Application of sesquiterpene lactone compound in whitening aspect

Abstract

The invention belongs to the technical field of cosmetics, and discloses application of sesquiterpene lactone compounds in whitening. The invention finds that the arnica lactone D and artemisinin have related whitening effects for the first time, specifically, the arnica lactone D and artemisinin are capable of inhibiting melanogenesis and tyrosinase activity, good in inhibition effect, low in onset concentration and non-irritant to red blood cells, so that the arnica lactone D and artemisinin have certain safety, also have relatively good anti-inflammatory activity, can improve hyperpigmentation after inflammation, and can be used for preventing and treating inflammation. The method has great potential in the fields related to cosmetics.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and particularly relates to the application of sesquiterpene lactone compounds in whitening. Background Art

[0002] Melanin is mainly synthesized by melanocytes. Under the catalysis of related enzymes, such as tyrosinase (TYR) and tyrosinase-related protein 1 / 2 (TRP1 / 2), a series of oxidative synthesis reactions are performed to generate a high-molecular complex, the content and distribution of which determine the color of human skin. Once melanin is abnormally synthesized, metabolized, and accumulated in the body, it will lead to some common abnormal pigmentation diseases, such as sun spots and chloasma. Excessive pigmentation of the skin after inflammation can even become an inducing factor for the occurrence of melanoma, which constitutes a serious aesthetic and health problem for people. At present, the only registered whitening agent approved by my country's Food and Drug Administration is phenylethyl resorcinol. Over the years, the development of whitening agents has been relatively slow, while the share and demand of the whitening market have been gradually expanding. The number and categories of existing whitening agents are difficult to meet the development needs of the existing whitening market. Existing whitening ingredients include natural, synthetic monomer components, extracts and other forms. Small molecule compounds usually have good transdermal absorption, and they often have stronger whitening effects than raw materials such as large molecular peptides and plant extracts. They occupy a major position in the current cosmetic whitening raw materials, but there are also some synthetic small molecules in the application of whitening cosmetics due to their irritation and poor safety, resulting in limitations in their application in this field, such as rhododendron alcohol and kojic acid. Natural plant-derived small molecule compounds are often safer than some artificial and chemically synthesized ingredients. In addition, modern whitening is based on the concept of "returning to nature", and in order to better solve the shortcomings of irritation and allergies of some existing whitening ingredients, screening safe, efficient and mild whitening ingredients from natural products has become a hot spot in cosmetic research and development.

[0003] Arnica lactone D (CAS: 34532-68-8) is a sesquiterpene lactone component found in coriander. Studies have shown that it has a wide range of anti-tumor activity and has a certain inhibitory effect on colon cancer, liver cancer, breast cancer, osteosarcoma, nasopharyngeal carcinoma, etc. (References: PMID: 38652277; PMID: 38472168; PMID: 32669950; PMID: 38967079; PMID: 24588282; PMID: 3110896). The existing published patents around arnica lactone D mainly focus on its application in the fields of medical technology and pharmaceutical technology. For example, the existing patent technology shows that arnica lactone D can be used to prepare antiviral drugs, such as herpes simplex virus, hepatitis B virus, and human cytomegalovirus (patent publication number: CN108743583A), and for the preparation of drugs for anti-inflammatory and prevention and treatment of autoimmune diseases and non-alcoholic fatty liver disease (patent publication number: CN116472038A). There are no reports on the application of arnica lactone D in the whitening direction.

