Application of retinol derivative as skin ferroptosis inhibitor in cosmetic preparation

Abstract

The invention discloses application of a retinol derivative as a skin ferroptosis inhibitor in cosmetic preparation, and belongs to the technical field of cosmetics. The structural formula of the retinol derivative is shown in the specification, in the formula, R is fatty acyl, aromatic acyl or alkyl, the aromatic acyl is selected from acetyl, propionyl and the like, and the alkyl is selected from methyl, ethyl and the like. By inhibiting skin tissue lipid peroxidation (reducing MDA and 4-HNE levels), activating glutathione peroxidase 4 (GPX4) activity and adjusting skin iron ion homeostasis, targeted inhibition of skin ferroptosis is realized, and then skin aging (fine lines and laxity), sensitive redness, light damage darkness and barrier damage related to ferroptosis are improved. The composition can be prepared into essence, emulsion, cream and other cosmetic dosage forms, is high in safety and low in irritation, and is suitable for long-term skin care scenes.

Description

Technical Field

[0001] This invention relates to the interdisciplinary field of cosmetics and skin cell biology, specifically to a retinol derivative composition with skin ferroptosis inhibition function, and its application in the preparation of cosmetics that improve ferroptosis-related skin problems. Background Technology

[0002] Ferroptosis is an iron-dependent regulated form of cell death. Its core mechanism involves excessive lipid peroxidation of intracellular polyunsaturated fatty acids catalyzed by iron ions, and the inability of the GPX4-mediated antioxidant system to clear peroxidation products, ultimately leading to cell death. As a peripheral barrier organ, the skin's ferroptosis of keratinocytes and fibroblasts is directly related to various common skin problems: skin ferroptosis leads to collagen fiber degradation and elastin loss, causing fine lines, sagging, and other signs of aging; it also disrupts the tight junctions of the stratum corneum, resulting in increased TEWL (transient endothelial protein levels) and inducing sensitivity and redness; furthermore, the accumulation of lipid peroxidation products damages the skin barrier, exacerbating barrier dysfunction.

[0003] Inhibiting skin ferroptosis is crucial for maintaining skin homeostasis and improving skin problems. On the one hand, it can reduce skin cell damage caused by ferroptosis and slow down the aging process; on the other hand, it can repair barrier damage caused by ferroptosis and alleviate sensitivity and redness. However, the cosmetic industry currently lacks effective ingredients that target skin ferroptosis: traditional antioxidants (such as vitamin C and vitamin E) can only scavenge a small number of free radicals and cannot block iron-dependent lipid peroxidation cascades; iron chelators (such as deferoxamine) can reduce iron ions, but long-term use can easily lead to iron deficiency in the skin and affect normal physiological functions.

[0004] Retinol and its derivatives are classic ingredients in cosmetics, but their application is limited to promoting keratinocyte renewal and stimulating collagen synthesis. No studies have yet found an inhibitory effect on skin ferroptosis. Furthermore, traditional retinol suffers from poor stability and strong skin irritation, failing to meet the requirement of "long-term, gentle intervention" for ferroptosis inhibition. Therefore, this invention proposes using retinol derivatives with specific structures as skin ferroptosis inhibitors in cosmetics. By optimizing the molecular structure and excipient compatibility, targeted inhibition of skin ferroptosis can be achieved, while simultaneously improving stability and reducing irritation. Summary of the Invention

[0005] In order to overcome the above-mentioned defects and deficiencies in the prior art, the present invention provides an application of retinol derivatives as skin ferroptosis inhibitors in cosmetic preparation.

[0006] To address the aforementioned technical problems, this invention provides an application of a retinol derivative as a skin ferroptosis inhibitor in cosmetic preparation. The core of this invention lies in the discovery that the retinol derivative shown in structural formula (I) has significant skin ferroptosis inhibitory activity. It can improve ferroptosis-related skin problems by inhibiting lipid peroxidation, activating GPX4, and regulating iron ion homeostasis. At the same time, through optimization of the ceramide-sodium hyaluronate composite carrier, its transdermal absorption efficiency and skin tolerance are improved, avoiding the irritation problems of traditional retinol.

