Use of compound for preparing cosmetic

Abstract

The present invention relates to the technical field of cosmetics and particularly to use of the compound drimendiol or the compound epidrimendiol for preparing a cosmetic. The prepared cosmetic has moisturizing, repairing, firming, nourishing, anti-wrinkle, and soothing effects, and is mild, non-irritating, and suitable for sensitive skin.

Description

Uses of compounds in the preparation of cosmetics Technical Field

[0001] This invention relates to the field of cosmetic technology, and more particularly to the use of compounds Drimendiol and Epidrimendiol in the preparation of cosmetics. Background Technology

[0002] In 1995, Geoffrey D. Brown first reported the isolation of a new compound, Drimendiol, from the Chilean plant *Drimys winteri* (Geoffrey D. Brown, *Journal of Essential Oil Research*, 1995, 7:6, 705-707); Cristian Paza et al. reported the isolation of the compound Drimendiol from *Drimys winteri* and studied its querum sensing effect, finding that Drimendiol could inhibit the formation of querum sensing in *Chromobacterium violaceum* ATCC 12472, reduce the synthesis of quercetin, and reduce the formation of biofilms in *Pseudomonas syringae* (Cristian Paza et al., *Natural Product Communications*, 2013, Vol.8, No.2, 147-148); in 2013, Marcos... Derita et al., through their research on the structure-activity relationship between natural seripentine sesquiterpenes and antifungal activity, disclosed that the compound Drimendiol exhibits antifungal activity against Candida albicans, Saccharomyces cerevisiae, Cryptococcus neoformans, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Microsporum gypseum, Trichophyton rubrum, and Trichophyton mentagrophytes, with MIC values ​​exceeding 125 μg / mL. (Marcos Derita, Structural Requirements for the Antifungal Activities of Natural Drimane Sesquiterpenes and Analogues, Supported by Conformational and Electronic...) Studies, Molecules, 2013,18,2029-2051.); 2016, S.Mohanty reports that the compound Drimendiol has been isolated from Australian pepperberry. Extensive research has been conducted on the antibacterial activity of Drimendiol, revealing its effects against Alcaligenes faecalis, Staphylococcus aureus (ATCC), Serratia marcescens, Klebsiella pneumoniae, Escherichia coli (ATCC), Salmonella typhi, Enterococcus faecalis (ATCC), and Pseudomonas aeruginosa. ATCC), Proteus mirabilis, Streptococcus pyogenes, and Bacillus cereus have antibacterial activity, and the MIC values ​​for inhibition against various bacteria have been disclosed; S. Mohanty proposed that the compound Drimendiol inhibited 8 out of 11 tested bacterial strains, exhibiting a relatively broad spectrum of antibacterial activity (S. Mohanty, Bioactive Properties of Australian Native Fruits, Tasmania lanceolata and Terminalia ferdinandiana: The Characterization of their Active Compounds, 2016, Thesis (PhD Doctorate), Griffith University). However, the researchers in this application tested the MIC values ​​of the compound Drimendiol against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and found that the MIC values ​​of Drimendiol against these three strains were all greater than 1000 μg / mL. The strong inhibitory activity against E. coli and Staphylococcus aureus proposed by S. Mohanty was not detected. Purity N. Kipangaa et al., through studying the compound Drimendiol isolated from W. ugandensis in Uganda, conducted biofilm inhibition tests on Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis, and obtained a BIC (Biological Inhibition Certificate). 50The values ​​were 25.5±8 μg / mL, 65.1±24 μg / mL, and 67.1±12 μg / mL, respectively (Purity N. Kipangaa, Biofilm inhibiting properties of compounds from the leaves of Warburgia ugandensis Sprague subsp ugandensis against Candida and staphylococcal biofilms, Journal of Ethnopharmacology, 2019); In 2020, Cristian Paz et al. reported the isolation of the compound Drimendiol from the plant Drimys winteri and tested its inhibitory activity against the wheat take-all pathogen Gaeumannomyces graminis (LC50). 50 The concentration was 60 μg / mL (Cristian Paz, Applied and Environmental Microbiology, December 2020, Volume 86, Issue 24, e01834-20); In 2022, Nicole Cortez et al. reported that the compound Drimendiol was obtained by reducing polygodial, and the compound was tested against three Candida strains. The minimum inhibitory concentrations against Candida parapsilosis, Candida krusei, and Candida albicans were 25 μg / mL, 30 μg / mL, and 50 μg / mL, respectively (Nicole Cortez, Drimane Sesquiterpene Alcohols with Activity against Candida Yeast Obtained by Biotransformation with Cladosporium antarcticum, Int., J.Mol.Sci.2022,23,12995.). However, the researchers in this application tested the minimum inhibitory concentration (MIC) of the compound Drimendiol against Candida albicans and found that its MIC value was approximately 1000 μg / mL, which is 20 times higher than reported in the literature. Ivan Montenegro et al., through a study on the cytotoxicity of natural sterane sesquiterpenoid compounds, showed that the compound Drimendiol had no cytotoxic activity, and its IC50 value against four cell lines was [not specified]. 50All were greater than 200 μM (Ivan Montenegro, Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines, Molecules 2014, 19, 18993-19006); Lindon WK Moodie et al. studied the relationship between the structure and scale-inhibiting properties of squirtyl aldehyde and its derivatives. The results showed that, compared with other derivatives, the compound Drimendiol did not have significant inhibitory activity against tunicates C. savignyi and barnacles B. improvisus (Lindon WK Moodie, J. Nat. Prod. 2017, 80, 515-525).

[0003] As can be seen from the above existing technology reports, to date, most reports on the compound Drimendiol have focused on its antimicrobial activity, cytotoxic activity, and antiscaling properties. There are no reports on the cosmetic efficacy and applications of the compound Drimendiol.

[0004] In 2013, Marcos Derita et al. studied the structure-activity relationship between natural styraxane sesquiterpenes and their antifungal activity. Among their findings, they disclosed that the compound Epidrimendiol exhibited antifungal activity against *Candida albicans*, *Saccharomyces cerevisiae*, *Cryptococcus neoformans*, *Aspergillus niger*, *Aspergillus flavus*, *Aspergillus fumigatus*, *Microsporum gypseum*, *Trichophyton rubrum*, and *Trichophyton mentagrophytes*, with a MIC value exceeding 125 μg / mL. (Marcos Derita, *Structural Requirements for the Antifungal Activities of Natural Drimane Sesquiterpenes and Analogues*, Supported by Conformational and Electronic...) Studies, Molecules, 2013, 18, 2029-2051; Ivan Montenegro et al., through a study on the cytotoxicity of natural sesquiterpenoid compounds, showed that the compound Epidrimendiol had no cytotoxic activity, and its IC50 value was low for four cell lines. 50All values ​​were greater than 200 μM (Ivan Montenegro, Study on the Cytotoxic Activity of Drimane Sesquiterpene and Nordrimane Compounds against Cancer Cell Lines, Molecules 2014, 19, 18993-19006); In 2022, Nicole Cortez et al. reported that Epidrimendiol was obtained by reducing isotadeonal (isopolygodial), and the compound was tested against three Candida strains. The minimum inhibitory concentrations against Candida parapsilosis, Candida krusei, and Candida albicans were 25 μg / mL, 12.5 μg / mL, and 15 μg / mL, respectively (Nicole Cortez, Drimane Sesquiterpene Alcohols with Activity against Candida Yeast Obtained by Biotransformation with Cladosporium). (Antarcticum, Int., J.Mol.Sci.2022,23,12995.). However, the researchers in this application conducted minimum inhibitory concentration (MIC) tests on the compound Epidrimendiol to inhibit Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger, and found that its MIC values ​​were all greater than 1000 μg / mL.

[0005] As can be seen from the above existing technology reports, to date, most reports on the compound Epidrimendiol have focused on its antimicrobial activity, with no reports on its cosmetic efficacy or use. Summary of the Invention

[0006] The technical problem to be solved by this invention is: the use of compounds Drimendiol or Epidrimendiol in the preparation of cosmetics.

[0007] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0008] The use of compounds Drimendiol or Epidrimendiol in cosmetic preparation is evaluated by testing their cosmetic efficacy in humans and cell models.

[0009] The chemical structural formula of Drimendiol is:

[0010] The chemical structural formula of Epidrimendiol is as follows:

[0011] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products with moisturizing, repairing, anti-wrinkle, firming, nourishing and / or soothing effects.

[0012] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products with 72-hour moisturizing effects.

[0013] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products suitable for sensitive skin.

[0014] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetics that do not cause irritation.

[0015] The compounds Drimendiol or Epidrimendiol are used in cosmetic applications to prepare products that promote cheekbone elevation and / or reduce jaw angle.

[0016] The compound Epidrimendiol is used in the preparation of cosmetics with exfoliating properties.

[0017] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products that positively regulate the expression of the acid sphingomyelinase SMPD1 gene and the lobe protein LOR gene, thereby improving the skin barrier.

[0018] The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products that positively regulate the expression of the elastin ELN gene, thereby improving skin elasticity and firmness.

[0019] The compounds Drimendiol or Epidrimendiol are used to prepare cosmetic products that negatively regulate the expression of tumor necrosis factor-α, interleukin-1α and prostaglandin E2 genes, and improve skin inflammation and soothe sensitive skin.

[0020] The compounds Drimendiol or Epidrimendiol are used in cosmetic applications to prepare products that negatively regulate the expression of the vanillin-1 receptor gene with transient receptor potential, thereby achieving analgesic and anti-inflammatory effects on the skin.

[0021] The compound Drimendiol is used in cosmetic applications to increase the synthesis of hyaluronic acid in skin cells.

[0022] The beneficial effects of this invention are as follows: It investigates new uses of compounds Drimendiol or Epidrimendiol in the preparation of cosmetics, resulting in cosmetics with 72-hour moisturizing, hydrating, repairing, firming, nourishing, anti-wrinkle, and soothing effects; they are also gentle and non-irritating, suitable for sensitive skin; they positively regulate the expression of the acid sphingomyelinase SMPD1 gene and the LOR gene, improving the skin barrier function; they positively regulate the expression of the elastin ELN gene, improving skin elasticity and firmness; they negatively regulate the expression of tumor necrosis factor-α, interleukin-1α, and prostaglandin E2 genes, improving skin inflammation and soothing sensitive skin; they negatively regulate the expression of the transient receptor potential vanillin-1 receptor gene, achieving analgesic and anti-inflammatory soothing effects; and they increase the synthesis of hyaluronic acid in skin cells. Attached Figure Description

[0023] Figure 1 is a comparison of the moisture content of the stratum corneum of the cheek skin of the subjects before and after using the sample in Example 1;

[0024] Figure 2 is a comparison of the moisture content of the stratum corneum of the arm skin before and after the use of the sample area and blank area in Example 2.

[0025] Figure 3 is a comparison of the increase in moisture content of the stratum corneum of the arm skin after the sample area and the blank area of ​​the subject in Example 2.

[0026] Figure 4 is a comparison of transepidermal water loss rate of the subjects before and after using the sample in Example 3.

[0027] Figure 5 is a comparison of the SEr value of the cheek skin roughness parameter of the subjects before and after using the sample in Example 4;

[0028] Figure 6 is a comparison of the SEsm values ​​of the cheek skin smoothness parameter before and after the subjects used the sample in Example 4.

[0029] Figure 7 is a comparison of the SEr value of the elbow skin roughness parameter before and after the subject used the sample in Example 4;

[0030] Figure 8 is a comparison of the SEsm values ​​of the elbow skin smoothness parameter before and after the subjects used the sample in Example 4.

[0031] Figure 9 shows a comparison of skin glossiness of the subjects before and after using the sample in Example 4;

[0032] Figure 10 is a comparison of the skin elasticity R2 values ​​of the subjects before and after using the sample in Example 4;

[0033] Figure 11 is a comparison of the dermal layer thickness of the subject's skin before and after using the sample in Example 4;

[0034] Figure 12 is a comparison of the dermal density of the skin of the subjects before and after using the sample in Example 4;

[0035] Figure 13 is a comparison of the a* values ​​of the skin red area of ​​the subjects before and after using the sample in Example 5;

[0036] Figure 14 is a comparison of skin color L* values ​​of the subjects before and after using the sample in Example 5;

[0037] Figure 15 is a comparison of the F4 values ​​of skin firmness of the subjects before and after using the sample in Example 6;

[0038] Figure 16 is a comparison of the proportion of under-eye wrinkles before and after the subjects used the sample in Example 7;

[0039] Figure 17 is a comparison of the mandibular angle of the subjects before and after using the sample in Example 8;

[0040] Figure 18 is a comparison of the upward movement of the apple cheeks of the subjects before and after using the sample in Example 8;

[0041] Figure 19 is a comparison chart of the subjective skin sensation evaluation (ten-point questionnaire) of the subjects before and after using the sample in Example 10;

[0042] Figure 20 shows the self-assessment results of the subjects in Example 10 after using the sample for 28 days.

[0043] Figure 21 is a comparison of the changes in skin smoothness of the subjects before and after using the sample in Example 4;

[0044] Figure 22 is a rendering comparison of the changes in skin smoothness before and after the subjects used the sample in Example 4;

[0045] Figure 23 is a comparison of the changes in skin thickness / density before and after the subjects used the sample in Example 4;

[0046] Figure 24 is a comparison of the skin color improvement effect of the subjects before and after using the sample in Example 5;

[0047] Figure 25 is a comparison of the changes in skin redness before and after the subjects used the sample in Example 5;

[0048] Figure 26 is a comparison of the improvement in under-eye wrinkles before and after the subjects used the sample in Example 7;

[0049] Figure 27 is a comparison of the improvement in mandibular angle before and after the subjects used the sample in Example 8;

[0050] Figure 28 is a comparison of the improvement in the upward movement of the apple cheeks before and after the subjects used the sample in Example 8;

[0051] Figure 29 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 11;

[0052] Figure 30 is a bar chart showing the relative expression levels of the SMPD1 gene in each group in Example 11;

[0053] Figure 31 is a bar chart showing the relative expression levels of LOR genes in each group in Example 11;

[0054] Figure 32 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 12;

[0055] Figure 33 is a bar chart showing the relative expression levels of the ELN gene in each group in Example 12;

[0056] Figure 34 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 13;

[0057] Figure 35 is a bar chart showing the relative expression levels of the TNF-α gene in each group in Example 13;

[0058] Figure 36 is a bar chart showing the relative expression levels of the IL-1α gene in each group in Example 13;

[0059] Figure 37 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 14;

[0060] Figure 38 is a bar chart showing the relative expression levels of the TRPV1 gene in each group in Example 14;

[0061] Figure 39 is a bar chart showing the relative expression levels of the PGE2 gene in each group in Example 14;

[0062] Figure 40 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 15;

[0063] Figure 41 is a bar chart of the average HA concentration in each group in Example 15;

[0064] Figure 42 is a graph showing the moisture content analysis of the stratum corneum before and after use in Example 16;

[0065] Figure 43 is an analysis of the changes in stratum corneum moisture content before and after use in Example 17;

[0066] Figure 44 is a graph showing the transepidermal water loss rate before and after use in Example 18;

[0067] Figure 45 is a graph showing the SEsm values ​​before and after use in Example 19;

[0068] Figure 46 shows the gloss analysis before and after use in Example 19;

[0069] Figure 47 is a graph showing the R0 values ​​before and after use in Example 19;

[0070] Figure 48 is a graph showing the R2 values ​​before and after use in Example 19;

[0071] Figure 49 is a diagram showing the thickness analysis of the dermis before and after use in Example 19;

[0072] Figure 50 shows the before and after dermal density analysis diagrams used in Example 19;

[0073] Figure 51 is a graph showing the analysis of a* values ​​before and after use in Example 20;

[0074] Figure 52 is a graph showing the L* values ​​before and after use in Example 20;

[0075] Figure 53 is an analysis chart of the area ratio of under-eye wrinkles before and after using Example 22;

[0076] Figure 54 is a diagram showing the volume analysis of sagging cheeks before and after use in Example 23.

[0077] Figure 55 is an analysis diagram of the outline length of the drooping part of the mandibular border in Example 23;

[0078] Figure 56 is a graph showing the pre- and post-Bauman Questionnaire scoring analysis in Example 24.

[0079] Figure 57 is a graph showing the analysis of the DI values ​​of the desquamation index before and after use in Example 25;

[0080] Figure 58 is a comparison of the changes in the volume of sagging cheeks before and after use in Example 23;

[0081] Figure 59 is a comparison diagram of the changes in the outline of the drooping part of the mandibular border before and after using Example 23;

[0082] Figure 60 is a comparison of the changes in under-eye wrinkles before and after using Example 22;

[0083] Figure 61 is a comparison of the changes in skin smoothness before and after use in Example 19;

[0084] Figure 62 is a comparison of skin changes before and after exfoliation in Example 25;

[0085] Figure 63 is a comparison of the changes in dermal thickness and density before and after use in Example 19;

[0086] Figure 64 is a comparison of skin redness changes before and after use in Example 20;

[0087] Figure 65 is a bar chart showing the relative cell viability of each group in the first MTT experiment in Example 27;

[0088] Figure 66 is a bar chart showing the relative cell viability of each group in the second MTT experiment in Example 27;

[0089] Figure 67 is a bar chart of the relative expression levels of the SMPD1 gene in each group during the first efficacy test in Example 27;

[0090] Figure 68 is a bar chart of the relative expression levels of the SMPD1 gene in each group during the second efficacy test in Example 27;

[0091] Figure 69 is a bar chart showing the relative expression levels of LOR genes in each group during the first efficacy test in Example 27.

[0092] Figure 70 is a bar chart showing the relative expression levels of LOR genes in each group during the second efficacy test in Example 27;

[0093] Figure 71 is a bar chart showing the relative cell viability of each group in the first MTT experiment in Example 28;

[0094] Figure 72 is a bar chart showing the relative cell viability of each group in the second MTT experiment in Example 28;

[0095] Figure 73 is a bar chart of the relative expression levels of the ELN gene in each group during the first efficacy test in Example 28;

[0096] Figure 74 is a bar chart showing the relative expression levels of the ELN gene in each group during the second efficacy test in Example 28.

