Whitening polypeptide compound, cosmetics and preparation method thereof

Abstract

This patent application relates to whitening polypeptide compounds, cosmetics, and their preparation methods. This application discloses that Dichotomin D has dopa oxidase inhibitory activity. Furthermore, animal experiments demonstrate that cosmetics containing Dichotomin D as a primary ingredient exhibit significant whitening efficacy. The application also discloses a series of whitening toners, facial masks, and skin creams containing Dichotomin D as a primary ingredient, as well as the corresponding preparation processes.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and in particular relates to a polypeptide compound with whitening effect, a whitening cosmetic containing the compound and a preparation process thereof. Background Art

[0002] Skin color is determined by the types and amounts of pigments in the epidermis and dermis, including melanin, hemoglobin, and leucophyllum. These components are not fixed and are controlled by various external and internal factors.

[0003] In the high and cold Northern Europe (frigid zone), people are not exposed to the scorching sun and have very little melanin in their bodies, so their skin color is mostly white; in the tropics where sunlight is concentrated at the equator, people are often exposed to strong sunlight (ultraviolet rays), so the body regulates and produces a large amount of melanin to protect the skin, so the skin is black or brown-black; in the temperate zone, the skin color is neutral yellow or brown-yellow.

[0004] Melanin is primarily synthesized in the skin by melanocytes and is activated by ultraviolet light, hormone secretion, and stimulatory factors released by surrounding keratinocytes. Melanin's primary function is to mitigate skin disorders caused by ultraviolet light. However, excessive melanin synthesis and subsequent abnormal metabolism can lead to localized pigmentation, resulting in so-called brown spots and freckles, a major cosmetic problem.

[0005] To improve pigment deposition on the skin, it is possible to consider inhibiting melanin production in melanocytes (e.g., inhibiting tyrosinase and dopa oxidase activity), reducing the already formed melanin, promoting the excretion of melanin in the epidermis (e.g., activating melanin metabolic enzymes), and selective toxicity to melanocytes.

[0006] Among them, antioxidants such as L-ascorbic acid and its derivatives having a reducing effect are currently widely used as whitening substances, but sufficient whitening effects have not been achieved.

[0007] In addition, tyrosinase inhibitors such as hydroquinone, arbutin, kojic acid, licorice extract, and placenta extract are also used as whitening agents. However, these substances have problems with stability and safety, so the development of new whitening agents is desired.

[0008] Inhibiting dopa oxidase can also have a whitening effect. There are already many plant extracts that inhibit dopa oxidase activity and have whitening effects. For example, Melia toosendan Sieb.et Zucc., Amomum tsao-ko Crevostet Lemaire, Senecio doria L, Veratrum nigrum L, Angelica archangelica, Benthamidia florida, Euphorbia kansui Liou, Rhus chinensis Mill., Cnidium monnieri (L.) Cuss., Agrimonia pilosa Ledeb., Diuranthera minor (CH Wright) Hemsl., Berberis aristata, Pseudolarix kamepferi, Indigofera tinctoria, Datura metel, and pomegranate (Punica granatum) flowers.

[0009] However, to date, there are no reports that Bupleurum chinense or ingredients extracted from Bupleurum chinense have whitening effects.

[0010] Gupta Rajul, Agarwal Shalini*, Pathak Devender, Pharmacologically active cyclic peptides from the roots of Stellaria dichotoma, International Journal of Pharmaceutical Erudition, May 2012, 2(1), 17-23. Eleven cyclic peptides (dichotomin AK) extracted from the roots of Bupleurum chinense were studied. The extraction methods, chemical structures, and pharmacological activities of dichotomins A-K were reported. Dichotomin D exhibited cyclooxygenase (COX) inhibitory activity (72.6% at 100 μM) regardless of isoform.

[0011] The amino acid sequence of Dichotomin D is: Cyclo-(Gly-L-Val-Gly-L-Phe-L-Tyr-L-Ile), CAS number: 172998-29-7, molecular weight: 636.7, X log p3 = 2.8, and the chemical structure is as follows:

[0012] Summary of the Invention

[0013] In view of the current public's desire for skin whitening, the applicant conducted in-depth research on compounds with potential whitening effects and unexpectedly found that Dichotomin D not only has cyclooxygenase inhibitory activity, but also has dopa oxidase inhibitory activity, and can be administered transdermally to achieve skin whitening effects.