[0007] (I); The retinol derivative has the structural formula shown in (I). The selection of the R group is based on the balance principle of "ferroptosis inhibitory activity-stability-irritantness": Wherein, R is an aliphatic acyl, aromatic acyl, or alkyl group; the aromatic acyl group is selected from acetyl, propionyl, isobutyryl, butyryl, benzoyl, lauroyl, palmitoyl, cinnamoyl, or p-methoxycinnamoyl; and the alkyl group is selected from methyl, ethyl, n-propyl, isopropyl, butyl, or tert-butyl.

[0008] 1) Preferred aromatic acyl groups (such as acetyl and p-methoxycinnamoyl): can enhance molecular stability (resistance to photo and oxygen degradation), and at the same time have a stronger activation effect on GPX4 (glutathione peroxidase 4), with an MDA (malondialdehyde) inhibition rate of 28%-32%; 2) Secondary alkyl groups (such as methyl and ethyl): less irritating, suitable for cosmetics for sensitive skin, with a free iron ion reduction rate of 15%-20%; 3) Fatty acyl groups (such as lauroyl and palmitoyl): combine stability and skin affinity, suitable for lotion, cream and other formulations, and the GPX4 activation rate can reach 25%-28%.

[0009] The excipient is a ceramide-sodium hyaluronate composite carrier: ceramide can repair skin barrier damage caused by ferroptosis and reduce the irritation of retinol derivatives to the skin; sodium hyaluronate can increase skin moisture content and, as a transdermal penetration enhancer, improve the penetration efficiency of retinol derivatives in the stratum corneum, ensuring that they reach the skin cell layers where ferroptosis occurs (such as the basal layer of the epidermis and the superficial dermis). The preferred mass ratio of the two is 1:0.5 (e.g., ceramide NP 1.5% + sodium hyaluronate 0.75%), at which the transdermal efficiency is increased by 2 times, while the TEWL reduction rate can reach 30%-35%.

[0010] The retinol derivative of this invention synergistically inhibits skin ferroptosis through a triple pathway: 1) Inhibition of lipid peroxidation: Downregulates lipoxygenase (LOX) activity, reduces the conversion of arachidonic acid to lipid peroxides, and simultaneously removes existing MDA and 4-HNE (4-hydroxynonenal), with MDA reduction reaching 20%-32%; 2) Activation of the GPX4 pathway: Upregulates the expression of GPX4 mRNA and protein in skin cells, promotes the binding of glutathione (GSH) to lipid peroxidation products, and blocks their toxic accumulation. The expression level of GPX4 can be increased by 25%-32%. 3) Regulate iron homeostasis: Inhibit TfR1 expression to reduce the uptake of iron ions by skin cells; at the same time promote ferritin expression to convert free iron ions into stored iron, reducing its ability to participate in lipid peroxidation. The reduction of free iron ions can reach 15%-21%.

[0011] The beneficial technical effects achieved by the present invention are as follows: The present invention provides a cosmetic or skin care composition containing a novel retinol derivative, which can improve skin ferrodesorption-related skin problems, including skin aging (fine lines, wrinkles, sagging), sensitivity and redness (increased transepidermal water loss (TEWL), abnormal erythema index) and impaired skin barrier function by applying it to the skin surface. Detailed Implementation

[0012] The present invention will be further described below with reference to specific embodiments. These embodiments are only used to more clearly illustrate the technical solutions of the present invention and should not be construed as limiting the scope of protection of the present invention. The present invention will be further described below with reference to the embodiments.

[0013] Example 1: Antioxidant Repair Serum

[0014] (1) The formula composition is shown in Table 1 Table 1

[0015] (2) Preparation process 1. Oil phase preparation: Ceramide NP and tocopherol were heated to melt at 75°C, and retinol-4-acetoxycinnamate was added. The mixture was stirred at 300 rpm for 10 minutes until completely dissolved. 2. Aqueous phase preparation: Dissolve sodium hyaluronate, glycerol, and butylene glycol in purified water, heat and stir at 75°C until clear, and homogenize at 5000 rpm for 5 minutes; 3. Emulsification and cooling: Slowly pump the oil phase into the aqueous phase, homogenize at 10,000 rpm for 8 minutes, cool to 45°C at a rate of 1°C / min, add phenoxyethanol and stir until homogeneous. 4. Filling: Vacuum degassing below 40℃, then fill into brown light-proof bottles.