[0097] Figure 75 is a bar chart showing the relative cell viability of each group in the MTT experiment in Example 29;

[0098] Figure 76 is a bar chart showing the relative expression levels of the TNF-α gene in each group in Example 29;

[0099] Figure 77 is a bar chart showing the relative expression levels of the IL-1α gene in each group in Example 29;

[0100] Figure 78 is a bar chart showing the relative cell viability of each group in the first MTT experiment in Example 30;

[0101] Figure 79 is a bar chart showing the relative cell viability of each group in the second MTT experiment in Example 30;

[0102] Figure 80 is a bar chart showing the relative expression levels of the TRPV1 gene in each group during the first efficacy test in Example 30.

[0103] Figure 81 is a bar chart of the relative expression levels of the PGE2 gene in each group during the first efficacy test in Example 30;

[0104] Figure 82 is a bar chart showing the relative expression levels of the PGE2 gene in each group during the second efficacy test in Example 30. Detailed Implementation

[0105] To explain in detail the technical content, objectives, and effects of the present invention, the following description is provided in conjunction with the embodiments and accompanying drawings.

[0106] The "Standard for Evaluation of Cosmetic Efficacy Claims" (implemented on May 1, 2021) stipulates that cosmetic efficacy includes: moisturizing, hair care, whitening and freckle removal, sun protection, hair loss prevention, acne treatment, nourishing, repairing, anti-wrinkle, firming, soothing, oil control, exfoliation, anti-breakage, dandruff removal, claims of being mild (e.g., non-irritating), specific claims of suitability for sensitive skin, and tear-free formulas. It also clarifies the requirements for the claims of these cosmetic efficacy. Specifically, cosmetics with whitening, freckle removal, sun protection, hair loss prevention, acne treatment, nourishing, and repairing effects must undergo efficacy claim evaluation through human efficacy evaluation trials. Cosmetics with anti-wrinkle, firming, soothing, oil control, exfoliation, anti-breakage, and dandruff removal effects, as well as claims of being mild (e.g., non-irritating) or having quantifiable indicators (e.g., efficacy claim duration, efficacy claim-related statistical data, etc.), must undergo efficacy claim evaluation trials, which may also incorporate literature review or research data analysis results. Cosmetics that make specific claims (such as claims that they are suitable for sensitive skin or that they are tear-free formulas) should have their efficacy claims evaluated through human efficacy evaluation trials or consumer use tests.

[0107] The regulations also stipulate that the test methods used for evaluating the efficacy of cosmetics include: methods specified in my country's mandatory national standards and technical specifications for cosmetics; methods specified in other relevant laws, national standards, and industry standards in my country; methods specified in relevant foreign laws or technical standards; methods published in technical guidelines by authoritative domestic and foreign organizations, technical institutions, and industry associations; methods published in professional academic journals and periodicals; or methods that are independently developed and established. Before conducting efficacy evaluations, evaluation institutions should complete the necessary transfer, confirmation, or verification of test methods to ensure the scientific rigor and reliability of the evaluation work.

[0108] In this application, the cosmetic efficacy claims of compounds Drimendiol and Epidrimendiol, including 72-hour moisturizing (quantitative indicator), hydration, repair, anti-wrinkle, firming, nourishing, soothing, gentle and non-irritating, and suitability for sensitive skin, have all passed human efficacy evaluations. These conclusions were drawn through scientific statistical analysis of the evaluation results data using standard cosmetic efficacy evaluation methods. Other specific claimed facial lifting effects, such as jawline reduction and cheekbone elevation, were also determined through measurement and statistical analysis using human efficacy evaluations. The efficacy evaluation methods in this application all comply with the requirements of the "Cosmetic Efficacy Claim Evaluation Standard," which are specifically illustrated in the embodiments of this application.

[0109] The relationship between SMPD1 gene expression and skin stratum corneum hydration

[0110] Sphingomyelin phosphodiesterase 1 (SMPD1), also known as acid sphingomyelinase (ASM), is responsible for converting sphingomyelin into ceramide. It is encoded and expressed in the human body through the SMPD1 gene. SMPD1 gene deficiency can lead to Niemann-Pick disease (NPD), also known as sphingomyelin deposition disease. This disease is caused by a deficiency of sphingomyelinase, resulting in impaired sphingomyelin metabolism. Furthermore, a mutation at residue 302 of the SMPD1 gene, replacing leucine with proline, increases the risk of Parkinson's disease.

[0111] Ceramides play a crucial role in the integrity of the skin barrier, being an important component of the phospholipid bilayer of the stratum corneum cell membrane. Patients with SMPD1 deficiency exhibit abnormal skin barrier permeability due to abnormally low ceramide levels in the stratum corneum (Schmuth et al., 2000). They observed an increase in sphingomyelin content and a decrease in the thickness of the extracellular layer of the stratum corneum in nude mice after applying the SMPD1 inhibitors palmitoyl dihydrosphingosine and desipramine to the skin of mice. These mice exhibited delayed repair of skin barrier damage. Furthermore, applying a ceramide-containing cream to the damaged area improved the symptoms of skin barrier damage in mice treated with the inhibitors. This finding indicates that the loss of stratum corneum barrier function in SMPD1-deficient patients is not caused by the accumulation of sphingomyelin, but rather by an imbalance in the ratio of sphingomyelin to ceramides. A key reason for this is that SMPD1 fails to function properly, preventing the conversion of sphingomyelin to ceramides.

[0112] Furthermore, patients with eczema exhibit lower SMPD1 enzyme activity levels in the affected skin areas, leading to lower ceramide levels and abnormal skin barrier permeability. Clearly, normal skin function depends on the integrity of the epidermal cell membrane, and SMPD1 plays a crucial role in this process. Loss of SMPD1 enzyme activity results in compromised epidermal cell membrane integrity, allowing moisture in the stratum corneum to evaporate easily, leading to dry skin. Therefore, the activity level of SMPD1 enzyme is closely related to the moisture content of the stratum corneum. Low SMPD1 enzyme activity leads to a deficiency of ceramides in the stratum corneum, resulting in compromised stratum corneum integrity and moisture evaporation, manifesting as dry skin. High SMPD1 enzyme activity results in high ceramide levels in the stratum corneum, ensuring good stratum corneum integrity and allowing moisture to be easily retained, resulting in good skin hydration.

[0113] The compound described in this application was found to have a positive regulatory effect on the relative expression level of the SMPD1 gene. Based on the function of the SMPD1 enzyme, it can be inferred that with an increase in the expression level of the SMPD1 enzyme, the ceramide level in the stratum corneum of the skin is sufficient, the skin barrier integrity is good, and therefore the stratum corneum is adequately moisturized. Therefore, the compound described in this application can be used for moisturizing purposes in cosmetics by regulating the skin's SMPD1 gene.

[0114] The relationship between lipoprotein and skin barrier and moisturizing

[0115] The stratum corneum is the outermost layer of the human epidermis, composed of multiple layers of flattened, anucleate keratinocytes. Each keratinocyte is surrounded by the cornified cell envelope (CE), which contains envelope proteins such as involucrin, loricrin, proline-rich small protease protein (SPR), elastin, keratin filaments, filaggrin, cysteine ​​protease inhibitor-A, and desmosomes.

[0116] Loricrin is a major protein component of the keratinized capsule, accounting for approximately 80%. It is an insoluble polypeptide with a molecular weight of 26 kDa, and in humans, it is expressed via the LOR gene. Loricrin primarily strengthens the keratinocyte membrane and the keratin barrier function. It is expressed in the epidermis of all mammals, with the highest expression levels in tissues with high water content, such as the epidermis of newborns, the oral and anal mucosa, the esophagus, foreskin, vagina, and the epidermal portions of sweat ducts.

[0117] The expression level of nephritin is influenced by various factors, such as cell fusion, calcium ions, vitamin A deficiency, transglutaminase activity, and Nectin-1. These transcription factors act on nephritin activator protein (AP1), ultimately inducing epidermal differentiation. For example, nephritin expression is negatively regulated by retinoic acid, leading to the failure to form a keratinocyte capsule. Calcium ions affect nephritin transcription levels. When calcium ion levels are low, such as below 0.10 mM, nephritin and keratinocyte capsule formation are immature and fragile. At high cell densities, nephritin expression ceases at calcium ion levels of 0.05 mM. Mice with Nectin-1 knockout exhibit defective nephritin expression, resulting in a fragile keratinocyte capsule that is easily broken under mechanical forces. For example, under the attack of inflammatory factors, the stratum corneum of eczema patients is negatively regulated by the expression of filaggrin and naupliin genes, resulting in a significant decrease in barrier function, which in turn leads to an increase in water loss and makes the skin appear drier.

[0118] It is evident that scutellarin is crucial for the integrity of the keratinocyte capsule. More specifically, functionally, scutellarin is essential for maintaining the keratinocyte capsule and the keratinocyte's role in the skin barrier. From a cosmetic efficacy perspective, a healthy skin barrier results in a strong moisturizing ability of the stratum corneum; conversely, an imperfect skin barrier leads to weak moisturizing and easy water loss. The health of the skin barrier directly determines the moisture content of the stratum corneum. Therefore, to a large extent, the expression level of scutellarin in the stratum corneum capsule directly determines the moisture content of the stratum corneum. High gene expression of scutellarin in the stratum corneum capsule leads to increased scutellarin production, resulting in higher moisture content in the stratum corneum. Conversely, low gene expression of scutellarin in the stratum corneum capsule leads to lower scutellarin production, resulting in dryness of the stratum corneum.

[0119] During extensive research, the applicant discovered that the compound of this application positively regulates the expression of the LOR gene at a concentration of 2 ppm, with the relative expression level of the LOR gene reaching 205%. The specific examples illustrate and summarize this result in detail.

[0120] The relationship between elastin and skin anti-wrinkle and firming

[0121] Skin aging is a complex process influenced by both internal and external factors. Ultraviolet (UV) radiation is a representative cause of skin damage; after years of exposure, the skin undergoes photoaging. As we age, skin tissue also undergoes changes, such as a loss of elasticity due to reduced elastin synthesis, degradation, and other factors.

[0122] Elastin fibers are essential components of skin connective tissue. They are synthesized through the extracellular matrix and then secreted into skin fibroblasts. Through the assembly of elastin and numerous microtubule elements, they form a fibrous network structure that can extend and contract, exhibiting elasticity. Mature elastin fibers are primarily composed of elastin, which in humans is encoded by a single gene, ELN. This gene is located on chromosome 7 and differentiates into various cell types during development, expressing elastin.

[0123] Changes in collagen caused by natural aging and photoaging have been extensively studied. However, research on the composition of elastin in the skin is lacking. The FDA has not approved elastin substitutes or stimulants for elastin synthesis. Recent animal studies have shown that a zinc-containing complex can increase skin elastin staining, subcutaneous fat, and epidermal thickness. Histological studies have shown that after 10 days of topical application, the zinc complex can increase the deposition of functional elastin fibers. Clinical trials have reported that increased functional elastin promotes the improvement of fine lines and wrinkles (Leslie Baumann and Susan Weinkle, Improving Elasticity: The Science of Aging Skin, 2010).

[0124] Collagen and elastin are fibrous proteins that make up the skin's matrix. Cosmetic dermatologists have long used topical medical products, fillers, and light- and laser-based treatments to address collagen loss caused by aging. However, to date, no fillers or topical agents have been found to address the loss of elastin function, a key characteristic of photoaging. The decline in collagen, elastin, and other skin matrix components, combined with natural aging and photoaging, leads to wrinkles, sagging skin, and skin fatigue.

[0125] The role of elastin in skin aging

[0126] Elastin is an elastic connective tissue in the extracellular matrix. Elastin fibers are typically distributed around the edges of collagen bundles and around elastic skin. The precursor to elastin is the molecule protopoelastin. Elastin is formed by covalently cross-linking. Elastin further assembles into fibrils by forming microfibrils. The fibrils serve as templates for elastin deposition. The vast majority of elastin production is confined to a very narrow window of growth and development. Elastin is produced in large quantities during the fetal period, the prenatal period, and the early neonatal period. After maturity, elastin synthesis declines sharply.

[0127] Unlike collagen fibers, elastin fibers exist at various stages of maturation. Oxytalan fibers are the least mature elastin fibers, extending vertically from the dermal-epidermal junction to the top of the reticular dermis. Elaunin fibers are more mature elastin bundles attached to horizontal fiber tufts in the reticular dermis. The most mature elastin fibers, however, are unnamed and reside deeper in the top of the dermis.

[0128] This fibrous network, stretching from the top of the dermis to the bottom of the basement membrane, maintains the elasticity of youthful skin. This network of elastin fibers deteriorates with age; the loss or deterioration of elastin fibers is a major cause of sagging skin and the loss of youthful skin's resilience.

[0129] Initially, photoaging, based on levels of UV exposure, leads to the proliferation of elastin fibers. This is followed by a degenerative response, resulting in a loss of skin elasticity. Under a microscope, degraded elastin appears as amorphous material, accumulated in the dermis. The result is elastosis, a hallmark of photoaging due to the degradation of elastin fibers and the loss of elastin function. Elastin defects and damage lead to wrinkles, even without sun exposure or aging conditions. Children with dermatoglycemic syndromes show that elastin fiber defects are a primary cause. This illustrates the crucial role elastin plays in maintaining skin integrity.

[0130] Studies have shown that as skin ages, even in well-protected areas, the content of elastin gradually decreases. An Egyptian study showed that even in normal skin without UV radiation exposure, the relative elastin content decreased from 49% at age 10 to 30.4% at age 90. Another study of 91 Caucasians with unexposed buttocks skin showed a 51% decrease in elastin content from age 20 to 80.

[0131] For a long time, cosmetic dermatologists have emphasized promoting the formation of new collagen through collagen supplement injections or topical cosmetics. However, products targeting the improvement of skin elastin are less common. Although some cosmetics contain collagen and elastin and claim to increase the levels of these protein fibers in the skin, topical collagen and elastin are not convincing. This is because collagen and elastin have large molecular weights and are difficult to penetrate into the dermis.

[0132] In extensive cosmetic activity studies, the compounds of this application were found to have a significant positive regulatory effect on the expression level of the ELN gene in fibroblasts, with a relative ELN gene expression level reaching 2.8 to 6.5 times even at very low concentrations, for example, 5 to 20 ppm. Furthermore, the compounds of this application have a small molecular weight and strong permeability, easily penetrating into the dermis layer of the skin. Therefore, they are suitable for use in the preparation of cosmetics that promote the synthesis of elastin in the skin.

[0133] Increased synthesis of elastin in the skin results in an anti-wrinkle and firming effect on human skin. Human efficacy evaluation trials have also confirmed the significant anti-wrinkle and firming effects of the compound in this application.

[0134] The relationship between inflammatory factor inhibition and skin soothing

[0135] Human keratinocytes (KCs) are located in the epidermal layer of the skin, accounting for more than 80% of epidermal cells, and are the skin area most directly exposed to ultraviolet (UV) radiation from sunlight. UV radiation causes photoaging and photodamage to the skin. Under culture conditions, morphological changes in KC cells under UVB radiation were observed under a microscope, mainly manifested as cell swelling, shedding, increased cell debris, and cells floating on the culture medium. Excessive UVB doses can induce apoptosis in skin cells. Simultaneously, KCs are also an important component of the skin's immune system, secreting various cytokines. Tumor necrosis factor-α (TNF-α) is one of the main epidermal cytokines synthesized by KCs, participating in UV-induced skin inflammation and immune regulation, and playing a crucial role in UV-mediated apoptosis. Furthermore, UV radiation induces the secretion of TNF-α and other interleukins by KCs, such as IL-1α, IL-10, IL-6, and PGE2. With increasing UV irradiation dose, the secretion of TNF-α and other cytokines also increases, ultimately leading to KC cell apoptosis. The above describes the process of UV-induced inflammation of human keratinocytes and the production of some cytokines.

[0136] In addition to the skin's stratum corneum being exposed to UV rays, when the skin comes into contact with toxic, corrosive, or irritating chemicals, exogenous pathogens, or mechanical damage such as abrasions, these factors can trigger the skin's own immune system to repair the cell and tissue damage caused by these factors.

[0137] Much of this skin inflammation is triggered by a series of biochemical reactions involving epidermal cytokines and lipids. For example, activation of the kinin and arachidonic acid systems can spark a chain of protein and lipid responses, leading to the expression of pro-inflammatory cytokines.

[0138] Pro-inflammatory factors controlling inflammatory responses include IL-1α, IL-1β, IL-8, IL-6, PGE2, and TNF-α. Among these, IL-1α, IL-1β, and TNF-α are known as primary cytokines because they can directly and rapidly induce localized skin inflammation. Primary cytokines can stimulate the production of secondary cytokines, such as IL-6 and IL-8. Secondary cytokines play a supportive role in the inflammatory response. To regulate the inflammatory process, inflammatory cytokine receptor antagonists are used to inhibit inflammation.

[0139] Overexpression of pro-inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6, PGE2, and TNF-α in the skin can cause discomfort such as redness, stinging, and itching. In cosmetic dermatology, small molecule active ingredients can be used to inhibit the overexpression of pro-inflammatory factors and alleviate discomfort caused by various skin inflammatory factors in order to soothe allergic inflammatory reactions of the skin.

[0140] The compound of this application has an inhibitory effect on the gene expression of inflammatory factors TNF-α, IL-1α and PGE2 at low concentrations in the ppm range, and can be developed into a cosmetic with soothing effects for sensitive skin and sensitive predisposition, with good results.

[0141] TRPV1 and its relationship with skin soothing

[0142] Transient receptor potential channels play a crucial role in signal transduction between adjacent cells. To date, six major classes of transmembrane receptors have been discovered, each with various mechanisms of action. Among them, the mechanism of action of the TRPV1 (transient receptor potential vanilloid 1) receptor is relatively well understood. The TRPV1 receptor is a temperature-regulated calcium ion channel. TRPV1 is located on sensory nerve fibers.