[0014] Dichotomin D is mild, non-irritating, and has good safety for external skin use. It can be further prepared into whitening cosmetics.

[0015] The present invention first provides the use of Dichotomin D in preparing cosmetics for inhibiting the activity of dopa oxidase. The use of inhibiting the activity of dopa oxidase is to prevent and improve skin pigmentation, pigment spots, and freckles.

[0016] The present invention further provides cosmetics comprising Dichotomin D, which can be a facial mask, a facial cream, a skin care cream, an essence, or any other cosmetics that can be applied to the skin and have a whitening effect.

[0017] The Dichotomin D described in the present application can be prepared according to the extraction process provided by the prior art (GuptaRajul, Agarwal Shalini*, Pathak Devender, Pharmacologically active Cyclic Peptides from the Roots of Stellaria dichotoma, International Journal of Pharmaceutical Engineering, May 2012, 2(1), 17-23.), or can be directly purchased.

[0018] The extraction process of Dichotomin D provided in the above prior art is as follows:

[0019] The cyclic peptide Dichotomin AE was isolated from the root of Bupleurum chinense. A methanol extract of the root of Bupleurum chinense was partitioned between n-butanol and water. The n-butanol-soluble material was passed through a Diaion HP-20 column (macroporous adsorption resin column, water-methanol as the mobile phase). The 80% methanol elution fraction was chromatographed on a silica gel column and then on ODS (octadecylsilane bonded silica gel packing). Five cyclic peptide compounds, designated Dichotomin AE, were obtained (contents of 0.007%, 0.0004%, 0.003%, 0.0012%, and 0.0002%, respectively).

[0020] Dichotomin D is usually prepared with additives into external preparations or skin cosmetics for application.

[0021] The additives are oils or oily substances (greases, waxes, higher fatty acids, essential oils, silicone oils, white oils, caprylic / capric triglycerides, dimethicone, etc.), moisturizers (glycerin, sorbitol, gelatin, polyethylene glycol, sodium pyrrolidone carboxylate, NMF-50, hyaluronic acid, etc.), powders (chalk, talc, bleaching earth, kaolin, starch, rubber, etc.), pigments, emulsifiers (polysorbate 80), solubilizers, detergents, thickeners (carbomer, hydroxyethyl cellulose, xanthan gum), medicinal ingredients, spices (lemon essence), resins, antibacterial and antifungal agents (ethyl hydroxybenzoate, Germa-115), other plant extracts (crude drugs, traditional Chinese medicine, herbs), alcohols (ethanol), polyols (glycerol), inorganic acids (bicarbonate, carbonate , sodium chloride, potassium chloride, sodium sulfate, etc.), organic acids (succinic acid, glutaric acid, fumaric acid, glutamic acid, malic acid, citric acid, ascorbic acid, etc.), vitamins (vitamins A, vitamin E, vitamin B, vitamin C, folic acid, etc.), water-soluble polymers, anionic surfactants (alkylbenzenesulfonates, alkyl sulfates, etc.), cationic surfactants (alkyl quaternary ammonium salts, alkyl dimethylbenzylammonium salts, etc.), nonionic surfactants (polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, PEG-40 hydrogenated castor oil, sucrose cocoate, polysorbate 80, etc.), amphoteric surfactants (imidazolines with alkyl groups, carbonyl betaines, etc.), metal ion chelating agents (edetic acid and its salts), pH adjusters (triethanolamine), etc.

[0022] The concentration of Dichotomin D in topical preparations or skin cosmetics is 0.1%-10%.

