EP2178538A2 - Entzündungshemmende dermatologische zusammensetzung mit kortikosteroiden und hyaluronat-fragmenten und ihre verwendungen - Google Patents

Entzündungshemmende dermatologische zusammensetzung mit kortikosteroiden und hyaluronat-fragmenten und ihre verwendungen

Info

Publication number
EP2178538A2
EP2178538A2 EP08774984A EP08774984A EP2178538A2 EP 2178538 A2 EP2178538 A2 EP 2178538A2 EP 08774984 A EP08774984 A EP 08774984A EP 08774984 A EP08774984 A EP 08774984A EP 2178538 A2 EP2178538 A2 EP 2178538A2
Authority
EP
European Patent Office
Prior art keywords
composition according
fragments
kda
hyaluronate
molecular weight
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Withdrawn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
EP08774984A
Other languages
English (en)
French (fr)
Inventor
Christine Chaumont
Jean-Hilaire Saurat
Gürkan KAYAN
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.)
Pierre Fabre Dermo Cosmetique SA
Original Assignee
Pierre Fabre Dermo Cosmetique SA
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 Pierre Fabre Dermo Cosmetique SA filed Critical Pierre Fabre Dermo Cosmetique SA
Publication of EP2178538A2 publication Critical patent/EP2178538A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a dermatological composition comprising corticosteroids and hyaluronate fragments, as well as its uses.
  • Hyaluronate is the major component of the extracellular matrix and is found in significant amounts in the skin.
  • HA is a linear glycosaminoglycan nonsulphate composed of repetitive units of D-glucuronic acid and N-acetyl-D-glucosamine (Tammi R., Agren UM., Tuhkanen AL., Tammi M. Hyaluronan metabolism in skin. Prog Histochem & Cytochem 29: 1-81, 1994).
  • HA is synthesized primarily by dermal fibroblasts and epidermal keratinocytes (Tammi R., Agren UM., Tuhkanen AL., Tammi M. Hyaluronan metabolism in skin, Prog Histochem & Cytochem 29: 1-81, 1994 ). With its residues bearing a negative charge, the HA acts as a water pump to maintain the viscoelasticity of the skin. HA has a major role in controlling the diffusion of food, hormones, vitamins and inorganic salts of connective tissue and in cleaning up metabolic waste that can induce inflammatory reactions. With age, the amount of HA and its level of polymerization decrease, resulting in a decrease in the amount of water retained in the connective tissue.
  • HA exists as a high molecular weight polymer (600-1000 kDa).
  • the physiological degradation of HA in the skin is done by (i) internalization by keratinocytes via CD44 and (ii) intracellular fragmentation into smaller fragments by hyaluronidases.
  • the fragmented HA is released by the keratinocytes, passes the basement membrane and is released directly into the lymphatic vessels (Tammi R., Agren UM, Tuhkanen AL, Tammi M. Hyaluronan metabolism in skin, Prog Histochem & Cytochem 29: 1- 81.1994).
  • HA In inflammatory conditions, the accumulation of low molecular weight forms of HA has been demonstrated.
  • platelet chemotactic factors such as fibrin stimulate the influx and activation of fibroblasts that degrade HA by hyaluronidase secretion resulting in high tissue concentrations of small HA fragments.
  • the generation of these small fragments of HA is also done by a variety of other mechanisms such as depolymerization by reactive oxygen species released by granulocytes or in irradiated skin by ultraviolet light, or de novo synthesis of fragments of low molecular weight.
  • HA high and low molecular weight HA may have different biological effects on cells and tissues (McKee CM, Penno MB, Cowman M., Burdick MD, Strieter RM, Bao CI Noble PW).
  • Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44.J Clin Invest 98: 2403-2413, 1996.
  • Termer CC Hennies 1, Voith U., Ahrens T., Weiss JM.
  • CD44 the principal receptor of HA, is a polymorphic transmembrane glycoprotein that has several isoforms generated by alternative splicing and post-translational modifications.
  • CD44 two major functions of CD44 in murine skin are (i) regulation of keratinocyte proliferation in response to extracellular stimuli and (ii) maintenance of local homeostasis of HA (Kaya G., Rodriguez L. , Jorcano JL., Vassalli P., Stamenkovic I. Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and irregular keratinocyte proliferation. Genes Dev 11: 996-1007, 1997). A decrease in epidermal CD44 expression in patients with Sclero-atrophic lichen was also observed.
  • the authors of the present invention have surprisingly found that it is possible to prevent the occurrence of atrophy of the skin by the concomitant use of a corticosteroid and fragments of HA of molecular weight between 20 and 50OkDa.
  • these HA fragments should also inhibit the other effects of corticosteroids, whose main therapeutic effect is the anti-inflammatory effect.
  • the present invention allows somehow dissociation of the therapeutic effect of the major side effect of topical corticosteroids. It therefore allows the use of a single topical preparation composed of the combination of HA fragments and a corticosteroid.
  • dissociation of the therapeutic effect and the side effect therefore means reducing or even eliminating the atrophying properties of the corticosteroid while preserving its anti-inflammatory effect.
  • the invention therefore relates more precisely to an anti-inflammatory dermatological composition intended for topical administration, characterized in that it comprises 0.005 to 0.1%, preferably 0.01 to 0.05% by weight of a corticoid and 0.1 to 1%, preferably 0.5 to 1% by weight of hyaluronate fragments of average molecular weight between 20 and 500 kDa, preferably between 20 and 375 kDa, more preferably between 20 and 150 kDa.