[0143] The TRPV1 receptor is activated under conditions of temperature above 42°C, low pH, and chemical activators, placing it in an excited state. For example, capsaicin can activate TRPV1. Certain metabolites and cytokine-supported inflammatory responses, such as arachidonic acid and leukotrienes, can also activate the TRPV1 receptor.

[0144] When TRPV1 receptors are activated, they cause an outflow of calcium ions from the cell, and the activation signal is transferred to neurotrophic factors, which are then transmitted to the brain. TRPV1 activation leads to skin pain, burning, stinging, and tightness. These discomforts are typical symptoms of sensitive skin. The chemical activator capsaicin can activate TRPV1 in an ion channel activated state, causing a burning sensation on the skin. Interestingly, if capsaicin continuously stimulates TRPV1 receptors, the activation state of TRPV1 receptors is downregulated, eventually leading to desensitization. Conversely, the application of acidic substances leads to an increase in TRPV1 expression. Therefore, TRPV1 regulation is influenced by various external factors. In individuals with hypersensitive skin, TRPV1 receptors are easily activated, and the number of activated receptors is large, making the skin abnormally sensitive to changes in the external environment.

[0145] TRPV1 receptor antagonists can control calcium ion efflux, thus soothing the discomfort of sensitive skin. For example, capsaicin, a potent TRPV1 receptor antagonist, has an extremely low micromole-level IC50. 50 It can inhibit the efflux of calcium ions activated by TRPV1 induced by chemical agonists. The main reason for this is the complexity of the TRPV1 receptor conformation.

[0146] The compound of this application was found to have a negative regulatory effect on the relative expression level of the TRPV1 gene. Specific data are detailed in the examples. Based on the function of the TRPV1 gene, it can be inferred that it has a certain inhibitory effect on TRPV1 protein expression, reducing the expression of TRPV1 receptors in sensitive skin and reducing the skin's response to external stimuli. Therefore, the compound of this application can be used for skin soothing purposes in cosmetics.

[0147] The chemical structural formula of Drimendiol is:

[0148] Preparation method of Drimendiol:

[0149] 10.0 kg of Tasmannia lanceolata leaf powder was extracted with 60.0 kg of ethanol:water in a 1:1 ratio at 60°C by heating and stirring for 3 hours. After filtration, the Tasmannia lanceolata leaf residue was extracted again with 30.0 kg of ethanol:water in a 1:1 ratio at 60°C by heating for 2 hours. After filtration, the two filtrates were combined and concentrated under reduced pressure to obtain 650 g of extract.

[0150] 650g of pepperberry leaf extract was separated by 2kg silica gel column chromatography using a 200-300 mesh screen. The eluents were petroleum ether (PE) and PE:ethyl acetate (EA) at ratios of 10:1, 5:1, and 3:1. The eluents for each fraction were collected separately. The compound Drimendiol was mainly concentrated in the PE:EA = 5:1 eluent. This fraction was concentrated under reduced pressure to obtain a Drimendiol concentrate. Subsequently, it was separated again by 200-300 mesh silica gel column chromatography to remove impurities, yielding 16g of Drimendiol.

[0151] NMR data for compound Drimendiol:

[0152] δ 13 C-NMR: 39.1(C-1); 18.4(C-2); 42.0(C-3); 33.0(C-4); 49.4(C-5); 23.6(C-6); 127.7(C-7); 137.3 (C-8); 54.9 (C-9); 35.6 (C-10); 68.0 (C-11); 61.4 (C-12); 33.2 (C-13); 21.9 (C-14); 14.5 (C-15).

[0153] δ 1 H-NMR: 5.81 (H, m); 4.34~4.38 (H, d); 3.96~3.99 (H, d); 3.89~3.92 (H, dd); 3 .65~3.70(H,dd);3.6(2H,br,2OH);2.17(H,m);2.11~2.14(H,m);1.93~2.0 0(H,m); 1.85~1.91(H,m); 1.53~1.61(H,m); 1.48-1.52(H,m); 1.38~1.47(H ,m); 1.25(H,m); 1.13~1.19(2H,m); 0.89(3H,s); 0.88(3H,s); 0.76(3H,s).

[0154] To prepare a 20 ppm Drimendiol solution as a sample: First, dissolve 0.2 g of Drimendiol in 99.8 g of polyol (such as 1,3-butanediol or propylene glycol), stir and heat to dissolve, and obtain a 2000 ppm Drimendiol solution. Then, dilute the 2000 ppm Drimendiol solution 100 times with pure water to 20 ppm.

[0155] A 20 ppm Drimendiol solution was prepared as a sample to test various cosmetic applications for human health (Examples 1 to 10).

[0156] The prepared 2000ppm Drimendiol solution was used as a sample to test the cosmetic applications of various gene expression effects (Examples 11 to 15);

[0157] Test period: July 29, 2024 - August 26, 2024;

[0158] Test environment: Temperature: 21±1℃; Humidity: 50±10%RH;

[0159] Thirty-two subjects with sensitive skin were selected and subjected to the Baumann Skin Type Questionnaire. The results are shown in Table 1.

[0160] Table 1 Note: A score of 34-72 indicates very sensitive skin; a score of 30-33 indicates slightly sensitive skin; a score of 25-29 indicates relatively tolerant skin; a score of 18-24 indicates very tolerant skin. In summary, a score of 30-72 indicates sensitive skin (abbreviated as "S" type or S type), and a score of 18-29 indicates tolerant skin (abbreviated as R type).

[0161] Subject inclusion criteria:

[0162] 1) Healthy Chinese women aged 30-55;

[0163] 2) Sensitive skin (Bauman Questionnaire), visible under-eye wrinkles (under-eye wrinkle grade ≥2, refer to "Skin Aging Atlas"), loose, dry, and red facial skin, and a weak facial skin barrier (TEWL ≥15g / h / m). 2 )those;

[0164] 3) Physically healthy, with no other chronic diseases or diseases currently being treated;

[0165] 4) Participate in the evaluation voluntarily and sign an informed consent form;

[0166] 5) Willing to comply with all evaluation requirements.

[0167] Exclusion criteria for participants:

[0168] 1) Those who have used antihistamines in the past week or tried immunosuppressants in the past month;

[0169] 2) Those who have used any anti-inflammatory drugs at the test site within the past two months;

[0170] 3) Subjects with clinically unhealed inflammatory skin diseases;

[0171] 4) Patients with insulin-dependent diabetes mellitus;

[0172] 5) Patients with asthma or other chronic respiratory diseases who are currently receiving treatment;

[0173] 6) Individuals who have received anti-cancer chemotherapy within the past 6 months;

[0174] 7) Patients with immunodeficiency or autoimmune diseases;

[0175] 8) Breastfeeding or pregnant women;

[0176] 9) Patients who have undergone bilateral mastectomy and bilateral axillary lymph node dissection;

[0177] 10) If the determination of the test results is affected by scars, pigmentation, atrophy, port-wine stains, uneven skin color, folliculitis or other defects on the skin to be tested;

[0178] 11) Researchers participating in other clinical trials;

[0179] 12) Individuals with highly sensitive constitutions;

[0180] 13) Non-volunteer participants or those who cannot complete the prescribed content according to the test requirements.

[0181] Criteria for subject withdrawal midway:

[0182] 1) Not selected (e.g., not meeting the selection criteria or being excluded by the exclusion criteria, etc.);

[0183] 2) Subjects were determined to be ineligible after being selected (including but not limited to changes in other lifestyle, diet, skincare habits and skincare samples during the evaluation period);

[0184] 3) The participant chooses to withdraw;

[0185] 4) An adverse event or a serious adverse event occurs;

[0186] 5) Loss to follow-up;

[0187] 6) Force majeure;

[0188] 7) Others.

[0189] Test method basis:

[0190] 1) QT / ZHCA 005-2019 Test Method for the Effect of Cosmetics on Skin Elasticity

[0191] 2) QB / T 4256-2011 Guidelines for Evaluating the Moisturizing Efficacy of Cosmetics

[0192] 3) T / GDCA 009-2022 Method for Evaluating the Repairing Efficacy of Cosmetics on Human Body

[0193] 4) T / ZHCA 003-2018 Test Method for the Effects of Cosmetics on Transepidermal Moisture Loss

[0194] 5) T / CNMIA 0015-2020 Clinical Evaluation Standards for Soothing and Sensitive Skincare Products

[0195] 6) T / GDCDC 021-2022 Test Method for Soothing Efficacy of Cosmetics

[0196] 7) Wang Huan, Pan Yao. Evaluation of Cosmetic Efficacy (V) - Scientific Support for Claims of Soothing Efficacy [J]. Daily Chemical Industry, 2018, 48(05):247-254

[0197] 8) T / ZHCA 005-2019 Test Method for the Effect of Cosmetics on Skin Elasticity

[0198] 9) T / GDCDC 032-2023 Test Method for Exfoliating Efficacy of Cosmetics

[0199] 10) T / ZHCA 006-2019 Test Method for Anti-wrinkle Efficacy of Cosmetics

[0200] 11) T / TDCA 003-2021 Test Method for Firming Efficacy of Cosmetics

[0201] 12) T / CAB 0152-2022 Test Methods for Seven Efficacy Items in Cosmetics: Anti-wrinkle, Firming, Moisturizing, Oil Control, Repairing, Nourishing, and Soothing

[0202] 13) Liu, Weiyi; Zhou, Lin; Zhao, Hua. Cosmetic Efficacy Evaluation (XIII) – Consumer Use Testing [J]. Daily Chemical Industry, 2021, 51(06):485-490

[0203] 14) Cosmetic Safety Technical Specifications (2015 Edition)

[0204] 15) Cosmetic classification rules and classification catalog

[0205] 16) Standards for Evaluating Cosmetic Efficacy Claims

[0206] Test process:

[0207] D0:

[0208] 1) Subject information registration, understanding and signing of informed consent forms, and screening of subjects by laboratory technicians according to inclusion and exclusion criteria;

[0209] 2) Subjects cleaned their entire face with the designated facial cleanser sample, rinsed the inside of their arms with water, and dried them with a paper towel. They then sat quietly for 30 minutes in a laboratory with a temperature of 21±1℃ and a humidity of 50±10%RH.

[0210] 3) Mark two measurement areas on the inside of the subject's forearm. The area of ​​each test area is 3cm*3cm, and there should be at least 1cm between each test area.

[0211] 4) Before the formal test, sit quietly in a standard room for at least 30 minutes, without drinking water or beverages, with your forearms exposed and placed in the test position, and keep relaxed;

[0212] 5) The sample area and blank area are randomly distributed in the arm calibration area to ensure that the positions of all sample areas and blank areas are statistically balanced;

[0213] 6) Testing the baseline values ​​of the subject's facial skin: Bauman questionnaire, VECTRA H2 image acquisition, VISIA image acquisition, UC22 to test the density and thickness of the dermis, VC20 image acquisition, Glossymeter to test the skin luster, Corneometer to test the moisture content of the stratum corneum, Cutometer to test the R2 value of skin elasticity and the F4 value of skin firmness, and Tewameter to test the transepidermal water loss rate of the skin.

[0214] 7) Test the baseline values ​​of the subject's arm skin: use a Corneometer to measure the moisture content of the stratum corneum;

[0215] 8) Apply the test sample to the inside of the subject's arm at a concentration of (2.0±0.1) mg / cm². 2 Apply evenly to the sample area; leave the blank areas untreated.

[0216] 9) Note: Do not wash or apply any cosmetics, medicines, or other products that may affect the test results on the inside of your arm during the 72-hour period.

[0217] 10) Laboratory technicians will guide subjects on how to use the samples according to the sample usage requirements and application sites, and provide written test precautions and usage instructions;

[0218] 11) The subjects collect their samples and leave the laboratory.

[0219] T72h:

[0220] 1) Skin data values ​​of test subjects 72 hours after using the sample: Corneometer test of skin stratum corneum moisture content;

[0221] 2) Subjects completed a self-assessment questionnaire.

[0222] D28:

[0223] 1) Subjects cleaned their faces with the specified facial cleanser sample and sat quietly for 30 minutes in a laboratory with a temperature of 21±1℃ and a humidity of 50±10%RH.

[0224] 2) Skin data values ​​of test subjects after 28 days of sample use: Bauman questionnaire, VECTRA H2 image acquisition, VISIA image acquisition, UC22 to test dermal density and dermal thickness, VC20 image acquisition, Glossymeter to test skin luster, Corneometer to test stratum corneum moisture content, Cutometer to test skin elasticity R2 value and skin firmness F4 value, Tewameter to test transepidermal water loss rate;

[0225] 3) Subjects completed self-assessment questionnaires, and samples and usage logs were collected.

[0226] Note: D0 refers to the visit before the subject uses the sample, T72h refers to the visit 72 hours after the subject uses the sample, D7 refers to the visit 7 days after the subject uses the sample, D14 refers to the visit 14 days after the subject uses the sample, D21 refers to the visit 21 days after the subject uses the sample, and D28 refers to the visit 28 days after the subject uses the sample.

[0227] In Examples 1-10 below, statistical analysis software was used to perform statistical analysis of the data. All statistical analyses were two-tailed tests, with a significance level of α = 0.05.

[0228] Instrument measurements: If the measurement conforms to the normal distribution requirement, a paired t-test is used for comparisons before and after the measurement; otherwise, a rank-sum test of two related samples is used.

[0229] Instrument measurement (sample area / blank area): If the test sample area and blank area meet the requirements of normal distribution, a paired t-test is used; otherwise, a rank-sum test of two related samples is used.

[0230] Evaluation on a 10-point scale: The comparison before and after is performed using the rank-sum test of two relevant samples.

[0231] In Examples 1 to 10 below, the significance of the experimental results is indicated by the following method: "ns" indicates no significant difference, P≥0.05; "*" indicates significant difference, 0.01≤P<0.05; "**" indicates significant difference, 0.001≤P<0.01; "***" indicates significant difference, P<0.001.

[0232] Example 1

[0233] The compound Drimendiol is used in the preparation of cosmetics with moisturizing effects.

[0234] Test criteria: If the skin stratum corneum moisture content at any follow-up point (28 days) after using the sample showed a significant improvement compared to before use (P<0.05), the sample was deemed to have moisturizing effect; otherwise, the sample was deemed not to have moisturizing effect.

[0235] Test item: Moisture content of the stratum corneum of facial skin;

[0236] Test instrument / method: Corneometer CM825;

[0237] Test time: D0 / D28;

[0238] Test area: cheek;

[0239] Parameter Description: This instrument is based on the fact that the dielectric constant (<7) of water (81) and other substances varies considerably. Depending on the water content, the measuring capacitor will change with the change in the skin's capacitance, and since the skin's capacitance is within the measurement range, the skin's water content can be measured. The higher the measured value, the higher the water content of the stratum corneum.

[0240] The test results are shown in Tables 2 and 3 and Figure 1;

[0241] Table 2. Results of moisture content test in the stratum corneum of facial skin (sample size = 32) Note: 1) The higher the measured value, the higher the moisture content of the stratum corneum. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0242] Table 3. Statistical Analysis of the Test Results of Moisture Content in the Stratum Corneum of Facial Skin

[0243] Referring to Figure 1, after 28 days of sample use, the moisture content of the stratum corneum of the subject's cheek skin increased by 45.84%, which was statistically significant.

[0244] Example 2

[0245] The compound Drimendiol is used in the preparation of cosmetics with 72-hour moisturizing effects.

[0246] Test criteria: 72-hour moisturizing efficacy: Compared with before use, if the skin stratum corneum moisture content at any follow-up point (72 hours) after using the sample is significantly improved (P<0.05), or compared with the blank area, if the increase in skin stratum corneum moisture content at any follow-up point (72 hours) after using the sample is significantly higher than that in the blank area (P<0.05), the sample is judged to have 72-hour moisturizing efficacy; otherwise, the sample is judged not to have 72-hour moisturizing efficacy.

[0247] Test item: Moisture content of the stratum corneum of arm skin;

[0248] Test instrument / method: Corneometer CM825;

[0249] Test time point: D0 / T72h;

[0250] Test site: Inner side of the arm (sample area / blank area);

[0251] Parameter description: This instrument is based on the fact that the dielectric constant (<7) of water (81) and other substances varies considerably. Depending on the water content, the measuring capacitor will change with the change in the skin's capacitance, and the skin's capacitance is within the measurement range. Therefore, the water content of the skin can be measured.

[0252] The higher the measured value, the higher the moisture content of the stratum corneum of the skin.

[0253] The test results are shown in Tables 4 and 5, Figure 2 and Figure 3;

[0254] Table 4. Results of the test on the moisture content of the stratum corneum of arm skin (sample size = 32) Note: 1) The higher the measured value, the higher the moisture content of the stratum corneum. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0255] Referring to Figure 2, compared with before use, after 72 hours of using the test sample, the moisture content of the stratum corneum of the skin in the sample area of ​​the arm increased by 55.59%, which was significant; after 72 hours, the moisture content of the stratum corneum of the skin in the blank area of ​​the arm increased by 0.70%, which was not significant.

[0256] Table 5. Statistical analysis of differences in the test results of moisture content in the stratum corneum of arm skin. Note: Test value after incremental use - Test value before use

[0257] Referring to Figure 3, compared with the blank area, after using the sample for 72 hours, the increase in the stratum corneum moisture content of the arm skin in the sample area was significantly higher than that in the blank area.

[0258] Example 3

[0259] The compound Drimendiol is used in the preparation of cosmetics with repairing effects.

[0260] Test criteria: If the transepidermal water loss rate of the skin at any follow-up point (28 days) after using the sample is significantly improved compared with before use (P<0.05), the sample is judged to have repair effect; otherwise, the sample is judged not to have repair effect.

