Resveratrol Formulations and Uses

Abstract

The present disclosure provides a method of improving skin health parameters and / or reducing signs of skin aging, comprising administering an effective amount of resveratrol to a human subject in need thereof.

Description

[Technical field]

[0001] The present disclosure relates to novel uses of resveratrol, for example, to enhance the health, condition and signs of aging of the skin. [Background technology]

[0002] Resveratrol (3,5,4'-trihydroxy-stilbene) is a phytoalexin, a polyphenol synthesized by plants in response to external stressors. It exists in two isomeric forms, cis and trans, with the trans form being biologically active. Resveratrol is found in numerous plant species, as well as in red wine, grapes, dark chocolate, peanuts and berries, and is used in topical and oral formulations for its antioxidant activity. Summary of the Invention [Problem to be solved by the invention]

[0003] Visible signs of skin aging include accumulation of wrinkles (fine and deep), dryness, sagging, translucency, uneven pigmentation and prominent pores. While intrinsic aging is primarily dependent on genetic processes, extrinsic factors such as lifestyle choices, sun exposure and pollution significantly accelerate skin aging. Furthermore, disruption of the skin barrier can lead to adverse health consequences such as stimulating inflammatory skin diseases and allowing microbial pathogens to invade the skin, potentially increasing inflammation in the systemic circulation. Improved approaches are needed to improve skin function and reduce the signs of skin aging. [Means for solving the problem]

[0004] The present disclosure provides novel methods and kits for improving skin health parameters and / or signs of skin aging using resveratrol. In particular, the present disclosure provides methods for oral administration and / or topical application of resveratrol to improve skin health parameters and / or signs of skin aging compared to a placebo product, for example as measured by: a. image analysis to measure one or more of, for example, wrinkles (fine and / or deep), uneven pigmentation, skin elasticity, hydration, pore visibility, skin tone, sebum, and / or skin temperature), e.g., images are taken under normal light, UV light, and polarized light and measure pore size, pigmentation, number and depth of wrinkles, sebum, hydration, skin elasticity, skin tone, and skin temperature; and / or b. Blood analysis, e.g., measuring one or more of oxidative stress markers and / or blood antioxidant profiles, e.g., total antioxidant capacity, derivatives of reactive oxidative metabolites (DROMs), and / or the ratio of oxidized glutathione to reduced glutathione (E(h)GSH) and cysteine ​​(E(h)CySH). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0005] In a first embodiment, the present disclosure provides a method (Method 1) for improving skin health parameters and / or reducing signs of skin aging, comprising administering to a human subject in need thereof an effective amount of both an oral dosage of resveratrol and a topical formulation of resveratrol. For example, Method 1 includes the following methods:

[0006] 1.1 Method 1, wherein the resveratrol is 3,5,4'-trihydroxy-trans-stilbene (i.e., trans-resveratrol).

[0007] 1.2 Method 1 or 1.1, wherein the oral dosage of resveratrol is between 50 mg and 1000 mg per day, such as between 100 mg and 200 mg per day, in particular about 150 mg per day.

[0008] 1.3 The method of any preceding claim, wherein the oral dosage of resveratrol is administered twice daily in divided doses.

[0009] 1.4 The method of any preceding claim, wherein the oral dosage of resveratrol is 150 mg per day, administered in divided doses of 75 mg in the morning and 75 mg in the evening.

[0010] 1.5 Resveratrol topical formulations are approximately 2 mg / cm 2 The method of any preceding claim, wherein the composition is administered to the skin in an amount of

[0011] 1.6 The method of any preceding claim, wherein the topical formulation of resveratrol comprises 0.5 weight percent (wt%) to 2.5 wt% resveratrol, in particular about 1.5 wt% resveratrol, e.g. a cream.

[0012] 1.7 Topical formulations of resveratrol are available in doses ranging from 2 mg to 20 mg per 100 cm of skin. 2 For example, 4mg to 10mg / 100cm of skin 2 For example, about 6 mg / 100 cm of skin 2 Any of the preceding methods 1 to 1.5, wherein the resveratrol is administered at a daily dosage of 100 mg.