[0004] Artemisinin (CAS: 63968-64-9) is a sesquiterpene lactone component found in Artemisia annua. It is a well-known antimalarial active ingredient. There are also a large number of literatures pointing out that it has anti-tumor, antibacterial, antiviral and anti-inflammatory activities (references: PMID: 32710388; PMID: 34983312; PMID: 38018178; PMID: 33138094). There are also related research reports mentioning that artemisinin has a certain protective effect on the nervous system and a certain improvement effect on Parkinson's disease (PMID: 38056239). It has a certain protection against ischemic injury diseases, such as ovarian ischemia-reperfusion injury and ischemic stroke (PMID: 35864966; PMID: 37263547). Artemisia annua (Artemisia annua) extract is currently used as a raw material ingredient in cosmetics. It usually has antibacterial, acne-removing, soothing and anti-inflammatory effects. Therefore, existing patents also focus on the application of Artemisia annua extract in daily chemical products such as dandruff removal, acne removal, soothing and repairing (patent publication numbers: CN118787574A; CN118512362A; CN118105321A; CN117653582A). There are also related technologies that mention that Artemisia annua extract has certain whitening effects, but as a mixture containing complex ingredients, there are no reports on the application of artemisinin in whitening. Summary of the invention

[0005] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention provides the application of sesquiterpene lactone compounds in whitening. The present invention first discovered that arnica lactone D and artemisinin have the effect of inhibiting melanin production and inhibiting tyrosinase activity, with good inhibitory effect, low effective concentration and low irritation. In addition, both have good anti-inflammatory effects, and have great potential for application in cosmetics-related fields.

[0006] The first aspect of the present invention is the use of a sesquiterpene lactone compound in the preparation of a product with whitening effect, wherein the sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

[0007] In some embodiments of the present invention, the amount of the sesquiterpene lactone compound added to the product is ≤10wt%, preferably ≤5wt%, and more preferably ≤1wt%.

[0008] In some embodiments of the present invention, the amount of the sesquiterpene lactone compound added to the product is 0.0000001wt% (0.001ppm)-1wt%, preferably 0.000016wt% (0.16ppm)-1wt%, and further preferably 0.0001wt% (1ppm)-1wt%.

[0009] In some embodiments of the present invention, the amount of the sesquiterpene lactone compound added to the product is 0.001wt%-1wt%, preferably 0.01wt%-1wt%, more preferably 0.01wt%-0.5wt%, and even more preferably 0.01wt%-0.2wt%.

[0010] In some embodiments of the present invention, the whitening comprises at least one of inhibiting tyrosinase activity, inhibiting melanin production, and improving post-inflammatory pigmentation.

[0011] The second aspect of the present invention provides a composition, which includes a sesquiterpene lactone compound or one or more of its pharmaceutically acceptable acids, bases, salts, esters, solvates, stereoisomers, and tautomers, wherein the sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

[0012] In some embodiments of the present invention, the sesquiterpene lactone compound is used as one of the whitening active ingredients in the composition.

[0013] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the composition is ≤10 wt %, preferably ≤5 wt %, and more preferably ≤1 wt %.

[0014] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the composition is 0.0000001wt% (0.001ppm)-1wt%, preferably 0.000016wt% (0.16ppm)-1wt%, and further preferably 0.0001wt% (1ppm)-1wt%.

[0015] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the composition is 0.001wt%-1wt%, preferably 0.01wt%-1wt%, more preferably 0.01wt%-0.5wt%, and even more preferably 0.01wt%-0.2wt%.

[0016] The third aspect of the present invention provides a cosmetic comprising a sesquiterpene lactone compound or one or more of its pharmaceutically acceptable acids, bases, salts, esters, solvates, stereoisomers, and tautomers, wherein the sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

[0017] In some embodiments of the present invention, the sesquiterpene lactone compound is used as one of the whitening active ingredients in the cosmetic.

[0018] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the cosmetic is ≤10wt%, preferably ≤5wt%, and more preferably ≤1wt%.

[0019] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the cosmetic is 0.0000001wt% (0.001ppm)-1wt%, preferably 0.000016wt% (0.16ppm)-1wt%, and further preferably 0.0001wt% (1ppm)-1wt%.

[0020] In some embodiments of the present invention, the content of the sesquiterpene lactone compound in the cosmetic is 0.001wt%-1wt%, preferably 0.01wt%-1wt%, more preferably 0.01wt%-0.5wt%, and even more preferably 0.01wt%-0.2wt%.

