Use of a polar extract of Skeletonema in photodynamic therapy

Abstract

The invention relates to a dermatological composition for photodynamic treatment comprising at least one polar extract of an algae of the genus Skeletonema or a photosensitizer derived therefrom, preferably for the treatment of acne or bacterial infections; as well as a method for decontaminating a surface using a polar extract of an algae of the genus Skeletonema or a photosensitizer derived therefrom.

Description

Title of the invention: Use of a polar extract of Skeletonema in photodynamic therapy Field of invention

[0001] The present invention relates to a composition intended to be used in photodynamic therapy (PDT) in particular for treating skin disorders such as acne. State of the art

[0002] Acne is associated with an over-secretion of sebum by the sebaceous glands which leads to the obstruction of the pores of the skin. The lesions caused can then be complicated by inflammation, resulting from bacterial proliferation in the sebum associated with Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus pyogenes, Streptococcus agalactiae or Acarus folliculorum.

[0003] During puberty, acne begins when the sebaceous glands mature due to hormonal stimulation by androgens. In adults, acne is the result of stimulation of the sebaceous glands with parallel poor sebum secretion due to makeup or an increase in the synthesis of adrenal corticosteroid hormone due to stress.

[0004] The basic concept of photodynamic therapy (PDT) is the exposure of a photosensitizer to light, which results in the production of singlet oxygen and other reactive oxygen species (ROS) that cause the death of nearby organisms (bacteria that cause inflammation in acne).

[0005] In this acne-associated PDT, the photosensitizer is applied topically to the skin surface. It is then absorbed at the sebaceous gland. The area to be treated is then illuminated using a laser or pulsed light, which illumination allows the activation of the photosensitizer and the genesis of singlet oxygen and ROS. The presence of singlet oxygen, which constitutes a hyper-reactive chemical species, leads to the death of bacteria proliferating in the pores of the skin and localized desquamation of the skin allowing the clogged pores to be freed.

[0006] To be effective, the photosensitizer, when not activated in the absence of photostimulation, must be stable in vivo and exhibit strong photoreactivity after illumination.

[0007] Now, it is important that the photosensitizer preserves, as much as possible, the skin cells and does not increase the inflammation resulting from acne. Summary of the invention:

[0008] The inventors have now demonstrated that a polar extract of Skeletonema marinoï simultaneously exhibits the characteristics of a photosensitizer, an anti-inflammatory and a lipogenesis inhibitor.

[0009] Algae need light to grow and reproduce. To photosynthesize, they absorb light through the pigments in their chloroplasts. They produce oxygen and transform light energy to make their own material.

[0010] Clearly, the compounds of Skeletonema marinoï involved in photosynthesis have particularly interesting properties, notably for the treatment of acne.

[0011] Accordingly, a first subject matter relates to a composition for photodynamic treatment (PDT) comprising at least one polar extract of an algae of the genus Skeletonema or a photosensitizer derived therefrom.

[0012] Preferably, this composition is a dermatological composition.

[0013] Advantageously, this composition may also aim to prevent and / or treat acne in a subject by the topical application of the composition to a skin surface of the subject in combination with light exposure of this skin surface so as to allow the activation of the photosensitizer.

[0014] More broadly, this composition may aim to prevent and / or treat a bacterial infection in a subject by the topical application of the composition to an epithelium surface of the subject in combination with light exposure of this epithelium surface so as to allow the activation of the photosensitizer.

[0015] A second subject relates to a photodynamic treatment method which comprises the steps of:

[0016] 1) topical application to an epithelium surface of a subject of a therapeutic amount possibly effective of a composition as described above; and

[0017] 2) light exposure of this epithelium surface so as to allow activation of the photosensitizer.

[0018] Advantageously, the photodynamic treatment aims to prevent and / or treat acne in a subject.

[0019] Advantageously, the photodynamic treatment aims to prevent and / or treat a bacterial infection in a subject.

[0020] A third subject of the invention relates to a cosmetic treatment method for eliminating skin imperfections such as comedones and / or blackheads comprising the steps of:

[0021] 1) topical application to an epithelium surface of a subject of an effective amount of a composition as previously described; and

[0022] 2) light exposure of this epithelium surface so as to allow activation of the photosensitizer.

