EP3448403A1 - Composition useful for the preparation of a suppository - Google Patents

Composition useful for the preparation of a suppository

Info

Publication number
EP3448403A1
EP3448403A1 EP17725173.3A EP17725173A EP3448403A1 EP 3448403 A1 EP3448403 A1 EP 3448403A1 EP 17725173 A EP17725173 A EP 17725173A EP 3448403 A1 EP3448403 A1 EP 3448403A1
Authority
EP
European Patent Office
Prior art keywords
mixture
composition
wax
saccharomyces boulardii
medical device
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP17725173.3A
Other languages
German (de)
French (fr)
Inventor
Anne BENOIST
Emilie Fargier
Marie-Emmanuelle Le Guern
Marc Verleye
Patrice TEWA
Xavier ZEISSER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biocodex SAS
Original Assignee
Biocodex SAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biocodex SAS filed Critical Biocodex SAS
Publication of EP3448403A1 publication Critical patent/EP3448403A1/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9728—Fungi, e.g. yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin

Definitions

  • the present invention relates to a composition useful for the preparation of an egg, as well as a medical device, a drug, or a cosmetic product comprising it.
  • Vulvovaginal infections are low genital infections affecting the vulva and / or vagina. They are manifested by irritation, itching, pain and abnormal vaginal discharge. These infections are very common. This is indeed the most common cause of medical consultation in women.
  • Vulvovaginal infections are mainly of bacterial or mycotic origin, with parasitic infections, mainly Trichomonas, accounting for only about 10% of these infections.
  • Vulvovaginal bacterial infections account for about 50 to 60% of all infections of the vulva and vagina. The most common infections in these infections are Gardnerella vaginalis, Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species and Ureaplasma urealyticum.
  • Mycotic vulvovaginal infections are mainly candidiasis.
  • Bacterial and parasitic infections are mainly treated with antibiotics / antiparasitic agents of the nitroimidazole family, such as metronidazole, whereas mycotic infections are usually treated with antifungal agents of the imidazole family, such as econazole, miconazole or fluconazole.
  • the present invention stems from the unexpected finding by the inventors that it was possible to formulate eggs from a mixture of lyophilized Saccharomyces boulardii yeast cells and wax and that these eggs were able to release cells.
  • live S. vagardii yeast in the vaginal mucosa which helps to fight against vulvovaginal infections, including the secretion of capric acid.
  • antibiotic treatments for vulvovaginal infections usually result in depletion of the protective vaginal flora, which promotes recurrence and re-infection.
  • the use of ovules according to the invention in the context of antibiotic therapy therefore limits the risk of recurrence or reinfection that would be related to an imbalance of the saprophytic flora.
  • the present invention relates to a composition
  • a composition comprising, or consisting of, a mixture of yeast Saccharomyces boulardii cells and a wax.
  • the present invention also relates to a medical device, a medicament or a cosmetic product comprising, or consisting of, a composition as defined above.
  • the invention relates to the medical device or the medicament as defined above, for its use as an ovum, for its use in the prevention or treatment of vulvovaginal infections or for its use in the rebalancing of the vaginal flora, especially after treatment with a local or systemic anti-infective, and / or to help consolidate the healing after taking a local vaginal anti-infective treatment, and / or to prevent recurrences vaginal infections.
  • the present invention also relates to the use of a composition as defined above for the preparation of an egg, a medicament or a medical device intended for the prevention or treatment of vulvovaginal infections, or intended for the rebalancing of the vaginal flora, in particular after treatment with a local or systemic anti-infective, and / or to help to consolidate healing after taking local vaginal anti-infective therapy, and / or preventing recurrence of vaginal infections.
  • the present invention also relates to the cosmetic use of a composition as defined above or a cosmetic product as defined above for the intimate hygiene or personal hygiene of an individual.
  • the present invention also relates to a method for preventing or treating a vulvovaginal infection in an individual, as well as a method for rebalancing the vaginal flora, especially after treatment with a local or systemic anti-infective, and / or to help consolidate healing after taking a local vaginal anti-infective treatment, and / or to prevent recurrence of vaginal infections in an individual, in which the individual is administered a composition as defined above , in particular in a prophylactically or therapeutically effective amount.
  • the present invention also relates to a method of intimate hygiene or personal hygiene of an individual, wherein the individual is administered a composition as defined above or a cosmetic product as defined above, in particular in a cosmetically effective amount.
  • the present invention also relates to a process for obtaining a composition as defined above, comprising the following steps:
  • the wax is maintained in the liquid state at a temperature below 42 ° C. and Saccharomyces boulardii yeast cells are added with stirring;
  • the mixture is allowed to cool with stirring while maintaining it liquid until a temperature of less than 36 ° C .;
  • the mixture is poured into a mold
  • the mixture is demolded after solidification.
  • the term “comprising” means “including”, “containing” or “encompassing”, that is to say that when an object “includes” one or more elements, other elements that those mentioned can also be included in the object.
  • the expression “consisting of” means “consisting of”, that is, when an object "consists of In one or more elements, the object can not include other elements than those mentioned.
  • Saccharomyces boulardii is a yeast well known to those skilled in the art. It is especially described in Hennequin et al. (2001) J. Clin. Microbiol. 39: 551-559. As used herein, the nomenclatures "Saccharomyces boulardii” and “Saccharomyces cerevisiae var boulardii” (abbreviated S. cerevisiae var boulardii) are considered equivalent.
  • yeast Saccharomyces boulardii cells according to the invention are obtained from pharmaceutical products of Bioflor® brand, Bioflora®, Codex®, Econorm®, Enflor®, Enterol®, Florastor®, Floratil®, Florestor®, Inteflora ®, Perenterol®, Perenteryl®, Precosa®, Reflor®, Ultra-Levura® or Ultra-Levure®.
  • the yeast Saccharomyces boulardii cells according to the invention can also be identical to the deposit made with the American Type Culture Collection (ATCC, USA) under the reference 7401 2, from the National Collection of Culture and Microorganisms (CNCM, Pasteur Institute, France) under the reference 1-745 or from the Centraalbureau voor Schimmelcultures (CBS, The Netherlands) under the reference Hansen CBS 5926.
  • ATCC American Type Culture Collection
  • CCM National Collection of Culture and Microorganisms
  • CBS Centraalbureau voor Schimmelcultures
  • yeast Saccharomyces boulardii cells according to the invention are mixed with the wax in powder form, in particular freeze-dried form.
  • the viability or vitality of yeast Saccharomyces boulardii cells derived from lyophilizates is greater than that obtainable with other methods of preserving yeast cells, such as drying, for example.
  • lyophilization is a preservation process in which live Saccharomyces boulardii yeast cells are frozen and are then sublimated with the frozen water they contain to yield a lyophilisate in the form of a dry yeast powder preferably containing less than 2% water and more preferably less than 1% water.
  • lyophilized Saccharomyces boulardii yeast cells are obtained from concentrated cells.
  • Many freeze-drying methods well known to those skilled in the art can be used to produce lyophilized Saccharomyces boulardii yeast cells according to the invention.
  • Saccharomyces boulardii yeast cells according to the invention are lyophilized using the following lyophilization process:
  • yeast Saccharomyces boulardii cells are cultured in a liquid culture medium until the cells reach a stationary phase; the yeast cells Saccharomyces boulardii are concentrated and the concentrate is frozen, optionally in the presence of a cryoprotectant, such as lactose;
  • the concentrate is lyophilized.
  • the lyophilized Saccharomyces boulardii yeast cells are in the form of a powder.
  • Saccharomyces boulardii is the only probiotic included in the mixture, the composition, the drug, the medical device or the cosmetic product according to the invention.
  • no other probiotic such as bacteria of the genus Lactobacillus, in particular L. rhamnosus, L. fermentum, L. crispatus, L. jensinii or L. gasseri, of the genus Enterococcus, in particular Enterococcus faecium, or yeasts of the genus Saccharomyces genus, especially S. cerevisiae, is present in the mixture, the composition, the drug, the medical device or the cosmetic product.