[0021] In some embodiments of the present invention, the cosmetic further comprises an auxiliary material, wherein the auxiliary material comprises at least one of an emulsifier, a moisturizer, a thickener, a chelating agent and a preservative.

[0022] In some embodiments of the present invention, the dosage form of the cosmetic includes any one of an aqueous solution, an emulsion, a spray, a cream, an essence or a mask.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] The present invention discovers for the first time that arnica lactone D and artemisinin have whitening-related effects, which are specifically manifested in that they can inhibit melanin production and tyrosinase activity, have good inhibitory effects, have low effective concentrations, and are non-irritating to red blood cells, indicating that they have certain safety. At the same time, they have good anti-inflammatory activity, can improve post-inflammatory pigmentation, and have great potential for application in cosmetics-related fields. DETAILED DESCRIPTION

[0025] In order to make the technical scheme of the present invention more clearly understood by those skilled in the art, the following embodiments are listed for illustration. It should be pointed out that the following embodiments do not limit the protection scope of the present invention.

[0026] Unless otherwise specified, the raw materials, reagents and devices used in the following examples can be obtained from conventional commercial sources or by existing known methods.

[0027] Example 1

[0028] This embodiment provides a sesquiterpene lactone compound, arnica lactone D (CAS: 34532-68-8).

[0029] Example 2

[0030] This embodiment provides a sesquiterpene lactone compound, artemisinin (CAS: 63968-64-9).

[0031] Comparative Example 1

[0032] This comparative example provides a phenolic structural compound, phenethyl resorcinol (CAS: 85-27-8).

[0033] Comparative Example 2

[0034] This comparative example provides a phenolic structural compound, resveratrol (CAS: 501-36-0).

[0035] Comparative Example 3

[0036] This comparative example provides a flavonoid structural compound, hydroquinone (CAS: 123-31-9).

[0037] Comparative Example 4

[0038] This comparative example provides a phenolic structural compound, 4-butylresorcinol (CAS: 18979-61-8).

[0039] Comparative Example 5

[0040] This comparative example provides a synthetic derivative of lysine, tranexamic acid (CAS: 1197-18-8).

[0041] Comparative Example 6

[0042] This comparative example provides an amide derivative, nicotinamide (CAS: 98-92-0).

[0043] Comparative Example 7

[0044] This comparative example provides a flavonoid structural compound, phloretin (CAS: 60-82-2).

[0045] Comparative Example 8

[0046] This comparative example provides a sesquiterpene lactone compound, curcuminol (CAS: 19431-84-6).

[0047] Comparative Example 9

[0048] This comparative example provides an alcohol compound, D-panthenol (CAS: 81-13-0).

[0049] Experimental Example 1 Melanin synthesis and tyrosinase activity inhibition experiment

[0050] 1.1 Preparation of sample solution

[0051] Using dimethyl sulfoxide (DMSO) as a solvent for dissolution, Example 1 was prepared into sample solutions with concentrations of 0.5 μM, 1 μM, and 2.5 μM, Example 2 was prepared into a sample solution with a concentration of 3.5 μM, Comparative Examples 1-3 and 8 were prepared into sample solutions with concentrations of 1 μM and 5 μM, Comparative Example 4 was prepared into a sample solution with concentrations of 2 μM and 10 μM, and Comparative Example 7 was prepared into a sample solution with concentrations of 1 μM and 2.5 μM for testing;

[0052] Deionized water was used as a solvent for dissolution, and comparative examples 5 and 6 were prepared into sample solutions with concentrations of 1 μM and 10 μM, respectively, for testing.

[0053] 1.2 Experimental Principle

[0054] Melanin is a biological pigment synthesized and secreted by melanocytes. In melanocytes, tyrosine is catalyzed by tyrosinase and undergoes a series of reactions to eventually generate melanin.

