EP3134086A2 - Composition à usage topique - Google Patents

Composition à usage topique

Info

Publication number
EP3134086A2
EP3134086A2 EP15728157.7A EP15728157A EP3134086A2 EP 3134086 A2 EP3134086 A2 EP 3134086A2 EP 15728157 A EP15728157 A EP 15728157A EP 3134086 A2 EP3134086 A2 EP 3134086A2
Authority
EP
European Patent Office
Prior art keywords
skin
composition
trehalose
treatment
prevention
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP15728157.7A
Other languages
German (de)
English (en)
Inventor
Ruffo BENEDETTI
Enzo EMANUELE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biodue SpA
Original Assignee
Biodue SpA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biodue SpA filed Critical Biodue SpA
Publication of EP3134086A2 publication Critical patent/EP3134086A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016Disaccharides, e.g. lactose, lactulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/4172Imidazole-alkanecarboxylic acids, e.g. histidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/32Manganese; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • A61K8/602Glycosides, e.g. rutin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

Definitions

  • TITLE "COMPOSITION FOR TOPIC USE"
  • the present invention regards a composition comprising trehalose, an antioxidant and at least one pharmaceutical excipient and the use of said composition for the treatment and the prevention of skin and eye diseases.
  • non-melanoma skin cancer NMSC
  • non-melanoma skin cancers such as basal cell carcinoma and squamous cell carcinoma (Bowen's disease)
  • Bowen's disease basal cell carcinoma and squamous cell carcinoma
  • UV ultraviolet rays
  • UVB rays 290-320 nm
  • UVA rays 320-400 nm
  • UVA rays 320-400 nm
  • the mechanism of formation of the photo-induced damage at skin level comprises the interaction between UV radiations and DNA of epidermal cells.
  • the DNA sites with adjacent pyrimidine bases are the preferred sites of formation of the photo lesions induced by UV rays, with formation of pyrimidine dimers, such as CPDs (cyclobutane pyrimidine dimers).
  • CPDs may be repaired by enzymes naturally present in the cell nucleus which operate by excision of the damaged nucleotides. Examples of enzymes which cooperate in this type of repair are helicases, endonucleases, DNA polymerases and ligases. In most organisms, CPDs may be repaired by the photolyase enzymes, which act after photoactivation.
  • CPDs may be generated by UV-B or UV-A radiations. It is known that the protection of human skin against damage to DNA caused by UV-A radiations is very low (Mouret, S. et al. Proc Natl Acad Sci USA 2006, 103, 13765).
  • compositions currently known for the prevention of the photo-induced skin damage and diseases derived therefrom are agents which block the radiations (high SPF solar filters) and which should be applied before any exposure to radiations.
  • Compositions containing enzymes and other substances capable of repairing damage to DNA are also known.
  • these compositions only act on damage initially caused to nucleic acids and they do not block damages that may be caused by radiations on the protein in vivo, for example by breaking sulphide bridges and for inducing protein aggregation. Damages at protein level are the first to be directly caused by radiation, while damage to DNA is always delayed.
  • preparations containing DNA repair enzymes - in the light of the high specificity of the catalytic mechanisms that characterise them - have an action limited on some photo-products on DNA (such as CPDs), but without specifically acting on the wholeness of the proteome.
  • An object of the present invention is to provide a composition for the prevention and treatment of damages caused by UV radiations, and diseases associated thereto, without the disadvantages of the prior art compositions.
  • Another object of the present invention is to provide a topical composition capable of contrasting the ageing of the skin.
  • Figure 1 shows the Western blot analysis carried out on nuchal bioptic samples taken from 10 patients of beclin protein and amyloid peptides respectively measured at baseline and after 45 days of treatment with a topical composition of the invention containing trehalose encapsulated in liposomes.
  • Figure 2 shows, in quantitative form, the results of the Western Blot analysis referred to by figure 1 carried out on nuchal bioptic samples taken from 10 patients of beclin protein and amyloid peptides respectively measured at baseline and after 45 days of treatment with a topical composition of the invention containing trehalose encapsulated in liposomes.
  • compositions as described above for use in the treatment or prevention of a disorder and/or of a skin disease, skin and eye annexes caused by exposure to solar radiations, ultraviolet or ionising in a subject, and for use in the treatment and prevention of skin ageing.
