WO2018002113A1 - Product for vaginal application - Google Patents
Product for vaginal application Download PDFInfo
- Publication number
- WO2018002113A1 WO2018002113A1 PCT/EP2017/065954 EP2017065954W WO2018002113A1 WO 2018002113 A1 WO2018002113 A1 WO 2018002113A1 EP 2017065954 W EP2017065954 W EP 2017065954W WO 2018002113 A1 WO2018002113 A1 WO 2018002113A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vaginal
- product
- phase
- probiotic
- hydrogel
- Prior art date
Links
- 239000006041 probiotic Substances 0.000 claims abstract description 45
- 235000018291 probiotics Nutrition 0.000 claims abstract description 45
- 150000002632 lipids Chemical class 0.000 claims abstract description 36
- 239000000017 hydrogel Substances 0.000 claims abstract description 30
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims abstract description 26
- 230000000529 probiotic effect Effects 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 230000001580 bacterial effect Effects 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 235000019482 Palm oil Nutrition 0.000 claims description 6
- 206010046914 Vaginal infection Diseases 0.000 claims description 6
- 238000013016 damping Methods 0.000 claims description 6
- 239000002540 palm oil Substances 0.000 claims description 6
- 201000008100 Vaginitis Diseases 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 229920002674 hyaluronan Polymers 0.000 claims description 5
- 239000003921 oil Substances 0.000 claims description 5
- 235000019198 oils Nutrition 0.000 claims description 5
- 241000218492 Lactobacillus crispatus Species 0.000 claims description 4
- 239000003240 coconut oil Substances 0.000 claims description 4
- 235000019864 coconut oil Nutrition 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 3
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 claims description 3
- 235000013871 bee wax Nutrition 0.000 claims description 3
- 239000012166 beeswax Substances 0.000 claims description 3
- 229960003160 hyaluronic acid Drugs 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 239000012188 paraffin wax Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 229920000936 Agarose Polymers 0.000 claims description 2
- 241000222122 Candida albicans Species 0.000 claims description 2
- 241000186606 Lactobacillus gasseri Species 0.000 claims description 2
- 241001324870 Lactobacillus iners Species 0.000 claims description 2
- 241001561398 Lactobacillus jensenii Species 0.000 claims description 2
- 241000186783 Lactobacillus vaginalis Species 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 235000009470 Theobroma cacao Nutrition 0.000 claims description 2
- 244000299461 Theobroma cacao Species 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 claims description 2
- 229940099552 hyaluronan Drugs 0.000 claims description 2
- 230000002209 hydrophobic effect Effects 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 229920005615 natural polymer Polymers 0.000 claims description 2
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 2
- 235000003441 saturated fatty acids Nutrition 0.000 claims description 2
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 2
- 229920001059 synthetic polymer Polymers 0.000 claims description 2
- 244000199866 Lactobacillus casei Species 0.000 claims 2
- 206010007134 Candida infections Diseases 0.000 claims 1
- 240000001046 Lactobacillus acidophilus Species 0.000 claims 1
- 240000006024 Lactobacillus plantarum Species 0.000 claims 1
- 201000003984 candidiasis Diseases 0.000 claims 1
- -1 coconut oil Chemical compound 0.000 claims 1
- 239000012071 phase Substances 0.000 description 61
- 238000000926 separation method Methods 0.000 description 13
- 210000000981 epithelium Anatomy 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- GNWCZBXSKIIURR-UHFFFAOYSA-N (2-docosanoyloxy-3-hydroxypropyl) docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCCCCCC GNWCZBXSKIIURR-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 230000001050 lubricating effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000004746 Atrophic Vaginitis Diseases 0.000 description 1
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 230000003534 oscillatory effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
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- 230000008719 thickening Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Definitions
- the present invention relates to a product for vaginal application, in particular to a product for vaginal application for use in the treatment of vaginal dryness.
- Products for vaginal application and in particular for the treatment of vaginal dryness are known from the state of the art. These are generally creams, lubricants or gels and more particularly hydrogels containing about 90% water and possibly hyaluronic acid.
- vaginal dryness when the vaginal tissue is no longer well lubricated and healthy. This problem can affect all women but is found more particularly in those who are menopausal, pregnant or in young mothers. In these three cases, the main factor responsible for vaginal dryness is a decrease in estrogen production and, in this case, we also speak of atrophic vaginitis. Other factors may also be at the origin of this problem, such as stress or anxiety, taking alcohol, tobacco or drugs, or even certain medications (eg drugs or hormones used in treatment of breast cancer, endometriosis, fibroids or infertility). Surgery for removal of the ovaries but also for contraception are also factors responsible for vaginal dryness.
- vaginal dryness In the case of a vaginal dryness, the vaginal tissue shrinks and becomes thinner which is essentially manifested by a lack of hydration of the vagina and inflammation of the vagina. Such inflammation causes other secondary symptoms such as redness of the external genitalia, itching, irritation and / or local inflammation, burning sensation (especially when urinating) and painful and bloody intercourse. to micro-injuries. More particularly, it is recognized that vaginal dryness inevitably gives rise to secondary opportunistic complications (secondary opportunistic problems), the four main ones being (1) inflammations and infections notably responsible for irritations, itching and sensations.
- secondary opportunistic problems secondary opportunistic problems
- vaginal bacterial flora essentially composed of Lactobacillus-type bacteria
- vaginal dryness many factors, besides vaginal dryness, can contribute to a rapid imbalance of this bacterial flora.
- the means of contraception, antibiotic intake, excessive or neglected personal hygiene or the wearing of tight clothing may cause a real imbalance of the vaginal bacterial flora.
- vaginal mycoses and / or vaginoses of bacterial origin appear, for example caused by the pathogen Candida albicans.
- lubricant in order to treat a problematic vaginal dryness, it is presently proposed to use the use of lubricant and the use of compounds with properties to protect the vaginal epithelium to prevent the appearance of wounds and cracks but also in order to treat these.
- lubricating gels containing hyaluronic acid are available to simultaneously moisten (rehydrate) the environment vaginal and protect the vaginal epithelium (formation of a protective film on the vaginal epithelium).
- vaginal dryness mainly observed in postmenopausal women (but not exclusively), is a primary problem that stems from secondary problems, namely inflammations and infections, the appearance of lesions of the mucous membranes and the epithelium.
- vaginal a significant change in the pH of the vaginal environment and a significant disturbance of bacterial flora specific to the vaginal environment, these primary and secondary problems therefore meeting generally simultaneously.
- probiotics in the vaginal environment for example through suppositories or tablets, including probiotics
- lubricating and / or moisturizing formulations treatment of the primary problem
- the object of the invention is to overcome the drawbacks of the state of the art by providing an invention making it possible to dispense with such a particularly restrictive treatment and requiring the use of several different products, each of these products being designed to process independently a given problem, that is to say either the problem of vaginal dryness itself, or inflammations and infections, lesions of the vaginal mucosa and epithelium, or a significant change in the pH of the environment vaginal, a major disturbance of the bacterial flora specific to the vaginal environment.
- the object of the invention is to propose a product that makes it possible, in a single application, to simultaneously treat the primary problem (vaginal dryness) and at least one or even all of the secondary problems. arising from it and appearing simultaneously.
- the object of the invention is to provide a product which makes it possible to treat at the same time, that is to say, thanks to a single application, both the primary problematic of vaginal dryness and at least one of the four secondary opportunistic problems mentioned above. .
- the invention therefore aims to treat and / or avoid secondary opportunistic problems at the same time as vaginal dryness.
- the product according to the invention thus makes it possible to carry out a prophylactic and / or curative treatment.
- a first phase in the form of a hydrogel a first phase in the form of a hydrogel
- a second lipid phase including at least one probiotic a second lipid phase including at least one probiotic.
- probiotics in the vaginal environment through for example suppositories, tablets or creams including probiotics.
- the objectives pursued by such applications of probiotics are multiple but are essentially made on the one hand to correct or restore the vaginal pH and to recolonize the vaginal bacterial flora.
- Bacterial recolonization ensures the maintenance of an adequate vaginal pH and ensures above all a protection of the vaginal environment against various pathogens responsible for infections.