[0023] The beneficial effects of this application are as follows:

[0024] Dichotomin D, and topical preparations or cosmetics containing Dichotomin D, described herein, exhibit a significant inhibitory effect on dopa oxidase when applied to the skin. Compared to a control group, the inhibitory effect increases with increasing concentration, reaching approximately 40% in vitro at a concentration of 2%. These agents can effectively reduce melanin content in the skin, thereby preventing and improving skin pigmentation, spots, freckles, or whitening the skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Attachment Figure 1 :Inhibitory effects of different concentrations of Dichotomin D glycerol ethanol solution (50:50) on dopa oxidase

[0026] Attachment Figure 2 : Example 8 Schematic diagram of sample application on the back of a single guinea pig

[0027] Attachment Figure 3 : Schematic diagram of the ΔL value test results of each sample in Example 8 DETAILED DESCRIPTION

[0028] The present invention is further described below with reference to specific examples, which, however, are not intended to limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the art.

[0029] Example 1 Acute skin irritation test on experimental animals

[0030] 1. Materials and Methods

[0031] 1. The test substance is 10% Dichotomin D glycerol ethanol (50:50) solution

[0032] 2. Test animals: 4 ordinary white New Zealand rabbits

[0033] 3. Test Method: 24 hours prior to the test, shave the hair on both sides of the animal's spine, leaving an area approximately 3 cm x 3 cm on each side. During the test, apply 0.5 mL of the test substance evenly to a 2.5 cm x 2.5 cm area on the left side of the animal's back. Apply distilled water to the right side as a control. Apply the test substance once daily for 7 consecutive days. Starting on the second day, shave the hair before application and rinse with warm water. After 1 hour, observe the skin reaction and compare it with the control to calculate the skin irritation score. At the end of the test, calculate the total score for 14 days, the mean score for each animal over the 14 days, the mean score for each animal each day, and the skin irritation intensity grade.

[0034] 2. Scoring Criteria

[0035]

[0036]

[0037] Skin irritation intensity classification

[0038] Integral mean strength 0-0.5 Non-irritating 0.5-2.0 Mild irritation 2.0-6.0 Moderate irritation 6.0-8.0 Strong irritation

[0039] 3. Test results

[0040] Table 1 Results of multiple skin irritation tests

[0041]

[0042] As shown above, 10% Dichotomin D glycerol ethanol showed no irritation to the skin of standard-grade white New Zealand rabbits after 14 days of continuous contact. This allows for further testing.

[0043] Example 2 Skin occlusive patch test

[0044] Dichotomin D glycerol-ethanol (50:50) solutions of varying concentrations were used as the test group, while a glycerol-ethanol (50:50) solution was used as the control group. Ten healthy adult Hartley brown guinea pigs (hair removed from the same area on the back, 2.5 cm × 2.5 cm) were tested in each group. A qualified spot tester was selected according to the "Technical Specifications for Safety of Cosmetics" (2015 edition). The test substance was placed in the small chamber of the spot tester at a volume of 0.020 mL. The control well served as a blank solvent control. The spot tester containing the test substance was applied to the hairless area on the back of the test animal using hypoallergenic tape. Gently press the tester with the palm of your hand to evenly adhere to the skin for 48 hours.

[0045] After removing the test piece, observe the skin reaction according to the standard 30 minutes (after the indentation disappears), 24 hours, and 48 hours. Record the observation results.

[0046] Table 2 Skin occlusive patch test

[0047]

[0048] If more than two of the 10 test animals experience a grade "++" adverse skin reaction, or if any one of the 10 test animals experiences a grade "+++" or higher adverse skin reaction, the test substance is considered to have an adverse reaction on the test animal. The relevant test results are shown in the following table.

[0049]

[0050]

[0051] As shown in the table above, no adverse skin reactions were observed in the test animals in the Dichotomin D glycerol ethanol (50:50) solution and the solvent control group 0.5, 24, and 48 hours after the spot tester was removed. This result indicates that the Dichotomin D glycerol ethanol (50:50) solution is highly safe and did not cause adverse reactions to the skin of the test animals.

[0052] Example 3 In vitro dopa oxidase activity test of Dichotomin D (implemented with reference to Chinese patent CN103313696B)

[0053] (1) Cell culture

[0054] Melanocytes from normal neonatal epidermis were plated in 96-well plates at a density of 1 × 10 4 The cells were seeded at a density of 100 cells / well (100 μL / well) and cultured at 37°C under 5% CO 2 . The culture medium was Medium 254.

