CN112402316A - Whitening composition and preparation method and application thereof - Google Patents

Abstract

The invention discloses a whitening composition and a preparation method and application thereof. The composition comprises the following components: 2.5-5 parts of mulberry leaf extract, 2.5-10 parts of 4-butyl resorcinol, 5-15 parts of nicotinamide, 2.5-10 parts of honey extract, 0.5-2.5 parts of retinol propionate, 2.5-10 parts of bis-diethoxy diglycol cyclohexane 1, 4-dicarboxylic ester, 5-10 parts of emulsifier, 20-30 parts of polyhydric alcohol and the balance of water to 100 parts. The composition can be applied to cosmetic products such as astringent, essence, lotion, cream, facial mask, etc., and the addition range is 10-20 parts. The composition has the advantages of obvious synergistic effect among the components, good tyrosinase inhibition effect, good melanin transfer inhibition effect, good transdermal absorption effect and small irritation to skin.

Description

Whitening composition and preparation method and application thereof

Technical Field

The invention belongs to the technical field of cosmetics, and particularly relates to a whitening composition and a preparation method and application thereof.

Background

When skin is stimulated by external factors such as ultraviolet rays and pressure, an instruction for synthesizing melanin is sent to a melanin cell of a basal layer, tyrosine is catalyzed by tyrosinase to form dopa, dopa is further oxidized into dopaquinone, melanin is finally formed after multiple conversions, the melanin is transferred to epidermis and distributed on a horny layer, and the skin color of the skin is darkened due to excessive melanin.

The skin is divided into epidermis, dermis and subcutaneous tissue, wherein the epidermis is composed of horny layer, stratum lucidum, stratum granulosum, acanthocyte layer and stratum basale from outside to inside, and melanocytes are firstly in the stratum basale, then are metabolized and transformed layer by layer, and then are transferred to the stratum corneum, so the transdermal absorbability of the whitening product is very important.

Most whitening products in the current market have the following defects:

1. the whitening effect is realized only by inhibiting the activity of tyrosinase or reversing the transportation of melanin, and the whitening mode is single;

2. the transdermal absorbability is poor, and if the whitening product can only stay on the surface of the skin, the whitening effect is greatly reduced;

3. at present, many whitening products are used to be 'hard-to-wear drugs', the content of a single whitening component is very high, or some skin refreshing components such as tartaric acid and salicylic acid are added, but the irritation to the skin is greatly increased, sensitive skin or thin skin users are often dare to use, and the skin problems such as stinging and redness can be caused by the result of reluctant use.

Therefore, how to reduce the distribution of melanin on skin in various dimensions and in various ways, ensure the permeability of the product, ensure the transdermal absorbability of the whitening components, reduce skin irritation and ensure safety is a problem which needs to be solved urgently at present.

Disclosure of Invention

In order to solve the defects of single whitening mode, poor transdermal absorption and large skin irritation of cosmetics in the prior art, the invention provides a composition with multiple whitening modes, good transdermal absorption and small skin irritation.

The application is realized by the following technical scheme:

the invention provides a whitening composition: comprises 2.5 to 5 parts of mulberry leaf extract, 2.5 to 10 parts of 4-butyl resorcinol, 5 to 15 parts of nicotinamide, 2.5 to 10 parts of honey extract, 0.5 to 2.5 parts of retinol propionate, 2.5 to 10 parts of bis-diethoxy diglycol cyclohexane 1, 4-dicarboxylic ester, 5 to 10 parts of emulsifier, 20 to 30 parts of polyhydric alcohol and the balance of water to 100 parts by weight.

The mulberry leaf extract can absorb part of ultraviolet rays, and can prevent part of melanin from being generated from the source. The nicotinamide reverses melanin transport, and reduces the transfer of synthesized melanin to the skin surface; the second effect of niacinamide is that it increases the skin barrier, reduces the irritation of "narcotics" to the skin, and greatly increases the skin tolerance. Bis-diethoxydiol cyclohexane 1, 4-dicarboxylate is a powerful penetration enhancer, and can increase the transdermal absorption of whitening components.