  • a "probiotic” refers to a living (or revivable) microorganism, such as a bacterium or yeast, which when administered in an adequate amount, provides a beneficial effect on the health of the individual to whom it is administered.
  • the mixture according to the invention comprises from 1.5 ⁇ 10 9 to 2.5 ⁇ 10 10 , in particular from 2 ⁇ 10 9 to 2 ⁇ 10 10 , Colony Forming Units (CFU) of Saccharomyces yeast cells. boulardii.
  • CFU Colony Forming Units
  • the mixture according to the invention comprises, or consists of, 15 to 35% (w / w) of yeast Saccharomyces boulardii cells in powder form, in particular lyophilized form.
  • Wax 15 to 35% (w / w) of yeast Saccharomyces boulardii cells in powder form, in particular lyophilized form.
  • the term "wax” refers to a composition based on one or more esters of an alcohol, especially glycerol, and fatty acids, which is solid at room temperature (18-23 ° C. ).
  • the wax according to the invention is based on "hard fat", within the meaning of the European Pharmacopoeia (Ph.Eur.), Namely a mixture of triglycerides, diglycerides and monoglycerides, which can in particular be obtained either by the esterification of glycerol by fatty acids of natural origin, or by transesterification of natural fats.
  • the fatty acids according to the invention are saturated or unsaturated, preferably saturated.
  • the fatty acids according to the invention preferably comprise at least 8 carbon atoms (C8) or at least 12 carbon atoms (Cl 2).
  • the fatty acids according to the invention comprise at most 18 carbon atoms (Cl 8).
  • the wax according to the invention comprises or is based on triglycerides, especially saturated.
  • the invention comprises or is based on saturated C8-C18 or C12-C18 triglycerides.
  • the wax according to the invention may comprise additives, such as at least one lubricant or at least one emulsifier, in particular selected from the group consisting of glycerol monoricinoleate, a polyethylene glycol monocetyl ether, in particular the Ceteth-20, polyethylene glycol monostearic ether, especially Steareth-20, and lecithin.
  • additives such as at least one lubricant or at least one emulsifier, in particular selected from the group consisting of glycerol monoricinoleate, a polyethylene glycol monocetyl ether, in particular the Ceteth-20, polyethylene glycol monostearic ether, especially Steareth-20, and lecithin.
  • the wax according to the invention has a melting point of greater than 32 ° C. Also preferably, the wax according to the invention has a melting point below 37 ° C. More preferably, the wax of the invention has a melting point of greater than 32 ° C and less than 37 ° C.
  • the melting point is preferably measured under normal pressure.
  • a normal pressure is a pressure of 1 bar.
  • the wax according to the invention is selected from the group consisting of SUPPOCIRE® NA PASTILLES (Gattefossé), OVUCIRE® 3460 PASTILLES (Gattefossé) and SUPPOCIRE® AML PASTILLES (Gattefossé).
  • the wax according to the invention has a relative humidity of 20% to 35% before mixing.
  • the mixture according to the invention has a melting point greater than 32 ° C. Also preferably, the mixture according to the invention has a melting point less than 37 ° C. More preferably, the mixture according to the invention has a melting point of greater than 32 ° C and less than 37 ° C.
  • the melting point is preferably measured under normal pressure.
  • a normal pressure is a pressure of 1 bar.
  • the mixture according to the invention has a liquefaction time of less than 10 min. in water at 37 ° C.
  • the mixture according to the invention has a breaking strength greater than 5.4 kg at a temperature of 23 ° C.
  • the mixture according to the invention comprises, or consists of, 15 to 35% (w / w) of yeast Saccharomyces boulordii cells in powder form, in particular lyophilized, and from 65 to 85% (w / w). ) of wax according to the invention. More preferably, the mixture according to the invention comprises, or consists of, 30% (m / m) of yeast Saccharomyces boulardii cells in powder form, in particular freeze-dried form, and 70% (m / m) of wax according to US Pat. invention.
  • the composition, in particular pharmaceutical, according to the invention, the medical device according to the invention, the drug according to the invention or the cosmetic product according to the invention comprises, or consists of, mixing into a unit mass of 1 g at 5 g, especially about or exactly 2 g.
  • the pharmaceutical composition according to the invention, the medical device according to the invention, the medicament according to the invention or the cosmetic product according to the invention comprises a unit mass of 0.15 g to 1, 75 g, in particular from 0.3 to 0.7 g, of yeast Saccharomyces boulardii cells in powder form, in particular lyophilized form. More preferably, the pharmaceutical composition according to the invention, the medical device according to the invention, the medicinal product according to the invention or the cosmetic product according to the invention, comprises a unit mass of 0.6 g, yeast Saccharomyces boulardii in powder form, especially lyophilized. applications
  • the composition according to the invention may be a pharmaceutical composition.
  • the pharmaceutical composition may comprise one or more pharmaceutically acceptable excipients or carriers in addition to the mixture.
  • the vulvovaginal infections according to the invention are infections of the vulva and / or the vagina.
  • the vulvovaginal infections according to the invention may be infections:
  • Gardnerella vaginalis Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species
  • Trichomonas including Trichomonas.
  • the anti-infectives according to the invention may in particular be:
  • antibiotics especially from the family of nitroimidazoles, such as metodinazole;
  • antifungals in particular from the family of imidazoles, such as econazole, miconazole or fluconazole; or
  • antiparasitic agents in particular from the family of nitroimidazoles, such as metodinazole;
  • rebalancing of vaginal flora refers to the restoration of normal or healthy vaginal flora, particularly in terms of the diversity and amount of vaginal microorganisms.
  • composition according to the invention may be a cosmetic composition.
  • the cosmetic composition may comprise one or more cosmetically acceptable excipients or vehicles in addition to the mixture.
  • the cosmetic product according to the invention may comprise one or more cosmetically acceptable excipients or vehicles in addition to the composition according to the invention.
  • the intimate hygiene or the private toilet designates the toilet of the vulva and / or the vagina.
  • the pharmaceutical composition according to the invention, the medical device according to the invention, the drug according to the invention or the cosmetic product according to the invention is administered by the vaginal route, in particular in the form of an egg.
  • ovum is considered equivalent to “vaginal ovum” or “gynecological ovum”.
  • the individual according to the invention is a mammal, more preferably a human, in particular a female.
  • Example 1 a mammal, more preferably a human, in particular a female.
  • SUPPOCIRE® containing an egg / suppository at low
  • AML PASTILLES phospholipid hydroxyl number (6 mg
  • the yeast used is Saccharomyces boulardii in freeze-dried powder form (Ultra-Levure®, Biocodex, Lot 7316).
  • the suppository mass is heated to 55 ° C until complete fusion.
  • the mixture is poured into a 2 g ruler mold (the ideal egg casting temperature was determined from a thermo-rheogram of the mixture made with a Rheomat apparatus 1 1 5 (LabMakelaar Benelux BV)).
  • the eggs are cooled to room temperature for 4 minutes.
  • This method determines the temperature at which the egg becomes sufficiently liquid to slip into a U - shaped capillary tube (1.5 mm ID). This method is a simple and reliable way to compare egg melting points. This melting point must be below 37 ° C. Three eggs are tested per lot.
  • This method determines the breaking strength of eggs.
  • the value defined corresponds to the mass needed to generate their overwriting.
  • the egg is positioned on a jaw and connected to a rod on which are added successively weights. The force exerted on the egg is increased until the egg is crushed. Eggs must be able to withstand a weight of at least 1800-2000 g. Five eggs are tested per lot.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
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  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Reproductive Health (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Gynecology & Obstetrics (AREA)
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  • Botany (AREA)
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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to a composition comprising a mixture of Saccharomyces boulardii yeast cells and a wax.

Description

COMPOSITION UTILE POUR LA PREPARATION D'UN OVULE  COMPOSITION USEFUL FOR PREPARING AN OVA
Domaine de l 'invention Field of the invention
La présente invention concerne une composition utile pour la préparation d'un ovule, ainsi qu 'un dispositif médical, un médicament, ou un produit cosmétique la comprenant.  The present invention relates to a composition useful for the preparation of an egg, as well as a medical device, a drug, or a cosmetic product comprising it.
