Pharmaceutical composition comprising a combination of lipoic acid and taurine as an osmoprotective agent

Description

FIELD OF INVENTION

[0001] The present invention relates to a pharmaceutical composition suitable for topical application comprising a combination of lipoic acid and taurine for use as an osmoprotective agent for the prevention and treatment of skin and mucous membrane disorders associated with osmotic imbalance. STATE OF THE ART

[0002] Osmotic imbalance is observed in skin and mucous membrane disorders in mammals, particularly humans, generally in the form of dry skin or xerosis, which may be a sign of atopic dermatitis, ichthyosis, eczema, psoriasis; or in the form of dry eyes, which may be a sign of Meibomian gland dysfunction, hyperevaporative syndrome, or lacrimal insufficiency, as well as in the form of ocular edema.

[0003] The usual treatments for these skin or mucous membrane conditions range from the application of moisturizing, emollient creams, or even creams or ointments based on corticosteroids, or even local immunomodulators.

[0004] Taurine is a naturally occurring aminosulfonic acid produced by the pancreas of mammals through the conversion of cysteine. It is known to be used as a food additive in energy drinks. Taurine is also described in ophthalmic preparations for its ability to modulate calcium ion levels in cells, which is thought to prevent macular degeneration (US 2006 / 188492), or as a chelating agent (US 5,817,630).

[0005] Lipoic acid, also known as thioctic acid (CAS No. 0001077-28-7), and its derivatives are known for their antioxidant properties. It is used as a dietary supplement in tablet form (Liponsäure-ratiopharm®< marketed in Germany by Ratiopharm) or by injection as diluted injectable solutions (Neurium®< marketed in Germany by Hexal), sometimes as part of treatment for diabetic patients. Ophthalmic or cosmetic compositions that may include lipoic acid as an antioxidant are described in patent applications (US 2006 / 127505, US 2001 / 031744, US 5 817 630, US 2012 / 258168, US 6649195 B1, WO 2005 / 027950, US 6 620 425 B1, EP 2 311 454 A2, CN 102 144 780 A, US 2006 / 188492, US 2004 / 265345, US 5 817 630, WO 02098345, DE10229995, WO 01 / 93824, US 2005 / 192229, BR PI0 800). 818, CN 103 860 625 and JP 2013 241398).

[0006] Its antimicrobial properties have also been described for use in BDT-based lens cleaning solutions (US 6 162 393).

[0007] The antioxidant properties of lipoic acid have also been highlighted to study its effectiveness on cataracts in diabetic rats (Masami Kojima & col., Japanese Journal of Ophthalmology, January 2007, Volume 51, Issue 1, pp 10-13).

[0008] After testing lipoic acid on corneal cells, the inventors found that the observed antioxidant effect was quite weak, weaker than the effect expected from what is described for food supplements.

[0009] They have now found that lipoic acid possesses significant and advantageous osmoprotective properties that allow its use in the prevention and treatment of skin and mucous membrane conditions, particularly those affecting the eye, either as a replacement for or in addition to conventional treatments, unrelated to the conditions purported to be treated by prior art lipoic acid compositions. In particular, they observed that combining lipoic acid with taurine increases and prolongs the osmoprotective effect of this combination compared to the effects observed separately for each component. Lipoic acid acts rapidly after application, while the osmoprotective effect of taurine appears and continues to develop as that of lipoic acid begins to diminish. DESCRIPTION OF THE INVENTION

[0010] The present invention relates to a pharmaceutical composition suitable for topical application comprising a combination of lipoic acid and taurine, and a pharmaceutically acceptable vehicle for its use in the prevention or treatment of a skin condition in which dry skin occurs, the skin condition being selected from atopic dermatitis, ichthyosis, eczema or psoriasis, or of an eye condition related to dry eye, the eye condition being selected from Meibomian gland dysfunction, hyperevaporative syndrome or lacrimal insufficiency, the lipoic acid / taurine weight ratio ranging from 0.004 to 0.05. Embodiments of the invention are described in the attached set of claims. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention relates to a pharmaceutical composition suitable for topical application comprising an association of lipoic acid and taurine for use as an osmoprotective agent for the prevention and treatment of skin and mucous membrane conditions, particularly of the eye, associated with dry skin or eye, the lipoic acid / taurine weight ratio ranging from 0.004 to 0.05.

