Glutamine / tannic acid complexes and the use of same in the treatment of pigmentation spots

Abstract

The invention relates to a glutamine / tannic acid complex and to a pharmaceutical or cosmetic composition comprising said complex. The present invention also relates to said complex as well as to said composition for use in the prevention and / or treatment of dermatological lesions in a patient, as well as to the use thereof in a cosmetic method for the prevention and / or treatment of pigmentation spots in a subject.

Description

[0001] GLUTAMINE - TANNIC ACID COMPLEXES AND THEIR USE IN THE TREATMENT OF PIGMENTED SPOTS

[0002] Field of invention

[0003] The present patent application relates to a glutamine-tannic acid complex, as well as to a pharmaceutical or cosmetic composition comprising said complex. The present invention also relates to said complex as well as to said composition for use in the prevention and / or treatment of dermatological lesions in a patient, as well as its use in a cosmetic method for the prevention and / or treatment of pigment spots in a subject.

[0004] Back-

[0005] Glutamine (L-glutamine) is the most abundant free amino acid in human plasma. Although classified as a non-essential amino acid, glutamine can become so under severe stress conditions in which intracellular and plasma glutamine concentrations can decrease by more than 50% and 30%, respectively (Kovacevic Z., McGivan J. Mitochondrial metabolism of glutamine and glutamate and its physiological significance. Physiol Rev. 1983;63:547-605).

[0006] Glutamine is also known to play an important role in the treatment of dermatological conditions, and is particularly involved in collagen synthesis. In this context, glutamine accelerates and promotes the restructuring of damaged skin cells, thus ensuring good health.

[0007] However, unlike other amino acids, glutamine is unstable in solution, which limits its use in topical formulations, whether for cosmetic or therapeutic purposes.

[0008] Another obstacle to the use of glutamine in topical formulations is its low solubility. Indeed, the solubility of glutamine at 20°C is only about 25 grams per liter of distilled water.

[0009] There is therefore a need to provide stabilized forms of glutamine with an extended shelf life and sufficient solubility in aqueous solvents to enable the preparation of industrially acceptable cosmetic and therapeutic formulations. Furthermore, these new stabilized forms must also be able to be produced simply and at a reasonable cost. Summary of the invention

[0010] The inventors have surprisingly discovered that the present invention addresses the above-mentioned problems.

[0011] According to a first aspect, the present invention relates to a glutamine - tannic acid complex, in which the tannic acid : glutamine molar ratio is between 1 : 1 and 1 : 6.

[0012] Preferably, the glutamine - tannic acid complex according to the invention has a tannic acid : glutamine molar ratio of between 1 : 1 and 1 : 5. In other words, preferably, the present invention relates to a glutamine - tannic acid complex, in which the tannic acid : glutamine molar ratio is between 1 : 1 and 1 : 5.

[0013] Preferably, the glutamine-tannic acid complex according to the invention has a tannic acid:glutamine molar ratio of between 1:3 and 1:6. In other words, preferably, the present invention relates to a glutamine-tannic acid complex, in which the tannic acid:glutamine molar ratio is between 1:3 and 1:6.

[0014] Even more preferably, the glutamine-tannic acid complex according to the invention has a tannic acid:glutamine molar ratio of 1:5. In other words, even more preferably, the present invention relates to a glutamine-tannic acid complex, in which the tannic acid:glutamine molar ratio is 1:5.

[0015] According to another aspect, the present invention relates to a composition comprising a therapeutically or cosmetically active amount of the glutamine - tannic acid complex according to any one of the preceding claims and at least one pharmaceutically or cosmetically acceptable excipient.

[0016] According to another aspect, the present invention also relates to a non-therapeutic use of the glutamine - tannic acid complex or of the composition comprising said complex, for the treatment or prevention of pigment spots.