[0023] A fourth object of the invention relates to a kit intended for photodynamic treatment, which comprises:

[0024] 1) a composition as described above; and

[0025] 2) a light source.

[0026] A fifth subject of the invention relates to a method for decontaminating a surface, which method comprises at least the steps of:

[0027] 1) application of an effective amount of at least one polar extract of an algae of the genus Skeletonema or a photosensitizer derived therefrom; and

[0028] 2) light exposure of this surface so as to allow the activation of the photo sensitizer.

[0029] Advantageously, this method is used in hospital hygiene. In this context, the surface to be decontaminated is a surface of medical devices, prostheses or implants.

[0030] Advantageously, this process is used in the food industry and the surface to be decontaminated is a food surface (meat, fish, etc.), a metal surface (machine, work surface, etc.), a floor or even a wall.

[0031] A sixth subject of the invention relates to a method of photocoagulation of a wound of a subject, which method comprises at least the steps of:

[0032] 1) application of an effective amount of at least one polar extract of an algae of the genus Skeletonema or a photosensitizer derived therefrom on the surface of a wound of the subject; and

[0033] 2) light exposure of this surface so as to allow the activation of the photo sensitizer. Detailed description of the invention

[0034] Algae of the genus Skeletonema are unicellular algae which are also diatoms (Bacillariophytd).

[0035] As an example of such algae, we can cite in particular Skeletonema ardens, Skeletonema barbadense, Skeletonema costatum, Skeletonema cylindraceum, Skeletonema denticulatum, Skeletonema dohmii, Skeletonema grethae, Skeletonema grevillei, Skeletonema japonicum, Skeletonema marinoi, Skeletonema mediterraneum, Skeletonema menzelii, Skeletonema mirabile, Skeletonema potamos, Skeletonema probabile, Skeletonema pseudocostatum, Skeletonema simbirskianum Skeletonema subsalum, Skeletonema tropicum, Skeletonema utriculosa and Skeletonema ventricosum.

[0036] Preferably, the alga of the genus Skeletonema is selected from the group comprising Skeletonema costatum, Skeletonema grethae, Skeletonema marinoi, Skeletonema menzellii and Skeletonema subsalsum.

[0037] Particularly preferably, the algae of the genus Skeletonema corresponds to Skeletonema marinoï which is a relatively common species in the Atlantic (it is often the major species in coastal waters in the Atlantic). The cells of this species remain attached to each other after cell divisions. Also, the algae of this species appear in the form of chains of 3 to 15 cells.

[0038] By "polar extract of an algae of the genus Skeletonema", we mean a composition obtained by an extraction carried out on an algae of the genus Skeletonema by a polar solvent.

[0039] By "polar solvent" is meant a solvent consisting of molecules having a dipole moment. This polar solvent can be protic or aprotic depending on whether or not it is capable of releasing acidic H+ ions.

[0040] As examples of aprotic polar solvent, mention may be made of ketones (e.g. acetone or butanone), sulfoxides (e.g. DMSO), N,N disubstituted amides (N,N dimethyl formamide), nitriles (e.g. acetonitrile), esters (e.g. ethyl acetate), tertiary amines (e.g. triethylamine), nitrogen heterocycles (e.g. pyridine).

[0041] Examples of protic polar solvents include water, alcohols, carboxylic acids (e.g. formic acid and acetic acid) or primary and secondary amines.

[0042] Preferably, the polar solvent used will be a protic polar solvent and, among them, it will be preferred to use an alcohol.

[0043] Among the alcohols that can be used, mention may be made of methanol, ethanol, or even isopropanol, with a preference for ethanol and isopropanol.

[0044] The polar extract of an algae of the genus Skeletonema used will preferably be a polar extract obtained from a microalgae having undergone a prior step of cell lysis.

[0045] Such a cell lysis step can be carried out simply by freezing / thawing (preferably at a temperature below -20°C), by microwave treatment or by ultrasound treatment of this algae.

[0046] The polar extract of an algae of the genus Skeletonema results from a maceration of this algae in the polar solvent for a period of at least 5 minutes, preferably at least 10 minutes. Typically, this maceration time is less than 24 hours, preferably less than 12, or even less than 6 hours. For example, such a polar extract of the algae of the genus Skeletonema will be obtained by maceration of this algae in the polar solvent for a period of between 10 and 60 minutes, preferably between 20 and 40 minutes. Ideally, this maceration with a polar solvent at room temperature or less so as to preserve as much as possible the photosensitizers of the polar extract obtained.