[0055] B16-F10 mouse melanoma cells are widely used as test cells for the efficacy determination of whitening chemicals. α-MSH is α-melanin-stimulating hormone, which can promote B16-F10 to secrete melanin and increase intracellular tyrosinase activity. α-MSH is used to induce B16-F10 to determine the inhibitory effect of the test substance on melanin synthesis and tyrosinase activity.

[0056] 1.3 Experimental methods

[0057] (1) Cell culture and treatment

[0058] B16-F10 cells were cultured with 1640 complete medium (1640 medium + 10% FBS by volume + double antibody) in a carbon dioxide incubator at 37° C. and 5% CO 2 , and passaged every 2-3 days.

[0059] (2) Determination of intracellular melanin content

[0060] Select B16-F10 cells in the logarithmic growth phase, digest them with 0.25% trypsin, and inoculate them in 6-well culture plates, 2 mL of culture medium per well, and place them in a 37°C, 5% CO2 incubator. On the second day after inoculation, add culture medium containing different concentrations of the test substance and α-MSH (1 μM), and set up a control group (containing only 1 μM α-MSH), 2 mL per well, and do 3 parallels for each concentration. After incubation at 37°C, 5% CO2 for 48 hours, discard the supernatant, add 0.5 mL of 0.25% trypsin digestion solution to each well and digest for 1 minute at room temperature. Add 1 mL of culture medium to stop digestion, and blow into a single cell suspension. Take 20 μL for cell counting, take 0.7 mL of cell suspension and centrifuge at 2000 r / min for 5 min, discard the supernatant, add 1 mL of 1 mol / L NaOH solution (containing 10% DMSO by mass), and incubate in an 80°C water bath for 30 min, then measure the absorbance at 490 nm on a microplate reader.

[0061] (3) Determination of intracellular tyrosinase activity

[0062] After the cells treated with the above drugs were digested and counted with trypsin (the specific steps are the same as 1.3-(2)), 0.7 mL of the cell suspension was centrifuged at 2000 r / min for 5 min, the supernatant was discarded, 1 mL of 0.5% sodium deoxycholate solution was added, and the cells were ice-bathed for 15 min to lyse the cells to prepare an extract containing tyrosinase. After preheating at 37°C, 0.5 mL of 0.3% dopa solution was added, and the reaction was carried out at 37°C for 10 min, and the absorbance was measured at 475 nm on an ELISA reader.

[0063] (4) Result Statistics

[0064] The test OD value was calibrated based on the cell number.

[0065] Melanin production inhibition rate (%) = [1-(As / Ds) / (Ac / Dc)] × 100;

[0066] Tyrosinase activity inhibition rate (%) = [1-(As / Ds) / (Ac / Dc)] × 100;

[0067] Where: As is the absorbance value of the sample group, Ac is the absorbance value of the control group, Ds is the cell concentration of the sample group, and Dc is the cell concentration of the control group.

[0068] 1.4 Experimental Results

[0069] The results are shown in Table 1.

[0070] Table 1

[0071]

[0072]

[0073] It is understandable that melanin is mainly produced by melanocytes. The level of melanin in the skin is closely related to the depth, dullness, spots, uneven pigmentation and other issues of human skin color. Tyrosinase is the key enzyme that catalyzes the synthesis of melanin. Therefore, melanocytes can be used to judge the whitening effect of the test substance by evaluating the melanin content and tyrosinase activity.

[0074] Phenylethylresorcinol (Comparative Example 1), resveratrol (Comparative Example 2), hydroquinone (Comparative Example 3), 4-butylresorcinol (Comparative Example 4) of phenolic structure, tranexamic acid (Comparative Example 5), nicotinamide (Comparative Example 6) of amino acid and amide derivatives, and phloretin (Comparative Example 7) of flavonoid structure are all recognized as raw materials for cosmetics with good whitening effect. From the results in Table 1, it can be seen that Example 1 (arnica lactone D) shows obvious effects of inhibiting melanin production and tyrosinase activity. At a micromolar concentration (1 μM), its melanin inhibition rate can reach 15.46%, and its tyrosinase inhibition rate can reach 33.01%. Example 2 (artemisinin) at a micromolar concentration (3.5 μM), its melanin inhibition rate can reach 31.59%, and its tyrosinase inhibition rate can reach 19.80%.