[0055] After 3 days of culture, 20 μL of a 50:50 solution of Dichotomin D at different concentrations was added, along with endothelin-1 (ET-1), SCF (stem cell growth factor), α-MSH (α-melanocyte stimulating hormone), histamine, and PGE2 (prostaglandin E2) adjusted to a final concentration of 1 nM in the culture medium, to achieve the final concentrations listed in Table 3. An equal volume of 50:50 solution of glycerol was used as a negative control, and the cells were cultured for 3 days at 37°C and 5% CO2. As a control, an equal volume of 50:50 solution of glycerol was added.

[0056] (2) Determination of dopa oxidase activity

[0057] After the incubation period, the cells were washed with PBS and 20 μL / well of extraction buffer (0.1 M Tris-HCl (pH 7.2)), 1% NP-40 (Nonidet P 40, ethylphenyl polyethylene glycol), 0.01% SDS (sodium dodecyl sulfate), 100 μM PMSF (phenylmethylsulfonyl fluoride), 1 μg / ml aprotinin) was added. 20 μL / well of assay buffer (4% dimethylformamide, 100 mM sodium phosphate buffer (pH 7.1)) was added and the cells were solubilized at 4°C for 3 hours. DOPA oxidase activity was measured. DOPA oxidase activity was measured according to the MBTH method (Winder A. et al., 1991, Eur. J.

[0058] Biochem. 198: 317-326), according to the following method.

[0059] To each well of the solubilized cell solution, 80 μL of the above-described assay buffer, 60 μL of a 20.7 mM MBTH (3-methyl-2-benzothiazolinone hydrazone) solution, and 40 μL of a 5 mM L-DOPA (L-dihydroxyphenylalanine) solution as a substrate were added. The cells were reacted at 37°C for 30-60 minutes, and the color reaction was measured by absorbance at 490 nm (N = 3). The measured values are expressed relative to the results of the blank control.

[0060] (3) Results

[0061] The results are shown in Table 3 and Figure 1 After the addition of Dichotomin D glycerol ethanol (50:50), the cellular dopa oxidase activity was inhibited in a Dichotomin D concentration-dependent manner.

[0062] Table 3 In vitro inhibitory activity of Dichotomin D against dopa oxidase

[0063] Addition concentration Dichotomin D final concentration Dopa oxidase activity (%) 0.5％ 0.05％ 93.4％ 1.0％ 0.1％ 92.6％ 2.0％ 0.2％ 91.2％ 5.0％ 0.5％ 89.7％ 10.0％ 1.0％ 75.6％ 20.0％ 2.0％ 58.8％ .

[0064] Example 4: In vitro melanin inhibition activity test of Dichotomin D (implemented with reference to Chinese Patent CN103313696B)

[0065] The three-dimensional skin culture model was cultured at 37°C and 5% CO2 using ET1-100-NMM-113 medium containing ET-1 (endothelin-1) and SCF (stem cell growth factor) at a final concentration of 10 nM. Starting on the first day of culture, a glycerol-ethanol solution of Dichotomin D was added to a final concentration of 2 v / v%. As a control, an equal amount of glycerol-ethanol (50:50) was added.

[0066] The culture medium was exchanged every three days. After 14 days, the three-dimensional cultured skin, along with the cup serving as the culture support, was washed with PBS. The skin slices were peeled off with tweezers and transferred to a test tube, and then washed three more times with PBS. After washing three times with 50% ethanol and twice with 100% ethanol, they were left to dry completely at room temperature overnight. Finally, 200 μL of 2M NaOH was added and dissolved at 100°C. The absorbance of the supernatant obtained by centrifugation was measured at a wavelength of 405 nm to calculate the melanin content. The final results were expressed as relative values compared to the measured values of the sample and the control group.

[0067] Compared to cells without Dichotomin D, the amount of melanin in 3D cultured skin cells was reduced by 70.2% by adding 2% Dichotomin D.