[0047] As for this polar extract of an algae of the genus Skeletonema still, it results from an extraction using at least 1 mL of polar solvent per gram of microalgae (expressed as dry weight), preferably at least 10 mL of polar solvent per gram of microalgae and, particularly preferably, at least 20 mL of polar solvent per gram of microalgae. For example, the polar extract of an alga of the genus Skeletonema is obtained using between 1 and 200 mL of polar solvent per gram of microalgae (expressed as dry weight), preferably between 10 and 100 mL of polar solvent per gram of microalgae and, particularly preferably, between 20 and 50 mL of polar solvent per gram of microalgae (expressed as dry weight).

[0048] Advantageously, the polar extract of an algae of the genus Skeletonema will have undergone at least one filtration (e.g. 0.2 pm, 0.4 pm or other filter) and / or at least one centrifugation (with recovery of only the supernatant) following the extraction.

[0049] By "photosensitizer derived from a polar extract of an alga of the genus Skeletonema" is meant a compound purified from a polar extract of an alga of the genus Skeletonema (e.g. by HPLC) or a compound present in a polar extract of an alga of the genus Skeletonema which, when activated by light, allows the production of singlet oxygen and ROS

[0050] The content of extract of an algae of the genus Skeletonema in the composition for a photodynamic treatment is between 0.001% and 5% (by dry weight of extract relative to the total weight of the composition), preferably between 0.01% and 2% and, particularly preferably, between 0.1% and 1%.

[0051] When preparing the composition of the invention, the integration of the polar extract will preferably be carried out under an inert atmosphere (e.g. nitrogen or argon) and / or in the dark. Such integration conditions make it possible to best protect the active molecules of the extract.

[0052] As regards the form of the composition, it can take any desirable form depending on the desired mode of administration. Now, the composition is preferably applied to an epithelial surface such as the skin. Also, it will preferably take the form of a dermatological composition such as an ointment, a cream, a lotion or even a gel.

[0053] Preferably, the composition may further comprise at least one antioxidant agent. As examples of antioxidant agents that can be used in such a composition, mention may be made of provitamins A, vitamin C, vitamin E, polyphenols or lycopene. Preferably, a provitamin A, vitamin C or vitamin E will be chosen.

[0054] Now and generally, this composition may comprise numerous types of adjuvants or active ingredients used in pharmaceutical or cosmetic formulations, preferably dermatological, whether fatty substances, organic solvents, thickeners, gelling agents, softeners, antioxidants, opacifiers, stabilizers, foaming and / or detergent surfactants, emollients, superfatting agents, perfumes, ionic or non-ionic emulsifiers, fillers, sequestering agents, chelators, preservatives, essential oils, coloring matters, pigments, hydrophilic or lipophilic active ingredients, humectants, such as glycerin or glycols, preservatives, colorants, cosmetic active ingredients, mineral and / or organic sunscreens, mineral fillers, synthetic fillers, silicone elastomers, or plant extracts or lipid vesicles, or any other ingredient usually used in cosmetics.

[0055] Examples of oils include paraffins, isoparaffins, white mineral oils, vegetable oils (from flowers, fruits, vegetables, trees, cereals, oilseeds, etc.), animal oils, synthetic oils, silicone oils and fluorinated oils;and more particularly: oils of vegetable origin, 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, cottonseed oil, alfalfa oil, poppy seed oil, pumpkin oil, evening primrose oil, millet oil, barley oil, rye oil, safflower oil, candlenut oil, passionflower oil, hazelnut oil, palm oil, shea butter, apricot kernel oil, calophyllum oil, sisymbra officinalis oil, avocado oil, calendula, oils from flowers or vegetables; ethoxylated vegetable oils; oils of animal origin, such as squalene, squalane; mineral oils, such as paraffin oil, vaseline oil and isoparaffins;synthetic oils, including fatty acid esters such as butyl myristate, propyl myristate, cetyl myristate, isopropyl palmitate, butyl stearate, hexadecyl stearate, isopropyl stearate, octyl stearate, isocetyl stearate, dodecyl oleate, hexyl laurate, propylene glycol dicaprylate;esters derived from lanolic acid, such as isopropyl lanolate, isocetyl lanolate, monoglycerides, diglycerides and triglycerides of fatty acids such as glycerol triheptanoate, alkylbenzoates, polyalphaolefins, polyolefins such as polyisobutene, synthetic isoalkanes such as isohexadecane, isododecane, perfluorinated oils and silicone oils. Among the latter, we can more particularly cite dimethylpolysiloxanes, methylphenylpolysiloxanes, silicones modified by amines, silicones modified by fatty acids, silicones modified by alcohols, silicones modified by alcohols and fatty acids, silicones modified by polyether groups, modified epoxy silicones, silicones modified by fluorinated groups, cyclic silicones and silicones modified by alkyl groups.