Arrière-plan technique Technical background
Les infections vulvo-vaginales sont des infections génitales basses touchant la vulve et/ou le vagin. Elles se manifestent par une irritation, des démangeaisons, des douleurs et des pertes vaginales anormales. Ces infections sont très courantes. Il s'agit en effet de la cause de consultation médicale la plus fréquente chez les femmes.  Vulvovaginal infections are low genital infections affecting the vulva and / or vagina. They are manifested by irritation, itching, pain and abnormal vaginal discharge. These infections are very common. This is indeed the most common cause of medical consultation in women.
Les infections vulvo-vaginales sont principalement d'origine bactérienne ou mycosique, les infections parasitaires, principalement à Trichomonas, ne représentant qu 'environ 10% de ces infections.  Vulvovaginal infections are mainly of bacterial or mycotic origin, with parasitic infections, mainly Trichomonas, accounting for only about 10% of these infections.
Les infections vulvo-vaginales bactériennes représentent environ 50 à 60 % de toutes les infections de la vulve et du vagin. Les germes les plus souvent rencontrés dans ces infections sont Gardnerella vaginalis, Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species et Ureaplasma urealyticum.  Vulvovaginal bacterial infections account for about 50 to 60% of all infections of the vulva and vagina. The most common infections in these infections are Gardnerella vaginalis, Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species and Ureaplasma urealyticum.
Environ 70 % des femmes présentent une infection vulvo-vaginale mycosique durant leur vie. Par ailleurs, l'infection mycosique se retrouve chez 40% des femmes porteuses d 'infection vulvo-vaginale bactérienne. Les infections vulvo-vaginales mycosiques sont essentiellement des candidoses.  About 70% of women have mycotic vulvovaginal infection during their lifetime. In addition, mycotic infection is found in 40% of women with bacterial vulvovaginal infection. Mycotic vulvovaginal infections are mainly candidiasis.
Les infections bactériennes et parasitaires sont principalement traitées à l 'aide d'antibiotiques/antiparasitaires de la famille des nitroimidazoles, tel que le métronidazole, tandis que les infections mycosiques sont habituellement traitées à l'aide d 'antifongiques de la famille des imidazolés, tels que l'éconazole, le miconazole ou le fluconazole.  Bacterial and parasitic infections are mainly treated with antibiotics / antiparasitic agents of the nitroimidazole family, such as metronidazole, whereas mycotic infections are usually treated with antifungal agents of the imidazole family, such as econazole, miconazole or fluconazole.
Cependant, malgré la prise en charge thérapeutique, environ 5% des femmes présentent une infection vulvo-vaginale récurrente, définie par plus de 4 infections par an. En outre, la moitié des femmes traitées pour une infection vulvo-vaginale bactérienne présente une récidive dans les 12 mois. Les traitements des infections vulvo-vaginales proposés ne sont donc pas pleinement satisfaisants et il reste nécessaire de trouver des traitements alternatifs, permettant notamment de limiter les récidives. Résumé de l 'invention However, despite the therapeutic management, about 5% of women have a recurrent vulvovaginal infection, defined by more than 4 infections per year. In addition, half of women treated for a bacterial vulvovaginal infection have a recurrence within 12 months. The proposed treatments for vulvovaginal infections are therefore not fully satisfactory and it remains necessary to find alternative treatments, in particular to limit recurrences. Summary of the invention
La présente invention découle de la mise en évidence inattendue, par les inventeurs, qu 'il était possible de formuler des ovules à partir d 'un mélange de cellules de levure Saccharomyces boulardii lyophilisée et de cire et que ces ovules étaient capables de libérer des cellules de levure S. boulardii vivantes au niveau de la muqueuse vaginale, ce qui permet de lutter contre les infections vulvo-vaginales, notamment par la sécrétion d'acide caprique. De plus, les traitements antibiotiques des infections vulvo-vaginales entraînent généralement un appauvrissement de la flore vaginale protectrice, ce qui favorise les récidives et les réinfections. L'utilisation d'ovules selon l'invention dans le cadre d'une antibiothérapie permet donc de limiter les risques de récidive ou de réinfection qui serait lié à un déséquilibre de la flore saprophyte.  The present invention stems from the unexpected finding by the inventors that it was possible to formulate eggs from a mixture of lyophilized Saccharomyces boulardii yeast cells and wax and that these eggs were able to release cells. live S. vagardii yeast in the vaginal mucosa, which helps to fight against vulvovaginal infections, including the secretion of capric acid. In addition, antibiotic treatments for vulvovaginal infections usually result in depletion of the protective vaginal flora, which promotes recurrence and re-infection. The use of ovules according to the invention in the context of antibiotic therapy therefore limits the risk of recurrence or reinfection that would be related to an imbalance of the saprophytic flora.
Ainsi, la présente invention concerne une composition comprenant, ou consistant en, un mélange de cellules de levure Saccharomyces boulardii et d 'une cire.  Thus, the present invention relates to a composition comprising, or consisting of, a mixture of yeast Saccharomyces boulardii cells and a wax.
La présente invention concerne également un dispositif médical, un médicament ou un produit cosmétique comprenant, ou consistant en, une composition telle que définie ci-dessus.  The present invention also relates to a medical device, a medicament or a cosmetic product comprising, or consisting of, a composition as defined above.
Dans un mode de réalisation particulier, l'invention concerne le dispositif médical ou le médicament tel que défini ci-dessus, pour son utilisation à titre d'ovule, pour son utilisation dans la prévention ou le traitement des infections vulvo-vaginales ou pour son utilisation dans le rééquilibrage de la flore vaginale, notamment après traitement par un anti-infectieux local ou systémique, et/ou pour contribuer à consolider la guérison après la prise d'un traitement anti-infectieux local vaginal, et/ou pour prévenir les récidives d'infections vaginales.  In a particular embodiment, the invention relates to the medical device or the medicament as defined above, for its use as an ovum, for its use in the prevention or treatment of vulvovaginal infections or for its use in the rebalancing of the vaginal flora, especially after treatment with a local or systemic anti-infective, and / or to help consolidate the healing after taking a local vaginal anti-infective treatment, and / or to prevent recurrences vaginal infections.
La présente invention concerne également l'utilisation d'une composition telle que définie ci-dessus pour la préparation d'un ovule, d'un médicament ou d'un dispositif médical destiné à la prévention ou au traitement des infections vulvo- vaginales, ou destiné au rééquilibrage de la flore vaginale, notamment après traitement par un anti-infectieux local ou systémique, et/ou à contribuer à consolider la guérison après la prise d'un traitement anti-infectieux local vaginal, et/ou à prévenir les récidives d'infections vaginales. The present invention also relates to the use of a composition as defined above for the preparation of an egg, a medicament or a medical device intended for the prevention or treatment of vulvovaginal infections, or intended for the rebalancing of the vaginal flora, in particular after treatment with a local or systemic anti-infective, and / or to help to consolidate healing after taking local vaginal anti-infective therapy, and / or preventing recurrence of vaginal infections.
La présente invention concerne également l'utilisation cosmétique d'une composition telle que définie ci-dessus ou d'un produit cosmétique tel que défini ci- dessus pour l'hygiène intime ou la toilette intime d'un individu.  The present invention also relates to the cosmetic use of a composition as defined above or a cosmetic product as defined above for the intimate hygiene or personal hygiene of an individual.
La présente invention concerne également une méthode de prévention ou de traitement d'une infection vulvo-vaginale chez un individu, ainsi qu'une méthode de rééquilibrage de la flore vaginale, notamment après traitement par un anti-infectieux local ou systémique, et/ou pour contribuer à consolider la guérison après la prise d'un traitement anti-infectieux local vaginal, et/ou pour prévenir les récidives d'infections vaginales chez un individu, dans laquelle on administre à l'individu une composition telle que définie ci-dessus, notamment en une quantité prophylactiquement ou thérapeutiquement efficace.  The present invention also relates to a method for preventing or treating a vulvovaginal infection in an individual, as well as a method for rebalancing the vaginal flora, especially after treatment with a local or systemic anti-infective, and / or to help consolidate healing after taking a local vaginal anti-infective treatment, and / or to prevent recurrence of vaginal infections in an individual, in which the individual is administered a composition as defined above , in particular in a prophylactically or therapeutically effective amount.
