BE1025110B1 - CAPSULE COMPRISING A PROBIOTIC MICROORGANISM FOR USE IN A DEVICE FOR PRODUCTION AND DISTRIBUTION OF COMPOSITIONS - Google Patents

Abstract

The invention relates to a capsule (I) comprising a cup comprising at least one side wall (2) and a bottom wall (4); and a lid (3), for use in a device for producing and dispensing compositions, the capsule (1) comprising at least one ingredient for producing extemporaneously a personalized cosmetic and / or pharmaceutical composition by mixing said ingredient with at least one physiologically acceptable vector, wherein said ingredient is a probiotic microorganism improving the balance of the cutaneous microbiome.

Description

(30) Priority data:

12/16/2016 EP 16204649.4 (73) Holder (s):

NESTLE SKIN HEALTH

1018, LAUSANNE

Switzerland (72) Inventor (s):

BAENSCH Johannes 1093 CONVERSION Switzerland (54) CAPSULE COMPRISING A PROBIOTIC MICROORGANISM FOR USE IN A DEVICE FOR PRODUCING AND DISPENSING COMPOSITIONS (57) The invention relates to a capsule (I) comprising a cup composed of at least one side wall ( 2) and a bottom wall (4); and a cover (3), for use in a device for producing and distributing compositions, the capsule (1) comprising at least one ingredient for producing extemporaneously a personalized cosmetic and / or pharmaceutical composition by mixing said ingredient with at least one physiologically acceptable carrier, wherein said ingredient is a probiotic microorganism improving the balance of the skin microbiome.

BE2017 / 5929

CAPSULE COMPRISING A PROBIOTIC MICROORGANISM FOR USE

IN A DEVICE FOR PRODUCING AND DISTRIBUTING COMPOSITIONS

The invention relates to the field of dermatology and, more particularly, the self-manufacture or the extemporaneous preparation of personalized cosmetic and / or pharmaceutical compositions, in particular for use in the treatment of skin dermatological disorders or diseases. The invention also relates to capsules comprising active ingredients improving the balance of the skin microbiome, to be mixed with at least one physiologically acceptable vector, for the extemporaneous preparation of personalized cosmetic and / or pharmaceutical compositions.

The human body is home to an extremely complex and rich microbial community. The human microbiome has ten times more microbial cells than human cells. These microorganisms are generally harmless and contribute to a healthy state by producing vitamins, participating in the digestion of food, or by stimulating the immune system. The human microbiota is found mainly on the surface and in the deep layers of the skin, in saliva and oral mucosa, in the conjunctiva and in the gastrointestinal tract.

It has been shown, primarily in the gut, that the human microbiota plays a key role in human health and disease. The skin is colonized by many microorganisms, most of which are beneficial or harmless.

However, the skin microbiome has specific compositions for skin diseases that differ from healthy skin. Diseases such as acne are associated with major changes and disturbances in the microbiome.

Thus, to modify the microbiome and more particularly the skin microbiome, different approaches have been developed.

A preferred approach consists in developing pharmaceutical compositions, healthy, without antibiotics and respectful of the environment. Application WO16122889 discloses in particular a method making it possible to modify the presence in profusion of a bacterial taxon in the microbiota of a human subject. The method comprises administering to the human subject a pharmaceutical composition comprising prebiotics, such as a glycan-based therapeutic preparation, in an amount sufficient to modify the presence in profusion of the bacterial taxon.

Another approach, disclosed in particular in application WO16086208 consists in modifying the microbiome by administering directly to a human subject a probiotic composition comprising an anti-inflammatory bacterial population, isolated in order to reduce the inflammation of which the subject is affected.

However, the preparation of cosmetic and / or pharmaceutical compositions comprising prebiotics or prebiotic microorganisms generates new formulation problems, in particular in terms of stability from the physical and chemical point of view. Maintain focus

BE2017 / 5929 probiotic microorganisms under control in these cosmetic and / or pharmaceutical compositions also represents a challenge.

Furthermore, an additional problem with cosmetic and / or pharmaceutical compositions comprising probiotic microorganisms is that they generally have a short shelf life.

In this context, the Applicant proposes to develop alternative solutions for producing and supplying extemporaneous cosmetic and / or pharmaceutical compositions comprising one or more probiotic microorganisms. These compositions are preferably used topically, for the prevention and / or treatment of skin dermatological diseases or disorders, such as, for example, acne, the formation of folds, eczema, erythema, and in particular erythema. rosacea, erythema acne or acute erythema, blushing, skin inflammation not related to rosacea, psoriasis, purpura, rosacea, sagging skin, telangiectasia and / or aging of the skin, or a symptom associated therewith.

In particular, these personalized compositions comprising probiotic microorganisms considerably reduce the duration of the treatment and make it possible to further reduce the symptoms of skin diseases. In addition, the extemporaneous cosmetic and / or pharmaceutical compositions according to the invention provide a definite advantage in terms of efficacy and tolerance which makes it possible to increase the therapeutic effect at similar doses, or to maintain the same therapeutic effect, while by decreasing the doses.

From a general point of view, the embodiments of the present invention relate to a capsule for use in a device for the production and distribution of compositions, the capsule comprising at least one probiotic microorganism for producing extemporaneously a cosmetic composition and / or personalized pharmaceutical, in particular by mixing said probiotic microorganism with at least one physiologically acceptable vector.

Surprisingly, using capsules according to the invention, the Applicant has developed a way of producing and distributing a ready-to-use personalized cosmetic and / or pharmaceutical composition, which in particular proves to be stable from the physical point of view and chemical, when administered to a subject or when applied to the subject's skin.

The present invention further relates to a system for producing and distributing a composition, said system comprising:

- at least one capsule according to the invention,

- at least one container comprising a physiologically acceptable vector, and

- A device for the production and distribution of compositions, in which the device comprises means for mixing the content of the capsule with the content of the container and means for producing and supplying temporarily a personalized cosmetic and / or pharmaceutical composition.

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The present invention also relates to a method for supplying a cosmetic composition from a production and distribution device, said method comprising the steps intended for

mixing the content of the capsule according to the invention with the content of at least one container comprising a physiologically acceptable vector, and

- produce and supply said cosmetic composition.