[0261] Test item: Transepidermal water loss rate

[0262] Test instrument / method: Tewameter™ Hex;

[0263] Test time points: D0 / D28;

[0264] Test area: cheek;

[0265] Parameter description: The Tewameter™ Hex probe contains 30 pairs of relative humidity and temperature sensors. The probe acts like a camera, allowing you to see the distribution of relative humidity and temperature inside the cavity. By collecting a large amount of data from each measurement, the probe can quickly complete accurate and repeatable tests of the TEWL value.

[0266] The smaller the measured value, the less transepidermal water loss per unit time and per unit cross-sectional area, indicating a better skin barrier.

[0267] The test results are shown in Tables 6 and 7 and Figure 4;

[0268] Table 6 Results of transepidermal water loss rate test (sample size = 32) Note: 1) The smaller the measured value, the less transepidermal water loss per unit time and per unit cross-sectional area, indicating a better skin barrier;

[0269] 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%;

[0270] Table 7 Statistical Analysis of Skin Transepidermal Moisture Loss Rate Test Results

[0271] Referring to Figure 4, compared with before use, after 28 days of use, the rate of transepidermal water loss from the skin decreased by 22.25%, which was statistically significant.

[0272] Example 4

[0273] The compound Drimendiol is used in the preparation of cosmetics with nourishing effects.

[0274] Test criteria: Compared with before use, if two or more of the following parameters (skin roughness parameter SEr value / skin smoothness parameter SEsm value), skin gloss, skin elasticity R2 value, and skin dermal density) are significantly improved at any follow-up point (28 days) after using the sample (P<0.05), the sample is judged to have nourishing effects; otherwise, the sample is judged not to have nourishing effects.

[0275] Test Item 1: Cheek skin roughness parameter SEr value, skin smoothness parameter SEsm value; Elbow skin roughness parameter SEr value, elbow skin smoothness parameter SEsm value;

[0276] Test instrument / method: VisioScanVC20plus;

[0277] Test time points: D0 / D28;

[0278] Test area: cheek;

[0279] Parameter description: This instrument uses a dermatoscope consisting of a uniform ring-shaped ultraviolet (UVA) illumination source and a black and white high-resolution CCD camera to capture images of the skin surface. The images are then transmitted to the host for digital processing and analysis.

[0280] The higher the SEr value, the less rough the skin.

[0281] The lower the SEsm value, the better the skin smoothness.

[0282] The test results of the facial skin roughness parameter SEr value and skin smoothness parameter SEsm value are shown in Tables 8, 9, 5, 10, 11 and 6.

[0283] Table 8. Results of the SEr value test for cheek skin roughness parameter (sample size = 32) Note: 1) The higher the SEr value, the lower the skin roughness. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0284] Table 9. Statistical Analysis of Cheek Skin Roughness Parameter SEr Value Test Results

[0285] Please refer to Figure 5. Compared with before use, after 28 days of sample use, the skin roughness parameter SEr value of the cheek increased by 56.67%, which is a significant difference.

[0286] Table 10. Results of SEsm value test for cheek skin smoothness (sample size = 32) Note: 1) The lower the SEsm value, the better the skin smoothness. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0287] Table 11 Statistical Analysis of SEsm Value Test Results for Cheek Skin Smoothness Parameter

[0288] Referring to Figures 6, 21, and 22, compared with before use, after 28 days of sample use, the SEsm value of the cheek skin smoothness parameter decreased by 11.22%, which was statistically significant.

[0289] The test results of the skin roughness parameter SEr value of the elbow are shown in Table 12, Table 13 and Figure 7;

[0290] Table 12 Statistical Analysis of Elbow Skin Roughness Parameter SEr Value Test Results Note: 1) The higher the SEr value, the lower the skin roughness. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0291] Table 13 Statistical Analysis of Elbow Skin Roughness Parameter SEr Value Test Results

[0292] Please refer to Figure 7. Compared with before use, after 28 days of sample use, the skin roughness parameter SEr value of the elbow increased by 48.84%, which is significant.

[0293] The results of the SEsm value test for elbow skin smoothness are shown in Table 14, Table 15 and Figure 8;

[0294] Table 14 Results of SEsm value test for elbow skin smoothness parameter (sample size = 32) Note: 1) The lower the SEsm value, the better the skin smoothness. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0295] Table 15 Statistical Analysis of SEsm Value Test Results for Elbow Skin Smoothness Parameter

[0296] Referring to Figure 8, compared with before use, after 28 days of sample use, the SEsm value of elbow skin smoothness parameter decreased by 9.92%, which was statistically significant.

[0297] Test item 2: Skin radiance;

[0298] Test instrument / method: Glossymeter GL 200

[0299] Test time points: D0 / D28;

[0300] Test area: cheek;

[0301] Parameter description: This instrument reflects the direct and diffuse reflection of light that hits the skin surface.

[0302] The higher the value, the more radiant the skin.

[0303] The test results are shown in Tables 16 and 17 and Figure 9;

[0304] Table 16 Results of Skin Glossiness Test (Sample Size = 32) Note: 1) The higher the value, the higher the skin radiance. 2) Improvement rate (%) = (Post-use test value - Pre-use test value) / Pre-use test value * 100%

[0305] Table 17 Statistical Analysis of Skin Glossiness Test Results

[0306] Referring to Figure 9, compared with before use, after 28 days of use, the skin radiance improved by 38.28%, which was statistically significant.

[0307] Test item 3: Skin elasticity R2 value;

[0308] Test instrument / method: Cutometer dual MPA580

[0309] Test time points: D0 / D28;

[0310] Test area: cheek;

[0311] Parameter description: The testing principle of this instrument is based on the principle of suction and stretching. A negative pressure is generated on the surface of the skin being tested, which draws the skin into a specific test probe. The depth to which the skin is drawn into the test probe is measured by a non-contact optical testing system.

[0312] The higher the R2 value, the better the skin elasticity.

[0313] The test results are shown in Tables 18 and 19 and Figure 10;

[0314] Table 18 Results of Skin Elasticity R² Value Test (Sample Size = 32) Note: 1) The higher the R2 value, the better the skin elasticity. 2) Lifting rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0315] Table 19 Statistical Analysis of Skin Elasticity R² Value Test Results

[0316] Referring to Figure 10, compared with before use, after 28 days of use, the skin elasticity R2 value increased by 13.21%, which was statistically significant.

[0317] Test item 4: Dermal layer thickness and dermal layer density;

[0318] Test instrument / method: Ultrascan UC22

[0319] Test time points: D0 / D28;

[0320] Test area: cheek;

[0321] Parameter Description: The pulse generator produces short electrical pulse signals, which are converted into 22MHz ultrasonic signals via piezoelectricity. These ultrasonic signals are then emitted into the skin, where uneven textures such as cell formations and blood vessels reflect or create echoes. These echoes are received by the sensor and converted into electrical signals. A motor-controlled receiver receives and processes these ultrasonic signals to generate a cross-sectional image. The ultrasonic signals are then digitized, stored, and analyzed by a computer to ultimately form an ultrasonic image. Through the separation and digitization of the high-frequency ultrasonic signals, a high-resolution skin ultrasound image with good contrast is obtained.

[0322] The higher the value, the thicker the dermis layer of the skin.

[0323] The higher the value, the greater the density of the dermis layer of the skin.

[0324] The results of the dermal layer thickness test are shown in Tables 20 and 21 and Figure 11;

[0325] Table 20 Results of dermal layer thickness test (sample size = 32) Note: 1) The higher the value, the greater the thickness of the dermis. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0326] Table 21 Statistical Analysis of Dermal Layer Thickness Test Results

[0327] Referring to Figures 11 and 23, compared with before use, the dermal layer thickness of the skin increased by 10.89% after 28 days of use, which was statistically significant.

[0328] The results of the dermal density test are shown in Tables 22 and 23 and Figure 12;

[0329] Table 22 Results of dermal density test (sample size = 32) Note: 1) The higher the value, the greater the density of the dermis. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0330] Table 23 Statistical Analysis of Skin Dermal Density Test Results

[0331] Referring to Figures 12 and 23, compared with before use, the dermal density of the skin increased by 24.99% after 28 days of use, which was statistically significant.

[0332] Example 5

[0333] The compound Drimendiol is used in the preparation of cosmetics with soothing effects.

[0334] Test criteria: If the a* value of the skin red area at any follow-up point (28 days) after using the sample showed a significant improvement compared to before use (P<0.05), the sample was deemed to have a soothing effect; otherwise, the sample was deemed not to have a soothing effect.

[0335] Test Item 1: a* value of the red zone of the skin

[0336] Test instrument / method: IPP;

[0337] Test time points: D0 / D28;

[0338] Test area: cheek;

[0339] Parameter explanation: The smaller the value, the less redness of the skin;

[0340] The test results are shown in Tables 24 and 25 and Figure 13;

[0341] Table 24 Results of a* value test in the red zone of skin (sample size = 32)

[0342] Table 25 Statistical Analysis of a* Value Test Results in the Skin Red Zone Note: 1) The smaller the value, the milder the skin redness.

[0343] 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0344] Referring to Figures 13 and 25, compared with before use, after 28 days of sample use, the a* value of the skin red area decreased by 5.46%, which was statistically significant.

[0345] Test Item 2: Skin Color L* Value

[0346] Test instrument / method: IPP;

[0347] Test time points: D0 / D28;

[0348] Test area: cheek;

[0349] Parameter description: The larger the L* value, the brighter the skin.

[0350] The test results are shown in Tables 26 and 27 and Figure 14;

[0351] Table 26 Results of Skin Color L* Value Test (Sample Size = 32) Note: 1) The higher the L* value, the higher the skin brightness. 2) Improvement rate (%) = (Test value after use - Test value before use) / Test value before use * 100%

[0352] Table 27 Statistical Analysis of Skin Color L* Value Test Results

[0353] Referring to Figures 14 and 24, compared with before use, the skin color L* value increased by 1.82% after 28 days of use, which was statistically significant.

[0354] Example 6

[0355] The compound Drimendiol is used in the preparation of cosmetics with firming effects.

[0356] Test criteria: If, compared with before use, any parameter of skin elasticity R2 value or firmness F4 value at any follow-up point (28 days) after using the sample shows a significant improvement (P<0.05), the sample is judged to have a firming effect; otherwise, the sample is judged not to have a firming effect.

[0357] Test item: Skin firmness F4 value

[0358] Test instrument / method: Cutometer dual MPA580;

[0359] Test time points: D0 / D28;

[0360] Test area: cheek;

[0361] Parameter description: The testing principle of this instrument is based on the principle of suction and stretching. A negative pressure is generated on the surface of the skin being tested, which draws the skin into a specific test probe. The depth to which the skin is drawn into the test probe is measured by a non-contact optical testing system.

[0362] The lower the F4 value, the better the skin firmness.

[0363] The test results are shown in Tables 28 and 29 and Figure 15;

[0364] Table 28 Results of Skin Tightness F4 Value Test (Sample Size = 32) Note: 1) The lower the F4 value, the better the skin firmness. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0365] Table 29 Statistical Analysis of Skin Tightness F4 Value Test Results

[0366] Referring to Figure 15, compared with before use, after 28 days of use, the skin firmness F4 value decreased by 15.42%, which was statistically significant.

[0367] Example 7

[0368] The compound Drimendiol is used in the preparation of cosmetics with anti-wrinkle effects.

[0369] Test criteria: If any wrinkle parameter at any follow-up point (28 days) after using the sample showed a significant improvement compared to before use (P<0.05), the sample was deemed to have anti-wrinkle effect; otherwise, the sample was deemed not to have anti-wrinkle effect.

[0370] Test item: Percentage of under-eye wrinkles

[0371] Test instrument / method: IPP;

[0372] Test time points: D0 / D28;

[0373] Test area: cheek;

[0374] Parameter explanation: The smaller the value, the smaller the area of ​​under-eye wrinkles;

[0375] The test results are shown in Tables 30 and 31 and Figure 16;

[0376] Table 30 Results of the test on the proportion of under-eye wrinkles (sample size = 32) Note: 1) The smaller the value, the smaller the area of ​​under-eye wrinkles. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0377] Table 31 Statistical Analysis of Test Results for Under-Eye Wrinkle Area Percentage

[0378] Referring to Figures 16 and 26, compared with before use, after 28 days of sample use, the area of ​​under-eye wrinkles decreased by 15.42%, which was statistically significant.

[0379] Example 8

[0380] The compound Drimendiol is used in the preparation of cosmetics that can increase the height of the cheekbones and the angle of the jawline.

[0381] Test items: distance of upward movement of cheekbone, angle of mandible

[0382] Test instrument / method: VECTRA H2;

[0383] Test time points: D0 / D28;

[0384] Test area: cheek;

[0385] Specifications: This instrument is a portable stereoscopic imaging device that presents the facial, breast, and body contours in 360 degrees, analyzing the condition of the skin and the optimal golden ratio;

[0386] The smaller the value, the better the facial lifting effect;

[0387] The smaller the value, the better the facial lifting effect;

[0388] The test results are shown in Tables 32 and 33, Figure 17, Table 34, Table 35 and Figure 18;

[0389] Table 32 Mandibular angle test results (sample size = 32) Note: 1) The smaller the value, the better the facial lifting effect. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0390] Table 33 Statistical Analysis of Mandibular Angle Angle Test Results

[0391] Referring to Figures 17 and 27, compared with before use, the mandibular angle decreased by 1.53% after 28 days of sample use, which was statistically significant.

[0392] Table 34 Results of the test on the upward movement distance of the apple cheek (sample size = 32) Note: 1) The smaller the value, the better the facial lifting effect. 2) Reduction rate (%) = (Test value before use - Test value after use) / Test value before use * 100%

[0393] Table 35 Statistical Analysis of Apple Cheek Upward Movement Distance Test Results

[0394] Referring to Figures 18 and 28, compared with before use, the reduction rate of the upward displacement of the cheekbone was 2.53% after 28 days of sample use.

[0395] Example 9

[0396] The compound Drimendiol is used in the preparation of cosmetics suitable for sensitive skin.

[0397] Since all subjects had sensitive skin, no adverse skin reactions were observed in any of them within 28 days after using cosmetic samples containing the compound Drimendiol. Furthermore, the sensitivity of the skin showed significant improvement in symptoms such as stinging, burning, tightness, itching, overall discomfort, and redness.

[0398] Improvement rate = (Self-assessment score before use - Self-assessment score after use) / Self-assessment score before use * 100%

[0399] Questionnaire on a 10-point scale: Skin tingling sensation: The milder the skin tingling sensation, the lower the score; Skin burning sensation: The milder the skin burning sensation, the lower the score; Skin tightness sensation: The milder the skin tightness sensation, the lower the score; Skin itching sensation: The milder the skin itching sensation, the lower the score; Overall skin discomfort sensation: The milder the skin discomfort sensation, the lower the score; Skin redness sensation: The milder the skin redness sensation, the lower the score.

[0400] Referring to Figure 19, compared with before use, after 28 days of sample use, subjects reported significant improvements in skin stinging, burning, tightness, itching, overall discomfort, and redness, with improvement rates of 69.68%, 69.74%, 77.34%, 78.97%, 79.51%, and 79.09%, respectively. This demonstrates that the compound Drimendiol can be used to prepare cosmetic products suitable for sensitive skin.

[0401] The self-assessment results of the subjects after using the sample are shown in Tables 36 and 37 and Figure 19;

[0402] Table 36: Results of the 10-point questionnaire

[0403] Table 37 Subjective Skin Feelings Before and After Using the Sample

[0404] Evaluation index (feelings after using the sample - 1): 1 point represents "yes" and 2 points represent "no"; the degree of agreement is the percentage of "2 points no".

[0405] Example 10

[0406] The compound Drimendiol is used in the preparation of mild, non-irritating cosmetic products.

[0407] The adverse reaction feedback of 32 subjects during the use of the sample is shown in Tables 38 and 39;

[0408] Table 38 Results of Human Trial

[0409] Table 39 Grading Standards for Adverse Skin Reactions Note: This information is based on the grading standards for adverse skin reactions during human trials as specified in the 2015 edition of the "Cosmetic Safety Technical Specifications".

[0410] Result description:

[0411] 72 hours after using the sample, the skin reaction in the observation area was grade 0, and no adverse skin reaction occurred.

[0412] Seven days after using the sample, the skin reaction in the observation area was grade 0, and no adverse skin reactions occurred.

[0413] After 14 days of using the sample, the skin reaction in the observation area was grade 0, and no adverse skin reaction occurred.

[0414] After 21 days of using the sample, the skin reaction in the observation area was grade 0, and no adverse skin reactions occurred.

[0415] After 28 days of sample use, the skin reaction in the observation area was grade 0, and no adverse skin reactions occurred.

[0416] The subjective evaluations of 32 participants are shown in Table 40 and Figure 20.

[0417] Table 40 Subjects' self-report results 28 days after sample use.

[0418] Evaluation indicators (feelings after using the sample - 2): 1 point indicates disagreement, 2 points indicates partial disagreement, 3 points indicates neither disagreement nor agreement, 4 points indicates partial agreement, and 5 points indicates agreement; the degree of agreement is the sum of the percentages of "4 points" and "5 points".

[0419] The above results of human trials and statistical analysis of adverse skin reactions demonstrate that the compound Drimendiol can be used to prepare mild and non-irritating cosmetic products.

[0420] In summary, based on the results of 28 consecutive days of use of the test sample (20ppm Drimendiol) by 32 subjects with sensitive skin (Baumann Questionnaire), the following effects can be observed:

[0421] 1) Compared with before use, after 72 hours of use, the moisture content of the stratum corneum of the skin in the sample area of ​​the arm was significantly increased (P<0.05), with an increase rate of 55.59%; compared with the blank area, after 72 hours of use, the increase in moisture content of the stratum corneum of the skin in the sample area of ​​the arm was significantly higher than that in the blank area (P<0.05), indicating that the sample has a 72-hour moisturizing effect under the experimental conditions.