La présente invention concerne également une méthode d'hygiène intime ou de toilette intime d'un individu, dans laquelle on administre à l'individu une composition telle que définie ci-dessus ou un produit cosmétique tel que défini ci- dessus, notamment en une quantité cosmétiquement efficace.  The present invention also relates to a method of intimate hygiene or personal hygiene of an individual, wherein the individual is administered a composition as defined above or a cosmetic product as defined above, in particular in a cosmetically effective amount.
La présente invention concerne également un procédé d'obtention d'une composition telle que définie ci-dessus, comprenant les étapes suivantes :  The present invention also relates to a process for obtaining a composition as defined above, comprising the following steps:
- si nécessaire on chauffe la cire jusqu'à la rendre liquide ; if necessary, heat the wax until it becomes liquid;
- on maintient la cire à l'état liquide à une température inférieure à 42°C et on ajoute des cellules de levure Saccharomyces boulardii sous agitation ;  the wax is maintained in the liquid state at a temperature below 42 ° C. and Saccharomyces boulardii yeast cells are added with stirring;
- on laisse refroidir le mélange sous agitation en le maintenant liquide jusqu'à une température inférieure à 36°C ;  the mixture is allowed to cool with stirring while maintaining it liquid until a temperature of less than 36 ° C .;
- on coule le mélange dans un moule ; the mixture is poured into a mold;
- on démoule le mélange après solidification.  the mixture is demolded after solidification.
Description détaillée de l'invention Detailed description of the invention
A titre préliminaire, on rappellera que le terme « comprenant » signifie « incluant », « contenant » ou « englobant », c'est-à-dire que lorsqu'un objet « comprend » un élément ou plusieurs éléments, d'autres éléments que ceux mentionnés peuvent également être compris dans l'objet. A contrario, l'expression « consistant en » signifie « constitué de », c'est-à-dire que lorsqu'un objet « consiste en » un élément ou plusieurs éléments, l 'objet ne peut pas comprendre d'autres éléments que ceux mentionnés. As a preliminary, it will be recalled that the term "comprising" means "including", "containing" or "encompassing", that is to say that when an object "includes" one or more elements, other elements that those mentioned can also be included in the object. On the other hand, the expression "consisting of" means "consisting of", that is, when an object "consists of In one or more elements, the object can not include other elements than those mentioned.
Saccharomyces boulardii Saccharomyces boulardii
Saccharomyces boulardii, abréviée S. boulardii, est une levure bien connue de l' homme du métier. Elle est notamment décrite dans Hennequin et al. (2001 ) J. Clin. Microbiol. 39:551 -559. Comme on l'entend ici, les nomenclatures "Saccharomyces boulardii" et "Saccharomyces cerevisiae var. boulardii" (abréviée S. cerevisiae var. boulardii) sont considérées équivalentes.  Saccharomyces boulardii, abbreviated S. boulardii, is a yeast well known to those skilled in the art. It is especially described in Hennequin et al. (2001) J. Clin. Microbiol. 39: 551-559. As used herein, the nomenclatures "Saccharomyces boulardii" and "Saccharomyces cerevisiae var boulardii" (abbreviated S. cerevisiae var boulardii) are considered equivalent.
De préférence, les cellules de levure Saccharomyces boulardii selon l 'invention sont obtenues à partir des produits pharmaceutiques de marque Bioflor®, Bioflora®, Codex®, Econorm®, Enflor®, Enterol®, Florastor®, Floratil®, Florestor®, Inteflora®, Perenterol®, Perenteryl®, Precosa®, Reflor®, Ultra-Levura® ou Ultra-Levure®. Les cellules de levure Saccharomyces boulardii selon l'invention peuvent également être identiques au dépôt réalisé auprès de American Type Culture Collection (ATCC, USA) sous la référence 7401 2, auprès de la Collection Nationale de Culture et de Microorganismes (CNCM, Institut Pasteur, France) sous la référence 1-745 ou auprès du Centraalbureau voor Schimmelcultures (CBS, The Netherlands) sous la référence Hansen CBS 5926.  Preferably, the yeast Saccharomyces boulardii cells according to the invention are obtained from pharmaceutical products of Bioflor® brand, Bioflora®, Codex®, Econorm®, Enflor®, Enterol®, Florastor®, Floratil®, Florestor®, Inteflora ®, Perenterol®, Perenteryl®, Precosa®, Reflor®, Ultra-Levura® or Ultra-Levure®. The yeast Saccharomyces boulardii cells according to the invention can also be identical to the deposit made with the American Type Culture Collection (ATCC, USA) under the reference 7401 2, from the National Collection of Culture and Microorganisms (CNCM, Pasteur Institute, France) under the reference 1-745 or from the Centraalbureau voor Schimmelcultures (CBS, The Netherlands) under the reference Hansen CBS 5926.
De préférence les cellules de levure Saccharomyces boulardii selon l 'invention sont mélangées avec la cire sous forme de poudre, notamment lyophilisées.  Preferably, the yeast Saccharomyces boulardii cells according to the invention are mixed with the wax in powder form, in particular freeze-dried form.
Avantageusement, la viabilité ou la vitalité de cellules de levure Saccharomyces boulardii issues de lyophilisats est supérieure à celle pouvant être obtenue avec d 'autres méthodes de conservation des cellules de levure, telles que le séchage par exemple.  Advantageously, the viability or vitality of yeast Saccharomyces boulardii cells derived from lyophilizates is greater than that obtainable with other methods of preserving yeast cells, such as drying, for example.
Comme on l 'entend ici, la "lyophilisation" est un procédé de conservation dans lequel des cellules de levure Saccharomyces boulardii vivantes sont congelées puis sont soumises à une sublimation de l 'eau congelée qu 'elles contiennent pour donner un lyophilisât sous forme d'une poudre de levure sèche contenant de préférence moins de 2% d 'eau et plus préférablement moins de 1 % d'eau. De préférence, les cellules de levure Saccharomyces boulardii lyophilisées sont obtenues à partir de cellules concentrées. De nombreuses méthodes de lyophilisation bien connues de l ' homme du métier peuvent être utilisées pour produire des cellules de levure Saccharomyces boulardii lyophilisées selon l'invention. Toutefois, on préfère que les cellules de levure Saccharomyces boulardii selon l 'invention soient lyophilisées à l 'aide du procédé de lyophilisation suivant : As used herein, "lyophilization" is a preservation process in which live Saccharomyces boulardii yeast cells are frozen and are then sublimated with the frozen water they contain to yield a lyophilisate in the form of a dry yeast powder preferably containing less than 2% water and more preferably less than 1% water. Preferably, lyophilized Saccharomyces boulardii yeast cells are obtained from concentrated cells. Many freeze-drying methods well known to those skilled in the art can be used to produce lyophilized Saccharomyces boulardii yeast cells according to the invention. However, it is preferred that Saccharomyces boulardii yeast cells according to the invention are lyophilized using the following lyophilization process:
on cultive les cellules de levure Saccharomyces boulardii dans un milieu de culture liquide jusqu 'à ce que les cellules atteignent une phase stationnaire ; - on concentre les cellules de levure Saccharomyces boulardii et on congèle le concentré, éventuellement en présence d 'un cryoprotecteur, tel que le lactose ;  yeast Saccharomyces boulardii cells are cultured in a liquid culture medium until the cells reach a stationary phase; the yeast cells Saccharomyces boulardii are concentrated and the concentrate is frozen, optionally in the presence of a cryoprotectant, such as lactose;
on lyophilise le concentré.  the concentrate is lyophilized.
Les cellules de levure Saccharomyces boulardii lyophilisées sont sous forme d'une poudre.  The lyophilized Saccharomyces boulardii yeast cells are in the form of a powder.