The invention is more detailed in the following description with reference to the accompanying drawings, in which:

Figures la, 1b, le, 2a, 2b and 2c show schematic sections of capsules according to the invention;

Figure 3 is a three-quarter view of the upper part of a capsule according to the invention;

Figure 4 is a three-quarter view of the lower part of a capsule according to the invention;

Figure 5 is a three-quarter view of the upper part of another capsule according to the invention; and

Figure 6 is a three-quarter view of the bottom of another capsule according to the invention.

For the preparation of the extemporaneous cosmetic and / or pharmaceutical compositions according to the invention, capsules are used.

The capsules were developed in the food science and consumer goods sector. The capsules are described in particular in documents EP0512468 and EPI 784344.

In summary, these capsules generally consist of:

- a hollow body and an injection wall which is impermeable to liquids and to air and which is connected to the body and adapted to be pierced, for example, by an injection needle of the system,

- a room comprising a product to be extracted,

- a membrane, preferably made of aluminum, disposed at the lower end of the capsule, closing said capsule, to maintain the internal pressure in the chamber, said membrane being associated with drilling means, for drilling distribution holes in said aluminum membrane when said internal pressure inside the chamber reaches a certain predetermined value,

- Optionally, means configured to break the jet of fluid in order to reduce the speed of the jet of fluid injected into the capsule and distribute the liquid over the layer of the substance at a reduced speed.

The capsule according to the invention, which comprises a probiotic microorganism, is used for the extemporaneous self-production of a personalized cosmetic and / or pharmaceutical composition when it is mixed with at least one physiologically acceptable vector. The composition prepared is of therapeutic interest for treating and / or preventing a related skin disease.

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As shown in FIGS. 1 to 6, the capsule 1 according to the invention generally comprises:

- a cup composed of one or more side wall (s) 2 and a bottom wall 4;

- a cover 3 and

- a bedroom 5.

The cup, which is the main part of the capsule, is composed of one or more side wall (s) 2 and a bottom wall 4. The cup 2 is preferably a frustoconical element (Figures la, 1 b, le, 3, 4, 5 and), or hemispherical (Figures 2a, 2b and 2c). The bottom wall 4 also called base of the cup is not necessarily flat, it can also have the aforementioned geometric shapes. The cup is preferably made of aluminum, pure plastic, multilayer plastic or a multilayer film, or a combination of these.

More preferably, the cup 2 is composed:

- of aluminum between 10 and 150 μm thick, preferably between 20 μm and 100 μm thick, and more preferably between 50 and 60 μm thick;

- pure plastic;

- multilayer plastic, possibly with an oxygen barrier layer, such as EVOH (copolymer of ethylene and vinyl alcohol) or PVDC (polyvinylidene chloride); or

- a multilayer film, such as cardboard / aluminum / plastic or cardboard / plastic with possibly an oxygen barrier layer, such as EVOH or PVDC.

In a first variant of the invention as shown in FIG. 1b, the lower wall 4 comprises one or more internal layers 4L

In a second variant of the invention, as shown in FIG. 1 a, the cup comprises an additional layer 21 capable of dividing the chamber of the capsule 5 into two separate chambers 51 and 52.

In a third variant of the invention, as shown in FIGS. 2 b and 6, the lower wall 4 comprises a part covered with a layer of elastic material 42 which must preferably be pierced during the extraction of the contents of the capsule. .

The cover 3 of the cup or the upper membrane 3 is preferably welded at the end of the cup by heat-bonding, the elements to be welded comprising a colorless weld on their opposite faces. Alternatively, as shown in FIG. 2a, the lower edge of the cup can also be folded over the cover for crimping 33.

The cover 3 of the capsule 1 can preferably be made of aluminum or of a multilayer film. More preferably, the cover is composed:

- aluminum 15 to 60 μm thick,

- an elastic material, or

- a multilayer film comprising:

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i. either paper 20 to 60 g / m ² , plastic, such as polyethylene 20 to 60 μm thick, and aluminum 5 to 20 μm thick;

ii. or EVOH or PVDC 5 to 30 μm thick and plastic (PP for polypropylene, PE for polyethylene, PA for polyamide) 20 to 100 μm thick or PET (polyester) 5 to 30 μm thick and plastic (PP, PE) 20 to 100 μm thick or metallized TEP or PET with an upper barrier layer, such as SiO2 (silicon dioxide).

The cover 3 of the capsule 1 can also consist of a multilayer combination of paper and aluminum.

In a first variant of the invention, the cover is an upper membrane comprising a single layer 3, as illustrated in FIGS. 1 a and 2 b, of elastic material (that is to say a membrane called a monolayer).

In a second alternative of the invention, as shown in FIG. 1 a, the cover is an upper membrane composed of a laminate composed of several superimposed layers 31 which are at least partially joined together, so that at least one of the constituent layers of the laminate is made of elastic material. Preferably, the stratification in the area where the needle pierces the upper membrane has weaker adhesion (or no adhesion) compared to other regions of the membrane, in order to facilitate the reclosing movement of the elastic layer.

In a third variant of the invention (not shown), the cover 3 is an upper membrane comprising a non-elastic film, at least part of which is covered with a layer of elastic material. The elastic material is preferably applied to said film in a liquid phase, which is then solidified by a heat treatment, electron beam or UV light.

In a fourth variant of the invention as illustrated in Figures 1b, 2c and 3, the cover 3 is an upper membrane comprising a non-elastic film, at least part of which is covered with a layer of elastic material 32 using an adhesive applied “as a sticker” or by using heat welding or ultrasonic sealing.

In a fifth variant of the invention, the upper membrane of the capsule 3 is coated on at least part of its surface with a layer of silicone which is applied during the melting temperature (i.e. in liquid form), so that it solidifies as it cools on the membrane to which it is applied ("hot-melt application").