[0017] According to another aspect, the present invention relates to the glutamine-tannic acid complex or the composition comprising said complex for use as a medicament, in particular in the treatment and / or prevention of dermatological lesions in a patient. detailed description of the invention

[0018] The term “comprising,” as used in the context of the invention, should not be construed as being limited to the means listed thereafter; it does not exclude the presence of other elements or steps. It should be interpreted as specifying the presence of the listed features, elements, steps, or components referred to, but does not exclude the presence or addition of one or more other features, elements, steps, or components, or groups thereof. Thus, the scope of the expression “a composition comprising A and B” should not be limited to the composition composed solely of A and B. This means that, in the context of the present invention, the only relevant elements are A and B. Accordingly, the terms “comprising” and “including” encompass the more restrictive terms “consisting essentially of” and “consisting of.”

[0019] In the context of the present invention, the terms "glutamine" and "L-glutamine" are used interchangeably to refer to the alpha amino acid used in protein biosynthesis.

[0020] In the context of the present invention, the term "tannic acid" has the usual meaning known in the art. Tannic acid, also known as tannin, gallotannin, gallotannic acid or digallic acid, occurs as a yellow to brownish amorphous powder, having an approximate composition corresponding to the formula C76H52O46 and a molecular weight of about 1701 grams / mole. Although tannic acid is typically extracted from gall nuts, it can be produced from the bark and fruits of many plants. Tannic acid is very soluble in water, glycerin and alcohol. Tannic acid can be obtained either by extraction from natural products or by chemical synthesis.

[0021] In the context of the present invention, the terms "patient" and "subject" include humans as well as other animals.

[0022] In the context of the present invention, the term "therapeutically active amount" means the amount of a pharmaceutically active ingredient that will elicit the biological or medical response in a tissue or system, animal or human, as sought by a researcher, physician, veterinarian or other clinical practitioner (e.g., reduction of dermatological lesions).

[0023] In the context of the present invention, the term "cosmetically active amount" means the amount of a cosmetically active ingredient that will elicit the cosmetic response in a tissue or system, animal or human, as sought by a researcher, physician, veterinarian or other clinical or aesthetic practitioner (e.g., reduction of pigment spots).

[0024] In the context of the present invention, the terms "composition", "pharmaceutical composition" and "cosmetic composition" refer to both the raw compositions and the individual dosage units comprising the active ingredient and at least one excipient, for example the glutamine - tannic acid complex and at least one (for example two) excipient(s).

[0025] In the context of the present invention, the terms "prevent" or "prevention" refer to the administration of a compound or composition before the onset of symptoms.

[0026] The present invention relates to a glutamine-tannic acid complex, in which the tannic acid:glutamine molar ratio is between 1:1 and 1:6.

[0027] Preferably, the glutamine - tannic acid complex according to the invention has a tannic acid : glutamine molar ratio of between 1 : 1 and 1 : 5. In other words, preferably, the present invention relates to a glutamine - tannic acid complex, in which the tannic acid : glutamine molar ratio is between 1 : 1 and 1 : 5.

[0028] Preferably, the glutamine-tannic acid complex according to the invention has a tannic acid:glutamine molar ratio of between 1:3 and 1:6. In other words, preferably, the present invention relates to a glutamine-tannic acid complex, in which the tannic acid:glutamine molar ratio is between 1:3 and 1:6.

[0029] Even more preferably, the glutamine-tannic acid complex according to the invention has a tannic acid:glutamine molar ratio of 1:5. In other words, even more preferably, the present invention relates to a glutamine-tannic acid complex, in which the tannic acid:glutamine molar ratio is 1:5.

[0030] Advantageously, according to the invention, the glutamine - tannic acid complex is in solid form.

[0031] Glutamine is known for its effect on the treatment and prevention of dermatological lesions and pigmentation spots. Therefore, the glutamine-tannic acid complex, as described above, is a complex suitable for use in non-therapeutic cosmetic methods for the treatment and / or prevention of pigmentation spots in a subject. Furthermore, the glutamine-tannic acid complex, as described above, is also suitable for use as a medicament, in particular in the treatment and / or prevention of dermatological lesions in a patient. The inventors have surprisingly discovered that the glutamine-tannic acid complex, as described above, has a high stability allowing an extended shelf life, in particular in aqueous solvents. This property makes it possible to formulate glutamine in cosmetic and pharmaceutical preparations for industrial use.

