CA2881267C - Inhibition of the adhesion of pathogenic microorganisms by a sucrose stearate and/or a sorbitan ester in the cosmetic treatment of cutaneous atopy - Google Patents
Inhibition of the adhesion of pathogenic microorganisms by a sucrose stearate and/or a sorbitan ester in the cosmetic treatment of cutaneous atopy Download PDFInfo
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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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
- A61K8/60—Sugars; Derivatives thereof
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- 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
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- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier 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
- A61Q17/005—Antimicrobial preparations
-
- 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
- A61Q19/007—Preparations for dry skin
Abstract
A composition for topical application comprising: -at least one sucrose stearate comprising at least 70% by weight of monoesters of sucrose and of stearic acid, the rest being composed of diesters, triesters and polyesters of sucrose and of stearic acid, -and/or a sorbitan ester, for use in the therapeutic treatment of cutaneous atopy, as an agent for inhibiting the adhesion of Staphylococcus aureus to human nasal mucosa and skin.
Description
INHIBITION OF THE ADHESION OF PATHOGENIC MICROORGANISMS BY A SUCROSE
ATOPY
SUMMARY OF THE INVENTION
The invention relates to a cosmetic treatment process for human atopic dermatitis based on coating the surface of the skin with a cosmetic composition that forms a film on it.
According to the invention, this film¨by virtue of its constituents __ inhibits the adhesion of pathogenic micro-organisms to the skin and reinforces the skin barrier.
More specifically, the cosmetic composition contains an ester of sucrose and/or an ester of sorbitan capable of blocking the adhesion of Staphylococcus aureus to the skin and nasal mucosa, thereby inhibiting the proliferation of pathogenic flora. The effect of this inhibition is to protect the cutaneous barrier by limiting the breakdown of lipids, especially ceramides, which is indirectly due to Staphylococcus aureus.
PRIOR ART
Atopic dermatitis or cutaneous atopy is an inflammatory, pruriginous skin condition associated with a hereditary immune predisposition and abnormalities of the cutaneous barrier. In clinical terms, this hereditary predisposition can also manifest as allergic rhinitis and asthma.
Atopic dermatitis leads to hypersensitivity to environmental allergens which are tolerated by healthy subjects.
In atopic dermatitis, eczema represents a delayed-type hypersensitivity reaction mediated by Th2 lymphocytes (which produce IL-4 and IL-5) and antigen-presenting cells.
ATOPY
SUMMARY OF THE INVENTION
The invention relates to a cosmetic treatment process for human atopic dermatitis based on coating the surface of the skin with a cosmetic composition that forms a film on it.
According to the invention, this film¨by virtue of its constituents __ inhibits the adhesion of pathogenic micro-organisms to the skin and reinforces the skin barrier.
More specifically, the cosmetic composition contains an ester of sucrose and/or an ester of sorbitan capable of blocking the adhesion of Staphylococcus aureus to the skin and nasal mucosa, thereby inhibiting the proliferation of pathogenic flora. The effect of this inhibition is to protect the cutaneous barrier by limiting the breakdown of lipids, especially ceramides, which is indirectly due to Staphylococcus aureus.
PRIOR ART
Atopic dermatitis or cutaneous atopy is an inflammatory, pruriginous skin condition associated with a hereditary immune predisposition and abnormalities of the cutaneous barrier. In clinical terms, this hereditary predisposition can also manifest as allergic rhinitis and asthma.
Atopic dermatitis leads to hypersensitivity to environmental allergens which are tolerated by healthy subjects.
In atopic dermatitis, eczema represents a delayed-type hypersensitivity reaction mediated by Th2 lymphocytes (which produce IL-4 and IL-5) and antigen-presenting cells.
2 Like any immune reaction mediated by antigen-specific T lymphocytes, the inflammatory reaction of the eczema of atopic dermatitis proceeds through three phases.
The first phase is asymptomatic sensitisation. This phase is clinically inapparent and leads to the amplification of antigen-specific T lymphocytes. Typically, sensitisation occurs in young childhood through exposure to environmental allergens which are captured by dendritic cells.
In a second phase, eczema develops. After re-exposure to the allergen in question, Langerhans cells migrate and activate antigen-specific, cytokine-producing Th2 lymphocytes which, in turn, activate a variety of different cell-types in the skin. This mechanism helps recruit leukocytes into the dermis and epidermis where they produce inflammatory mediators. This phase of variable duration is characterised by eczema lesions.
In most patients, it is accompanied by high levels of antigen-specific IgE
antibodies, some of which are bound to the surface of Langerhans cells.
Finally, the lesions regress in the third phase. The eczema of atopic dermatitis develops in flare-ups separated by periods of spontaneous remission. The mechanisms involved in regulating the inflammation remain poorly understood.
Atopic dermatitis affects 10-30% of the population but its prevalence is constantly on the rise in developed countries, having doubled or tripled in the last twenty years.
Atopic dermatitis is characterised by pruriginous flare-ups of acute eczema separated by periods of remission. It is most common in children. It onsets a matter of months after birth in the form of lesions on the cheeks and areas of skin subject to rubbing. It then develops in the form of attacks between one and two years of age. During this time, the skin is dry and has red, oozing patches, especially on the inner surfaces of skinfolds. After five years of age, attacks tend to disappear but the skin remains dry and sensitive. In some people, atopic dermatitis can persist into adulthood.
=
The first phase is asymptomatic sensitisation. This phase is clinically inapparent and leads to the amplification of antigen-specific T lymphocytes. Typically, sensitisation occurs in young childhood through exposure to environmental allergens which are captured by dendritic cells.
In a second phase, eczema develops. After re-exposure to the allergen in question, Langerhans cells migrate and activate antigen-specific, cytokine-producing Th2 lymphocytes which, in turn, activate a variety of different cell-types in the skin. This mechanism helps recruit leukocytes into the dermis and epidermis where they produce inflammatory mediators. This phase of variable duration is characterised by eczema lesions.
In most patients, it is accompanied by high levels of antigen-specific IgE
antibodies, some of which are bound to the surface of Langerhans cells.
Finally, the lesions regress in the third phase. The eczema of atopic dermatitis develops in flare-ups separated by periods of spontaneous remission. The mechanisms involved in regulating the inflammation remain poorly understood.
Atopic dermatitis affects 10-30% of the population but its prevalence is constantly on the rise in developed countries, having doubled or tripled in the last twenty years.
Atopic dermatitis is characterised by pruriginous flare-ups of acute eczema separated by periods of remission. It is most common in children. It onsets a matter of months after birth in the form of lesions on the cheeks and areas of skin subject to rubbing. It then develops in the form of attacks between one and two years of age. During this time, the skin is dry and has red, oozing patches, especially on the inner surfaces of skinfolds. After five years of age, attacks tend to disappear but the skin remains dry and sensitive. In some people, atopic dermatitis can persist into adulthood.
=
3 Two phenomena follow on from atopic dermatitis. Firstly, the cutaneous barrier is weakened and secondly, the skin gets colonised by a flora of pathogenic micro-organisms.
The main tissue of the cutaneous barrier is the stratum corneum, the outermost layer of the epidermis comprised of corneocytes and special lipids, including cholesterol, free fatty acids, cerebrosides and ceramides. These lipids act as intercellular cement and make the stratum corneum water-proof.
Analysis of the stratum corneum of patients with atopic dermatitis show marked deficiencies in certain proteins and cutaneous lipids. There are deficiencies in both filaggrin, 'a protein involved in aggregating keratin filaments in corneocytes, and involucrin, a protein essential to constructing the protein skeleton of the stratum corneum.
The lipids that are most notably deficient are ceramides 1 and 3.
Ceramides are particularly important in regulating skin barrier function by limiting the evaporation of water.
These protein and lipid deficiencies mean that corneocytes adhere to one another less strongly, compromising the cohesion and integrity of the stratum corneum. This manifests as a significant reduction in the thickness of the stratum corneum in these patients.
Atopic dermatitis manifests as a significant loss of cutaneous proteins and lipids which, as mentioned above, leads to evaporation of moisture and dry skin. This is known to make it = easier for allergens to enter the skin.
Atopic dermatitis therefore triggers a vicious cycle: the evaporation of intracellular water leads to cutaneous dehydration and dry skin which in turn increases cutaneous permeability. Greater cutaneous permeability makes it easier for allergens to penetrate through the tissue which sustains the skin's irritability.
The main tissue of the cutaneous barrier is the stratum corneum, the outermost layer of the epidermis comprised of corneocytes and special lipids, including cholesterol, free fatty acids, cerebrosides and ceramides. These lipids act as intercellular cement and make the stratum corneum water-proof.
Analysis of the stratum corneum of patients with atopic dermatitis show marked deficiencies in certain proteins and cutaneous lipids. There are deficiencies in both filaggrin, 'a protein involved in aggregating keratin filaments in corneocytes, and involucrin, a protein essential to constructing the protein skeleton of the stratum corneum.
The lipids that are most notably deficient are ceramides 1 and 3.
Ceramides are particularly important in regulating skin barrier function by limiting the evaporation of water.
These protein and lipid deficiencies mean that corneocytes adhere to one another less strongly, compromising the cohesion and integrity of the stratum corneum. This manifests as a significant reduction in the thickness of the stratum corneum in these patients.