[0012] Lipoic acid, according to the invention, means 5-(1,2-dithiolan-3-yl)pentanoic acid, in racemic form or its enantiomers in all proportions, in particular the R enantiomer, pure or in a mixture where the proportion of the R enantiomer is greater than that of the S enantiomer, and their pharmaceutically acceptable salts.

[0013] Pharmaceutically acceptable salts, according to the invention, advantageously include addition salts of lipoic acid with a pharmaceutically acceptable base, whether an organic base, particularly one containing an amino group, such as ammonia, lysine, arginine, and other compounds known in the pharmacopoeia, or a pharmaceutically acceptable inorganic base such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and other inorganic bases known in the pharmacopoeia. Preferably, the pharmaceutically acceptable salt is a salt of an alkali metal (sodium, potassium), an alkaline earth metal (calcium, magnesium), or an aluminum ion, more preferably a sodium salt.

[0014] According to a preferred embodiment of the invention, the lipoic acid used in the composition according to the invention is a salt of the R enantiomer of lipoic acid, in particular a sodium (CAS 176110-81-9) or magnesium salt.

[0015] According to the invention, taurine means 2-aminoethanesulfonic acid, its diastereomers, pure or their mixtures in any proportions and their pharmaceutically acceptable salts.

[0016] It can be of natural or synthetic origin.

[0017] Taurine salts can be acid or base salts. Advantageously, the taurine used in the composition according to the invention is a mixture of diastereomers of 2-aminoethanesulfonic acid, in particular obtained by chemical synthesis.

[0018] The composition includes lipoic acid and taurine in a lipoic acid / taurine weight ratio of 0.004 to 0.05, preferably about 0.005 to about 0.02, especially about 0.005, 0.01, 0.02 or 0.04.

[0019] Topical compositions are well known to those skilled in the art in the cosmetic and pharmaceutical fields.

[0020] They are presented in all the usual forms known to those skilled in the art for topical application, in particular as a suspension or dispersion in solvents or fatty substances, as a vesicular dispersion or as an emulsion such as a cream or a milk, as an ointment, gel, saturating ointment, solid stick, aerosol foam or spray.

[0021] The compositions of the invention may include the usual additives used in the preparation of such formulations, such as fats, organic solvents, ionic, zwitterionic, or non-ionic surfactants, emollients, antioxidants, opacifiers, stabilizers, ionic or non-ionic thickeners, silicones, antifoaming agents, moisturizing agents, vitamins, perfumes, preservatives, fillers, sequestrants, colorants, bases or acids necessary for pH regulation, or any other ingredient commonly used in the preparation of cosmetic or pharmaceutical compositions. The compositions according to the invention are prepared using techniques well known to those skilled in the art.

[0022] According to one embodiment of the invention, the combination of lipoic acid and taurine is used in association with other active ingredients, such as another osmoprotective agent, an anti-inflammatory agent and / or an antioxidant agent.

[0023] Other osmoprotective agents that may be used according to the invention include glycerin, L-carnitine, erythritol, trehalose, ectoine, betaine, sarcosine, urea, preferably glycerin.

[0024] Among the anti-inflammatory agents that may be used with lipoic acid are dexamethasone, flurbiprofen, fluorometholone, salicylic acid, hydrocortisone, triamcinolone, rimexolone, preferably flurbiprofen and dexamethasone.

[0025] Other active ingredients include derivatives or analogues of retinoic acid, in particular retinol and its derivatives, especially its esters, particularly its fatty acid esters such as retinyl palmitate.

[0026] Lipoic acid and other anti-inflammatory agents, in particular hydrocortisone and dexamethasone, may be used together in the same composition or in separate compositions.