- the primary problem is a vaginal dryness and the secondary problem is a disturbance of the vaginal bacterial flora
- a bi-phasic product comprising a first phase in the form of a hydrogel and a second lipid phase including at least one probiotic
- Combined treatment in one step, allows simultaneous treatment of vaginal dryness and at least restoring / correcting vaginal bacterial flora, which current products do not propose since current devices and application forms only include a hydrogel or only a formulation comprising probiotics.
- a product according to the invention it is therefore possible to simultaneously treat the primary problem (vaginal dryness) and at least one and preferably at least all of the four secondary opportunistic problems (complications). mentioned above. This results in a combined and simplified treatment of all the problems encountered simultaneously with vaginal dryness.
- a first phase in the form of a hydrogel that is to say a first substantially aqueous phase (hydrophilic environment containing up to 90% water or more)
- a second lipid phase comprising probiotics
- probiotics are particularly sensitive to the presence of water and they are even simply deactivated or killed in the presence of water, it was not expected that, even if they are present in a lipid phase, their survival rate is not reduced in a bi-phasic product according to the invention in which the aqueous phase (the hydrogel) is nevertheless the majority (up to 95% of the product by volume).
- a clear separation (interface) is established between the two phases (one aqueous and the other lipidic), this separation being stable and long lasting. over time and that the two phases are immiscible.
- a clear, stable and lasting separation over time has the advantage of being able to allow manipulation of the composition previously packaged in a container without having to take excessive precautions whether during storage or during transport.
- the separation being established between the two phases according to the invention is such that it resists the movements of the container and the shocks that the latter may suffer.
- a fall or agitation of a bi-phasic product according to the invention contained for example in a vaginal applicator does not cause a mixture first and second phases.
- the probiotics remain isolated from the first phase in the form of a hydrogel, which makes it possible to guarantee a high survival rate over time.
- the terms "interface” or “separation” mean a separation, an interface or a barrier which is established naturally between two phases, in this case between an aqueous phase (hydrogel) and a lipid phase (including probiotics). It is not therefore a physical physical separation (for example an impermeable membrane) or a separation provided by an additional phase.
- said first phase in the form of a hydrogel and said second lipid phase including at least one probiotic of a product according to the invention constitute respectively 90 to 95% and 5 to 10% by volume relative to the total volume of said product.
- said first phase in the form of a hydrogel of a product according to the invention comprises a liquid component and a solid component, said liquid component being water and said solid component being chosen from the group consisting of polyvinyl alcohol, sodium polyacrylate, agarose, methylcellulose, hyaluronan, natural or synthetic polymers and copolymers, and mixtures thereof.
- said second lipid phase including at least one probiotic of a product according to the invention consists of at least one hydrophobic fatty substance selected from the group consisting of glycerine, paraffin, glycerol, saturated fatty acids. such as coconut oil, cocoa oil, palm oil or beeswax, and their blends.
- glycerine paraffin
- glycerol saturated fatty acids.
- coconut oil cocoa oil, palm oil or beeswax
- Such fats and their mixtures have been defined as to form an adequate lipid phase to ensure the survival of probiotics in the lipid phase and maintain them in a dispersed form in this lipid phase.
- These fatty substances have also been identified as enabling a clear, stable and durable interface formation (separation) over time between the hydrogel phase and the lipid phase.
- said second lipid phase including at least one probiotic according to the invention has a yield strength measured using a CSL 2 (Controlled Stress Rheometer - TA Instruments Inc.) of between 250 and 750 Pa, preferably a yield strength of between 400 and 500 Pa, preferably a yield strength of 450 Pa.
- the elastic limit is the stress from which a material stops deforming elastically, reversibly and starts therefore to deform irreversibly. It has been determined that such a yield point or yield strength of the lipid phase makes it possible to ensure that the interface (separation) between the two phases (hydrogel vs lipid phase) is stable, durable and clean, which ensures survival probiotics in the lipid phase where they are dispersed.
- said second lipid phase including at least one probiotic according to the invention has a loss factor or damping factor measured by oscillatory rheometry using an oscillation-mode rotational rheometer (ARES-G2, TA Instruments Inc) between 0, 11 and 0.15, preferably a loss factor or damping factor equal to 0.12.
- the loss factor or damping factor of a material is calculated as the ratio of the lost strain energy to the stored strain energy. This factor is an indicator of the relationship between viscosity and elasticity during viscoelastic deformation.
- the subject of the invention is also a product according to the invention comprising a first phase in the form of a hydrogel and a second lipid phase including at least one probiotic, said product being intended for use in the treatment of vaginal dryness and / or or vaginitis and / or vaginosis and / or vaginal candidiasis and / or disturbance of vaginal pH and / or a change in vaginal bacterial flora.
- the present invention also relates to an applicator for vaginal application, said applicator comprising a product according to the invention, that is to say a product comprising a first phase in the form of a hydrogel and a second lipid phase including at least a probiotic.
- said applicator is a disposable applicator of the syringe type or of the cannula type or of any other type making it possible to perform a vaginal application.
- the present invention also relates to a use of an applicator according to the invention for the treatment of vaginal dryness and / or vaginitis and / or vaginosis and / or vaginal candidiasis and / or a disturbance of the pH vaginal and / or modification of the vaginal bacterial flora.
- Figure 1 is a schematic view of an applicator according to the invention which comprises a bi-phasic product according to the invention.
- the applicator 1 consists of a tank 2 filled with air connected to a longitudinal body 4, one end is closed by a removable closure means 3.
- a first phase 6 in the form of a hydrogel filling about 95% of the volume of the applicator 1 and a second lipid phase 5 including at least one probiotic.
- the first phase 6 in the form of a hydrogel contains at least 90% water and the second phase 5 has a yield strength of between 250 and 750 Pa.
- a separation or interface 7 is established between the first phase 6 under form of a hydrogel and the second phase 5 such that this interface 7 is stable, durable and resistant to movement (agitation or fall of the applicator 1 for example).
- This interface 7 makes it possible to ensure that the probiotics included in the second lipid phase 5 are protected from the water contained in the first phase 6 in the form of a hydrogel. This makes it possible to ensure a high survival rate of the probiotics included in the second lipid phase 5.
- Such a separation or interface 7 with such properties is essentially due to the properties of the second lipid phase 5.
- the first phase in the form of a hydrogel was prepared by mixing the various pharmaceutical grade components according to the amounts shown in Table 1 below. Table 1
- MCT medium chain triglycerides
- EP European Pharmacopeia
- beeswax, glycerol dibehenate, and the like were mixed in MCT oil at a temperature of 75 ° C with stirring (80 RPM) until complete dissolution.
- the mixture thus obtained was homogenized before performing a cooling step in a tank to a temperature of the order of 15 to 20 ° C with constant stirring (60 RPM) and under vacuum to perform a degassing.
- nitrogen in the form of small bubbles was introduced from the bottom of the tank for 10 minutes until reaching the Patm. before observing a rest period of 2 hours at room temperature.
- a probiotic powder including L.
- a vaginal applicator formed according to the Blow-Fill-Seal (BFS) method was filled in. injecting sequentially (sequentially) or simultaneously each of the two phases of a product according to the invention.
- a bi-phasic product for vaginal application according to the invention was obtained as follows: a) preparation of the first phase of a product according to the invention in the form of a hydrogel
- the first phase in the form of a hydrogel was prepared as indicated in Example 1. b) Preparation of the second lipid phase of a product according to the invention including at least one probiotic
- the second lipid phase including at least one probiotic was obtained by mixing the various components according to the amounts shown in Table 3 below.
- EP European Pharmacopeia
- a vaginal applicator formed according to the Blow-Fill-Seal (BFS) method was filled in. there sequentially (sequentially) or simultaneously injecting each of the two phases of a product according to the invention.
Abstract
The present invention relates to a product for vaginal application, particularly to a product for vaginal application designed to be used in the treatment of vaginal dryness, said product comprising: - a first phase in the form of a hydrogel, and - a second lipid phase comprising at least one probiotic.
Description
PRODUIT POUR UNE APPLICATION VAGINALE PRODUCT FOR VAGINAL APPLICATION
La présente invention se rapporte à un produit pour une application vaginale, en particulier à un produit pour une application vaginale destiné à être utilisé dans le traitement de la sécheresse vaginale. The present invention relates to a product for vaginal application, in particular to a product for vaginal application for use in the treatment of vaginal dryness.