Atopic dermatitis manifests as a significant loss of cutaneous proteins and lipids which, as mentioned above, leads to evaporation of moisture and dry skin. This is known to make it = easier for allergens to enter the skin.
Atopic dermatitis therefore triggers a vicious cycle: the evaporation of intracellular water leads to cutaneous dehydration and dry skin which in turn increases cutaneous permeability. Greater cutaneous permeability makes it easier for allergens to penetrate through the tissue which sustains the skin's irritability.
4 The skin's barrier function is also consolidated by the local ecosystem which consists of a flora of saprophytic bacteria.
A saprophytic bacterial flora is a natural, permanent feature of the surface of the skin. The density of bacteria on the surface of the skin is estimated at between 102 and 105/cm2. The most common species are staphylococci, notably coagulase-negative Staphylococcus epidermidis and related species (Micrococcus) and coryneform bacteria, both aerobic (Corynebacterium, Brevibacterium) and anaerobic (Propionibacterium acnes).
These bacteria are established on the stratum corneum where they adhere to corneocytes to form a protective biofilm.
This saprophytic bacterial flora therefore reinforces barrier function since it occupies potential adhesion sites for other micro-organisms __________________ which might be pathogenic .. and inhibit their proliferation.
However, if the skin is damaged as it is in atopic dermatitis, impaired cutaneous barrier function promotes water evaporation and creates a skin surface environment that is conducive to colonisation by bacteria, viruses or fungi. This permissive environment is exacerbated by the rise in skin temperature that occurs during an attack of eczema.
Thus, a pathogenic bacterial flora can grow temporarily on the surface of the skin. Most of these species are found in the normal environment, including species belonging to the genera Pseudomonas and Acinetobacter; others derive from the digestive or buccal flora such as enterobacteria, streptococci or species of the genus Clostridium.
These bacteria are not usually capable of proliferating on the surface of human skin but they can cause infection if cutaneous barrier function is compromised as in atopic dermatitis in which they can form a pathogenic bacterial biofilm.
Among the bacteria of the transient pathogenic flora, Staphylococcus aureus (S. aureus) is the potentially most pathogenic species being the most common member of the genus which is found in the nasal passages and throat of 15-30% of healthy people.
This Gram-positive bacterium establishes itself on the skin by adhering to skin cells.
Recent studies have shown that the skin of 90% of patients with atopic dermatitis is
A saprophytic bacterial flora is a natural, permanent feature of the surface of the skin. The density of bacteria on the surface of the skin is estimated at between 102 and 105/cm2. The most common species are staphylococci, notably coagulase-negative Staphylococcus epidermidis and related species (Micrococcus) and coryneform bacteria, both aerobic (Corynebacterium, Brevibacterium) and anaerobic (Propionibacterium acnes).
These bacteria are established on the stratum corneum where they adhere to corneocytes to form a protective biofilm.
This saprophytic bacterial flora therefore reinforces barrier function since it occupies potential adhesion sites for other micro-organisms __________________ which might be pathogenic .. and inhibit their proliferation.
However, if the skin is damaged as it is in atopic dermatitis, impaired cutaneous barrier function promotes water evaporation and creates a skin surface environment that is conducive to colonisation by bacteria, viruses or fungi. This permissive environment is exacerbated by the rise in skin temperature that occurs during an attack of eczema.
Thus, a pathogenic bacterial flora can grow temporarily on the surface of the skin. Most of these species are found in the normal environment, including species belonging to the genera Pseudomonas and Acinetobacter; others derive from the digestive or buccal flora such as enterobacteria, streptococci or species of the genus Clostridium.
These bacteria are not usually capable of proliferating on the surface of human skin but they can cause infection if cutaneous barrier function is compromised as in atopic dermatitis in which they can form a pathogenic bacterial biofilm.
Among the bacteria of the transient pathogenic flora, Staphylococcus aureus (S. aureus) is the potentially most pathogenic species being the most common member of the genus which is found in the nasal passages and throat of 15-30% of healthy people.
This Gram-positive bacterium establishes itself on the skin by adhering to skin cells.
Recent studies have shown that the skin of 90% of patients with atopic dermatitis is
5 colonised by S. aureus, compared with with only 5% of healthy subjects.
Remarkably, atopic dermatitis is also a proven risk factor for colonisation of the nasal mucosa by S. aureus which then provides a reservoir in the environment of atopic patients (Pascolini et al., 2011).
Some studies have also suggested that ceramides produced by the cutaneous flora are activated in the presence of S. aureus. Ceramidases hydrolyse ceramides in the stratum corneum which might suggest that colonisation of the skin by S. aureus is partly responsible for the deficiency in this type of lipid in the atopic epidermis (Kita et al., 2002).
S. aureus is also a source of superantigens (proteinaceous toxins) which, in subjects with atopic dermatitis, interact with immune cells, amplifying the inflammatory response and thereby triggering flare-ups.
There is therefore a tangible link between the proliferation of S. aureus on the epidermal surface and impairment of cutaneous barrier function as a result of ceramide deficiency, especially in atopic subjects (remembering that impaired barrier function promotes sensitisation to environmental allergens and maintenance of inflammation of the skin).
The two main viruses responsible for infections are herpes simplex virus (HSV) and vaccinia virus. Colonisation by the yeast Malassezia has also been observed in patients with atopic dermatitis.
Current treatment modalities for atopic dermatitis are based on managing the inflammation and controlling bacterial colonisation.
Remarkably, atopic dermatitis is also a proven risk factor for colonisation of the nasal mucosa by S. aureus which then provides a reservoir in the environment of atopic patients (Pascolini et al., 2011).
Some studies have also suggested that ceramides produced by the cutaneous flora are activated in the presence of S. aureus. Ceramidases hydrolyse ceramides in the stratum corneum which might suggest that colonisation of the skin by S. aureus is partly responsible for the deficiency in this type of lipid in the atopic epidermis (Kita et al., 2002).
S. aureus is also a source of superantigens (proteinaceous toxins) which, in subjects with atopic dermatitis, interact with immune cells, amplifying the inflammatory response and thereby triggering flare-ups.
There is therefore a tangible link between the proliferation of S. aureus on the epidermal surface and impairment of cutaneous barrier function as a result of ceramide deficiency, especially in atopic subjects (remembering that impaired barrier function promotes sensitisation to environmental allergens and maintenance of inflammation of the skin).
The two main viruses responsible for infections are herpes simplex virus (HSV) and vaccinia virus. Colonisation by the yeast Malassezia has also been observed in patients with atopic dermatitis.
Current treatment modalities for atopic dermatitis are based on managing the inflammation and controlling bacterial colonisation.
6 Modalities aimed at managing the inflammation include the administration of glucocorticosteroids and calcineurin inhibitors like pimecrolimus and tacrolimus. These products are usually combined with emollient products.
Bacterial control has been extensively reported on, notably involving the administration of broad-spectrum antibiotics and the application of antiseptic solutions. First-line treatment is becoming difficult because of antibiotic-resistant bacteria. Moreover, both types of treatment not only kill the pathogens present on the skin but also the beneficial saprophytic bacteria.
The main disadvantage of both these modalities is that they destroy a component that is required for effective barrier function, namely the saprophytic bacterial flora.
Recent studies have shown that the topical application of compositions containing certain sugars inhibit the adhesion of pathogenic bacteria to the skin.
Document WO 2006/106220 reports that certain sugars¨mono- and oligo-saccharides such as rhamnose, galactose, mannose and lauryl glucoside¨inhibit the adhesion of bacteria to corneocytes from atopic dogs, especially bacteria of the genus Staphylococcus (S.
intermedius).
Document 'WO 96/23479 suggests that certain sugars can be used to inhibit the adhesion of certain micro-organisms. Singled out are monosaccharides like raffinose, mannose and rhamnose, disaccharides, oligosaccharides, aminated sugars and esters of various sugars including esters of glucose such as cetearylglucoside, caprylglucoside and decylgincoside.
These various sugars can be blended into the compositions of cosmetic or dermatological preparations to inhibit bacterial adhesion, e.g. that of S. aureus, and/or for therapeutic purposes, notably the treatment of atopic dermatitis.
Document EP0875239A2 lists various esters of sugars including esters of sucrose, for their activity against certain Gram-positive species like Staphylococcus epidermidis,
Bacterial control has been extensively reported on, notably involving the administration of broad-spectrum antibiotics and the application of antiseptic solutions. First-line treatment is becoming difficult because of antibiotic-resistant bacteria. Moreover, both types of treatment not only kill the pathogens present on the skin but also the beneficial saprophytic bacteria.
The main disadvantage of both these modalities is that they destroy a component that is required for effective barrier function, namely the saprophytic bacterial flora.
Recent studies have shown that the topical application of compositions containing certain sugars inhibit the adhesion of pathogenic bacteria to the skin.
Document WO 2006/106220 reports that certain sugars¨mono- and oligo-saccharides such as rhamnose, galactose, mannose and lauryl glucoside¨inhibit the adhesion of bacteria to corneocytes from atopic dogs, especially bacteria of the genus Staphylococcus (S.
intermedius).
Document 'WO 96/23479 suggests that certain sugars can be used to inhibit the adhesion of certain micro-organisms. Singled out are monosaccharides like raffinose, mannose and rhamnose, disaccharides, oligosaccharides, aminated sugars and esters of various sugars including esters of glucose such as cetearylglucoside, caprylglucoside and decylgincoside.