[0013] 1.8 The method of any preceding claim, wherein the topical formulation of resveratrol is administered in divided doses twice daily.

[0014] 1.9 The method of any preceding claim, wherein a topical formulation of resveratrol is administered to the face of the subject.

[0015] 1.10 The method of any preceding claim, wherein the topical formulation of resveratrol is a cream containing about 1.5 wt% resveratrol and administered to the subject's face in a dosage of about 1 g in the morning and about 1 g in the evening.

[0016] 1.11 a. Resveratrol is 3,5,4'-trihydroxy-trans-stilbene; b. The oral dosage of resveratrol is 150 mg per day, administered in divided doses of 75 mg in the morning and 75 mg in the evening; c. the topical formulation of resveratrol is a cream containing about 1.5 wt% resveratrol and administered to the subject's face in a dosage of about 1 g in the morning and about 1 g in the evening; 2. A method according to any preceding claim.

[0017] 1.12 The method according to any of the preceding clauses, wherein the duration of resveratrol treatment is at least 4 weeks, such as at least 8 weeks.

[0018] 1.13 The method of any preceding claim, wherein the subject is female.

[0019] 1.14 The method of any preceding clause, wherein the subject is over 40 years of age.

[0020] 1.15 The method of any preceding clause, wherein the subject's skin health parameters are improved and / or the signs of skin aging in the subject are reduced, compared to the average of a control population not receiving resveratrol.

[0021] 1.16 Any method 1.15, wherein one or more of the subject's skin health parameters remain the same or do not deteriorate significantly, and / or one or more of the subject's signs of skin aging remain the same or do not increase significantly, between the start and end of resveratrol treatment.

[0022] 1.17 Any of the preceding methods 1-1.15, wherein the subject has improved skin health parameters and / or reduced signs of skin aging compared to the subject's condition at the start of resveratrol treatment.

[0023] 1.18 The method of any preceding clause, wherein the signs of skin aging include one or more of increased wrinkles (e.g. an increase in the number and / or depth of fine lines and / or wrinkles), increased pore size, increased areas of pigmentation, reduced sebum, reduced moisture, reduced skin elasticity, reduced skin tone and reduced skin temperature.

[0024] 1.19 The method of any preceding claim, wherein the signs of skin aging include an increase in the number and depth of wrinkles in the eye area.

[0025] 1.20 The method of any preceding clause, wherein the signs of skin aging are assessed using image analysis, wherein the image analysis measures one or more or all of pore size, pigmentation, number and depth of wrinkles, sebum, moisture, skin elasticity, skin tone, and skin temperature, for example, the image analysis is performed using an A-ONE Smart measurement system (Bomtech Electronics Co. Ltd., Seoul, Korea).

[0026] 1.21 The method according to any of the preceding clauses, wherein the signs of skin ageing are assessed using image analysis under normal light, UV light and / or polarised light, e.g. images are obtained under normal light, UV light and / or polarised light.

[0027] 1.22 Either method of 1.20 or 1.21, wherein image analysis measures the number and depth of wrinkles, pore size, pigmented areas, sebum, moisture, skin elasticity and skin temperature.

[0028] 1.23 Any of the preceding methods 1-1.17, wherein the skin health parameter is assessed using a blood analysis measuring, for example, one or more of oxidative stress markers and / or blood antioxidant profile, such as total antioxidant capacity, derivatives of reactive oxidative metabolites (DROMs), and / or the ratio of oxidized glutathione to reduced glutathione (E(h)GSH) and cysteine ​​(E(h)CySH).

[0029] In another embodiment, the disclosure provides resveratrol for use in improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, wherein the human subject receives both an effective amount of an oral dosage and a topical formulation of resveratrol, e.g., according to any of methods 1-1.23 above.