[0016] (3) Verification of ferroptosis inhibition Thirty subjects aged 25-40 years with ferroptosis-related photodamage (skin MDA content ≥8 nmol / mg protein, TEWL ≥20 g / (m²・h)) were included. Each night after cleansing, 0.8 ± 0.2 g (approximately the size of a soybean) was applied to the exposed areas of the face and neck affected by photodamage for 8 weeks. The specific testing methods are as follows: (1) MDA content detection Detection method: Thiobarbituric acid (TBA) colorimetric method.

[0017] Procedure: After adding TBA reagent to the sample, boil it in a water bath for 15 minutes, cool it, centrifuge it, collect the supernatant, and measure the absorbance at a wavelength of 532 nm using a UV spectrophotometer. Calculate the MDA concentration by referring to the standard curve.

[0018] Instrument: UV-Vis spectrophotometer (Model: UV-2600, Shimadzu).

[0019] (2) Detection of GPX4 protein expression Detection method: Western blot.

[0020] Procedure: Total protein was extracted and quantified from the sample. After SDS-PAGE electrophoresis, membrane transfer, and blocking, GPX4 specific primary antibody (1:1000 dilution) and fluorescent secondary antibody (1:5000 dilution) were added. The gray value of the bands was detected using a chemiluminescence imaging system, and the relative expression level was calculated with β-actin as an internal reference.

[0021] Instrument: Chemiluminescence imaging system (model: ChemiDocXRS+, Bio-Rad).

[0022] (3) Detection of free iron ion content Detection method: Ferrozine colorimetric method.

[0023] Procedure: After adding ferriazine reagent to the sample, incubate at room temperature for 20 minutes, measure the absorbance at a wavelength of 562 nm, and calculate the concentration using the iron ion standard curve.

[0024] Instrument: Microplate reader (Model: MultiskanFC, Thermo Fisher Scientific).

[0025] (4) TEWL detection Detection method: Direct measurement using an epidermal moisture loss meter.

[0026] Operating procedure: The subject relaxes their face, the instrument probe is placed vertically against the skin on the outer side of the cheekbone (adjacent to the sample collection area), the value is recorded after 30 seconds of stabilization, and the average value is taken after 3 consecutive tests.

[0027] Instrument: Transepidermal moisture loss meter (Model: MPA580, CK, Germany).

[0028] Tests showed that skin MDA content decreased from 8.5 nmol / mg protein to 6.1 nmol / mg protein (a decrease of 28%), GPX4 protein expression increased by 32%, free iron ion content decreased by 18%, and TEWL decreased to below 14 g / (m²・h).

[0029] Example 2: Sensitive Skin Repair Lotion

[0030] (1) The formula composition is shown in Table 2. Table 2

[0031] (2) Preparation process 1. Oil phase preparation: Ceramide 3 and polydimethylsiloxane were heated to 70°C to melt, and retinyl-4-palmitoylcinnamate was added and stirred to dissolve; 2. Aqueous phase preparation: Sodium hyaluronate and glycerol are dissolved in purified water and heated at 70°C with stirring until dissolved; 3. Emulsification and cooling: Slowly add the oil phase to the aqueous phase, homogenize at 8000 rpm for 6 minutes, cool to 45°C and add phenoxyethanol; 4. Filling: After reaching room temperature, fill into press-type emulsion bottles.

[0032] (3) Verification of the inhibitory effect of ferroptosis (animal experiment) A ferroptosis-associated sensitive muscle model was established in SD rats by capsaicin induction (skin free iron content ≥12μmol / L, TEWL ≥28g / (m²・h)): I. Preparations before modeling 1. Selection and adaptation of laboratory animals SPF-grade SD rats, female (with more stable skin sensitivity, suitable for sensitive skin research scenarios), 6-8 weeks old, weighing 180-220g, were selected. Animal housing environment: constant temperature (23±2℃), constant humidity (55±5%RH), 12-hour light-dark alternation, free access to water and food, acclimatization to the environment for 3 days, avoiding stress affecting skin condition.

[0033] 2. Preprocessing of the modeling region Hair removal on both sides of the spine on the back of rats: Two symmetrical patches of skin (each 3cm×3cm) were shaved off with an electric shaver. After hair removal, the skin was cleaned with physiological saline and allowed to air dry.

[0034] Observe for 24 hours after hair removal: ensure that the skin is free of scratches, redness, or other damage, and retain only the intact and healthy epidermal barrier to avoid interference with the modeling effect from pretreatment.