These various sugars can be blended into the compositions of cosmetic or dermatological preparations to inhibit bacterial adhesion, e.g. that of S. aureus, and/or for therapeutic purposes, notably the treatment of atopic dermatitis.
Document EP0875239A2 lists various esters of sugars including esters of sucrose, for their activity against certain Gram-positive species like Staphylococcus epidermidis,
7 Staphylococcus aureus, Corynebacterium and Propionibacterium, involved in a list of pathologies on which atopic dermatitis appears. The esters listed are palmitate/stearate diester, stearate diester, laurate monoester, myristate monoester, and stearate triester and tetraester.
Document EP1340486A1 lists various sugar esters, including esters of sucrose, fructose, glucose and trehalose. Only the esters of fructose, glucose and trehalose are tested for their ability to inhibit the growth of Staphylococcus aureus. Sucrose esters are not tested for this activity. Only one representative of this family, namely sucrose stearate, is tested and this only for bleaching activity (see Table 7). Finally, this document does not address atopic dermatitis.
Document EP0815841A1 reports a composition to control skin redness due to nappies rubbing. This is not a treatment for atopic dermatitis as described above.
This document describes the inhibitory effect on the growth of Staphylococcus aureus and Staphylococcus epidermidis of a mixture of monoesters of sucrose with palmitic acid and stearic acid or a mixture of monoesters with palmitic acid and lauric acid.
Document EP2210588A1 describes foaming compositions containing polysorbate 80, i.e.
an ester of sorbitan. Polysorbate 80 is a very common emulsifying agent.
Document W04/037225A2 describes compositions free of either alcohol or propylene glycol as a vehicle for foaming aerosols. Atopic dermatitis is mentioned among other diseases that could be treated using the aerosol supplemented with some specific active substance. Sucrose stearate and polysorbate 80 mentioned in the examples are commonly used a surface-active agents.
Document EP1340486A1 lists various sugar esters, including esters of sucrose, fructose, glucose and trehalose. Only the esters of fructose, glucose and trehalose are tested for their ability to inhibit the growth of Staphylococcus aureus. Sucrose esters are not tested for this activity. Only one representative of this family, namely sucrose stearate, is tested and this only for bleaching activity (see Table 7). Finally, this document does not address atopic dermatitis.
Document EP0815841A1 reports a composition to control skin redness due to nappies rubbing. This is not a treatment for atopic dermatitis as described above.
This document describes the inhibitory effect on the growth of Staphylococcus aureus and Staphylococcus epidermidis of a mixture of monoesters of sucrose with palmitic acid and stearic acid or a mixture of monoesters with palmitic acid and lauric acid.
Document EP2210588A1 describes foaming compositions containing polysorbate 80, i.e.
an ester of sorbitan. Polysorbate 80 is a very common emulsifying agent.
Document W04/037225A2 describes compositions free of either alcohol or propylene glycol as a vehicle for foaming aerosols. Atopic dermatitis is mentioned among other diseases that could be treated using the aerosol supplemented with some specific active substance. Sucrose stearate and polysorbate 80 mentioned in the examples are commonly used a surface-active agents.
8 Document FR2798591A1 describes the use of special vegetable oil to enhance the synthesis of cutaneous lipids, in particular for the treatment of atopic dermatitis. Sucrose distearate and sorbitan tristearate are commonly used as surface-active agents.
Document EP1639989A1 describes the generation of micro-emulsions containing esters of sugar or sorbitan used as surface-active agents.
In Examples 5 and 8 of document US2005/158348A1, the compositions respectively contain polysorbate 80 and a sucrose ester. These compositions are intended for the treatment of pain and inflammation. Esters of sorbitan and sucrose are used in the excipient.
Document US2010/080768A1 describes the presence of various ceramides and sphingolipids in compositions intended for the treatment of various diseases, including atopic dermatitis.
Document US2011/101135 describes using sorbitan monocaprylate as a preservative in a cosmetic composition. Various bacterial strains are tested, including Staphylococcus aureus.
There is nevertheless a need for more effective alternatives to the various modalities currently available for managing atopic dermatitis.
It is in this context that the Applicant discovered, surprisingly and unexpectedly, that certain sugar esters like esters of sucrose and sorbitan, strongly inhibit the adhesion of pathogenic micro-organisms to the skin and mucous membranes.
Document EP1639989A1 describes the generation of micro-emulsions containing esters of sugar or sorbitan used as surface-active agents.
In Examples 5 and 8 of document US2005/158348A1, the compositions respectively contain polysorbate 80 and a sucrose ester. These compositions are intended for the treatment of pain and inflammation. Esters of sorbitan and sucrose are used in the excipient.
Document US2010/080768A1 describes the presence of various ceramides and sphingolipids in compositions intended for the treatment of various diseases, including atopic dermatitis.
Document US2011/101135 describes using sorbitan monocaprylate as a preservative in a cosmetic composition. Various bacterial strains are tested, including Staphylococcus aureus.
There is nevertheless a need for more effective alternatives to the various modalities currently available for managing atopic dermatitis.
It is in this context that the Applicant discovered, surprisingly and unexpectedly, that certain sugar esters like esters of sucrose and sorbitan, strongly inhibit the adhesion of pathogenic micro-organisms to the skin and mucous membranes.
9 Inhibition of the adhesion of S. a=treus to the surface of the skin prevents the proliferation of pathogenic micro-organisms, even in the absence of antibiotic or topical antiseptic.
One of the advantages of inhibiting the adhesion of pathogenic micro-organisms to the skin, in particular S. aureus, is to maintain the saprophytic bacterial flora and reinforce cutaneous barrier function by cutting down breakdown of its component lipids.
Sugar esters can be advantageously combined with lipids that occur naturally in the epidermis to form a film that acts still more effectively against breakdown of the epidermal barrier and colonisation of the skin by pathogens.
Other aims and aspects of the invention will emerge on reading the following detailed description which is given for the purposes of illustration and is in no way limiting.
DETAILED DESCRIPTION OF THE INVENTION
A first aspect of the invention relates to a cosmetic composition for topical application containing at least one sucrose ester and/or sorbitan ester as an agent to inhibit the adhesion of Staphylococcus aureus to human skin and nasal mucosa.
More specifically, the invention concerns a composition for topical application containing at least one sucrose ester and/or sorbitan ester for use in the treatment of atopic dermatitis, as an agent to inhibit the adhesion of Staphylococcus aureus to human skin and nasal mucosa.
A sugar ester is a sugar in which at least one free alcohol group has been esterified with a fatty acid Chain.
A series of different families of sugar ester have been described. Notably, there are esters of glucose, sucrose and sorbitan (Piccicuto et at., 2001). They have the advantage of being non-toxic and non-irritant and are therefore in widespread use in the food processing, pharmaceutical and cosmetic industries, often for their surface-active properties.
Out of these three distinct families, this Application only concerns esters of sucrose and .. sorbitan.
These are non-ionic surfactants with a hydrophilic group consisting of sucrose or sorbitan joined through an ester linkage to a hydrophobic group consisting of a fatty acid. The surface-active properties of these esters also make them easily to combine with lipids in cosmetic compositions, especially emulsions.
=
a-D-glucopyranosyl-P-D-fructofuranoside or sucrose carries eight free alcohol groups and can therefore be esterified with up to eight fatty acids.
Sorbitan is generated by the dehydration of sorbitol, a polyhydroxylated compound which is itself obtained by reducing the aldehyde group of glucose to create an alcohol group.
Sorbitan carries four free alcohol groups, each of which can be esterified by a fatty acid.
In the context if the present invention, sorbitan esters means esters of the "Span" type, e.g.
with the following developed structural formula:
OH
HO OH
in which R is a fatty acid, in this case a monoesterified span The present invention also concerns "Tween"-type polyethoxylated sorbitan esters, e.g. the following formula:
o(cH2cH2o>1H
op-1204201w ____________________ R
H(OCH2CH2ixo 0(CH2CH20)1FI
in which R is a fatty acid, in this case a monoesterified tween.
The carbon chains of the fatty acids may be short or long, e.g. mention could be made of lauric acid, myristic acid, palmitic acid and stcaric acid with respective chains of C12, C14, C16 and C18. The fatty acid may also be chosen from among saturated and unsaturated fatty acids, e.g. oleic acid (a C18 carbon chain).
Thus, according to another characteristic of the invention, the cosmetic composition contains sucrose and/or sorbitan with at east one alcohol group esterified with a fatty acid from the group with carbon chains of between C12 and C22, advantageously between C12 and C18.
Depending on the ratio of fatty acids to sucrose, esterification can yield the monoester, diester, triester or polyester (up to the octa-ester), or a mixture of all these forms. The esterification of sorbitan can yield the monoester, diester, triester, tetra-ester or a mixture of these various forms.
According to another embodiment, the cosmetic composition of the invention contains sucrose and/or sorbitan in which some or all of the alcohol groups have been esterified with the same fatty acid.
In this case and advantageously, the sucrose ester will be selected from the group containing sucrolaurate, sucromyristate, sucropalmitate and sucrostearate, and the sorbitan ester will be selected from the group containing sorbitan laurate (Span 20), sorbitan monostearate (Span 60), sorbitan oleate (Span 80) and sesquioleate sorbitan (Montane 83).
In an advantageous embodiment, the sucrose ester is a sucrose stearate containing at least 70%, advantageously at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid.