[0075] At the same concentration (1 μM), the inhibitory effect of Example 1 is significantly better than that of Comparative Examples 1-3 and Comparative Examples 5-7. Compared with Comparative Example 4, the effect of Example 1 (1 μM) is significantly better than that of Comparative Example 4 at a higher concentration (2 / 10 μM). At a concentration of 2.5 μM, the effect of Example 1 is better than or close to that of Comparative Examples 1-7 at other higher concentrations. At a concentration of 3.5 μM, the effect of Example 2 is better than that of Comparative Examples 2-6 at other higher concentrations, and the effect of Example 2 at 3.5 μM in inhibiting melanin is better than that of Comparative Example 1 at 5 μM. In addition, Comparative Example 8, which also has a sesquiterpenoid structure, does not have a significant effect of inhibiting melanin production and tyrosinase activity.

[0076] The results in Table 1 above show that Example 1 (arnica lactone D) and Example 2 (artemisinin) have strong inhibitory effects on melanin production and tyrosinase activity, and the effective concentration is low, which suggests that Example 1 may achieve a whitening effect by adding a small amount in actual application. At the same time, the effects of Example 1 and Example 2 have the uniqueness of certain ingredients, and not all sesquiterpene lactone compounds have obvious inhibitory effects.

[0077] Test Example 2 Red blood cell hemolysis test

[0078] 1.1 Experimental Principle

[0079] Eye irritants can denature proteins or dissolve cell membranes. The test substance is applied to red blood cells to detect whether hemolysis occurs and whether the hemoglobin released from the cells is denatured. The amount of hemoglobin leaked and the degree of denaturation are measured to evaluate the degree of damage to the cell membrane by the test substance and to infer whether it may be eye irritating. The red blood cell hemolysis experiment simulates damage similar to the cornea.

[0080] 1.2 Experimental methods (refer to EURL ECVAM DB-ALM Protocol No.99 and EURL ECVAM DB-ALM Protocol No.37)

[0081] (1) The test substances - Example 1-2, Comparative Examples 1-2, 5-7 were prepared into a series of gradient suspensions with mass fractions of 0.001%, 0.01%, 0.1%, 1%, 10%, 20%, 30%, 40%, etc. respectively using physiological saline as solvent, mixed with red blood cell suspension in equal volume ratio, cultured at 37°C for 3 hours, centrifuged and supernatant was collected, and absorbance was measured at 410nm, 540nm, and 575nm on an ELISA reader, and the results were calculated and statistically analyzed. Physiological saline was used as a negative control (i.e., completely non-hemolyzed), and 0.1% SDS solution was used as a positive control (i.e., completely hemolyzed).

[0082] (2) Results Statistics

[0083] Hemolysis rate (%) = (A 410nm -C 410nm ) / (B 410nm -C 410nm )×100;

[0084] Protein denaturation index DI (%) = (A 575nm / A 540nm ) / (B 575nm / B 540nm )×100;

[0085] Wherein, A is the test sample, B is the positive control, and C is the average absorbance of the negative control. The DI% calculation refers to the average absorbance value of the A / B sample at a concentration of 1%.

[0086] A curve was drawn with the sample concentration as the abscissa and the hemolysis rate as the ordinate, and the test substance concentration HC50 (mg / L) that caused 50% hemolysis of red blood cells was determined based on the regression equation.

[0087] (3) Result determination

[0088] Calculate the L / D value of the sample based on the HC50 value and DI value: L / D = HC50 / DI;

[0089] According to the RBC test classification standard of the European Center for Validation of Alternative Methods (ECVAM), the degree of irritation of cosmetics is classified. The classification standard is shown in Table 2.