In all of the embodiments mentioned above, the elastic material is preferably a food grade silicon, very particularly a liquid mono component silicone which is fixed by reaction with atmospheric humidity (that is to say at room temperature ). Examples of elastic materials include, but are not limited to, for example: a food grade thermoplastic elastomer such as SBCs (styrene block copolymers),

BE2017 / 5929 silicone or liquid silicone rubber, ethylene vinyl alcohol (EVA) - based, EPDM (ethylene - propylene - diene - monomer) or an isoprene rubber.

The capsule 1 according to the invention can vary in size depending on the volume and the probiotic concentration of the product to be prepared, that is to say the personalized cosmetic and / or pharmaceutical composition.

The dose of the personalized cosmetic and / or pharmaceutical composition to be supplied can preferably vary from 0.5 g to 100 g, preferably from 2 to 10 g.

Preferably, the diameter of the cover 3 of the capsule 1 is between 5 and 50 mm, more preferably between 8 and 48 mm, more preferably between 15 and 35 mm.

Preferably, the diameter of the cup of the capsule 1 is between 3 and 45 mm, more preferably between 5 mm and 35 mm, more preferably still between 10 mm and 30 mm.

The capsule 1 according to the invention is filled with at least one probiotic microorganism.

By "probiotic microorganism" is meant a microorganism which, when used in sufficient quantity, proves beneficial to the health of its host and can improve the balance of the skin microbiome.

By "skin microbiome" is meant the microorganisms present in healthy human skin, which is generally composed of a balanced set of commensal skin microorganisms. The skin microbiome of a human host can include a variety of resident microorganisms that help promote the health and / or appearance of the host's skin.

In a preferred embodiment, the probiotic microorganism of the invention is selected from Acetobacter, Actinomyces, Acinetobacter, Aerococcus, Akkermansia, Anabaena, Anaerococcus, Anaerofustis, Anaerostipes, Anaerotruncus, Arthrospira, Arthrobacter, Aureobasidium, Bacillus Bactero, Bactero, Bactero , Brachybacterium, Brevibacterium, Butyrivibrio, Carnobacterium, Clostridium, Coprococcus, Corynebacterium, Cyanobacterium, Deinococcus, Enhydrobacter, Enterococcus, Eubacterium, Eaecalibacterium, Fibrobacter, Fusobacterium, Gluconacetobacter, Gluconacetobacter, Gluconacetobacter , Melissococcus, Micrococcus, Neisseria, Nitrosococcus, Nitrosocystis, Nitrosolobus, Nitrosomonas, Nitrosospria, Nitrosovibrio, Oenococcus, Oscillospira, Pediococcus, Peptoniphilus, Peptostreptococcus, Propionibacterinusususumususumususococcus, Soccorususococcus, llus, Staphylococcus, Stenotrophomonas, Streptococcus, Tetragenococcus, Weissella taken alone or in combination, preferably Bifidobacterium and / or Lactobacillus.

Preferably, the probiotic microorganism useful for the present invention is chosen from

Bifidobacterium adolescent, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, Lactobacillus casei,

BE2017 / 5929

Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus rhamnosus, taken alone or in combination, more preferably from the group consisting of Lactobacillus casei,

Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus rhamnosus, taken alone or in combination.

Even more preferably, the probiotic microorganism useful for the present invention is Lactobacillus johnsonii LAI NCC 533 (deposit number CNCM 1-1225).

Lactobacillus johnsonii NCC533 LAI (1-1225 CNCM) has been deposited, according to the Budapest Treaty, at the National Collection of Cultures of Microorganisms (CNCM), Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France, 30 June 1992, under the reference CNCM 1-1225.

Preferably, the probiotic microorganism according to the invention is an unprocessed probiotic microorganism, i.e. a natural, non-genetically modified, non-pathogenic and non-invasive microorganism of the human microbiome, preferably the skin microbiome of a healthy (non-sick) human subject.

The probiotic microorganism can be used in a viable, semi-inactivated or inactivated form but preferably in an inactivated form also known as non-replicated form. In particular, the probiotic microorganism is used in a non-reproducible form, for example by means of heat treatment.

Inactivated microorganisms can have intact or ruptured cell membranes. As such, the term "inactivated" also denotes extracts of microorganisms and lysates comprising fractions and / or metabolites.

In what follows, Lactobacillus johnsonii NCC533 LAI (CNCMI-1225), in particular Lactobacillus johnsonii NCC533 LAI (CNCMI-1225) non reproducible, for example a heat treatment Lactobacillus johnsonii NCC533 LAI (CNCMI-1225) will be called RMN LAI.

The “non-reproducible” probiotic microorganisms and in particular Lactobacillus johnsonii LAI NCC533 can be inactivated, dead or not viable.

The probiotic microorganisms and in particular Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) can be used at least partially not reproducible.

Non-reproducible forms, especially heat-treated microorganisms such as Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) have the advantage of being even more effective than their living counterparts. The use of non-reproducible microorganisms, such as thermotreated probiotic microorganisms such as Lactobacillus johnsonii NCC533 LAI (CNCMI1225) unlike their living counterparts, have the advantage of:

- reduce the potential risk of sepsis associated with live probiotics in sensitive target populations,

- represent a safe alternative for immunocompromised patients.

BE2017 / 5929

On the other hand, thanks to the reduction of obstacles to processing, non-reproducible microorganisms can be integrated into stable liquid products with a long shelf life.

Thermal inactivation can occur at least around 70 ° C and any type of heat treatment can be used to inactivate probiotic microorganisms such as Lactobacillus johnsonii LAI NCC533 (CNCM 1-1225). For example, probiotic microorganisms such as Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) can be made non-reproducible from 110 ^° C. to 140 ° C. for 1 to 30 seconds, for example 10-20 seconds.

Consequently, in an embodiment of the present invention, at least 90%, for example at least 95% preferably at least 98%, more preferably 99%, ideally at least 99.9%, or all the probiotic microorganisms such as Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) are not reproducible.

Scientific studies suggest that probiotic microorganisms such as Lactobacillus johnsonii NCC533 (CNCM 1-1225), in particular in non-reproducible forms, for example heat-treated Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225), have shown superior effects on induction of the expression of antimicrobial peptides compared to those previously identified and described in previous studies.

