WO2018109018A1

WO2018109018A1 - Capsule comprising a probiotic microorganism for use in a device for producing and distributing compositions

Info

Publication number: WO2018109018A1
Application number: PCT/EP2017/082651
Authority: WO
Inventors: Johannes Baensch
Original assignee: Nestle Skin Health Sa
Priority date: 2016-12-16
Filing date: 2017-12-13
Publication date: 2018-06-21
Also published as: FR3060393A1; BE1025110B1; CH713308A2; BE1025110A1; NL2020080B1

Abstract

The invention relates to a capsule (1) comprising a cup composed of a least one lateral wall (2) and a lower wall (4); and a cover (3), for use thereof in a device for producing and distributing compositions, the capsule (1) comprising at least one ingredient for extemporaneously producing a personalised cosmetic and/or pharmaceutical composition by mixing said ingredient with at least one physiologically acceptable carrier, wherein said ingredient is a probiotic microorganism that improves the balance of the skin microbiome.

Description

CAPSULE COMPRISING A PROBIOTIC MICROORGANISM FOR USE IN A DEVICE FOR PRODUCTION AND DISTRIBUTION OF COMPOSITIONS

The invention relates to the field of dermatology and, more particularly, the self-manufacturing or the extemporaneous preparation of cosmetic and / or personalized pharmaceutical compositions, in particular for use in the treatment of disorders or cutaneous dermatological diseases. The invention furthermore relates to capsules comprising active ingredients improving the balance of the cutaneous 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 hosts 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, by 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, first of all in the intestine, that the human microbiota plays a determining role in human health and diseases. The skin is colonized by many microorganisms, most of them being beneficial or harmless.

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

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

A preferred approach is to develop pharmaceutical compositions, healthy, antibiotic-free and environmentally friendly. The application WO1 6122889 discloses in particular a method for modifying the 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 alter the profuse presence of the bacterial taxon. Another approach, disclosed in particular in the application WOl 6086208 is to modify the microbiome by directly administering 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 probiotic microorganisms generates new problems of formulation, in particular in terms of stability from the physical and chemical point of view. Maintaining the concentration of probiotic microorganisms under control in these cosmetic and / or pharmaceutical compositions is also a challenge.

On the other hand, an additional problem with cosmetic and / or pharmaceutical compositions comprising probiotic microorganisms is that they generally exhibit a short shelf life.

In this context, the Applicant proposes to develop alternative solutions for producing and providing 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 cutaneous dermatological diseases or disorders, such as, for example, acne, wrinkling, eczema, erythema, and especially erythema. rosacea, erythema of acne or acute erythema, redness, inflammations of the skin not related to rosacea, psoriasis, purpura, rosacea, sagging skin, telangiectasia and / or skin aging, or a symptom associated with these.

In particular, these custom compositions comprising probiotic microorganisms significantly reduce the duration of treatment and can further reduce the symptoms of skin diseases. In addition, the extemporaneous cosmetic and / or pharmaceutical compositions according to the invention provide a certain 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 producing and dispensing compositions, the capsule comprising at least one probiotic microorganism for producing extemporaneously a cosmetic composition and / or personalized pharmaceutical composition, in particular by mixing said probiotic microorganism with at least one physiologically acceptable vector.

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

The present invention further relates to a system for producing and dispensing 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 producing and distributing compositions,

wherein the device comprises means for mixing the contents of the capsule with the contents of the container and means for producing and providing extemporaneously a personalized cosmetic and / or pharmaceutical composition.

The present invention also relates to a method for providing a cosmetic composition from a production and dispensing device, said method comprising the steps of:

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

producing and supplying said cosmetic composition.

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

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

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

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

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

Figure 6 is a view of three quarters of the lower part of another capsule according to the invention.

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

The capsules have been developed in the agri-food science and consumer goods sector. The capsules are described in particular in the documents EP0512468 and EPI 784344.

In summary, these capsules usually consist of:

a hollow body and an injection wall which is impervious 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 chamber comprising a product to be extracted,

a membrane, preferably of aluminum, disposed at the lower end of the capsule, closing said capsule, for maintaining the internal pressure in the chamber, said membrane being associated with piercing means, for drilling distribution holes in said aluminum membrane when said internal pressure inside the chamber reaches a 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 autofabrication 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.