Des produits pour une application vaginale et en particulier pour le traitement de la sécheresse vaginale sont connus de l'état de la technique. Il s'agit généralement de crèmes, de lubrifiants ou de gels et plus particulièrement d'hydrogels contenant de l'ordre de 90% d'eau et éventuellement de l'acide hyaluronique. Products for vaginal application and in particular for the treatment of vaginal dryness are known from the state of the art. These are generally creams, lubricants or gels and more particularly hydrogels containing about 90% water and possibly hyaluronic acid.
On parle de sécheresse vaginale lorsque le tissu vaginal n'est plus bien lubrifié et sain. Cette problématique peut toucher toutes les femmes mais se rencontre plus particulièrement chez celles qui sont ménopausées, enceintes ou chez les jeunes mamans. Dans ces trois cas, le facteur principal responsable de la sécheresse vaginale est une diminution de la production d'oestrogènes et, dans ce cas, on parle également de vaginite atrophique. D'autres facteurs peuvent également être à l'origine de cette problématique comme par exemple le stress ou l'anxiété, la prise d'alcool, de tabac ou de drogues, voire de certains médicaments (par exemple les médicaments ou les hormones utilisés dans le traitement du cancer du sein, de l'endométriose, des fibroïdes ou de l'infertilité). La chirurgie relative au retrait des ovaires mais aussi la prise d'un moyen contraceptif constituent également des facteurs responsables de la sécheresse vaginale. Dans le cas d'une sécheresse vaginale, le tissu vaginal se rétrécit et devient plus mince ce qui se manifeste essentiellement par un manque d'hydratation du vagin et une inflammation de ce dernier. Une telle inflammation provoque d'autres symptômes secondaires comme une rougeur au niveau des organes génitaux externes, des démangeaisons, des irritations et/ou des inflammations locales, une sensation de brûlure (surtout lorsqu'on urine) et des rapports sexuels douloureux et sanguinolents dus à des micro-blessures.
Plus particulièrement, il est reconnu que la sécheresse vaginale donne inévitablement lieu à des complications opportunistes d'ordre secondaires (problématiques opportunistes secondaires) dont les quatre principales sont (1) des inflammations et des infections notamment responsables d'irritations, de démangeaisons et de sensations de brûlures avec des risques de surinfections (vaginose, vaginite, ...), (2) l'apparition de lésions des muqueuses et de l'épithélium vaginaux (micro-trauma à l'origine de fissures, de plaies tissulaires et de micro-blessures), (3) une modification significative du pH de l'environnement vaginal et (4) une perturbation importante de la flore bactérienne propre à l'environnement vaginal. We talk about vaginal dryness when the vaginal tissue is no longer well lubricated and healthy. This problem can affect all women but is found more particularly in those who are menopausal, pregnant or in young mothers. In these three cases, the main factor responsible for vaginal dryness is a decrease in estrogen production and, in this case, we also speak of atrophic vaginitis. Other factors may also be at the origin of this problem, such as stress or anxiety, taking alcohol, tobacco or drugs, or even certain medications (eg drugs or hormones used in treatment of breast cancer, endometriosis, fibroids or infertility). Surgery for removal of the ovaries but also for contraception are also factors responsible for vaginal dryness. In the case of a vaginal dryness, the vaginal tissue shrinks and becomes thinner which is essentially manifested by a lack of hydration of the vagina and inflammation of the vagina. Such inflammation causes other secondary symptoms such as redness of the external genitalia, itching, irritation and / or local inflammation, burning sensation (especially when urinating) and painful and bloody intercourse. to micro-injuries. More particularly, it is recognized that vaginal dryness inevitably gives rise to secondary opportunistic complications (secondary opportunistic problems), the four main ones being (1) inflammations and infections notably responsible for irritations, itching and sensations. of burns with risks of secondary infections (vaginosis, vaginitis, ...), (2) the appearance of lesions of the vaginal mucous membranes and epithelium (micro-trauma causing cracks, tissue wounds and micro -injury), (3) a significant change in the pH of the vaginal environment, and (4) a significant disturbance of the bacterial flora specific to the vaginal environment.
Notons ici qu'il est largement démontré que la flore bactérienne vaginale, essentiellement composée de bactéries de type Lactobacilles, constitue une véritable barrière face aux infections vaginales. Toutefois, il est également largement reconnu que de nombreux facteurs, outre une sécheresse vaginale, peuvent contribuer à un déséquilibre rapide de cette flore bactérienne. A titre d'exemples, les moyens de contraception, une prise d'antibiotiques, une hygiène intime excessive ou au contraire négligée ou encore le port de vêtements trop serrés peuvent être à l'origine d'un véritable déséquilibre de la flore bactérienne vaginale. Fréquemment, suite à un déséquilibre de la flore bactérienne vaginale, apparaissent d'ailleurs des mycoses vaginales et/ou des vaginoses d'origine bactériennes, par exemple causée par le pathogène Candida albicans. It should be noted here that it is widely demonstrated that the vaginal bacterial flora, essentially composed of Lactobacillus-type bacteria, constitutes a real barrier to vaginal infections. However, it is also widely recognized that many factors, besides vaginal dryness, can contribute to a rapid imbalance of this bacterial flora. By way of example, the means of contraception, antibiotic intake, excessive or neglected personal hygiene or the wearing of tight clothing may cause a real imbalance of the vaginal bacterial flora. Frequently, following an imbalance of the vaginal bacterial flora, vaginal mycoses and / or vaginoses of bacterial origin appear, for example caused by the pathogen Candida albicans.
Comme indiqué plus haut, afin de traiter une sécheresse vaginale problématique, il est actuellement proposé de recourir à l'utilisation de lubrifiant et à l'utilisation de composés présentant des propriétés leur permettant de protéger l'épithélium vaginal afin de prévenir l'apparition des plaies et de fissures mais aussi afin de traiter ces dernières. Par exemple, i! existe des gels lubrifiants contenant de l'acide hyaluronique pour simultanément humidifier (réhydrater) l'environnement
vaginal et protéger l'épithélium vaginal (formation d'un film protecteur sur l'épithélium vaginal). As mentioned above, in order to treat a problematic vaginal dryness, it is presently proposed to use the use of lubricant and the use of compounds with properties to protect the vaginal epithelium to prevent the appearance of wounds and cracks but also in order to treat these. For example, i! lubricating gels containing hyaluronic acid are available to simultaneously moisten (rehydrate) the environment vaginal and protect the vaginal epithelium (formation of a protective film on the vaginal epithelium).
Il ressort de ceci qu'une sécheresse vaginale, essentiellement observée chez les femmes ménopausées (mais pas exclusivement) constitue une problématique primaire dont découle des problématiques secondaires, à savoir des inflammations et des infections, une apparition de lésions des muqueuses et de l'épithélium vaginaux, une modification significative du pH de l'environnement vaginal et une perturbation importante de la flore bactérienne propre à l'environnement vaginal, ces problématiques primaire et secondaires se rencontrant donc généralement simultanément. It follows from this that vaginal dryness, mainly observed in postmenopausal women (but not exclusively), is a primary problem that stems from secondary problems, namely inflammations and infections, the appearance of lesions of the mucous membranes and the epithelium. vaginal, a significant change in the pH of the vaginal environment and a significant disturbance of bacterial flora specific to the vaginal environment, these primary and secondary problems therefore meeting generally simultaneously.