  • the expression powder trehalose is used to indicate trehalose that is not contained in liposomes.
  • the expression trehalose in liposomal or liposome form is used to indicate trehalose contained or comprised in liposomes.
  • the two "and/or" conjunctions - which join two components - are used to indicate that the component after this expression is present in association with the component before the aforementioned expression.
  • the conjunction is “and”; or the component can be present as an alternative to the first component of said expression, in this case the "or" conjunction is applied.
  • excipient is used to indicate a substance commonly used in the formulation of pharmaceutical or cosmetic preparations or medical devices, as known to a man skilled in the art.
  • the expression divalent manganese is used to indicate the Mn 2+ ion which can be present in free, hydrated or complexed form, for example as a chelate, in form of salt, conjugate, oxide, suspension or aqueous solution.
  • manganese ascorbate, manganese aspartate, manganese bisglycinate or manganese pidolate may be used.
  • dermatoheliosis or photoageing is used to indicate the chronic and progressive damage of the skin caused by the harmful action of ultraviolet rays on the skin cells. Dermatoheliosis or photoageing occurs through a series of lesions of various levels including wrinkles, loss of skin elasticity, occurrence of skin dyschromia and fine telangiectasias, deterioration and compaction of elastic fibres in the superficial dermal layer, ephelides, actinic keratosis, purpura, vascular lesions such as angiomas and telangiectasias, sebaceous hyperplasia and skin tumours.
  • proteome is used to indicate the entirety of the proteins of an organism or biological system, i.e. proteins produced by the genome.
  • the term “proteome” indicates the entirety of the proteins of skin cells that can be damaged due to exposure to solar, ultraviolet (UVA and UV-B as defined above) or ionising radiations.
  • the present invention regards a composition comprising trehalose, an antioxidant and at least one excipient suitable for pharmaceutical use.
  • trehalose is comprised in a liposome when the topical application regards the skin and it is in particular applied in this form for the treatment and prevention of skin ageing.
  • Liposomes are vesicles formed by lipids, generally phospholipids or cholesterol, that may have dimensions varying between 25 nm and 1 ⁇ by diameter. They are normally constituted by at least one double spherical and closed layer of phospholipids or cholesterol.
  • trehalose in a liposome allows obtaining a high concentration of active ingredient at epidermis and dermis level, which guarantees an efficient action of preventing photo-induced damage on proteome, as well as fighting skin ageing.
  • Liposomes can be prepared by utilising microfluidification techniques (as described in EP2633852, US5853753 and references mentioned therein), i.e. for self- aggregation of phospholipids in an aqueous phase in which the amphiphilic molecules of the phospholipids spontaneously generate spherical vesicles (double layers) to try to segregate the hydrophobic part of their molecules from the aqueous environment, while the polar part remains at contact with the aqueous phase.
  • the method for preparing liposomes comprises 3 steps: hydration of phospholipids, dimensioning of liposomes and removal of non-encapsulated material. Hydration occurs through a mechanical method: a thin lipid film is deposited by a solution in organic solvent on the wall of a glass flask (rotating evaporator). The film is hydrated under stirring at a temperature higher than the critical temperature of the phospholipid having the highest critical temperature. This allows obtaining multilamellar vesicles (MLV) with large dimensional distribution (greater than 0.1 ⁇ ).
  • MLV multilamellar vesicles
  • the homogenisation method is used: the dimensional distribution curve is narrowed making the dispersion of liposomes pass through a high pressure homogeniser. This allows obtaining a bimodal dimensional distribution (with two maximum frequencies), with particles around 1,000 nm.
  • the last step consists in removing the organic solvent and all non-encapsulated material.
  • the INCI (International Nomenclature of Cosmetic Ingredients) formula of the liposomes containing Trehalose at 5% by weight/total weight of the liposome (PMLs containing Trehalose) according to the present invention is: water, butylene glycol, trehalose, hydrogenated lecithin, carbomer, carrageenan ⁇ Chondrus crispus), sodium phosphate, sodium hydroxide, sodium hydroxymethylglycinate.
  • liposomes in the composition of the present invention may comprise (all percentages are by weight/ total weight of the liposome): 0.25-2.75% of butylene glycol, 0.04-0.44% of phospholipids, 0.0005 - 0.0055% of carrageenan, 0.0028 - 0.0308% of carbomer, 0.75-0.85% of sodium phosphate, 0.10-0.12% of sodium hydroxymethylglycinate.