[0032] Without being bound by theory, the inventors are of the opinion that the glutamine - tannic acid complex according to the invention consists on average of five glutamine molecules associated by Van der Waals type interactions (non-covalent) with the five labile hydrogens of tannic acid.

[0033] As described above, the tannic acid:glutamine molar ratio in the complex according to the invention varies between 1:1 and 1:6, preferably between 1:3 and 1:6. The glutamine-tannic acid complex according to the invention has a tannic acid:glutamine molar ratio of between 1:1 and 1:6, preferably between 1:3 and 1:6, preferentially between 1:4 and 1:6, even more preferably approximately 1:5, even more preferably 1:5.

[0034] Preferably, the tannic acid:glutamine molar ratio in the complex according to the invention is between 1:1 and 1:5.

[0035] More preferably still, the tannic acid:glutamine molar ratio in the complex according to the invention is 1:5.

[0036] According to a preferred variant of the invention, the glutamine-tannic acid complex is in essentially dry form.

[0037] The expression "essentially dry" in relation to a complex means that said complex does not comprise ingredients in liquid form in an amount greater than 10% by weight, preferably not in an amount greater than 7%, even more preferably not in an amount greater than 5% relative to the total weight of said complex.

[0038] The complex developed by the inventors also has significant solubility in aqueous solvents, thus allowing the formulation of acceptable pharmaceutical or cosmetic compositions with a high glutamine dosage. Such formulations are advantageous in that they allow the number of daily doses to be reduced and thus ensure better compliance of the patient or subject treated with the treatment.

[0039] Thus, the complex according to the invention is advantageously soluble in distilled water at a temperature of 20°C in an amount of 100 g / L, preferably in an amount of 150 g / L, even more preferably in an amount of 200 g / L.

[0040] The present invention further relates to a composition comprising a therapeutically or cosmetically active amount of the glutamine - tannic acid complex according to the invention and at least one pharmaceutically or cosmetically acceptable excipient.

[0041] The excipients provide the composition according to the invention with optimal physical and (bio-)chemical properties.

[0042] Thus, the present invention therefore relates to a composition comprising a therapeutically active amount of the glutamine-tannic acid complex according to the invention and at least one pharmaceutically acceptable excipient. Furthermore, the present invention also relates to a composition comprising a cosmetically active amount of the glutamine-tannic acid complex according to the invention and at least one cosmetically acceptable excipient.

[0043] Advantageously, the composition according to the invention comprises from 0.5 to 10.0% by weight of the glutamine-tannic acid complex according to the invention, more advantageously from 1.5 to 8.0%, even more advantageously from 2.0 to 6.0% by weight of said complex relative to the total weight of said composition.

[0044] Advantageously, the composition according to the invention comprises several pharmaceutically or cosmetically acceptable excipients. The excipients allow the composition according to the invention to acquire certain beneficial properties in order to achieve the desired therapeutic or cosmetic effects.

[0045] Advantageously, the composition according to the invention further comprises a pharmaceutically or cosmetically acceptable amount of an additional active ingredient. Advantageously, the composition according to the invention comprises several additional active ingredients.

[0046] Advantageously, the composition according to the present invention comprises a solubilizing agent. The solubilizing agent according to the invention makes it possible to increase the bioaccessibility of the active ingredients present in the composition. Such a solubilizing agent is advantageously a polar organic solvent miscible in water, preferably a glycol ether, even more preferably the humectant is diethylene glycol monoethyl ether (DEGEE). Advantageously, a solubilizing agent such as the product known under the trade name Transcutol® CG will be used in the context of the present invention. Preferably, said composition comprises from 1.0 to 10.0% by weight of said solubilizing agent, more advantageously from 1.5 to 5.0%, even more advantageously from 2.0 to 4.0% by weight of said solubilizing agent relative to the total weight of said composition.