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 lid 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 (FIGS. b, 1, 3, 4, 5 and 6), or hemispherical (Figures 2a, 2b and 2c). The bottom wall 4 also called the 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 thereof.

More preferably, the cup 2 is composed of:

- Aluminum between 10 and 150 μιτι thick, preferably between 20 μιτι and

100 μιτι thick, and more preferably between 50 and 60 μιτι thick;

- pure plastic;

multilayer plastic with possibly an oxygen barrier layer, such as EVOH (ethylene copolymer 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 bottom wall 4 comprises one or more internal layers 41.

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

In a third variant of the invention as shown in Figures 2b and 6, the bottom wall 4 comprises a portion covered with a layer of an elastic material 42 to be preferentially pierced during the extraction of the contents of the capsule .

The lid 3 of the cup or the upper membrane is preferably welded (e) to the end of the cup by heat sealing, the elements to be welded having a colorless solder on their opposite faces. Alternatively, as shown in FIG. 2a, the lower edge of the cup may also be folded over the lid for crimping 33.

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

aluminum 15 to 60 μιτι thick,

an elastic material, or

a multilayer film comprising:

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

ii. or EVOH or PVDC 5 to 30 μιτι thick and plastic (PP for polypropylene, PE for polyethylene, PA for polyamide) 20 to 100 μιτι thick or PET (polyester) 5 to 30 μιτι thickness and plastic (PP, PE) 20 to 100 μιτι thick or metallized PET or PET with an upper barrier layer, such as SiO 2 (silicon dioxide).

The lid 3 of the capsule 1 may also consist of a multilayer combination of paper and aluminum.

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

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

In a third variant of the invention (not shown), the lid 3 is an upper membrane comprising a non-elastic film, at least a portion of which is covered with a layer of an elastic material. The elastic material is preferentially 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 FIGS. 1b, 2c and 3, the cover 3 is an upper membrane comprising a non-elastic film, at least a portion of which is covered with a layer of an elastic material. 32 using a glue applied "like a sticker" or by using a thermo welding or ultrasonic sealing.

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

In all the embodiments mentioned above, the elastic material is preferably a food grade silicon, in particular a liquid mono-component silicone which is fixed by reaction with atmospheric moisture (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), silicone or liquid silicone rubber, ethylene vinyl alcohol ( EVA) - based, EPDM (ethylene - propylene - diene - monomer) or isoprene rubber.

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

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

Preferably, the diameter of the lid 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 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, is beneficial to the health of its host and can improve the balance of the cutaneous microbiome.

By "cutaneous microbiome", reference is made to microorganisms present on healthy human skin, which is generally composed of a balanced set of commensal skin microorganisms. The cutaneous microbiome of a human host may include a variety of resident microorganisms that help promote the health and / or appearance of the skin of the host.

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, Bacteroides, Bifidobacterium, Blautia. , Brachybacterium, Brevibacterium, 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, Peptoniphilus, Peptostreptococcus, Propionibacterium, Pseudomonas, Roseburia, Ruminococcus, Salinicoccus, Sphingomonas, Sporolactobacil Staphylococcus, Stenotrophomonas, Streptococcus, Tetragenococcus, Weissella alone or in combination, preferably Bifidobacterium and / or Lactobacillus.

Preferably, the probiotic microorganism useful for the present invention is chosen from Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breva, 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.

More preferably still, the probiotic microorganism useful for the present invention is Lactobacillus johnsonii LAI NCC 533 (deposit number CNCM I-1,225).

Lactobacillus johnsonii NCC533 LAI (1-1225 CNCM) was 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 1 5, France, the June 30, 1992, under the reference CNCM 1-1225. Preferably, the probiotic microorganism according to the invention is a non-transformed probiotic microorganism, i.e. a natural, non - genetically modified, non - pathogenic and non - invasive microorganism of the human microbiome, preferentially a cutaneous microbiome of a healthy human subject (not sick).

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

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

In the following, Lactobacillus johnsonii NCC533 LA1 (CNCMI-1 225), in particular Lactobacillus johnsonii NCC533 LA1 (CNCMI-1225) not reproducible, for example a Lactobacillus johnsonii NCC533 LA1 heat treatment (CNCMI-1225) will be called LAI NMR.