  • anti-inflammatory is intended to mean the conventional inhibition of topical manifestations such as redness, edema, vesicles, pain and pruritus, which are induced by a large number of patients. pathologies at the level of the skin and which are attenuated by the application of topical corticosteroids.
  • the term "potentiator” is intended to mean avoiding the main side effect of topical corticosteroid such as cutaneous atrophy, while obtaining a better anti-inflammatory effect than that which would be obtained with the same amount of topical corticosteroid alone, or the same anti-inflammatory effect as that which would be obtained with a smaller amount of corticosteroid.
  • the hyaluronate fragments of the present invention are capable of being obtained by heat treatment at a temperature above 100 ° C. of high molecular weight sodium hyaluronate fibers.
  • the hyaluronate fragments are also capable of being obtained by ultrasonic treatment of high molecular weight sodium hyaluronate fibers for 10 to 90 minutes, advantageously 45 minutes, at 400W and at 4 ° C., followed by filtration on gel, advantageously on Sephacryl S-400 gel.
  • the composition according to the invention advantageously comprises 0.05% by weight of a corticoid and 0.5% by weight of hyaluronate fragments.
  • composition according to the invention advantageously comprises 0.01% by weight of a corticoid and 1% by weight of hyaluronate fragments.
  • the corticoid may advantageously be chosen from alclometasone dipropionate, amcinonide, beclometasone dipropionate, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, budesonide, clobetasol propionate and clobetasol butyrate.
  • the corticosteroid is advantageously clobetasol propionate.
  • the invention also relates to a pharmaceutical composition comprising a composition as defined above and one or more pharmaceutically acceptable excipients.
  • the pharmaceutical composition according to the invention advantageously comprises a pharmaceutically acceptable emollient base.
  • the term “emollient base” refers to any cosmetic product which contributes to relaxing the tissues, calming inflammation and softening the skin.
  • the pharmaceutical composition according to the invention also advantageously comprises other dermato excipients logically acceptable for its presentation in the form of cream, balm, gel, spray, ointment, lotion, film-forming solution, transdermal system, for example a patch, mousse, shampoo.
  • the subject of the invention is also a composition according to any one of the preceding claims as a medicament, advantageously intended to treat inflammatory dermatoses which are commonly listed as indications of topical corticosteroids, and more particularly those which are localized on the fragile zones. such as the face, areas where the side effects of topical corticosteroids are particularly marked. Indeed, thanks to the dissociation of the therapeutic effect and the major side effect of topical corticosteroids, and to the potentiation of the anti-inflammatory effect, these fragile areas can be treated at a lower level. risk.
  • the subject of the invention is also a combination product comprising, on the one hand, a corticoid in the form of cream and, on the other hand, hyaluronate fragments of average molecular weight between 20 and 500 kDa, advantageously between 20 and 375 kDa, more preferably between 20 and 150 kDa, also in cream form, for separate dermatological use, simultaneous or spread over time, in inflammatory dermatitis therapy.
  • Hairless SKH1 mice received 2 times daily for 5 days a topical treatment on the back with a steroid (0.05% clobetasol propionate or 0.1% desonide) with or without HA fragments (molecular weight between 20%). and 500 kDa, and obtained by the method comprising the sonication and filtration steps described above). These fragments will be designated in the following examples by HAF.
  • the dermal and epidermal atrophy and the cutaneous hyaluronate concentration were respectively determined by the measurement of the dermis-epidermal thickness by optical microscopy and by ELISA.
  • TPA-Induced Inflammation in Mouse Ear Skin inflammation was induced by topical application of 0.005% TPA (12-o-tetradecanoylphorbol-13-acetate) in acetone to the ears of C57B1 / 6 mice; the control animals received the same volume of acetone.
  • Clobetasol propionate (0.05%) and HAF (1%) were dissolved in 100 ⁇ l of vehicle, and were applied together with TPA for 4 days; the control animals received the same vehicle volume.
  • Inflammation was determined by measuring the thickness of the ears by a clip and dermal-epidermal thickness in light microscopy and by the assay of myeloperoxidase activity. The animals were sacrificed 24 hours after the last application. Biopsies of 6 mm were taken, frozen in liquid nitrogen and then stored at -70 ° C. until the day of the analysis. The rest of the tissue was fixed with formalin and analyzed by immunohistology.
  • Myeloperoxidase activity was determined in the supernatant of homogenates of ear biopsies.
  • the biopsies immersed in 1.5 ml of 50 mM sodium phosphate buffer pH 6.0 containing 0.5% of hexadecyltrimethylammonium bromide (HTAB), were milled for 45 seconds at 0 ° C. in a Polytron PT 1200 homogenizer.
  • the enzymatic activity of myeloperoxidase was determined according to the method of Bradley et al. modified for the use of the photometric plate reader.