Malheureusement, actuellement, lorsque les problématiques primaire et secondaires sont rencontrées simultanément, plusieurs traitements distincts doivent être suivis, chaque traitement traitant soit la problématique primaire elle-même, soit une seule des problématiques secondaires mais certainement pas plusieurs à la fois. En ce sens, si les problématiques rencontrées simultanément sont (1) une sécheresse vaginale (problématique primaire) et (2) une perturbation de la flore bactérienne propre à l'environnement vaginal (problématique secondaire), il convient d'une part de restaurer/rééquilibrer la flore bactérienne vaginale et, d'autre part, d'hydrater/réhydrater les muqueuses et l'épithélium vaginaux. A cette fin, actuellement la solution proposée est d'appliquer d'une part des probiotiques dans l'environnement vaginal (par l'intermédiaire par exemple de suppositoires ou de comprimés, comprenant des probiotiques) (traitement de la problématique secondaire) et, d'autre part, d'appliquer des formulations lubrifiantes et/ou hydratantes (traitement de la problématique primaire). Unfortunately, currently, when primary and secondary problems are encountered simultaneously, several distinct treatments must be followed, each treatment dealing with the primary problematic itself, or only one of the secondary problems but certainly not several at the same time. In this sense, if the problems encountered simultaneously are (1) a vaginal dryness (primary problem) and (2) a disturbance of the bacterial flora specific to the vaginal environment (secondary problem), it is necessary on the one hand to restore / rebalance the vaginal bacterial flora and, on the other hand, to moisturize / rehydrate the vaginal mucosa and epithelium. To this end, currently the solution proposed is to apply on the one hand probiotics in the vaginal environment (for example through suppositories or tablets, including probiotics) (treatment of the secondary problem) and, on the other hand, to apply lubricating and / or moisturizing formulations (treatment of the primary problem).
Les femmes concernées par ces problématiques primaire et secondaires rencontrées simultanément doivent donc se soumettre à deux traitements distincts, ce qui est particulièrement contraignant puisqu'il faut procéder à deux applications de deux produits différents, parfois en ayant
à respecter des temps d'attente entre chacune des applications de chacun des produits. Bien entendu, actuellement, si d'autres complications secondaires liées à une sécheresse vaginale sont rencontrées, il est hautement probable qu'un traitement additionnel soit nécessaire, ceci complexïfïant plus encore le traitement à mettre en place. The women concerned by these primary and secondary problems encountered simultaneously must therefore submit to two separate treatments, which is particularly restrictive since it is necessary to make two applications of two different products, sometimes having to meet waiting times between each of the applications of each of the products. Of course, currently, if other secondary complications associated with vaginal dryness are encountered, it is highly likely that additional treatment is required, further complicating the treatment to be performed.
L'invention a pour but de pallier les inconvénients de l'état de la technique en procurant une invention permettant de se dispenser d'un tel traitement particulièrement contraignant et nécessitant de disposer de plusieurs produits distincts, chacun de ces produits étant prévu pour traiter indépendamment une problématique donnée, c'est-à-dire soit la problématique de sécheresse vaginale elle-même, soit des inflammations et des infections, soit des lésions des muqueuses et de l'épithélium vaginaux, soit une modification significative du pH de l'environnement vaginal, soit une perturbation importante de la flore bactérienne propre à l'environnement vaginal. En d'autres termes, l'invention a pour but de proposer un produit permettant, en une seule et unique application, un traitement simultané de la problématique primaire (sécheresse vaginale) et d'au moins une voire de l'ensemble des problématiques secondaires en découlant et apparaissant simultanément. The object of the invention is to overcome the drawbacks of the state of the art by providing an invention making it possible to dispense with such a particularly restrictive treatment and requiring the use of several different products, each of these products being designed to process independently a given problem, that is to say either the problem of vaginal dryness itself, or inflammations and infections, lesions of the vaginal mucosa and epithelium, or a significant change in the pH of the environment vaginal, a major disturbance of the bacterial flora specific to the vaginal environment. In other words, the object of the invention is to propose a product that makes it possible, in a single application, to simultaneously treat the primary problem (vaginal dryness) and at least one or even all of the secondary problems. arising from it and appearing simultaneously.
L'invention a pour objet de procurer un produit permettant de traiter en même temps, c'est-à-dire grâce à une seule application, tant la problématique primaire de sécheresse vaginale qu'au moins une des quatre problématiques opportunistes secondaires mentionnées plus haut. L'invention a donc pour objet de traiter et/ou d'éviter les problématiques opportunistes secondaires en même temps que la sécheresse vaginale. Le produit selon l'invention permet donc de réaliser un traitement prophylactique et/ou curatif. The object of the invention is to provide a product which makes it possible to treat at the same time, that is to say, thanks to a single application, both the primary problematic of vaginal dryness and at least one of the four secondary opportunistic problems mentioned above. . The invention therefore aims to treat and / or avoid secondary opportunistic problems at the same time as vaginal dryness. The product according to the invention thus makes it possible to carry out a prophylactic and / or curative treatment.
Pour résoudre ce problème, il est prévu suivant l'invention, un produit tel qu'indiqué au début, ledit produit comprenant : To solve this problem, there is provided according to the invention, a product as indicated at the beginning, said product comprising:
- une première phase sous forme d'un hydrogel, et a first phase in the form of a hydrogel, and
- une deuxième phase lipidique incluant au moins un probiotique.
Notons qu'il est connu d'appliquer des probiotiques dans l'environnement vaginal par l'intermédiaire par exemple de suppositoires, de comprimés ou encore de crèmes comprenant des probiotiques. Les objectifs poursuivis par de telles applications de probiotiques (en particulier les probiotiques spécifiques au milieu vaginal comme par exemple Lactobacillus crispatus, L. gasseri, L. iners, L. jensenii et L. vaginalis) sont multiples mais sont essentiellement réalisés d'une part afin de corriger ou de rétablir le pH vaginal et, d'autre part, pour recoloniser la flore bactérienne vaginale. Une recolonisation bactérienne permet d'assurer le maintien d'un pH vaginal adéquat et assure surtout une protection de l'environnement vaginal face à divers pathogènes responsables d'infections. a second lipid phase including at least one probiotic. Note that it is known to apply probiotics in the vaginal environment through for example suppositories, tablets or creams including probiotics. The objectives pursued by such applications of probiotics (in particular probiotics specific to the vaginal environment, for example Lactobacillus crispatus, L. gasseri, L. iners, L. jensenii and L. vaginalis) are multiple but are essentially made on the one hand to correct or restore the vaginal pH and to recolonize the vaginal bacterial flora. Bacterial recolonization ensures the maintenance of an adequate vaginal pH and ensures above all a protection of the vaginal environment against various pathogens responsible for infections.
Selon la présente invention, lorsque la problématique primaire est une sécheresse vaginale et que la problématique secondaire est une perturbation de la flore bactérienne vaginale, un tel produit bi- phasique, comprenant une première phase sous forme d'un hydrogel et une deuxième phase lipidique incluant au moins un probiotique permet de ne procéder qu'à une seule application permettant d'appliquer simultanément et en une seule manipulation un hydrogel et au moins un probiotique, le produit ainsi appliqué permettant notamment de restaurer le milieu vaginal naturel. Il n'est donc plus nécessaire de procéder à deux applications distinctes de deux produits différents conditionnés dans des contenants différents. Un traitement combiné, en une seule étape permet donc de traiter simultanément la sécheresse vaginale et au moins de restaurer/corriger la flore bactérienne vaginale, ce que les produits actuels ne propose pas puisque les dispositifs et formes d'application actuels comportent uniquement un hydrogel ou uniquement une formulation comprenant des probiotiques. Avec un produit selon l'invention, il est donc possible de traiter simultanément la problématique primaire (sécheresse vaginale) et au moins une et de préférence au moins l'ensemble des quatre problématiques (complications) opportunistes secondaires
mentionnées plus haut. Il en résulte donc un traitement combiné et simplifié de l'ensemble des problématiques rencontrées simultanément à une sécheresse vaginale. According to the present invention, when the primary problem is a vaginal dryness and the secondary problem is a disturbance of the vaginal bacterial flora, such a bi-phasic product, comprising a first phase in the form of a hydrogel and a second lipid phase including at least one probiotic makes it possible to carry out only one application making it possible to apply simultaneously and in a single manipulation a hydrogel and at least one probiotic, the product thus applied making it possible in particular to restore the natural vaginal environment. It is therefore no longer necessary to make two separate applications of two different products packaged in different containers. Combined treatment, in one step, allows simultaneous treatment of vaginal dryness and at least restoring / correcting vaginal bacterial flora, which current products do not propose since current devices and application forms only include a hydrogel or only a formulation comprising probiotics. With a product according to the invention, it is therefore possible to simultaneously treat the primary problem (vaginal dryness) and at least one and preferably at least all of the four secondary opportunistic problems (complications). mentioned above. This results in a combined and simplified treatment of all the problems encountered simultaneously with vaginal dryness.