[0027] Antioxidant agents that can be used with lipoic acid include vitamin E, glutathione, vitamin A, and vitamin C.

[0028] The combination of lipoic acid and taurine, along with other antioxidants, can be used together in the same formulation or in separate formulations. Advantageously, the ratio of lipoic acid to antioxidant(s) used in the same formulation or in separate formulations ranges from 0.001 to 0.01.

[0029] According to a particular embodiment of the invention, the combination of lipoic acid and taurine is used with another osmoprotective agent and / or at least one anti-inflammatory agent and / or at least one antioxidant agent in the same composition, preferably in the proportions described above.

[0030] According to another embodiment of the invention, the composition also comprises a mucomimetic polymer, in particular hyaluronic acid and its salts.

[0031] The composition comprising the combination of lipoic acid and taurine according to the invention may further comprise agents with moisturizing, healing, anti-inflammatory, anti-aging, soothing, anti-irritant, restructuring, emollient action, alone or in mixtures in any proportion.

[0032] According to a particular embodiment of the invention, the composition also comprises hyaluronic acid or its salts, preferably at a concentration of 0.05 to 2% by weight relative to the total weight of the composition. The various forms of hyaluronic acid and its salts used in pharmaceutical or cosmetic compositions are well known to those skilled in the art and are suitable for use in compositions according to the invention. Sodium hyaluronate, with an intrinsic viscosity of 1 to 2.5 m³ / kg, is a prime example.

[0033] According to a preferred embodiment of the invention, the composition containing the combination of lipoic acid and taurine according to the invention is a preservative-free composition.

[0034] The preservatives commonly used in topical compositions (cosmetics, pharmaceuticals, ophthalmics, etc.) to prevent contamination by germs are well known to those skilled in the art. These include quaternary ammonium compounds, notably benzalkonium chloride, alkyl-dimethyl-benzylammonium, cetrimide, cetylpyridinium chloride, benzododecinium bromide, benzothonium chloride, and cetalkonium chloride; mercurial preservatives, such as phenylmercuric nitrate / acetate / borate and thiomersal; alcoholic preservatives, such as chlorobutanol, benzyl alcohol, phenylethanol, and phenylethyl alcohol; carboxylic acids, such as sorbic acid; phenols, particularly methyl / propylparaben; amidines, for example, chlorhexidine digluconate; and / or chelating agents such as EDTA alone or in combination with at least one other preservative.

[0035] According to the invention, "preservative-free" means a composition substantially devoid of such preservatives to meet the requirement of being "preservative-free". Its preservative content is less than or equal to 10 ppm, more particularly less than or equal to 1 ppm, preferably equal to 0 ppm, with no preservatives being included in its composition.

[0036] In the absence of preservatives, the composition must undergo special treatment during its preparation and packaging to avoid and prevent contamination by pathogens. These treatments and procedures are well known to those skilled in the art. In this respect, a preservative-free composition according to the invention differs from a simple composition comprising the same ingredients obtained without demonstrating any special precautions or describing any process steps that would allow for achieving the sterility characteristic of the compositions according to the invention, particularly ophthalmic compositions.

[0037] According to a first particular embodiment of the invention, the combination of lipoic acid and taurine is used in the form of a topical composition suitable for application to the skin, particularly chosen from creams, ointments, gels, salves, solutions, lotions and emulsions.

[0038] The combination of lipoic acid and taurine is advantageously used as an osmoprotective agent for the prevention and treatment of a skin condition in which dry skin appears, including atopic dermatitis, ichthyosis, eczema, psoriasis.

[0039] A person skilled in the art knows how to prepare topical pharmaceutical or cosmetic compositions in these various forms, whether they be water-in-oil or oil-in-water emulsions, solutions, suspensions, or gels. The constituents of these compositions and the proportions in which they are used are well known to a person skilled in the art, described in particular in the French Pharmacopoeia.

[0040] Advantageously, the topical compositions according to the invention are free of preservatives.

