WO2009019509A2 - Amélioration de la fonction assurée par la barrière cutanée - Google Patents

Amélioration de la fonction assurée par la barrière cutanée Download PDF

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Publication number
WO2009019509A2
WO2009019509A2 PCT/GB2008/050654 GB2008050654W WO2009019509A2 WO 2009019509 A2 WO2009019509 A2 WO 2009019509A2 GB 2008050654 W GB2008050654 W GB 2008050654W WO 2009019509 A2 WO2009019509 A2 WO 2009019509A2
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Prior art keywords
stratum corneum
skin
activity
skin protease
acts
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PCT/GB2008/050654
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English (en)
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WO2009019509A3 (fr
Inventor
Simon Ward
Michael Cork
Alice Macgowan
Manar Moustafa
Simon Danby
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York Pharma Plc
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Publication of WO2009019509A2 publication Critical patent/WO2009019509A2/fr
Publication of WO2009019509A3 publication Critical patent/WO2009019509A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • the epithelium serves as a first line of defence between the body and the environment. Disturbance of the epidermal barrier can favour the penetration of microbes and allergens.
  • the barrier to the penetration of irritants and allergens is located in the lower part of the stratum corneum.
  • the structural integrity of the stratum corneum is maintained by the presence of modified desmosomes, called corneodesmosomes.
  • Corneodesmosomes lock the corneocytes together and provide tensile strength to the stratum corneum to resist shearing forces.
  • the stratum corneum can be visualised as being similar to a brick wall, with the corneocytes analogous to bricks and the lipid lamellae acting as cement. Extending this model, the corneodesmosomes can be thought of as analogous to iron rods that pass down through holes in the bricks to give the wall its tensile strength.
  • Corneocytes are flattened cells that represent the final differentiation stages of the outermost keratinocytes of the granular layer, when these cells lose their sub- cellular organelles and nuclei and become densely packed with keratin fibres.
  • stratum corneum In human subjects the stratum corneum has an average of 20 corneocyte layers, with each corneocyte being approximately 30 micrometres in diameter.
  • the thickness of the stratum corneum can vary in different body regions to increase the level of protection to areas that experience greater friction, such as the soles of the feet and palms of the hands.
  • the current model of the processes involved in desquamation involves a network of degradatory proteases regulated by protease inhibitors, which break down the extracellular corneodesmosomal adhesion proteins that bind the corneocytes together and in doing so allow the corneocytes to shed from the skin surface.
  • Such conditions particularly atopic and non atopic eczema or dermatitis, irritant contact dermatitis and sensitive skin, all arise partially or completely as a result of a defective skin or epidermal barrier.
  • a first aspect to the present invention provides a method of increasing or maintaining corneocyte size.
  • a second aspect to the present invention provides a method of increasing or maintaining stratum corneum thickness.
  • a third aspect to the present invention provides a method of increasing or maintaining corneocyte size and stratum corneum thickness.
  • a fourth aspect to the present invention provides a method of increasing or maintaining stratum corneum thickness and reducing the activity of at least one skin protease which acts in the stratum corneum.
  • a fifth aspect to the present invention provides a method of increasing or maintaining stratum corneum thickness and reducing trans-epidermal water loss
  • a sixth aspect to the present invention provides a method of increasing or maintaining corneocyte size and reducing the activity of at least one skin protease which acts in the stratum corneum.
  • a seventh aspect to the present invention provides a method of increasing or maintaining corneocyte size and reducing TEWL.
  • An eighth aspect to the present invention provides a method of increasing or maintaining corneocyte size and stratum corneum thickness and reducing the activity of at least one skin protease which acts in the stratum corneum.
  • a tenth aspect to the present invention provides a method of increasing or maintaining stratum corneum thickness and reducing the activity of at least one skin protease which acts in the stratum corneum and reducing TEWL.
  • An eleventh aspect to the present invention provides a method of increasing or maintaining corneocyte size and reducing the activity of at least one skin protease which acts in the stratum corneum and reducing TEWL.
  • a twelfth aspect to the present invention provides a method of improving or increasing the protease inhibitory activity index (PIAI) score of the skin barrier.
  • PIAI protease inhibitory activity index
  • Each of the above aspects of the present invention can be achieved by a method comprising topically applying a skin protease inhibitor to induce a sustained reduction in the activity of at least one skin protease which acts in the stratum corneum.