[0422] 2) Compared with before use, after 72 hours of sample use, the stratum corneum moisture content of the skin in the sample area of ​​the arm was significantly increased (P<0.05), with an increase rate of 55.59%; compared with the control area, after 72 hours of sample use, the increase in stratum corneum moisture content of the skin in the sample area of ​​the arm was significantly higher than that in the control area (P<0.05); compared with before use, after 28 days of sample use, the stratum corneum moisture content of the skin on the cheek was significantly increased (P<0.05), with an increase rate of 45.84%; compared with before use, after 28 days of sample use, the transepidermal water loss rate was significantly reduced (P<0.05), with a reduction rate of 22.25%, indicating that the sample has moisturizing and repairing effects under the experimental conditions;

[0423] 3) Compared with before use, after 28 days of use, the skin elasticity R2 value was significantly increased (P<0.05), with an increase rate of 13.21%; compared with before use, after 28 days of use, the skin firmness F4 value was significantly decreased (P<0.05), with a decrease rate of 15.42%, indicating that the sample has a firming effect under the test conditions.

[0424] 4) Compared with before use, after 28 days of sample use, the skin roughness parameter SEr of the cheek significantly increased (P<0.05), with an increase rate of 56.67%; compared with before use, the skin smoothness parameter SEsm of the cheek significantly decreased (P<0.05), with a decrease rate of 11.22%; compared with before use, the skin roughness parameter SEr of the elbow significantly increased (P<0.05), with an increase rate of 48.84%; compared with before use, the skin smoothness parameter SEsm of the elbow significantly decreased (P<0.05), with a decrease rate of 9.92%; compared with before use, the skin gloss significantly increased (P<0.05), with an increase rate of 38.28%.

[0425] Compared with before use, after 28 days of sample use, the skin elasticity R2 value significantly increased (P<0.05), with an increase rate of 13.21%; compared with before use, the skin firmness F4 value significantly decreased (P<0.05), with a decrease rate of 15.42%; compared with before use, the skin dermal density significantly increased (P<0.05), with an increase rate of 24.99%; indicating that the sample has nourishing effects under the experimental conditions.

[0426] 5) Compared with before use, after 28 days of use, the proportion of under-eye wrinkles was significantly reduced (P<0.05), with a reduction rate of 15.42%, indicating that the sample has anti-wrinkle effect under the test conditions;

[0427] 6) Compared with before use, after 28 days of use, the a* value of the skin red area was significantly reduced (P<0.05), with a reduction rate of 5.46%, indicating that the sample has a soothing effect under the test conditions;

[0428] 7) Compared with before use, after 28 days of use, the skin color L* value improved by 1.82%, which was statistically significant. This indicates that the sample has a skin-brightening effect under the experimental conditions.

[0429] 8) Compared with before use, after 28 days of use, the reduction rate of the upward displacement of the cheekbones was 2.53%, which was statistically significant. This indicates that the sample has an effect on lifting the cheekbones under the experimental conditions.

[0430] 9) Compared with before use, after 28 days of sample use, the mandibular angle reduction rate was 1.53%, which was statistically significant. This demonstrates that the sample has a mandibular angle improvement effect under the experimental conditions.

[0431] 10) After 28 days of sample use, no adverse skin reactions related to the sample were observed in any of the subjects with sensitive skin. 100% of the subjects agreed that the sample was mild and non-irritating and that it was suitable for sensitive skin. This indicates that under the experimental conditions, the sample was mild and non-irritating and suitable for sensitive skin.

[0432] Conclusion: Under the experimental conditions, the sample has the effects of moisturizing, hydrating, repairing, firming, nourishing, anti-wrinkle, soothing, brightening the skin, lifting the cheekbones, and improving the jaw angle for 72 hours; and it is gentle and non-irritating, suitable for sensitive skin.

[0433] Example 11

[0434] The compound Drimendiol is used in the preparation of cosmetic products that positively regulate the expression of the acid sphingomyelinase SMPD1 gene and the lobe protein LOR gene, thereby improving the skin barrier function.

[0435] 1. Experimental Principle

[0436] Acidic sphingomyelinase (SMPD1) is a key lipid-degrading enzyme that exhibits the highest activity at low pH. Acidic pH also affects the interactions of the lipid bilayer in the stratum corneum; an acidic stratum corneum significantly improves skin integrity and adhesion. The integrity of the skin barrier is crucial for maintaining skin hydration.

[0437] Loricrin, a major component of keratinocytes, accounts for approximately 80% of the total keratinocyte proteins. It is primarily found in the granular layer of the epidermis and plays a crucial role in the epidermal barrier function. The main functions of loricrin include: (1) strengthening the keratinocyte barrier and enhancing the permeability barrier; and (2) interacting with intermediate filaments to increase the flexibility of the keratinocyte structure. Loricrin itself does not directly possess moisturizing functions, but rather indirectly affects the skin's moisturizing status through its role in the skin barrier.

[0438] A method was established using quantitative real-time PCR (RT-qPCR) to detect the relative expression levels of SMPD1 and LOR mRNA as the endpoint. By comparing the differences in the relative expression levels of factor mRNA after administration of the blank control and the test substance, the ability of the test substance to upregulate moisturizing-related genes was evaluated.

[0439] 2. Test materials and test samples

[0440] 2.1 Experimental Reagents

[0441] High-glucose DMEM medium, fetal bovine serum, trypsin / EDTA solution, PBS, penicillin and streptomycin mixed solution, trypan blue staining solution, thiazolyl blue MTT, total RNA extraction kit, reverse transcription kit, real-time PCR kit, cell line: human immortalized epidermal cell line.

[0442] 2.2 Experimental Apparatus

[0443] CO2 incubator, biosafety cabinet, analytical balance, inverted microscope, ELISA reader, refrigerated centrifuge, quantitative PCR instrument, PCR instrument.

[0444] 2.3 Test sample: 2000ppm Drimendiol 1,3-butanediol solution.

[0445] 3. Experimental Procedure

[0446] 3.1 Cell viability assay (MTT)

[0447] 3.1.1 Routine cell culture. The cell suspension was seeded into 96-well cell culture plates and cultured for 24 hours.

[0448] 3.1.2 Take 300 μL of sample and dissolve it in 1200 μL of culture medium until fully dissolved.

[0449] 3.1.3 Add the same volume of test sample with different concentrations to each well and return to the incubator for incubation.

[0450] 3.1.4 Add MTT solution to each well and incubate in an incubator.

[0451] 3.1.5 Discard the liquid in the wells, add DMSO to each well, shake well, and then measure the absorbance using a microplate reader.

[0452] 3.2 Determination of relative gene expression levels of SMPD1 and LOR.

[0453] 3.2.1 Conduct the test according to the test plan shown in the table below.

[0454] 3.2.2 Routine cell culture. The cell suspension was seeded into 6-well cell culture plates and cultured for 24 hours.

[0455] Table 41 is the experimental group processing information table.

[0456] Table 41 Experimental Grouping Information Table

[0457] 3.2.3 Aspirate the culture medium from the wells and add different treatment groups to each well according to the table above. Place the 6-well plate back into the cell culture incubator and incubate for 48 hours. Collect the cells into centrifuge tubes.

[0458] 3.2.4 Total RNA was extracted according to the total RNA extraction kit.

[0459] 3.2.5 The extracted total RNA was reverse transcribed into cDNA according to the reverse transcription kit steps.

[0460] 3.2.6 Prepare primers, probes, and multiplex PCR reaction system, dispense them into each reaction tube, and add cDNA to each tube.

[0461] 3.2.7 Open the PCR reaction program, set the appropriate experiment type and mode, start running, and obtain experimental data.

[0462] 4. Data Analysis

[0463] 4.1 Relative cell viability

[0464] Assuming the cell viability of the blank control group is 100%, calculate the relative cell viability of each group.

[0465] OD TA The three-fold average of the optical density of the tested sample group.

[0466] OD B The average of three measurements of optical density in the blank control group.

[0467] 4.2 Expression level of the gene to be tested

[0468] ΔCT (treatment group) = CT (test gene) - CT (mean value of internal reference gene)

[0469] ΔCT (control group) = CT (test gene) - CT (mean value of internal reference gene)

[0470] ΔΔCT = ΔCT (treatment group) - ΔCT (control group)

[0471] Relative expression level of the gene to be tested = 2^–△△ CT Take 2^–△△ CT mean

[0472] 5. Experimental Results

[0473] 5.1 Cell viability test results

[0474] The MTT assay was performed following the steps in 3.1. Five sample concentrations were designed for this cell viability test (as shown in Figure 29). Cell viability was greater than 90% when the sample concentration was ≤0.1%, and all of these concentrations were suitable for subsequent experiments. Table 42 shows the relative cell viability (Mean ± SD) for each group.

[0475] Table 42 Relative cell viability (Mean ± SD) in each group

[0476] Sample concentrations of 0.025%, 0.05%, and 0.1% were selected as the concentrations for subsequent efficacy experiments.

[0477] 5.2 Relative expression level of SMPD1 gene

[0478] Based on the sample concentration selected in 5.1, the expression level of SMPD1 was detected, and the test results are shown in Table 43 and Figure 30.

[0479] Table 43. Relative SMPD1 expression levels in each group (Mean ± SD)

[0480] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0481] 5.3 Relative expression level of LOR gene

[0482] Based on the sample concentration selected in 5.1, the expression level of LOR was detected, and the test results are shown in Table 44 and Figure 31.

[0483] Table 44. Relative expression levels of LOR in each group (Mean ± SD)

[0484] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0485] Conclusion: At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the SMPD1 gene in the samples were 1.61 ± 0.01, 1.54 ± 0.02, and 1.38 ± 0.04, respectively, all significantly higher than the blank control (P < 0.01). This indicates that the samples at these concentrations upregulated the SMPD1 gene.

[0486] At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the LOR gene in the samples were 1.86 ± 0.11, 1.64 ± 0.08, and 2.05 ± 0.13, respectively, all significantly higher than the blank control (P < 0.01). This indicates that the samples at these concentrations upregulated the LOR gene.

[0487] Example 12

[0488] The compound Drimendiol is used in the preparation of cosmetic products that positively regulate the expression of the elastin ELN gene, improving skin elasticity and firmness.

[0489] 1. Experimental Principle

[0490] When UVA rays stimulate human skin fibroblasts, oxidative damage occurs, triggering changes in the expression of aging-related genes and enzymes. This induces an inflammatory cascade and reduces elastin expression, leading to signs of aging such as sagging and wrinkles. Elastin (ELN) is an important protein in the skin, giving it firmness and elasticity, allowing it to stretch and return to its original shape. With age, elastin levels in the skin gradually decrease, causing loss of elasticity and firmness, resulting in wrinkles and sagging.

[0491] This project uses a human dermal fibroblast model and quantitative real-time PCR (RT-qPCR) to detect the relative expression level of mRNA as the endpoint. By comparing the difference in the relative expression level of factor mRNA after administration of the blank control and the test substance, the gene regulatory effect of the test substance on ELN is evaluated.

[0492] 2. Test materials and test samples

[0493] 2.1 Experimental Reagents

[0494] High-glucose DMEM medium, fetal bovine serum, penicillin-streptomycin mixture, trypan blue dye, PBS, thiazolyl blue MTT, RNA extraction kit, reverse transcription kit, real-time quantitative PCR detection kit, cell line: human skin fibroblasts.

[0495] 2.2 Experimental Apparatus

[0496] Cell culture incubator, biosafety cabinet, inverted microscope, real-time quantitative PCR instrument, centrifuge

[0497] 2.3 Test sample: 2000ppm Drimendiol 1,3-butanediol solution.

[0498] 3. Experimental Procedure

[0499] 3.1 Cell viability assay (MTT)

[0500] 3.1.1 Routine cell culture. The cell suspension was seeded into 96-well cell culture plates and cultured for 24 hours.

[0501] 3.1.2 Take 300 μL of sample and dissolve it in 1200 μL of culture medium until fully dissolved.

[0502] 3.1.3 Add the same volume of test sample with different concentrations to each well and return to the incubator for incubation.

[0503] 3.1.4 Add MTT solution to each well and incubate in an incubator.

[0504] 3.1.5 Discard the liquid in the wells, add DMSO to each well, shake well, and measure the absorbance using a microplate reader.

[0505] 3.2 Measurement of relative gene expression levels of ELN

[0506] 3.2.1 Conduct the test according to the test plan shown in the table below.

[0507] 3.2.2 Routine cell culture. The cell suspension was seeded into 6-well cell culture plates and cultured for 24 hours.

[0508] Table 45 Experimental Grouping Information Table

[0509] 3.2.3 Aspirate the culture medium from the wells and add different treatment groups to each well according to the table above. Place the 6-well plate back into the cell culture incubator and incubate for 24 hours. Collect the cells into centrifuge tubes.

[0510] 3.2.4 RNA extraction: Sample lysis—removal of genomic DNA—adsorption of RNA—removal of impurities—elution of RNA—determination of RNA purity and concentration.

[0511] 3.2.5 RNA reverse transcription: removal of genomic DNA—reverse transcription—to obtain cDNA.

[0512] 3.2.6 Prepare primers, probes, and multiplex PCR reaction system, dispense them into each reaction tube, and add cDNA to each tube.

[0513] 3.2.7 Open the PCR reaction program, set the appropriate experiment type and mode, start running, and obtain experimental data.

[0514] 4. Data Analysis

[0515] 4.1 Relative cell viability

[0516] Assuming the cell viability of the blank control group is 100%, calculate the relative cell viability of each group.

[0517] OD TA The three-fold average of the optical density of the tested sample group.

[0518] OD B The average of three measurements of optical density in the blank control group.

[0519] 4.2 Expression level of the gene to be tested

[0520] ΔCT (treatment group) = CT (test gene) - CT (mean value of internal reference gene)

[0521] ΔCT (control group) = CT (test gene) - CT (mean value of internal reference gene)

[0522] ΔΔCT = ΔCT (treatment group) - ΔCT (control group)

[0523] Relative expression level of the gene to be tested = 2^–△△ CT Take 2^ – △△ CT mean

[0524] 5. Experimental Results

[0525] 5.1 Cell viability test results

[0526] The MTT assay was performed according to step 3.1. Five sample concentrations were designed for this cell viability test (as shown in Figure 32). When the sample concentration was ≤1%, the cell viability was greater than 90%, and all of these concentrations could be used for subsequent experiments.

[0527] Table 46 shows the relative cell activity (Mean ± SD) for each group.

[0528] Table 46 Relative cell viability (Mean ± SD) in each group

[0529] In Figure 32, sample concentrations of 0.25%, 0.5%, and 1.0% were selected as the concentrations for subsequent efficacy experiments.

[0530] 5.2 Relative expression level of ELN gene

[0531] Based on the sample concentration selected in 5.1, ELN expression levels were detected, and the test results are shown in Table 47 and Figure 33.

[0532] Table 47. Relative ELN expression levels in each group (Mean ± SD)

[0533] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0534] Conclusion: At concentrations of 0.25% (5 ppm Drimendiol), 0.5% (10 ppm Drimendiol), and 1% (20 ppm Drimendiol), the relative expression levels of the ELN gene in the samples were 3.85±0.13, 2.86±0.20, and 6.57±0.37, respectively, all significantly upregulated compared to the blank control (P<0.01). This indicates that the samples at these concentrations upregulated the ELN gene, which can serve as evidence supporting claims of firming and anti-wrinkle effects.

[0535] Example 13

[0536] The compound Drimendiol is used in the preparation of cosmetic applications that negatively regulate the expression of tumor necrosis factor-α and interleukin-1α genes, and improve skin inflammation and soothe sensitive skin.

[0537] 1. Experimental Principle

[0538] Solar ultraviolet (UVB) radiation can cause photodamage to the skin, thereby inducing epidermal HACAT cells to release inflammatory factors and secrete a series of pro-inflammatory cytokines (such as tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α)). This project uses a UVB-induced HACAT cell inflammatory response model and establishes a method based on the relative expression levels of TNF-α and IL-1α mRNA detected by quantitative real-time PCR (RT-qPCR) as the detection endpoint. By comparing the differences in the relative expression levels of factor mRNA measured after administration of the negative control and the test substance, the anti-inflammatory effect of the test substance is evaluated.

[0539] 2. Test materials and test samples

[0540] 2.1 Experimental Reagents

[0541] High-glucose DMEM medium, fetal bovine serum, penicillin-streptomycin mixture, trypan blue dye, PBS, thiazolyl blue MTT, dexamethasone, RNA extraction kit, reverse transcription kit, real-time quantitative PCR detection kit, cell line: HACAT.

[0542] 2.2 Experimental Apparatus

[0543] Carbon dioxide cell culture incubator, biosafety cabinet, inverted microscope, electric thermostatic water bath, ELISA reader, real-time quantitative PCR instrument, centrifuge, and ultraviolet crosslinker.

[0544] 2.3 Test sample: 2000ppm Drimendiol 1,3-butanediol solution.

[0545] 3. Experimental Procedure

[0546] 3.1 Cell viability assay (MTT method)

[0547] 3.1.1 Routine cell culture. The cell suspension was seeded into 96-well cell culture plates and cultured for 24 hours.

[0548] 3.1.2 Take 300 μL of sample and dissolve it in 1200 μL of culture medium until fully dissolved.

[0549] 3.1.3 Add the same volume of test sample with different concentrations to each well and return to the incubator for incubation.

[0550] 3.1.4 Add MTT solution to each well and incubate in an incubator.

[0551] 3.1.5 Discard the liquid in the wells, add DMSO to each well, shake well, and then measure the absorbance using a microplate reader.

[0552] 3.2 Determination of relative gene expression levels of TNF-α and IL-1α

[0553] 3.2.1 Conduct the test according to the test plan shown in Table 48.

[0554] 3.2.2 Routine cell culture. The cell suspension was seeded into 6-well cell culture plates and cultured for 24 hours.

[0555] Table 48 shows the cell grouping and processing information for TNF-α and IL-1α content testing.

[0556] Table 48. Cell grouping and processing information for TNF-α and IL-1α content testing.