[0041] In these topical compositions for use in the prevention or treatment of a skin condition in which dry skin appears, the lipoic acid content is advantageously from 0.0001 to 0.1% by weight relative to the total weight of the composition, preferably from 0.001 to 0.05%, in particular about 0.01%.

[0042] The taurine content is advantageously from 0.001% to 1.0% by weight relative to the total weight of the composition, preferably from 0.01% to 0.1%, more preferably about 0.05%.

[0043] The weight ratio of lipoic acid to taurine in a pharmaceutical composition is 0.004 to 0.05, in particular 0.01 to 0.05, more preferably about 0.02.

[0044] Advantageously, the dry matter content is between 0.001 and 0.05% by weight. Dry matter consists of all the constituents of the formulation, with the exception of water.

[0045] According to another embodiment, the composition comprising the combination of lipoic acid and taurine is an ophthalmic composition (solution, gel, emulsion, suspension). The invention also relates to this ophthalmic composition comprising the combination of lipoic acid and taurine for its use in the prevention and treatment of ocular conditions related to dry eye, which may be a sign of Meibomian gland dysfunction, hyperevaporative syndrome, or lacrimal insufficiency, and its use in ocular edema, particularly corneal edema.

[0046] The composition comprising the combination of lipoic acid and taurine is advantageously used in the form of an ophthalmic composition suitable for application to the eye of a subject, human or animal, particularly human. Consequently, the ophthalmic composition must meet specific technical characteristics for ophthalmic compositions, particularly those related to the selection of its components. These components, which are "ophthalmically acceptable," must not, individually or in combination within the composition, cause any adverse eye reactions other than the intended effect of the composition and its active ingredients. Since the eye is an organ particularly sensitive to environmental stress, the composition must not cause unwanted irritation or allergic-type reactions to the detriment of the intended effect, especially in the case of ophthalmic compositions intended to treat an ophthalmic condition.The choice of components in the composition is therefore very important, as it distinguishes an ophthalmic composition from a simple composition unsuitable for ophthalmic use. A professional skilled in the art is able to select these components and differentiate an ophthalmic composition from a simple composition intended for another purpose.

[0047] The ophthalmic composition preferably has a pH between 5 and 7.5. It therefore generally includes a buffer suitable for ophthalmic use, known to those skilled in the art. Examples include trisodium citrate dihydrate and citric acid monohydrate, used alone or in mixtures.

[0048] The ophthalmic composition must also be sterile to prevent the introduction of pathogens that could develop and cause ophthalmic complications. For the purposes of this invention, "sterile" means the absence of germs as defined in the European Pharmacopoeia, 8th edition (2014). Preferably, the ophthalmic composition comprising the combination of lipoic acid and taurine according to the invention is a preservative-free composition.

[0049] Ophthalmic compositions are generally available as liquids, solutions, or emulsions, but also as gels or ointments. The ophthalmic composition according to the invention is preferably a liquid solution or emulsion for application by instilling one or more drops into the eye. The viscosity of the liquid composition is nevertheless chosen to allow it to remain on the eye, particularly on the cornea, for a sufficient time to enable it to act.

[0050] The ophthalmic composition according to the invention preferably has a viscosity ranging from 5 to 100 centipoise. This viscosity is measured according to the recommendations of the European Pharmacopoeia 2.2.10, using a rotary viscometer at 25°C and 100 s⁻¹. Other measuring devices and methods suitable for measuring the viscosity of solutions are known to those skilled in the art and provide similar results.

[0051] The viscosity of the ophthalmic composition according to the invention depends on its form (solution or emulsion) and is adjusted by adding "ophthalmically acceptable" viscosity-modifying agents. Those skilled in the art are well acquainted with the viscosity-modifying agents that can be used in the preparation of ophthalmic compositions and the quantities required to obtain the desired viscosity. Examples include hydroxypropyl methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, carbomers, agar gels, polyvinylpyrrolidone, and polyvinyl alcohol.