Preferably, the 4-butyl resorcinol is 10 parts. 4-butyl resorcinol is a very strong tyrosinase inhibitor and can effectively inhibit the activity of tyrosinase;

preferably, the retinol propionate is 2.5 parts. The retinol propionate can be converted into tretinoin through hydrolysis and oxidation layer by layer in the skin, which can promote the renewal of epidermal cells and regulate the proliferation and differentiation of epidermal cells, thereby accelerating the metabolism of the skin and metabolizing melanin out more quickly, and simultaneously, the retinol propionate, the nicotinamide and 4-butyl resorcinol can play a synergistic effect, so that the 4-butyl resorcinol can be helped to effectively inhibit tyrosinase and accelerate the transfer of melanin by the nicotinamide.

Preferably, the honey extract is 10 parts. The honey extract has mild effect and exfoliates cutin, thereby reducing melanin already shown on epidermis; the honey extract is honey fermented by a natural method, contains high-concentration gluconic acid, has a very good skin rejuvenation effect, reduces the distribution of melanin on the horny layer, is pH-independent, can be used in a wide pH range, and can still exert the capability of exfoliating even when the pH is neutral, thereby ensuring the mildness of the honey extract. The skin-refreshing composition does not have the irritation and redness caused by fruit acid, salicylic acid and other skin-refreshing components.

Preferably, the emulsifier is one or more selected from PEG-40 hydrogenated castor oil, hydrogenated lecithin, polysorbate-20, polysorbate-80, PEG-60 hydrogenated castor oil, C12-20 alkyl glucoside, cetearyl glucoside, and cetearyl alcohol.

Preferably, the polyhydric alcohol is one or more selected from propylene glycol, 1, 3-butanediol, 1, 2-butanediol, 1, 4-butanediol, 2, 3-butanediol, dipropylene glycol, 1, 2-pentanediol and octylene glycol.

Further preferably, the emulsifier is PEG-40 hydrogenated castor oil; the polyalcohol is 1, 3-butanediol.

The invention also provides an application of the composition, and the composition is added into cosmetics, wherein the cosmetics comprise astringent, essence, emulsion, cream and mask.

Preferably, the composition is added in an amount of 10 to 20 parts per hundred parts by weight of the cosmetic.

The invention also provides a preparation method of the composition, which comprises the following steps:

1) adding deionized water, folium Mori extract, Mel extract and nicotinamide into a reactor, stirring to clarify;

2) mixing the emulsifier and the retinol propionate, adding the mixture into a reactor, and uniformly stirring;

3) and uniformly mixing the polyhydric alcohol, the bis-diethoxydiol cyclohexane 1, 4-dicarboxylate and the 4-butyl resorcinol, adding the mixture into a reactor, and uniformly stirring to obtain the composition.

Compared with the prior art, the application can obtain the following technical effects:

the components have better synergistic effect, and have better effect of inhibiting the transfer of melanin compared with single components or common combined components. Wherein, the retinol propionate can improve the tyrosinase inhibition effect of 4-butyl resorcinol and improve the melanin transport inhibition effect of nicotinamide.

Drawings

FIG. 1 is a graph showing a melanin change test rate in Experimental example 1 of the present invention;

FIG. 2 is a face luminance change rate test chart of Experimental example 1 of the present invention;

FIG. 3 is a graph showing a test for the in vitro melanin transport inhibition in Experimental example 4 of the present invention;

FIG. 4 is a graph showing the absorption rate of the active substance in Experimental example 5 of the present invention.

Detailed Description

Embodiments of the present application will be described in detail by examples, so that how to apply technical means to solve technical problems and achieve technical effects of the present application can be fully understood and implemented.

The raw materials and equipment used in the present application are all common raw materials and equipment in the field, and are all from commercially available products, unless otherwise specified. The methods used in this application are conventional in the art unless otherwise indicated.

The preparation method comprises the following steps:

(1) and sequentially adding the components in the phase A into a main pot, stirring at the speed of 200rpm/min until the mixture is clear and has no lumps.

(2) Mixing the phase B, adding into a main pot, and starting homogenizing at 3000rpm/min for 10min until the material is uniform.

(3) And uniformly mixing the components of the phase C, adding the mixture into a main pot, and stirring until the material body is uniform.

Compositions of examples 1 to 4 and comparative examples 1 to 3 were prepared by the above method according to the formulation shown in Table 1, the percentages shown in Table 1 being percentages by weight.