[0557] 3.2.3 Aspirate the culture medium from the wells, and perform different treatment groups for each well according to the table above. Place the 6-well plate back into the cell culture incubator and incubate for 24 hours, then collect the cells into centrifuge tubes.

[0558] 3.2.4 RNA extraction: Sample lysis—removal of genomic DNA—adsorption of RNA—removal of impurities—elution of RNA—determination of RNA purity and concentration.

[0559] 3.2.5 RNA reverse transcription: removal of genomic DNA—reverse transcription—to obtain cDNA.

[0560] 3.2.6 Prepare primers, probes, and multiplex PCR reaction system, dispense them into each reaction tube, and add cDNA to each tube.

[0561] 3.2.7 Open the PCR reaction program, set the appropriate experiment type and mode, start running, and obtain experimental data.

[0562] 4. Data Analysis

[0563] 4.1 Relative cell viability

[0564] Assuming the cell viability of the blank control group is 100%, calculate the relative cell viability of each group.

[0565] OD TA OD, the three-fold average of the optical density of the tested sample group C ;

[0566] The three-fold average of the optical density of the tested sample group

[0567] OD B The average of three measurements of optical density in the blank control group.

[0568] OD C The average of three optical density measurements in the negative control group.

[0569] 4.2 Expression level of the gene to be tested

[0570] ΔCT (treatment group) = CT (test gene) - CT (mean value of internal reference gene)

[0571] ΔCT (control group) = CT (test gene) - CT (mean value of internal reference gene)

[0572] ΔΔCT = ΔCT (treatment group) - ΔCT (control group)

[0573] Relative expression level of the gene to be tested = 2^–△△ CT Take 2^–△△ CT mean

[0574] 5. Experimental Results

[0575] 5.1 Cell viability test results

[0576] The MTT assay was performed according to step 3.1. Five sample concentrations were designed for this cell viability assay (as shown in Figure 34). When the sample concentration was ≤0.1%, the cell viability was greater than 90%, and all of these concentrations could be used for subsequent experiments.

[0577] Table 49 shows the relative cell activity (Mean ± SD) for each group.

[0578] Table 49 Relative cell viability (Mean ± SD) in each group

[0579] In Figure 34, sample concentrations of 0.025%, 0.05%, and 0.1% were selected as the concentrations for subsequent efficacy experiments.

[0580] 5.2 Relative expression level of TNF-α gene

[0581] Based on the sample concentration selected in 5.1, the TNF-α content was detected, and the test results are shown in Table 50 and Figure 35.

[0582] Table 50 Relative expression levels of TNF-α in each group (Mean ± SD)

[0583] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0584] 5.3 Relative expression level of IL-1α gene

[0585] Based on the sample concentration selected in 5.1, the IL-1α content was detected, and the test results are shown in Table 51 and Figure 36.

[0586] Table 51. Relative expression levels of IL-1α in each group (Mean ± SD)

[0587] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0588] Conclusion: At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the inflammatory cytokine TNF-α gene in the sample were 0.13±0.02, 0.23±0.01, and 0.15±0.04, respectively, all significantly downregulated compared to the negative control (P<0.01). This indicates that the sample at these concentrations has an inhibitory effect on the TNF-α gene, which can serve as evidence supporting the claim of soothing efficacy.

[0589] At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the inflammatory cytokine IL-1α gene in the sample were 0.24 ± 0.04, 0.34 ± 0.00, and 0.35 ± 0.02, respectively, all significantly downregulated compared to the negative control (P < 0.01). This indicates that the sample at these concentrations has an inhibitory effect on the IL-1α gene, which can serve as evidence supporting the claim of soothing efficacy.

[0590] Example 14

[0591] The compound Drimendiol is used to prepare cosmetic applications that negatively regulate the expression of transient receptor potential vanillin-1 receptor and prostaglandin E2 genes, achieving analgesic, anti-inflammatory, and soothing effects on the skin.

[0592] The experiment is as follows:

[0593] 1. Experimental Principle

[0594] Transient receptor potential vanillin-1 (TRPV1) receptor is a highly calcium-permeable, non-selective cation channel widely expressed in nociceptive neurons and various non-neuronal cells, including keratinocytes, fibroblasts, and endothelial cells. In keratinocytes, TRPV1 receptors can be activated by various endogenous and exogenous factors, such as high temperature, low pH (protons), and capsaicin. When TRPV1 receptors are activated, it leads to Na+... + and Ca 2+ Increased permeability / inflow of the TRPV1 pathway activates related signal transduction pathways and produces regulatory effects. Given its important role in skin cells, the TRPV1 pathway has become an important target for developing anti-inflammatory and analgesic drugs for treating skin diseases.

[0595] This project uses a capsaicin-stimulated cellular inflammatory response model and establishes a method based on the relative expression level of TRPV1 mRNA detected by quantitative real-time PCR (RT-qPCR) as the detection endpoint. The anti-inflammatory effect of the test substance is evaluated by comparing the difference in relative expression levels of factor mRNA after administration of the negative control and the test substance.

[0596] Prostaglandin E2 (PGE2) is an important mediator that can promote the migration and differentiation of fibroblasts by activating related signaling pathways, thereby accelerating the wound healing process. The immune system, upon triggering skin nerve fibers, receives skin sensitivity, which activates keratinocytes, mast cells, antigen-presenting cells, and T cells in the skin, leading to the release of PGE2.

[0597] 2. Test materials and test samples

[0598] 2.1 Experimental Reagents

[0599] High-glucose DMEM medium, fetal bovine serum, penicillin-streptomycin mixture, trypan blue dye, PBS, thiazolyl blue MTT, capsaicin (CAP), trans-4-tert-butylcyclohexanol (4TB), RNA extraction kit, reverse transcription kit, real-time quantitative PCR detection kit, cell line: HACAT.

[0600] 2.2 Experimental Apparatus

[0601] Carbon dioxide cell culture incubator, biosafety cabinet, inverted microscope, electric thermostatic water bath, ELISA reader, real-time quantitative PCR instrument, centrifuge, and ultraviolet crosslinker.

[0602] 2.3 Test sample: 2000ppm Drimendiol 1,3-butanediol solution.

[0603] 3. Experimental Procedure

[0604] 3.1 Cell viability assay (MTT)

[0605] 3.1.1 Routine cell culture. The cell suspension was seeded into 96-well cell culture plates and cultured for 24 hours.

[0606] 3.1.2 Take 300 μL of sample and dissolve it in 1200 μL of culture medium until fully dissolved.

[0607] 3.1.3 Add the same volume of test sample with different concentrations to each well and return to the incubator for incubation.

[0608] 3.1.4 Add MTT solution to each well and incubate in an incubator.

[0609] 3.1.5 Discard the liquid in the wells, add DMSO to each well, shake well, and then measure the absorbance using a microplate reader.

[0610] 3.2 Determination of relative gene expression level of TRPV1

[0611] 3.2.1 Conduct the test according to the test plan shown in Table 52.

[0612] 3.2.2 Routine cell culture. The cell suspension was seeded into 6-well cell culture plates and cultured for 24 hours.

[0613] Table 52 shows the cell grouping and processing information for TRPV1 content testing.

[0614] Table 52 Information on cell grouping and processing for TRPV1 content testing

[0615] 3.2.3 Aspirate the culture medium from the wells and add different treatment groups to each well according to the table above. Place the 6-well plate back into the cell culture incubator and incubate for 24 hours. Collect the cells into centrifuge tubes.

[0616] 3.2.4 RNA Extraction: Sample lysis—removal of genomic DNA—RNA adsorption—impurity removal—RNA elution—RNA purity and concentration detection

[0617] 3.2.5. RNA Reverse Transcription: Removal of genomic DNA—Reverse Transcription—Generating cDNA

[0618] 3.2.6 Prepare primers, probes, and multiplex PCR reaction system, dispense them into each reaction tube, and add cDNA to each tube.

[0619] 3.2.7 Open the PCR reaction program, set the appropriate experiment type and mode, start running, and obtain experimental data.

[0620] 4. Data Analysis

[0621] 4.1 Relative cell viability

[0622] Assuming the cell viability of the blank control group is 100%, calculate the relative cell viability of each group.

[0623] OD TA OD, the three-fold average of the optical density of the tested sample group C ;

[0624] The three-fold average of the optical density of the tested sample group

[0625] OD B The average of three measurements of optical density in the blank control group.

[0626] OD C The average of three optical density measurements in the negative control group.

[0627] 4.2 Expression level of the gene to be tested

[0628] ΔCT (treatment group) = CT (test gene) - CT (mean value of internal reference gene)

[0629] ΔCT (control group) = CT (test gene) - CT (mean value of internal reference gene)

[0630] ΔΔCT = ΔCT (treatment group) - ΔCT (control group)

[0631] Relative expression level of the gene to be tested = 2 ^ –△△ CT Take 2 ^ –△△ CT mean

[0632] 5. Experimental Results

[0633] 5.1 Perform the MTT assay following the steps in 3.1. Five sample concentrations were designed for this cell viability assay (as shown in Figure 37). When the sample concentration was ≤0.1%, the cell viability was greater than 90%, and all of these concentrations could be used for subsequent experiments.

[0634] Table 53 Relative cell activity (Mean ± SD) in each group

[0635] In Figure 37, sample concentrations of 0.025%, 0.05%, and 0.1% were selected as the concentrations for subsequent efficacy experiments.

[0636] 5.2 Relative expression level of TRPV1 gene

[0637] Based on the sample concentration selected in 5.1, the TRPV1 content was detected, and the test results are shown in Table 54 and Figure 38.

[0638] Table 54. Relative TRPV1 expression levels in each group (Mean ± SD)

[0639] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0640] 5.3 Relative expression level of PGE2 gene

[0641] Based on the sample concentration selected in 5.1, the PGE2 content was detected, and the test results are shown in Table 55 and Figure 39.

[0642] Table 55. Relative PGE2 expression levels in each group (Mean ± SD)

[0643] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0644] Conclusion: At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the inflammatory cytokine TRPV1 gene in the sample were 0.56 ± 0.01, 0.50 ± 0.02, and 0.48 ± 0.01, respectively, all significantly downregulated compared to the negative control (P < 0.01). This indicates that the sample at these concentrations has an inhibitory effect on the TRPV1 gene, which can serve as evidence supporting the claim of soothing efficacy.

[0645] At concentrations of 0.025% (0.5 ppm Drimendiol), 0.05% (1 ppm Drimendiol), and 0.1% (2 ppm Drimendiol), the relative expression levels of the inflammatory cytokine PGE2 gene in the sample were 0.69±0.02, 0.58±0.01, and 0.66±0.01, respectively, all significantly downregulated compared to the negative control (P<0.01). This indicates that the sample at these concentrations has an inhibitory effect on the PGE2 gene, which can serve as evidence supporting the claim of soothing efficacy.

[0646] Example 15

[0647] The compound Drimendiol is used in the preparation of cosmetics that increase the synthesis of hyaluronic acid in skin cells.

[0648] The experiment is as follows:

[0649] 1. Experimental Principle

[0650] Hyaluronic acid, also known as hyaluronic acid, is a glycosaminoglycan composed of D-glucuronic acid and N-acetylglucosamine. It is synthesized intracellularly by human immortalized epidermal cells (HaCaT) and secreted extracellularly. Hyaluronic acid can enhance the skin's barrier function and reduce moisture loss by increasing the intercellular spaces. It can promote intracellular and extracellular communication in the skin, improve skin metabolism, and increase the skin's ability to absorb moisture and nutrients. Human immortalized epidermal cells (HaCaT) can be used as a cell model to study the effect of cosmetics on increasing hyaluronic acid content. By measuring the upregulation of hyaluronic acid content after administration of blank controls, positive controls, and test substances, the efficacy of test substances in promoting hyaluronic acid synthesis can be evaluated. The determination of hyaluronic acid content uses enzyme-linked immunosorbent assay (ELISA). The specific principle is as follows: a capture antibody is coated onto an ELISA plate to capture hyaluronic acid in the sample and standards. A biotinylated detection antibody binds to the hyaluronic acid, and the SABC complex binds to the biotinylated detection antibody to form an immune complex. After adding TMB chromogenic solution, the reaction wells will turn blue if hyaluronic acid is present; adding stop solution will turn them yellow. Unbound components are washed away during the detection process. The OD value is measured at 450 nm using an ELISA reader. The hyaluronic acid concentration is directly proportional to the OD value. The concentration of hyaluronic acid in the sample is calculated by plotting a standard curve, thus enabling qualitative or relative quantitative analysis of the sample.

[0651] 2. Test materials and test samples

[0652] 2.1 Experimental Reagents

[0653] DMEM cell culture medium, trypsin / EDTA solution, fetal bovine serum, penicillin-streptomycin mixture, PBS, trypan blue staining solution, thiazolyl blue-MTT, Human HA enzyme-linked immunosorbent assay kit, cell line: human immortalized epidermal cells (HaCaT).

[0654] 2.2 Experimental Apparatus

[0655] Cell culture incubator, biosafety cabinet, inverted microscope, electric thermostatic water bath, analytical balance, enzyme-linked immunosorbent assay (ELISA) reader.

[0656] 2.3 Test sample: 2000ppm Drimendiol 1,3-butanediol solution.

[0657] 3. Experimental Procedure

[0658] 3.1 Cell viability assay (MTT)

[0659] 3.1.1 Routine cell culture. The cell suspension was seeded into 96-well cell culture plates and cultured for 24 hours.

[0660] 3.1.2 Weigh 300 μL of sample and dissolve it in 1200 μL of culture medium until fully dissolved.

[0661] 3.1.3 Add the same volume of test sample with different concentrations to each well and incubate in the incubator for 24 hours.

[0662] 3.1.4 Add MTT solution to each well and incubate in an incubator for 4 hours.

[0663] 3.1.5 Discard the liquid in the wells, add DMSO to each well, shake well, and then measure the absorbance using a microplate reader.

[0664] 3.2 Determination of HA content

[0665] 3.2.1 Conduct the test according to the test plan shown in Table 56.

[0666] Table 56 Grouping Processing Information

[0667] 3.2.2 Routine cell culture. The cell suspension was seeded into 6-well cell culture plates and cultured for 24 hours.

[0668] 3.2.3 Aspirate the culture medium from the wells and add a different control group to each well. Place the 6-well plate back into the cell culture incubator and incubate for 24 hours.

[0669] 3.2.4 Use the ELISA kit's instruction manual to detect the HA content in the samples.

[0670] 4. Data Analysis

[0671] 4.1 Relative cell viability

[0672] Assuming the cell viability of the blank control group is 100%, calculate the relative cell viability of each group.

[0673] OD TA The three-fold average of the optical density of the tested sample group.

[0674] OD P The average of three optical density measurements in the positive control group.

[0675] OD B The average of three measurements of optical density in the blank control group.

[0676] 5. Experimental Results

[0677] 5.1 Perform the MTT assay following the steps in 3.1. Five sample concentrations were designed for this cell viability assay (as shown in Figure 40). When the sample concentration was ≤0.1%, cell viability was greater than 90%, and all concentrations could be used for subsequent experiments. 0.025%, 0.05%, and 0.1% were selected as the concentrations for subsequent efficacy experiments.

[0678] Table 57 shows the relative cell activity (Mean ± SD) for each group.

[0679] Table 57 Relative cell viability (Mean ± SD) in each group

[0680] In Figure 40, sample concentrations of 0.025%, 0.05%, and 0.1% were selected as the concentrations for subsequent efficacy experiments.

[0681] 5.2 Calculation results of HA content

[0682] Based on the sample concentration selected in 5.1, the HA content was detected, and the test results are shown in Table 58 and Figure 41.

[0683] Table 58 HA concentrations in each group (Mean ± SD)

[0684] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0685] Conclusion: At a concentration of 0.1% (2 ppm Drimendiol), the HA concentration of the sample was 1.8883 ± 0.0965 ng / mL, which was significantly higher than that of the blank control (P < 0.05). This indicates that the test substance has the ability to promote hyaluronic acid synthesis at this test concentration, which can serve as evidence to support the claim of moisturizing efficacy.

[0686] The chemical structural formula of Epidrimendiol is:

[0687] Preparation method of Epidrimendiol:

[0688] 10 kg of Tasmannia lanceolata leaf powder was extracted with 60 kg of ethanol:water in a 1:1 ratio at 60 °C by heating and stirring for 3 h. After filtration, the Tasmannia lanceolata leaf residue was extracted again with 30.0 kg of ethanol:water in a 1:1 ratio at 60 °C by heating for 2 h. After filtration, the two filtrates were combined and concentrated under reduced pressure to obtain 650 g of waxy extract.

[0689] The above-mentioned waxy extract was dissolved by heating with ethanol:water = 1:1, and then extracted with n-hexane to obtain a component containing polydextral. After separation by silica gel column chromatography with gradient elution using petroleum ether and ethyl acetate, 60g of the polydextral compound was obtained after purification.

[0690] 60g of the above-mentioned polydialdehyde was dissolved in ethyl acetate, and 12g of potassium carbonate was added. The mixture was stirred at room temperature (25-35℃) for 6 hours. Thin-layer chromatography showed that approximately 50% of the polydialdehyde was converted to polydiisodialdehyde. After filtration, the mixture was concentrated to obtain 60g of the isomer mixture. The polydialdehyde and polydiisodialdehyde were separated by silica gel column chromatography using a gradient elution with petroleum ether and ethyl acetate, yielding 25g of the polydialdehyde compound.

[0691] 25 g of polydipsia hydrate isodialdehyde was dissolved in 1000 mL of ethyl acetate. 20 g of NaBH4 was added in portions, and the mixture was stirred at room temperature (25–35 °C) for 6 h. Thin-layer chromatography was used to monitor the completeness of the reaction. 1.0 kg of pure water and 0.9 kg of 10% hydrochloric acid were added dropwise to adjust the pH to 2–3. The aqueous and ethyl acetate phases were separated. The aqueous phase was extracted three times with 0.5 kg of ethyl acetate each time. The organic phases were combined and washed three times with pure water. The organic phase was concentrated to obtain 23 g of crude Epidrimendiol. Separation was performed by silica gel column chromatography with gradient elution of petroleum ether and ethyl acetate to obtain 20 g of pure Epidrimendiol.