De préférence, Saccharomyces boulardii est le seul probiotique compris dans le mélange, la composition, le médicament, le dispositif médical ou le produit cosmétique selon l'invention. En d 'autres termes, aucun autre probiotique, tel que des bactéries du genre Lactobacillus, notamment L. rhamnosus, L. fermentum, L. crispatus, L. jensinii ou L gasseri, du genre Enterococcus, notamment Enterococcus faecium, ou des levures du genre Saccharomyces, notamment S. cerevisiae, n'est présent dans le mélange, la composition, le médicament, le dispositif médical ou le produit cosmétique. Comme cela a été défini par l 'Organisation des Nations Unies pour l'alimentation et l 'agriculture (FAO), un « probiotique » désigne un micro-organisme vivant (ou revivifiable), tel qu 'une bactérie ou une levure, qui, lorsqu 'il est administré en une quantité adéquate, procure un effet bénéfique sur la santé de l 'individu auquel il est administré.  Preferably, Saccharomyces boulardii is the only probiotic included in the mixture, the composition, the drug, the medical device or the cosmetic product according to the invention. In other words, no other probiotic, such as bacteria of the genus Lactobacillus, in particular L. rhamnosus, L. fermentum, L. crispatus, L. jensinii or L. gasseri, of the genus Enterococcus, in particular Enterococcus faecium, or yeasts of the genus Saccharomyces genus, especially S. cerevisiae, is present in the mixture, the composition, the drug, the medical device or the cosmetic product. As defined by the Food and Agriculture Organization of the United Nations (FAO), a "probiotic" refers to a living (or revivable) microorganism, such as a bacterium or yeast, which when administered in an adequate amount, provides a beneficial effect on the health of the individual to whom it is administered.
De préférence, le mélange selon l 'invention comprend de 1 ,5 x 1 09 à 2,5 x 1 010, notamment de 2 x 109 à 2 x 1010, Unités Formant Colonies (UFC) de cellules de levure Saccharomyces boulardii. Preferably, the mixture according to the invention comprises from 1.5 × 10 9 to 2.5 × 10 10 , in particular from 2 × 10 9 to 2 × 10 10 , Colony Forming Units (CFU) of Saccharomyces yeast cells. boulardii.
De préférence, le mélange selon l'invention comprend, ou est constitué de, 1 5 à 35% (m/m) de cellules de levure Saccharomyces boulardii sous forme de poudre, notamment lyophilisée. Cire  Preferably, the mixture according to the invention comprises, or consists of, 15 to 35% (w / w) of yeast Saccharomyces boulardii cells in powder form, in particular lyophilized form. Wax
Comme on l 'entend ici, le terme « cire » désigne une composition à base d'un ou plusieurs esters d'un alcool, notamment le glycérol, et d 'acides gras, qui est solide à température ambiante (18-23°C) . De préférence, la cire selon l'invention est à base de « hard fat », au sens de la Pharmacopée Européenne (Ph. Eur.), à savoir un mélange de triglycérides, de diglycérides et de monoglycérides, qui peuvent notamment être obtenus soit par l'estérification du glycérol par des acides gras d'origine naturelle, soit par transestérification de graisses naturelles. As used herein, the term "wax" refers to a composition based on one or more esters of an alcohol, especially glycerol, and fatty acids, which is solid at room temperature (18-23 ° C. ). Preferably, the wax according to the invention is based on "hard fat", within the meaning of the European Pharmacopoeia (Ph.Eur.), Namely a mixture of triglycerides, diglycerides and monoglycerides, which can in particular be obtained either by the esterification of glycerol by fatty acids of natural origin, or by transesterification of natural fats.
Les acides gras selon l 'invention sont saturés ou insaturés, de préférence saturés. Par ailleurs, les acides gras selon l 'invention comprennent de préférence au moins 8 atomes de carbone (C8) ou au moins 12 atomes de carbone (Cl 2) . De préférence également, les acides gras selon l 'invention comprennent au plus 18 atomes de carbone (Cl 8) .  The fatty acids according to the invention are saturated or unsaturated, preferably saturated. In addition, the fatty acids according to the invention preferably comprise at least 8 carbon atoms (C8) or at least 12 carbon atoms (Cl 2). Also preferably, the fatty acids according to the invention comprise at most 18 carbon atoms (Cl 8).
De préférence, la cire selon l'invention comprend des, ou est à base de, triglycérides, notamment saturés. En particulier, l 'invention comprend des, ou est à base de, triglycérides en C8-C 18 ou en C 12-C 18 saturés.  Preferably, the wax according to the invention comprises or is based on triglycerides, especially saturated. In particular, the invention comprises or is based on saturated C8-C18 or C12-C18 triglycerides.
Par ailleurs, la cire selon l 'invention peut comprendre des additifs, tels qu 'au moins un lubrifiant ou au moins un émulsifiant, notamment sélectionnés dans le groupe constitué du monoricinoléate de glycérol, d'un éther monocétylique de polyéthylène glycol, en particulier le Ceteth-20, d'un éther monostéarique de polyéthylène glycol, en particulier le Steareth-20, et de la lécithine.  Furthermore, the wax according to the invention may comprise additives, such as at least one lubricant or at least one emulsifier, in particular selected from the group consisting of glycerol monoricinoleate, a polyethylene glycol monocetyl ether, in particular the Ceteth-20, polyethylene glycol monostearic ether, especially Steareth-20, and lecithin.
De préférence, la cire selon l 'invention a un point de fusion supérieur à 32°C. De préférence également, la cire selon l 'invention a un point de fusion inférieur à 37°C. Plus préférablement, la cire selon l 'invention a un point de fusion supérieur à 32°C et inférieur à 37°C.  Preferably, the wax according to the invention has a melting point of greater than 32 ° C. Also preferably, the wax according to the invention has a melting point below 37 ° C. More preferably, the wax of the invention has a melting point of greater than 32 ° C and less than 37 ° C.
Comme cela apparaîtra clairement à l' homme du métier, le point de fusion est de préférence mesuré sous une pression normale. Comme on l'entend ici, une pression normale est une pression de 1 bar.  As will be clear to those skilled in the art, the melting point is preferably measured under normal pressure. As used herein, a normal pressure is a pressure of 1 bar.
De préférence, la cire selon l'invention est sélectionnée dans le groupe constitué de SUPPOCIRE® NA PASTILLES (Gattefossé), OVUCIRE® 3460 PASTILLES (Gattefossé) et SUPPOCIRE® AML PASTILLES (Gattefossé) .  Preferably, the wax according to the invention is selected from the group consisting of SUPPOCIRE® NA PASTILLES (Gattefossé), OVUCIRE® 3460 PASTILLES (Gattefossé) and SUPPOCIRE® AML PASTILLES (Gattefossé).
De préférence, la cire selon l'invention a une humidité relative de 20% à 35% avant mélange.  Preferably, the wax according to the invention has a relative humidity of 20% to 35% before mixing.
Mélange Mixed
De préférence, le mélange selon l'invention a un point de fusion supérieur à 32°C. De préférence également, le mélange selon l 'invention a un point de fusion inférieur à 37°C. Plus préféra blemenf, le mélange selon l 'invention a un point de fusion supérieur à 32°C et inférieur à 37°C. Preferably, the mixture according to the invention has a melting point greater than 32 ° C. Also preferably, the mixture according to the invention has a melting point less than 37 ° C. More preferably, the mixture according to the invention has a melting point of greater than 32 ° C and less than 37 ° C.
Comme cela apparaîtra clairement à l' homme du métier, le point de fusion est de préférence mesuré sous une pression normale. Comme on l'entend ici, une pression normale est une pression de 1 bar.  As will be clear to those skilled in the art, the melting point is preferably measured under normal pressure. As used herein, a normal pressure is a pressure of 1 bar.
De préférence, le mélange selon l'invention a un temps de liquéfaction inférieur à 1 0 min. dans une eau à 37°C.  Preferably, the mixture according to the invention has a liquefaction time of less than 10 min. in water at 37 ° C.