[0056] As other fatty substances, mention may be made of linear or branched, saturated or unsaturated fatty alcohols, mixtures of linear and / or branched, saturated and / or unsaturated fatty alcohols, or linear or branched, saturated or unsaturated fatty acids, mixtures of linear or branched, saturated or unsaturated fatty acids.

[0057] Among the thickening and / or emulsifying polymers that can be used, there are, for example, homopolymers or copolymers of acrylic acid or acrylic acid derivatives, homopolymers or copolymers of methacrylic acid or methacrylic acid derivatives, homopolymers or copolymers of acrylamide, homopolymers or copolymers of acrylamide derivatives, homopolymers or copolymers of acrylamidomethyl propanesulfonic acid, homopolymers or copolymers of vinyl monomers, homopolymers or copolymers of trimethylaminoethylacrylate chloride, hydrocolloids of plant or biosynthetic origin such as, for example, xanthan gum, karaya gum, carrageenans, alginates; silicates; cellulose and its derivatives; starch and its hydrophilic derivatives; polyurethanes.

[0058] Among the polyelectrolyte type polymers that can be used in the production of a gelled aqueous phase suitable for use in the preparation of W / O, O / W, W / O / W or O / W / O emulsions, or of an aqueous gel comprising SEPIBIO™ POTENTILLA 217, there are, for example, copolymers of acrylic acid and 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid (AMPS), copolymers of acrylamide and 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid, copolymers of 2-methyl-[(1-oxo-2-propenyl)amino] 1-propane sulfonic acid and (2-hydroxyethyl)acrylate, 2-methyl-[(l-oxo-2-propenyl)amino]-1-propanesulfonic acid homopolymer, acrylic acid homopolymer, copolymers of acryloyl ethyl trimethyl ammonium chloride and acrylamide, copolymers of AMPS and vinylpyrrolidone, copolymers of AMPS and N,N-dimethylacrylamide., terpolymers of AMPS, acrylic acid and N,N-dimethylacrylamide, copolymers of acrylic acid and alkyl acrylates whose carbon chain comprises between ten and thirty carbon atoms, copolymers of AMPS and alkyl acrylates whose carbon chain comprises between ten and thirty carbon atoms.

[0059] Among the waxes that can be used in the compositions according to the invention, mention may be made, for example, of beeswax, carnauba wax, Candelilla wax, Ouricoury wax, Japanese wax, Chinese wax, rice bran wax, Montan wax, cork or sugar cane fiber wax, paraffin waxes, lignite waxes, microcrystalline waxes, lanolin wax, ozokerite, polyethylene wax, hydrogenated oils, silicone waxes, alkenone waxes, vegetable waxes, fatty alcohols and fatty acids that are solid at room temperature, glycerides that are solid at room temperature, and glycerides that are solid at room temperature. room temperature.

[0060] Among the emulsifiers that can be used in the compositions according to the invention, mention may be made of:

[0061] - fatty esters of alkylpolyglycosides, optionally alkoxylated;

[0062] - alkoxylated fatty esters;

[0063] - fatty chain polyalkylene glycol carbamates;

[0064] - fatty acids, ethoxylated fatty acids, fatty acid esters of sorbitol, ethoxylated fatty acid esters, polysorbates, polyglycerol esters, ethoxylated fatty alcohols, sucrose esters, alkylpolyglycosides, sulfated and phosphated fatty alcohols or mixtures of alkylpolyglycosides and fatty alcohols;

[0065] - combinations of emulsifying surfactants chosen from alkylpoly glycosides;

[0066] - combinations of alkylpolyglycosides and fatty alcohols, polyglycerol esters or polyglycols or polyols.