Advantageously, the cosmetic composition according to the invention contains a polyethoxylated sorbitan ester. Mention could be made of the ethoxylated sorbitan monolaurate (Polysorbate 20), polyoxyethylene sorbitan monostearate 20 (Polysorbate 60) and polyoxyethylene sorbitan mono-oleate (Polysorbate 80). In a preferred embodiment, the sorbitan ester is polysorbate 20 or polysorbate 80.
According to an alternative embodiment, the cosmetic composition can be made up with sucrose and/or sorbitan in which some or all of the alcohol groups have been esterified with at least two different fatty acids.
In this case and advantageously, the sucrose ester will be selected from the group containing sucropalmitate stearate and sucrotetrastearate triacetate, and the sorbitan ester will be selected from the group containing the oleate/stearic acid ester of sorbitan (Montane 481) and sorbitan esterified with fatty acids from olive oil (olivate sorbitans).
According to a preferred embodiment, the sucrose ester in the cosmetic composition according to the invention is the sucrostearate, i.e. sucrose esterified with at least one molecule of stearic acid (a C18 fatty acid).
Those skilled in the art are aware that, for a given fatty acid carbon chain length, the proportion of monoesters in the mix will affect the hydrophobicity/hydrophilicity of the sugar ester.
These properties are characterised by means of the Hydrophile/Lipophile Balance (HLB) index. A value of between 1 and 10 indicates a lipophilic sugar ester, corresponding to relatively few monoesters and therefore a relatively high proportion of polyesters. But a value of between 11 and 20 indicates a hydrophilic sugar ester, corresponding to a high proportion of monoesters and therefore a relatively low proportion of polyesters.
In a particular embodiment of, the invention, the sucrostearate has a HLB of 16, corresponding to a relative proportion of sucrose monoesters and stearic acid of between 75% and 80% in weight. Hereafter, this product is referred to as sucrose monostearate.
Preferably, the sucrose ester and/or the sorbitan ester represents 0.1-5% of the composition by weight,,advantageously between 1% and 3%.
Advantageously, the cosmetic composition also contains lipids that are capable of restoring the cutaneous barrier, respectively:
- at least one lipid not found naturally in the skin, advantageously an oil; and/or - a mixture of constituents that occur naturally in the skin, including ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
In practice, supplementation with certain specific lipids can help restore the lipid layer between skin cells, i.e. the extracellular cement, thereby helping to restore the cutaneous barrier. As a result, the evaporation of water from the skin is cut down together with the risk of S. aureus adhering on the surface of the skin and proliferating there.
This action combines with the effects of the esters of the invention which inhibit the adhesion of S.
aureus and prevent the hydrolysis of ceramidcs in the stratum corneum.
Lipids that are not naturally found in the skin, like oils, mediate short-term moisturisation of the tissue. They are'advantageously selected from the group including sunflower oil and rapeseed oil (canola) because of the high concentrations of essential omega-6 and omega-3 fatty acids in these oils.
In a particular embodiment of the invention, the cosmetic composition contains lipids not found naturally in skin, respectively sunflower oil representing 3-15% of the composition by weight and rapeseed oil (canola) representing 0.05-10% of the composition by weight.
Supplementation with lipids that occur naturally in the skin can correct the deficiency in certain stratum corneum lipids seen in patients suffering from atopic dermatitis. This can help restore a functional cutaneous barrier in the long term, especially when combined with the effects of the esters described above.
In a particular embodiment, the mixture of naturally-occurring constituents corresponds to a lipid composition with an INCI designation, namely Water, Ceramide 3, Ceramide 611, Ceramide 1, Phytosphingosine, Cholesterol, Sodium Lauroyl Lactylate, Carbomer, Xanthan Gum. This lipid composition is advantageously supplied as a commercial product, SK
Influx VTM (Evonik Industries).
Preferably, the lipid composition represents 0.01-5% of the overall composition by weight.
Advantageously, the cosmetic composition also contains at least one additional polyhydroxylated compound selected from the group containing rhamnose, xylitol and rnannitol.
These additional polyhydroxylated compounds like rhamnose and xylitol help inhibit the adhesion of pathogenic bacteria such as S. aureus to human skin and nasal mucosa.
Mannitol also has free radical-quenching activity.
In a particular embodiment of the invention, the cosmetic composition contains a mixture of three of the additional polyhydroxylated compounds mentioned above.
Advantageously, rhamnose represents 0.01-1% of the composition by weight, xylitol represents 0.05-2% of the composition by weight and mannitol represents 0.005-1% of the composition by weight.
Advantageously, the composition also contains at least one anti-pruriginous agent selected from the group containing in particular:
- palmitoyl ethanolamide, CAS Number 544-31-0;
- hydroxy-a-sanshool, CAS Number 83883-10-7, part of the composition of zanthaleneTM
- a lipo-dipeptide based on tyrosyl-arginine, part of the composition of 'calmosensineTm ;
5 - ichtyol or ammonium ichthosulphonate, CAS Number 8029-68-3.
Advantageously, the cosmetic composition according to the invention can also include at least one anti-inflammatory agent, preferably selected from the group containing:
- beta-sitosterol, CAS Number 83-46-5;
One of the advantages of inhibiting the adhesion of pathogenic micro-organisms to the skin, in particular S. aureus, is to maintain the saprophytic bacterial flora and reinforce cutaneous barrier function by cutting down breakdown of its component lipids.
Sugar esters can be advantageously combined with lipids that occur naturally in the epidermis to form a film that acts still more effectively against breakdown of the epidermal barrier and colonisation of the skin by pathogens.
Other aims and aspects of the invention will emerge on reading the following detailed description which is given for the purposes of illustration and is in no way limiting.
DETAILED DESCRIPTION OF THE INVENTION
A first aspect of the invention relates to a cosmetic composition for topical application containing at least one sucrose ester and/or sorbitan ester as an agent to inhibit the adhesion of Staphylococcus aureus to human skin and nasal mucosa.
More specifically, the invention concerns a composition for topical application containing at least one sucrose ester and/or sorbitan ester for use in the treatment of atopic dermatitis, as an agent to inhibit the adhesion of Staphylococcus aureus to human skin and nasal mucosa.
A sugar ester is a sugar in which at least one free alcohol group has been esterified with a fatty acid Chain.
A series of different families of sugar ester have been described. Notably, there are esters of glucose, sucrose and sorbitan (Piccicuto et at., 2001). They have the advantage of being non-toxic and non-irritant and are therefore in widespread use in the food processing, pharmaceutical and cosmetic industries, often for their surface-active properties.
Out of these three distinct families, this Application only concerns esters of sucrose and .. sorbitan.
These are non-ionic surfactants with a hydrophilic group consisting of sucrose or sorbitan joined through an ester linkage to a hydrophobic group consisting of a fatty acid. The surface-active properties of these esters also make them easily to combine with lipids in cosmetic compositions, especially emulsions.
=
a-D-glucopyranosyl-P-D-fructofuranoside or sucrose carries eight free alcohol groups and can therefore be esterified with up to eight fatty acids.
Sorbitan is generated by the dehydration of sorbitol, a polyhydroxylated compound which is itself obtained by reducing the aldehyde group of glucose to create an alcohol group.
Sorbitan carries four free alcohol groups, each of which can be esterified by a fatty acid.
In the context if the present invention, sorbitan esters means esters of the "Span" type, e.g.
with the following developed structural formula:
OH
HO OH
in which R is a fatty acid, in this case a monoesterified span The present invention also concerns "Tween"-type polyethoxylated sorbitan esters, e.g. the following formula:
o(cH2cH2o>1H
op-1204201w ____________________ R
H(OCH2CH2ixo 0(CH2CH20)1FI
in which R is a fatty acid, in this case a monoesterified tween.
The carbon chains of the fatty acids may be short or long, e.g. mention could be made of lauric acid, myristic acid, palmitic acid and stcaric acid with respective chains of C12, C14, C16 and C18. The fatty acid may also be chosen from among saturated and unsaturated fatty acids, e.g. oleic acid (a C18 carbon chain).
Thus, according to another characteristic of the invention, the cosmetic composition contains sucrose and/or sorbitan with at east one alcohol group esterified with a fatty acid from the group with carbon chains of between C12 and C22, advantageously between C12 and C18.
Depending on the ratio of fatty acids to sucrose, esterification can yield the monoester, diester, triester or polyester (up to the octa-ester), or a mixture of all these forms. The esterification of sorbitan can yield the monoester, diester, triester, tetra-ester or a mixture of these various forms.
According to another embodiment, the cosmetic composition of the invention contains sucrose and/or sorbitan in which some or all of the alcohol groups have been esterified with the same fatty acid.
In this case and advantageously, the sucrose ester will be selected from the group containing sucrolaurate, sucromyristate, sucropalmitate and sucrostearate, and the sorbitan ester will be selected from the group containing sorbitan laurate (Span 20), sorbitan monostearate (Span 60), sorbitan oleate (Span 80) and sesquioleate sorbitan (Montane 83).
In an advantageous embodiment, the sucrose ester is a sucrose stearate containing at least 70%, advantageously at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid.
Advantageously, the cosmetic composition according to the invention contains a polyethoxylated sorbitan ester. Mention could be made of the ethoxylated sorbitan monolaurate (Polysorbate 20), polyoxyethylene sorbitan monostearate 20 (Polysorbate 60) and polyoxyethylene sorbitan mono-oleate (Polysorbate 80). In a preferred embodiment, the sorbitan ester is polysorbate 20 or polysorbate 80.