[0047] Advantageously, the composition according to the invention comprises a humectant. The humectant according to the invention is a hygroscopic compound allowing the composition according to the invention to have moisturizing properties. Such a humectant is advantageously an organic alcohol, preferably a glycol, even more preferably a butylene glycol. Advantageously, a solubilizing agent such as the product known under the trade name Greendiol® will be used in the context of the present invention. Preferably, said composition comprises from 1.0 to 20.0% by weight of said humectant, more advantageously from 2.0 to 10.0%, even more advantageously from 3.0 to 7.0% by weight of said humectant relative to the total weight of said composition.

[0048] Advantageously, the composition according to the invention comprises a thickening agent. The thickening agent according to the invention makes it possible to increase the viscosity of the composition according to the invention so as to improve its attractiveness and its texture. Such a thickening agent is advantageously a polysaccharide, preferably a branched polysaccharide, even more preferably a xanthan gum. Advantageously, a thickening agent such as the product known under the trade name Xanthan gum FNCSP-PC® will be used in the context of the present invention. Preferably, said composition comprises from 0.01 to 2.0% by weight of said thickening agent, more advantageously from 0.05 to 1.0%, even more advantageously from 0.1 to 0.7% by weight of said thickening agent relative to the total weight of said composition.

[0049] Advantageously, the composition according to the invention comprises an antifungal agent. The antifungal agent according to the invention makes it possible to prevent the development of fungal contamination in the composition. Such an antifungal agent is advantageously a salt of an organic acid, preferably a salt of benzoic acid, even more preferably the preservative is sodium benzoate. Preferably, said composition comprises from 0.05 to 2.0% by weight of said antifungal agent, more advantageously from 0.1 to 1%, even more advantageously from 0.2 to 0.5% by weight of said antifungal agent relative to the total weight of said composition.

[0050] Advantageously, the composition according to the invention comprises an antibacterial agent. The antibacterial agent according to the invention makes it possible to prevent the development of bacterial contamination in the composition. Such an antibacterial agent is advantageously a mixture of organic acids of plant origin and their salts, preferably a mixture comprising a salt of levulinic acid (CeHsCh), preferably sodium levulinate. Advantageously, an antibacterial agent such as the product known under the trade name Dermosoft® 700B will be used in the context of the present invention. Preferably, said composition comprises from 0.1 to 10.0% by weight of said antibacterial agent, more advantageously from 0.2 to 5.0%, even more advantageously from 0.5 to 3.0% by weight of said antibacterial agent relative to the total weight of said composition. Advantageously, the composition according to the invention comprises hyaluronic acid or one of its salts.Hyaluronic acid or one of its salts according to the invention has numerous benefits, in particular for the hydration and cohesion of tissues, the control of angiogenesis, inflammatory processes and healing. Preferably, the hyaluronic acid or one of its salts according to the invention is sodium hyaluronate. Advantageously, the composition according to the invention comprises at least two types of sodium hyaluronate having different molecular weights. Preferably, the composition according to the invention comprises sodium hyaluronate having an average molecular weight of approximately 50 kDa and sodium hyaluronate having an average molecular weight of approximately 300 kDa. Preferably, said composition comprises from 0.01 to 2% by weight of said hyaluronic acid or one of its salts, more advantageously from 0.05 to 1%, even more advantageously from 0.1 to 0.5% by weight of said hyaluronic acid or one of its salts relative to the total weight of said composition.

[0051] According to a preferred variant of the invention, the composition according to the invention is intended for topical administration, preferably on the skin.

[0052] The composition according to the invention may be in solid form or in liquid form. Preferably, said composition is in the form of a solution, a gel, a lotion, a cream, an ointment, a foam, an emulsion, a microemulsion, a milk, a serum, an aerosol, a spray, a dispersion or a soap. Even more preferably, the composition according to the invention is in the form of a serum, preferably a serum based on water and polyols.

[0053] Advantageously, the composition according to the invention therefore comprises water. Preferably, the composition according to the invention comprises at least 50.0% by weight of water, preferably at least 60.0%, more preferably at least 70.0%, preferentially at least 80.0% of water relative to the total weight of said composition.