[0067] Among the surfactants which can be used in the compositions according to the invention, mention may be made of: topically acceptable anionic, cationic, amphoteric or non-ionic surfactants usually used in this field of activity.

[0068] Among the anionic surfactants which can be used in the compositions according to the invention, mention will be made in particular of the alkali metal salts, the alkaline earth metal salts, the ammonium salts, the amino acid salts, the amino alcohol salts of the following compounds: alkyl ether sulfates, alkyl sulfates, alkylamidoether sulfates, alkylarylpolyether sulfates, monoglyceride sulfates, alpha-olefinsulfonates, paraffin sulfonates, alkylphosphates, alkyletherphosphates, alkylsulfonates, alkylamidesulfonates, alkylarylsulfonates, alkylcarboxylates, alkylsulfosuccinates, alkylethersulfosuccinates, alkylami-desulfosuccinates, alkylsulfoacetates, alkylsarcosinates, acylisethionates, N-acyltaurates, acyllactylates.

[0069] Among the amphoteric surfactants which can be used in the compositions according to the invention, mention may be made of alkylbetaines, alkylamidobetaines, sultaines, alkylamidoalkylsulfobetaines, imidazoline derivatives, phosphobetaines, amphopolyacetates and amphopropionates.

[0070] In order to further potentiate the activity obtained by the composition according to the invention, it may be combined with other active ingredients, in particular those known for their anti-aging, firming, restructuring, stimulating, energizing, anti-wrinkle, relaxing, moisturizing, antimicrobial, sebum-regulating, purifying, soothing, relaxing, decontracting, anti-stress, lightening, immunomodulating, cell renewal stimulating, lifting, plumping, complexion radiance improving action, etc.

[0071] With regard to the light exposure of the area to be treated allowing activation of the photosensitizer present in this extract, it is an exposure to a light wave having a wavelength between 400 and 800 nm, preferably between 450 and 700 nm, and an intensity (fluence) between U / cm2 and 100 J / cm2, preferably between 1 and 10 J / cm2.

[0072] Such a light wave can be obtained by means of a laser, pulsed light, or even LEDs. In the context of therapeutic use and, in particular, dermatological use, the use of LEDs will be preferred in view of the absence of heating undergone by the subject's cells so as to limit the damage suffered by his dermis and his epidermis. Now, such a light wave could possibly also correspond to daylight.

[0073] The exposure time will be between 1 minute and 2 hours, preferably between 1 and 30 minutes, or even between 1 and 10 minutes and, particularly preferably, between 2 and 5 minutes.

[0074] The demonstration of a photosensitizing activity associated with the polar extract of Skeletonema makes its use in any type of photodynamic treatment (PDT) possible.

[0075] By "photodynamic treatment" is meant a treatment by light exposure of the composition, after its application, so as to allow the activation of the photosensitizer present in the polar extract of an algae of the genus Skeletonema.

[0076] Multiple photodynamic treatments are conceivable, such as, for example, the treatment of acne, the treatment of bacterial infections of the skin or gums, the treatment of hirsutism by the destruction of follicles, the treatment of baldness by stimulation of the scalp in areas of hair loss, the treatment of inflammatory keratoses, the treatment of pre-melanoma dermal areas, the treatment of psoriasis, the treatment of benign skin conditions such as port-wine stains, warts, the treatment of different forms of hydros adenitis such as suppurative hydradenitis, Verneuil's disease, or even an anti-angiogenic treatment, in particular that of rosacea.

[0077] Preferably, the dermatological composition is aimed at the treatment of acne in a subject by the topical application of the composition to a skin surface of the subject in combination with light exposure of this skin surface so as to allow the activation of the photosensitizer present in the extract.

[0078] In relation to acne, this can correspond just as well to acne vulgaris, polymorphic acne, nodulocystic acne, acne conglobata as to secondary acne (e.g. solar acne or acne associated with treatment).

[0079] Now, the composition according to the invention can also aim at the prevention and / or treatment of a bacterial infection in a subject by the topical application of the composition on an epithelium surface of the subject in combination with an exposure light from this epithelium surface so as to allow the activation of the photosensitizer present in the extract.

