 1 The grafting rate of glutamic acid was determined to be 87% by H NMR.

[0076] Preparation Example 2 Preparation of HA-GLU (2)

[0077] Low molecular weight hyaluronic acid (denoted as UMW-HA) was swollen in ethanol and then acidified. After washing with anhydrous ethanol, the mixture was filtered. The filter cake was dissolved in water and the pH was adjusted to neutral using tetrabutylammonium hydroxide. The mixture was filtered and dried to obtain solid hyaluronic acid TBA salt (denoted as HA-TBA). The molecular weight of the low molecular weight hyaluronic acid was 2.6 wDa.

[0078] 2.0 g of HA-TBA was dissolved in N,N-dimethylformamide (DMF). After dissolution, 0.79 g of 2-chloro-1-methylpyridinium iodide (CMPI), 1.0 g of L-glutamic acid diethyl ester hydrochloride, and 0.81 g of triethylamine were added to the system and stirred at room temperature overnight. After the reaction was completed, purified water and alkali were added to the reaction system for hydrolysis, and then the pH was adjusted to weak acidity with acid. The mixture was precipitated and purified with an organic solvent, and the filter cake was obtained by filtration. After drying, the sample was recorded as HA-GLU (2). The molecular weight of HA-GLU (2) was 3.1 wDa, and it was determined by nuclear magnetic resonance spectroscopy. 1 The grafting rate of glutamic acid was determined to be 80% by H NMR.

[0079] Among them, HA-GLU(1) 1 H NMR spectrum Figure 1 Table 2 shows 1 Attribution of peaks in the H NMR spectrum.

[0080] Table 2 1 Attribution of peaks in H NMR spectra

[0081]

[0082]

[0083] Chemical Shift: indicates chemical shift; Coupling splitting indicates the number of coupled splitting peaks; Relative proton ratio indicates the relative number of protons

[0084] From Table 2 and Figure 1 The HA-GLU (1) was detected by nuclear magnetic resonance. 1 The H NMR spectrum shows that the chemical shifts of the methine and methylene groups of the grafted compound derived from glutamic acid are both shifted to the downfield relative to glutamic acid.

[0085] The characteristic peaks of the methylene group of glutamic acid or its salt appear at chemical shifts δ = 1.71-2.10 ppm and δ = 2.10-2.25 ppm, respectively; preferably, the characteristic peak of the methine -CH- of glutamic acid or its salt appears at δ = 4.00-4.15 ppm, and the characteristic peaks of -CH- of hyaluronic acid or its salt appear at δ = 4.30-4.40 ppm and δ = 4.40-4.48 ppm, respectively.

[0086] HA-GLU(2) 1 Corresponding characteristic peaks also appeared at the corresponding positions in the H NMR spectrum. Compared with glutamic acid, the chemical shifts of the methine and methylene groups of the HA-GLU (2) derived from glutamic acid also shifted to the low field.

[0087] Experimental example

[0088] First prepare the complete culture medium solution: mix DMEM basal culture medium, FBS fetal bovine serum, and PS double antibody solution in a mass ratio of 89:10:1.

[0089] According to the test formula in Table 3, the compositions were weighed respectively and dissolved in complete culture medium solution to form a test mixture, with the total content of each mixture being 150 μg / mL.

[0090] In the composition of Example 1, the total amount of HA-GLU (1) and PT-7 was 0.009 g, the concentration of HA-GLU (1) was 30 μg / mL, the concentration of PT-7 was 120 μg / mL, and the mass ratio of the grafted compound to PT-7 was 1:4.

[0091] The only difference between Example 2 and Example 1 is that the grafted compound is HA-GLU (2).

[0092] The only difference between Example 3 and Example 1 is that the concentration of HA-GLU (1) is 75 μg / mL, the concentration of PT-7 is 75 μg / mL, and the mass ratio of the grafted compound to PT-7 is 1:1.

[0093] The only difference between Example 4 and Example 1 is that the concentration of HA-GLU (1) is 120 μg / mL, the concentration of PT-7 is 30 μg / mL, and the mass ratio of the grafted compound to PT-7 is 4:1.

[0094] The only difference between Comparative Example 1 and Example 1 is that the concentration of HA-GLU (1) is 15 μg / mL, the concentration of PT-7 is 135 μg / mL, and the mass ratio of the grafted compound to PT-7 is 1:9.