[0054] Advantageously, the composition according to the invention comprises, relative to the total weight of the composition: from 0.5 to 10.0% by weight of the glutamine-tannic acid complex according to the invention; from 1.0 to 10.0% by weight of a solubilizing agent; from 1.0 to 20.0% by weight of a humectant; from 0.01 to 2.0% by weight of a thickening agent; from 0.05 to 2.0% by weight of an antifungal agent; from 0.1 to 10.0% by weight of an antibacterial agent; from 0.01 to 2.0% by weight of hyaluronic acid or one of its salts; and at least 50.0% of water.

[0055] According to a preferred variant of the invention, the composition according to the invention comprises, relative to the total weight of the composition: from 0.5 to 10.0% by weight of the glutamine-tannic acid complex according to the invention; from 1.0 to 10.0% by weight of diethylene glycol monoethyl ether (DEGEE); from 1.0 to 20.0% by weight of butylene glycol; from 0.01 to 2.0% by weight of xanthan gum; from 0.05 to 2% by weight of sodium benzoate; from 0.1 to 10.0% by weight of a mixture of organic acids and their salts comprising sodium levulinate; from 0.01 to 2.0% by weight of sodium hyaluronate; and at least 50.0% of water.

[0056] Even more advantageously, the composition according to the invention is a serum comprising, relative to the total weight of the composition: from 2.0 to 6.0% by weight of the glutamine - tannic acid complex according to the invention; from 2.0 to 4.0% by weight of diethylene glycol monoethyl ether (DEGEE); from 3.0 to 7.0% by weight of butylene glycol; from 0.1 to 0.7% by weight of xanthan gum; from 0.2 to 0.5% by weight of sodium benzoate; from 0.5 to 3.0% by weight of a mixture of organic acids and their salts comprising sodium levulinate; from 0.1 to 0.5% by weight of sodium hyaluronate; and at least 80.0% of water.

[0057] Advantageously, the pH of the composition according to the invention is between 3.0 and 8.0, preferably between 4.0 and 7.0, even more preferably between 5.0 and 6.0, preferably the pH of the composition according to the invention is approximately 5.5.

[0058] In another aspect, the present invention relates to the complex according to the invention and / or the composition according to the invention for use as a medicament.

[0059] All the definitions, preferences and preferred aspects described above for the complex according to the invention and for the composition according to the invention also apply mutatis mutandis to their use as a medicament. Advantageously, the complex according to the invention or the composition according to the invention is used in the treatment and / or prevention of dermatological lesions in a patient.

[0060] Thus, the present invention therefore relates to the glutamine - tannic acid complex according to the invention for use in the treatment and / or prevention of dermatological lesions in a patient. Furthermore, the present invention also relates to the composition according to the invention for use in the treatment and / or prevention of dermatological lesions in a patient.

[0061] Non-limiting examples of dermatological lesions include, but are not limited to, bruises, preferably post-operative bruises, vascular disorders of the skin, spider veins, varicose veins, facial spots, purpura on the face, body or legs, telangiectasias, irritation following a chemical peel, Schamberg's disease, radiodermatitis, rosacea, progressive pigmentary dermatitis or a mixture thereof.

[0062] Preferably, the complex according to the invention or the composition according to the invention is used in the treatment and / or prevention of dermatological lesions caused by sclerotherapy and / or laser treatment, for example by vascular laser. Indeed, sclerotherapy treatment and (vascular) laser have been used in the treatment of spider veins and varicose veins for many years. However, many patients who have undergone this type of treatment have bruises around the treated area. The inventors have surprisingly discovered that such lesions can be effectively treated by the complex or the composition according to the invention.

[0063] In another aspect, the present invention relates to the non-therapeutic, cosmetic use of the complex according to the invention or the composition according to the invention for the treatment or prevention of pigment spots. The inventors have in fact surprisingly discovered that the general appearance of a subject can be improved following the use of the complex or the composition according to the invention thanks to the treatment or prevention of pigment spots.

