HK1225646A1 - Cosmetic use of an artemia salina extract to protect skin from thermal stress - Google Patents

Description

Cosmetic use of artemia salina extract for protecting skin from thermal stress

Technical Field

The present invention is in the field of beauty, more specifically in the field of protective beauty and skin care. The present invention relates to the cosmetic use of Artemia salina (Artemia salina) extracts for protecting the skin against damage caused by thermal stress, in particular cold thermal stress or repeated temperature changes.

Another object of the present invention is a cosmetic care method comprising topically applying to at least a portion of the skin of the body or face an artemia extract in a composition comprising a physiologically acceptable medium, in order to obtain a protective effect, more particularly to protect the skin from damages caused by thermal stress.

Background

The main function of the epidermis is to ensure a protective barrier between the external environment and the body. Skin in direct contact with the external environment is exposed to a variety of changes in environmental conditions. Depending on the nature and extent of the changes, they may cause damage resulting from physical, chemical or biological stresses. The main stresses are thermal stress, exposure to oxygen radicals, ultraviolet and infrared radiation, heavy metals, osmotic shock (osmotic shock) and pressure shock (compressive shock), and pathological conditions such as fever, inflammation, viral infection, etc.

Thermal stress is defined as stress that affects the body's optimal function and exceeds the body's physiological thermoregulatory mechanisms. Thermal stress is generated after a decrease (cold thermal stress) or an increase (hot thermal stress) in the temperature of the environmental source or the internal source. A deviation of a few degrees from the optimum temperature may have significant consequences.

Thermal shock is defined as stress caused by a sudden and significant temperature change (a temperature change of at least 10 ℃).

Skin can be exposed to thermal stress in many physiological or incidental situations. The average skin temperature can be evaluated as a constant value of about 33 ℃ in optimal function and can change rapidly depending on exposure to the environment, for example, the average skin temperature drops to 27 ℃ after immersion in a bath at 24 ℃ (Marino and Booth,1998) and can rise to over 37 ℃ after sun exposure.

Cold thermal stress may include deep hypothermia (where the temperature of tissues and organs drops below 25 ℃ (such as exposure to extremely cold temperatures or in certain medical techniques to protect organs and tissues from hypoxia)) and moderate hypothermia (temperatures between 25 ℃ and 35 ℃ (e.g., repeated exposure to air conditioning, or bathing when moving between indoor and outdoor daily in summer and winter).

The skin is often subjected to moderate cold and thermal stress and subsequent continuous warming. The following are the physiological effects of cold exposure (Fujita et al):

increased protein denaturation and depolymerization

Slowing down the progression of the cell cycle, generally the G1 phase being the most sensitive

Inhibition of transcription and translation, which leads to a general reduction in protein synthesis

-a component which disrupts the cytoskeleton

Changes in membrane permeability, which leads to cytosolic Na⁺And H⁺The ions increase.

Furthermore, repeated skin exposure to repeated temperature changes can lead to deleterious effects on the cell phenotype or structure and lipid composition of the cell membrane, thereby altering the barrier function of the skin and causing irritation, dryness or cracking. These effects caused by temperature changes and cold thermal stress accelerate the aging process of the skin.

Resistance to thermal stress is enabled by the establishment of specific cellular responses. In the case of cold-heat stress, cells establish a protective system by inducing the transcription of specific gene families that lead to the synthesis and intracellular accumulation of cold shock proteins or "CSPs" (which are distinct from heat shock proteins or "HSPs").

In CSP, cold-inducible RNA binding protein or CIRBP is a protein encoded in humans by the CIRBP gene. These proteins are constitutively expressed and are expressed after exposure to cold. CIRBP plays a key role in controlling cellular responses to a variety of cellular stresses, including short wavelength ultraviolet light, hypoxia and hypothermia. During moderate hypothermia, its expression increases rapidly and significantly (Fujita et al, J.mol. Microbiol. Biotechnol., 1999; Larry et al, J.Appl. physiol.,2002), and the other effects of CIRBP are:

inhibition of RNA degradation

Increasing the transcription of specific target genes by means of the components of the promoter regions of these genes,

alternative splicing of mRNA precursors

The special properties of CIRBPs make them interesting biological markers of physical response to temperature shock.

Artemia salina extracts have been used in cosmetic agents. For example, document FR 2817748 describes artemia extracts for preventing skin ageing caused by UV damage, document FR 2835743 describes artemia extracts for limiting the side effects of retinoids, and application WO 1999038483 describes cosmetic products based on artemia extracts for the regeneration and stimulation of skin cells.