According to an alternative embodiment, the cosmetic composition can be made up with sucrose and/or sorbitan in which some or all of the alcohol groups have been esterified with at least two different fatty acids.
In this case and advantageously, the sucrose ester will be selected from the group containing sucropalmitate stearate and sucrotetrastearate triacetate, and the sorbitan ester will be selected from the group containing the oleate/stearic acid ester of sorbitan (Montane 481) and sorbitan esterified with fatty acids from olive oil (olivate sorbitans).
According to a preferred embodiment, the sucrose ester in the cosmetic composition according to the invention is the sucrostearate, i.e. sucrose esterified with at least one molecule of stearic acid (a C18 fatty acid).
Those skilled in the art are aware that, for a given fatty acid carbon chain length, the proportion of monoesters in the mix will affect the hydrophobicity/hydrophilicity of the sugar ester.
These properties are characterised by means of the Hydrophile/Lipophile Balance (HLB) index. A value of between 1 and 10 indicates a lipophilic sugar ester, corresponding to relatively few monoesters and therefore a relatively high proportion of polyesters. But a value of between 11 and 20 indicates a hydrophilic sugar ester, corresponding to a high proportion of monoesters and therefore a relatively low proportion of polyesters.
In a particular embodiment of, the invention, the sucrostearate has a HLB of 16, corresponding to a relative proportion of sucrose monoesters and stearic acid of between 75% and 80% in weight. Hereafter, this product is referred to as sucrose monostearate.
Preferably, the sucrose ester and/or the sorbitan ester represents 0.1-5% of the composition by weight,,advantageously between 1% and 3%.
Advantageously, the cosmetic composition also contains lipids that are capable of restoring the cutaneous barrier, respectively:
- at least one lipid not found naturally in the skin, advantageously an oil; and/or - a mixture of constituents that occur naturally in the skin, including ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
In practice, supplementation with certain specific lipids can help restore the lipid layer between skin cells, i.e. the extracellular cement, thereby helping to restore the cutaneous barrier. As a result, the evaporation of water from the skin is cut down together with the risk of S. aureus adhering on the surface of the skin and proliferating there.
This action combines with the effects of the esters of the invention which inhibit the adhesion of S.
aureus and prevent the hydrolysis of ceramidcs in the stratum corneum.
Lipids that are not naturally found in the skin, like oils, mediate short-term moisturisation of the tissue. They are'advantageously selected from the group including sunflower oil and rapeseed oil (canola) because of the high concentrations of essential omega-6 and omega-3 fatty acids in these oils.
In a particular embodiment of the invention, the cosmetic composition contains lipids not found naturally in skin, respectively sunflower oil representing 3-15% of the composition by weight and rapeseed oil (canola) representing 0.05-10% of the composition by weight.
Supplementation with lipids that occur naturally in the skin can correct the deficiency in certain stratum corneum lipids seen in patients suffering from atopic dermatitis. This can help restore a functional cutaneous barrier in the long term, especially when combined with the effects of the esters described above.
In a particular embodiment, the mixture of naturally-occurring constituents corresponds to a lipid composition with an INCI designation, namely Water, Ceramide 3, Ceramide 611, Ceramide 1, Phytosphingosine, Cholesterol, Sodium Lauroyl Lactylate, Carbomer, Xanthan Gum. This lipid composition is advantageously supplied as a commercial product, SK
Influx VTM (Evonik Industries).
Preferably, the lipid composition represents 0.01-5% of the overall composition by weight.
Advantageously, the cosmetic composition also contains at least one additional polyhydroxylated compound selected from the group containing rhamnose, xylitol and rnannitol.
These additional polyhydroxylated compounds like rhamnose and xylitol help inhibit the adhesion of pathogenic bacteria such as S. aureus to human skin and nasal mucosa.
Mannitol also has free radical-quenching activity.
In a particular embodiment of the invention, the cosmetic composition contains a mixture of three of the additional polyhydroxylated compounds mentioned above.
Advantageously, rhamnose represents 0.01-1% of the composition by weight, xylitol represents 0.05-2% of the composition by weight and mannitol represents 0.005-1% of the composition by weight.
Advantageously, the composition also contains at least one anti-pruriginous agent selected from the group containing in particular:
- palmitoyl ethanolamide, CAS Number 544-31-0;
- hydroxy-a-sanshool, CAS Number 83883-10-7, part of the composition of zanthaleneTM
- a lipo-dipeptide based on tyrosyl-arginine, part of the composition of 'calmosensineTm ;
5 - ichtyol or ammonium ichthosulphonate, CAS Number 8029-68-3.
Advantageously, the cosmetic composition according to the invention can also include at least one anti-inflammatory agent, preferably selected from the group containing:
- beta-sitosterol, CAS Number 83-46-5;
10 - ,enoxolone or glycyrrhetinic acid, CAS Number 471-53-4.
Advantageously, the cosmetic composition also includes Vitamin PP which is known to stimulate lipid synthesis in the stratum corneum, including that of ceramides, free fatty acids and cholesterol. Vitamin PP acts by stimulating the activity of serine palmitoyl 15 transferase, a key enzyme in the synthesis of sphingosine which is the precursor for ceramide production.
Another aspect of the invention concerns a cosmetic composition for the cosmetic treatment of atopic dermatitis.
The invention also concerns a cosmetic treatment process for atopic dermatitis based on forming a film on the skin to protect the epidermis by means of the composition described hereafter.
=
In an advantageous embodiment, the treatment process involves applying to the skin a film-forming composition, notably containing a sucrose and/or sorbitan ester to inhibit the adhesion of S. aureus to the surface of the skin, together with lipids, e.g.
fatty acids, ceramides and cholesterol, to reinforce the skin's defences against insults from micro-organisms, and notably against enzymes secreted by such micro-organisms that hydrolyse constituents of the stratum corneum.
This film can be applied to the skin according to the stage of the disease, in order to:
- arrest its progress;
- act during flare-ups of the disease;
- prevent recurrence.
Advantageously, the composition used to stop progression contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 4% of a mixture of rhamnose, xylitol and mannitol.
Advantageously, the composition used to treat flare-ups contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 4% of a mixture of rhamnose, xylitol and mannitol;
between 0.01% and 1% of an anti-pruriginous agent;
- = between 0.5% and 1% of an anti-inflammatory agent;
Advantageously, the composition used notably to prevent recurrence contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 3% of a mixture of rhamnose, xylitol and mannitol;
between 0.01% and 1% of an anti-pruriginous agent;
between 0.01% and 2% Vitamin PP.
=
These various compositions are film-forming, i.e. they can create a film over the surface of the skin to protect it against insults from pathogenic micro-organisms.
A number of advantages emerge from reading about the invention:
reducing S. aureus adhesion to atopic skin prevents the growth of a pathogenic bacterial flora at the same time as maintaining the saprophytic bacterial flora;
it is known that a bacterial biofilm grows on the surface of the skin in a series of different phases from bacterial adhesion through growth, maturation and expansion of the film. Therefore, inhibiting the adhesion of S. aureus to atopic skin leads to inhibition of the formation of a pathogenic biofilm;
using a non-toxic, non-irritant sucrose and/or sorbitan ester cuts down the need for antimicrobial agents such as antibiotics and topical antiseptic products;
the presence of lipids that do not occur naturally in the skin restores barrier function and helps cut down the evaporation of water from the epidermis;
complementary action by the sucrose and/or sorbitan ester and the lipids reduces the burden of S. aureus as a result of the inhibition of adhesion and then restores the stratum corneum's barrier function;
the sucrose and/or sorbitan ester and the lipids therefore form a film on the epidermis that protects it against insults from pathogenic micro-organisms = and prevents breakdown of the barrier function.
EXAMPLES
ONTO A SOLID MATRIX.
1) Method The following protocol was used:
- S. aureus was grown in the Clinical Bacteriology Laboratory at La Timone Hospital (CIP 65-8) in 'Nutrient Broth N 2' (Oxoid), for 12 hours at 37 C;
- The culture was centrifuged at 9,000 g for 10 min and then the bacterial pellet was resuspended in phosphate-buffered saline (PBS);
- This suspension was diluted 50-fold in an aqueous solution or in an aqueous solution containing the test polyhydroxylated compound. This was either xylitol or sucrostearate HLB 16 (SURFHOPETM C1816);
- The bacteria were pre-incubated with the test polyhydroxylated compound. for mm at 37 C;
- The mixture (100 I) was then spotted into a well on a glass cytology slide, of fixed surface area (0.8 cm2) with walls, i.e. a special slide for cell culture (Chamber Slide System, Labtek);
- The bacterial cultures were then incubated at 37 C for 60 mm after which they were rinsed with UltraPure water to wash off any bacteria that had not stuck to the surface of the well;
- Adherent bacteria were stained with Crystal Violet for 10 seconds, rinsed and dried at 25 C for 12 hours;
- Finally, the bacteria were examined by microscope at a magnification of X
1,000 (oil immersion) with perfectly homogeneous fields;
- Finally, the number of bacteria in each well was counted automatically using appropriate software.