[0035] 3. Preparation of capsaicin inducer Formula: Weigh capsaicin (purity ≥98%) and dissolve it in anhydrous ethanol to prepare a 0.8% (w / w) capsaicin ethanol solution. Then mix it with medical petroleum jelly at a ratio of 1:4 and stir evenly to prepare a cream-like inducer (final capsaicin concentration 0.16%).

[0036] Preparation requirements: Prepare and use immediately, store in a dark and sealed container, maintain a temperature of 25℃ during stirring to ensure that capsaicin is evenly dispersed without precipitation.

[0037] II. Step-by-step modeling operation 1. Induction phase (days 1-3): Gently initiate inflammation and barrier damage. Administration method: Take 0.2g of inducer with a sterile cotton swab and apply it evenly to the pre-treatment area on the back of the rat, with a thickness of about 0.5mm, to ensure complete coverage of the skin surface.

[0038] Frequency: Once daily, administered at a fixed time between 9:00 and 10:00 AM to avoid inconsistent stimulation intensity due to time fluctuations.

[0039] Core objective: To stimulate TRPV1 channel activation through capsaicin, triggering a mild inflammatory response in the skin, initially disrupting the epidermal lipid barrier, and laying the foundation for ferroptosis.

[0040] 2. Enhancement Period (Days 4-7): Intensified stimulation induces ferroptosis. Dosage adjustment: Keep the application amount (0.2g / time) and frequency unchanged, and extend the skin exposure time after application (from 30 minutes to 1 hour) to enhance the penetration effect of capsaicin.

[0041] Auxiliary stimulation: One hour after daily administration, gently wipe the application area with sterile saline (with light pressure to avoid scratching) to simulate daily skin friction and further weaken the barrier function.

[0042] Core objective: Persistent inflammatory stress induces lipid peroxidation, inhibits GPX4 activity, leading to the accumulation of free iron ions and triggering ferroptosis-related pathological changes.

[0043] III. Criteria and Detection for Successful Modeling 1. Determine the time point 24 hours after modeling is completed (day 8), the indicators are checked to confirm whether the model is qualified.

[0044] 2. Core detection indicators and methods (1) Detection of free iron ion content in the skin Sample collection: Skin tissue from the modeling area was taken using a skin biopsy punch (6mm in diameter), subcutaneous fat was removed, and the tissue was rinsed with saline and then cut into a homogenate.

[0045] Detection method: The ferroazine colorimetric method was used. The tissue homogenate was ultrasonically broken, centrifuged (12000 r / min, 10 min), and the supernatant was collected. Ferroazine reagent was added and incubated at room temperature for 20 min. The absorbance was measured at 562 nm using a microplate reader, and the concentration was calculated by referring to the standard curve.

[0046] Standard: Free iron ion content ≥12μmol / L.

[0047] (2) TEWL (Transepidermal Water Loss) Detection Testing instrument: Transepidermal moisture loss meter (model: MPA580, CK, Germany).

[0048] Procedure: The rats were placed in a constant temperature and humidity laboratory to acclimatize for 30 minutes. The instrument probe was then placed vertically against the skin of the modeling area. After stabilizing for 30 seconds, the values ​​were recorded. The average value was taken after three consecutive tests.

[0049] Standard: TEWL ≥ 28 g / (m²・h).

[0050] (3) Auxiliary judgment indicators Skin appearance: Observe whether redness, swelling, erythema, and slight peeling appear in the modeled area, which are consistent with the phenotype of sensitive skin.

[0051] 4-HNE content detection: The 4-HNE level in skin tissue was detected using an ELISA kit. The level needed to be ≥30% higher than that in normal rats to verify lipid peroxidation activation.

[0052] 3. Model selection and grouping Only rats that met both core indicators were retained (individuals that did not meet the indicators were culled to ensure model consistency). These rats were randomly divided into a control group (no treatment) and an experimental group (treated with the target emulsion). Each group consisted of at least 10 rats to ensure statistical power. The selected models were divided into two groups: a control group (no treatment) and an experimental group (applied the lotion of this example), once daily for 14 days. Tests showed that the skin free iron ion content in the experimental group decreased to 9.5 μmol / L (a 21% reduction), 4-HNE content decreased by 18%, and TEWL decreased to 18 g / (m²・h), significantly better than the model group (p<0.01). The application amount and testing methods were the same as in Example 1.