The "non-reproducible" probiotic microorganisms and in particular Lactobacillus johnsonii LA1 NCC533 can be inactivated, dead or nonviable.

Probiotic microorganisms and in particular Lactobacillus johnsonii NCC533 LA1 (CNCM 1-1 225) can be used at least partially non-reproducible.

Non-reproducible forms, particularly heat-treated microorganisms such as Lactobacillus johnsonii NCC533 LA1 (CNCM I-1225) have the advantage of being even more effective than their living counterparts. The use of non-reproducible microorganisms, such as heat-treated probiotic microorganisms such as Lactobacillus johnsonii NCC533 LA1 (CNCMI-1225) in contrast to their living counterparts, also has the advantage of:

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

- represent a safe alternative for immunocompromised patients.

On the other hand, by reducing the obstacles to processing, non-reproducible microorganisms can be incorporated into stable liquid products with a long shelf life.

Thermal inactivation can occur at least about 70 ° C and any type of heat treatment can be used to inactivate probiotic microorganisms such as Lactobacillus johnsonii LA1 NCC533 (CNCM I-1225). For example, probiotic microorganisms such as Lactobacillus johnsonii NCC533 LA1 (CNCM I-1,225) can be made non-reproducible from 110 ° C to 140 ° C for 1 to 30 seconds, for example 10-20 seconds. Therefore, in one 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 probiotic microorganisms such as Lactobacillus johnsonii NCC533 LAI (CNCM 1-1 225) are non-reproducible.

Scientific studies suggest that probiotic microorganisms such as Lactobacillus johnsonii NCC533 (CNCM 1-1,225), particularly in non-reproducible forms, for example Lactobacillus johnsonii NCC533 LAI (CNCM 1-1,225) heat-treated, have shown superior effects on the induction of the expression of antimicrobial peptides compared to those previously identified and described in previous studies.

The patent application WO 201 0/1 30662 from Nestec discloses that Lactobacillus johnsonii NCC533 LAI (CNCM 1-1,225) strongly promotes the constitutive expression of human beta-defensins 1 (hBD1), and that Lactobacillus johnsonii NCC533 LAI (CNCM 1-1225) heat-stimulated more actively stimulates hBD1 than its living counterpart.

The probiotic microorganisms to be extracted, which are 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; evaporatively drying an unfrozen solution in a vacuum oven or centrifugal evaporator at a temperature of about -20 ° to 500 ° C, followed by milling to achieve the desired particle size. The resulting powder particles are glassy or crystalline internally with a majority of vitreous materials coating the surface. Covering probiotic microorganisms with vitreous materials has the advantage of increasing the physical stability of the product and reducing 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 proceeds in three main steps including:

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

(2) a primary vacuum drying step 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 vitreous amorphous material under full vacuum and elevated temperature for a time sufficient to reduce the water activity of the dried formulation to 0.3 Aw or less. Dried and stable probiotic microorganisms can be used directly as flakes or powdered.

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

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

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

By "prebiotic", reference is made to a selectively fermented ingredient that allows for specific changes in both the composition and / or activity of the microflora that are beneficial to the wellbeing of the skin of the host. . Prebiotics can be administered orally or topically and can promote the growth of desired microorganisms (probiotics) and thereby improve the benefits to 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, fructos and the like. oligosaccharides (FOS), galactooligosaccharides (GOS), glucomannan oligosaccharides, gluco-oligosaccharides, hemicelluloses, high amylose corn starch (HAS), inulin, isomalto-oligosaccharides, lactosucrose, lactulose, lignin, mannan oligosaccharides (MOS), neosugar, oligodextrose, oligofructose, oligofructose - enriched inulin, palatinose, pectin, polydextrose, psyllium, raffinose, sorbitol, oligosaccharides of. soybean, starch, tagatose, trans-galactooligosaccharides, xylitol, xylooligosaccharides (XOS) and combinations thereof.

Preferably, the prebiotic is selected from fructooligosaccharides (FOS), galactooligosaccharides, glucomannan oligosaccharides, inulin, isomalto-oligosaccharides, lactosucrose, lactulose, neosugar, palatinose, raffinose, sorbitol, soy oligosaccharides, xylitol and xylooligosaccharides, preferentially the prebiotic is a glucomannan oligosaccharide.