  • Inducing a sustained reduction in the activity of at least one skin protease which acts in the stratum corneum means reducing the activity of at least one such enzyme for at least three hours. In embodiments, the reduction in skin protease activity level is maintained, for, or at least for, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, 24, 36 or 48 hours.
  • a skin protease inhibitor is an agent that is capable of inducing a reduction in the activity of at least one skin protease that is active in the stratum corneum. Such agents are also referred to as skin protease modulators.
  • the inhibited skin protease can be one or more of those known to be active in the stratum corneum, including stratum corneum chymotryptic enzyme (SCCE) and stratum corneum tryptic enzyme (SCTE).
  • SCCE stratum corneum chymotryptic enzyme
  • SCTE stratum corneum tryptic enzyme
  • Figure 2 illustrates how eczematous skin is different from normal skin with the additional indication of increasing protease activity (1, 5, 6, 7, 8 represent respectively increasing protease activity) and reduction of corneocyte size (9, 10, 11, 12 respectively) as skin barrier damage increases.
  • FIG 3 illustrates high (i.e., abnormal) protease activity.
  • the corneocytes 13 are small, the stratum corneum is thin and the corneodesmosomes 14 are significantly weakened (by analogy, "rusted away") due to high protease activity.
  • allergens can penetrate through the damaged stratum corneum, interacting with the immune system and triggering a flare of the eczema.
  • Figure 4 compares the pictures of skin with low 15 and high 16 protease activity.
  • Figure 5 illustrates the effect of short duration/transient protease inhibition.
  • the protease activity has diminished, as shown by the change in shading, indicating that the protease activity has been transiently inhibited, but not fully. Because the inhibition of protease activity is of short duration, there has not been time for the appearance of the stratum corneum to change. The corneocytes, therefore, are still small and the stratum corneum still thin.
  • FIG 7 shows that transient, short-term, protease inhibition 19 transforms into sustained protease inhibition 20 when the SPI has a sustained effect and protease inhibition is maintained in the skin.
  • the structure of the stratum corneum changes; the corneocytes become bigger 21 and the stratum corneum increases in thickness.
  • the corneodesmosomes 22 are no longer weakened and the normal structural integrity of the stratum corneum has been restored. Allergens are now unable to penetrate. Functional change in structural integrity of the stratum corneum can be measured as a decrease in the trans-epidermal water loss (TEWL).
  • TEWL trans-epidermal water loss
  • Figure 8 shows that repetitive washing reduces skin barrier integrity.
  • Figure 9 shows that skin barrier integrity is increased by anti-protease treatment relative to vehicle alone.
  • Figure 12 shows the effect of another treatment with a skin protease inhibitor cream on skin protease activity.
  • the model describes a network of degradatory proteases, regulated by protease inhibitors, breaking down the extracellular corneodesmosomal adhesion proteins that bind the corneocytes together, allowing the corneocytes to shed from the surface of the skin.
  • the normal turnover time for the stratum corneum is 14 days.
  • TEWL trans-epidermal water loss
  • TEWL is a measure of skin barrier or stratum corneum integrity, and it is affected by the level of skin protease activity.
  • the integrity of the skin barrier or the integrity of the stratum corneum can be increased, and consequently TEWL reduced, by one or more of increasing or maintaining corneocyte size and increasing or maintaining stratum corneum thickness.
  • Examples of dermatological conditions that can be treated in accordance with the present invention include eczema, dermatitis and like conditions such as atopic and non atopic eczema or dermatitis, intrinsic atopic eczema or dermatitis, extrinsic atopic eczema or dermatitis, sebarrhoeic eczema, irritant contact dermatitis, cosmetic eczema or dermatitis, allergic contact dermatitis, dry skin, dry/ sensitive skin and other sensitive skin conditions, particularly those that cause or are associated with pruritus.
  • eczema dermatitis and like conditions such as atopic and non atopic eczema or dermatitis, intrinsic atopic eczema or dermatitis, extrinsic atopic eczema or dermatitis, sebarrhoeic eczema, irritant contact dermatitis,
  • Examples of other dermatological conditions that can be treated in accordance with the present invention include ichthyosis vulgaris, X-linked recessive ichthyosis, X-linked hypohidrotic ectodermal dysplasia, Darier's disease, hand dermatitis, face dermatitis, skin dermatoses, diaper/nappy rash, psoriasis, allergic skin diseases, anaphylaxis, hypersensitivity reactions to foods, drugs and insects, hypertrophic scars/keloids, blistering diseases and T-cell lymphoma.