[0090] Table 2

[0091] L / D Grading ﹥100 Non-irritating 10﹤L / D≤100 Slightly irritating 1﹤L / D≤10 Mild irritant 0.1﹤L / D≤1 Moderate irritation L / D≤0.1 Severe irritation

[0092] 1.3 Experimental Results

[0093] The results are shown in Table 3.

[0094] Table 3

[0095]

[0096]

[0097] Comparative Examples 1-2 and 5-7 are all currently effective and popular cosmetic raw material ingredients in the whitening field. As shown in Table 3, by comparing the irritation of different samples to red blood cells, Examples 1-2 are non-irritating and relatively mild, which is similar to the above comparative examples. Therefore, from the perspective of safety, Example 1 (arnica lactone D) and Example 2 (artemisinin) discovered by the present invention both have the potential to be applied in the cosmetic field.

[0098] Although arnica lactone D and artemisinin are not currently included in the list of acceptable cosmetic raw materials, they are less irritating and have good whitening effects. The above characteristics provide good data support for their application in the cosmetics field, especially in whitening products.

[0099] Anti-inflammatory activity

[0100] High concentrations of chemokines at the site of inflammation can interact with corresponding receptors on the surface of macrophages, inducing cell activation and recruitment to the site of infection. Activated macrophages can release various proinflammatory factors such as IL-1β, IL-6 and TNF-α, inducing and enhancing local inflammatory responses. LPS is an endotoxin and an important group-specific antigen that can bind to the LPS receptors on macrophages and activate macrophages to release proinflammatory factors. LPS is used to induce macrophages to release the proinflammatory factor TNF-α, and RT-PCR, ELISA and other detection methods are used to detect changes in the content of related inflammatory factors.

[0101] The relevant detection method is to use RAW264.7 mouse mononuclear macrophage leukemia cells, perform corresponding plate-attaching operations on cell culture, then add the inflammatory inducer LPS (100 ng / mL~1 μg / mL), and set up a blank group, a control group, and a sample treatment group at the same time. After 24 hours, the cell supernatant or cell pellet is collected and the corresponding ELISA or RT-PCR test is performed.

[0102] There are related documents about the anti-inflammatory activity of arnica lactone D. Specifically, the reference PMID: 36838711 (NCBI database) discloses the inhibitory effect of arnica lactone D at a test concentration of 3 μg / mL (converted to a molar concentration of 9 μM) on RAW264.7-related inflammatory factors interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α).

[0103] There are related documents on the anti-inflammatory activity of artemisinin. Specifically, reference PMID: 33359851 (NCBI database) discloses the inhibitory effects of artemisinin at test concentrations of 10 μM and 100 μM on interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α).

[0104] UV or other external stimuli can also induce skin inflammation. When pro-inflammatory mediators are released, they will affect the formation of melanin. These mediators include IL-1β, IL-6 and TNF-α. There are also related literature (PMID: 36466945) pointing out that post-inflammatory hyperpigmentation (PIH) is positively correlated with the release of these factors. Because of this, some cosmetic raw materials with good anti-inflammatory and soothing effects, such as dipotassium glycyrrhizinate and centella asiatica, have been found to have certain whitening effects, especially improving post-inflammatory hyperpigmentation. Dipotassium glycyrrhizinate (reference: Wang Xuewen, Liu Hui, Wang Qian, et al. Dipotassium glycyrrhizinate promotes skin repair by regulating macrophage polarization [J]. Daily Chemical Industry (Chinese and English), 2024, 54(11): 1355-1361) and asiatica glycoside (reference: Jiang Xian, Zhang Zhuo, Li Xiaobing, et al. Effect of asiatica glycoside on inflammatory factors of RAW264.7 cells stimulated by LPS [J]. Pharmacology and Clinical Medicine of Traditional Chinese Medicine, 2008, (01): 23-25) can inhibit the production of inflammatory factors IL-6 and TNF-α, and arnica lactone D and artemisinin in Examples 1 and 2 of the present invention also have good anti-inflammatory effects, and can significantly inhibit the production of IL-1β, IL-6 and TNF-α, and the micromolar concentration can achieve a certain whitening and anti-inflammatory effect. These data indicate that arnica lactone D and artemisinin in Examples 1 and 2 of the present invention can improve post-inflammatory pigmentation in practical applications. In addition, they can inhibit tyrosinase activity and melanin production, and are applied to whitening products to achieve multi-pathway whitening.