[0068] Example 5: Dichotomin D Whitening and Moisturizing Toner

[0069] Components Recipe 1 Recipe 2 Recipe 3 Recipe 4 Glycerol:Ethanol (50:50) 50 50 50 50 Dichotomin D 0.1 2 5 10 Sodium pyrrolidone carboxylate 5 5 5 5 NMF-50 (amino acid moisturizer) 3 3 3 3 EDTA-2Na 0.05 0.05 0.05 0.05 1% hyaluronic acid 5 5 5 5 Ethylparaben 0.1 0.1 0.1 0.1 PEG-40 hydrogenated castor oil 0.3 0.3 0.3 0.3 Jema-115 0.03 0.03 0.03 0.03 lemon essence 0.03 0.03 0.03 0.03 0.1M citric acid aqueous solution appropriate amount appropriate amount appropriate amount appropriate amount Deionized water to volume Up to 100ml Up to 100ml Up to 100ml Up to 100ml .

[0070] Note: The data in the table above are in g for solids and ml for liquids.

[0071] Preparation method:

[0072] Step 1: Take the prescribed amount of glycerin: ethanol (50:50), add the prescribed amount of ethyl paraben, PEG-40 hydrogenated castor oil, Germa-115, lemon essence, and Dichotomin D in sequence, stir and dissolve to obtain solution A;

[0073] Step 2: Take 30% of the prescription amount of deionized water, add sodium pyrrolidone carboxylate, NMF-50, EDTA-2Na, and 1% hyaluronic acid in sequence, stir and dissolve to obtain solution B;

[0074] Step 3: Add the solution A obtained in step 1 to the solution B obtained in step 2 under stirring, and stir to mix the two uniformly to obtain solution C;

[0075] Step 4: Adjust the pH value of solution C to 6.5-7.5 with 0.1 M citric acid aqueous solution and dilute to 100 ml with deionized water to obtain Dichotomin D whitening and moisturizing toner.

[0076] Example 6 Dichotomin D Whitening Mask

[0077] The whitening facial mask of this embodiment is composed of the following components:

[0078] Components Recipe 1 Recipe 2 Recipe 3 Recipe 4 Glycerol:Ethanol (50:50) 50 50 50 50 Dichotomin D 0.1 2 5 10 Carbomer 940P 0.20 0.20 0.20 0.20 Hydroxyethyl cellulose 0.20 0.20 0.20 0.20 Xanthan gum 0.15 0.15 0.15 0.15 Sodium hyaluronate 0.08 0.08 0.08 0.08 Ethylparaben 0.50 0.50 0.50 0.50 lemon essence 0.04 0.04 0.04 0.04 PEG-40 hydrogenated castor oil 0.40 0.40 0.40 0.40 triethanolamine appropriate amount appropriate amount appropriate amount appropriate amount Deionized water to volume 100 100 100 100 .

[0079] Note: The data in the table above are in g for solids and ml for liquids.

[0080] The preparation steps are as follows:

[0081] Step 1: Take 30% of the prescribed amount of deionized water, and slowly add sodium hyaluronate, xanthan gum, carbomer 940P, and hydroxyethyl cellulose in sequence under rapid stirring, and stir to dissolve to obtain a light yellow uniform hydrogel;

[0082] Step 2: Take the prescribed amount of glycerol and ethanol (50:50), add the prescribed amount of ethyl paraben, lemon essence, PEG-40 hydrogenated castor oil, and Dichotomin D in sequence, stir and dissolve to obtain a uniform solution;

[0083] Step 3, slowly adding the solution obtained in step 2 to the hydrogel obtained in step 1 under stirring conditions, and stirring to obtain a viscous liquid;

[0084] Step 4: Adjust the pH of the viscous liquid obtained in step 3 to 6.5-7.5 with triethanolamine, and dilute to 100 ml with deionized water. Stir and mix well to obtain a light yellow transparent liquid, which is the Dichotomin D whitening facial mask.

[0085] Example 7Dichotomin D Whitening Skin Cream

[0086]

[0087]

[0088] Note: The data in the table above are in g for solids and ml for liquids.