However, no one has so far established a link between artemia extract and the protection of the skin from damage caused by thermal stress.

The inventors have demonstrated that the application of an effective amount of artemia extract enables the protection of cells from thermal stress, in particular cold thermal stress or repeated temperature changes, which may lead to skin damage.

The invention and the advantages obtained will be better understood on reading the description.

Disclosure of Invention

The present invention relates to the cosmetic and/or dermatological use of artemia extracts for protecting the skin against damage caused by thermal stress.

According to the invention, the term "skin" includes all the keratinous appendages present on the surface of the body, in particular body hair, eyelashes, eyebrows, nails and hair.

Thus, in the sense of the present invention, "protection of the skin from damage caused by temperature changes" is understood to mean that the artemia extract is used to reduce or prevent skin damage and irritation caused by repeated changes in temperature or cold-heat stress. Repeated skin damage is considered unsightly and is often associated with accelerated skin aging.

The invention also relates to the cosmetic and/or dermatological use of artemia extract for protecting the skin against damage caused by cold and thermal stress.

The invention also relates to the cosmetic and/or dermatological use of an artemia extract for protecting the skin against damage caused by sudden and/or repeated temperature changes.

The invention also relates to the cosmetic and/or dermatological use of artemia extract for maintaining physiological levels of CIRBP in skin cells exposed to cold and thermal stress.

In fact, artemia are small crustaceans living in brackish water. When environmental conditions become difficult (dehydration, increased mineral content), artemia form cysts and enter a resting period where it can remain for years. When the conditions become favorable again, the artemia rehydrate and continue its developmental cycle smoothly.

Artemia can develop important adaptation skills due to adaptation to their highly mineralized (hypermineralized) biological cells: it synthesizes GP4G (diguanosine tetraphosphate), a precursor of ATP, GTP and G-protein activators. It has cells that specifically regulate permeability, a necessary consequence of good hydromineral balance of plankton.

In one embodiment, the artemia extract comprises 120-195 mg/liter guanosine tetraphosphate, preferably at least 150 mg/liter guanosine tetraphosphate.

Hereinafter, the terms "active agent" and "artemia extract" are used interchangeably.

"topical administration" is understood to mean the act of applying or coating (spread) the active agent of the invention or a composition comprising said active agent to or on the surface of the skin or mucosa.

By "physiologically acceptable" is understood to mean that the active agents of the invention or compositions comprising them are suitable for contact with the skin or mucous membranes without causing toxic or intolerable reactions.

"damage caused by heat stress" is understood to mean exposure to cold, resulting in the area of skin that has been damaged being weakened, dry, irritated or cracked.

In a particular embodiment, the artemia extract according to the invention may be diluted in one or more physiologically suitable solvents, such as water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diethylene glycol, cyclic polyols or any mixture of these solvents.

Another object of the present invention is a cosmetic care method comprising topically applying an artemia extract in a composition comprising a physiologically acceptable medium on at least a portion of the skin of the body or face to protect the skin from damage caused by thermal stress.

The present invention also relates to a cosmetic care method comprising topically applying to at least a portion of the skin of the body or face an artemia extract in a composition comprising a physiologically acceptable medium to protect the skin from damage caused by repeated temperature changes and/or cold and thermal stresses.

Advantageously, the artemia extract is present in a concentration of 0.0001% to 20% by total weight of the composition, preferably in a concentration of 0.01% to 10% by total weight of the composition, more preferably in a concentration of 0.05% to 5% by total weight of the composition in a physiologically acceptable medium.

According to another advantageous embodiment of the invention, the active agent may be encapsulated or contained in a cosmetic carrier (for example liposomes or any other microcapsules used in the cosmetic field), or adsorbed on powdered organic polymers, mineral supports (supports) such as talc and bentonite.

The compositions used in the practice of the present invention may be in particular aqueous, hydroalcoholic or oily solutions; the oil-in-water emulsion, the water-in-oil emulsion or the composite emulsion exists; they may also be present in the form of suspensions or powders suitable for application on the skin, mucous membranes, lips and/or hair.

These compositions may be more or less fluid and have the appearance of a cream, lotion, milk (milk), serum (serum), pomade, gel, paste or foam. They may also be present in solid form, for example as sticks (stick), or may be applied to the skin in the form of an aerosol.