2) Results In this protocol, the effect of the polyhydroxylated compounds was analysed vis-a-vis inhibition of the adhesion of S. aureus onto the solid matrix. The tests were carried out with xylitol at a final concentration of 0.5% and the HLB16 sucrostearate (sucrose monostearate, SURFHOliE C18-C16) at a final concentration of 1%.
Table 1: Effects of xylitol (0.5%) and HLB 16 sucrostearate (1%) on the adhesion of S.
aureus to the surface of glass slides. Results are presented as the mean count of three fields .. together with the corresponding standard deviation.
Condition Number of cells per Inhibition of adhesion (% with respect field to the water control) Water (control) 99 11 0%
Xylitol (0.5%) 91 6 8%
HLB 16 12 1 88%
sucrostearate (1%) 3) Conclusion Strong inhibition of the adhesion of S. aureus to the surface of glass slides was observed in the presence of 1% HLB 16 sucrostearate.
2/ EFFECT OF ESTERS OF THE INVENTION ON EX VIVO ADHESION OF S. AUREUS ON HUMAN
CORNEOCYTES.
To corroborate the in vitro findings, an ex vivo adhesion test on human corneocytes was adapted from a method developed on dogs (McEwan et al., 2005).
1) Bacterial strain A clinical* strain of S. aureus (CIP 65-8) was isolated from a patient in the Clinical Bacteriology Laboratory at La Timone Hospital in Marseille.
2) Protocol S. aureus was inoculated into 10 ml of 'Nutrient Broth N 2' (Oxoid) and incubated with stirring at 37 C for 12 hours. The culture was centrifuged and the bacterial pellet was 10 resuspended in PBS. Bacterial density was adjusted to about 106 CFU/ml with osmotically purified water.
Target areas were marked out on the arms of a human volunteer. On each area, cutaneous debris was removed with 5 successive "pre-stripping" procedures with discs of 15 SellotapeTmOriginal (diameter 22 mm). Corneocytes were then collected from each target area using D-SquameTM sticky discs (diameter 22 mm) with a D-Squame disc applicator set to a pressure of 150 g/cm2.
The discs were then placed in Petri dishes (diameter 35 mm) and covered with 0.5 ml water 20 or 0.5 ml of a suspension of S. aureus at a density of 106 CFU/ml, containing the test polyhydroxylated compound (triplicate areas for each).
The polyhydroxylated compounds tested in this way were:
xylitol, at a final concentration of 0.5%;
HLB 16 sucrose stearate (sucrose monostearate, SURFHOPE C1816,) at a final concentration of 1%, sucrose laurate monoester (SURFHOPE C1216, 80% monoester), at a final concentration of 0.1%, polysorbate 60, :t a final concentration of 0.1%;
polysorbate 60, at a final concentration of 1%;
polysorbate 20, at a final concentration of 0.1%;
All solutions were made up in water and put in contact with S. aureus at room temperature 45 mm before the start of the adhesion experiment. The dishes were then incubated at 37 C
for 60 min. Then the discs were rinsed in osmotically purified water to remove any bacteria that had not stuck to the corneocytes. Adherent bacteria were stained with oxalated Crystal Violet for 10 seconds. Finally, the discs were rinsed off with osmotically purified water, placed on a microscope slide and air-dried for 24 hours.
3) Image acquisition and bacterial counts Adherent bacteria were photographed using an Olympus BX 53 microscope fitted with a digital camera. The images were then analysed using UTHSCSA Image Tool software (Reindeer Graphics Inc.). The mean number of bacteria per disc was calculated from 10-12 images, corresponding to the surfaces of about 100 corneocytes. Means were compared using Statgraphics Plus software (Manugistics Inc.).
4) Results and conclusion These test ,results show that xylitol inhibits the adhesion of S. aureus to corneocytes by a _____________________________________________________________ factor of about 20% (Table 2). Very strong inhibitory activity 50% or over was observed with the HLB 16 sucrostearate and polysorbate 60 at final concentrations of 1%
(Table 2). Polysorbate 20 and 60 at 0.1% gave very promising inhibitory activity. In contrast, sucrose laurate monoester induced a significant increase in adhesion.
Table 2: Effect of xylitol and sugars of the invention on the adhesion of S.
aureus on human corneocytes.
Inhibition of S. aureus adhesion (%) PolyhYdroxylated compound (final Test 1 Test 2 concentration) Xylitol (0.5%) 21,0 20,2 HLB 16 sucrostearate (1%) 57Ø 49.6.
Sucrose laurate (0.1%) -22.8.
Polysorbate 60 (0.1%) 39.8.
Polysorbate 60 (1%) 54.
Polysorbate 20 (0.1%) 57.
Each sugar was tested in two independent experiments for xylitol and sucrose stearate (1%).
These ex vivo results therefore confirm the in vitro results, i.e. that the presence of HLB 16 sucrostearate in its surroundings inhibits the adhesion of S. aureus to both a solid matrix like a cytology slide and to human corneocytes.
ATODERMTm STOP EVOLUTIVE
Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 0.61.
Water Q.s. 100 =
ATODERMTm STOP CRISE
Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 0.61.
Anti-pruriginous agent 0.3.
Anti-inflammatory agent 0.5.
Water Q.s. 100 ATODERMTm STOP RECIDIVE
, Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 1.1.
Anti-pruriginous agent 0.3.
Vitamin PP 0.3.
Water Q.s. 100 REFERENCES
Kita K., Sueyoshi N., Okino N., Inagaki M., Ishida H., Kiso M., Imayama S., Nakamura T., Ito M. 2002. Activation of bacterial ceramidase by anionic glycerophOspholipids : possible involvement in ceramide hydrolysis on atopic skin by Pseudomonas ceramidase. Biochem J., 362, p. 619-626.
McEwan N.A., Kalna G. and Mellor D. 2005. A comparison of adherence by four strains of Staphylococcus intermedius and Staphylococcus hominis to canine corneocytes collected from normal dogs and dogs suffering from atopic dermatitis. Research in Veterinary Science, Vol. 78, p. 193-198.
Piccicuto S., Blecker C., Brohee J.C., Mbampara A., Lognay G., Deroanne C., Paquot M. and Manlier M. 2001. Les esters de sucres : voies de synthese et potentialites d 'utilisation [Sugar esters: synthetic pathways and potential uses].
Biotechnol. Agron. Soc.
Environ., Vol. 5(4), p. 209-219.
Pascolini C., Sinagra J., Pecetta S., Bordignon V., De Santis A., CM L., Cafiso V., Prignano G., Capitanio B., Passariello C., Stefani S., Cordiali-Fei P., Ensoli F. 2011.
Molecular and immunological characterization of Staphylococcus aureus in pediatric atopic dermatitis: implications for prophylaxis and clinical management. Clin Dev Imnuazol. 2011 Oct 27 (Epub).
Advantageously, the cosmetic composition also includes Vitamin PP which is known to stimulate lipid synthesis in the stratum corneum, including that of ceramides, free fatty acids and cholesterol. Vitamin PP acts by stimulating the activity of serine palmitoyl 15 transferase, a key enzyme in the synthesis of sphingosine which is the precursor for ceramide production.
Another aspect of the invention concerns a cosmetic composition for the cosmetic treatment of atopic dermatitis.
The invention also concerns a cosmetic treatment process for atopic dermatitis based on forming a film on the skin to protect the epidermis by means of the composition described hereafter.
=
In an advantageous embodiment, the treatment process involves applying to the skin a film-forming composition, notably containing a sucrose and/or sorbitan ester to inhibit the adhesion of S. aureus to the surface of the skin, together with lipids, e.g.
fatty acids, ceramides and cholesterol, to reinforce the skin's defences against insults from micro-organisms, and notably against enzymes secreted by such micro-organisms that hydrolyse constituents of the stratum corneum.
This film can be applied to the skin according to the stage of the disease, in order to:
- arrest its progress;
- act during flare-ups of the disease;
- prevent recurrence.
Advantageously, the composition used to stop progression contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 4% of a mixture of rhamnose, xylitol and mannitol.
Advantageously, the composition used to treat flare-ups contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 4% of a mixture of rhamnose, xylitol and mannitol;
between 0.01% and 1% of an anti-pruriginous agent;
- = between 0.5% and 1% of an anti-inflammatory agent;
Advantageously, the composition used notably to prevent recurrence contains (in percentage weight of the composition):
between 1% and 5% sucrose monostearate and/or a sorbitan ester;
between 3% and 25% of a mixture of oils;
between 0.01% and 5% SK Influx VTM;
between 0.06% and 3% of a mixture of rhamnose, xylitol and mannitol;
between 0.01% and 1% of an anti-pruriginous agent;
between 0.01% and 2% Vitamin PP.
=
These various compositions are film-forming, i.e. they can create a film over the surface of the skin to protect it against insults from pathogenic micro-organisms.
A number of advantages emerge from reading about the invention:
reducing S. aureus adhesion to atopic skin prevents the growth of a pathogenic bacterial flora at the same time as maintaining the saprophytic bacterial flora;
it is known that a bacterial biofilm grows on the surface of the skin in a series of different phases from bacterial adhesion through growth, maturation and expansion of the film. Therefore, inhibiting the adhesion of S. aureus to atopic skin leads to inhibition of the formation of a pathogenic biofilm;
using a non-toxic, non-irritant sucrose and/or sorbitan ester cuts down the need for antimicrobial agents such as antibiotics and topical antiseptic products;
the presence of lipids that do not occur naturally in the skin restores barrier function and helps cut down the evaporation of water from the epidermis;
complementary action by the sucrose and/or sorbitan ester and the lipids reduces the burden of S. aureus as a result of the inhibition of adhesion and then restores the stratum corneum's barrier function;
the sucrose and/or sorbitan ester and the lipids therefore form a film on the epidermis that protects it against insults from pathogenic micro-organisms = and prevents breakdown of the barrier function.