Patent application WO 2010/130662 from Nestec describes that Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) strongly encourages the constitutive expression of human beta-defenins 1 (hBDl), and that Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) stimulates hBDl more actively than its living counterpart.

The probiotic microorganisms to be extracted, which are found in the chamber 5 of the capsule 1 are preferably in a dry form. They are obtained by conventional methods such as spray drying; lyophilization followed by grinding to micronize the powder; atomization on a cold surface, followed by sublimation and collection of the micronized powder; drying by evaporation of an unfrozen solution in a vacuum oven or a centrifugal evaporator at a temperature ranging from about -20 ° to 500 ° C, followed by milling to reach the desired particle size. The resulting powder particles are glassy or crystalline internally with a majority of glassy materials coating the surface. Coating probiotic microorganisms with glassy materials has the advantage of increasing the physical stability of the product and reducing the deleterious intermolecular reactions within the particle.

In a preferred embodiment, the frozen particles are loaded onto trays and immediately transferred to a vacuum drying chamber where the drying process takes place in three main stages comprising:

(1) a step of optional short purging and stabilization of the structure of frozen particles under vacuum pressure of less than 2000 mTORR,

BE2017 / 5929 (2) a primary step of drying under vacuum pressure of more than 2000 mTORR and at a temperature of about -20 ° to 500 ° C, and (3) a secondary and final step of drying the amorphous material vitreous under pressure under total vacuum and at elevated temperature for a time sufficient to reduce the water activity of the dried formulation to 0.3 Aw or less.

The dried and stable probiotic microorganisms can be used directly in the form of a flake or ground into a powder.

In a preferred embodiment, the probiotic microorganisms are in the form of small dry particles, and with at least 90% of dry matter per gram, preferably at least 93% of dry matter per gram. The dry particles are preferably for the most part regular and identical.

Preferably, the cosmetic and / or pharmaceutical composition personalized according to the invention also comprises a prebiotic.

Thus, before the production and distribution of the personalized cosmetic and / or pharmaceutical composition, the prebiotic can be present directly in the capsule according to the invention, in the physiologically acceptable carrier or in a second capsule, apart, preferably in a second separate capsule.

By "prebiotic" is meant a selectively fermented ingredient which allows specific changes, both in the composition and / or in the activity of the microflora, beneficial for the well-being of the host's skin. . Prebiotics can be administered orally or topically and can promote the growth of desired microorganisms (probiotics) and thereby improve the benefits for the host.

In particular, the prebiotic of the invention is selected from complex carbohydrates, complex sugars, guar gum, beta-glucans, biotin, cellulose, chitin, chitosan, dextrins, fructans, fructo -oligosaccharide (FOS), galactooligosaccharides (GOS), glucomannan oligosaccharide, gluco-oligosaccharides, hemicelluloses, high amylose corn starch (HAS), inulin, isomalto-oligosaccharides, lactosucrose , lactulose, lignin, mannan oligosaccharides (MOS), neosugar, oligodextrose, oligofructose, inulin enriched in oligofructose, oligosaccharides, palatinose, pectin, polydextrose, psyllium, raffinose, sorbitol, soy oligosaccharide, starch, tagatose, transgalactooligosaccharide, xylitol and xyloooligosaccharides XOS) and combinations thereof.

Preferably, the prebiotic is selected from fructo-oligosaccharides (FOS), galactooligosaccharide, glucomannan oligosaccharide, inulin, isomalto-oligosaccharides, lactosucrose, lactulose, neosugar, palatinose, raffinose, sorbitol, soy oligosaccharide, xylitol and xylooligosaccharide, preferably the prebiotic is a glucomannan oligosaccharide.

BE2017 / 5929

Preferably, the capsule for producing extemporaneously and providing a personalized pharmaceutical composition according to the invention can be used in the treatment and / or prevention of a skin disease in a subject. The personalized pharmaceutical composition provided can be administered topically to a skin area of the subject, where the skin surface is, or is likely to be, affected by the skin disease.

As indicated herein, the term "treatment" or "treat" refers to an improvement, prophylaxis or regression of the skin disease or associated dermatological disorder or at least one noticeable symptom thereof or thereof this. It also refers to an improvement, prophylaxis or regression of at least one measurable physical parameter, associated with the disease or skin disorder under treatment, which is not necessarily perceptible in or by the subject. In another embodiment, "treatment" or "treat" refers to inhibiting or slowing the progression of a disease or disorder, either physically, for example, stabilizing a noticeable symptom; physiologically, for example, the stabilization of a physical parameter or both. "Treatment" or "treat" also refers to delaying the onset of an illness or disorder, for example, by reducing or delaying the onset of redness of the skin affected by erythema or the symptom. In certain embodiments, compounds of interest are administered preventively. In this context, "prevention" or "prevent" refers to a reduction in the risk of contracting a specific disease or disorder.

One or more skin diseases or disorders can be treated using the personalized pharmaceutical composition of the invention. Skin diseases or disorders include inflammatory skin diseases and non-inflammatory skin diseases. Skin diseases or disorders include, but are not limited to acne, keratosis, actinic telangiectasia, alopecia areata, stomatitis, chapping, dermatitis, toxiderma, toxiderma, dry skin , eczema, erythema, erythema multiforme, erythema nodosa, mycoses, annular granuloma, herpes simplex, ichthyosis vulgaris, impetigo, intetrigo, keloids, actinic keratosis , chronic lichen simplex, milia, molluscum contagiosum, pemphigus, perioral dermatitis, pink pityriasis from Gibert, pruritus, pseudo folliculitis of barba, psoriasis, purpura, rashes, rhinophyma, rosacea, skin cancer, sunburn, telangiectasia, hives, vascular tumors and deformities and xerosis, or combinations thereof, or a symptom associated with them.

Preferably, the skin disease or disorder is rosacea, telangiectasia, psoriasis, purpura, acne, eczema, atopic dermatitis, erythema, in particular erythema of rosacea, erythema of acne or acute erythema, skin inflammations unrelated to rosacea, reddening, sagging skin, wrinkles and / or skin aging, or a symptom associated with them.