These compositions may also comprise any additives commonly used in the application areas covered, as well as adjuvants required for their formulation, such as solvents, thickeners, diluents, antioxidants, colorants, sunscreens, self-tanning agents, pigments, fillers, preservatives, fragrances, odor absorbers, cosmetic or pharmaceutical active ingredients, essential oils, vitamins, essential fatty acids, surfactants, film-forming polymers, etc.

In all cases, the skilled person will ensure that these adjuvants and their proportions are selected so as not to impair the desired beneficial properties of the compositions of the invention. For example, these adjuvants may represent 0.01 to 20% of the total weight of the composition. When the composition of the invention is an emulsion, the fatty phase may represent 5 to 80% by weight, preferably 5 to 50% by weight, of the total weight of the composition. The emulsifiers and co-emulsifiers used in the composition will be chosen from those conventionally used in the field under consideration. For example, they may be used in a proportion of 0.3 to 30% by weight, based on the total weight of the composition.

Advantageously, in addition to the active agents of the present invention, the compositions useful for carrying out the present invention may comprise at least one other active agent which provides similar and/or complementary effects to those of the present invention. According to the present invention, the active agent will be defined as "additional active agent".

For example, the additional active agent may be selected from: anti-aging agents, solidifying agents, clarifying agents, moisturizing agents, drainage agents, microcirculation promoting agents, exfoliating agents, desquamating agents, extracellular matrix stimulating agents, energy metabolism activating agents, antibacterial agents, antifungal agents, soothing agents, anti-radiation agents, anti-UV agents, anti-acne agents, anti-inflammatory agents, anesthetic agents, heat-gaining sensates, cold-gaining sensates, weight-reducing agents.

Such additional agents may be selected from:

-vitamin A, in particular retinoic acid, retinol propionate, retinol palmitate,

vitamin B3, more particularly niacinamide, niacin vitamin E,

-vitamin B5, vitamin B6, vitamin B12, panthenol,

vitamin C, in particular ascorbic acid, ascorbyl glucoside, ascorbyl tetrapalmitate, magnesium ascorbyl phosphate and sodium ascorbyl phosphate,

vitamin E, vitamin F, vitamin H, vitamin K, vitamin PP, coenzyme Q10,

-a metalloproteinase inhibitor or a TIMP activator,

DHEA, its precursors and its derivatives,

amino acids, such as arginine, ornithine, hydroxyproline dipalmitate, palmitoylglycine, hydroxylysine, methionine and derivatives thereof, N-acyl amino acid compounds,

natural or synthetic peptides, including di-, tri-, tetra-, penta-and hexapeptides and lipophilic derivatives, isomers thereof, and complexes with other substances such as metal ions (e.g. copper, zinc, manganese, magnesium, etc.). For example, withCOLLAXYL^TM、PEPTIDE VINCI 02^TM、CHRONOGEN^TM、LAMINIXYL IS^TM、PEPTIDE Q10^TMThe name of (a) is a commercially known peptide,

-vegetable peptide extracts, such as extracts of soya, spelt, grapevine, rapeseed, linseed, rice, maize, peas,

-a yeast extract, which is a yeast extract,

-dehydroacetic acid (DHA),

-a synthetic or natural phytosterol,

salicylic acid and its derivatives, alpha-and beta-hydroxy acids, silanols,

-aminosugars, glucosamine, D-glucosamine, N-acetylglucosamine, N-acetyl-D-glucosamine, mannosamine, N-acetylmannosamine, galactosamine, N-acetylgalactosamine,

extracts of polyphenols, isoflavones and flavonoids, such as grape extract, pine extract, olive extract,

lipids, such as ceramides or phospholipids; oils of animal origin, such as squalene or squalane; vegetable oils, such as sweet almond oil, coconut oil, castor oil, jojoba oil, olive oil, rapeseed oil, peanut oil, sunflower oil, wheat germ oil, corn germ oil, soybean oil, cotton oil, alfalfa oil, poppy seed oil, winter squash oil, evening primrose oil, millet oil, barley oil, rye oil, safflower oil, passion flower oil, hazelnut oil, palm oil, almond oil, avocado oil, calendula oil; ethoxylated vegetable oil, shea butter,