[0030] In another embodiment, the present disclosure provides the use of resveratrol in the manufacture of a medicament in the form of an oral dosage formulation and a topical formulation for improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, for example according to any of methods 1-1.23 above.

[0031] In another embodiment, the disclosure provides a kit including both an oral dosage of resveratrol and a topical formulation of resveratrol together with instructions for use, e.g., according to any of methods 1-1.23 above.

[0032] The term "about" preceding a numerical value "X" is used herein to refer to an interval ranging from X minus 10% of X to X plus 10% of X.

[0033] According to the invention, resveratrol can be administered orally and / or topically as the sole active ingredient or in combination with other active ingredients, in particular as the sole active ingredient.

[0034] In a second embodiment, the present disclosure provides a method (Method 2) for improving skin health parameters and / or reducing signs of skin aging, comprising administering an effective amount of resveratrol to a human subject in need thereof as an oral dosage of resveratrol. For example, Method 2 includes the following method.

[0035] 2.1. Method 2, wherein the resveratrol is 3,5,4'-trihydroxy-trans-stilbene.

[0036] 2.2 Method 2 or 2.1, wherein the oral dosage of resveratrol is between 50 mg and 1000 mg per day, for example between 100 mg and 200 mg per day, in particular about 150 mg per day.

[0037] 2.3 The method of any preceding claim, wherein the oral dosage of resveratrol is administered twice daily in divided doses.

[0038] 2.4 The method of any preceding claim, wherein the oral dosage of resveratrol is 150 mg per day, administered in divided doses of 75 mg in the morning and 75 mg in the evening.

[0039] 2.5 Resveratrol is 3,5,4'-trihydroxy-trans-stilbene, The method of any preceding claim, wherein the oral dosage of resveratrol is 150 mg per day, administered in divided doses of 75 mg in the morning and 75 mg in the evening.

[0040] 2.6 The method according to any of the preceding clauses, wherein the duration of resveratrol treatment is at least 4 weeks, such as at least 8 weeks.

[0041] 2.7 The method of any preceding claim, wherein the subject is female.

[0042] 2.8 The method of any preceding clause, wherein the subject is over 40 years of age.

[0043] 2.9 The method of any preceding clause, wherein the subject's skin health parameters are improved and / or the signs of skin aging in the subject are reduced, as compared to the average of a control population not receiving resveratrol.

[0044] 2.10 Any of the methods of 2.9, wherein one or more of the subject's skin health parameters remain the same or do not deteriorate significantly, and / or one or more of the subject's signs of skin aging remain the same or do not increase significantly, between the start and end of resveratrol treatment.

[0045] 2.11 Any of the preceding methods 2-2.9, wherein the subject has improved skin health parameters and / or reduced signs of skin aging compared to the subject's condition at the start of resveratrol treatment.

[0046] 2.12 The method of any preceding clause, wherein the signs of skin aging include one or more of increased wrinkles (e.g. an increase in the number and / or depth of fine lines and / or wrinkles), increased pore size, increased areas of pigmentation, reduced sebum, reduced moisture, reduced skin elasticity, reduced skin tone and reduced skin temperature.

[0047] 2.13 The method of any preceding claim, wherein the signs of skin aging include an increase in the number and depth of wrinkles in the eye area.

[0048] 2.14 The method of any preceding clause, wherein the signs of skin aging are assessed using image analysis, wherein the image analysis measures one or more or all of pore size, pigmentation, number and depth of wrinkles, sebum, moisture, skin elasticity, skin tone, and skin temperature, for example, the image analysis is performed using an A-ONE Smart measurement system (Bomtech Electronics Co. Ltd., Seoul, Korea).

[0049] 2.15 The method according to any of the preceding clauses, wherein the signs of skin aging are assessed using image analysis under normal light, UV light and / or polarized light, e.g. images are obtained under normal light, UV light and / or polarized light.

[0050] 2.16 Either method of 2.14 or 2.15, wherein image analysis measures the number and depth of wrinkles, pore size, pigmented areas, sebum, moisture, skin elasticity and skin temperature.