[0080] For example, we can notably cite the prevention or treatment of gingivitis (inflammation of the gums resulting from a bacterial infection) or periodontitis (inflammation of the periodontium resulting from a bacterial inflammation), the prevention of a bacterial infection of the skin such as angular cheilitis, intertrigo, erysipelas, impetigo, or even whitlow.

[0081] Preferably, the bacterial infection is a Gram-positive bacterial infection.

[0082] The epithelium surface on which the dermatological composition is applied may correspond to the gum (gingivitis or periodontitis) or to a skin surface, such as the face, trunk, legs, back or fingers, preferably the face.

[0083] As for the subject, it is a mammal, preferably a human.

[0084] In the case of acne treatment, the subject will typically be between 10 and 20 years old. Now, since acne can appear around 7-8 years old and persist after 20 years, the subject could be younger than 10 years old and older than 20 years old.

[0085] The composition according to the invention is applied to the affected epithelial surface (skin, gum, etc.) at least once a day.

[0086] The combination of the application of the composition according to the invention and the light exposure is carried out for at least one week to obtain the best effectiveness and, preferably over a period of between 4 and 12 weeks.

[0087] In connection with the photodynamic treatment method according to the invention, the latter naturally uses the composition as described previously.

[0088] Photodynamic treatment corresponds to one of the treatments considered previously.

[0089] Advantageously, the method according to the invention aims to prevent and / or treat acne in a subject.

[0090] Advantageously, the method according to the invention aims to prevent and / or treat a bacterial infection in a subject.

[0091] By "therapeutically effective amount" is meant an amount sufficient to achieve the desired biological effect.

[0092] Now in connection with the cosmetic treatment method according to the invention, the latter also uses the composition as described previously.

[0093] For this one, the subject is as previously considered.

[0094] Advantageously, this aims to eliminate comedones and / or blackheads.

[0095] Now concerning the kit according to the invention, this comprises, in addition to the composition as described previously, a light source capable of inducing the activation of the photosensitizer present in the algae extract.

[0096] Typically, such a light source emits light radiation having a wavelength of between 400 and 800 nm, preferably between 450 and 700 nm, with an intensity (fluence) of between U / cm2 and 100 J / cm2, preferably between 1 and 10 J / cm2.

[0097] Such a light source is typically chosen from a laser, pulsed light, or even an LED, preferably between pulsed light and an LED.

[0098] Now concerning the process of decontaminating a surface, this can be aimed at food (agri-food) or hospital use. In the medical field, it is possible to sterilize medical devices, prostheses, implants or other. In the agri-food field, it can then be used for the decontamination of a food surface (meat, fish, etc.) and we will then speak of conservation, the decontamination of a metal surface (machine, work surface, etc.), or that of a floor or even a wall.

[0099] In the case of the method according to the invention, it will be preferable to use a formulation of the extract allowing its vaporization on the surface to be decontaminated. In this respect, a spray-type formulation constitutes a particularly suitable formulation.

[0100] The invention will be better understood in light of the following examples, which are given purely for illustrative purposes and are not intended to limit the scope of the invention, defined by the appended claims. Examples

[0101] Example 1: Obtaining a polar extract from an algae of the genus Skeletonema:

[0102] Preferably, the entire extraction is carried out under an inert atmosphere (nitrogen saturation) in order to avoid pronounced degradation of the active molecules.

[0103] For this extraction we use 10 grams of biomass (Skeletonema marinoï).

[0104] Preferably, the algae are frozen at -20°C before being immersed in 400 mL of ethanol with stirring at room temperature for at least one hour (typically 4 hours).

[0105] After this maceration step, the extract is then centrifuged to remove the pellet containing the silica in particular, then the supernatant is filtered (e.g. 0.2 pm filter).

[0106] Finally, an extract is obtained with approximately 40 ml per gram of material.

[0107] The polar extract obtained is then analyzed by HPLC chromatography (UV-DAD) using a C18 column. The elution gradient used, at a flow rate of ImL / min, is presented in Table 1 below.

[0108] [Tableauxl] Time (min) %Methanol / water (80 / 20) %Acetonitrile / water (90 / 10) %Ethyl acetate (100) 0 100 0 0 3 0 100 0 35 0 30 70 38 0 0 100 41 0 0 100 43 0 100 0 45 100 0 0 47 100 0 0

[0109] The absorption analysis of the elution fractions shows numerous absorbance peaks.