[0064] All of the definitions, preferences and preferred aspects described above for the complex according to the invention and for the composition according to the invention also apply mutatis mutandis for their non-therapeutic use in the treatment or prevention of pigment spots.

[0065] Preferably, the complex according to the invention or the composition according to the invention is used in the treatment or prevention of pigment spots on the face, body or legs, preferably in the treatment or prevention of dark circles. Indeed, dark circles are difficult to treat, in particular because their etiology depends on genetic factors and phototypes.

[0066] Thus, the present invention therefore relates to the non-therapeutic use of the glutamine - tannic acid complex according to the invention for the treatment and / or prevention of dark circles in a subject. Furthermore, the present invention also relates to a non-therapeutic cosmetic method for the treatment and / or prevention of dark circles comprising the administration of the composition according to the invention to a subject.

[0067] The present invention further relates to a method for producing the glutamine-tannic acid complex according to the invention, comprising reacting tannic acid and glutamine in a solvent so as to obtain a solution and, optionally, recovering said complex from said solution by drying.

[0068] According to a preferred variant of the process according to the invention, the solvent is an aqueous solvent, preferably water.

[0069] Advantageously, during the reaction step, the tannic acid and the glutamine are dissolved in a tannic acid:glutamine molar ratio of between 1:1 and 1:6, preferably in a tannic acid:glutamine molar ratio of between 1:3 and 1:6, preferentially in a tannic acid:glutamine molar ratio of between 1:1 and 1:5, more preferentially in a tannic acid:glutamine molar ratio of approximately 1:5, even more preferentially, in a tannic acid:glutamine molar ratio of 1:5. Preferably, the reaction step is carried out, at least partially, at a temperature of at least 35°C.

[0070] According to a preferred variant of the process according to the invention, said complex is recovered from said solution by drying, preferably by freeze-drying, spray drying or vacuum drying, preferably by freeze-drying.

[0071] All the definitions, preferences and preferred aspects described above for the complex according to the invention also apply mutatis mutandis to the method of producing said complex.

[0072] The invention will now be described in more detail with reference to the following examples, which detail non-limiting illustrations of different aspects of the invention. Preparation of the glutamine tannic acid complex on a laboratory scale.

[0073] An aqueous solution of tannic acid was prepared by dissolving 222.22 g of tannic acid (10% H2O) in 1000 mL of MilliQ water. The pH of the solution is 3.08. The aqueous solution of tannic acid is heated to 50 °C and L-glutamine (95.45 g) is added with stirring in successive portions of 10 g until complete dissolution. The aqueous solution obtained is homogeneous and has a brown color. Once this solution is returned to room temperature, the pH is measured at 4.08. 30 mL of an antibacterial agent (Dermasoft® Eco 1338) is added to the solution and the pH is measured at 4.47. The solution thus obtained is then stirred at room temperature for 48 hours before being filtered to remove residual solid residues. The aqueous solution of the glutamine-tannic acid complex thus obtained has a volume of 1210 mL and a weight of 1382.7 g. The glutamine-tannic acid complex is isolated by lyophilization of this solution.

[0074] Preparation of glutamine tannic acid complex on a pilot scale.

[0075] An aqueous solution of tannic acid was prepared by dissolving 2888.96 g of tannic acid in 1300 L of demineralized water at 30 °C in 500 g portions. The pH of the solution was 3.00. L-glutamine (1240.85 g) was then added with stirring to the aqueous tannic acid solution in 500 g portions. After adding all of the L-glutamine, the solution was heated to 45 °C. After 7 hours of incubation with stirring, 390 g of an antibacterial agent (Dermasoft® Eco 1338) was added. The resulting solution was then stirred at room temperature for 12 h before being filtered to remove any residual solids. The pH of the solution was measured at 4.16. The aqueous solution of the glutamine-tannic acid complex thus obtained has a density of 1.0969. The glutamine-tannic acid complex is isolated by lyophilization of this solution.