  • the following reagents were added in wells of 96-well plates: 50 ⁇ l of supernatant, 50 ⁇ l of phosphate buffer + HTAB, 50 ⁇ l of o-dianisidine 0.68 mg / ml dissolved in water; the reaction was initiated by the addition of 0.003% hydrogen peroxide prepared extemporaneously. The density optical was measured at 450 nm. The enzymatic activity was compared to that of the ears biopsies treated only with TPA. The expression of CD44, CD44v3 and pro-HB-EGF was analyzed by immunohistochemistry and western blotting according to methods already described (PLoS Med 3 (12): e493, 2006).
  • the epidermal and cutaneous thicknesses were measured by an ocular micrometer. Ten measurements were performed per mouse. The results are summarized in Table 1 below.
  • the prevention index is the ratio between control treated with clobetasol propionate (PC) alone and PC + HAF composition.
  • Figure 1 shows histological sections of the dermis and epidermis of hematoxylin-eosin stained mice.
  • the epidermal thickness was measured by an ocular micrometer after treatment at different concentrations of desonide. Ten measurements were performed per mouse. The results are shown in Table 2.
  • the prevention index is the ratio, at a given corticoid concentration, between the control treated with the corticosteroid alone and with the corticosteroid + HAF composition. Table 2
  • the epidermal thickness was measured by an ocular micrometer after treatment with different corticosteroids. Ten measurements were performed per mouse. The results are collated in Table 3.
  • the prevention index is the ratio between control treated with corticosteroid alone and the corresponding composition including HAF. Table 3.
  • HAFs prevent epidermal atrophy induced by various topical corticosteroids (CS).
  • Untreated hyaluronic acid, fragments obtained by the action of hyaluronidase, as well as HAF were compared for their preventive effects.
  • the epidermal thickness was measured by an ocular micrometer. Ten measurements were performed per mouse. The results are shown in Table 4.
  • the prevention index is the ratio between the control treated with the corticosteroid alone and each corticosteroid composition + HAF. Table 4
  • hyaluronidase-prepared fragments do not prevent epidermal atrophy induced by clobetasol propionate or desonide.
  • Figure 2 is an immunohistochemical analysis of mouse sections by anti-CD44. It shows that HAFs restore and enhance the expression of CD44 in mouse skin treated with clobetasol propionate.
  • Figure 3 is a Western blot analysis of mouse skin protein extracts with an anti-CD44v3 antibody. It shows that the fragments of HAF restore and increase the expression of CD44v3 in mouse skin treated with desonide and thus the potentiating effect of HAF.
  • Figure 4 is a western blot analysis of mouse skin protein extracts with 25 kDa anti-pro-HB-EGF antibody, A representing vehicle, B, clobetasol propionate and C clobetasol propionate + HAF. It shows that HAFs restore and enhance expression of pro-HB-EGF in mouse skin treated with clobetasol propionate.
  • the epidermal inflammation induced by the application of Phorbol TPA ester was measured after application of TPA, then after treatment with clobetasol propionate, and after treatment with the composition comprising clobetasol propionate and HAF. Ten measurements were performed per mouse. The results are summarized in Table 5 below.
  • the anti-inflammation index is the ratio between the control treated with TPA, and the composition TPA + PC or TPA + PC + HAF.
  • the dermal inflammation induced by the application of Phorbol TPA ester was measured after application of TPA, then after treatment with clobetasol propionate, and after treatment with the composition comprising clobetasol propionate and HAF. Ten measurements were performed per mouse. The results are collated in Table 6 below.
  • the anti-inflammation index is the ratio between the control treated with TPA, and the association TPA + PC or TPA + PC + HAF.
  • the dermal cellularity induced by the application of Phorbol TPA ester was measured after application of TPA, then after treatment with clobetasol propionate, and after treatment with the composition comprising clobetasol propionate and HAF. Ten measurements were performed per mouse. The results are shown in Table 7.
  • the anti-inflammation index is the ratio between the control treated with TPA, and the association TPA + PC or TPA + PC + HAF.
  • the cutaneous myeloperoxidase activity induced by the application of Phorbol TPA ester was measured, after application of TPA, then after treatment with clobetasol propionate, and after treatment with the composition comprising clobetasol propionate and HAF. Ten measurements were performed per mouse. The results are summarized in Table 8.
  • the anti-inflammation index is the ratio between the control treated with TPA, and the association TPA + PC or TPA + PC + HAF.
  • HAFs do not inhibit the anti-inflammatory effect of clobetasol propionate but, on the contrary, potentiate its anti-inflammatory effect.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP08774984A 2007-07-16 2008-07-10 Entzündungshemmende dermatologische zusammensetzung mit kortikosteroiden und hyaluronat-fragmenten und ihre verwendungen Withdrawn EP2178538A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0756515A FR2918892B1 (fr) 2007-07-16 2007-07-16 Composition dermatologique anti-inflammatoire comprenant des corticoides et des fragments de hyaluronate, et ses utilisations
PCT/EP2008/059021 WO2009010448A2 (fr) 2007-07-16 2008-07-10 Composition dermatologique anti-inflammatoire comprenant des corticoïdes et des fragments de hyaluronate, et ses utilisations