[0110] Example 2: Antibacterial action of a polar extract of an algae of the genus Ske-letonema:

[0111] The antibacterial activity of the obtained polar extract is then tested in an agar diffusion test on the following strains: Cutibacterium acnes (CIP 53.117T), Staphylococcus aureus (CIP76.25), Staphylococcus epidermidis (CIP109.562).

[0112] For each strain, a 1 / 10 dilution of a bacterial suspension taken in the exponential growth phase is carried out. 1 mL of diluted bacterial suspension is inoculated onto nutrient agar in a Petri dish, then deposition zones are created in the agar.

[0113] These drop zones are filled with:

[0114] - 50pl of polar extract diluted to 1 / 20th

[0115] - 50pl of polar extract diluted to 1 / 2

[0116] - 50pl of gentamicin, as a control of the correct functioning of the test, the antibiotic having proven biological activity on the strains tested

[0117] - 50pl of nutrient medium, supplemented with ethanol as a solvent control (noted “And5%”).

[0118] After depositing the solutions, the Petri dishes are subjected or not to illumination with light sources delivering either white light (total fluence of 25 J / cm2), or red light (total fluence of 37.5 J / cm2). A condition without illumination is carried out to determine whether the extract has antibacterial activity (toxicity) or not, in the absence of illumination.

[0119] The antibacterial activity is revealed by the presence of an inhibition zone of growth around sample deposition areas.

[0120] The results under white light are presented in Table 2 below.

[0121] [Tables2] Bacterial growth inhibition C. acnes S. aureus S. epidermidis With illumination Polar extract 1 / 2 ++ ++ ++ Polar extract l / 20th + + + Gentamicin ++ ++ +++ Solvent control - - - Without illumination Polar extract 1 / 2 + / - + / - + / - Polar extract l / 20th - - - Gentamicin ++ ++ ++ Solvent control - - -

[0122] The results under red light are presented in Table 3 below.

[0123] [Tables3] Inhibition of bacterial growth C. acnes S. aureus S. epidermidis With illumination Polar extract 1 / 2 ++ + ++ Polar extract 1 / 20th + + + Gentamicin + +++ +++ Without illumination Polar extract 1 / 2 + + / - + / - Polar extract 1 / 20th - - - Gentamicin ++ ++ +++

[0124] As expected, the results show a zone of inhibition of bacterial growth for each strain with gentamicin whether without illumination or with illumination with white or red light. Similarly, no inhibition of bacterial growth is observed in relation to the negative control whether with or without illumination. As for the polar extract of the alga Skeletonema marinoï, little or no inhibition of bacterial growth is observed in the absence of illumination. On the other hand, an inhibition of bacterial growth of S. aureus, S. epidermidis and C. acnes is observed, which is all the stronger as the extract is less diluted.

[0125] In conclusion, the results show that the polar extract does not have antibiotic activity or toxicity against bacterial models in the dark. On the other hand, the extract is indeed photoactivatable since it generates growth inhibition zones in both white and red light. In addition, there is a dose effect since a greater growth inhibition zone is observed with the extract diluted to 20th compared to the extract diluted to half.

[0126] The same experiments are carried out for polar extracts obtained by the same protocol, but from cultures of

[0127] Example 3: Determination of the MIC (Minimum Inhibitory Concentration) and the MBC (Minimum Bactericidal Concentration) of a polar extract of an algae of the genus Skeletonema:

[0128] The MIC and MBC of the polar extract are determined by a 96-well plate micromethod. The MIC of the extract corresponds to the smallest concentration of polar extract sufficient to inhibit the growth of a bacterial strain. The MBC of the extract corresponds to the smallest concentration of extract sufficient to kill 99.99% of the bacteria in the initial inoculum. Bacteria (C. acnes, S. aureus, etc.) in the exponential growth phase are incubated in the presence of different concentrations of the polar extract. The bacteria in the presence of the polar extract are then subjected to illumination, either white light (total fluence of 25 J / cm2) or red light (total fluence of 37.5 J / cm2). A condition without illumination is carried out to determine whether the polar extract has antibacterial activity (toxicity) or not, in the absence of illumination (darkness).After the illumination period, the 96-well plates are then incubated in an oven, respecting the optimal conditions for bacterial growth.