[0051] 2.17 Any of the preceding methods 2-2.11, wherein the skin health parameter is assessed using a blood analysis measuring, for example, one or more of an oxidative stress marker and / or a blood antioxidant profile, such as total antioxidant capacity, derivatives of reactive oxidative metabolites (DROMs), and / or the ratio of oxidized glutathione to reduced glutathione (E(h)GSH) and cysteine ​​(E(h)CySH).

[0052] In another embodiment, the disclosure provides resveratrol for use in improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, wherein the human subject receives an effective amount of oral dosage of resveratrol, for example according to any of Methods 2-2.17 above.

[0053] In another embodiment, the present disclosure provides the use of resveratrol in the manufacture of a medicament in the form of an oral dosage formulation for improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, for example according to any of methods 2-2.17 above.

[0054] In a third embodiment, the present disclosure provides a method (Method 3) for improving skin health parameters and / or reducing signs of skin aging, comprising administering an effective amount of resveratrol as a topical formulation of resveratrol to a human subject in need thereof. For example, Method 3 includes the following methods:

[0055] 3.1. Method 3, wherein the resveratrol is 3,5,4'-trihydroxy-trans-stilbene.

[0056] 3.2 Resveratrol topical formulations are approximately 2 mg / cm 2 to the skin in an amount of 0.1 to 0.5% by weight,

[0057] 3.3 The method according to any preceding claim, wherein the topical formulation of resveratrol comprises 0.5wt% to 2.5wt% resveratrol, in particular about 1.5wt% resveratrol, e.g. a cream.

[0058] 3.4 Topical formulations of resveratrol are available in doses ranging from 2 mg to 20 mg per 100 cm of skin. 2 For example, 4mg to 10mg / 100cm of skin 2 For example, about 6 mg / 100 cm of skin 2 Any of the methods of preceding 3 to 3.2, wherein the resveratrol is administered at a daily dosage of 100 mg / kg.

[0059] 3.5 The method of any preceding claim, wherein the topical formulation of resveratrol is administered in divided doses twice daily.

[0060] 3.6 The method of any preceding claim, wherein a topical formulation of resveratrol is administered to the subject's face.

[0061] 3.7 The method of any preceding claim, wherein the topical formulation of resveratrol is a cream containing about 1.5 wt% resveratrol and administered to the subject's face in a dosage of about 1 g in the morning and about 1 g in the evening.

[0062] 3.8 a. Resveratrol is 3,5,4'-trihydroxy-trans-stilbene; b. The method of any preceding claim, wherein the topical formulation of resveratrol is a cream containing about 1.5 wt% resveratrol and administered to the subject's face in a dosage of about 1 g in the morning and about 1 g in the evening.

[0063] 3.9 The method of any preceding claim, wherein the duration of resveratrol treatment is at least 4 weeks, such as at least 8 weeks.

[0064] 3.10 The method of any preceding claim, wherein the subject is female.

[0065] 3.11 The method of any preceding clause, wherein the subject is over 40 years of age.

[0066] 3.12 The method of any preceding clause, wherein the subject's skin health parameters are improved and / or the signs of skin aging in the subject are reduced, as compared to the average of a control population not receiving resveratrol.

[0067] 3.13 Any of the methods of 3.12, wherein one or more of the subject's skin health parameters remain the same or do not deteriorate significantly, and / or one or more of the subject's signs of skin aging remain the same or do not increase significantly, between the start and end of resveratrol treatment.

[0068] 3.14 Any of the preceding methods 3-3.12, wherein the subject has improved skin health parameters and / or reduced signs of skin aging compared to the subject's condition at the start of resveratrol treatment.

[0069] 3.15 The method of any preceding clause, wherein the signs of skin aging include one or more of increased wrinkles (e.g. an increase in the number and / or depth of fine lines and / or wrinkles), increased pore size, increased areas of pigmentation, reduced sebum, reduced moisture, reduced skin elasticity, reduced skin tone, and reduced skin temperature.