[0089] Preparation method:

[0090] Step 1) Take 70% deionized water, add glycerol ethanol, Dichotomin D, sucrose cocoate, and xanthan gum in sequence, stir and dissolve to obtain an aqueous phase solution, heat to 85° C., and set aside;

[0091] Step 2) heating white oil, caprylic / capric triglyceride, polysorbate 80, and dimethicone to 85° C., melting, and mixing to obtain a homogeneous, clear solution, which is the oil phase;

[0092] Step 3) The oil phase obtained in step 2) was slowly added to the aqueous phase obtained in step 1) under stirring, and homogenized at 3000 rpm for 5 minutes;

[0093] Step 4) Stop homogenization, keep stirring, add triethanolamine, adjust the pH of the mixture to 6.5-7.5, and add deionized water to volume;

[0094] Step 5) Cool the material obtained in step 4) to 50° C., add lemon essence, continue stirring, cool to room temperature, and discharge the material to obtain Dichotomin D whitening skin cream.

[0095] Example 8 Model Animal Whitening Test

[0096] Experimental animals:

[0097] Fifteen healthy adult Hartley brown guinea pigs weighing 367±20 g were used.

[0098] Sample: Cosmetics of various formulas obtained in Examples 5-7.

[0099] Negative control: deionized water

[0100] Positive control: 0.1% kojic acid aqueous solution

[0101] Animal handling:

[0102] Select a 3×5cm area on the guinea pig's back 2 After hair removal, use UV-B light source at 16.5mJ / cm 2 The irradiation was carried out for 10 days with a dose of 165 mJ / cm2. The irradiation intensity was measured with a UVB type ultraviolet radiometer before and after each irradiation. 2 After repeated exposure to a low-dose of UVB (16.5 mJ / day) for 5 to 7 days, pigmentation began to appear on the guinea pig's back skin, reaching its peak on the 10th day. During the exposure period, no typical acute UVB damage, such as flushing, erythema, or dandruff, was observed.

[0103] Sample application:

[0104] After irradiation, the blackened back skin was divided into 15 1×1 cm 2 Area, by attachment Figure 2 Schematic diagram showing the uniform administration of the negative control, positive control, and each formulation of Examples 5-7. Five test animals were administered each formulation twice daily for a total of four weeks.

[0105] Detection:

[0106] For the test animals, the L value change (ΔL) of the test area of the animal skin before and after application of the sample was measured using a colorimeter once a week. The ΔL value of each sample (n=5) is shown in the following table:

[0107]

[0108] The L value measured by the measuring instrument is a quantitative indicator of skin darkness. The higher the L value, the whiter the skin. 用药后 -L 用药前 ) Changes in medication duration are shown in the attached Figure 3 shown.

[0109] After stopping UV-B irradiation of the test animals, the melanin caused by UV-B irradiation is metabolized by the guinea pig skin itself as it recovers. Therefore, the ΔL of the negative control group of each example also increases with time.

[0110] For the positive control group, since kojic acid as a whitening agent was applied, it has a clear whitening effect. As time goes by, the change of ΔL is more significant than that of the negative control group.

[0111] As the concentration of Dichotomin D increased, the ΔL values of the samples in each example gradually increased. When 0.1% Dichotomin D was added, the corresponding ΔL was comparable to or even better than that of the positive control. This indicates that cosmetics containing 0.1% to 10% Dichotomin D had a significant whitening effect on the test animals.

[0112] The above embodiments are preferred implementations of the present invention, but the implementation of the present invention is not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be regarded as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. Use of Dichotomin D for preparing cosmetics with whitening efficacy, wherein the cosmetics act by inhibiting dopa oxidase, characterized in that: The chemical structure of DichotominD is as follows: 。 2. The use according to claim 1, characterized in that The cosmetic contains Dichotomin D at a concentration of 0.1%-10%, w / v.