  • the PMLs in the composition of the present invention may have, for example, a dimension between 500 and 1000 nm and/or a pH comprised between 5.5 and 7.0 preferably between 5.7 and 6.7.
  • Trehalose in liposomal form may be used for the formulation of creams, gels, lotions, sprays and solutions with the following excipients: with regards to creams, water, oils, emulsifiers, preservatives, pH corrector; with regards to gels, water, rheological additives, preservatives, pH corrector; with regards to lotions and spray, water, dispersants, preservatives, pH corrector.
  • the formulations may be applied 1 to 3 times a day according to dosages regarding the sites to be treated.
  • Trehalose in liposomal form may be used in concentration between 0.01 and 10% by weight/weight of the liposome and it is associated, in various concentrations, to powder trehalose, ectoine, carnosine, ergothioneine and manganese.
  • the composition according to the invention comprises liposomes having a dimension between 500 and 1000 nm.
  • liposomes in the composition according to the invention comprise trehalose amounting to 1-10% by weight/weight of the liposome, more preferably 1-5% by weight/weight of the liposome.
  • the phospholipids are hydrogenated soy lecithin.
  • the liposomes comprising trehalose range between 90 and 99% by weight/total weight of the composition. (I deleted the entire sentence since the range of trehalose in liposomal form is the same, independent of the type of antioxidant present)
  • the antioxidant is selected from among powder trehalose at least one amino acid such as ergothioneine, a peptide such as carnosine, ectoine (1,4,5, 6-tetrahydro-2-methyl-4-pyrimidine-carboxylic acid), a salt or a divalent manganese complex and their mixtures. More preferably, the antioxidant is at least one from among powder trehalose, ergothioneine, ectoine, carnosine, a salt or a divalent manganese complex and their mixtures. More preferably the antioxidant is a salt or a divalent manganese complex. More preferably the antioxidant is selected from among powder trehalose and ectoine.
  • the composition according to the invention comprises - as a salt or a divalent manganese complex - at least one among manganese ascorbate, manganese aspartate, manganese bisglycinate or manganese pidolate.
  • the amount of divalent manganese in the composition of the invention is between 0.01 and 0.1% by weight/ total weight of the composition.
  • the amount of ectoine in the composition of the invention is between 0.001 and 2% by weight/total weight of the composition, more preferably between 0.1 and
  • the amount of ergothioneine in the composition of the invention is between 0.005 and 1% by weight/total weight of the composition.
  • the amount of carnosine in the composition of the invention is between 0.1 and 5% by weight/total weight of the composition.
  • the composition of the invention comprises powder trehalose, more preferably at an amount between 1 and 10% by weight/total weight of the composition. It was observed that in presence of powder trehalose, in addition to trehalose in liposomal form, there is obtained the advantageous synergic effect which results in effects for the prevention and treatment of damages caused to proteome by UV radiations exceeding the effects of the sum of the single components of the composition.
  • the composition of the present invention may be in a form known to a man skilled in the art and suitable for administering to a subject, human or animal, through topical means, for example as cosmetic composition, pharmaceutical composition or medical device.
  • medical device comprises a preparation with prevalent physical and/or mechanical effect.
  • Examples of medical device in the present invention are creams, gels and lotions.
  • the composition of the present invention is in a form suitable for administering to a subject, human or animal, through topical means directly on the point where exposure to radiations occurred or will occur.
  • the composition of the present invention is in form of cream, gel, spray or lotion suitable for topical use or as solution, suspension or spray for ophthalmic use.
  • the composition of the present invention comprises trehalose and/or trehalose in non-liposome form.
  • ophthalmic formulation according to the present invention and formulation for skin use, for use in the treatment of diseases caused by exposure to solar, ionising and ultraviolet radiations.
  • the present invention regards the composition comprising trehalose in liposomal form and an antioxidant as described above for use in the treatment or in the prevention of a skin/skin and eye annexes disorder and/or disease, caused by exposure to solar, ultraviolet or ionising radiations or by oxidative damage in a subject.