[0052] Preferably, the ophthalmic composition according to the invention comprises hydroxypropylmethylcellulose or carboxymethylcellulose, preferably with a content of 0.05 to 0.5% by weight of hydroxypropylmethylcellulose or carboxymethylcellulose, advantageously from 0.1 to 0.4% by weight, more advantageously from 0.2 to 0.3% by weight, particularly about 0.25% by weight.

[0053] Unless otherwise stated, percentages are expressed as a percentage of the total weight of the composition.

[0054] The ophthalmic composition for use in the prevention or treatment of an eye condition related to dry eye comprising lipoic acid according to the invention advantageously comprises from 0.0001 to 0.1% by weight of lipoic acid relative to the total weight of the composition, and preferably of at least 0.001%, more preferably of about 0.001%.

[0055] The taurine content is advantageously from 0.01% to 1.0% by weight relative to the total weight of the composition, preferably from 0.01% to 0.05%.

[0056] The lipoic acid / taurine weight ratio ranges from 0.004 to 0.05.

[0057] Among the preferred ophthalmic compositions according to the invention, the following compositions will be mentioned.

[0058] According to a preferred embodiment of the invention, the ophthalmic composition comprising lipoic acid according to the invention is an oil-in-water emulsion.

[0059] The appropriate amount of the lipoic acid and taurine combination applied will depend on the condition being treated, as well as its severity. The patient's age or body size may also influence the practitioner's choice of dosage.

[0060] The appropriate dose can be applied in one application, or in several daily applications, for the time necessary to obtain the desired effect, i.e. the prevention or treatment of skin and mucous membrane conditions, particularly of the eye, associated with osmotic imbalance.

[0061] In the case of a liquid ophthalmic composition to be instilled, the appropriate quantity will be given in number of drops to be instilled. DESCRIPTION OF THE FIGURES

[0062] THE figures 1 to 4 represent the results of cell viability after osmotic stress for different concentrations of lipoic acid, alone (comparative) or associated with glycerin (comparative) and / or taurine (invention). EXAMPLES

[0063] The compositions given as examples below are prepared according to standard methods in the technical field. Special sanitary precautions are taken for the preparation and packaging of preservative-free compositions to prevent contamination. Example 1 : Dermatological composition (comparative)

[0064] Components Quantity Caprylic / capric triglyceride 20,00 % Tribehenin PEG-20 Esters 3,00 % Niacinamide 3,00 % Taurine 0.50 % Glycerin 0.50 % Allantoin 0.20 % Sodium lipoate 0.01 % Ceramide 3 0.10 % Sodium Hyaluronate 0.20 % Sodium lipoate 0.01 % Sodium hydroxide (10% solution) 1.50 % Reverse osmosis water Qsp 100% Example 2 : Dermatological composition (according to the invention)

[0065] Components Quantity Cocamidopropyl Betaine 10,00 % Decyl glucoside 5,00 % Glycerin 5,00 % Niacinamide 2,00 % Tri-sodium citrate dihydrate 1,45 % Xanthan gum 0,75 % Taurine 0,50 % Allantoin 0,20 % Sodium hyaluronate 0,10 % citric acid 0,025 % Lipid acid 0,005 % Water Qsp 100% Example 3 : Dermatological composition (comparative)

[0066] Components Quantity Caprylic / capric triglyceride 25,00 % Niacinamide 4,00 % Tribehenin PEG-20 Esters 3,50 % Glycerin 3,00 % Trisodium citrate 1,45 % Xanthan gum 0,80 % Taurine 0,50 % Allantoin 0,50 % Sodium Hyaluronate 0,10 % Ceramide NP 0,10 % Citric acid 0,05 % Lipid acid 0,05 % Water Qsp 100% Example 4 : Dermatological composition (according to the invention)