De préférence, le mélange selon l'invention a une résistance à la rupture supérieure à 5,4 kg à une température de 23°C.  Preferably, the mixture according to the invention has a breaking strength greater than 5.4 kg at a temperature of 23 ° C.
De préférence, le mélange selon l'invention comprend, ou est constitué de, 1 5 à 35% (m/m) de cellules de levure Saccharomyces boulordii sous forme de poudre, notamment lyophilisée, et de 65 à 85% (m/m) de cire selon l 'invention. Plus préférablement le mélange selon l'invention comprend, ou est constitué de, 30% (m/m) de cellules de levure Saccharomyces boulardii sous forme de poudre, notamment lyophilisée, et de 70% (m/m) de cire selon l'invention.  Preferably, the mixture according to the invention comprises, or consists of, 15 to 35% (w / w) of yeast Saccharomyces boulordii cells in powder form, in particular lyophilized, and from 65 to 85% (w / w). ) of wax according to the invention. More preferably, the mixture according to the invention comprises, or consists of, 30% (m / m) of yeast Saccharomyces boulardii cells in powder form, in particular freeze-dried form, and 70% (m / m) of wax according to US Pat. invention.
De préférence, la composition, notamment pharmaceutique, selon l'invention, le dispositif médical selon l 'invention, le médicament selon l'invention ou le produit cosmétique selon l 'invention comprend, ou consiste en, le mélange en une masse unitaire de 1 g à 5 g, notamment d 'environ ou exactement 2 g.  Preferably, the composition, in particular pharmaceutical, according to the invention, the medical device according to the invention, the drug according to the invention or the cosmetic product according to the invention comprises, or consists of, mixing into a unit mass of 1 g at 5 g, especially about or exactly 2 g.
De préférence également, la composition, notamment pharmaceutique, selon l'invention, le dispositif médical selon l'invention, le médicament selon l'invention ou le produit cosmétique selon l 'invention, comprend une masse unitaire de 0, 15 g à 1 ,75 g, notamment de 0,3 à 0,7 g, de cellules de levure Saccharomyces boulardii sous forme de poudre, notamment lyophilisée. Plus préférablement, la composition, notamment pharmaceutique, selon l 'invention, le dispositif médical selon l 'invention, le médicament selon l 'invention ou le produit cosmétique selon l'invention, comprend une masse unitaire de 0,6 g, de cellules de levure Saccharomyces boulardii sous forme de poudre, notamment lyophilisée. Applications  Preferably also, the pharmaceutical composition according to the invention, the medical device according to the invention, the medicament according to the invention or the cosmetic product according to the invention, comprises a unit mass of 0.15 g to 1, 75 g, in particular from 0.3 to 0.7 g, of yeast Saccharomyces boulardii cells in powder form, in particular lyophilized form. More preferably, the pharmaceutical composition according to the invention, the medical device according to the invention, the medicinal product according to the invention or the cosmetic product according to the invention, comprises a unit mass of 0.6 g, yeast Saccharomyces boulardii in powder form, especially lyophilized. applications
La composition selon l'invention peut être une composition pharmaceutique. Dans ce cas, la composition pharmaceutique peut comprendre un ou plusieurs excipients ou véhicules pharmaceutiquement acceptables en plus du mélange. Les infections vulvo-vaginales selon l'invention sont des infections de la vulve et/ou du vagin. Les infections vulvo-vaginales selon l'invention peuvent être des infections : The composition according to the invention may be a pharmaceutical composition. In this case, the pharmaceutical composition may comprise one or more pharmaceutically acceptable excipients or carriers in addition to the mixture. The vulvovaginal infections according to the invention are infections of the vulva and / or the vagina. The vulvovaginal infections according to the invention may be infections:
bactériennes, notamment à Gardnerella vaginalis, Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species et including Gardnerella vaginalis, Gardnerella mobiluncus, Chlamydia trachomatis, Mycoplasma hominis, Peptostreptococcus species
Ureaplasma urealyticum, Ureaplasma urealyticum,
mycosiques, notamment à Candida, ou  fungal infections, especially in Candida, or
parasitaires, notamment à Trichomonas.  parasites, including Trichomonas.
Les anti-infectieux selon l'invention peuvent notamment être :  The anti-infectives according to the invention may in particular be:
- des antiseptiques ;  - antiseptics;
- des antibiotiques, notamment de la famille des nitroimidazoles, tel que le métrodinazole ;  antibiotics, especially from the family of nitroimidazoles, such as metodinazole;
- des antifongiques, notamment de la famille des imidazolés, tels que l'éconazole, le miconazole ou le fluconazole ; ou  antifungals, in particular from the family of imidazoles, such as econazole, miconazole or fluconazole; or
- des antiparasitaires, notamment de la famille des nitroimidazoles, tel que le métrodinazole ;  antiparasitic agents, in particular from the family of nitroimidazoles, such as metodinazole;
Comme on l 'entend ici, le « rééquilibrage de la flore vaginale » désigne le rétablissement d'une flore vaginale normale ou saine, notamment en termes de diversité et de quantité de micro-organismes vaginaux.  As used herein, "rebalancing of vaginal flora" refers to the restoration of normal or healthy vaginal flora, particularly in terms of the diversity and amount of vaginal microorganisms.
La composition selon l 'invention peut être une composition cosmétique. Dans ce cas, la composition cosmétique peut comprendre un ou plusieurs excipients ou véhicules cosmétiquement acceptables en plus du mélange. De même, le produit cosmétique selon l'invention peut comprendre un ou plusieurs excipients ou véhicules cosmétiquement acceptables en plus de la composition selon l'invention.  The composition according to the invention may be a cosmetic composition. In this case, the cosmetic composition may comprise one or more cosmetically acceptable excipients or vehicles in addition to the mixture. Similarly, the cosmetic product according to the invention may comprise one or more cosmetically acceptable excipients or vehicles in addition to the composition according to the invention.
Comme on l 'entend ici, l ' hygiène intime ou la toilette intime désigne la toilette de la vulve et/ou du vagin.  As it is understood here, the intimate hygiene or the private toilet designates the toilet of the vulva and / or the vagina.
De préférence, la composition, notamment pharmaceutique, selon l'invention, le dispositif médical selon l 'invention, le médicament selon l'invention ou le produit cosmétique selon l 'invention, est administré par la voie vaginale, notamment sous la forme d 'un ovule.  Preferably, the pharmaceutical composition according to the invention, the medical device according to the invention, the drug according to the invention or the cosmetic product according to the invention, is administered by the vaginal route, in particular in the form of an egg.
Comme on l 'entend ici, le terme « ovule » est considéré équivalent à « ovule vaginal » ou « ovule gynécologique ».  As it is understood here, the term "ovum" is considered equivalent to "vaginal ovum" or "gynecological ovum".
De préférence, l'individu selon l 'invention est un mammifère, plus préférablement un humain, notamment de sexe féminin. Exemple Preferably, the individual according to the invention is a mammal, more preferably a human, in particular a female. Example
Matériels et méthodes Materials and methods
1 .1 . Cires 1 .1. waxes
Les différentes cires utilisées pour la formulation des ovules incorporant Saccharomyces boulardii sont décrites dans le Tableau suivant :  The various waxes used for the formulation of eggs incorporating Saccharomyces boulardii are described in the following table:
NOM LAST NAME
Commercial Définition Description Application  Commercial Definition Description Application
(Gattefossé)  (Gattefossé)
Glycérides semi- Semi-glycerides
Voie vaginale : masse pour synthétiques C12-C18 Vaginal route: mass for synthetic C12-C18
SUPPOCI E® Hard fat ovules/supposifoires à indice saturés (triglycérides)  SUPPOCI E® Hard fat ovules / suppositories with saturated index (triglycerides)
NA PASTILLES EP/NF/JPE. d'hydroxyle moyen (43 mg  NA PASTILLES EP / NF / JPE. of medium hydroxyl (43 mg
Point de fusion : 34,5- KOH/g) .  Melting point: 34.5 KOH / g).