  • Preferred examples of dermatological conditions that can be treated in accordance with the present invention include irritant/allergic contact eczema or dermatitis of the hand and allergic/irritant contact facial eczema or dermatitis and atopic eczema or dermatitis.
  • Sustained inhibition of at least one of the skin proteases which act in the stratum corneum leads to one or more of a reduction in TEWL, an increase in corneocyte size, an increase in the thickness of the stratum corneum, and an improved or increased PIAI score of the skin barrier.
  • a sustained inhibition of the activity of at least one skin protease which acts in the stratum corneum means an inhibition in the activity of at least one such enzyme which lasts for at least three hours.
  • the reduction in skin protease activity level is maintained for 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, 24, 36 or 48 hours. It is with sustained inhibition of the activity of at least one skin protease which acts in the stratum corneum that effective and beneficial changes are seen in the stratum corneum and repair or maintenance of the skin barrier is achieved.
  • the at least one skin protease can be one or more of those known to be active in the stratum corneum, including stratum corneum chymotryptic enzyme (SCCE) and stratum corneum tryptic enzyme (SCTE).
  • the inhibition in the activity of skin proteases which act in the stratum corneum is a reduction in activity to achieve the level of protease activity found in a corresponding region of skin in an individual unaffected by the above mentioned skin conditions. Reducing the activity of skin proteases which act in the stratum corneum to normal levels helps to re-establish the fine balance in the desquamation processes. Complete inhibition of the skin proteases which act in the stratum corneum would also be detrimental to the integrity of the stratum corneum and the skin barrier.
  • corneocyte size is an important histological marker or effect of the action of skin protease inhibitors.
  • An aim of the present invention is to increase or maintain the size of the corneocytes in the stratum corneum. This allows treatment or prevention of conditions involving abnormally small corneocyte size, such as those listed above.
  • corneocytes can vary according to the region of the body and a person's age. Normal corneocytes on the face of individuals aged 20 to 30 years old have a surface area of about 550 ⁇ m 2 to 560 ⁇ m 2 . The average surface area of the corneocytes on the upper arm, forearm and abdomen is 980-1010 ⁇ m 2
  • the present invention preferably aims, in those aspects which involve increasing corneocye size, to bring the size of the corneocytes in the treated area of skin up towards the size of the corneocytes found in a corresponding region of normal skin. Where maintenance of corneocyte size is the objective, it is preferred for these cells to be maintained at the size found in a corresponding region of normal skin.
  • Another aim of the present invention is to decrease skin protease activity in the stratum corneum, preferably by inhibiting skin protease activity in the stratum corneum, or reducing the protease activity in the stratum corneum, to normal levels.
  • Skin protease inhibitors of use in the present invention are those which have a sustained inhibitory effect on at least one skin proteases which acts in the stratum corneum. This not only prevents further breakdown of the corneodesmosomes, but also allows a period in which the differentiation pathway of corneocytes can proceed normally.
  • a further example of a skin protease inhibitor in accordance with the present invention is lactic acid.
  • This organic carboxylic acid is dermatologically absorbable and hence penetrates into the stratum corneum and has its effect within the stratum corneum. Once the pH of the stratum corneum is lowered this can reduce the activity of the skin proteases which have their effect for several hours.
  • composition is made by heating oil (emollient and structuring components) and water (actives and solvent/humectant) phase components separately to 75°C. Mixing whilst stirring intensively. Cooling to room temperature whilst stirring, and adding preservative mixture.
  • Example 2 A cream formulation for use in and in accordance with the invention. Emulsion with Glucam E20
  • This composition was made as follows. Heat oil (emollient and structuring components) and water (actives and solvent/humectant) phase components separately to 75°C. Mix whilst stirring intensively. Homogenise for 1 minute at 75°C.
  • This composition was made as follows. Heat oil (emollient and structuring components) and water (actives and solvent/humectant) phase components separately to 75°C.