  • Said disorder and/or disease is one from among melanoma, skin cancer different from melanoma, dermatoheliosis (photoageing) or oxidative damage in a subject. More preferably, said disorder and/or disease is dermatoheliosis (photoageing).
  • the composition according to the present invention is applied from one to three times a day.
  • UVB radiations Radiation with UVB radiations was carried out using a Spectrolinker XL -1500 (Spectronics, Westbur NY, USA), UV polymerising device which emits most of its energy in the UVB range (280-320 nm) with a peak at 312 nm.
  • the UV dose was measured with a UVX Radiometer (UVP Inc., Upland, CA, USA).
  • UVP Inc. Upland, CA, USA
  • the cells were exposed to UVB radiation at a dose of 20 mJ/cm 2 .
  • Antioxidants and cytoprotective compounds (manganese, ectoine, carnosine, ergothioneine) were tested as regards their protective effect combined with liposomes containing trehalose.
  • the main markers used are apoptosis markers (fragmentation of DNA) and proinflammatory molecules levels (IL- ⁇ and TNF-a).
  • the DNA fragmentation percentage was evaluated 24 hours after treatment with the Sellins and Cohen method.
  • about 3 x 10 6 cells were lysed using 200 ml of lysis buffer and centrifuged at 13000 g for 10 min.
  • DNA from all samples in the supernatant and pellets was precipitated in trichloroacetic acid 12.5 % (TCA) at 4°C overnight and quantified using diphenylamine reagent after hydrolysis in 5% TCA at 90°C for 20 min.
  • TCA trichloroacetic acid 12.5 %
  • a Western blot analysis is carried out to detect the expression levels of IL- ⁇ and TNF-a in irradiated HaCaT using specific antibodies. The results are expressed in arbitrary units (regarding the non- irradiated sample) and summarised in table 1.
  • a further aspect of the present invention regards compositions for topical skin use containing trehalose in liposomal form for use in the prevention and treatment of skin ageing.
  • trehalose in liposome form preferably in concentrations comprised between 2 and 8% more preferably at concentrations of 5% is capable of fighting skin ageing.
  • the applicant experimentally revealed both at molecular level and from a clinical point of view the efficiency of topical application of liposomes containing trehalose (in particular at 5% concentrations in a carrier).
  • autophagy is a highly conserved degradation process in which pathological or aged proteins are sequestrated in a double membrane vesicle (autophagosome) and transported to the lysosomes for degradation.
  • This activity was directly evaluated determining, through Western blot analysis, the variation of expression in nuchal skin biopsies, taken from the aforementioned patients, of beclin, a known autophagy marker (an increase of such marker represents an increase of autophagy), as well as indirectly evaluating (still through Western blot analysis) the skin expression variation of peptides derived from amyloid, which is deemed a known skin ageing marker.
  • the reduction of this parameter represents a direct demonstration of an increase of autophagy.
  • the data indicated in the table uniformly revealed statistically considerable improvements with regards to the uniformity of the skin colour, the hydration of the corneal layer and the crow's feet wrinkles visibility index.
  • the increase of the skin autophagy represents an innovative mechanism for removing excess pigment at i o skin level.
  • a reduction of the crow's feet wrinkles volume was observed by a clinically appreciable degree, although it was not statistically significant.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Organic Chemistry (AREA)
  • Birds (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Toxicology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne une composition comprenant du tréhalose, un antioxydant et au moins un excipient pharmaceutique, et l'utilisation de ladite composition pour le traitement et la prévention de maladies de peau et de troubles oculaires.
EP15728157.7A 2014-04-22 2015-04-21 Composition à usage topique Withdrawn EP3134086A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI20140748 2014-04-22
PCT/IB2015/052895 WO2015162552A2 (fr) 2014-04-22 2015-04-21 Composition à usage topique

Publications (1)

Publication Number Publication Date
EP3134086A2 true EP3134086A2 (fr) 2017-03-01

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EP15728157.7A Withdrawn EP3134086A2 (fr) 2014-04-22 2015-04-21 Composition à usage topique

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EP (1) EP3134086A2 (fr)
WO (1) WO2015162552A2 (fr)

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* Cited by examiner, † Cited by third party
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EP3481411A4 (fr) * 2016-07-11 2020-07-22 University of North Texas Health Science Center at Fort Worth Traitement du glaucome et d'autres maladies oculaires
US12012238B2 (en) 2021-05-26 2024-06-18 Bausch + Lomb Ireland Limited Packaging solutions

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