[0067] Components Quantity Caprylic / capric triglyceride 20,00 % Tribehenin PEG-20 Esters 3,00 % Glycerin 3,00 % Trisodium citrate 1,45 % Xanthan gum 0,80 % Sodium Hyaluronate 0,50 % Taurine 0,50 % Allantoin 0,20 % Helianthus Annuus (sunflower oil), Retinyl Palmitate 0,10 % Citric acid 0,05 % Lipid acid 0,01 % Water Qsp 100% Example 5: Ophthalmic composition (comparative)

[0068] Components Quantity Sodium hyaluronate 0.20 % Taurine 0.5% Sodium Lipoate 0.001% Caprylic / Capric Triglyceride 0,05% Soy lecithin 0,15% Sodium Carboxymethylcellulose 0,15% Trisodium citrate dihydrate 0.05% Citric acid 0.02% NaOH (1 N) Qsp pH 6.7 Sodium chloride qsp 150mOsmol / L PPI water Qsp 100% Example 6 : Ophthalmic composition (according to the invention)

[0069] Components Quantity Sodium chloride 5.00 % Sodium hyaluronate 0.18 % Taurine 0.1% Lipoic acid 0.001 % Sodium Carboxymethylcellulose 0.3 % Disodium citrate dihydrate 1.5 % Citric acid monohydrate Qsp pH 7 Purified water Qsp 100% Example 7 : Osmoprotective activity of lipoic acid and taurine alone or in mixtures

[0070] A study was conducted to determine the osmoprotective capacity of sodium lipoate (A) during hyperosmolar stress on human conjunctival (WKD) and corneal (HCE) cells.

[0071] In a second step, tests were carried out to compare the effect of lipoic acid, glycerin (B), and taurine (C), alone and when the molecules were combined, on HCE cells under hyperosmolar stress conditions.

[0072] The osmoprotective activity of A, and then A with B and C, was evaluated by measuring cell viability. For this purpose, cells were pre-incubated for 17 h with the test substance(s). The medium was then removed, and the cells were subjected to hyperosmolar stress by adding sodium chloride (100 mM NaCl) to the culture medium (M199 for WKD cells and KSFM for HCE cells). Cells in the cell growth control were placed in contact with isotonic medium. Cell viability was analyzed before osmotic stress (0 h) to measure the effect of the molecules that remained in contact with the cells during the 17 h incubation, and then at 4 h, 8 h, and 24 h after the induction of osmotic stress. Cell viability was measured using an XTT assay.

[0073] Different concentrations of A were tested for the "single molecule" tests: 0.0005%, 0.001%, 0.005%, 0.01% and 0.05% w / v. For the molecule mixture tests, the following concentrations were tested: for A: 0.001%, 0.005%, and 0.01% w / v; for B: 0.25% w / v; and for C: 0.5% and 1% w / v.

[0074] To ensure the validity and significance of the data, the results obtained were statistically analyzed. The results presented below are the average of 3 independent replicates, performed on different days. Cell viability measurements for different concentrations of lipoic acid (sodium lipoate) with WKD cells

[0075] 0h 4h 8h 24h A 0,0005% 99,90% 62,70% 38,50% 18,80% A 0,001% 98,50% 69,60% 42,40% 18,50% A 0,005% 102,80% 109,40% 76,10% 12,60% A 0,01% 98,10% 119,90% 82,90% 8,90% A 0,05% 56,30% 46,00% 27,80% 2,70% Nacl 98,80% 50,70% 33,50% 25,80% Hidc 92,30% 68,80% 50,40% 56,40%

[0076] Cell viability measurements for different concentrations of lipoic acid (sodium lipoate) with HCE cells are shown on the figure 1 .

[0077] Lipoic acid exhibits strong osmoprotective activity against osmotic stress at 0.005% and 0.001% (w / v) at 4h and 8h after stress.

[0078] THE figures 2 to 4 represent the viability results obtained with different mixtures of A with B, C and B+C.