[0053] Example 3: Anti-aging Repairing Face Cream

[0054] (1) The formula composition is shown in Table 3. Table 3

[0055] (2) Preparation process 1. Oil phase melting: Shea butter, beeswax, ceramide AP, and butylated hydroxytoluene are heated to 80°C to melt, and retinol-4-p-methoxycinnamoyl is added and stirred to dissolve; 2. Aqueous phase preparation: Sodium hyaluronate and glycerol are dissolved in purified water and heated to 80°C; 3. Emulsification and cooling: Pour the oil phase into the aqueous phase, homogenize at 10,000 rpm for 10 minutes, and cool to 45°C; 4. Molding: Stir at room temperature until the cream solidifies, then fill.

[0056] (3) Verification of ferroptosis inhibition Twenty-five subjects aged 35-50 years (skin GPX4 expression level ≤0.8 μg / mg protein, number of fine lines ≥15) underwent treatment. The treatment was administered nightly for 12 weeks. Results showed that skin GPX4 expression level increased to 1.02 μg / mg protein (an increase of 28%), MDA decreased by 25%, and the number of fine lines decreased by 22%. The application dosage and testing methods were the same as in Example 1.

[0057] Example 4: Soothing and Repairing Mask

[0058] (1) The formula composition is shown in Table 4. Table 4

[0059] (2) Preparation process 1. Dissolve sodium hyaluronate, glycerin, and butylene glycol in purified water and stir at 50°C until dissolved; 2. Add ceramide EOP and stir until homogeneous; 3. Cool to 40℃, add retinol-4-benzoylcinnamyl and phenoxyethanol, and stir until well mixed; 4. Filling: Inject the mask liquid into the non-woven fabric mask substrate and seal the package.

[0060] (3) Verification of ferroptosis inhibition Twenty subjects with acute ferroptosis-related sensitivities (skin 4-HNE content ≥6 nmol / mg protein, erythema index ≥30) were treated with the product three times a week for 15 minutes each time for four weeks. Results showed that skin 4-HNE content decreased to 4.9 nmol / mg protein (a reduction of 18%), the erythema index decreased to 18, and free iron ions decreased by 15%. The application dosage and testing methods were the same as in Example 1.

[0061] Example 5: Anti-wrinkle eye cream around the eyes

[0062] (1) The formula composition is shown in Table 5. Table 5

[0063] (2) Preparation process 1. Oil phase preparation: Squalane, hydrogenated lecithin, and ceramide NP are heated to 75°C to melt, and retinol-4-lauroylcinnamyl is added to dissolve them; 2. Aqueous phase preparation: Sodium hyaluronate and glycerol are dissolved in purified water and heated to 75°C; 3. Emulsification and cooling: Add the oil phase to the water phase, homogenize at 8000 rpm for 8 minutes, and cool to 50℃; 4. Filling: After cooling to 40℃, fill the eye cream bottle.

[0064] (3) Verification of the inhibitory effect of ferroptosis Twenty-two subjects with periocular ferromorbidity-related aging (periocular skin MDA ≥ 7 nmol / mg protein, fine line length ≥ 0.8 mm) were treated with topical application around the eyes daily at night for 8 weeks. Results showed that periocular MDA decreased to 5.5 nmol / mg protein (a 21% reduction), GPX4 increased by 25%, and fine line length shortened to 0.6 mm. The application dosage and testing methods were the same as in Example 1.

[0065] Example 6: Brightening and Repairing Toner

[0066] (1) The formula composition is shown in Table 6. Table 6

[0067] (2) Preparation process 1. Dissolve glycerol and butylene glycol in purified water and stir at 50°C; 2. Add ceramide 3 and sodium hyaluronate, and stir until dissolved; 3. Cool to 40℃, then add retinol-4-butyrylcinnamyl, lactic acid, and phenoxyethanol; 4. Filtration and filling: After filtration through a 0.22μm filter membrane, the toner is filled into a light-proof bottle.

[0068] (3) Verification of ferroptosis inhibition Eighteen subjects with impaired ferroptosis-related barrier function (TEWL ≥ 22 g / (m²・h), TfR1 expression increased by 20%) were treated with topical application after cleansing in the morning and evening for 6 weeks. Results showed that TEWL decreased to 16 g / (m²・h) (a 27% reduction), TfR1 expression decreased by 18%, and free iron ions decreased by 16%. The application amount and testing methods were the same as in Example 1.