[0105] Test Example 3 Human-related efficacy test

[0106] 1.1 Preparation of test samples

[0107] Comparative Example 9 (D-panthenol) was added to the formula base, and the specific formula is shown in Table 4.

[0108] Table 4

[0109]

[0110] 1.2 Experimental plan

[0111] 30 subjects were recruited, aged 18-60 years old, with sensitive skin and facial problems such as acne, acne marks, and acne. After meeting the basic test conditions and signing the corresponding informed consent, a single-blind test was conducted. The subjects used the product on their faces once in the morning and once in the evening. After one week of use, the skin condition after using the product was evaluated through a questionnaire and the product's use effect was analyzed.

[0112] 1.3 Result determination

[0113] The questionnaire design is divided into four dimensions: very inconspicuous, inconspicuous, obvious, and very obvious; effective proportion = effective number of people (obvious + very obvious) / total number of people.

[0114] 1.4 Experimental Results

[0115] As shown in Table 5.

[0116] Table 5

[0117] Options Effective number of people (percentage) Invalid number (percentage) Products that enhance skin radiance 3(10.00％) 27(90.00％) Products that brighten your skin 3(10.00％) 27(90.00％) Products to reduce acne marks 4(13.33％) 26(86.67％) Products to improve yellowing of skin 7(23.33％) 23(76.67％) Products to improve dull skin 5(16.67％) 25(83.33％) Products to improve skin redness 24(80.00％) 6(20.00％) Products to relieve skin irritation 26(86.67％) 4(13.33％) The product has a soothing effect 26(86.67％) 4(13.33％)

[0118] Comparative Example 9 (D-panthenol) is a soothing, anti-inflammatory and repairing raw material commonly used in cosmetics. It is also widely reported to have relevant inhibitory and soothing effects. Relevant literature (PMID: 37074393, 33577057) shows that this substance can inhibit the production and secretion of inflammatory factors IL-10, TNF-α, IL-1β, and IL-6 when inducing inflammation (model group). After the use of this ingredient by humans, ≥80% of the subjects believed that it had the effects of soothing, improving skin redness and irritation. This result is also consistent with the relevant literature research reports and industry cognition, and most of the subjects (>75%) of this ingredient believed that it had poor effects on skin color improvement, whitening and brightening, and post-inflammatory pigmentation. Therefore, the relevant data of Comparative Example 9 (D-panthenol) show that not all soothing ingredients can achieve the effects of improving skin color, whitening, and improving post-inflammatory pigmentation. It may be necessary to have certain adjustments to the pathways related to whitening itself (such as tyrosinase) to better achieve skin color related improvements. This also reflects to a certain extent that Examples 1 and 2 of the present invention have certain application prospects in whitening and improving post-inflammatory pigmentation due to the characteristics of the compounds themselves.

[0119] Application Example 1

[0120] A composition consists of 5 wt% arnica lactone D and the balance of physiological saline solvent.

[0121] Application Example 2

[0122] A composition consists of 1wt% artemisinin and the remainder physiological saline solvent.

[0123] Application Example 3

[0124] A composition consists of 0.01 wt% arnica lactone D and the balance of physiological saline solvent.

[0125] Application Example 4

[0126] A composition consists of 1 ppm artemisinin and the balance physiological saline solvent.

[0127] Application Example 5

[0128] A composition consists of 0.16 ppm of arnica lactone D and the balance of a physiological saline solvent.