TABLE 1

The compositions prepared in the examples 1 to 4 and the comparative examples 1 to 3 are applied to whitening essence according to the formula shown in Table 2.

The preparation method of the whitening essence comprises the following steps:

(1) adding the components of the phase A into a main pot, heating while stirring (200-300rpm), heating to about 75 ℃, and fully stirring until the material body is uniform and clear without lumps.

(2) Adding the components of phase B into oil pan, heating under stirring to about 75 deg.C, and stirring to dissolve

(3) Adding phase B into the main pot, starting homogenization at 3500-4000rpm for 5 min, and cooling

(4) When the temperature is reduced to below 45 ℃, the components of the phase C are sequentially added into the main pot, and the stirring is continued until the material body is uniform, and then the material is discharged.

(5) And filling after the detection is qualified to obtain the whitening essence.

TABLE 2

Experimental example 1

35 subjects were recruited, aged 22-40 years, and divided into 7 groups of 5 persons, each of which was administered the whitening essence of examples 5-8 and comparative examples 4-6, respectively, at night for 3 months, and during the test period, no other essence was administered, and the remaining skin care products were identical to those before the test.

And (3) test results:

1. melanin change test

Subjects were tested for facial melanin changes after 3 months of continuous use using the VISIA skin color analysis system. As shown in fig. 1, the melanin change test showed that the melanin reduction effect of example 8 was the best.

2. Luminance change test

Subjects were tested for changes in facial brightness using the VISIA skin color analysis system after 3 months of continuous use. As shown in fig. 2, the luminance variation test showed that example 8 was most effective in enhancing luminance.

3. Spot sticker safety test

Selecting qualified spot test materials, sucking 0.025ml of a substance to be tested and blank control distilled water by a liquid-moving machine, respectively dripping the substance and the blank control distilled water on a filter paper sheet, pasting the spot test device with whitening essence on the curved side of the forearm of a subject, lightly pressing the spot test device with a palm to uniformly paste the spot test device on the skin for 24 hours. The skin reaction is observed after the plaque remover is removed, and if the result is negative, the skin reaction is observed again after 24h and 48 h.

All 35 subjects had negative reactions and no adverse reactions.

To summarize: the above tests show that example 8 has the best effect on reducing melanin and improving brightness, wherein the whitening components in examples 5-8 are different, while the comparative examples 4-6 have missing components, and example 8 adds the whitening composition of the present invention in its entirety and has reasonable components, which proves that the components of the whitening composition of the present invention are synergistic with each other to exert the best effect, and the subject does not find a case of sensitive, reddish, prickling, etc. during the test period, thus proving that the composition is very excellent and mild in safety and can be used for a long time.

In addition to the above experiments, the present invention also tested different components and their synergistic effects.

EXAMPLE 2 tyrosinase inhibition experiment

1. 0.1M phosphate buffer (pH6.8), L-tyrosine solution, and Agaricus campestris tyrosinase (1041.6u/ml) were prepared.

2. Accurately weighing a certain mass of tyrosinase inhibitor powder samples (respectively 4-butyl resorcinol, arbutin, kojic acid, 4-hexyl resorcinol and phenethyl resorcinol), fixing the volume to 25mL by pure water to obtain sample solutions with corresponding concentrations, performing two-time gradient dilution, and diluting for 4 times to obtain sample diluting reagents.

3. 0.3ml of substrate, 2ml of buffer solution and 0.2ml of tyrosinase inhibitor sample solution or pure water were added to each tube, and the color removal group was replaced with a sample dilution reagent. After each tube was placed in an ice bath for 10 minutes, 0.1ml of agaricus bisporus tyrosinase solution or pure water was added, shaken up, taken out from the water bath at 37 ℃ for 20 minutes, placed in the ice bath for about 10 minutes, and the OD value was measured at 470 nm. The specific feed formulations are shown in table 3 below.

TABLE 3

4. Computing

The OD value of the sample is the measured OD value of the test sample, and the OD value of the color of the sample is the measured OD value of the color removing group.