36,5°C  36.5 ° C
Hard Fat  Hard Fat
EP/NF/JPE (and) Glycérides semi- lyceryl synfhétiques C12-C18 Voie vaginale : masse pour EP / NF / JPE (and) Semi-lyceryl synfhetic glycerides C12-C18 Vaginal route: mass for
OVUCIRE® gOVUCIRE® g
e (and) saturés (triglycérides) ovules/supposifoires à indice e (and) saturated (triglycerides) ovules / suppositories with index
3460 ricinoléat 3460 ricinoleate
contenant des additifs d'hydroxyle élevé (65 mg PASTILLES  containing high hydroxyl additives (65 mg PELLETS
Cefefh- Point de fusion 32,5- KOH/g)  Cefefh- melting point 32.5- KOH / g)
20/S†eare†h-20 34,0°C  20 / S † eare † h-20 34.0 ° C
EP/NF.  EP / NF.
Glycérides semi- synfhéfiques C8-C18  Semi-synfhafic Glycerides C8-C18
saturés (triglycérides) Voie rectale : masse pour saturated (triglycerides) Rectal way: mass for
SUPPOCIRE® contenant un ovules/supposifoires à faible SUPPOCIRE® containing an egg / suppository at low
Hard fat NF/JPE  Hard fat NF / JPE
AML PASTILLES phospholipide indice d'hydroxyle (6 mg  AML PASTILLES phospholipid hydroxyl number (6 mg
(lécifhine) KOH/g) .  (lecifhine) KOH / g).
Point de fusion : 35,0- 36,5°C  Melting point: 35.0-36.5 ° C
1 .2. Levure 1 .2. Yeast
La levure utilisée est Saccharomyces boulardii sous forme de poudre lyophilisée (Ultra- Levure®, Biocodex, Lot 7316).  The yeast used is Saccharomyces boulardii in freeze-dried powder form (Ultra-Levure®, Biocodex, Lot 7316).
1 .3. Fabrication des ovules 1 .3. Manufacture of eggs
1 . La masse à suppositoire est chauffée à 55°C jusqu'à sa complète fusion.  1. The suppository mass is heated to 55 ° C until complete fusion.
2. Sous agitation magnétique, le mélange est refroidi jusqu'à 40 - 41 °C, puis les levures sont ajoutées. 3. Une homogénéisation à haute vitesse (9000 tr/min) est faite pendant une minute afin d'assurer une bonne dispersion des levures dans la masse à suppositoire. 2. With magnetic stirring, the mixture is cooled to 40 - 41 ° C, then the yeasts are added. 3. Homogenization at high speed (9000 rpm) is done for one minute to ensure a good dispersion of the yeasts in the suppository mass.
4. L'agitation est alors diminuée et maintenue à 500 tr/min pendant le reste du refroidissement.  4. The stirring is then decreased and maintained at 500 rpm during the rest of the cooling.
5. A 30 - 36 °C, le mélange est versé dans un moule à réglette de 2 g (la température de coulée idéale des ovules a été déterminée à partir d'un thermo-rhéogramme du mélange réalisé à l'aide d'un appareil Rhéomat 1 1 5 (LabMakelaar Bénélux BV)).  5. At 30-36 ° C, the mixture is poured into a 2 g ruler mold (the ideal egg casting temperature was determined from a thermo-rheogram of the mixture made with a Rheomat apparatus 1 1 5 (LabMakelaar Benelux BV)).
6. Les ovules sont refroidis à température ambiante pendant 4 minutes.  6. The eggs are cooled to room temperature for 4 minutes.
7. Les ovules sont démoulés après 6 minutes à température ambiante.  7. The eggs are demolded after 6 minutes at room temperature.
1 .4. Test physique de caractérisation des ovules 1 .4. Physical test of egg characterization
Point de fusion : Fusion point :
Cette méthode détermine la température à laquelle l 'ovule devient suffisamment liquide pour glisser dans un tube capillaire en forme de U ( 1 ,5 mm de diamètre intérieur). Cette méthode est un moyen simple et fiable pour comparer les points de fusion des ovules. Ce point de fusion doit être inférieur à 37°C. Trois ovules sont testés par lot. This method determines the temperature at which the egg becomes sufficiently liquid to slip into a U - shaped capillary tube (1.5 mm ID). This method is a simple and reliable way to compare egg melting points. This melting point must be below 37 ° C. Three eggs are tested per lot.
Résistance mécanique : Mechanical resistance :
Cette méthode détermine la résistance à la rupture des ovules. La valeur définie correspond à la masse nécessaire pour générer leur écrasement. L'ovule est positionné sur une mâchoire et relié à une tige sur laquelle sont ajoutés successivement des poids. La force exercée sur l'ovule est augmentée jusqu 'à l 'écrasement de l 'ovule. Les ovules doivent être capables de résister à un poids au moins égal à 1800-2000 g. Cinq ovules sont testés par lot.  This method determines the breaking strength of eggs. The value defined corresponds to the mass needed to generate their overwriting. The egg is positioned on a jaw and connected to a rod on which are added successively weights. The force exerted on the egg is increased until the egg is crushed. Eggs must be able to withstand a weight of at least 1800-2000 g. Five eggs are tested per lot.
Temps de liquéfaction : Liquefaction time:
Cette méthode (référence Ph. Eur. 2.9.22 édition en vigueur) détermine le temps nécessaire pour qu'un ovule maintenu dans une eau à 37°C ramollisse suffisamment pour se faire déformer et traverser par une tige rigide. Ce temps doit être inférieur à 20 minutes. Trois ovules sont testés par lot. Exemple 1 This method (reference Ph. Eur 2.9.22 edition in force) determines the time required for an egg held in water at 37 ° C to soften sufficiently to be deformed and pass through a rigid rod. This time must be less than 20 minutes. Three eggs are tested per lot. Example 1
* Spécifications de la Pharmacopée Européenne, édition en vigueur  * Specifications of the European Pharmacopoeia, edition in force
Exemple 2 Example 2
Formulation Pour 100 ovules Pour 1 ovule (formulation unitaire)  Formulation For 100 eggs For 1 egg (unit formulation)
Levure 60 g 600 mgYeast 60 g 600 mg
Ovucire® 3460 140 g 1 400 mg Ovucire® 3460 140 g 1,400 mg
Total 200 g 2 000 mg Tests Normes Résultats Total 200 g 2,000 mg Tests Standards Results
Résistance mécanique > 1 kg 800 - 2 kg > 5.40 kg Mechanical resistance> 1 kg 800 - 2 kg> 5.40 kg
Temps de liquéfaction < 20 minutes* 7 min 37 s ± 7 s Liquefaction time <20 minutes * 7 min 37 s ± 7 s
Point de fusion < 37°C 36,3 ± 0,1 °C Melting point <37 ° C 36.3 ± 0.1 ° C
CONCLUSION CONFORME CONCLUDING CONCLUSION
* Spécifications de a Pharmacopée Européenne  * Specifications of a European Pharmacopoeia
Exemple 3 Example 3
Tests Normes Résultats Tests Standards Results
Résistance mécanique > 1 kg 800 - 2 kg > 5.40 kg Mechanical resistance> 1 kg 800 - 2 kg> 5.40 kg
Temps de liquéfaction < 20 minutes* 8 min 14 s ± 2 s Liquefaction time <20 minutes * 8 min 14 s ± 2 s
Point de fusion < 37°C 36,0 ± 0,1 °C Melting point <37 ° C 36.0 ± 0.1 ° C
CONCLUSION CONFORME CONCLUDING CONCLUSION
* Spécifications de a Pharmacopée Européenne  * Specifications of a European Pharmacopoeia

Claims

REVENDICATIONS
1. Composition comprenant un mélange de cellules de levure Saccharomyces boulardii et d 'une cire. A composition comprising a mixture of yeast Saccharomyces boulardii cells and a wax.
2. Composition selon la revendication 1 , dans laquelle le mélange a un point de fusion supérieur à 32°C et inférieur à 37°C, sous une pression normale. The composition of claim 1 wherein the mixture has a melting point above 32 ° C and below 37 ° C under normal pressure.