[0069] Example 7: Repairing Essential Oil

[0070] (1) Formulation composition table 7 Table 7

[0071] (2) Preparation process 1. Base oil mixing: Heat sweet almond oil and jojoba oil to 40°C and stir to mix; 2. Addition of active ingredients: Add retinol-4-isooctylcinnamyl and vitamin E, and stir for 20 minutes; 3. Filling: Fill brown, light-proof essential oil bottles under nitrogen protection.

[0072] (3) Verification of ferroptosis inhibition Twenty subjects with dry ferroptosis-related skin problems (skin MDA ≥ 7.8 nmol / mg protein, TEWL ≥ 24 g / (m²·h)) were treated with topical application every night for 8 weeks. Results showed that MDA decreased to 6.1 nmol / mg protein (a 22% reduction), GPX4 increased by 26%, and TEWL decreased to 17 g / (m²·h). The application dosage and testing methods were the same as in Example 1.

[0073] Example 8: Body Moisturizing Lotion

[0074] (1) The formula composition is shown in Table 8. Table 8

[0075] (2) Preparation process 1. Oil phase preparation: Liquid paraffin and polysorbate-60 are heated to 70°C and mixed, and ceramide 3 is added and stirred to dissolve; 2. Aqueous phase preparation: Sodium hyaluronate, glycerol, and propylene glycol are dissolved in purified water and heated to 70°C; 3. Emulsification and cooling: Pour the oil phase into the aqueous phase, homogenize at 6000 rpm for 5 minutes, cool to 45℃ and add retinol-4-isopropylcinnamoyl and phenoxyethanol; 4. Filling: Stir until room temperature, then fill into body lotion bottles.

[0076] (3) Verification of ferroptosis inhibition Twenty-five subjects with skin ferroptosis-related dryness (skin free iron ≥11 μmol / L, TEWL ≥25 g / (m²・h)) were treated with topical application after daily bathing for 4 weeks. Results showed that skin free iron decreased to 9.2 μmol / L (a 16% reduction), 4-HNE decreased by 17%, and TEWL decreased to 18 g / (m²・h). The application dosage and testing methods were the same as in Example 1.

[0077] Example 9: Firming Repair Gel

[0078] (1) The formula composition is shown in Table 9. Table 9

[0079] (2) Preparation process 1. Aqueous phase preparation: Glycerol and propylene glycol are dissolved in purified water, and carbomer is added and stirred to swell; 2. Ingredient addition: Add sodium hyaluronate, trehalose, and ceramide AP, and stir until dissolved; 3. pH adjustment and homogenization: Add triethanolamine to adjust the pH, and homogenize at 3000 rpm for 3 minutes; 4. Addition of active ingredients and filling: Cool to 40℃, add retinol-4-n-butylcinnamoyl and phenoxyethanol, stir well and then fill.

[0080] (3) Verification of ferroptosis inhibition Twenty subjects with oily skin and ferroptosis-related laxity (skin GPX4 ≤ 0.75 μg / mg protein, skin elasticity R² ≤ 0.6) were treated with the product twice daily for 10 weeks. Results showed that skin GPX4 increased to 0.94 μg / mg protein (a 25% increase), MDA decreased by 20%, and the R² value increased to 0.72. The application dosage and testing methods were the same as in Example 1.

[0081] Example 10: Hand Cream

[0082] (1) The formula composition is shown in Table 10. Table 10

[0083] (2) Preparation process 1. Oil phase melting: Lanolin, petrolatum, beeswax, and ceramide NP are heated to 75℃ to melt; 2. Aqueous phase preparation: Glycerin and sodium hyaluronate are dissolved in purified water and heated to 75°C; 3. Emulsification and cooling: Add the oil phase to the water phase, homogenize at 8000 rpm for 7 minutes, cool to 45℃ and add retinol-4-tert-butylcinnamoyl and phenoxyethanol; 4. Shaping: Stir until solidified, then fill into hand cream tubes.

[0084] (3) Verification of ferroptosis inhibition Twenty-eight subjects with hand ferromorbidity-related roughness (hand skin MDA ≥ 8.2 nmol / mg protein, TEWL ≥ 26 g / (m²・h)) were treated with topical application after daily hand washing for 4 weeks. Results showed that hand MDA decreased to 6.5 nmol / mg protein (a 21% reduction), free iron decreased by 15%, and TEWL decreased to 19 g / (m²・h). The application dosage and testing methods were the same as in Example 1.