Taking the concentration of the sample as an abscissa and the melanin inhibition rate of the sample as an ordinate to make a standard curve; determining the concentration (X) of the sample when the inhibition rate (Y) is 50%;

the inhibition experiments for various tyrosinase inhibitors described above gave the data shown in table 4 below. The results confirmed that 4-butylresorcinol exhibited the best inhibitory effect.

TABLE 4

Tyrosinase inhibitors	IC50(ppm)
		4-butylresorcinol	0.13
Arbutin	18
		Kojic acid	8.1
4-hexylresorcinol	2.7
		Phenethylresorcinol	0.85

Experimental example 3 Retinol propionate tyrosinase inhibition promoting experiment

1. 0.1M phosphate buffer (pH6.8), L-tyrosine solution, Agaricus campestris tyrosinase (1041.6u/ml), and 1% TritonX-100 solution were prepared.

2. And accurately weighing a certain mass of tyrosinase inhibitor powder samples respectively, wherein the tyrosinase inhibitor powder samples are 4-butyl resorcinol, retinol propionate, 4-butyl resorcinol + retinol propionate respectively. The weight ratio of 4-butylresorcinol to retinol propionate in the 4-butylresorcinol + retinol propionate group is 4: 1. And (3) fixing the volume to 25mL by using pure water to obtain a sample solution with corresponding concentration, performing two-time gradient dilution, and diluting for 4 times to obtain the sample diluent. When the sample was retinol propionate, 1% TritonX-100 solution was used as a diluent instead of pure water.

3. 0.3ml of substrate, 2ml of buffer solution, and 0.2ml of tyrosinase inhibitor sample solution or pure water were added to each tube, and the color removal group was replaced with a sample dilution reagent. After each tube was placed in an ice bath for 10 minutes, 0.1ml of agaricus bisporus tyrosinase solution or pure water was added, shaken up, taken out from the water bath at 37 ℃ for 20 minutes, placed in the ice bath for about 10 minutes, and the OD value was measured at 470 nm. The specific feed formulations are shown in table 5 below.

TABLE 5

4. Computing

The OD value of the sample is the measured OD value of the test sample, and the OD value of the color of the sample is the measured OD value of the color removing group.

Taking the concentration of the sample as an abscissa and the melanin inhibition rate of the sample as an ordinate to make a standard curve; determining the concentration (X) of the sample when the inhibition rate (Y) is 50%;

through the inhibition experiments on various tyrosinase inhibitors, the data shown in the following table 6 are obtained, and the fact that the retinol propionate can obviously promote the inhibition effect of 4-butyl resorcinol on tyrosinase is proved.

TABLE 6

Tyrosinase inhibitors	IC50(ppm)
		4-butylresorcinol	0.13
Retinol propionate	396
		4-Butylresorcinol + Retinol propionate	0.07

Experimental example 4 Retinol propionate in vitro melanin transport promotion experiment

1. The mouse melanocyte and the mouse keratinocyte were cultured separately.

2. The mouse melanocytes were inoculated into 6-well cell culture plates¹⁴C-TU labeling, 12 hours later, labeled melanocytes were collected and inoculated into an already-adherent culture medium of mouse keratinocytes for co-culture.

3. Respectively adding test samples with certain concentrations into a co-culture system, wherein the test samples are respectively as follows: keratinocytes + melanocytes, keratinocytes + melanocytes + retinol propionate, keratinocytes + melanocytes + nicotinamide, keratinocytes + melanocytes + nicotinamide, and nicotinamide + retinol propionate. Wherein the content of retinol propionate in the keratinocyte + melanocyte + retinol propionate is 0.25 g/L; the nicotinamide content in the keratinocyte + melanocyte + nicotinamide is 1.5 g/L; in the plastid forming cells + melanocytes + nicotinamide + retinol propionate, 1.5g/L of nicotinamide and 0.25g/L of retinol propionate are contained.

4. Separating melanocyte and keratinocyte, treating the separated keratinocyte with sodium hydroxide and hydrochloric acid, collecting to scintillation vial, adding scintillation liquid, and measuring keratinocyte content with liquid scintillation counter¹⁴C radioactivity.

5. Computing

The specific results are shown in FIG. 3. The data in fig. 3 prove that the melanin transport inhibition rate of nicotinamide can reach 41% after the retinol propionate is added, which indicates that the retinol propionate can obviously promote the inhibition effect of the nicotinamide on the melanin transport.