  • This composition was made as follows. Weigh ZnL, glycerine, phenoxyethanol and water into 400 ml beaker; stir until ZnL completely in solution; weigh Carbopol Aqua CC into 400 ml beaker; add lactic acid very carefully drop wise and stir (spatula) to constant pH. At around pH 5.20 gelation starts and extra care is needed. Final pH adjustment requires single drop additions and stirring to constant pH of 4.52.
  • Skin diseases characterised by a disrupted epidermal barrier such as atopic eczema
  • atopic eczema can be modelled by creating experimental damage to the stratum corneum. This is achieved in a number of ways, such as treating the skin with topical steroids, or by repeated washing.
  • Glucocorticosteroid-treated skin shares characteristics with conditions affecting barrier function such as atopic dermatitis (AD), including elevated protease activity, reduced barrier integrity, delayed barrier recovery, and thinning of the stratum corneum (SC).
  • AD atopic dermatitis
  • SC stratum corneum
  • a steroid-induced model of skin barrier damage was established by applying two finger-tip units of betamethasone valerate 0.1% to the medial forearm of volunteers (full consent provided) for 4 weeks. Skin barrier function measurements were then taken (see below).
  • the integrity of the skin barrier can be assessed by measuring markers of skin barrier function, such as trans-epidermal water loss (TEWL), corneocyte size, skin thickness or protease activity. Improvements in skin barrier function, for example, after treatment with an anti-protease treatment, can be evaluated using these techniques.
  • markers of skin barrier function such as trans-epidermal water loss (TEWL), corneocyte size, skin thickness or protease activity. Improvements in skin barrier function, for example, after treatment with an anti-protease treatment, can be evaluated using these techniques.
  • Skin barrier integrity can be measured using a combination of TEWL readings and tape stripping.
  • TEWL values increase upon skin barrier damage. Removal of the upper layers of the stratum corneum by tape stripping with D-Squame " discs disrupts the skin barrier. A healthy skin barrier requires more disruption than a damaged barrier or one thinned in a disease state.
  • the number of tape strips required to reach a set TEWL value of 100 g/m 2 /h was measured in volunteers. Skin barrier damage was induced using the washing protocol described in section 1.2 and TEWL measurements were taken before and after washing. Skin barrier integrity is decreased after washing, as determined by the decreased number of tape strips needed to reach a TEWL value of 100 g/m 2 /h as shown in Figure 8. The decreased number of tape strips required indicates an elevated TEWL.
  • Figure 8 shows that repetitive washing reduces skin barrier integrity.
  • Stratum corneum integrity was determined in 9 subjects before and after a regime of forearm washing with liquid soap. Stratum corneum integrity is measured as the number of D-Squame disc-skin strippings required per site to reach a TEWL of 100 g/m 2 /h. Each dot represents an individual subject with lines connecting the paired observations. The means of the two groups were analysed using a paired two-tailed t-test and found to be significantly different.
  • the increased number of tape strips needed to reach a TEWL value of 100 g/m 2 /h indicates a higher degree of skin barrier integrity has been restored to the damaged stratum corneum by the application of the anti- protease gel than by the vehicle alone.
  • the increased number of tape strips required is indicative of decreased TEWL and improved skin barrier function and integrity.
  • Figure 9 shows that the skin barrier integrity is increased by anti-protease treatment relative to vehicle. Following a repetive washing protocol, anti- protease gel or vehicle was applied over a 24 hour period to the volar forearm. The number of tape strips needed to reach a TEWL of 100 g/m 2 /h was recorded before and after washing and the percentage change calculated.
  • Corneocyte size is has been reported to be decreased in diseases characterised by an impaired skin barrier and in areas of skin or in disease states where there is increased epidermal turnover. Increased protease activity results in increased epidermal turnover, therefore, protease activity could be expected to decrease corneocyte size.
  • Figure 10 shows the corneocyte surface area ( ⁇ m 2 ) before and after intensive washing.
  • the bars represent the mean surface area for 8 volunteers tested before and after washing of both forearms with liquid soap, with error bars showing the standard error of the mean. Using the paired two-tailed t-test a significant difference was reported. 2.3 Protease activity
  • Increased protease activity results in an increased rate of turnover of the stratum corneum, and, ultimately, to a thinner skin barrier. Volunteers underwent the protocol described in section 1.1 to induce skin barrier damage and were then treated for 24 hours with an anti-protease cream (Fl) containing zinc lactate at pH 4.5. Protease activity was demonstrated by zymography using tissue sections of punch biopsies collected immediately following steroid/Fl treatment.