[0095] The only difference between Comparative Example 2 and Example 1 is that the concentration of HA-GLU (1) is 129 μg / mL, the concentration of PT-7 is 21 μg / mL, and the mass ratio of the grafted compound to PT-7 is 6:1.

[0096] The only difference between Comparative Example 3 and Example 1 is that the concentration of HA-GLU (1) is 135 μg / mL, the concentration of PT-7 is 15 μg / mL, and the mass ratio of the grafted compound to PT-7 is 9:1.

[0097] The only difference between Comparative Example 4 and Example 1 is that it contains only HA-GLU (1), and the concentration of HA-GLU (1) is 150 μg / mL.

[0098] The only difference between Comparative Example 5 and Example 1 is that it contains only HA-GLU (2), and the concentration of HA-GLU (2) is 150 μg / mL.

[0099] The only difference between Comparative Example 6 and Example 1 is that only PT-7 is contained, and the concentration of PT-7 is 150 μg / mL.

[0100] The cytology test method is as follows:

[0101] 1) Cell seeding: 1×10 5 Fibroblasts were seeded into 6-well plates at a seeding density of 100 cells / well and incubated in an incubator (37° C., 5% CO 2 ) for 24 h.

[0102] 2) Modeling: According to the experimental groups, the sample group and the model control group were exposed to ultraviolet light therapy device (wavelength 280-320nm, 80mJ / cm 2 ) for UVB irradiation.

[0103] 3) Dosing: Dosing was performed in groups according to the test protocol in Table 2. Complete medium containing the test substance working solution was added to the sample group wells, with 1 mL of sample added to each well. Three replicates were set up for each group. After dosing, the 6-well plates were placed in an incubator (37°C, 5% CO2) and incubated for 24 hours.

[0104] 4) Cell collection: After culturing for 24 hours, collect the cell supernatant, wash twice with 1 mL / well D'Hanks buffer, lyse the cells by pipetting, and collect the sample.

[0105] 5) Gene expression detection: After the cells were treated with RNA-Quick Purification Kit, samples were collected and RNA extraction, reverse transcription and fluorescence quantitative PCR were performed according to the kit instructions. -△△Ct Method is used to calculate the results and obtain the test results.

[0106] 6) Statistical analysis of results: t-test statistical analysis was used for comparison among the groups.

[0107] The results are shown in Table 3, with a standard deviation of 0.01. The lower the relative expression of IL-6, the stronger the efficacy of the test sample in inhibiting IL-6 expression. If the relative expression of IL-6 in the composition of the same amount is lower than that of a single graft or PT-7, it indicates that the composition has a synergistic effect. The composition of the present application has a lower relative expression of IL-6 than that of the graft or PT-7 alone, indicating that the graft has a synergistic effect.

[0108] Table 3

[0109]

[0110]

[0111] Note: HA-GLU represents a hyaluronic acid-glutamic acid grafted compound, and PT-7 represents palmitoyl tetrapeptide-7.

[0112] Although the present invention has been disclosed above with reference to the embodiments, they are not intended to limit the present invention. Anyone with ordinary knowledge in the art may make slight changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the scope of the patent application attached hereto.

Claims

1. A cosmetic composition comprising palmitoyl tetrapeptide-7 and a grafted compound, wherein: The grafted compound is a grafted compound of hyaluronic acid or a salt thereof and glutamic acid or a salt thereof, wherein at least a portion of the carboxyl groups of the hyaluronic acid or a salt thereof are connected to the amino groups of the glutamic acid or a salt thereof in the form of an amide bond; The mass ratio of the grafted compound to the palmitoyl tetrapeptide-7 is in the range of 1:4 to 4:

1.

2. The composition according to claim 1, wherein The general formula of the grafted compound is shown in formula (I): Wherein, in formula (I), R is a metal ion or H, 0≤x<1, 0<y≤1, x+y=1, and n is a positive integer from 1 to 2000.

3. The composition according to claim 1, wherein The grafting rate of the grafted compound is greater than 20%.

4. The composition according to claim 3, wherein The grafting rate of the grafted compound is greater than 50%.

5. The composition according to claim 3, wherein The grafting rate of the grafted compound is 70% to 100%.

6. The composition according to claim 1, wherein The molecular weight of the grafted compound is 3k-500kDa.

7. Use of the composition according to any one of claims 1 to 6 in the preparation of a preparation for preventing and / or alleviating skin discomfort caused by inflammation.

8. Use of the composition according to any one of claims 1 to 6 in the preparation of an anti-inflammatory preparation.

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