De façon surprenante, il a été démontré, dans le cadre de la présente invention, qu'une première phase sous forme d'un hydrogel, c'est-à-dire qu'une première phase essentiellement aqueuse (environnement hydrophile contenant jusqu'à 90% d'eau voire plus), peut coexister avec une deuxième phase lipidique comprenant des probiotiques, ceci en assurant que le taux de survie de ces derniers ne soit pas diminué. Ceci était particulièrement inattendu du fait de la présence d'une phase aqueuse voisine et véritablement accolée à la deuxième phase lipidique contenant les probiotiques de telle façon à former un produit bi-phasique. En effet, dès lors que les probiotiques sont particulièrement sensibles à la présence d'eau et qu'ils sont même tout simplement désactivés ou tués en présence d'eau, il n'était pas attendu que, même s'ils sont présents dans une phase lipidique, leur taux de survie ne soit pas réduit dans un produit bi-phasique selon l'invention dans lequel la phase aqueuse (l'hydrogel) est pourtant majoritaire (jusqu'à 95% du produit en volume). Surprisingly, it has been demonstrated in the context of the present invention that a first phase in the form of a hydrogel, that is to say a first substantially aqueous phase (hydrophilic environment containing up to 90% water or more), can coexist with a second lipid phase comprising probiotics, this ensuring that the survival rate of the latter is not decreased. This was particularly unexpected because of the presence of a neighboring aqueous phase and truly contiguous to the second lipid phase containing the probiotics so as to form a bi-phasic product. Indeed, since probiotics are particularly sensitive to the presence of water and they are even simply deactivated or killed in the presence of water, it was not expected that, even if they are present in a lipid phase, their survival rate is not reduced in a bi-phasic product according to the invention in which the aqueous phase (the hydrogel) is nevertheless the majority (up to 95% of the product by volume).
Plus spécifiquement, dans le cadre de la présente invention, il a été déterminé qu'une séparation (une interface) nette s'établit entre les deux phases (l'une aqueuse et l'autre lipidique), cette séparation étant stable et durable au cours du temps et faisant en sorte que les deux phases soient non miscibles. Outre le fait d'assurer un taux de survie élevé des probiotiques dans le produit bi-phasique, une telle séparation nette, stable et durable au cours du temps (au-delà d'un an voire de deux ans) a pour avantage de pouvoir permettre une manipulation de la composition préalablement conditionnée dans un contenant sans avoir à prendre de précautions excessives que ce soit pendant le stockage ou durant le transport. En effet, avec un produit suivant l'invention, la séparation s'établissant entre les deux phases selon l'invention est telle qu'elle résiste
aux mouvements du contenant et aux chocs que ce dernier peut subir. Par exemple, il a été déterminé, dans le cadre de la présente invention, qu'une chute ou qu'une agitation d'un produit bi-phasique suivant l'invention contenu par exemple dans un applicateur vaginal, n'entraine pas un mélange de la première et de la deuxième phases. Par conséquent, les probiotiques restent isolés de la première phase sous forme d'un hydrogel, ce qui permet d'en garantir un taux de survie élevé au cours du temps. More specifically, in the context of the present invention, it has been determined that a clear separation (interface) is established between the two phases (one aqueous and the other lipidic), this separation being stable and long lasting. over time and that the two phases are immiscible. In addition to ensuring a high survival rate of probiotics in the bi-phasic product, such a clear, stable and lasting separation over time (beyond one or even two years) has the advantage of being able to allow manipulation of the composition previously packaged in a container without having to take excessive precautions whether during storage or during transport. Indeed, with a product according to the invention, the separation being established between the two phases according to the invention is such that it resists the movements of the container and the shocks that the latter may suffer. For example, it has been determined, in the context of the present invention, that a fall or agitation of a bi-phasic product according to the invention contained for example in a vaginal applicator, does not cause a mixture first and second phases. As a result, the probiotics remain isolated from the first phase in the form of a hydrogel, which makes it possible to guarantee a high survival rate over time.
Par les termes « interface » ou « séparation », on entend, au sens de la présente invention, une séparation, une interface ou encore une barrière qui s'établit naturellement entre deux phases, en l'occurrence entre une phase aqueuse (hydrogel) et une phase lipidique (comprenant des probiotiques). Il ne s'agit donc pas d'une séparation physique matérielle (par exemple une membrane imperméable) ni d'une séparation assurée par une phase additionnelle. For the purposes of the present invention, the terms "interface" or "separation" mean a separation, an interface or a barrier which is established naturally between two phases, in this case between an aqueous phase (hydrogel) and a lipid phase (including probiotics). It is not therefore a physical physical separation (for example an impermeable membrane) or a separation provided by an additional phase.
Avantageusement, ladite première phase sous forme d'un hydrogel et ladite deuxième phase lipidique incluant au moins un probiotique d'un produit selon l'invention constituent respectivement 90 à 95% et 5 à 10% en volume par rapport au volume total dudit produit. Advantageously, said first phase in the form of a hydrogel and said second lipid phase including at least one probiotic of a product according to the invention constitute respectively 90 to 95% and 5 to 10% by volume relative to the total volume of said product.
De préférence, ladite première phase sous forme d'un hydrogel d'un produit selon l'invention comprend une composante liquide et une composante solide, ladite composante liquide étant de l'eau et ladite composante solide étant choisie dans le groupe constitué de l'alcool polyvinylique, du polyacrylate de sodium, de l'agarose, de la méthylcellulose, de l'hyaluronane, des polymères et des copolymères naturels ou de synthèse, et de leurs mélanges. Preferably, said first phase in the form of a hydrogel of a product according to the invention comprises a liquid component and a solid component, said liquid component being water and said solid component being chosen from the group consisting of polyvinyl alcohol, sodium polyacrylate, agarose, methylcellulose, hyaluronan, natural or synthetic polymers and copolymers, and mixtures thereof.
Préférentiellement, ladite deuxième phase lipidique incluant au moins un probiotique d'un produit selon l'invention est constituée d'au moins un corps gras hydrophobe choisi dans le groupe constitué de la glycérine, de la paraffine, du glycérol, , des acides gras saturés comme l'huile de coco, l'huile de cacao, l'huile de palme ou la cire d'abeille, et de leurs mélanges. De tels corps gras et leurs mélanges ont été défini comme
permettant de former une phase lipidique adéquate permettant d'assurer la survie des probiotiques dans la phase lipidique et de les maintenir sous une forme dispersée dans cette phase lipidique. Ces corps gras ont également été identifiés comme permettant une formation d'une interface (séparation) nette, stable et durable au cours du temps entre la phase sous forme d'un hydrogel et la phase lipidique. Preferably, said second lipid phase including at least one probiotic of a product according to the invention consists of at least one hydrophobic fatty substance selected from the group consisting of glycerine, paraffin, glycerol, saturated fatty acids. such as coconut oil, cocoa oil, palm oil or beeswax, and their blends. Such fats and their mixtures have been defined as to form an adequate lipid phase to ensure the survival of probiotics in the lipid phase and maintain them in a dispersed form in this lipid phase. These fatty substances have also been identified as enabling a clear, stable and durable interface formation (separation) over time between the hydrogel phase and the lipid phase.
De préférence, ladite deuxième phase lipidique incluant au moins un probiotique selon l'invention présente une limite d'élasticité mesurée à l'aide d'un CSL2 (Controlled Stress Rheometer - TA Instruments Inc) comprise entre 250 et 750 Pa, de préférence une limite d'élasticité comprise entre 400 et 500 Pa, préférentiellement une limite d'élasticité égale à 450 Pa. La limite d'élasticité est la contrainte à partir de laquelle un matériau arrête de se déformer d'une manière élastique, réversible et commence donc à se déformer de manière irréversible. Il a été déterminé qu'une telle limite d'élasticité (« yield point » ou « yield strength ») de la phase lipidique permet d'assurer que l'interface (la séparation) entre les deux phases (hydrogel vs phase lipidique) soit stable, durable et nette, ce qui permet d'assurer une survie des probiotiques dans la phase lipidique où ils sont dispersés. Preferably, said second lipid phase including at least one probiotic according to the invention has a yield strength measured using a CSL 2 (Controlled Stress Rheometer - TA Instruments Inc.) of between 250 and 750 Pa, preferably a yield strength of between 400 and 500 Pa, preferably a yield strength of 450 Pa. The elastic limit is the stress from which a material stops deforming elastically, reversibly and starts therefore to deform irreversibly. It has been determined that such a yield point or yield strength of the lipid phase makes it possible to ensure that the interface (separation) between the two phases (hydrogel vs lipid phase) is stable, durable and clean, which ensures survival probiotics in the lipid phase where they are dispersed.