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One or more of the skin symptoms or changes can also be treated using the personalized pharmaceutical composition of the invention, including skin inflammation, reddening, telangiectasia and erythema.

In addition, one or more cosmetic skin alterations can also be treated using the personalized pharmaceutical composition of the invention, in particular loss of skin firmness, scaly skin, loss of skin radiance, oily skin, dry skin and skin tone.

As used herein, the term "subject" means any animal, preferably a mammal, more preferably a man, male or female, to whom will be or has been administered topical compounds or compositions according to the embodiments of the invention. Preferably, a subject needs, or has been the object of observation or of treatment experience or has known the prevention of a skin disease.

The term "topical composition", "topically administrable composition" or "topical formulation", as used herein, means any pharmaceutical and / or cosmetic formulation or composition acceptable for topical administration of the compounds specified according to the embodiments of the invention. Exemplary forms of formulation which may be used for topical administration in embodiments of the present invention include, but are not limited to sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, ointments, emulsions and suspensions.

The term "topically administrable composition" as used herein also includes locally applied and locally acting formulations such as formulations for use with prostheses, injections or patches.

The choice of composition for topical administration will depend on several factors, including but not limited to, the nature of the symptoms to be treated or prevented, the physico-chemical characteristics of the compound to be administered and other excipients present, their stability in formulation, aesthetics of any given formulation, available manufacturing equipment, and budgetary constraints.

These compositions are prepared according to the usual methods.

The pH of the topical compositions of the invention preferably lies in a physiologically acceptable pH range, for example, in a range from approximately 5 to 7, preferably in the range from approximately 5 to 6.

As used herein, the term "composition" is intended to include a product comprising the ingredient specified in the quantity specified, as well as any product resulting, directly or indirectly, from combinations of the ingredient specified in the quantity specified .

In an alternative embodiment of the invention, the capsule is intended to be used only to produce extemporaneously and to provide a personalized cosmetic composition,

BE2017 / 5929 specifically designed to prevent and / or treat the subject's disease or skin disorder. The personalized cosmetic composition provided can be administered topically to a skin area of the subject.

In a further embodiment, the present invention relates to a system intended for producing and distributing a composition, said system comprising:

- at least one capsule according to the invention,

- at least one container comprising a physiologically acceptable vector, and

- A device for the production and distribution of compositions, in which the device comprises means for mixing the content of the capsule with the content of the container and means for producing and temporarily supplying a personalized cosmetic and / or pharmaceutical composition.

The main part of the system according to the invention is the device for the production and distribution of compositions.

Such a device can extract the content of the capsule according to the invention, and mix it with the content of the container comprising a physiologically acceptable vector in order to produce and distribute a personalized cosmetic and / or pharmaceutical composition.

Such a device and its associated process for extracting the contents of the capsule are described in particular in documents EP0512142 and WO2014080093. The production and distribution device according to these patent applications allows the contents of the capsule to be extracted under good conditions.

To extract the contents of the capsule, it is either the upper membrane 3 or the lower wall 4 of the capsule 1 which tears under the effect of the extraction fluid which is a physiologically acceptable vector, initially present in a container.

An alternative device is notably described in documents EP2989260 and WO2011107221 which disclose diffusion devices suitable for receiving a capsule, in particular a capsule according to the invention.

According to the invention, the container comprises a physiologically acceptable carrier which can be in liquid, more or less fluid, pasty or solid form. Preferably, the physiologically acceptable vector is in liquid form.

The physiologically acceptable vector is preferably chosen from vectors well known in the art for the topical administration of pharmaceutical products. For example, the vector may include, but is not limited to, one or more of the following agents: solvents, emulsifiers, suspending agents, decomposers, binders, chelating agents, stabilizing agents, diluents, antioxidants, gelling agents, preservatives, lubricants, agents slowing absorption, skin penetrating agents, liposomes, dyes, odor absorbers or pigments and a mixture thereof.

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The amounts of the various constituents of the compositions according to the invention are those usually used in the sector concerned.

As used herein, "physiologically acceptable carrier" refers to an acceptable carrier or diluent comprising excipients and auxiliaries that facilitate the processing of the active ingredients into preparations that can be pharmaceutically used. The vector must be "acceptable" in the sense that it must be compatible with the other ingredients of the compositions and not be harmful to the beneficiary of these. The vector is compatible with human skin.

According to a particular embodiment of the invention, the vector is preferably fresh water.

By way of nonlimiting example of usable fresh water, mention may be made of drinking water such as mineral water, spring water, water rich in electrolytes or osmosis water.

Preferably, the water used in the capsule according to the invention is drinking water, the container of which can be a reservoir such as a bottle (bottled water), an aerosol or even a water tower (tap water).

More preferably, the usable fresh water is water rich in electrolytes in which the presence of electrolytes is detected at a minimum concentration of 30 mg / 1, often at a concentration greater than 100 mg / l. By way of nonlimiting example of water rich in electrolyte, mention may be made of water rich in mineral salts and / or trace elements such as thermal waters, for example Vichy, Avène, Uriage water, Jonzac, Bourbonne-les-Bains, Rochefort-sur-mer, Balaruc-les-bains, or La Roche Posay.

According to the invention, the personalized cosmetic and / or pharmaceutical composition intended to be produced and distributed by the device is preferably in the form of ointments, ointments, emulsions, creams, milks, ointments, powders, impregnated pads, bars, wipes, solutions. , gels, sprays or aerosols, foams, suspensions, lotions, sticks, shampoos or washing bases, preferably in the form of ointments, ointments, emulsions, creams, milks, ointments, solutions, gels, foams, suspensions or lotions.

Preferably, the personalized cosmetic and / or pharmaceutical composition used in the present invention is in the form of an emulsion, a cream, a standard lotion, a gel or a solution and, more preferably under the form of an emulsion. For example, it may be in the form of an optionally gelled oily solution, an optionally two-phase dispersion of the standard lotion, an emulsion obtained by dispersion of a fatty phase into an aqueous phase (O / W) or vice versa (W / O) or a triple emulsion (W / O / W or O / W / O) or a vesicular dispersion of ionic and / or non-ionic type. They can also be in the form of suspensions of microspheres or nanospheres or lipids or polymeric vesicles or polymeric patches and hydrogels with controlled release. These cosmetic and / or pharmaceutical compositions

BE2017 / 5929 are personalized for a topical application and can be in anhydrous form, in aqueous form or in the form of an emulsion.