[0079] An improvement in the osmoprotective effect of lipoic acid is observed when it is combined with glycerin (B) and taurine (C) or both. This improvement results in greater cell viability than that observed with lipoic acid alone, glycerin alone, or taurine alone. It is particularly marked for the lipoic acid + taurine combination ( figure 3 ), which increases this osmoprotective action over time, up to 24 hours after stress. Example 8: Osmoprotective activity of mixtures of lipoic acid and taurine

[0080] The protocol from Example 7 was repeated with the 11 mixtures M1 to M11 of sodium lipoate (A) and taurine (C). The cell viability results obtained confirmed the increased osmoprotective effect over time observed for the mixtures in Example 7. Cell viability measurements for different concentrations of lipoic acid (sodium lipoate - (A) and taurine (C) with WKD cells

[0081] A% C% A / C t=0h t=4h t=8h t=24h M1 0,0001 0,10 0,001 81 % 63 % 50 % 33 % M2 0,0002 0,10 0,002 84 % 66 % 51 % 32 % M3 0,0050 1,00 0,005 84 % 70 % 67 % 54 % M4 0,0050 0,50 0,010 93 % 72 % 66 % 52 % M5 0,0050 0,25 0,020 96 % 78 % 65 % 46 % M6 0,0100 0,50 0,020 96 % 73 % 69 % 51 % M7 0,0200 1,00 0,020 82 % 63 % 58 % 50 % M8 0,0200 1,00 0,020 90 % 64 % 57 % 40 % M9 0,0050 0,10 0,050 92 % 74 % 58 % 36 % M10 0,0500 0,25 0,200 61 % 49 % 40 % 21 % M11 0,0500 0,10 0,500 73 % 52 % 27 % 19 % NaCl control 94 % 68 % 46 % 22 %

[0082] The osmoprotective improvement effect appears even more pronounced for a lipoic acid / taurine weight ratio of 0.004 to 0.05 (mixtures M3 to M9 according to the invention). M1 and M2 are comparators. REFERENCES

[0083] US 5 817 630 US 6 162 393 US 2004 / 265345 US 2005 / 192229 US 2006 / 188492 WO 01 / 93824 WO 02098345 DE10229995 BR PI0 800 818 CN 103 860 625 JP 2013 241398 Masami Kojima & col., Japanese Journal of Ophthalmology, January 2007, Volume 51, Issue 1, pp 10-13

Claims

1. Pharmaceutical composition suitable for topical application comprising an association of lipoic acid and taurine, and a pharmaceutically acceptable carrier for its use in the prevention or treatment of a skin condition in which cutaneous dryness occurs, said skin condition being chosen from atopic dermatitis, ichthyosis, eczema or psoriasis, or of an eye condition related to eye dryness, said eye condition being chosen from Meibomian gland dysfunction, hyper-evaporative syndrome or lacrimal insufficiency, characterized in that the weight ratio lipoic acid / taurine ranges from 0.004 to 0.05.

2. Composition for its use according to claim 1 in the prevention or treatment of a skin condition in which cutaneous dryness occurs, characterized in that it is suitable for application on the skin, chosen from creams, ointments, gels, lotions, solutions, emulsions and pomades.

3. Composition for its use according to claim 2 in the prevention or treatment of a skin condition in which cutaneous dryness occurs, characterized in that it comprises from 0.0001 to 0.1% by weight of lipoic acid relative to the total weight of the composition.

4. Composition for its use according to one of claims 2 or 3 in the prevention or treatment of a skin in which cutaneous dryness condition appears, characterized in that it comprises from 0.001 to 1.0% by weight of taurine relative to the total weight of the composition.

5. Ophthalmic composition for its use according to claim 1 in the prevention or treatment of an eye condition associated with eye dryness, characterized in that it comprises from 0.0001 to 0.1% by weight of lipoic acid relative to the total weight of the composition.

6. Ophthalmic composition for its use according to one of claims 1 or 5 in the prevention or treatment of an eye condition associated with eye dryness, characterized in that it comprises from 0.01 to 1.0% by weight of taurine relative to the total weight of the composition.

7. Composition for its use according to one of claims 1, 5 or 6 for use in ocular edema, particularly corneal edema.