[0129] Application Example 6

[0130] A lotion, comprising the following components in percentage by mass:

[0131] Glycerin 6%, Sodium Hyaluronate 0.08%, Xanthan Gum 0.05%, Parahydroxyacetophenone 0.4%, 1,2 Hexanediol 1%, Arnica Lactone D 5% and the balance is water.

[0132] Application Example 7

[0133] A facial mask, comprising the following components in percentage by mass:

[0134] Glycerin 6%, disodium EDTA 0.02%, sodium hyaluronate 0.08%, xanthan gum 0.05%, carbomer 0.15%, p-hydroxyacetophenone 0.4%, 1,2-hexanediol 1%, artemisinin 1% and water as the balance.

[0135] Application Example 8

[0136] An emulsion consisting of the following components in percentage by weight:

[0137] Glycerin 10%, Disodium EDTA 0.01%, Ammonium Acryloyldimethyltaurate / VP Copolymer 0.1%, Sodium Hyaluronate 0.05%, Parahydroxyacetophenone 0.4%, 1,2 Hexanediol 1%, Squalane 1.5%, Arnica Lactone D 0.01% and the balance is water.

[0138] Application Example 9

[0139] An emulsion consisting of the following components in percentage by weight:

[0140] Glycerin 10%, disodium EDTA 0.01%, ammonium acryloyldimethyltaurate / VP copolymer 0.1%, sodium hyaluronate 0.05%, p-hydroxyacetophenone 0.4%, 1,2-hexanediol 1%, squalane 1.5%, artemisinin 1ppm and water as the balance.

[0141] Application Example 10

[0142] An essence, composed of the following components in percentage by weight:

[0143] Carbomer 0.3%, aminomethyl propanol 0.1%, dipotassium glycyrrhizinate 0.3%, trehalose 0.6%, 1,2-hexanediol 0.5%, p-hydroxyacetophenone 0.4%, ethanol 8%, arnica lactone D 0.16ppm and water as the balance.

[0144] It can be understood that the compositions of Application Examples 1-5 and the cosmetics of Application Examples 6-10 of the present invention have good whitening effects because they contain the arnica lactone D and artemisinin of the present invention respectively.

[0145] The preferred embodiments of the present invention are specifically described above, but the invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. The use of sesquiterpene lactone compounds in the preparation of products with whitening effects, characterized in that: The sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

2. The use according to claim 1, characterized in that: The amount of the sesquiterpene lactone compound added to the product is ≤10wt%.

3. The use according to claim 1, characterized in that: The whitening comprises at least one of inhibiting tyrosinase activity, inhibiting melanin production and improving post-inflammatory pigmentation.

4. A composition, characterized in that The composition comprises a sesquiterpene lactone compound or one or more of its pharmaceutically acceptable acids, bases, salts, esters, solvates, stereoisomers and tautomers, wherein the sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

5. The composition according to claim 4, characterized in that The content of the sesquiterpene lactone compound in the composition is ≤10 wt%.

6. The composition according to claim 4, characterized in that The sesquiterpene lactone compound is used as one of the whitening active ingredients in the composition.

7. A cosmetic, characterized in that: The cosmetic comprises a sesquiterpene lactone compound or one or more of its pharmaceutically acceptable acids, bases, salts, esters, solvates, stereoisomers, and tautomers, and the sesquiterpene lactone compound is selected from arnica lactone D and / or artemisinin.

8. The cosmetic according to claim 7, characterized in that: The content of the sesquiterpene lactone compound in the cosmetic is ≤10wt%.

9. The cosmetic according to claim 7, characterized in that: The sesquiterpene lactone compound is used as one of the whitening active ingredients in the cosmetics.

10. The cosmetic according to claim 7, characterized in that: The dosage form of the cosmetic includes any one of an aqueous solution, an emulsion, a spray, a cream, an essence or a facial mask.

Images