After use, the capsule can be easily removed with a minimum of waste (packaging material or personalized cosmetic and / or pharmaceutical composition).

For the extemporaneous preparation of the personalized cosmetic and / or pharmaceutical composition, one or more capsules can be used. This advantage notably makes it possible to personally adapt the composition according to the skin disease (s) or skin condition (s) or the subject's disorders.

In addition, the extemporaneous mixing of the various ingredients of the personalized cosmetic and / or pharmaceutical composition solves many stability problems from the physical and chemical point of view.

In a particular embodiment of the invention, the personalized cosmetic and / or pharmaceutical composition is prepared using two or more capsules.

In a first variant, for the extemporaneous preparation of the personalized cosmetic and / or pharmaceutical composition, only a first capsule comprising a probiotic microorganism is used. The capsule is mixed with the physiologically acceptable carrier from the container, before dispensing the ready-to-use composition.

In a second variant, for the extemporaneous preparation of the personalized cosmetic and / or pharmaceutical composition, a first capsule comprising a probiotic microorganism is used, together with a second additional capsule, comprising a probiotic microorganism and / or a prebiotic compound. The two capsules are mixed with the physiologically acceptable carrier coming from the container, before the distribution of the ready-to-use composition.

In a third variant, for the extemporaneous preparation of a personalized pharmaceutical composition, at least one capsule according to the invention, a second capsule or the container also comprises an active ingredient chosen from the group comprising, but not limited to, antibiotics , antibacterial agents, antivirals, antiparasitics, antifungals, anesthetics, analgesics, antiallergic agents, retinoids, free radical scavengers, antipruritics, antihistamines, immunosuppressants, corticosteroids, keratolytic agents , intravenous immunoglobulins, anti-angiogens, anti-inflammatories and / or a mixture thereof. Preferably, the active ingredient is selected from the list consisting of acetaminophen, acetylsalicylic acid, acitretin, acyclovir, adapalene, alpha-tocopherol or their esters, amorolfm, amphotericin B, anthranoids, tetracycline class antibiotics, antibodies, ascorbic acid and their esters, benzoyl peroxide, betamethasone valerate, brimonidine, calcipotriol, calcitriol, ciclopirox , citric acid and

BE2017 / 5929 fruit acids, clindamycin phosphate, clobetasol 17-propionate, crotamiton, cyproheptadine, diclofenac and salts and their derivatives, dioxyanthranol, econazole, erythromycin, estradiol, d , fluocinolone acetonide, glycolic acid, glycyrrhetinic acid, hormone peptides, hydrocortisone, hydroquinone, ibuprofen and salts or derivatives thereof, isotretinoin , ivermectin, ketoconazole, kojic acid, lactic acid, lidocaine, lidocaine hydrochloride, malic acid, mequinol, metronidazole, miconazole or salts and their derivatives, minoxidil, d octopirox, pilocaine and their derivatives, progesterone, pyrethrinoids, retinoic acid, retinol, rucinol, salicylic acid, salicylic acid, superoxide dismutases, tazarotene, terbinafine, tetracaine, thenaldine, tretinoin, trimeprazine, zinc pyrithione and combinations thereof.

The above-mentioned active ingredients are present in concentration:

- in the capsule according to the invention,

- in a second separate capsule and / or

- In the container, so that their final concentration in the personalized cosmetic and / or pharmaceutical composition is in a cosmetically and / or therapeutically effective amount of these active ingredients.

Finally, in a last embodiment, the invention relates to a process for providing a cosmetic composition from a production and distribution device, said process comprising the steps intended for:

mixing the content of the capsule according to the invention with the content of a container comprising at least one physiologically acceptable vector, and

- produce and supply said cosmetic composition.

Other aspects and advantages of the invention will be revealed in the illustrative section which follows.

Example: 1 capsule according to the invention

As illustrated in FIG. 1 a, the capsule 1 comprises a cup 2 with a base 5 and a frustoconical side wall. The cup is made of aluminum with a thickness of 50 μm. Capsule 1 is filled with a composition comprising a probiotic microorganism according to the invention.

The capsule 1 is closed by a cover 3 4 of aluminum and paper.

The composition comprising a probiotic microorganism according to the invention is composed of 50% to 99%, preferably from 75% to 98% of Lactobacillus johnsonii NCC533 LAI (CNCM I225), by weight relative to the total weight of the composition.

Example 2: Preparation of a personalized cosmetic and / or pharmaceutical composition according to the invention

BE2017 / 5929

After mixing:

- the contents of the capsule with

- The content of the container comprising at least one physiologically acceptable vector, and in the device for the production and distribution of compositions, a personalized cosmetic and / or pharmaceutical composition has been prepared.

The personalized cosmetic and / or pharmaceutical composition of the invention comprises from 0.01% to 5%, preferably from 0.03% to 1% and more specifically from 0.03%, 0.1% and 1% of the probiotic microorganism , in particular Lactobacillus johnsonii NCC533 LAI (CNCM 1-225), by weight relative to the total weight of the composition. In a more specific aspect, the topical pharmaceutical composition of the invention comprises an amount of the probiotic microorganism, especially Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) corresponding to about 10 ⁴ to 10 ¹² cfu or about 0.005 mg - 1000 mg per daily dose.