[0692] NMR data for compound Epidrimendiol:

[0693] δ 13 C-NMR: 36.6(C-1); 18.9(C-2); 42.7(C-3); 33.2(C-4); 54.2(C-5); 24.3(C-6); 127.7(C-7); 137.2 (C-8); 43.4 (C-9); 36.1 (C-10); 67.8 (C-11); 63.2 (C-12); 22.1 (C-13); 21.8 (C-14); 33.1 (C-15).

[0694] δ 1 H-NMR: 5.83 (H, m); 4.11~4.14 (H, d); 3.99~4.01 (H, d); 3.89~3.92 (H, dd); 3.63~3 .66(H,dd);2.23(2H,br,-OH);2.11-2.16(H,m);1.87~1.93(H,m);1.74~1.76(H, m); 1.60~1.66(H,m); 1.57~1.60(H,m); 1.42-1.52(H,m); 1.42~1.51(H,m); 1.48( H,m); 1.31~1.37(H,m); 1.16~1.24(H,m); 0.90(3H,s); 0.89(3H,s); 0.86(3H,s).

[0695] To prepare a 20 ppm Epidrimendiol solution as a sample: First, dissolve 0.2 g of Epidrimendiol in 99.8 g of polyol (such as 1,3-butanediol or propylene glycol), stir and heat to dissolve, and obtain a 2000 ppm Epidrimendiol solution. Then, dilute the 2000 ppm Epidrimendiol solution 100 times with pure water to 20 ppm.

[0696] The prepared 20ppm Epidrimendiol was used as a sample to test various human efficacy cosmetic uses (Examples 16 to 26);

[0697] Using 2000ppm Epidrimendiol as a sample, the efficacy of various gene expression methods and cosmetic applications were tested (Examples 27 to 30);

[0698] Testing period: November 6, 2024 - December 3, 2024;

[0699] Test environment: Temperature: 21±1℃; Humidity: 50±10%RH;

[0700] Thirty-two subjects with sensitive skin were selected and subjected to the Baumann Skin Type Questionnaire. The results are shown in Table 59.

[0701] Table 59

[0702] Selection criteria

[0703] (1) Healthy Chinese women aged 35-60 (at the start of the trial);

[0704] (2) The Bauman questionnaire indicates sensitive skin (Bauman questionnaire sensitivity score range 30-68);

[0705] (3) Fine lines under the eyes have a VAS score of ≥2;

[0706] (4) Self-perceived facial sagging;

[0707] (5) The baseline value of the moisture meter in the forearm test area is between 15 and 45 (au);

[0708] (6) Able to cooperate well with the sample, understand and fill out the project questionnaire, and cooperate with the staff;

[0709] (7) Able to cooperate well with the test subjects and maintain a regular lifestyle during the research period;

[0710] (8) Able to read and understand all the contents of the informed consent form and voluntarily sign the informed consent form;

[0711] (9) During the trial, you agree not to use any cosmetics, drugs and health products that may affect the results.

[0712] Exclusion criteria

[0713] (1) Individuals with allergic constitution, allergic dermatitis, or a history of skin diseases (severe freckles, atopic dermatitis, psoriasis, eczema, severe acne, etc.) who are clinically deemed unsuitable to participate in this project;

[0714] (2) The test site has large areas of birthmarks, scratches, vitiligo, pigmented nevi, keloids and other skin characteristics that may affect the test;

[0715] (3) Pregnancy, lactation, and menopause;

[0716] (4) Other requirements that affect this test;

[0717] (5) Individuals who have participated in other clinical trials within the past two months;

[0718] (6) In addition, the person in charge of the experiment judged that the group was not suitable to be the subjects of this experiment.

[0719] Restrictions

[0720] (1) During the trial, treatments that would affect the test site are prohibited;

[0721] (2) During the test, it is prohibited to use other skin care samples or other samples that may affect the test.

[0722] (3) During the test, the daily necessities must be the same as those used before the test began, and no changes are allowed.

[0723] Test method basis:

[0724] (1) QT / ZHCA 005-2019 Test Method for the Effect of Cosmetics on Skin Elasticity

[0725] (2) QB / T 4256-2011 Guidelines for Evaluation of Moisturizing Efficacy of Cosmetics

[0726] (3) T / GDCA 009-2022 Method for evaluating the repair efficacy of cosmetics on human body

[0727] (4) T / ZHCA 003-2018 Test Method for Cosmetics' Influence on Transepidermal Moisture Loss

[0728] (5) T / CNMIA 0015-2020 Clinical Evaluation Standards for Soothing and Sensitive Skincare Products

[0729] (6) T / GDCDC 021-2022 Test Methods for Soothing Efficacy of Cosmetics

[0730] (7) Wang Huan, Pan Yao. Cosmetic Efficacy Evaluation (V) - Scientific Support for Claims of Soothing Efficacy [J]. Daily Chemical Industry, 2018, 48(05):247-254

[0731] (8) T / ZHCA 005-2019 Test Method for the Effect of Cosmetics on Skin Elasticity

[0732] (9) T / GDCDC 032-2023 Test Method for Exfoliating Efficacy of Cosmetics

[0733] (10) T / ZHCA 006-2019 Test Method for Anti-wrinkle Efficacy of Cosmetics

[0734] (11) T / TDCA 003-2021 Test Method for Firming Efficacy of Cosmetics

[0735] (12) T / CAB 0152-2022 Test Methods for Seven Efficacy Items of Cosmetics: Anti-wrinkle, Firming, Moisturizing, Oil Control, Repairing, Nourishing, and Soothing

[0736] (13) Liu, Weiyi; Zhou, Lin; Zhao, Hua. Evaluation of cosmetic efficacy (XIII) – Consumer usage test [J]. Daily Chemical Industry, 2021, 51(06):485-490

[0737] (14) Cosmetic Safety Technical Specifications (2015 Edition)

[0738] (15) Cosmetic Classification Rules and Catalog

[0739] (16) Evaluation Standards for Cosmetic Efficacy Claims

[0740] Test process:

[0741] D0(BL):

[0742] (1) Recruit subjects according to requirements. When subjects visit the laboratory, laboratory staff explain the testing process to the subjects and the subjects sign a written informed consent form.

[0743] (2) Subjects were screened according to the experimental requirements.

[0744] (3) After the selected subjects cleaned their faces with standard facial cleanser, they used lint-free absorbent paper towels to dry their faces and then sat quietly in a constant temperature and humidity room for 30 minutes with their arms exposed.

[0745] (4) For qualified subjects, the tester will draw a 3cm×3cm square test area on the inside of each forearm. Then the test will proceed in the following order: VISIA-CR (three sides) → Evaface (three sides) → VC 98 (cheek) → Corneometer (cheek) → Corneometer (left and right arms) → Glossymeter (face) → Tewameter (face) → DermaScan (face).

[0746] (5) Staff members used a single sample on the inner forearm of the subject according to the random table in the appendix.

[0747] (6) After the subjects complete the test, the staff will distribute the test products and provide instructions on how to use the products and the amount to use.

[0748] T72h:

[0749] (7) Subjects were followed up at the prescribed time and sat quietly in a constant temperature and humidity room for 30 minutes after exposing the test site on the inner side of the forearm.

[0750] (8) Then proceed to the test, the test order is as follows: Corneometer (left and right arms) → self-assessment questionnaire.

[0751] D7, D14, D21:

[0752] (9) Subjects fill out the online questionnaire within the corresponding time period.

[0753] D28:

[0754] (10) Subjects were followed up and after using standard facial cleanser to clean their faces, they sat quietly in a constant temperature and humidity room for 30 minutes.

[0755] (11) Check the subjects’ usage records and weigh the product.

[0756] (12) The test then proceeds in the following order: VISIA-CR (three sides) → Evaface (three sides) → VC 98 (cheek) → Corneometer (face) → Glossymeter (face) → Tewameter (face) → DermaScan (face) → Self-assessment questionnaire (Bauman questionnaire, self-assessment questionnaire).

[0757] (13) The testing process is over.

[0758] Note: D0 refers to the visit before the subject uses the sample, T72h refers to the visit 72 hours after the subject uses the sample, D7 refers to the visit 7 days after the subject uses the sample, D14 refers to the visit 14 days after the subject uses the sample, D21 refers to the visit 21 days after the subject uses the sample, and D28 refers to the visit 28 days after the subject uses the sample.

[0759] In the following examples, EXCEL software is used to perform descriptive statistics on the measured values ​​at each test time point, including the mean and standard error.

[0760] For continuous data: Before and after the change, the Shapiro-Wilk Test was used in SPSS software to test the significance of the change in data distribution. If the data were normally distributed, a paired t-test was used; otherwise, a Wilcoxon rank-sum test for two related samples was used. The significance level α was set at 0.05.

[0761] Ordinal data: The comparison before and after use was performed using the Wilcoxon rank-sum test for two related samples, with a significance level of α of 0.05.

[0762] Questionnaire survey data: The results of the self-assessment questionnaire with any scoring criteria showed significant differences, indicating that the samples had corresponding efficacy. The significance level α was set at 0.05.

[0763] Change rate % = (Mean test value after sample use - Mean test value before sample use) / Mean test value before sample use * 100%

[0764] Note: In the test results of Examples 16 to 26 below, the significance markers are interpreted as follows: p ≥ 0.05, "ns" indicates no statistical difference; p < 0.05 indicates a significant difference; where "*" indicates 0.01 ≤ p < 0.05; "**" indicates 0.001 ≤ p < 0.01; "***" indicates p < 0.001. "*" indicates the difference before and after use.

[0765] Example 16

[0766] The compound Epidrimendiol is used in the preparation of cosmetics with moisturizing effects.

[0767] The subject's face was tested using a Corneometer;

[0768] Parameter explanation: The higher the parameter value, the higher the moisture content of the stratum corneum of the skin.

[0769] Result determination: After product use, the increase in the moisture content of the stratum corneum in the test area was significant, indicating that the tested product has a moisturizing effect.

[0770] After 4 weeks of use, the moisture content of the stratum corneum increased significantly by 69.41% compared to before use.

[0771] The specific test results are shown in Table 60 and Figure 42;

[0772] Table 60 Results of stratum corneum moisture content test (32 people) Unit: CU

[0773] Example 17

[0774] The compound Epidrimendiol is used in the preparation of cosmetics with 72-hour moisturizing effects.

[0775] The subjects' arms were tested using a Corneometer;

[0776] Parameter explanation: The larger the parameter value, the higher the moisture content of the stratum corneum.

[0777] Results: After a single use of the product, the increase in the moisture content of the stratum corneum in the test area was significantly higher than that in the control group, indicating that the test sample has a short-term moisturizing effect of 72 hours.

[0778] At 72 hours after application, compared with the control side, the change in stratum corneum moisture content on the sample side was significantly increased by 12.05%.

[0779] The specific test results are shown in Table 61, Table 62 and Figure 43;

[0780] Table 61 Results of stratum corneum moisture content test (32 people) Unit: CU

[0781] Example 18

[0782] The compound Epidrimendiol is used in the preparation of cosmetics with repairing effects.

[0783] The Tewameter was used to test one side of the subject's face for 40 seconds, and the average value was taken after 20 seconds. The test was repeated twice and the average value was taken.

[0784] Parameter explanation: The smaller the parameter value, the lower the rate of transepidermal water loss and the better the skin barrier.

[0785] Result determination: If the parameter values ​​in the test area decrease significantly after product use, it indicates that the tested product has a repairing effect.

[0786] After 4 weeks of use, the transepidermal moisture loss rate was significantly reduced by 22.28% compared to before use.

[0787] The specific test results are shown in Table 63 and Figure 44;

[0788] Table 63 Results of transepidermal water loss rate test (32 people) Unit: g / h / m2

[0789] Example 19

[0790] The compound Epidrimendiol is used in the preparation of cosmetics with nourishing effects.

[0791] Test judgment criteria: If at least two of the parameters of gloss, smoothness, firmness / elasticity, and dermal thickness / density in the test area are significantly improved after product use, it indicates that the tested product has nourishing effects.

[0792] Test 1: Smoothness

[0793] The subjects' cheeks were tested using VC20 and SEsm values ​​were analyzed.

[0794] Parameter explanation: The smaller the SEsm parameter value, the smoother the skin.

[0795] Result determination: After product use, the SEsm parameter value in the test area decreased significantly, indicating that the tested product has a skin-smoothing effect.

[0796] After 4 weeks of use, the SEsm value decreased significantly by 12.13% compared to before use.

[0797] The specific test results are shown in Table 64, Figure 45 and Figure 62;

[0798] Table 64 Skin SEsm Value Test Results (32 people) Unit: au

[0799] Test 2: Gloss

[0800] The subject's cheek was tested using a Glossymeter.

[0801] Parameter explanation: The higher the test value, the better the skin's radiance.

[0802] Result determination: After product use, the increase in parameter values ​​in the test area was significant, indicating that the tested product has the effect of improving skin radiance.

[0803] After 4 weeks of use, the gloss level increased significantly by 63.62% compared to before use.

[0804] The specific test results are shown in Table 65 and Figure 46;

[0805] Table 65 Skin Glossiness Test Results (32 people) Unit: au

[0806] Test 3: Firmness and Elasticity

[0807] The subject's cheek was tested using a cutometer.

[0808] Parameter explanation: The larger the R2 parameter value, the better the skin elasticity; the smaller the R0 parameter value, the better the skin firmness.

[0809] Results Interpretation: A significant increase in the R2 parameter value in the test area after product use indicates that the test sample has an effect on improving skin elasticity; a significant decrease in the R0 parameter value in the test area after product use indicates that the test sample has an effect on improving skin firmness.

[0810] After 4 weeks of use, compared with before use, the R0 value decreased significantly by 42.46%, and the R2 value increased significantly by 19.44%.

[0811] The specific test results are shown in Table 66, Figure 47 and Figure 48;

[0812] Table 66. Results of Firmness and Elasticity Tests (32 people)

[0813] Test 4: Genuine leather thickness / density

[0814] The subject's face was tested using DermaScan.

[0815] Parameter explanation: The larger the parameter value, the thicker and denser the dermis.

[0816] Result determination: After product use, the parameter values ​​in the test area showed a significant increase, indicating that the tested product has the effect of increasing the thickness and density of dermis.

[0817] After 4 weeks of use, compared with before use, the dermal thickness increased significantly by 11.41% and the dermal density increased significantly by 60.22%.

[0818] The specific test results are shown in Table 67, Figure 49, Figure 50 and Figure 64;

[0819] Table 67 includes results of skin thickness and density tests (32 people).

[0820] Example 20

[0821] The compound Epidrimendiol is used in the preparation of cosmetics with soothing effects.

[0822] Test 1: Take a picture using VISIA-CR and analyze the skin redness a* parameter value using IPP software.

[0823] Parameter explanation: The larger the parameter value, the redder the skin.

[0824] Result determination: A significant decrease in parameter values ​​in the test area after product use indicates that the tested product has a soothing effect.

[0825] After 4 weeks of use, the a* value decreased significantly by 21.37% compared to before use.

[0826] The specific test results are shown in Table 68, Figure 51 and Figure 65;

[0827] Table 68 Skin a* Value Test Results (32 people) Unit: au

[0828] Test 2: The subjects' cheeks were photographed using VISIA-CR and the L* value was analyzed using IPP.

[0829] Parameter explanation: The larger the L* value, the brighter the skin.

[0830] Result determination: After product use, the increase in L* value in the test area was significant, indicating that the tested product has the effect of brightening skin tone.

[0831] After 4 weeks of use, the L* value increased significantly by 14.35% compared with before use.

[0832] The specific test results are shown in Table 69 and Figure 52;

[0833] Table 69 Skin L* Value Test Results (32 people) Unit: au

[0834] Example 21

[0835] The compound Epidrimendiol is used in the preparation of cosmetics with firming effects.

[0836] See Table 66, Figure 47 and Figure 48 in Example 19.

[0837] Example 22

[0838] The compound Epidrimendiol is used in the preparation of cosmetics with anti-wrinkle effects.

[0839] The subjects' faces were photographed using VISIA-CR, and the area of ​​under-eye wrinkles was analyzed using IPP. Parameter explanation: The smaller the value of the wrinkle area percentage parameter, the better the anti-wrinkle effect.

[0840] Result determination: If the parameter value in the test area decreases significantly after product use, it indicates that the tested product has an anti-wrinkle effect.

[0841] After 4 weeks of use, the area of ​​under-eye wrinkles decreased significantly by 13.29% compared to before use.

[0842] The specific test results are shown in Table 70, Figure 53 and Figure 60;

[0843] Table 70 Results of the test on the percentage of under-eye wrinkles (32 people) Unit: %

[0844] Example 23

[0845] The compound Epidrimendiol is used in the preparation of cosmetics that have the effect of lifting the cheekbones and adjusting the jaw angle.

[0846] Test 1: Improve sagging cheeks

[0847] The EvaFACE was used to photograph the lower edge of the subject's cheekbone and analyze the volume of sagging cheekbone.

[0848] Parameter explanation: The larger the volume of sagging cheeks, the more severe the sagging.

[0849] Results: The reduction in the volume parameter value of sagging cheeks after product use was significant, indicating that the tested product has the effect of improving sagging cheeks.

[0850] After 4 weeks of use, the volume of sagging cheeks decreased significantly by 21.51% compared to before use.

[0851] The specific test results are shown in Table 71, Figure 54 and Figure 58;

[0852] Table 71 Results of apple cheek sagging volume test (32 people) Unit: mm 3

[0853] Test 2: Lifting the jawline

[0854] The EvaFACE was used to photograph the lower edge of the subject's mandible and to analyze the length of the contour line when the mandible droops.