Experimental example 5 active substance absorption test

1. Placing the cleaned skin model in a vertical diffusion cell

2. Adding PBS solution (phosphate buffer) into the receiving chamber, and adding certain concentration of test sample solution containing penetration enhancer into the supplying chamber, wherein the test sample solution is folium Mori extract, 4-butylresorcinol, nicotinamide, and Mel extract. In addition, samples without penetration enhancer are also arranged in each group of samples. The penetration enhancer used in this experimental example was bis-diethoxydiethylene glycol cyclohexane 1, 4-dicarboxylate.

3. And taking out the skin model after 6 hours, peeling 1-2 layers of horny layers by using an adhesive tape after cleaning, and quantitatively detecting the content of the test sample in the skin model.

The results are shown in fig. 4, where the penetration enhancer significantly promoted osmotic absorption.

There are many other possible embodiments of the present invention, which are not listed here, and the embodiments claimed in the claims of the present invention can be implemented.

The details not described in the specification of the present application belong to the common general knowledge of those skilled in the art.

In the following description and in the claims, the terms "include" and "comprise" are used in an open-ended fashion, and thus should be interpreted to mean "include, but not limited to. "substantially" means within an acceptable error range, and a person skilled in the art can solve the technical problem within a certain error range to substantially achieve the technical effect.

It is also noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a good or system that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such good or system. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a commodity or system that includes the element.

The foregoing description shows and describes several preferred embodiments of the present application, but as aforementioned, it is to be understood that the application is not limited to the forms disclosed herein, but is not to be construed as excluding other embodiments and is capable of use in various other combinations, modifications, and environments and is capable of changes within the scope of the inventive concept as expressed herein, commensurate with the above teachings, or the skill or knowledge of the relevant art. And that modifications and variations may be effected by those skilled in the art without departing from the spirit and scope of the application, which is to be protected by the claims appended hereto.

Claims (10)

1. A whitening composition is characterized by comprising 2.5-5 parts of mulberry leaf extract, 2.5-10 parts of 4-butylresorcinol, 5-15 parts of nicotinamide, 2.5-10 parts of honey extract, 0.5-2.5 parts of retinol propionate, 2.5-10 parts of bis-diethoxydiol cyclohexane 1, 4-dicarboxylate, 5-10 parts of emulsifier, 20-30 parts of polyhydric alcohol and the balance of water to 100 parts by weight.

2. The composition of claim 1, wherein the 4-butyl resorcinol is 10 parts.

3. The composition of claim 1, wherein the retinol propionate is 2.5 parts.

4. The composition of claim 1, wherein the honey extract is present in 10 parts.

5. The composition of claim 1, wherein the emulsifier is selected from one or more of PEG-40 hydrogenated castor oil, hydrogenated lecithin, polysorbate-20, polysorbate-80, PEG-60 hydrogenated castor oil, C12-20 alkyl glucoside, cetearyl glucoside, and cetearyl alcohol.

6. The composition of claim 1, wherein the polyol is selected from one or more of propylene glycol, 1, 3-butylene glycol, 1, 2-butylene glycol, 1, 4-butylene glycol, 2, 3-butylene glycol, dipropylene glycol, 1, 2-pentanediol, and octylene glycol.

7. The composition of claim 1, wherein the emulsifier is PEG-40 hydrogenated castor oil; the polyalcohol is 1, 3-butanediol.

8. Use of a composition according to claim 1, wherein the composition is added to a cosmetic product comprising a lotion, essence, emulsion, cream, mask.

9. The use according to claim 7, wherein the composition is added in an amount of 10 to 20 parts per hundred parts by weight of the cosmetic product.

10. A method of preparing the composition of claim 1, comprising the steps of:

1) adding deionized water, folium Mori extract, Mel extract and nicotinamide into a reactor, stirring to clarify;

2) mixing the emulsifier and the retinol propionate, adding the mixture into a reactor, and uniformly stirring;

3) and uniformly mixing the polyhydric alcohol, the bis-diethoxydiol cyclohexane 1, 4-dicarboxylate and the 4-butyl resorcinol, adding the mixture into a reactor, and uniformly stirring to obtain the composition.

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