Example 3: Cosmetic and / or pharmaceutical composition personalized according to the invention

Originally present in Trade name Name of ingredients % weight! weight Containing PLANTACARE 818UP Coconut glucoside 6.00 to 15.00 Containing PROTELAN LS9011 Sodium lauroyl sarcosinate 5.00 to 10.00 Containing PROTELAN AG 818 G Cocoyl sodium glutamate 7.00 to 15.00 Containing KELTROL CG-SFT Xanthan gum 0.10 to 0.80 Containing NATROSOL PLUS 330CS Cetyl Hydroxyethylcellulose 0.50 to 2.50 Containing PROBENZ SP Sodium benzoate 0.10 to 3.00 Containing ZEMEA 1, 3-Propanediol 2.00 to 10.00 Containing GLYCERIN 4810 PLANT Glycerin 2.00 to 5.00 Containing STEPAN MILD GCC Glyceryl caprylate / caprate 0.50 to 2.00 Containing D-PANTHENOL USP Panthenol 0.10 to 1.00 Containing SUPER MONEY PRESTIGE SOFT Mica / titanium dioxide 0.05 to 0.20 Containing MONO-HYDRATE Citric acid 0.20 to 2.00

BE2017 / 5929

CITRIC ACID Containing ACTIVE INGREDIENT Active ingredient 0.00 to 20.00 Capsule PROBIOTIC Probiotic 0.10 to 1.00 Capsule or container PREBIOTIC Prebiotic 0.00 to 10.00 Containing HYDROLITE 5 / 5P Pentylene glycol 0.00 to 5.00 Containing PURIFIED WATER Water Qsp 100

Example 4: Cosmetic and / or pharmaceutical composition personalized according to the invention

Originally present in Trade name Name of ingredients % w / w Containing SATIAXANE UCX911 Xanthan gum 0.10 to 1.50 Containing GLYCERIN 4810 PLANT Glycerin 1.00 to 5.00 Containing ZEMEA Propanediol 1.00 to 8.00 Containing D-PANTHENOL U SP Panthenol 0.20 to 1.20 Containing CERALUTION H Behenyl alcohol / glyceryl stearate / glyceryl stearate citrate / na dicocoylethylenediamine PEG-15 sulfate 1.00 to 5.00 Containing EMULGADE 1000NI Cetearyl alcohol and ceteareth-20 1.00 to 3.00 Containing OIL SUNFLOWER ORGANIC OLEIQUE Sunflower seed oil (helianthus annuus) 3.00 to 8.00 Containing SOFT SHEAR LIPEX Butyrospermum Parkii 0.00 to 20.00 Containing MIGLYOL812N Caprylic / capric triglyceride 2.00 to 7.00

BE2017 / 5929

Containing CETIOL CC Dicapryle carbonate 3.00 to 4.00 Containing LANETTE 16 Cetyl alcohol 1.00 to 3.00 Containing HYDROLITE CG Caprylyl Glycol 0.10 to 1.00 Containing INGREDIENT ACTIVE Active ingredient 0.00 to 20.00 Capsule PROBIOTIC Probiotic 0.01 to 5.00 Capsule or container PREBIOTIC Prebiotic 0.00 to 10.00 Containing TITRIPLEX III Disodium EDTA 0.05 to 0.20 Containing HYDROXIDE SODIUM (10% aqueous solution) Sodium hydroxide Qs pH 5-5.5 Containing PURIFIED WATER Water Qsp 100

Example 5: Cosmetic and / or pharmaceutical composition personalized according to the invention

Originally present in Trade name Name of ingredients % w / w Containing KELTROL CG-T Xanthan gum 0.10 to 1.50 Containing VIVAPUR COS5 Microcrystalline cellulose (and) gum Cellulose 0.00 to 5.00 Containing GLYCERIN 4810 PLANT Glycerin 1.00 to 5.00 Containing ZEMEA Propanediol 5.00 to 10.00 Containing EMULIUM KAPPA Candelilla / Jojoba / Sound of rice Polyglyceryl-3 Esters and) Glyceryl stearate (and) Cetearyl alcohol and) Sodium stearoyl-lactylate 0.00 to 8.00 Containing PROLIX RB Rice branate Polyglyceryl-3 2.00 to 6.00 Containing ACID LIP C8G Capryloyl Glycine 0.50 to 1.50 Containing LIP ACIDE UG Undecylenic glycine 0.00 to 0.50 Containing OIL SUNFLOWER OLEIQUE Sunflower seed oil (helianthus annuus) 3.00 to 8.00

BE2017 / 5929

ORGANIC DEODORIZED Containing ACTICIRE Jojoba esters / Acacia Decurrens flower wax / Helianthus Annuus seed wax (sunflower) / Polyglycerin-3 3.00 to 8.00 Containing ISOSTERATE ISOSTEARYLE Isostearyl of isosteres 2.00 to 7.00 Containing CETIOL CC Dicapryle carbonate 3.00 to 8.00 Containing CUTINA HVG Hydrogenated vegetable glycerides 0.00 to 0.50 Containing LIPOCIRE A Triglycerides C10-18 1.00 to 5.00 Containing DERMOSOFT 688 p-anisic acid 0.01 to 0.20 Containing D-PANTHENOL USP Panthenol 0.20 to 1.20 Containing ACTIVE INGREDIENT Active ingredient 0.00 to 20.00 Capsule PROBIOTIC Probiotic 0.01 to 5.00 Capsule or container PREBIOTIC Prebiotic 0.00 to 10.00 Containing HYDROXIDE SODIUM (10% aqueous solution) Sodium hydroxide Qs pH 5-5.5 Containing PURIFIED WATER Water Qsp 100

Example 6: Comparison of the conservation and stability of different capsules according to the invention comprising probiotics:

The conservation of three capsules according to the invention was compared.

As illustrated in Figure la, each of the three capsules is identical and includes a cup with a base and a frustoconical side wall. The cup is made of aluminum with a thickness of 50 μm.

Each capsule is filled with a composition comprising in particular a probiotic microorganism according to the invention, in lyophilized form or not.

Each capsule is closed with an aluminum and paper cover,

Capsule 1 includes in particular the Yo-Plus ™ product, the main ingredients of which are listed below:

skim milk, cream, and

- lactic ferments (including B. lactis, L.casei, L. acidophilus).

Capsule 2 includes in particular the Actimel ™ product, the main ingredients of which are

BE2017 / 5929 listed below:

• Fermented milk with Lactobacillus casei • liquid sugar • dextrose • vitamin B6, and • vitamin D.

Capsule 3 notably includes the product LC1 ™, the main ingredients of which are listed below:

• Whole milk, • lean milk, • milk proteins, • lactic ferments (including Lactobacillus johnsonii), • 2% sugar.