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

As indicated herein, the term "treatment" or "treating" refers to an improvement, prophylaxis or regression of the skin disease or dermatological disorder associated with or at least one perceptible symptom thereof or that 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 noticeable in or by the subject. In another embodiment, "treatment" or "treating" refers to the inhibition or slowing down of the progression of a disease or disorder, either physically, for example, the stabilization of a perceptible symptom; either physiologically, for example, the stabilization of a physical parameter or both. "Treatment" or "treating" also refers to delaying the onset of a disease or disorder, for example, by reducing or delaying the appearance of redness of the skin affected by erythema. or the symptom. In some embodiments, compounds of interest are administered preventively. In this context, "prevention" or "prevention" refers to a reduction in the risk of contracting a specified disease or disorder.

One or more skin diseases or disorders can be treated using the personalized pharmaceutical composition of the invention. Diseases or skin disorders include inflammatory skin diseases and non-inflammatory skin diseases. Diseases or skin disorders include, but are not limited to, acne, keratoses, actinic telangiectasia, alopecia areata, stomatitis, chapped skin, dermatitis, toxidermias, toxidermias, dry skin , eczema, erythema, erythema multiforme, erythema nodosum, mycoses, granuloma annulare, herpes simplex, ichthyosis vulgaris, impetigo, intertrigo, keloids, actinic keratosis , chronic lichen simplex, milia, molluscum contagiosum, pemphigus, perioral dermatitis, Gibert pink pityriasis, pruritus, barba pseudo folliculitis, psoriasis, purpura, rash, rhinophyma, rosacea, skin cancer, sunburn, telangiectasia, urticaria, vascular tumors and malformations and xerosis, or combinations thereof, or a symptom associated with them.

Preferentially, 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 inflammation not related to rosacea, redness, sagging skin, wrinkling and / or skin aging, or a symptom associated with them. One or more of the skin symptoms or alterations may also be treated with the custom pharmaceutical composition of the invention, including skin inflammation, redness, telangiectasia and erythema.

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

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

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

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

The choice of topically administrable composition will depend on a number of 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 budget constraints.

These compositions are prepared according to the usual methods.

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

As used herein, the term "composition" is intended to include a product comprising the specified ingredient in the specified amount, as well as any product resulting, directly or indirectly, from combinations of the specified ingredient in the specified amount. . In an alternative embodiment of the invention, the capsule is intended to serve only to produce extemporaneously and provide a personalized cosmetic composition, specifically designed to prevent and / or treat the subject's disease or skin disorder. The personalized cosmetic composition provided may be administered topically to a cutaneous area of the subject.

In a further embodiment, the present invention relates to a system for producing and dispensing 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 producing and distributing compositions,

The main part of the system according to the invention is the device for producing and dispensing compositions.

Such a device can extract the contents of the capsule according to the invention, and mix it with the contents 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 in 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 carrier, initially present in a container.

An alternative device is described in particular in documents EP2989260 and

WO201 1 107221 which disclose diffusion devices adapted to receive a capsule, in particular a capsule according to the invention.

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

The physiologically acceptable vector is preferentially chosen from the 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: solvents, emulsifiers, suspending agents, decomposers, binders, chelating agents, stabilizing agents, diluents, antioxidants, gelling agents, preservatives, lubricants, absorption slowing agents, skin penetrating agents, liposomes, dyes, odor absorbers or pigments and a mixture thereof.

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 treatment of active ingredients in pharmaceutically usable preparations. 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 recipient thereof. The vector is compatible with human skin.

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

As a non-limiting example of usable freshwater, 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 a drinking water whose container may 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 an electrolyte-rich water in which the presence of electrolytes is detected at a concentration of at least 30 mg / l, often at a concentration above 100 mg / l. By way of nonlimiting example of water rich in electrolyte, mention may be made of waters 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, powders, impregnated pads, bars, wipes, solutions, gels. , sprays or aerosols, foams, suspensions, lotions, sticks, shampoos or washing bases, preferentially 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 lotion type, a gel or a solution and, more preferably, under the form of an emulsion. For example, it can be in the form of a solution optionally gelled oily, an optionally two-phase dispersion of the lotion type, an emulsion obtained by dispersion of a fatty phase in 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 nonionic type. They can also be in the form of suspensions of microspheres or nanospheres or lipids or polymeric vesicles or polymeric patches and controlled release hydrogels. These personalized cosmetic and / or pharmaceutical compositions are preferably for topical application and may 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 cosmetic and / or personalized pharmaceutical composition).