  • Fl anti-protease cream
  • Frozen cross-sections (7-8 ⁇ m) of the epidermis/dermis were incubated with a highly quenched fluorescently labelled broad-spectrum protease substrate (casein- BODIPY FL conjugate) for 1 hour at 37 0 C, and subsequently analysed by confocal microscopy for regions of high fluorescence, synonymous with high rates of substrate cleavage (BODIPY FL release).
  • the fluorescent counterstain, propidium iodide was used to label cells, in order to easily identify the stratum corneum.
  • the stratum corneum is the uppermost layer of the epidermis, composed of highly keratinised corneocytes. As these cells are de-nucleated, they do not label with the counterstain. A high degree of protease activity is localised to the stratum corneum, and using in situ zymography, is visualised in this case as intense fluorescence (green) emitted from the liberated BODIPY FL dye.
  • Proteases such as stratum corneum chymotryptic enzyme (SCCE) contribute to this activity, and account for the rate of barrier breakdown.
  • SCCE stratum corneum chymotryptic enzyme
  • Treatment with steroids facilitates barrier breakdown by inducing the expression/activity of epidermal proteases.
  • the effect of 4-week, 0.1 % betamethasone treatment on protease activity in the epidermis can be seen in Figures 11 and 12. Compared to the control, the release of BODIPY FL dye, and hence the protease activity, is greater in tissue sections from biopsied skin that has been treated with steroid.
  • Figure 11 shows the effect of Fl treatment on protease activity.
  • F lateral right forearm, no treatment
  • B medial right forearm, steroid only
  • C lateral left forearm, Fl treatment only
  • D medial left forearm, steroid treated followed by Fl application.
  • Steroid treatment involved application of 0.1 % betamethasone for 4 weeks.
  • Fl treatment involved applications over a 24 h period post-steroid treatment and directly prior to collection of punch biopsies. Images are of epidermal cross-sections, with red fluorescent staining to highlight the cells.
  • Figure 12 is an example of an alternative protocol.
  • biopsies were collected following treatment of both forearms with steroid, and of the left forearm only with Fl for 24h.
  • Steroid-associated protease activity was suppressed by the application of Fl, as can be seen from Figure 12.
  • Figure 12 shows the effect of Fl treatment on protease activity.
  • Two sites on the forearms were treated in the following way: (A+C) right forearm, steroid induced control; (B +D) left forearm, steroid treated followed by F2 application.
  • Steroid treatment involved application of 0.1 % betamethasone for 4 weeks.
  • Fl treatment involved applications over a 24 h period post-steroid treatment and directly prior to collection of punch biopsies. Images are of epidermal cross- sections, with red fluorescent staining to highlight the cells. The stratum corneum is visible only by the presence of protease activity indicated by fluorescence from the released BODIPY FL dye (green). The analysis by in situ zymography was conducted twice on separate occasions with duplicate sections. The images shown are representative of these repeats.
  • Skin barrier thickness is known to be decreased in diseases such as atopic eczema.
  • a thinner stratum corneum presents less of a barrier to the penetration of irritants and allergens that can trigger a flare of eczema.
  • Figure 13 shows an example of a thinned skin barrier in a healthy volunteer treated for 30 days on the forearm with betamethasone valerate 0.1%.
  • Figure 13 shows that steroid treatment thins the skin barrier, it thins the stratum corneum (SC).
  • SC stratum corneum

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Abstract

L'épithélium constitue une première ligne de défense entre l'organisme et l'environnement. Une perturbation de la barrière épithéliale, la couche cornée, peut favoriser la pénétration de microbes et d'allergènes et joue un rôle dans des affections dermatologiques comme diverses formes d'eczéma et de dermatite, telles que l'eczéma ou la dermatite atopique et non atopique, l'eczéma séborrhéique, la dermatite de contact irritant, la dermatite de contact allergique et d'autres affections associées à une sensibilité cutanée. La présente invention concerne un procédé permettant de protéger l'intégrité de la couche cornée, en limitant l'activité de la protéase de la couche cornée et/ou en augmentant ou en maintenant la taille des cornéocytes et/ou en augmentant ou en maintenant l'épaisseur de la couche cornée et/ou en limitant la perte d'eau transépidermique et/ou en améliorant l'indice de l'activité d'inhibition de la protéase.