EXAMPLES
ONTO A SOLID MATRIX.
1) Method The following protocol was used:
- S. aureus was grown in the Clinical Bacteriology Laboratory at La Timone Hospital (CIP 65-8) in 'Nutrient Broth N 2' (Oxoid), for 12 hours at 37 C;
- The culture was centrifuged at 9,000 g for 10 min and then the bacterial pellet was resuspended in phosphate-buffered saline (PBS);
- This suspension was diluted 50-fold in an aqueous solution or in an aqueous solution containing the test polyhydroxylated compound. This was either xylitol or sucrostearate HLB 16 (SURFHOPETM C1816);
- The bacteria were pre-incubated with the test polyhydroxylated compound. for mm at 37 C;
- The mixture (100 I) was then spotted into a well on a glass cytology slide, of fixed surface area (0.8 cm2) with walls, i.e. a special slide for cell culture (Chamber Slide System, Labtek);
- The bacterial cultures were then incubated at 37 C for 60 mm after which they were rinsed with UltraPure water to wash off any bacteria that had not stuck to the surface of the well;
- Adherent bacteria were stained with Crystal Violet for 10 seconds, rinsed and dried at 25 C for 12 hours;
- Finally, the bacteria were examined by microscope at a magnification of X
1,000 (oil immersion) with perfectly homogeneous fields;
- Finally, the number of bacteria in each well was counted automatically using appropriate software.
2) Results In this protocol, the effect of the polyhydroxylated compounds was analysed vis-a-vis inhibition of the adhesion of S. aureus onto the solid matrix. The tests were carried out with xylitol at a final concentration of 0.5% and the HLB16 sucrostearate (sucrose monostearate, SURFHOliE C18-C16) at a final concentration of 1%.
Table 1: Effects of xylitol (0.5%) and HLB 16 sucrostearate (1%) on the adhesion of S.
aureus to the surface of glass slides. Results are presented as the mean count of three fields .. together with the corresponding standard deviation.
Condition Number of cells per Inhibition of adhesion (% with respect field to the water control) Water (control) 99 11 0%
Xylitol (0.5%) 91 6 8%
HLB 16 12 1 88%
sucrostearate (1%) 3) Conclusion Strong inhibition of the adhesion of S. aureus to the surface of glass slides was observed in the presence of 1% HLB 16 sucrostearate.
2/ EFFECT OF ESTERS OF THE INVENTION ON EX VIVO ADHESION OF S. AUREUS ON HUMAN
CORNEOCYTES.
To corroborate the in vitro findings, an ex vivo adhesion test on human corneocytes was adapted from a method developed on dogs (McEwan et al., 2005).
1) Bacterial strain A clinical* strain of S. aureus (CIP 65-8) was isolated from a patient in the Clinical Bacteriology Laboratory at La Timone Hospital in Marseille.
2) Protocol S. aureus was inoculated into 10 ml of 'Nutrient Broth N 2' (Oxoid) and incubated with stirring at 37 C for 12 hours. The culture was centrifuged and the bacterial pellet was 10 resuspended in PBS. Bacterial density was adjusted to about 106 CFU/ml with osmotically purified water.
Target areas were marked out on the arms of a human volunteer. On each area, cutaneous debris was removed with 5 successive "pre-stripping" procedures with discs of 15 SellotapeTmOriginal (diameter 22 mm). Corneocytes were then collected from each target area using D-SquameTM sticky discs (diameter 22 mm) with a D-Squame disc applicator set to a pressure of 150 g/cm2.
The discs were then placed in Petri dishes (diameter 35 mm) and covered with 0.5 ml water 20 or 0.5 ml of a suspension of S. aureus at a density of 106 CFU/ml, containing the test polyhydroxylated compound (triplicate areas for each).
The polyhydroxylated compounds tested in this way were:
xylitol, at a final concentration of 0.5%;
HLB 16 sucrose stearate (sucrose monostearate, SURFHOPE C1816,) at a final concentration of 1%, sucrose laurate monoester (SURFHOPE C1216, 80% monoester), at a final concentration of 0.1%, polysorbate 60, :t a final concentration of 0.1%;
polysorbate 60, at a final concentration of 1%;
polysorbate 20, at a final concentration of 0.1%;
All solutions were made up in water and put in contact with S. aureus at room temperature 45 mm before the start of the adhesion experiment. The dishes were then incubated at 37 C
for 60 min. Then the discs were rinsed in osmotically purified water to remove any bacteria that had not stuck to the corneocytes. Adherent bacteria were stained with oxalated Crystal Violet for 10 seconds. Finally, the discs were rinsed off with osmotically purified water, placed on a microscope slide and air-dried for 24 hours.
3) Image acquisition and bacterial counts Adherent bacteria were photographed using an Olympus BX 53 microscope fitted with a digital camera. The images were then analysed using UTHSCSA Image Tool software (Reindeer Graphics Inc.). The mean number of bacteria per disc was calculated from 10-12 images, corresponding to the surfaces of about 100 corneocytes. Means were compared using Statgraphics Plus software (Manugistics Inc.).
4) Results and conclusion These test ,results show that xylitol inhibits the adhesion of S. aureus to corneocytes by a _____________________________________________________________ factor of about 20% (Table 2). Very strong inhibitory activity 50% or over was observed with the HLB 16 sucrostearate and polysorbate 60 at final concentrations of 1%
(Table 2). Polysorbate 20 and 60 at 0.1% gave very promising inhibitory activity. In contrast, sucrose laurate monoester induced a significant increase in adhesion.
Table 2: Effect of xylitol and sugars of the invention on the adhesion of S.
aureus on human corneocytes.
Inhibition of S. aureus adhesion (%) PolyhYdroxylated compound (final Test 1 Test 2 concentration) Xylitol (0.5%) 21,0 20,2 HLB 16 sucrostearate (1%) 57Ø 49.6.
Sucrose laurate (0.1%) -22.8.
Polysorbate 60 (0.1%) 39.8.
Polysorbate 60 (1%) 54.
Polysorbate 20 (0.1%) 57.
Each sugar was tested in two independent experiments for xylitol and sucrose stearate (1%).
These ex vivo results therefore confirm the in vitro results, i.e. that the presence of HLB 16 sucrostearate in its surroundings inhibits the adhesion of S. aureus to both a solid matrix like a cytology slide and to human corneocytes.
ATODERMTm STOP EVOLUTIVE
Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 0.61.
Water Q.s. 100 =
ATODERMTm STOP CRISE
Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 0.61.
Anti-pruriginous agent 0.3.
Anti-inflammatory agent 0.5.
Water Q.s. 100 ATODERMTm STOP RECIDIVE
, Product % by weight in the composition HLB 16 sucrostearate (SURFHOPE 2Ø
C1816) Lipid phase 11Ø
Other polyhydroxylated compounds 1.1.
Anti-pruriginous agent 0.3.
Vitamin PP 0.3.
Water Q.s. 100 REFERENCES
Kita K., Sueyoshi N., Okino N., Inagaki M., Ishida H., Kiso M., Imayama S., Nakamura T., Ito M. 2002. Activation of bacterial ceramidase by anionic glycerophOspholipids : possible involvement in ceramide hydrolysis on atopic skin by Pseudomonas ceramidase. Biochem J., 362, p. 619-626.
McEwan N.A., Kalna G. and Mellor D. 2005. A comparison of adherence by four strains of Staphylococcus intermedius and Staphylococcus hominis to canine corneocytes collected from normal dogs and dogs suffering from atopic dermatitis. Research in Veterinary Science, Vol. 78, p. 193-198.
Piccicuto S., Blecker C., Brohee J.C., Mbampara A., Lognay G., Deroanne C., Paquot M. and Manlier M. 2001. Les esters de sucres : voies de synthese et potentialites d 'utilisation [Sugar esters: synthetic pathways and potential uses].
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Environ., Vol. 5(4), p. 209-219.
Pascolini C., Sinagra J., Pecetta S., Bordignon V., De Santis A., CM L., Cafiso V., Prignano G., Capitanio B., Passariello C., Stefani S., Cordiali-Fei P., Ensoli F. 2011.
Molecular and immunological characterization of Staphylococcus aureus in pediatric atopic dermatitis: implications for prophylaxis and clinical management. Clin Dev Imnuazol. 2011 Oct 27 (Epub).
Claims (18)
1. A cosmetic composition for topical application, comprising:
a sucrose stearate containing at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid, with a Hydrophile/Lipophile Balance (HLB) of 16, for use in the treatment of atopic dermatitis as an agent to inhibit the adhesion of Staphylococcus aureus on human skin and nasal mucosa.
a sucrose stearate containing at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid, with a Hydrophile/Lipophile Balance (HLB) of 16, for use in the treatment of atopic dermatitis as an agent to inhibit the adhesion of Staphylococcus aureus on human skin and nasal mucosa.
2. The cosmetic composition according to Claim 1, wherein the sucrose stearate represents 0.1-5% of the composition by weight.