For the extemporaneous preparation of the personalized cosmetic and / or pharmaceutical composition, one or more capsules may be used. This advantage allows in particular to personally adapt the composition according to the skin dermatological disease (s) or disorders of the subject.

In addition, the extemporaneous mixture of the various ingredients of the cosmetic and / or personalized pharmaceutical composition solves many problems of stability 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 prior to 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 from the container prior to dispensing 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 further comprises an active ingredient selected from the group comprising, but not limited to, antibiotics antibacterial agents, antivirals, antiparasitics, antifungals, anesthetics, analgesics, antiallergic agents, retinoids, free radical scavengers, antipruritic drugs, antihistamines, immunosuppressants, corticosteroids, keratolytic agents, intravenous immunoglobulins, anti-angiogenic agents, inflammatory agents 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, amorolfine, amphotericin B, anthranoids, antibiotics of the tetracycline class, antibodies, ascorbic acid and their esters, benzoyl peroxide, betamethasone valerate, brimonidine, calcipotriol, calcitriol, ciclopirox , citric acid and fruit acids, clindamycin phosphate, 17-clobetasol propionate, crotamiton, cyproheptadine, diclofenac and salts and their derivatives, dioxanthranol, econazole, erythromycin, estradiol, etretinate, fluocinolone acetonide, glycolic acid, glycyrrhetinic acid, hormone peptides, hydrocortisone, hydroquinone, ibuprofen and salts or derivatives thereof , isotretinoin, ivermectin, ketoconazole, kojiqu acid e, lactic acid, lidocaine, lidocaine hydrochloride, malic acid, mequinol, metronidazole, miconazole or salts and their derivatives, minoxidil, octopirox, pilocaine and their derivatives, progesterone, pyrethrinoids, retinoic acid, retinol, rucinol, salicylic acid, superoxide dismutases, tazarotene, terbinafine, tetracaine, thenaldine, tretinoin, trimeprazine, zinc pyrithione and combinations of of these.

The aforementioned active ingredients are present in concentration:

in the capsule according to the invention,

- in a second capsule apart and / or

- in the container,

so that their final concentration in the personalized cosmetic and / or pharmaceutical composition is in cosmetically and / or therapeutically effective amounts of these active ingredients.

Finally, in a final embodiment, the invention relates to a method for providing a cosmetic composition from a production and dispensing device, said method comprising the steps of:

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

producing and supplying said cosmetic composition.

Other aspects and advantages of the invention will be revealed in the following illustrative part. Example 1 Capsule According to the Invention

As illustrated in Figure 1a, 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 μιτι. The capsule 1 is filled with a composition comprising a probiotic microorganism according to the invention.

The capsule 1 is closed by a lid 34 of aluminum and paper.

The composition comprising a probiotic microorganism according to the invention is composed of 50% to 99%, preferably 75% to 98% of Lactobacillus johnsonii NCC533 LAI (CNCM 1-225), 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

After mixing:

- the contents of the capsule with

the contents of the container comprising at least one physiologically acceptable vector, and

in the device for producing and dispensing 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 1-1,225) corresponding to about 10 ⁴ to 10 ¹² cfu or about 0.005 mg-1000 mg. per daily dose.

Example 3: Personalized cosmetic and / or pharmaceutical composition according to the invention