all UV filters and sunscreens,

cyclic AMP and its derivatives, activators of adenylate cyclase and inhibitors of phosphodiesterase, Centella asiatica (Centella asiatica) extract, asiaticoside and asiatic acid, methylxanthines, caffeine and its derivatives, theophylline, theobromine, forskolin, esculin and esculoside, ACE inhibitors, peptide Val-Trp, neuropeptide Y inhibitors, enkephalin, biloba (Gingko biloba) extract, dioscorea extract, rutin, mate extract, guarana extract, oligosaccharides, polysaccharides, carnitine, ivy extract, fucus extract, selfheal (unella vulgaris) hydrolyzed extract, cockscomb (Celosia cristata) hydrolyzed extract, elm green (anogeus leiocarpus) extract, cassava (aristo manitis) leaf extract, palmitoyl carnitine, taurine, sudomassia japonica extract, prunus williamsii (prunus wilfordii) extract, prunus japonica (r) extract, prunus japonica extract, prunus salicina (r) extract, prunus sylvestris (prunus salicina), Seaweed extract such as palm Tree (Palmaria Palmata) extract, synthetic peptide of sequence Arg-Gly-Ser-NH2 (by name ATpeptide)^TMSales).

The compositions which can be used according to the invention will be administered by any suitable route, in particular orally or topically, and the person skilled in the art will adapt the formulation of the compositions.

Advantageously, the compositions of the present invention are in a form suitable for topical administration. These compositions must therefore comprise a physiologically acceptable medium, i.e. a medium compatible with the skin and epithelial appendages, and must cover all cosmetic forms.

It will be apparent, of course, that the present invention is directed generally to mammals and more specifically to humans.

Specific embodiments of the cosmetic treatment method are also derived from the previous description. Other advantages and characteristics of the invention will become clearer after reading the examples given for illustrative and non-limiting purposes.

FIG. 1: expression of CIRBP after cold and hot stress in cells treated with or without artemia extract.

FIG. 2: evaluation of IRBP mRNA after cold and hot stress in cells treated with or without artemia extract.

Examples 1 : preparation of artemia salina extract

50 grams of artemia cysts were rehydrated in 1 litre of distilled water at a temperature of 30 ℃ to 75 ℃, in a suitable medium (consisting essentially of water), and at a pH of 4-7, for 30 minutes to 6 hours. These cysts were then ground. The extract thus obtained was centrifuged and filtered. The extract was then sterilized by sterile filtration and heated to 65 ℃.

The extract is then processed to meet cosmetic requirements (color, aroma, appearance, sterility, etc.).

Then, measurement by High Performance Liquid Chromatography (HPLC) was carried out to confirm the diguanosine tetraphosphate content exceeding 150 mg/liter.

Examples 2 : in cells treated or not with the artemia extract according to the invention, after cold and hot stress CIRBP Expression of

The purpose of this study was to determine the effect of pre-treating keratinocytes subjected to hypothermic stress with artemia extract. Specifically, CIRBP (cold-induced RNA binding protein) was determined by western blotting of keratinocytes subjected to moderate hypothermia (32 ℃) with or without pretreatment with the artemia extract of example 1.

The scheme is as follows:the artemia extract of example 1 was treated by adding 1% and 3% to the growth medium of Normal Human Keratinocytes (NHK) from the skin. This administration was repeated once daily for 48 hours. Meanwhile, NHK cultures were maintained untreated to constitute untreated controls. The culture was carried out at 37 ℃.

The NHK cultures, pretreated or not, were then subjected to hypothermic stress by placing them at 32 ℃ for 6 hours. After this incubation, NHK was solubilized to analyze CIRBP expression by western blot. This conventional immunoblotting technique comprises the following steps: the transfer membrane was saturated with 1x TBS/5% milk solution for 1 hour, incubated with the primary antibody cirbp (novusbio) overnight at 4 ℃, and then incubated with the secondary antibody conjugated to peroxidase (Santa Cruz) for 1 hour at ambient temperature. Luminescence was shown by the addition of Substrate (SuperSignal West Dura Extended Duration Substrate, Thermo Scientific) using a camera (Chemi-Imager system, Alpha Inotech Corporation).

As a result:

referring to fig. 1, the results show that CIRBP expression increased by 27% when cells were incubated at 32 ℃ for 6 hours, compared to the control at 37 ℃, and is consistent with bibliographic data.

When cells were pretreated with 1% of the artemia extract of example 1, the CIRBP level was significantly reduced by 17% at 32 ℃ compared to the control at 32 ℃. When cells were pretreated with 3% of the artemia extract of example 1, the CIRBP level was significantly reduced by 28% at 32 ℃ compared to the control at 32 ℃.