3. Composition selon la revendication 1 ou 2, dans laquelle le mélange a un temps de liquéfaction inférieur à 10 min. dans une eau à 37°C. 3. Composition according to claim 1 or 2, wherein the mixture has a liquefaction time of less than 10 min. in water at 37 ° C.
4. Composition selon l 'une des revendications 1 à 3, dans laquelle le mélange a une résistance à la rupture supérieure à 5,4 kg à une température de 23°C. 4. Composition according to one of claims 1 to 3, wherein the mixture has a tensile strength greater than 5.4 kg at a temperature of 23 ° C.
5. Composition selon l'une des revendications 1 à 4, dans laquelle la cire a une humidité relative de 20% à 35% avant mélange. 5. Composition according to one of claims 1 to 4, wherein the wax has a relative humidity of 20% to 35% before mixing.
6. Composition selon l'une des revendications 1 à 5, dans laquelle la cire est à base de triglycérides en C8-C1 8 ou en Cl 2-C1 8 saturés. 6. Composition according to one of claims 1 to 5, wherein the wax is based on triglycerides C8-C1 8 or C1 2-C1 8 saturated.
7. Composition selon l 'une des revendications 1 à 6, dans laquelle la cire est sélectionnée dans le groupe constitué de SUPPOCIRE® NA PASTILLES (Gattefossé), OVUCIRE® 3460 PASTILLES (Gattefossé) et SUPPOCIRE® AML PASTILLES (Gattefossé) . 7. Composition according to one of claims 1 to 6, wherein the wax is selected from the group consisting of SUPPOCIRE® NA PASTILLES (Gattefossé), OVUCIRE® 3460 PASTILLES (Gattefossé) and SUPPOCIRE® AML PASTILLES (Gattefossé).
8. Composition selon l'une des revendications 1 à 7, dans laquelle les cellules de levure Saccharomyces boulardii sont mélangées sous forme de poudre, notamment lyophilisée. 8. Composition according to one of claims 1 to 7, wherein the yeast Saccharomyces boulardii cells are mixed in powder form, in particular freeze-dried.
9. Composition selon l'une des revendications 1 à 8, dans laquelle le mélange est formé de 15 à 35% (m/m) de cellules de levure Saccharomyces boulardii sous forme de poudre et de 65 à 85% (m/m) de cire. 9. Composition according to one of claims 1 to 8, wherein the mixture is formed from 15 to 35% (m / m) of yeast cells Saccharomyces boulardii in powder form and 65 to 85% (m / m). of wax.
10. Composition selon l'une des revendications 1 à 9, dans laquelle le mélange comprend de 1 ,5 x 109 à 2,5 x 1 010 Unités Formant Colonies (UFC) de cellules de levures Saccharomyces boulardii. The composition of any one of claims 1 to 9, wherein the mixture comprises from 1.5 x 10 9 to 2.5 x 10 10 colony forming units (CFU) of yeast cells Saccharomyces boulardii.
11. Dispositif médical ou médicament comprenant une composition telle que définie dans l'une des revendications 1 à 1 0. 11. A medical device or medicament comprising a composition as defined in one of claims 1 to 10.
12. Dispositif médical ou médicament selon la revendication 1 1 , comprenant le mélange en une masse unitaire de 1 g à 5 g. 12. The medical device or medicament according to claim 11, comprising mixing into a unit mass of 1 g to 5 g.
13. Dispositif médical ou médicament selon la revendication 1 1 ou 12, pour son utilisation à titre d 'ovule. 13. The medical device or medicament according to claim 1 1 or 12 for its use as an ovum.
14. Dispositif médical ou médicament selon la revendication 1 1 ou 12, pour son utilisation dans la prévention ou le traitement des infections vulvo-vaginales. 14. The medical device or medicament according to claim 1 1 or 12 for its use in the prevention or treatment of vulvovaginal infections.
15. Dispositif médical ou médicament selon la revendication 1 1 ou 12, pour son utilisation dans le rééquilibrage de la flore vaginale, notamment après traitement par un anti-infectieux local ou systémique, et/ou pour contribuer à consolider la guérison après la prise d'un traitement anti-infectieux local vaginal, et/ou pour prévenir les récidives d 'infections vaginales. 15. Medical device or medicament according to claim 1 1 or 12, for its use in the rebalancing of the vaginal flora, especially after treatment with a local or systemic anti-infective, and / or to help consolidate healing after taking local vaginal anti-infective treatment, and / or to prevent recurrence of vaginal infections.
16. Produit cosmétique comprenant une composition telle que définie dans l 'une des revendications 1 à 10. 16. Cosmetic product comprising a composition as defined in one of claims 1 to 10.
17. Produit cosmétique selon la revendication 1 6, comprenant le mélange en une masse unitaire de 1 g à 5 g. 17. Cosmetic product according to claim 1 6, comprising mixing into a unit mass of 1 g to 5 g.
18. Utilisation d 'un produit cosmétique selon la revendication 1 6 ou 1 7 pour l ' hygiène intime ou la toilette intime d'un individu. 18. Use of a cosmetic product according to claim 1 6 or 1 7 for the intimate hygiene or personal hygiene of an individual.
19. Procédé d 'obtention d 'une composition telle que définie dans l 'une des revendications 1 à 10, comprenant les étapes suivantes : 19. Process for obtaining a composition as defined in one of claims 1 to 10, comprising the following steps:
- si nécessaire on chauffe la cire jusqu 'à la rendre liquide ; - on maintient la cire à l'état liquide à une température inférieure à 42 C et on ajoute des cellules de levure Saccharomyces boulardii sous agitation ; if necessary, heat the wax until it becomes liquid; the wax is maintained in the liquid state at a temperature below 42 ° C. and yeast Saccharomyces boulardii cells are added with stirring;
- on laisse refroidir le mélange sous agitation en le maintenant liquide jusqu'à une température inférieure à 36°C ;  the mixture is allowed to cool with stirring while maintaining it liquid until a temperature of less than 36 ° C .;
- on coule le mélange dans un moule ; the mixture is poured into a mold;
- on démoule le mélange après solidification.  the mixture is demolded after solidification.
EP17725173.3A 2016-04-27 2017-04-27 Composition useful for the preparation of a suppository Pending EP3448403A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1670198A FR3050641B1 (en) 2016-04-27 2016-04-27 COMPOSITION USEFUL FOR PREPARING AN OVA
PCT/EP2017/060123 WO2017186877A1 (en) 2016-04-27 2017-04-27 Composition useful for the preparation of a suppository

Publications (1)

Publication Number Publication Date
EP3448403A1 true EP3448403A1 (en) 2019-03-06

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US (1) US20190142745A1 (en)
EP (1) EP3448403A1 (en)
KR (1) KR20190016949A (en)
CN (1) CN109195615A (en)
CA (1) CA3022447A1 (en)
FR (1) FR3050641B1 (en)
MX (1) MX2018013194A (en)
RU (1) RU2018141418A (en)
WO (1) WO2017186877A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999017788A1 (en) * 1997-10-06 1999-04-15 Abbott Laboratories Composition of treatment of candidiasis
US20050214364A1 (en) * 2004-03-23 2005-09-29 Hutman Herbert W Products and methods for treating vaginal infections
EP2505188A1 (en) * 2009-12-02 2012-10-03 Bettina Heil Suppository for rectal, vaginal or urethral administration
US8853269B2 (en) * 2010-02-04 2014-10-07 Copperhead Chemical Company Inc. Composition and method for treating infections and promoting intestinal health
FR2993179B1 (en) * 2012-07-13 2016-01-08 Lesaffre & Cie YEAST SACCHAROMYCES CEREVISIAE FOR PREVENTING AND / OR TREATING VAGINAL MYCOSES

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FR3050641A1 (en) 2017-11-03
CA3022447A1 (en) 2017-11-02
FR3050641B1 (en) 2018-04-13
MX2018013194A (en) 2019-05-27
KR20190016949A (en) 2019-02-19
RU2018141418A (en) 2020-05-27
CN109195615A (en) 2019-01-11
WO2017186877A1 (en) 2017-11-02
US20190142745A1 (en) 2019-05-16

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