Initially

Trade Name Ingredient Name% w / w present in

Container PLANTACARE 818UP Coconut Glucoside 6,00 to 15,00

Sodium Sarcosinate Container

PROTELAN LS901 1 5.00 to 10.00

lauroyl

Container PROTELAN AG 818 Sodium Glutamate

7.00 to 15.00

G cocoyl

Container KELTROL CG-SFT Xanthan Gum 0.10 to 0.80 Containing NATROSOL PLUS Cetyl

0.50 to 2.50

330CS Hydroxyethylcellulose

Container PROBENZ SP Sodium Benzoate 0.10 to 3.00

Containing ZEMEA 1, 3-Propanediol 2.00 to 10.00

GLYCERINE 4810 Container

Glycerin 2.00 to 5.00

PLANT

Caprylate / caprate container

STEPAN MILD GCC 0.50 to 2.00

glyceryl

Container D-PANTHENOL USP Panthenol 0.10 to 1, 00

Container SILVER SUPER MOU Mica / Dioxide

0.05 to 0.20

PRESTIGE titanium

MONO-HYDRATE container

Citric acid 0.20 to 2.00

CITRIC ACID

Container ACTIVE INGREDIENT Active Ingredient 0.00 to 20.00

PROBIOTIC Probiotic Capsule 0.10 to 1, 00

Capsule or

PREBIOTIC Prebiotic 0.00 to 10.00

containing

Container HYDROLITE 5 / 5P Pentylene glycol 0,00 to 5,00

PURIFIED WATER Container Water Qsp 100

Example 4 Cosmetic and / or Customized Pharmaceutical Composition According to the Invention

Initially% weight /

Trade Name Ingredient Name

present in weight

Container SATIAXANE

Xanthan gum 0.10 to 1, 50 UCX 91 1

GLYCERINE 4810 Container

Glycerin 1, 00 to 5,00 VEGETAL

Containing ZEMEA Propanediol 1, 00 to 8,00

Container D-PANTHENOL USP Panthenol 0.20 to 1, 20

Container Behenyl alcohol / stearate

of glyceryl / citrate

CERALUTION H glyceryl stearate / na 1.00 to 5.00

dicocoyiethylenediamine PEG-15 sulfate Containing cetearyl alcohol and

EMULGADE 1000NI 1, 00 to 3.00

ceteareth-20

OIL CONTAINER

Sunflower seed oil

SUNFLOWER 3,00 to 8,00

(helianthus annuus)

ORGANIC OLEIC

containing

KARITÉ MOU LIPEX Butyrospermum Parkii 0,00 to 20,00

Containing Triglyceride

MIGLYOL 812N 2.00 to 7.00

caprylic / capric

Containing CETIOL CC Dicapryl Carbonate 3.00 to 4.00

containing

LANETTE 16 Cetyl alcohol 1, 00 to 3.00

Container HYDROLITE CG Caprylyl Glycol 0.10 to 1, 00

Container ACTIVE INGREDIENT Active Ingredient 0.00 to 20.00

PROBIOTIC Probiotic Capsule 0.01 to 5.00

Capsule or

PREBIOTIC Prebiotic 0.00 to 10.00 containing

containing

TITRIPLEX III disodium EDTA 0.05 to 0.20

HYDROXIDE container

SODIUM (sodium hydroxide solution Qs pH 5-5.5 aqueous 10%)

PURIFIED WATER Container Water Qsp 100

Example 5 Cosmetic and / or Customized Pharmaceutical Composition According to the Invention

Initially

% w / o Trade Name Ingredient Name

weight in

Container KELTROL CG-T Xanthan Gum 0.10 to 1, 50

Containing microcrystalline cellulose (and) gum

VIVAPUR COS5 0,00 to 5,00

of Cellulose

GLYCERINE 4810 Container

Glycerin 1, 00 to 5,00 VEGETAL

Containing ZEMEA Propanediol 5.00 to 10.00

Containing Candelilla / Jojoba / Son of

Rice Polyglyceryl-3 Esters and) Stearate

EMULIUM KAPPA 0,00 to 8,00

glyceryl (and) cetearyl alcohol

and) Sodium stearoyl lactylate Container PROLIX RB Rice Branate Polyglyceryl-3 2.00 to 6.00

Containing LIPACIDE C8G Capryloyl Glycine 0.50 to 1, 50

Containing LIPACIDE UG Undecylenic Glycine 0.00 to 0.50

Container SUNFLOWER OIL

Sunflower seed oil

OLEIQUE 3,00 to 8,00

(helianthus annuus)