And (4) conclusion:

a reduction in CIRBP expression was observed in cells pretreated with 1% or 3% of the artemia extract of example 1 and subjected to cold thermal stress compared to untreated control cells.

Examples 3 : after cold and hot stress CIRBP mRNA Evaluation of (2)

The purpose of this study was to determine whether CIRBP mRNA was modulated by treatment with the artemia extract obtained in example 1 before moderate hypothermic stress (32 ℃). CIRBP mRNA levels were assessed by quantitative PCR (Q-PCR).

The scheme is as follows:normal Human Keratinocytes (NHK) were treated with 1% artemia extract in growth medium. Meanwhile, NHK cultures were maintained untreated to constitute untreated controls. The culture was carried out at 37 ℃. The treated and untreated cultures were then placed at 32 ℃ for 6 hours.

After this incubation, total RNA was extracted with RNeasy mini kit (QIAGEN,74104) and reverse transcribed with high capacity cDNA reverse transcription kit (Applied Biosystems,4368814) containing RNase inhibitor. Quantitative PCR was performed using a Step One Plus thermal cycler (Applied Biosystems). Primers and probes for the target CIRBP and endogenous control 18S were from Taqman Expression Assays (for 18S, Applied Biosystems, Hs99999901_ S1, and CIRBP: Hs00989762_ g1) diluted in sterile water from Master Mix (Applied Biosystems).

As a result:

as presented in figure 2, the results show a significant 59% increase in CIRBP mRNA expression in untreated keratinocytes subjected to moderate hypothermia (32 ℃) compared to controls at 37 ℃.

In the case of keratinocytes treated with 1% artemia extract prior to exposure to hypothermic stress, their CIRBP mRNA levels were increased by 12% compared to keratinocytes pretreated with extract at 37 ℃ and decreased by 33% compared to untreated control keratinocytes at 32 ℃.

And (4) conclusion:

lower levels of CIRBP mRNA were observed in keratinocytes pre-treated with the artemia extract of example 1 and subjected to hypothermia compared to untreated control cells.

Examples 4 : examples 1 The extract of (A) has effect on transdermal water loss (TEWL) Function of

The purpose is as follows:

this study evaluated the protective efficacy of artemia extracts obtained according to example 1 on skin exposed to thermal stress, in particular on the transdermal water loss (TEWL) during thermal/cold stress. Transdermal water loss (TEWL) is a parameter that indirectly reflects the permeability and barrier function of the skin (Toby Mathias et al, 1981). The thermal/cold stress simulates the difference in internal and external temperatures in summer and winter.

The scheme is as follows:

the study was conducted on 19 volunteers aged 21-52 years (including 9 in the "mature" group (ages 48-57) and 10 in the "young" group (ages 21-34)).

According to the volunteers, the skin was normal or dry in nature, free of skin pathology, and phenotypical 2-4.

The test was performed in a double blind method (with 1% of the artemia extract of example 1) and continued for 3 weeks.

The artemia extract and placebo of example 1 were applied 2 times daily (morning and evening) at product concentration on the same area of each thigh.

The amount of product administered was 2mg/cm²。

Thermal stress treatment: first, the heating pad (Electrical heating pad) was applied on the thigh for 10 minutes. Immediately thereafter, an ice pack is applied ((EZY WRAP) ice pack) for 10 minutes.

Use ofThe evaporator (Cortex Technology) evaluates the transcutaneous water loss (TEWL). Measured in g/m²Expressed as/h and interrupted when the standard deviation was 0.1 or after 60 seconds. The measurements were taken under controlled temperature and humidity conditions (21 ℃. + -. 1 and 50%. + -. 5).

The preparation method comprises the following steps:

1) the measurement of the baseline is carried out,

2) the application of the product is carried out by the user,

3) measurements from day 0 to day 21 before stress and day 21 after stress.

To analyze the results, we observed the time at which the plateau of the TEWL measurement was obtained. This time corresponds to the time it takes for the skin to recover (i.e., return to the baseline state after thermal stress). We call this time the "recovery time". We then statistically compared the recovery time of the areas treated with the extract of example 1 with those treated with placebo.

After stress, TEWL measurements were taken every 2 minutes.

As a result:

we note that the areas treated with artemia extract reached the plateau more quickly than the areas treated with placebo.

The recovery time for the areas treated with artemia extract was significantly faster by 27% than for the areas treated with placebo.