3. The cosmetic composition according to Claim 1, wherein the sucrose stearate represents 1-3% of the composition by weight.
4. The cosmetic composition according to Claim 1, wherein the composition further comprises a sorbitan ester, wherein the sorbitan ester is polysorbate 20.
5. The cosmetic composition according to Claim 4, wherein the sucrose stearate and/or the sorbitan ester represent 0.1-5% of the composition by weight.
6. The cosmetic composition according to Claim 4, wherein the sucrose stearate and/or the sorbitan ester represent 1-3% of the composition by weight.
7. The cosmetic composition according to any one of Claims 1 to 6, wherein the composition further comprises lipids that can restore cutaneous barrier function, respectively:
- at least one lipid not found naturally in the skin; and/or - a mixture of constituents that occur naturally in the skin, wherein the mixture of constituents comprises ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
- at least one lipid not found naturally in the skin; and/or - a mixture of constituents that occur naturally in the skin, wherein the mixture of constituents comprises ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
8. The cosmetic composition according to Claim 7, wherein the at least one lipid not found naturally in the skin is an oil.
9. The cosmetic composition according to Claim 7 or 8, wherein the mixture of constituents comprises: Water, Ceramide 3, Ceramide 611, Ceramide 1, Phytosphingosine, Cholesterol, Sodium Lauroyl Lactylate, Carbomer, and Xanthan Gum, the mixture of constituents representing between 0.01% and 5% of the composition by weight.
10. Use of a topical cosmetic composition for treatment of atopic dermatitis, the cosmetic composition comprising:
a sucrose stearate containing at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid, with a Hydrophile/Lipophile Balance (HLB) of 16, wherein the cosmetic composition inhibits the adhesion of Staphylococcus aureus on human skin and nasal mucosa.
a sucrose stearate containing at least 75% monoesters of sucrose and stearic acid by weight, the rest being di, tri and polyesters of sucrose and stearic acid, with a Hydrophile/Lipophile Balance (HLB) of 16, wherein the cosmetic composition inhibits the adhesion of Staphylococcus aureus on human skin and nasal mucosa.
11. The use according to Claim 10, wherein the sucrose stearate represents 0.1-5% of the composition by weight.
12. The use according to Claim 10, wherein the sucrose stearate represents 1-3% of the composition by weight.
13. The use according to Claim 10, wherein the composition further comprises a sorbitan ester, wherein the sorbitan ester is polysorbate 20.
14. The use according to Claim 13, wherein the sucrose stearate and/or the sorbitan ester represent 0.1-5% of the composition by weight.
15. The use according to Claim 13, wherein the sucrose stearate and/or the sorbitan ester represent 1-3% of the composition by weight.
16. The use according to any one of Claims 10 to 15, wherein the composition further comprises lipids that can restore cutaneous barrier function, respectively:
- at least one lipid not found naturally in the skin; and/or - a mixture of constituents that occur naturally in the skin, wherein the mixture of constituents comprises ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
- at least one lipid not found naturally in the skin; and/or - a mixture of constituents that occur naturally in the skin, wherein the mixture of constituents comprises ceramides 1, 3, 6, cholesterol, free fatty acids and phytosphingosine.
17. The use according to Claim 16, wherein the at least one lipid not found naturally in the skin is an oil.
18. The use according to Claim 16 or 17, wherein the mixture of constituents comprises: Water, Ceramide 3, Ceramide 611, Ceramide 1, Phytosphingosine, Cholesterol, Sodium Lauroyl Lactylate, Carbomer, and Xanthan Gum, the mixture of constituents representing between 0.01% and 5% of the composition by weight.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1257681A FR2994386B1 (en) | 2012-08-07 | 2012-08-07 | INHIBITION OF ADHESION OF PATHOGENIC MICROORGANISMS BY SUCROSE AND / OR SORBITAN ESTER IN THE COSMETIC TREATMENT OF SKIN ATOPIA |
| FR1257681 | 2012-08-07 | ||
| PCT/FR2013/051856 WO2014023895A2 (en) | 2012-08-07 | 2013-07-31 | Inhibition of the adhesion of pathogenic microorganisms by a sucrose stearate and/or a sorbitan ester in the cosmetic treatment of cutaneous atopy |
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| CA2881267A1 CA2881267A1 (en) | 2014-02-13 |
| CA2881267C true CA2881267C (en) | 2021-02-16 |
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| GB2565511B (en) | 2016-05-26 | 2022-04-13 | Kimberly Clark Co | Anti-adherent compositions and methods of inhibiting the adherence of microbes to a surface |
| FR3065372B1 (en) * | 2017-04-21 | 2019-12-20 | Jean Noel Thorel | COMPOSITION COMPRISING CARBOXY METHYL NARINGENINE CHALCONE FOR THE TREATMENT OF PRURITUS AND ATOPIC DERMATITIS |
| CN108524478B (en) * | 2018-06-11 | 2020-05-08 | 四川昇嘉科技有限公司 | Application of sanshool in preparation of external preparation for repairing skin photodamage |
| JP2022533348A (en) * | 2019-05-16 | 2022-07-22 | ユニリーバー・アイピー・ホールディングス・ベスローテン・ヴェンノーツハップ | Use of sugars or sugar alcohols |
| CN113509457B (en) * | 2020-09-07 | 2023-03-21 | 四川昇嘉科技有限公司 | Application of sanshool in preparation of medicine for treating eczema |
| KR20220083289A (en) | 2020-12-11 | 2022-06-20 | 정기순 | Drunk Driving Prevention System |
| FR3118416B1 (en) | 2020-12-24 | 2023-11-17 | Naos Inst Of Life Science | COSMETIC COMPOSITION CAPABLE OF STRENGTHENING EPIDERMAL TIGHT JUNCTIONS FOR THE PREVENTION AND/OR TREATMENT OF ATOPIC DERMATITIS |
| WO2022230925A1 (en) * | 2021-04-28 | 2022-11-03 | アスパック企業株式会社 | Pyoderma ameliorating agent |
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| NL1003524C2 (en) * | 1996-07-05 | 1998-01-12 | Cooperatie Cosun U A | Diaper rash prevention or treatment composition. |
| US5961997A (en) * | 1997-03-25 | 1999-10-05 | Swinehart; James M. | Antipruritic composition |
| DE19718777A1 (en) * | 1997-05-03 | 1998-11-05 | Beiersdorf Ag | Use of esters from fatty acids and di- and oligosaccharides against the adhesion of microorganisms |
| FR2798591B1 (en) * | 1999-09-22 | 2001-10-26 | Pharmascience Lab | USE OF A VEGETABLE OIL PRODUCT FOR INCREASING THE SYNTHESIS OF SKIN LIPIDS IN COSMETICS, PHARMACY OR DERMATOLOGY AND AS A FOOD ADDITIVE |
| JP2001181175A (en) * | 1999-12-27 | 2001-07-03 | Prosper & Company Kk | Cosmetic and quasi-drug |
| US20030027786A1 (en) * | 2001-06-06 | 2003-02-06 | Karsten Maeder | Lipase inhibiting composition |
| JP2003012492A (en) * | 2001-07-02 | 2003-01-15 | Noevir Co Ltd | Cosmetic |
| JP2003089660A (en) * | 2001-09-18 | 2003-03-28 | Mitsubishi-Kagaku Foods Corp | Method for preventing lotion from degeneration |
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| US7138394B2 (en) * | 2002-09-27 | 2006-11-21 | Alpharx Inc. | Vehicle for topical delivery of anti-inflammatory compounds |
| MXPA05004278A (en) * | 2002-10-25 | 2005-10-05 | Foamix Ltd | Cosmetic and pharmaceutical foam. |
| TWI365075B (en) * | 2004-09-22 | 2012-06-01 | Kao Corp | Microemulsion |
| WO2006134937A1 (en) * | 2005-06-14 | 2006-12-21 | Sekisui Chemical Co., Ltd. | Skin preparation for external use |
| JP2007332055A (en) * | 2006-06-13 | 2007-12-27 | Sekisui Chem Co Ltd | External preparation for skin |
| CN101468006B (en) * | 2007-12-25 | 2011-12-28 | 重庆华邦制药股份有限公司 | Compound pharmaceutical composition containing doxepin and nicotinic amide |
| KR20090108848A (en) * | 2008-04-14 | 2009-10-19 | 주식회사 씨에이팜 | The composition for the treatement of atopy |
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| JP5594868B2 (en) * | 2010-01-25 | 2014-09-24 | 株式会社ミルボン | Hairdressing composition |
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| ES2751878T3 (en) | 2020-04-02 |
| CA2881267A1 (en) | 2014-02-13 |
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| JP2018030852A (en) | 2018-03-01 |
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| CN104602668A (en) | 2015-05-06 |
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| EP3246013B1 (en) | 2019-10-09 |
| FR2994386A1 (en) | 2014-02-14 |
| KR20150040909A (en) | 2015-04-15 |
| EP2882413B1 (en) | 2018-04-11 |
| CN104602668B (en) | 2018-12-28 |
| JP2015528822A (en) | 2015-10-01 |
| PT3246013T (en) | 2019-10-29 |
| JP6408667B2 (en) | 2018-10-17 |
| EP2882413A2 (en) | 2015-06-17 |
| ES2668302T3 (en) | 2018-05-17 |
| KR102059919B1 (en) | 2019-12-27 |
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