[0070] 3.16 The method of any preceding claim, wherein the signs of skin aging include an increase in the number and depth of wrinkles in the eye area.

[0071] 3.17 The method of any preceding clause, wherein the signs of skin aging are assessed using image analysis, wherein the image analysis measures one or more or all of pore size, pigmentation, number and depth of wrinkles, sebum, moisture, skin elasticity, skin tone, and skin temperature, for example, the image analysis is performed using an A-ONE Smart measurement system (Bomtech Electronics Co. Ltd., Seoul, Korea).

[0072] 3.18 The method according to any of the preceding clauses, wherein the signs of skin aging are assessed using image analysis under normal light, UV light and / or polarized light, e.g. images are obtained under normal light, UV light and / or polarized light.

[0073] 3.19 Either method of 3.17 or 3.18, wherein image analysis measures wrinkle number and depth, pore size, pigmented areas, sebum, moisture, skin elasticity and skin temperature.

[0074] 3.20 Any of the preceding methods 3-3.14, wherein the skin health parameter is assessed using a blood analysis measuring, for example, one or more of oxidative stress markers and / or blood antioxidant profile, such as total antioxidant capacity, derivatives of reactive oxidative metabolites (DROMs), and / or the ratio of oxidized glutathione to reduced glutathione (E(h)GSH) and cysteine ​​(E(h)CySH).

[0075] In another embodiment, the disclosure provides resveratrol for use in improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, wherein the human subject receives an effective amount of a topical formulation, for example according to any of Methods 3-3.20 above.

[0076] In another embodiment, the present disclosure provides the use of resveratrol in the manufacture of a medicament in the form of a topical formulation for improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof, for example according to any of methods 3-3.20 above. EXAMPLES

[0077] Clinical Trials A double-blind, randomized, placebo-controlled clinical trial was conducted with 8 weeks of participation and 4 arms as follows: Investigational product: trans-resveratrol (referred to in this Examples section as "resveratrol" or "Resveratrol"). Dosage: 75 mg resveratrol in a single capsule with water twice daily (morning and evening) and / or 1 g cream (containing 1.5 wt% resveratrol) applied topically to the face twice daily (morning and evening) Duration: 8 weeks Number of proposed subjects: 140

[0078] The objective of this study is to evaluate the effectiveness of resveratrol compared to placebo on skin health parameters and signs of skin aging in otherwise healthy women over 40. The study is designed to show that oral administration and / or topical application of resveratrol improves skin health parameters and signs of skin aging including wrinkles (fine and / or deep wrinkles), uneven pigmentation, skin elasticity, moisturization, visibility of pores, skin tone, sebum, skin temperature and / or oxidative stress markers and blood antioxidant properties compared to a placebo product.

[0079] Resveratrol can be produced according to the process known in the art.Preferably, the resveratrol used in the clinical trials according to the present invention is produced by fermentation, for example, using genetically modified host cells (especially yeast cells), particularly as described in WO2006 / 089898 and WO2016 / 180956, and the resveratrol produced in this way can be purified, for example, as described in WO2018 / 141798.In particular, the resveratrol used in the clinical trials according to the present invention is Veri-te resveratrol (food grade >98%) from Evolva SA, Switzerland.

[0080] Subjects will be divided into four study arms: Group 1 - Resveratrol active treatment, oral and topical: The proposed number of subjects in this group is 35. The subjects will be instructed to take one capsule (75 mg resveratrol) with water twice a day (one capsule in the morning and one capsule in the evening) and to apply a 1 g amount of cream (containing 1.5 wt% resveratrol) to the face twice a day (once in the morning and once in the evening) after cleansing the face and before applying a moisturizer.

[0081] Resveratrol capsule composition:

[0082] [Table 1]

[0083] Resveratrol cream composition:

[0084] [Table 2]

[0085] Group 2 - Resveratrol active treatment, oral and placebo topical: The proposed number of subjects in this group is 35. Subjects will be instructed to take one capsule (75 mg resveratrol) with water twice a day (morning and evening) and apply the placebo topical product as in the active topical treatment group.