Publications (1)

Publication Number Publication Date
EP2178538A2 true EP2178538A2 (de) 2010-04-28

Family

ID=39015928

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08774984A Withdrawn EP2178538A2 (de) 2007-07-16 2008-07-10 Entzündungshemmende dermatologische zusammensetzung mit kortikosteroiden und hyaluronat-fragmenten und ihre verwendungen

Country Status (5)

Country Link
US (2) US20100197632A1 (de)
EP (1) EP2178538A2 (de)
JP (1) JP2010533673A (de)
FR (1) FR2918892B1 (de)
WO (1) WO2009010448A2 (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2493906B1 (de) 2009-10-28 2015-10-21 Basf Se Heteroleptische carben-komplexe und deren verwendung in der organischen elektronik
US20210000910A1 (en) 2019-07-03 2021-01-07 Jysk Skin Solutions Pte Ltd Topical compositions
FR3105922B1 (fr) 2020-01-08 2022-12-02 Le Rouge Francais Composition cosmétique pour le traitement des lèvres sous forme de solide compact contenant au moins un agent probiotique et au moins un composé choisi parmi l'acide hyaluronique et ses dérivés.
US12083204B2 (en) 2022-06-02 2024-09-10 L'oreal Topical composition for homeostatic delivery of nitric oxide and uses thereof
FR3148720A1 (fr) 2023-05-18 2024-11-22 Le Rouge Francais Composition cosmétique aqueuse contenant un agent probiotique, un composé choisi parmi l'acide hyaluronique et ses dérivés, un colorant particulier et une huile végétale.
FR3151215A1 (fr) 2023-07-23 2025-01-24 Le Rouge Francais Composition cosmétique topique anhydre pulvérulente comprenant un agent probiotique, de l'acide hyaluronique ou un de ses dérivés, un colorant particulier et une poudre minérale particulière.