[0085] Example 11: Lip Cream

[0086] (1) The formula composition is shown in Table 11 Table 11

[0087] (2) Preparation process 1. Oil phase melting: Petrolatum, cocoa butter, and ceramide EOP are heated to 70℃ to melt, and vitamin E is added and stirred to dissolve; 2. Addition of active ingredients: Cool to 50℃, add retinol-4-isobutyrylcinnamoyl and sodium hyaluronate dissolved in a small amount of purified water beforehand; 3. Molding and filling: Add phenoxyethanol and stir evenly, cool to room temperature to solidify, and fill into lip cream tubes.

[0088] (3) Verification of ferroptosis inhibition Twenty subjects with lip ferroptosis-related dryness and peeling (lip MDA ≥ 7.5 nmol / mg protein, barrier integrity score ≤ 6 points) were treated with daily as needed for 2 weeks. Results showed that lip MDA decreased to 6.1 nmol / mg protein (a 19% reduction), 4-HNE decreased by 17%, and the barrier integrity score improved to 9 points. The application dosage and testing methods were the same as in Example 1.

[0089] Example 12: Ampoule Essence

[0090] (1) The formula composition is shown in Table 12. Table 12

[0091] (2) Preparation process 1. Aqueous phase preparation: Glycerin and butanediol are dissolved in purified water, heated to 60°C, and ceramide 3 and sodium hyaluronate are added and stirred until dissolved; 2. Addition of active ingredients: Cool to 40℃, add retinol-4-cinnamoylcinnamoyl and phenoxyethanol, and stir until homogeneous; 3. Aseptic filling: After filtration through a 0.22μm filter membrane, the contents are aseptically filled into 10mL ampoules and sealed under nitrogen protection.

[0092] (3) Verification of ferroptosis inhibition Five subjects with severe ferroptosis-related skin problems (skin MDA ≥ 9 nmol / mg protein, GPX4 ≤ 0.6 μg / mg protein) were treated with one ampoule daily for 28 consecutive days. Results showed that skin MDA decreased to 6.3 nmol / mg protein (a 30% reduction), GPX4 increased to 0.78 μg / mg protein (a 30% increase), and free iron decreased by 20%. The dosage and testing methods were the same as in Example 1.

[0093] The present invention has been disclosed above with reference to preferred embodiments, but it is not intended to limit the present invention. All technical solutions obtained by adopting equivalent substitutions or equivalent transformations fall within the protection scope of the present invention.

Claims

1. The application of a retinol derivative as a skin ferroptosis inhibitor in cosmetic preparation, characterized in that: The retinol derivative has a mass fraction of 0.5%-5% in the cosmetic.

2. The application according to claim 1, characterized in that: The structural formula of the retinol derivative is shown in (I): （I）； Wherein, R is an aliphatic acyl, aromatic acyl, or alkyl group; the aromatic acyl group is selected from acetyl, propionyl, isobutyryl, butyryl, benzoyl, lauroyl, palmitoyl, cinnamoyl, or p-methoxycinnamoyl; and the alkyl group is selected from methyl, ethyl, n-propyl, isopropyl, butyl, or tert-butyl.

3. The application according to claim 1, characterized in that: The cosmetic also includes excipients, which are ceramide-sodium hyaluronate composite carriers.

4. The application according to claim 3, characterized in that: The ceramide is selected from ceramide NP or ceramide 3, and the mass ratio of ceramide to sodium hyaluronate is 1:0.3-0.

8.

5. The application according to claim 1, characterized in that: The dosage form of the cosmetic is selected from serum, lotion, cream, mask, liquid, essential oil or gel.

6. The application according to claim 1, characterized in that: The specific pathways by which the retinol derivatives inhibit skin ferroptosis include at least one of the following: (1) Reduce the content of lipid peroxidation products in skin tissue, including a reduction of MDA by ≥20% and a reduction of 4-HNE by ≥18%; (2) Activates GPX4 activity in skin cells, increasing GPX4 protein expression level by ≥25%; (3) Regulates the iron homeostasis of the skin, reduces the content of free iron ions in the skin by ≥15%, and inhibits the expression of TfR1 mRNA and protein.

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