PCT/GB2008/050654 2007-08-03 2008-08-01 Amélioration de la fonction assurée par la barrière cutanée WO2009019509A2 (fr)

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GB0715141.8 2007-08-03
GB0715141A GB0715141D0 (en) 2007-08-03 2007-08-03 Improving skin barrier function

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2316415A3 (fr) * 2009-07-28 2012-06-20 Sirvis Compositions pour les lèvres comprenant un composé contenant du zinc dissout dans une phase hydrophobique

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0413528A1 (fr) * 1989-08-15 1991-02-20 Ruey J. Dr. Yu Compositions amphotériques et formes polymériques des alpha-hydroxy-acides, et leur application thérapeutique
WO1997015282A1 (fr) * 1995-10-27 1997-05-01 Medicis Pharmaceutical Corporation Compositions destinees a etre utilisees dans le traitement d'affections dermatologiques et leurs procedes d'utilisation
WO1999063816A1 (fr) * 1998-06-09 1999-12-16 Embro William J Procede et composition pour le traitement d'irritations et d'infections epidermiques
WO2003026604A1 (fr) * 2001-09-24 2003-04-03 Pierre Fabre Dermo-Cosmetique Composition dermocosmetologique a visee anti-inflammatoire, en particulier pour le traitement de l'acne et de la dermite seborrheïque
WO2003059297A2 (fr) * 2002-01-21 2003-07-24 Slovakofarma A.S. Compositions dermatologiques topiques et procede pour leur preparation
EP1437124A1 (fr) * 2003-01-08 2004-07-14 L'oreal Composition pour le traitement d'une peau à tendance acnéique
US20050058672A1 (en) * 2003-09-14 2005-03-17 Bioderm Research Baby Care Skin Protectant Compositions for Diaper Rash
WO2007020479A2 (fr) * 2005-08-19 2007-02-22 York Pharma Plc Ameliorations apportees a des compositions pharmaceutiques
WO2008025837A1 (fr) * 2006-08-31 2008-03-06 York Pharma Plc Améliorations de compositions pharmaceutiques

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0413528A1 (fr) * 1989-08-15 1991-02-20 Ruey J. Dr. Yu Compositions amphotériques et formes polymériques des alpha-hydroxy-acides, et leur application thérapeutique
WO1997015282A1 (fr) * 1995-10-27 1997-05-01 Medicis Pharmaceutical Corporation Compositions destinees a etre utilisees dans le traitement d'affections dermatologiques et leurs procedes d'utilisation
WO1999063816A1 (fr) * 1998-06-09 1999-12-16 Embro William J Procede et composition pour le traitement d'irritations et d'infections epidermiques
WO2003026604A1 (fr) * 2001-09-24 2003-04-03 Pierre Fabre Dermo-Cosmetique Composition dermocosmetologique a visee anti-inflammatoire, en particulier pour le traitement de l'acne et de la dermite seborrheïque
WO2003059297A2 (fr) * 2002-01-21 2003-07-24 Slovakofarma A.S. Compositions dermatologiques topiques et procede pour leur preparation
EP1437124A1 (fr) * 2003-01-08 2004-07-14 L'oreal Composition pour le traitement d'une peau à tendance acnéique
US20050058672A1 (en) * 2003-09-14 2005-03-17 Bioderm Research Baby Care Skin Protectant Compositions for Diaper Rash
WO2007020479A2 (fr) * 2005-08-19 2007-02-22 York Pharma Plc Ameliorations apportees a des compositions pharmaceutiques
WO2008025837A1 (fr) * 2006-08-31 2008-03-06 York Pharma Plc Améliorations de compositions pharmaceutiques

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE EMBASE [Online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; June 2005 (2005-06), TJIOE M ET AL: "Anal pruritus" XP002517879 Database accession no. EMB-2005272867 & NEDERLANDS TIJDSCHRIFT VOOR DERMATOLOGIE EN VENEREOLOGIE 200506 NL, vol. 15, no. 5, June 2005 (2005-06), pages 221-223, ISSN: 0925-8604 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2316415A3 (fr) * 2009-07-28 2012-06-20 Sirvis Compositions pour les lèvres comprenant un composé contenant du zinc dissout dans une phase hydrophobique

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