[0086] Group 3 - Placebo oral and resveratrol active treatment, topical: The proposed number of subjects in this group is 35. Subjects will be instructed to take the placebo oral product as in the active oral treatment group and to apply a 1 g amount of the cream (containing 1.5 wt% resveratrol) to the face twice daily (morning and evening) after cleansing the face and before applying moisturizer.

[0087] Group 4 - Placebo oral and topical: The proposed number of subjects in this group is 35. Subjects will be instructed to take the placebo oral and topical products as in the active oral and topical treatment groups.

[0088] The placebo oral product consists of carboxymethylcellulose and magnesium stearate and appears to be identical to the resveratrol oral product. The placebo topical product is an aqueous cream (oil-in-water emulsion) that is made identical to the 1.5 wt% resveratrol cream but contains no resveratrol. Both active and placebo products were made to GMP standards.

[0089] Subject inclusion criteria were as follows: Women over 40 years old; Being otherwise healthy; You agree not to change your standard skin care routine.

[0090] The exclusion criteria were as follows: any clinically significant medical condition, including but not limited to uncontrolled cardiovascular, neurological, psychiatric, renal, gastrointestinal, immune, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormality; currently taking resveratrol or using a resveratrol cream; Cosmetic surgical procedures and procedures, including Botox and other injectables, microdermabrasion, and laser treatments; Medications for acne or other skin conditions, including topical retinoids (Rein-A, Retrieve), oral retinoids such as isotretinoin (Roaccutane), benzoyl peroxide, AHAs, serums, and chemical peels; active smoker, nicotine use, alcohol or drug (prescription or illicit substance) abuse; chronic past and / or current alcohol use (>14 alcohol drinks per week); Known to be pregnant or breastfeeding; Allergy or hypersensitivity to resveratrol; Any condition that, in the opinion of the investigator, makes the subject unsuitable for enrollment.

[0091] The study is a double-blind, randomized, placebo-controlled clinical trial with an 8-week treatment period, with active and placebo arms, along with baseline data collection. Upon enrollment in the study, subjects are randomly assigned with a 1:4 probability to one of four treatment arms. A baseline skin assessment and fasting blood test are completed at enrollment. Skin assessment includes characterization of wrinkles, pore size, pigmented areas, sebum, moisture, skin elasticity, and skin temperature. Prior to skin assessment and photographs, subjects remove all makeup and lipstick using a provided makeup removal wipe and brush hair off the face. Fasting blood samples measure oxidative stress markers, blood antioxidant profile, resveratrol concentrations, and metabolites.

[0092] Once subjects have completed the baseline measurements, they will be instructed to consume / apply their assigned product according to the prescribed dosing regimen. During the 8-week study period, subjects will be asked to attend the study site at the midpoint (week 4) and end (week 8) of the study for repeated baseline measurements. At the end of the study (week 8), subjects will be asked to complete an exit interview and questionnaire. Subjects will be asked to attend the site in a fasting state for all visits. At the end of week 8, study participation will be considered complete. Outcome measurements taken at baseline, week 4, and week 8 are listed in Table 1.

[0093] [Table 3]

[0094] [Table 4]

Claims

1. Use of resveratrol in the manufacture of a medicament in the form of an oral dosage formulation, a topical formulation, or both an oral dosage formulation and a topical formulation, for improving skin health parameters and / or reducing signs of skin aging in a human subject in need thereof.

2. The use according to claim 1, wherein the resveratrol is 3,5,4'-trihydroxy-trans-stilbene.

3. 3. The use according to claim 1 or 2, wherein the oral dosage of resveratrol is between 50 mg and 1000 mg per day, such as between 100 mg and 200 mg per day, in particular about 150 mg per day, for example the oral dosage of resveratrol is administered twice daily in divided doses, for example the oral dosage of resveratrol is 150 mg per day administered in divided doses of 75 mg in the morning and 75 mg in the evening.