Capsule 4 includes in particular the product Yogourmet ™ culture of yogurt with probiotics, the main ingredients of which are listed below:

• skimmed milk powder, • active bacterial culture (L. casei, B. longum, L. bulgaricus, S. thermophilus, and L.

acidophilus in lyophilized form).

The characteristics of the four different capsules are listed in the table below:

Information Capsule 1 Capsule 2 Capsule 3 Capsule 4 per 100g (Yoplus) (Actimel) (LC1) (freeze-dried) Energy (kj) / l 00g 252 307 346 341 Energy (kcal) / 100g 60 73 82 81 Fat (g) 3.1 L6 3.5 1.27 of which saturated fatty acids (g) 2.2 1 2.1 0.37 Carbohydrates (g) 4.7 10.8 6.6 43 Fibers (g) - - - - Proteins (g) 4.6 3 5.1 39.29 Salt (g) 0.04 0.1 0.11 - Calcium (mg) 146 120 Not measured 135.7 Vitamin B 6 (mg) Not measured 0.21 Not measured Not measured Vitamin D (pg) Not measured 0.75 Not measured Not measured Probiotics B. lactis L. casei and L. casei Lactobacillus johnsonii L. casei, B. longum,

BE2017 / 5929

L. acidophilus L. bulgaricus, S. thermophilus, and L. acidophilus CFU (Colony forming unit) in the starting product 1.7 x 10 ⁹ cfu (min) 10 x 10 ⁹ cfu (approx.) Not measured 100 x 10 ⁹ cfu (approx.) % of CFU remaining after 6 hours at 25 ° C 53.8% Not measured 91% 99.9% % of CFU remaining after 24 hours at 25 ° C 27.1% Not measured 44.8% 98% % of CFU remaining after 6 months at 25 ° C Unsuitable for the consumption Unsuitable for the consumption Unsuitable for the consumption 55% % of CFU remaining after 12 months at 25 ° C Unsuitable for the consumption Unsuitable for the consumption Unsuitable for the consumption 24%

As can be seen from the table above, it appears that the capsules comprising probiotics in lyophilized form (capsule 4) have a much longer shelf life and stability than the other three capsules comprising probiotics in non-lyophilized form and in an environment. requiring low temperature storage.

BE2017 / 5929

Claims (10)

1. Capsule (1) for its use in a device for the production and distribution of compositions, the capsule comprising at least one probiotic microorganism for producing extemporaneously a personalized cosmetic and / or pharmaceutical composition. 2. Capsule (1) according to claim 1, characterized in that the probiotic microorganism is selected from Acetobacter, Actinomyces, Acinetobacter, Aerococcus, Akkerman sia, Anabaena, Anaerococcus, Anaerofustis, Anaerostipes, Anaerotruncus, Arthrospira, Arthrobacter, Aureo basidium, Bacillus , Bacteroides, Bifidobacterium, Blautia, Brachybacteriiim, Brevihacterium, Butyrivibrio, Carnobacterium, Clostridium, Coprococcus, Corynebacterium, cyanobacterium, Deinococcus, Enhydrobacter, Enterococcus, Eubacterium, Faecalibacterium, Fibrobacter, Fusobacterium, Gluconacetobacter, Halobacterium, Helicobacter, Janthinobacterium, Kocuria, Lactobacillus, Lactococcus , Leuconostoc, Lysobacter, Macrococcus, Melissococcus, Micrococcus, Neisseria, Nitrosococcus, Nitrosocystis, Nitrosolobus, Nitrosomonas, Nitrosospria, Nitrosovibrio, Oenococcus, Oscillospira, Pediococcus Rus, Peptoniphilus, Peptoniphilus, Peptoniphilus, Peptoniphilus, Peptoniphilus, Peptoniphilus, Peptiphilus rolactobacillus, Staphylococcus, Stenotrophomonas, Streptococcus, Tetragenococcus, Weissella taken alone or in combination, preferably Bifidobacterium and / or Lactobacillus .. 3. Capsule (1) according to claim 2, characterized in that the probiotic microorganism is selected from Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus reuteri , Lactobacillus rhamnosus, taken alone or in combination, more preferably from the group consisting of Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus rhamnosus, taken alone or in combination. 4. Capsule (1) according to claim 3, characterized in that the probiotic microorganism is Lactobacillus johnsonii LAI NCC 533 (filing number CNCM 1-1225). 5. Capsule (1) according to any one of the preceding claims, characterized in that the probiotic microorganism is in the form of small dry particles, and with at least 90% of dry matter per gram, preferably at least 93% of matter dry per gram. BE2017 / 5929 6. Capsule (l) according to any one of the preceding claims, comprising: - a cup composed of at least one side wall (2) and a bottom wall (4) whose diameter is between 5 mm and 35 mm; and - a cover (3) whose diameter is between 8 and 48 mm in which said cup (2) is made of aluminum, pure plastic, multilayer plastic, a multilayer film or a combination of these this. 7. Capsule (l) according to any one of the preceding claims, for its use in the treatment and / or prevention of a skin disease or disorder in a subject, comprising topical administration on a surface of the subject's skin said topical composition, in which the surface of the skin is, or tends to be, affected by the skin disease or disorder. 8. Capsule (1) according to claim 7, characterized in that the skin disease or disorder is rosacea, telangiectasia, psoriasis, purpura, acne, eczema, erythema, or a symptom associated with these. 9. System intended for producing and distributing a composition, said system comprising: - at least one capsule (1) according to any one of claims 1 to 8, - at least one container comprising a physiologically acceptable vector, and - A device for producing and distributing compositions, in which the device comprises means for mixing the content of the capsule (1) with the content of the container and means for producing and supplying temporarily a personalized cosmetic and / or pharmaceutical composition. 10. Method for providing a cosmetic composition from a production and distribution device, said method comprising the steps intended for: - mixing the content of the capsule (1) according to any one of claims 1 to 8 with the content of at least one container comprising a physiologically acceptable vector, and - produce and supply said cosmetic composition. BE2017 / 5929