Préférentiellement, ladite deuxième phase lipidique incluant au moins un probiotique selon l'invention présente un facteur de perte ou facteur d'amortissement mesuré par rhéométrie oscillatoire en utilisant un rhéomètre rotationnel en mode oscillant (ARES-G2, TA Instruments Inc) compris entre 0,11 et 0,15, de préférence un facteur de perte ou facteur d'amortissement égal à 0,12. Le facteur de perte ou facteur d'amortissement d'un matériau est calculé comme étant le rapport entre l'énergie de déformation perdue et l'énergie de déformation stockée. Ce facteur est un indicateur du rapport entre la viscosité et l'élasticité lors d'une déformation viscoélastique. Il a été déterminé qu'un tel facteur de perte ou facteur d'amortissement (« loss factor » ou « damping factor ») de la phase lipidique permet d'assurer que l'interface (la séparation) entre les
préférence à raison d'au moins 106 CFU dans ledit produit, préférentiellement à raison de 108 CFU dans ledit produit et plus préférentiellement à raison de 109 CFU dans ledit produit. Preferably, said second lipid phase including at least one probiotic according to the invention has a loss factor or damping factor measured by oscillatory rheometry using an oscillation-mode rotational rheometer (ARES-G2, TA Instruments Inc) between 0, 11 and 0.15, preferably a loss factor or damping factor equal to 0.12. The loss factor or damping factor of a material is calculated as the ratio of the lost strain energy to the stored strain energy. This factor is an indicator of the relationship between viscosity and elasticity during viscoelastic deformation. It has been determined that such a loss factor or "damping factor" of the lipid phase ensures that the interface (separation) between the preferably at least 10 6 CFU in said product, preferably at 10 8 CFU in said product and more preferably at 10 9 CFU in said product.
L'invention a aussi pour objet un produit suivant l'invention comprenant une première phase sous forme d'un hydrogel et une deuxième phase lipidique incluant au moins un probiotique, ledit produit étant destiné à être utilisé dans le traitement de la sécheresse vaginale et/ou de la vaginite et/ou de la vaginose et/ou de la candidose vaginale et/ou d'une perturbation du pH vaginal et/ou d'une modification de la flore bactérienne vaginale. The subject of the invention is also a product according to the invention comprising a first phase in the form of a hydrogel and a second lipid phase including at least one probiotic, said product being intended for use in the treatment of vaginal dryness and / or or vaginitis and / or vaginosis and / or vaginal candidiasis and / or disturbance of vaginal pH and / or a change in vaginal bacterial flora.
D'autres formes de réalisation et d'utilisation du produit suivant l'invention sont indiquées dans les revendications annexées. Other embodiments and use of the product according to the invention are indicated in the appended claims.
La présente invention porte également sur un applicateur pour une application vaginale, ledit applicateur comprenant un produit selon l'invention, c'est-à-dire un produit comprenant une première phase sous forme d'un hydrogel et une deuxième phase lipidique incluant au moins un probiotique. The present invention also relates to an applicator for vaginal application, said applicator comprising a product according to the invention, that is to say a product comprising a first phase in the form of a hydrogel and a second lipid phase including at least a probiotic.
Avantageusement, selon l'invention, ledit applicateur est un applicateur à usage unique de type seringue ou de type canule ou de tout autre type permettant de réaliser une application vaginale. Advantageously, according to the invention, said applicator is a disposable applicator of the syringe type or of the cannula type or of any other type making it possible to perform a vaginal application.
D'autres formes de réalisation d'un applicateur suivant l'invention sont indiquées dans les revendications annexées. Other embodiments of an applicator according to the invention are indicated in the appended claims.
La présente invention concerne également une utilisation d'un applicateur suivant l'invention pour le traitement de la sécheresse vaginale et/ou de la vaginite et/ou de la vaginose et/ou de la candidose vaginale et/ou d'une perturbation du pH vaginal et/ou d'une modification de la flore bactérienne vaginale. The present invention also relates to a use of an applicator according to the invention for the treatment of vaginal dryness and / or vaginitis and / or vaginosis and / or vaginal candidiasis and / or a disturbance of the pH vaginal and / or modification of the vaginal bacterial flora.
D'autres formes d'utilisation d'un applicateur suivant l'invention sont indiquées dans les revendications annexées.
D'autres caractéristiques, détails et avantages de l'invention ressortiront de fa description donnée ci-après, à titre non limitatif et en faisant référence au dessin annexé. Other forms of use of an applicator according to the invention are indicated in the appended claims. Other features, details and advantages of the invention will emerge from the description given below, without limitation and with reference to the accompanying drawing.
La figure 1 est une vue schématique d'un applicateur selon l'invention qui comprend un produit bi-phasique suivant l'invention. Figure 1 is a schematic view of an applicator according to the invention which comprises a bi-phasic product according to the invention.
A la figure 1 , l'applicateur 1 se compose d'un réservoir 2 rempli d'air relié à un corps longitudinal 4 dont une extrémité est fermée par un moyen de fermeture 3 amovible. Dans le corps longitudinal 4 sont présentes une première phase 6 sous forme d'un hydrogel remplissant environ 95% du volume de l'applicateur 1 et une deuxième phase lipidique 5 incluant au moins un probiotique. La première phase 6 sous forme d'un hydrogel contient au moins 90% d'eau et la deuxième phase 5 présente une limite d'élasticité comprise entre 250 et 750 Pa. Une séparation ou interface 7 s'établit entre la première phase 6 sous forme d'un hydrogel et la deuxième phase 5 de telle sorte que cette interface 7 est stable, durable et résistante au mouvement (agitation ou chute de l'applicateur 1 par exemple). Cette interface 7 permet d'assurer que les probiotiques inclus dans la deuxième phase lipidique 5 sont protégés de l'eau contenue dans la première phase 6 sous forme d'un hydrogel. Ceci permet d'assurer un taux de survie élevé des probiotiques inclus dans la deuxième phase lipidique 5. Une telle séparation ou interface 7 avec de telles propriétés est essentiellement due aux propriétés que présente la deuxième phase lipidique 5. Lorsque le moyen de fermeture 3 amovible est retiré, une ouverture 8 de l'applicateur 1 permet une sortie des première phase 6 et deuxième phase 5 contenues dans l'applicateur 1 , ceci grâce à une poussée de ces dernières par l'air contenu dans le réservoir 2 qui doit être pressé par un utilisateur.