[0076] Evaluation of the stability of the tannic glutamine complex in an aqueous medium.

[0077] The stability of the glutamine-tannic acid complex thus obtained is evaluated over a period of 6 months in an aqueous medium. For this purpose, the quantities of impurities (degradation products) as well as the quantity of L-glutamine are measured at regular intervals. The stability of the complex is evaluated under normal storage conditions (25 °C, 60% relative humidity) at a concentration of 10 mM in distilled water. The result of this study is that the complex has a compliant quantity of L-glutamine (> 95%) over the entire duration of stability, i.e. 6 months. The complex according to the present invention therefore allows excellent stability in aqueous media over a period of at least 6 months.

[0078] Example 4: Preparation of a composition comprising the glutamine - tannic acid complex.

[0079] A composition according to the invention was prepared by mixing the different ingredients listed in Table 1, below. The composition of the composition is detailed below and is in the form of a serum.

[0080] Table 1

[0081] Example 5: Evaluation of the stability of the composition according to the invention.

[0082] The stability of the composition described in Example 4 is evaluated over a period of 6 months in an aqueous medium. For this purpose, the quantities of impurities (degradation products) as well as the quantity of L-glutamine are measured at regular intervals. The stability of the complex is evaluated under normal storage conditions (25°C, 60% relative humidity). The result of this study is that the composition has a compliant quantity of L-glutamine (> 95%) over the entire duration of stability, i.e. 6 months. The composition according to the present invention therefore allows excellent stability over a period of at least 6 months. Evaluation of the activity of the composition according to the invention in non-therapeutic use for the treatment of periocular dark circles.

[0083] Subjects are over 18 years old, male or female, and have a phenotype 2 to 4. Exclusion criteria are pursuing cosmetic surgery treatment, being pregnant, sensitivity to one of the active ingredients, use of depigmenting products, skin diseases (skin infections, eczema, psoriasis, rosacea, herpes, etc.) and severe allergies.

[0084] Dark circles are classified into 3 types using a Wood's lamp: pigmented (brown), vascular (blue to purple), and mixed. Subjects receive a 15 mL bottle containing the composition described in Example 4, above. The composition is applied only in the morning and evening. The amount of composition applied is adjusted for each side. In the morning, the subject can wash their eyelids, unlike in the evening when no product is applied after applying the composition. The treatment duration is 16 weeks.

[0085] The assessment of the subjects is both subjective (subjects) and objective (physician). The subjects are assessed 2, 4, 8 and 12 weeks after the start of treatment. The physician performs chromametry using a colorimeter (Dermacatch®). A numerical assessment is performed according to the following scale:

[0086] 0 = no improvement

[0087] 1 = moderate improvement

[0088] 2 = marked improvement

[0089] 3 = disappearance of dark circles

[0090] It appears that the composition according to the invention leads to a marked reduction in periocular dark circles. 7: Evaluation of the activity of the composition according to the invention in therapeutic use for the treatment of dermatological lesions.

[0091] Spider veins are typically treated with sclerotherapy or vascular laser treatment. However, many patients experience tingling, bruising, and hemosiderin deposits around the treated area. Other side effects of this type of treatment include skin depigmentation, discomfort, and raised red areas around the injection sites.

[0092] This study aims to evaluate the activity of the composition described in Example 4, above, on the treatment of dermatological lesions caused by the treatment of varicose veins by serotherapy or by vascular laser. The activity of the composition is evaluated for its activity on bruises in the treated areas.

[0093] Patients are over 18 years old, female, and have phenotype 1 to 4. Exclusion criteria are pregnancy, sensitivity to any of the active ingredients, use of depigmenting products, skin diseases (skin infections, eczema, psoriasis, rosacea, herpes, etc.) and severe allergies.

[0094] Subjects receive a 15 mL bottle containing the composition described in Example 4, above. The composition is applied only in the morning and evening to the bruises present on the legs. The amount of composition applied is adjusted for good penetration. The duration of treatment is 8 weeks.