3. The use according to claim 2, characterized in that The cosmetic is one of skin softener, facial mask or skin cream.

4. The use according to claim 3, characterized in that The formula and preparation method of the skin softening water are as follows: prescription: Component dosage 50ml of a 50:50 glycerol-ethanol mixture Dichotomin D 0.1g-10g Sodium pyrrolidone carboxylate 5.0g NMF-50 3.0g EDTA-2Na 0.05g 1% hyaluronic acid 5.0ml Ethyl paraben 0.1g PEG-40 hydrogenated castor oil 0.3g JEMA-115 0.03g Lemon essence 0.03g 0.1M citric acid aqueous solution Deionized water to 100ml Preparation method: Step 1: Take a glycerol-ethanol mixture with a volume ratio of 50:50, add the prescribed amount of ethyl paraben, PEG-40 hydrogenated castor oil, Germa-115, lemon essence, and Dichotomin D in sequence, stir and dissolve, and obtain solution A; Step 2: Take 30% of the prescription volume of deionized water (v / v), add sodium pyrrolidone carboxylate, NMF-50, EDTA-2Na, and 1% hyaluronic acid (w / v) in sequence, and stir to dissolve to obtain solution B; Step 3: Add the solution A obtained in step 1 to the solution B obtained in step 2 under stirring, and stir to mix the two uniformly to obtain solution C; Step 4: Adjust the pH value of solution C to 6.5-7.5 with 0.1M citric acid aqueous solution and dilute to 100ml with deionized water to obtain Dichotomin D whitening and moisturizing toner.

5. The use according to claim 3, characterized in that The prescription and preparation method of the facial mask are as follows: Component formula 50ml of a 50:50 glycerol-ethanol mixture Dichotomin D 0.1g-10g Carbomer 940P 0.20g Hydroxyethyl cellulose 0.20g Xanthan gum 0.15g Sodium hyaluronate 0.08g Ethyl paraben 0.50g Lemon essence 0.04g PEG-40 hydrogenated castor oil 0.40g Triethanolamine appropriate amount Deionized water to 100ml Preparation method: Step 1: Take 30% of the prescription amount of deionized water (v / v), and slowly add sodium hyaluronate, xanthan gum, carbomer 940P, and hydroxyethyl cellulose in sequence under rapid stirring, and stir to dissolve to obtain a light yellow uniform hydrogel; Step 2: Take a glycerol-ethanol mixture with a volume ratio of 50:50, add the prescribed amount of ethyl paraben, lemon essence, PEG-40 hydrogenated castor oil, and Dichotomin D in sequence, stir and dissolve to obtain a uniform solution; Step 3, slowly adding the solution obtained in step 2 to the hydrogel obtained in step 1 under stirring conditions, and stirring to obtain a viscous liquid; Step 4: Adjust the pH of the viscous liquid obtained in step 3 to 6.5-7.5 with triethanolamine, and dilute to 100 ml with deionized water. Stir and mix thoroughly to obtain a light yellow transparent liquid, which is the Dichotomin D whitening facial mask.

6. The use according to claim 3, characterized in that The prescription and preparation method of the skin care cream are as follows: Component formula 50ml of a 50:50 glycerol-ethanol mixture Dichotomin D 0.1g-10g Sucrose cocoate 1.0g Xanthan gum 0.5g 10g white oil Caprylic / capric triglyceride 10g Polysorbate 80 1.0g Dimethyl silicone oil 1.0g Triethanolamine appropriate amount Lemon essence 0.5g Deionized water to 100ml Preparation method: Step 1) Take 70% of the prescription volume of deionized water (v / v), add a 50:50 volume ratio of glycerol and ethanol mixture, Dichotomin D, sucrose cocoate, and xanthan gum, stir and dissolve to obtain an aqueous phase solution, heat to 85°C, and set aside; Step 2) Heat white oil, caprylic / capric triglyceride, polysorbate 80, and dimethicone to 85°C, melt, and mix well to obtain a homogeneous, clear solution, which is the oil phase; Step 3) The oil phase obtained in step 2) was slowly added to the water phase obtained in step 1) under stirring, and homogenized at 3000 rpm for 5 minutes; Step 4) Stop homogenization, keep stirring, add triethanolamine, adjust the pH of the mixture to 6.5-7.5, and add deionized water to make up to volume; Step 5) Cool the material obtained in step 4) to 50° C., add lemon essence, continue stirring, cool to room temperature, and discharge the material to obtain Dichotomin D whitening skin cream.

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