And (4) conclusion:

the TEWL values after cold-hot thermal stress returned to normal more rapidly on the area treated with the artemia extract of example 1 compared to placebo. The results indicate that artemia extract helps skin to recover more quickly after heat/cold thermal stress.

Examples 5 : preparation of the composition

1. Protective cream

Preparation method

1. Phase a was homogenized in the main tank.

2. Spray on phase B and homogenize for 10 minutes, then start heating to 50 ℃ and mix well for 30 minutes.

3. The temperature was reduced and phase C was added. Mix well to homogenize.

4. Prepare phase D in a beaker placed on one side, heat to 55-60 ℃ until homogenization, and reduce the temperature.

5. The ingredients of phase E were added one by one to the main tank and mixed thoroughly between each addition.

6. Add phase D (at ambient temperature) to the main vessel and mix until homogeneous.

7. At 25 ℃, add phase F and mix well.

8. Premix phase G and then add it to the main tank.

9. The ingredients of phase H were added one by one with thorough mixing between additions.

10. Stop at 25 ℃.

2. Moisturizing cream for men

Preparation method

1. Phase a was homogenized in the main tank.

2. Spray on phase B and homogenize for 10 minutes until homogeneous.

3. Phase C was prepared in a beaker placed on one side and homogenized until homogeneous. Spray phase D and mix well until homogeneous.

4. Add phase C + D to main vessel at 25 ℃ and mix until homogeneous.

5. Add phase E to the main vessel at 25 ℃ and mix until homogeneous.

6. Add phase C to the main vessel at 25 ℃ and mix until homogeneous.

7. Stop at 25 ℃.

3. Eye cream

Preparation method

1. Water was added to the main tank and heating was started to 80 ℃.

2. Spray onto phase B at 60 deg.C and mix well until homogeneous.

3. Add phase C at 80 ℃, mix well and add phase D.

4. The ingredients of phase E were added to a beaker placed on one side and heated to 75-80 ℃.

5. Phase E was added to the main tank at 80 ℃ and mixed well. The emulsion should be homogeneous.

6. Cooling was started.

7. At 65 ℃, add phase F and mix well.

8. Cool to 30 ℃, add phase G, then phase H, mix well between phases until homogeneous.

9. Stop at 25 ℃.

Claims (5)

1. A cosmetic care method for protecting skin from damage caused by cold thermal stress by maintaining physiological levels of CIRBP, comprising topically applying on at least a portion of the skin of the body or face a composition comprising a physiologically acceptable medium and an Artemia (Artemia salina) extract obtained by a method comprising the steps of: a) rehydrating artemia cysts in distilled water at a temperature of 30-75 ℃ and a pH of 4-7 for 30 minutes to 6 hours, b) then grinding said cysts, and c) centrifuging and filtering the extract thus obtained.

2. A cosmetic care method according to claim 1 for protecting the skin from irritation, dryness or cracking associated with damage caused by cold and thermal stress.

3. Cosmetic care method according to one of claims 1 or 2, wherein the artemia extract is diluted in one or more physiologically suitable solvents selected from the group consisting of water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diethylene glycol, cyclic polyols or any mixture of these solvents.

4. A cosmetic care method according to any one of claims 1 to 3, wherein the artemia extract is present at a concentration of from 0.0001% to 20% by total weight of the composition, and preferably at a concentration of from 0.05% to 5% by total weight of the composition.

5. Cosmetic care method according to any one of claims 1 to 4, wherein the composition additionally comprises at least one additional active agent selected from: vitamin A, retinoic acid, retinol, vitamin B3, vitamin B5, vitamin B6, vitamin B12, vitamin C, vitamin E, vitamin F, vitamin H, vitamin K, vitamin PP, coenzyme Q10, metalloproteinase inhibitors, amino acids, carnitine, carnosine, taurine, natural or synthetic peptides, plant peptide extracts, yeast extracts, natural or synthetic phytosterols, salicylic acid, oligosaccharides, polysaccharides, amino sugars, polyphenols, flavonoids, lipids, phospholipids, cyclic AMP and its derivatives, adenylate cyclase activators and phosphodiesterase inhibitors, caffeine, theophylline, theobromine, forskolin, esculin, ACE inhibitors, yam extract, guarana extract, ivy extract, fucus extract, seaweed extract such as Palmaria Palmata extract, Prunella vulgaris (Prunella vulgaris) hydrolysis extract or elderberry extract.