4. The topical formulation of resveratrol is about 2 mg / cm ２ for example, the topical formulation of resveratrol contains 0.5 wt % to 2.5 wt % resveratrol, in particular about 1.5 wt % resveratrol, e.g., a cream, or for example, the topical formulation of resveratrol is administered to the skin in an amount of 2 mg to 20 mg per 100 cm of skin. ２ , for example, 4 mg to 10 mg / 100 cm of skin ２ , for example, about 6 mg / 100 cm of skin ２ 3. The use of claim 1 or 2, wherein the topical resveratrol formulation is administered in a daily dosage of about 1 g in the morning and about 1 g in the evening, e.g., the topical resveratrol formulation is administered twice a day in divided doses, e.g., the topical resveratrol formulation is administered to the face of the subject, e.g., the topical resveratrol formulation is a cream comprising about 1.5 wt% resveratrol and administered to the face of the subject in a dosage of about 1 g in the morning and about 1 g in the evening.

5. a. the resveratrol is 3,5,4'-trihydroxy-trans-stilbene; b. the oral dosage of resveratrol is 150 mg per day, administered in divided doses of 75 mg in the morning and 75 mg in the evening; c. The use of claim 1, wherein the topical formulation of resveratrol is a cream containing about 1.5 wt% resveratrol and administered to the subject's face in a dosage of about 1 g in the morning and about 1 g in the evening.

6. 6. The use according to any one of claims 1, 2 and 5, wherein the duration of resveratrol treatment is at least 4 weeks, such as at least 8 weeks.

7. 6. The use of any one of claims 1, 2 and 5, wherein the subject is over 40 years old, for example, the subject is female.

8. The use of any one of claims 1, 2, and 5, wherein the subject's skin health parameters improve and / or the subject's signs of skin aging decrease compared to the average of a control population not receiving resveratrol, or wherein one or more of the subject's skin health parameters remain the same or do not worsen significantly and / or one or more of the subject's signs of skin aging remain the same or do not increase significantly between the start and end of resveratrol treatment, or wherein the subject has an improvement in skin health parameters and / or a decrease in signs of skin aging compared to the subject's condition at the start of resveratrol treatment.

9. 6. The use of any one of claims 1, 2 and 5, wherein the signs of skin aging include one or more of increased wrinkles, increased pore size, increased areas of pigmentation, reduced sebum, reduced moisture, reduced skin elasticity, reduced skin tone and reduced skin temperature, for example, the signs of skin aging include an increased number and depth of wrinkles in the eye area.

10. Use according to any one of claims 1, 2 and 5, wherein the signs of skin aging include increased wrinkles, such as an increase in the number and / or depth of fine lines and / or deep wrinkles.

11. The use described in any one of claims 1, 2 and 5, wherein the signs of skin aging include reduced sebum.

12. 6. The use according to any one of claims 1, 2 and 5, wherein the signs of skin aging are assessed using image analysis, wherein the image analysis measures one or more or all of pore size, pigmentation, number and depth of wrinkles, sebum, moisture, skin elasticity, skin tone and skin temperature, e.g., wherein the image analysis is carried out using an A-ONE Smart Measurement System (Bomtech Electronics Co. Ltd., Seoul, Korea), e.g., wherein the signs of skin aging are assessed using image analysis under normal light, ultraviolet light and / or polarized light, e.g., wherein images are taken under normal light, ultraviolet light and / or polarized light.

13. 6. The use of any one of claims 1, 2 and 5, wherein the skin health parameters are assessed using a blood analysis measuring, for example, one or more of oxidative stress markers and / or blood antioxidant properties, such as total antioxidant capacity, derivatives of reactive oxidative metabolites (DROMs), and / or the ratio of oxidized glutathione to reduced glutathione (E(h)GSH) and cysteine ​​(E(h)CySH).

14. A kit comprising both an oral dosage of resveratrol and a topical formulation of resveratrol, for example according to the use of any one of claims 1 to 13, together with instructions for use.