Exemples In Figure 1, the applicator 1 consists of a tank 2 filled with air connected to a longitudinal body 4, one end is closed by a removable closure means 3. In the longitudinal body 4 are present a first phase 6 in the form of a hydrogel filling about 95% of the volume of the applicator 1 and a second lipid phase 5 including at least one probiotic. The first phase 6 in the form of a hydrogel contains at least 90% water and the second phase 5 has a yield strength of between 250 and 750 Pa. A separation or interface 7 is established between the first phase 6 under form of a hydrogel and the second phase 5 such that this interface 7 is stable, durable and resistant to movement (agitation or fall of the applicator 1 for example). This interface 7 makes it possible to ensure that the probiotics included in the second lipid phase 5 are protected from the water contained in the first phase 6 in the form of a hydrogel. This makes it possible to ensure a high survival rate of the probiotics included in the second lipid phase 5. Such a separation or interface 7 with such properties is essentially due to the properties of the second lipid phase 5. When the removable closure means 3 is removed, an opening 8 of the applicator 1 allows an output of the first phase 6 and second phase 5 contained in the applicator 1, this through a thrust of the latter by the air contained in the tank 2 to be pressed by a user. Examples
Exemple 1 : produit pour une application vaginale selon ['invention Un produit bi-phasique pour une application vaginale selon l'invention a été obtenu comme suit : a) préparation de la première phase d'un produit selon l'invention sous forme d'un hydroqel EXAMPLE 1 Product for Vaginal Application According to the Invention A bi-phasic product for vaginal application according to the invention was obtained as follows: a) preparation of the first phase of a product according to the invention in the form of a hydroqel
La première phase sous forme d'un hydrogel a été préparée en mélangeant les différents composants de grade pharmaceutique selon les quantités reprises au tableau 1 ci-dessous. Tableau 1 The first phase in the form of a hydrogel was prepared by mixing the various pharmaceutical grade components according to the amounts shown in Table 1 below. Table 1
MCT = médium chain triglycérides MCT = medium chain triglycerides
EP = European Pharmacopeia EP = European Pharmacopeia
NF= National Formulary NF = National Formulary
Plus particulièrement, la cire d'abeilles, le dibéhénate de glycérol et rtïmïx® ont été mélangés dans l'huile MCT à une température de 75°C sous agitation (80 RPM) jusqu'à dissolution complète. Le mélange ainsi obtenu a été homogénéisé avant de réaliser une étape de refroidissement dans une cuve jusqu'à une température de l'ordre de 15 à 20°C sous agitation constante (60 RPM) et sous vide pour effectuer un dégazage. Ensuite de l'azote sous formes de petites bulles a été introduit par le bas de la cuve durant 10 min jusqu'à atteindre la Patm. avant de respecter une période de repos de 2 h à température ambiante. Une poudre de probiotiques (dont L. crispatus) revêtus d'un coating gras (mix huile de palme et huile de coco hydrogénées) a été introduite dans la cuve sous faible agitation (10 RPM) et, éventuellement, une homogénéisation a été effectuée. La composition finale obtenue a été stockée à température ambiante dans un contenant fermé.
c) Mise en place du produit dans un applicateur vaginal More particularly, beeswax, glycerol dibehenate, and the like were mixed in MCT oil at a temperature of 75 ° C with stirring (80 RPM) until complete dissolution. The mixture thus obtained was homogenized before performing a cooling step in a tank to a temperature of the order of 15 to 20 ° C with constant stirring (60 RPM) and under vacuum to perform a degassing. Then nitrogen in the form of small bubbles was introduced from the bottom of the tank for 10 minutes until reaching the Patm. before observing a rest period of 2 hours at room temperature. A probiotic powder (including L. crispatus) coated with a fatty coating (mixed palm oil and coconut oil hydrogenated) was introduced into the tank with gentle agitation (10 RPM) and possibly homogenization was carried out. The final composition obtained was stored at room temperature in a closed container. c) Placement of the product in a vaginal applicator
Suite à l'obtention de chacune des phases d'un produit selon l'invention comme décrit sous les points a) et b) ci-dessus, un applicateur vaginal formé selon le procédé Blow-Fill-Seal (BFS) a été rempli en y injectant de façon séquentielle (successive) ou simultanée chacune des deux phases d'un produit selon l'invention. Following obtaining each of the phases of a product according to the invention as described under points a) and b) above, a vaginal applicator formed according to the Blow-Fill-Seal (BFS) method was filled in. injecting sequentially (sequentially) or simultaneously each of the two phases of a product according to the invention.
Exemple 2 : produit pour une application vaginale selon l'invention Example 2 Product for a Vaginal Application According to the Invention
Un produit bi-phasique pour une application vaginale selon l'invention a été obtenu comme suit : a) préparation de la première phase d'un produit selon l'invention sous forme d'un hvdroqel A bi-phasic product for vaginal application according to the invention was obtained as follows: a) preparation of the first phase of a product according to the invention in the form of a hydrogel
La première phase sous forme d'un hydrogel a été préparée comme indiqué à l'exemple 1. b) préparation de la deuxième phase lipidique d'un produit selon l'invention incluant au moins un probiotique The first phase in the form of a hydrogel was prepared as indicated in Example 1. b) Preparation of the second lipid phase of a product according to the invention including at least one probiotic
La deuxième phase lipidique incluant au moins un probiotique a été obtenue en mélangeant les différents composants selon les quantités reprises au tableau 3 ci-dessous. The second lipid phase including at least one probiotic was obtained by mixing the various components according to the amounts shown in Table 3 below.
Tableau 3 Table 3
Composant Fonction Quantité par 100 g Grade/type Component Function Quantity per 100 g Grade / type
Huile de phase huileuse 85 g EP Oil phase oil 85 g EP
paraffine paraffin
Huile de palme épaississant 3,5 g EP
hydrogénée Thickening palm oil 3.5 g EP hydrogenated
Dibéhénate de gélifiant 4,5 g EP/NF glycérol Dibenenate gelling 4.5 g EP / NF glycerol
Ertimix® épaississant 2 g cosmétique Ertimix® thickener 2g cosmetic
Poudre probiotiques 5 g Probiotic powder 5 g
probiotiques probiotics
EP = Européen Pharmacopeia EP = European Pharmacopeia
NF= National Formulary NF = National Formulary
Plus particulièrement, l'huile de palme hydrogénée, le dibéhénate de glycérol et l'Ertimix® ont été mélangés dans l'huile de paraffine à une température de 75°C sous agitation (80 RPM) jusqu'à dissolution complète. Le mélange ainsi obtenu a été homogénéisé avant de réaliser une étape de refroidissement dans une cuve jusqu'à une température de l'ordre de 15 à 20°C sous agitation constante (60 RPM) et sous vide pour effectuer un dégazage. Ensuite de l'azote sous formes de petites bulles a été introduit par le bas de la cuve durant 10 min jusqu'à atteindre la Patm. avant de respecter une période de repos de 2 h à température ambiante. Une poudre de probiotiques (dont L. crispatus) revêtus d'un coating gras (mix huile de palme et huile de coco hydrogénées) a été introduite dans la cuve sous faible agitation (10 RPM) et, éventuellement, une homogénéisation a été effectuée. La composition finale obtenue a été stockée à température ambiante dans un contenant fermé. c) Mise en place du produit dans un applicateur vaginal More particularly, hydrogenated palm oil, glycerol dibehenate and Ertimix® were mixed in paraffin oil at a temperature of 75 ° C with stirring (80 RPM) until complete dissolution. The mixture thus obtained was homogenized before performing a cooling step in a tank to a temperature of the order of 15 to 20 ° C with constant stirring (60 RPM) and under vacuum to perform a degassing. Then nitrogen in the form of small bubbles was introduced from the bottom of the tank for 10 minutes until reaching the Patm. before observing a rest period of 2 hours at room temperature. A probiotic powder (including L. crispatus) coated with a fatty coating (mixed palm oil and coconut oil hydrogenated) was introduced into the tank with gentle agitation (10 RPM) and possibly homogenization was carried out. The final composition obtained was stored at room temperature in a closed container. c) Placement of the product in a vaginal applicator
Suite à l'obtention de chacune des phases d'un produit selon l'invention comme décrit sous les points a) et b) ci-dessus, un applicateur vaginal formé selon le procédé Blow-Fill-Seal (BFS) a été rempli en y
injectant de façon séquentielle (successive) ou simultanée chacune des deux phases d'un produit selon l'invention. Following obtaining each of the phases of a product according to the invention as described under points a) and b) above, a vaginal applicator formed according to the Blow-Fill-Seal (BFS) method was filled in. there sequentially (sequentially) or simultaneously injecting each of the two phases of a product according to the invention.
Il est bien entendu que la présente invention n'est en aucune façon limitée aux formes de réalisations décrites ci-dessus et que bien des modifications peuvent y être apportées sans sortir du cadre des revendications annexées.
It is understood that the present invention is in no way limited to the embodiments described above and that many modifications can be made without departing from the scope of the appended claims.
Claims
1. Produit pour une application vaginale, en particulier produit pour une application vaginale destiné à être utilisé dans le traitement de la sécheresse vaginale, ledit produit comprenant : 1. Product for vaginal application, in particular product for vaginal application intended to be used in the treatment of vaginal dryness, said product comprising:
- une première phase sous forme d'un hydrogel, et - a first phase in the form of a hydrogel, and
- une deuxième phase lipidique incluant au moins un probiotique. - a second lipid phase including at least one probiotic.