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61151122A (ja) * 1984-12-25 1986-07-09 Sekisui Chem Co Ltd 外用貼付剤
JP2945993B2 (ja) * 1989-12-05 1999-09-06 武田薬品工業株式会社 外用剤
CA2208916A1 (en) * 1997-07-03 1999-01-03 Hyal Pharmaceutical Corporation Promotion of wound healing utilizing steroids having reduced deterioroussystemic side effects typical of glucocorticoids, mineralocorticoids andsex steroids
IT1309588B1 (it) * 1999-03-05 2002-01-24 Altergon Sa Cerotto con spessore sottile contenente betametasone ed acidoialuronico per il trattamento di psoriasi, dermatite, dermatosi.
JP4451070B2 (ja) * 2003-02-03 2010-04-14 生化学工業株式会社 Ｃｄ４４切断誘導剤
FR2865651B1 (fr) * 2004-01-29 2007-09-28 Fabre Pierre Dermo Cosmetique Compositions topiques associant des fragments de hyaluronate de sodium et un retinoide utiles en dermatologie cosmetique et medicale
JP4022659B2 (ja) * 2005-05-24 2007-12-19 株式会社 糖質科学研究所 自己免疫疾患、炎症及び神経疾患の治療剤及び予防剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KAYA GUERKAN ET AL: "Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism", PLOS MEDICINE, PUBLIC LIBRARY OF SCIENCE, US, vol. 3, no. 12, 1 December 2006 (2006-12-01), pages 2291 - 2303, XP008146393, ISSN: 1549-1277, DOI: 10.1371/JOURNAL.PMED.0030493 *

Also Published As

Publication number Publication date
US20100197632A1 (en) 2010-08-05
JP2010533673A (ja) 2010-10-28
FR2918892A1 (fr) 2009-01-23
US20130059814A1 (en) 2013-03-07
FR2918892B1 (fr) 2010-02-12
WO2009010448A2 (fr) 2009-01-22
WO2009010448A3 (fr) 2009-06-04

Similar Documents

Publication Publication Date Title
CA2623529C (fr) Complexe polymere amphiphile-pdgf
US10912743B2 (en) Compositions for treating inflammation and methods of treating the same
CA2553725C (fr) Compositions topiques associant des fragments de hyaluronate de sodium et un retinoide
CA2686558A1 (fr) Preparations pharmaceutiques ou cosmetiques pour application topique et/ou parenterale, leurs procedes de preparation, et leurs utilisations
EP1965808A1 (de) Pharmazeutische oder kosmetische zubereitungen für topische und/oder parenterale anwendung, zubereitungsverfahren und verwendung
CA2946943C (fr) Association d'un acide hyaluronique et d'un polysaccharide sulfate
EP2178538A2 (de) Entzündungshemmende dermatologische zusammensetzung mit kortikosteroiden und hyaluronat-fragmenten und ihre verwendungen
CA2686505A1 (fr) Preparations pharmaceutiques ou cosmetiques pour application topique et/ou parenterale, leurs procedes de preparation, et leurs utilisations
AU2008214695B2 (en) Use of chitosans for the treatment of nail inflammatory diseases
WO2008139123A2 (fr) Preparations pharmaceutiques ou cosmetiques pour application topique et/ou parenterale, leurs procedes de preparation, et leurs utilisations
US20210244638A1 (en) Inhibitors of glycosphingolipid synthesis and methods of use
CA2686556A1 (fr) Preparations pharmaceutiques ou cosmetiques pour application topique et/ou parenterale, leurs procedes de preparation, et leurs utilisations
FR2977494A1 (fr) Compositions cosmetiques ou pharmaceutiques contenant des acides hyaluroniques de masses moleculaires differentes
FR2936708A1 (fr) Complexe associant un derive organique du silicium avec des fragments calibres d'acide hyaluronique, a action preventive et reparatrice des degradations cutanees.
EP2155186A2 (de) Pharmazeutische oder kosmetische präparate zur topischen und/oder parenteralen anwendung, verfahren zu ihrer herstellung und ihre anwendung
MC200122A1 (fr) Complexe associant un dérivé organique du siliciumavec des fragments calibrés d'acide hyaluronique, à action préventive et réparatrice des dégradatio ns cutanées

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100216

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

17Q First examination report despatched

Effective date: 20100616

DAX Request for extension of the european patent (deleted)
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20150623