[0129] The results under white light are presented in Table 4 below. The MIC and CMB results are expressed in pg / ml of polar extract.

[0130] [Tables4] MIC CMB S.aureus 62.5 62.5 C. Acnes 6.25 6.25

[0131] The results under red light are presented in Table 5 below. The MIC and CMB results are expressed in pg / ml of polar extract.

[0132] [Tables5] MIC CMB S.aureus 125 1000 C. acnes 125 < 1000

[0133] The results without illumination are presented in Table 6 below. The MIC and CMB results are expressed in pg / ml of polar extract.

[0134] [Tableauxô] MIC CMB S.aureus 250 < 1000 C. acnes < 1000 < 1000

[0135] The results confirm that photosensitizers in Skeletonema polar extract are responsible for inhibition of bacterial growth and lysis bacterial observed. Now, however, it appears that other compounds in this extract also contribute, but slightly, to the inhibition of S. aureus growth (cf. [Table 6]).

[0136] Example 4: Anti-inflammatory activity of the polar extract of an algae of the genus Skeletonema

[0137] Human epidermal keratinocytes NHEK are cultured at 37°C in the presence of 5% CO2 and antibiotics in a dedicated culture medium. After at least one day of culturing, the NHEK cells are pre-incubated in the presence or absence of different concentrations of the polar extract. As a positive control for anti-inflammatory activity, the NHEK cells are incubated in the presence of bafi-lomycin. The NHEK cells are then incubated for 24 hours in the presence of poly (I:C) so as to induce inflammation. The level of inflammation of the keratinocytes is then determined by ELISA by measuring the amounts of IL-6 and IL-8 secreted.

[0138] Example 5: Sebum synthesis inhibition activity

[0139] SEBO662AR human sebocytes are cultured at 37°C in the presence of 5% CO2 and antibiotics in a dedicated culture medium. After at least one day of culture, lipogenesis is induced in the SEBO662AR cells by their incubation in the presence of lipogenic and androgenic factors. The cells are then incubated in the presence or absence of 3 distinct concentrations of the polar extract. As a positive control for lipogenesis inhibitory activity, the SEBO662AR cells are incubated in the presence of cerulenin. At the end of the incubation period, total lipids are fluorescently labeled and the inhibition of lipogenesis is determined for each condition.

Claims

Claims

1. A dermatological composition comprising at least one polar extract of an algae of the genus Skeletonema in combination with light exposure for use in a photodynamic treatment of acne or a bacterial infection in a form suitable for topical application of the composition to a skin surface.

2. The composition according to any one of the preceding claims, characterized in that the alga of the genus Skeletonema is selected from the group comprising Skeletonema ardens, Skeletonema barbadense, Skeletonema costatum, Skeletonema cylindraceum, Skeletonema denticulatum, Skeletonema dohmii, Skeletonema grethae, Skeletonema grevillei, Skeletonema japonicum, Skeletonema marinoi, Skeletonema mediterraneum, Skeletonema menzelii, Skeletonema mirabile, Skeletonema potamos, Skeletonema probabile, Skeletonema pseudo-costatum, Skeletonema simbirskianum Skeletonema subsalum, Skeletonema tropicum, Skeletonema utriculosa and Skeletonema ventricosum.

3. The composition according to any one of the preceding claims, characterized in that the polar extract of an alga of the genus Skeletonema is obtained by an extraction carried out with an alcohol, preferably with ethanol or isopropanol.

4. The composition according to any one of the preceding claims, characterized in that the content of extract of an algae of the genus Skeletonema in the composition for photodynamic treatment is between 0.001% and 5% by dry weight of extract relative to the total weight of the composition, preferably between 0.01% and 1%.

5. The composition according to any one of the preceding claims, characterized in that the light exposure of the area to be treated so as to allow the activation of the photosensitizer present in this extract corresponds to an exposure to a light wave having a wavelength between 400 and 800 nm, preferably between 450 and 700 nm.

6. The composition according to any one of the preceding claims, characterized in that the light exposure of the area to be treated so as to allow the activation of the photosensitizer present in this extract corresponds to an exposure to a light wave having an intensity (fluence) of between U / cm2 and 100 J / cm2, preferably between 1 and 10 J / cm2.