[0855] Parameter explanation: The shorter the length of the contour line of the drooping part of the mandibular border, the more obvious the effect of lifting the mandibular border.

[0856] Results: After product use, the decrease in the length parameter of the drooping jawline was significant, indicating that the tested product has a jawline lifting effect.

[0857] After 4 weeks of use, the length of the drooping jawline contour decreased significantly by 2.36% compared to before use.

[0858] The specific test results are shown in Table 72, Figure 55 and Figure 59;

[0859] Table 72 Results of the test on the length of the contour line of the drooping part of the mandible (32 people) Unit: mm

[0860] Example 24

[0861] The compound Epidrimendiol is used in the preparation of cosmetics suitable for sensitive skin.

[0862] Improved sensitivity: Subjects were tested using the Bauman Sensitivity Questionnaire. Parameter interpretation: The higher the parameter value, the more sensitive the skin.

[0863] Results: The decrease in the Bowman Questionnaire score after product use was significant, indicating that the tested product has the effect of improving skin sensitivity.

[0864] After 4 weeks of use, the Bauman Questionnaire score decreased significantly by 34.60% compared to before use.

[0865] The specific test results are shown in Table 73 and Figure 56;

[0866] Table 73 Results of the Bauman Questionnaire (32 participants) Unit: points

[0867] Example 25

[0868] The compound Epidrimendiol is used in the preparation of cosmetics with exfoliating properties.

[0869] The subjects' faces were tested using VC98, and the desquamation index (DI) value was analyzed.

[0870] Parameter explanation: The smaller the DI (Desquamation Index) parameter value, the less stratum corneum desquamation.

[0871] Result determination: After product use, the DI parameter value of the exfoliation index in the test area decreased significantly, indicating that the tested product has the effect of exfoliation.

[0872] After 4 weeks of use, the skin desquamation index (DI) value decreased significantly by 9.23% compared to before use.

[0873] The specific test results are shown in Table 74, Figure 57 and Figure 62;

[0874] Table 74 Results of Skin Desquamation Index (DI) Test (32 people) Unit: au

[0875] Example 26

[0876] The compound Epidrimendiol is used in the preparation of cosmetics that do not cause irritation.

[0877] The adverse skin reactions of the subjects were assessed.

[0878] Parameter Explanation: Subjects selected as having sensitive skin were assessed for adverse skin reactions 7 days after using the sample. The "Skin Reaction Grading Standards for Human Trial Testing" in the 2015 edition of the *Cosmetic Safety Technical Specifications* was adopted, referring to Table 75.

[0879] Table 75 Grading Standards for Skin Reactions in Human Trial Use

[0880] Results: After using the product, the subjects reported no adverse reactions on their faces, indicating that the tested product had a mild (non-irritating) effect.

[0881] The number of adverse facial reactions among the subjects was counted.

[0882] Results: After using the product, 96.67% or more of the subjects reported no adverse reactions in their self-assessments, indicating that the test product is suitable for sensitive skin. It can be used to prepare non-irritating cosmetics suitable for sensitive skin.

[0883] The specific test results are shown in Table 76;

[0884] Table 76 Adverse reaction assessment results (32 people)

[0885] Participants completed a self-assessment questionnaire.

[0886] Parameter Explanation: Statistical scores > 3 indicate the number of people who found the items beneficial. Acceptance Rate = (Number of people who found the items beneficial / Total number of people) * 100%

[0887] Result determination: The differences in the results of any scoring criteria in the self-assessment questionnaire were statistically significant, indicating that the sample has the corresponding efficacy.

[0888] The questionnaire results are shown in Tables 77, 78, 79, 80, and 81:

[0889] Table 77: Day 3 Approval Survey Results (5-point scale) (32 people)

[0890] Table 78 shows the results of the week 1 approval survey (out of 5) (32 people).

[0891] Table 79 shows the results of the week 2 approval survey (out of 5) (32 people).

[0892] Table 80 shows the results of the week 3 approval survey (out of 5) (32 people).

[0893] Table 81 shows the results of the week 4 approval survey (out of 5) (32 people).

[0894] Based on the descriptions in Examples 16 to 26, and combining instrument testing, image analysis, visual evaluation, and questionnaires, 20 ppm of Epidrimendiol was used as a sample to test various performance uses of cosmetics. The results showed that the sample is suitable for sensitive skin, gentle (non-irritating), soothing, anti-wrinkle, provides 72-hour moisturizing, moisturizing, repairing, firming, exfoliating, and nourishing effects. It also showed effects in improving skin sensitivity, brightening skin tone, enhancing radiance, smoothing skin, increasing skin thickness and density, lifting cheekbones, and firming the jawline.

[0895] Example 27

[0896] The compound Epidrimendiol is used in the preparation of cosmetic products that positively regulate the expression of the acid sphingomyelinase SMPD1 gene and the LOR gene, thereby improving the skin barrier function.

[0897] 1. The experimental principle, experimental materials, experimental procedures, and data analysis methods are the same as those in Example 11.

[0898] 2. Test sample: 2000ppm Epidimendiol 1,3-butanediol solution.

[0899] 3. Experimental Results

[0900] 3.1 Cell viability test results

[0901] Two MTT assays were performed: First MTT assay: This cell viability assay designed eight sample concentrations (as shown in Figure 65). When the sample concentration was ≤0.1%, the cell viability was greater than 90%, and all samples could be used for subsequent experiments. Table 82 shows the relative cell viability (Mean ± SD) for each group.

[0902] Table 82 Relative cell activity (Mean ± SD) in each group

[0903] In the first efficacy test experiment, a sample concentration of 0.1% was selected as the subsequent test concentration for SMPD1; 0.05% and 0.1% were selected as the subsequent test concentrations for LOR.

[0904] In the second MTT assay, eight sample concentrations were designed for cell viability testing (as shown in Figure 66). When the sample concentration was ≤0.2%, cell viability was greater than 90%, and all samples could be used for subsequent experiments. Table 83 shows the relative cell viability (Mean ± SD) for each group.

[0905] Table 83 Relative cell activity (Mean ± SD) in each group

[0906] 0.2% was selected as the concentration for the subsequent second efficacy test.

[0907] 3.2 Relative expression level of SMPD1 gene

[0908] Based on the sample concentration selected in 3.1, the expression level of SMPD1 was detected. The results of the first efficacy test are shown in Table 84 and Figure 67.

[0909] Table 84. Relative SMPD1 expression levels in each group (Mean ± SD)

[0910] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0911] The results of the second efficacy test are shown in Table 85 and Figure 68.

[0912] Table 85. Relative SMPD1 expression levels in each group (Mean ± SD)

[0913] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0914] Based on the sample concentration selected in 3.1, the expression level of LOR was detected, and the results of the first efficacy test are shown in Table 86 and Figure 69.

[0915] Table 86. Relative expression levels of LOR in each group (Mean ± SD)

[0916] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0917] The results of the second efficacy test are shown in Table 87 and Figure 70.

[0918] Table 87. Relative expression levels of LOR in each group (Mean ± SD)

[0919] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0920] Conclusions: At a concentration of 0.1% (2 ppm Epidimendiol), the relative expression level of the SMPD1 gene in the sample was 1.52 ± 0.09, significantly higher than that in the control group (P < 0.05); at a concentration of 0.2% (4 ppm Epidimendiol), the relative expression level of the SMPD1 gene in the sample was 2.44 ± 0.12, significantly higher than that in the control group (P < 0.01). This indicates that the sample at these concentrations upregulated the SMPD1 gene. At concentrations of 0.05% (1 ppm Epidimendiol) and 0.1% (2 ppm Epidimendiol), the relative expression levels of the LOR gene in the sample were 1.50 ± 0.08 and 1.19 ± 0.04, respectively, both significantly higher than that in the control group (P < 0.05); at a concentration of 0.2%, the relative expression level of the LOR gene in the sample was 2.34 ± 0.17, significantly higher than that in the control group (P < 0.01). This indicates that the sample at the above concentration has the effect of upregulating the LOR gene.

[0921] Example 28

[0922] The compound Epidrimendiol is used in the preparation of cosmetic products that positively regulate the expression of the elastin ELN gene, improving skin elasticity and firmness.

[0923] 1. The experimental principle, experimental materials, experimental procedures, and data analysis methods are the same as in Example 12.

[0924] 2. Test sample: 2000ppm Epidimendiol 1,3-butanediol solution.

[0925] 3. Experimental Results

[0926] 3.1 Cell viability test results

[0927] Two MTT experiments were conducted.

[0928] First MTT assay: Eight sample concentrations were designed for this cell viability test (as shown in Figure 71). When the sample concentration was ≤1%, the cell viability was greater than 90%, and all of them could be used for subsequent experiments.

[0929] Table 88 shows the relative cell activity (Mean ± SD) for each group.

[0930] Table 88 Relative cell activity (Mean ± SD) in each group

[0931] 0.2% was selected as the concentration for the first efficacy test.

[0932] Second MTT assay: This cell viability assay was designed with 8 sample concentrations (as shown in Figure 72). When the sample concentration was ≤1%, the cell viability was greater than 90%, and all of them could be used for subsequent experiments.

[0933] Table 89 shows the relative cell activity (Mean ± SD) for each group.

[0934] Table 89 Relative cell viability (Mean ± SD) in each group

[0935] 0.5% and 1% were selected as the concentrations for the subsequent second efficacy test.

[0936] 3.2 Relative expression level of ELN gene

[0937] Based on the sample concentration selected in 3.1, the relative expression level of the ELN gene was detected, and the results of the first efficacy test are shown in Table 90 and Figure 73.

[0938] Table 90. Relative ELN expression levels (Mean ± SD) in each group.

[0939] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0940] The results of the second efficacy test are shown in Table 91 and Figure 74.

[0941] Table 91. Relative ELN expression levels in each group (Mean ± SD)

[0942] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the blank control group (B) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the blank control group (B) (P < 0.01).

[0943] in conclusion:

[0944] At concentrations of 0.2% (4 ppm Epidimendiol), 0.5% (10 ppm Epidimendiol), and 1% (20 ppm Epidimendiol), the relative expression levels of the ELN gene in the samples were 8.73±1.02, 9.13±0.38, and 5.87±0.57, respectively, all significantly upregulated compared to the blank control (P<0.01). This indicates that the samples at these concentrations upregulated the ELN gene, which can serve as evidence supporting claims of firming and anti-wrinkle effects.

[0945] Example 29

[0946] The compound Epidrimendiol is used in the preparation of cosmetic applications that negatively regulate the expression of tumor necrosis factor-α and interleukin-1α genes, improve skin inflammation, and soothe sensitive skin.

[0947] 1. The experimental principle, experimental materials, experimental procedures, and data analysis methods are the same as in Example 13.

[0948] 2. Test sample: 2000ppm Epidimendiol 1,3-butanediol solution.

[0949] 3. Experimental Results

[0950] 3.1 Cell viability test results

[0951] Conduct an MTT experiment.

[0952] Eight sample concentrations were designed for this cell viability assay (as shown in Figure 75). When the sample concentration was ≤0.1%, the cell viability was greater than 90%, and all of them could be used for subsequent experiments. Table 92 shows the relative cell viability (Mean±SD) for each group.

[0953] Table 92 Relative cell viability (Mean ± SD) in each group

[0954] 0.1% was selected as the concentration for subsequent efficacy testing.

[0955] 3.2 Relative expression level of TNF-α gene

[0956] Based on the sample concentration selected in 3.1, the TNF-α content was detected, and the test results are shown in Table 93 and Figure 76.

[0957] Table 93. Relative expression levels of TNF-α in each group (Mean ± SD)

[0958] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0959] 3.3 Relative expression level of IL-1α gene

[0960] Based on the sample concentration selected in 3.1, the IL-1α content was detected, and the test results are shown in Table 94 and Figure 77.

[0961] Table 94. Relative expression levels of IL-1α in each group (Mean ± SD)

[0962] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0963] Conclusion: At a concentration of 0.1% (2 ppm Epidimendiol), the relative expression level of the inflammatory cytokine TNF-α gene in the sample was 0.62 ± 0.08, which was significantly downregulated compared with the negative control (P < 0.05). This indicates that the sample has an inhibitory effect on the TNF-α gene at this concentration, which can serve as one of the supporting pieces of evidence for the claimed soothing efficacy.

[0964] At a concentration of 0.1% (2 ppm Epidimendiol), the relative expression level of the inflammatory cytokine IL-1α gene in the sample was 0.52 ± 0.04, which was significantly downregulated compared with the negative control (P < 0.05). This indicates that the sample has an inhibitory effect on the IL-1α gene at this concentration, which can serve as one of the supporting pieces of evidence for the claimed soothing efficacy.

[0965] Example 30

[0966] The compound Epidrimendiol is used to prepare cosmetic applications that negatively regulate the expression of transient receptor potential vanillin-1 receptor and prostaglandin E2 genes, achieving analgesic, anti-inflammatory, and soothing effects on the skin.

[0967] 1. The experimental principle, experimental materials, experimental procedures, and data analysis methods are the same as those in Example 14.

[0968] 2. Test sample: 2000ppm Epidimendiol 1,3-butanediol solution.

[0969] 3. Experimental Results

[0970] 3.1 Cell viability test results

[0971] Two MTT experiments were conducted.

[0972] First MTT assay: Eight sample concentrations were designed for this cell viability test (as shown in Figure 78). When the sample concentration was ≤0.1%, the cell viability was greater than 90%, and all of them could be used for subsequent experiments.

[0973] Table 95 shows the relative cell activity (Mean ± SD) for each group.

[0974] Table 95 Relative cell viability (Mean ± SD) in each group

[0975] 0.05% and 0.1% were selected as the concentrations for efficacy testing.

[0976] Second MTT assay: This cell viability assay was designed with 8 sample concentrations (as shown in Figure 79). When the sample concentration was ≤0.2%, the cell viability was greater than 90%, and all of them could be used for subsequent experiments.

[0977] Table 96 shows the relative cell activity (Mean ± SD) for each group.

[0978] Table 96 Relative cell viability (Mean ± SD) in each group

[0979] 3.2 Relative expression level of TRPV1 gene

[0980] Based on the sample concentration selected in 3.1, the TRPV1 content was detected, and the efficacy test results are shown in Table 97 and Figure 80.

[0981] Table 97. Relative TRPV1 expression levels in each group (Mean ± SD)

[0982] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0983] 3.3 Relative expression level of PGE2 gene

[0984] Based on the sample concentration selected in 3.1, the PGE2 content was detected, and the results of the first efficacy test are shown in Table 98 and Figure 81.

[0985] Table 98. Relative PGE2 expression levels in each group (Mean ± SD)

[0986] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0987] The results of the second efficacy test are shown in Table 99 and Figure 82.

[0988] Table 99. Relative PGE2 expression levels (Mean ± SD) in each group

[0989] Note: "ns" indicates no significant difference (P ≥ 0.05); * indicates a statistically significant difference compared to the negative control group (C) (0.01 ≤ P < 0.05); ** indicates an extremely significant difference compared to the negative control group (C) (P < 0.01).

[0990] Conclusion: At concentrations of 0.05% (1 ppm Epidimendiol) and 0.1% (2 ppm Epidimendiol), the relative expression levels of the inflammatory cytokine TRPV1 gene in the sample were 0.84±0.08 and 0.88±0.02, respectively, both significantly downregulated compared to the negative control (P<0.05). This indicates that the sample at these concentrations has an inhibitory effect on the TRPV1 gene, which can serve as evidence supporting the claim of soothing efficacy.

[0991] At concentrations of 0.05% (1 ppm Epidimendiol), 0.1% (2 ppm Epidimendiol), and 0.2% (4 ppm Epidimendiol), the relative expression levels of the inflammatory cytokine PGE2 gene in the sample were 0.66±0.07, 0.62±0.06, and 0.55±0.07, respectively, which were significantly downregulated compared to the negative control (P<0.05). This indicates that the sample at these concentrations has an inhibitory effect on the PGE2 gene, which can serve as one of the supporting pieces of evidence for the claimed soothing efficacy.

[0992] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent modifications made based on the content of the present invention specification and drawings, or direct or indirect applications in related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. The use of compounds Drimendiol or Epidrimendiol in the preparation of cosmetics; The chemical structural formula of Drimendiol is: The chemical structural formula of Epidrimendiol is as follows:

2. The compound Drimendiol or the compound Epidrimendiol is used in the preparation of cosmetic products with moisturizing, repairing, firming, nourishing, anti-wrinkle and / or soothing effects.

3. The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products with 72-hour moisturizing effects.

4. The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetic products suitable for sensitive skin.

5. The compounds Drimendiol or Epidrimendiol are used in the preparation of cosmetics that do not cause irritation.

6. The compound Drimendiol or the compound Epidrimendiol is used in the preparation of cosmetic products that have the effect of increasing the distance of the cheekbone and / or the angle of the jaw.

7. The compound Epidrimendiol is used in the preparation of cosmetics with exfoliating effects.

8. The compound Drimendiol or the compound Epidrimendiol is used in the preparation of cosmetic products that positively regulate the expression of the acid sphingomyelinase SMPD1 gene and the LOR gene of the sphingomyelinase, thereby improving the skin barrier function.

9. The compound Drimendiol or the compound Epidrimendiol is used in the preparation of cosmetic products that positively regulate the expression of the elastin ELN gene and improve skin elasticity and firmness.

10. The compound Drimendiol or the compound Epidrimendiol is used in the preparation of cosmetic products that have the effects of negatively regulating the expression of tumor necrosis factor-α, interleukin-1α and prostaglandin E2 genes, improving skin inflammation and soothing sensitive skin.

11. The compound Drimendiol or the compound Epidrimendiol is used to prepare cosmetic products that have negative regulatory expression of the transient receptor potential vanillin-1 receptor gene, thereby achieving analgesic and anti-inflammatory soothing effects on the skin.

12. The compound Drimendiol is used in the preparation of synthetic cosmetics that increase hyaluronic acid in skin cells.

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