ORGANIC DEODORIZED

Containing jojoba esters / flower wax

Acacia Decurrens / Seed Wax

ACTICIRE 3,00 to 8,00

of Helianthus Annuus

(Sunflower) / polyglycerin-3

ISOSTERATE container

Isosféaryle of isosfers 2,00 to 7,00 ISOSTEARYLE

Containing CETIOL CC Carbonate Dicapryle 3.00 to 8.00

Container CUTINA HVG Hydrogenated vegetable glycerides 0.00 to 0.50

Containing LIPOCIRE A Triglycerides Cl 0-18 1, 00 to 5.00

Container DERMOSOFT 688 p-anisic acid 0.01 to 0.20

Containing D-PANTHENOL USP Panfhénol 0.20 to 1, 20

Container ACTIVE INGREDIENT Active Ingredient 0.00 to 20.00

PROBIOTIC Probiotic Capsule 0.01 to 5.00

Capsule or

PREBIOTIC Prebiotic 0.00 to 10.00 containing

Container HYDROXIDE DE

SODIUM (sodium hydroxide solution Qs pH 5-5.5 aqueous 10%)

PURIFIED WATER Container Water Qsp 100

Example 6 Comparison of the Preservation and Stability of Different Capsules According to the Invention Comprising Probiotics

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

As illustrated in FIG. 1a, each of the three capsules is identical and comprises a cup with a base and a frustoconical side wall. The cup is made of aluminum with a thickness of 50 μιτι.

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 by a cover of aluminum and paper.

The capsule 1 includes the product Yo-Plus ™ whose main ingredients are listed below:

skimmed milk,

cream, and lactic ferments (including B.lactis, L.casei,

L.acidophilus).

The capsule 2 includes the product Actimel ™ whose main ingredients are listed below:

• Fermented milk with Lactobacillus casei

• liquid sugar

• dextrose

• vitamin B6, and

• vitamin D.

The capsule 3 includes the product LC1 ™ whose main ingredients are listed below:

• Whole milk,

• lean milk,

• milk proteins,

• lactic ferments (including Lactobacillus johnsonii),

• 2% sugar.

Capsule 4 includes the product Yogourmet ™ yogurt culture with probiotics, whose main ingredients are listed below:

• Skimmed milk powder,

• active bacterial culture (L casei, B. longum, L. bulgaricus, S. thermophilus, and L acidophilus in freeze-dried form).

The characteristics of the four different capsules are shown in the table

S. thermophilus, and

L. acidophilus

CFU (colony forming unit) 1, 7 x 10 ⁹ cfu 10 x 10 ⁹ cfu Not measured Ι ΟΟ χ 10 ⁹ cfu in the starting material (min) (approximately) (approximately)

% CFU remaining 53.8% Not measured 91% 99.9%

after 6h at 25 ° C

% CFU remaining 27.1% Not measured 44.8% 98%

after 24h at 25 ° C

% of CFU remaining Improper to improper to improper at 55%

after 6 months at 25 ° C consumption consumption consumption

% of CFU remaining Improper to Improper to Improper at 24%

after 12 months at 25 ° C consumption consumption consumption

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

Claims

1. Capsule (1) for use in a device for producing and dispensing 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, Akkermansia, Anabaena, Anaerococcus, Anaerofustis, Anaerostipes, Anaerotruncus, Arthrospira, Arthrobacter, Aureobasidium, Bacillus, Bacteroides , Bifidobacterium, Blautia, Brachybacterium, Brevibacterium, 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, Peptoniphilus, Peptostreptococcus, Propionibacterium, Pseudomonas, Roseburia, Ruminococcus, Salinicoccus, Sphingomonas, Spor olactobacillus, Staphylococcus, Stenotrophomonas, Streptococcus, Tetragenococcus, Weissella 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, Short Bifidobacterium, 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 (deposit 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 material. dry per gram.

6. Capsule (1) 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 (1) according to any one of the preceding claims, for its use in the treatment and / or prevention of a disease or a skin disorder in a subject, comprising an administration of said composition by topically on a surface of the subject's skin, wherein the surface of the skin is, or tends to be, affected by the disease or skin disorder (e).

8. Capsule (1) according to claim 7, characterized in that the disease or skin disorder (e) is rosacea, telangiectasia, psoriasis, purpura, acne, eczema, erythema, or a symptom associated with these.

A system for producing and dispensing 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, wherein the device comprises means for mixing the contents of the capsule (1) with the contents of the container and means for producing and providing extemporaneously a personalized cosmetic and / or pharmaceutical composition.

A method for providing a cosmetic composition from a production and dispensing device, said method comprising the steps of:

- mixing the contents of the capsule (1) according to any one of claims 1 to 8 with the contents of at least one container comprising a physiologically acceptable vector, and

producing and supplying said cosmetic composition.