[0095] The assessment of the subjects is both subjective (subjects) and objective (physician). The subjects are assessed 0, 4 and 8 weeks after the start of treatment. The physician performs chromametry using a colorimeter (Dermacatch®). A numerical assessment is performed according to the following scale:

[0096] 0 = no improvement

[0097] 1 = moderate improvement

[0098] 2 = marked improvement

[0099] 3 = disappearance of bruises

[0100] It appears that the composition according to the invention leads to a marked reduction in lesions. Example 8: Evaluation of the homogeneous nature of compositions comprising glutamine - tannic acid complexes having different tannic acid : glutamine molar ratios.

[0101] The compositions shown in Table 2 below were formulated by dissolving glutamine-tannic acid complexes with different tannic acid:glutamine molar ratios in water. The homogeneity of the solutions obtained, i.e. the presence or absence of a precipitate, was determined.

[0102] Table 2

[0103] As can be seen, only the compositions according to the present invention, that is to say the compositions for which the tannic acid:glutamine molar ratio is between 1:1 and 1:6, in particular for which the tannic acid:glutamine molar ratio is between 1:1 and 1:5, are homogeneous (no presence of precipitate).

Claims

Claims 1. Glutamine - tannic acid complex, in which the tannic acid : glutamine molar ratio is between 1 : 1 and 1 : 6, preferably between 1 : 1 and 1 : 5, preferably between 1 : 3 and 1 :

6.

2. The glutamine-tannic acid complex according to claim 1, wherein the tannic acid:glutamine molar ratio is about 1:5, preferably 1:

5.

3. The glutamine-tannic acid complex according to any one of the preceding claims, said complex being in essentially dry form.

4. The glutamine - tannic acid complex according to any one of the preceding claims, said complex being soluble in distilled water at a temperature of 20°C in an amount of 100 g / L, preferably in an amount of 150 g / L, preferentially in an amount of 200 g / L.

5. Composition comprising a therapeutically or cosmetically active amount of the glutamine-tannic acid complex according to any one of the preceding claims and at least one pharmaceutically or cosmetically acceptable excipient.

6. The composition of claim 5 further comprising a pharmaceutically or cosmetically acceptable amount of an additional active ingredient.

7. The composition according to claim 5 or 6, said composition being intended for topical administration, preferably on the skin.

8. The composition according to any one of claims 5 to 7, said composition being in the form of a solution, a gel, a lotion, a cream, an ointment, a mousse, an emulsion, a microemulsion, a milk, a serum, an aerosol, a spray, an aerosol, a spray, a dispersion, or a soap.

9. Glutamine-tannic acid complex according to any one of claims 1 to 4 or composition according to any one of claims 5 to 8, for use as a medicament.

10. The glutamine-tannic acid complex or composition for use according to claim 9, for use in the treatment and / or prevention of dermatological lesions in a patient.

11. The glutamine-tannic acid complex or composition for use according to claim 9 or 10, wherein the lesions are selected from the group consisting of bruises, vascular disorders of the skin, spider veins, varicose veins, facial spots, purpura on the face, body or legs, telangiectasias, irritation following chemical peeling, Schamberg's disease, radiodermatitis, rosacea, progressive pigmentary dermatitis or a mixture thereof, preferably in the treatment and / or prevention of dermatological lesions caused by sclerotherapy and / or laser treatment.

12. Non-therapeutic use of the glutamine-tannic acid complex according to any one of claims 1 to 4 or of the composition according to any one of claims 5 to 8 for the treatment or prevention of pigment spots, preferably dark circles.

13. A method of producing a glutamine-tannic acid complex according to any one of claims 1 to 4, said method comprising - react tannic acid and glutamine in a solvent to obtain a solution, and optionally - recovering said complex from said solution by drying.

14. The production method of claim 13, wherein said solvent is an aqueous solvent.

15. Production process according to claim 13 or 14, wherein the reaction of tannic acid and glutamine in a solvent is carried out with stirring and at a temperature of at least 35°C. A method according to any one of claims 13 to 15, wherein said complex is recovered from said solution by lyophilization.

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