2. Produit selon la revendication 1 , caractérisé en ce que ladite première phase sous forme d'un hydrogel et ladite deuxième phase lipidique incluant au moins un probiotique constituent respectivement 90 à 95% et 5 à 10% en volume par rapport au volume total dudit produit. 2. Product according to claim 1, characterized in that said first phase in the form of a hydrogel and said second lipid phase including at least one probiotic constitute respectively 90 to 95% and 5 to 10% by volume relative to the total volume of said product.
3. Produit selon la revendication 1 ou 2, caractérisé en ce que ladite première phase sous forme d'un hydrogel comprend une composante liquide et une composante solide, ladite composante liquide étant de l'eau et ladite composante solide étant choisie dans le groupe constitué de l'alcool polyvinylique, du polyacrylate de sodium, de i'agarose, de la méthylcellulose, de l'hyaluronane, des polymères et des copolymères naturels ou de synthèse, et de leurs mélanges. 3. Product according to claim 1 or 2, characterized in that said first phase in the form of a hydrogel comprises a liquid component and a solid component, said liquid component being water and said solid component being chosen from the group consisting of polyvinyl alcohol, sodium polyacrylate, agarose, methylcellulose, hyaluronan, natural or synthetic polymers and copolymers, and mixtures thereof.
4. Produit selon l'une quelconque des revendications 1 à 3, caractérisé en ce que ladite deuxième phase lipidique incluant au moins un probiotique est constituée d'au moins un corps gras hydrophobe choisi dans le groupe constitué de la glycérine, de la paraffine, du glycéroi, des acides gras saturés comme l'huile de coco, l'huile de cacao, l'huile de palme ou la cire d'abeille, et de leurs mélanges. 4. Product according to any one of claims 1 to 3, characterized in that said second lipid phase including at least one probiotic consists of at least one hydrophobic fatty substance chosen from the group consisting of glycerin, paraffin, glycerol, saturated fatty acids such as coconut oil, cocoa oil, palm oil or beeswax, and mixtures thereof.
5. Produit selon l'une quelconque des revendications 1 à 4, caractérisé en ce que ladite deuxième phase lipidique incluant au moins un probiotique présente une limite d'élasticité comprise entre 250 et 750 Pa, de préférence une limite d'élasticité comprise entre 400 et 500 Pa, préférentiellement une limite d'élasticité égale à 450 Pa.
5. Product according to any one of claims 1 to 4, characterized in that said second lipid phase including at least one probiotic has an elastic limit of between 250 and 750 Pa, preferably an elastic limit of between 400 and 500 Pa, preferably an elastic limit equal to 450 Pa.
6. Produit selon l'une quelconque des revendications 1 à 5, caractérisé en ce que ladite deuxième phase lipidique incluant au moins un probiotique présente un facteur de perte ou facteur d'amortissement compris entre 0,11 et 0,15, de préférence un facteur de perte ou facteur d'amortissement égal à 0,12. 6. Product according to any one of claims 1 to 5, characterized in that said second lipid phase including at least one probiotic has a loss factor or damping factor of between 0.11 and 0.15, preferably a loss factor or damping factor equal to 0.12.
7. Produit selon l'une quelconque des revendications 1 à 6, caractérisé en ce que ladite première phase sous forme d'un hydrogel comprend au moins 90% en poids d'eau. 7. Product according to any one of claims 1 to 6, characterized in that said first phase in the form of a hydrogel comprises at least 90% by weight of water.
8. Produit selon l'une quelconque des revendications 1 à 7, caractérisé en ce que ladite première phase sous forme d'un hydrogel comprend en outre de l'acide hyaluronique en une concentration comprise entre 0,5 et 5% en poids par rapport au poids total de ladite première phase sous forme d'un hydrogel. 8. Product according to any one of claims 1 to 7, characterized in that said first phase in the form of a hydrogel further comprises hyaluronic acid in a concentration of between 0.5 and 5% by weight relative to to the total weight of said first phase in the form of a hydrogel.
9. Produit selon l'une quelconque des revendications 1 à 8, caractérisé en ce que ledit au moins un probiotique inclus dans ladite deuxième phase lipidique est choisi dans le groupe constitué des probiotiques de type Lactobacillus crispatus, L. gasseri, L. iners, L. jensenii, L. vaginalis, L. acidophilus, L. casei, L. casei subv rhamnosus, L. planta rum et de leurs mélanges . 9. Product according to any one of claims 1 to 8, characterized in that said at least one probiotic included in said second lipid phase is chosen from the group consisting of probiotics of the Lactobacillus crispatus, L. gasseri, L. iners type, L. jensenii, L. vaginalis, L. acidophilus, L. casei, L. casei subv rhamnosus, L. planta rum and their mixtures.
0. Produit selon l'une quelconque des revendications 1 à 9, caractérisé en ce que ledit au moins un probiotique est présent à raison d'au moins 104 CFU dans ledit produit, de préférence à raison d'au moins 106 CFU dans ledit produit, préférentiellement à raison de 08 CFU dans ledit produit et plus préférentiellement à raison de 109 CFU dans ledit produit. 0. Product according to any one of claims 1 to 9, characterized in that said at least one probiotic is present in an amount of at least 10 4 CFU in said product, preferably in an amount of at least 10 6 CFU in said product, preferably at a rate of 0 8 CFU in said product and more preferably at a rate of 10 9 CFU in said product.
1 . Produit comprenant une première phase sous forme d'un hydrogel et une deuxième phase lipidique incluant au moins un probiotique selon l'une quelconque des revendications 1 à 10, ledit produit étant destiné à être utilisé dans le traitement de la sécheresse vaginale et/ou de la vaginite et/ou de la vaginose et/ou de la candidose
vaginale et/ou d'une perturbation du pH vaginal et/ou d'une modification de la flore bactérienne vaginale. 1. Product comprising a first phase in the form of a hydrogel and a second lipid phase including at least one probiotic according to any one of claims 1 to 10, said product being intended to be used in the treatment of vaginal dryness and/or vaginitis and/or vaginosis and/or candidiasis vaginal and/or a disturbance of the vaginal pH and/or a modification of the vaginal bacterial flora.
12. Applicateur pour une application vaginale, ledit applicateur comprenant un produit selon l'une quelconque des revendications 1 à 10. 12. Applicator for vaginal application, said applicator comprising a product according to any one of claims 1 to 10.
13. Applicateur selon la revendication 12, caractérisé en ce qu'il est prévu pour un usage unique de type seringue ou de type canule ou de tout autre type permettant de réaliser une application vaginale. 13. Applicator according to claim 12, characterized in that it is intended for single use of syringe type or cannula type or of any other type allowing vaginal application.
14. Utilisation d'un applicateur selon les revendications 12 ou 13 pour le traitement de la sécheresse vaginale et/ou de la vaginite et/ou de la vaginose et/ou de la candidose vaginale et/ou d'une perturbation du pH vaginal et/ou d'une modification de la flore bactérienne vaginale.
14. Use of an applicator according to claims 12 or 13 for the treatment of vaginal dryness and/or vaginitis and/or vaginosis and/or vaginal candidiasis and/or a disturbance in vaginal pH and /or a change in the vaginal bacterial flora.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| BE2016/5484 | 2016-06-28 | ||
| BE20165484A BE1023895B1 (en) | 2016-06-28 | 2016-06-28 | Product for vaginal application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2018002113A1 true WO2018002113A1 (en) | 2018-01-04 |
Family
ID=56549978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2017/065954 WO2018002113A1 (en) | 2016-06-28 | 2017-06-28 | Product for vaginal application |
Country Status (2)
| Country | Link |
|---|---|
| BE (1) | BE1023895B1 (en) |
| WO (1) | WO2018002113A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109674828A (en) * | 2019-02-18 | 2019-04-26 | 深圳汉朔建元健康管理有限公司 | A kind of preparation and preparation method thereof for rebuilding vaginal flora balance |
| WO2020249734A1 (en) * | 2019-06-13 | 2020-12-17 | Lactobio Aps | A gel composition comprising viable microorganisms |
| US11607369B2 (en) | 2017-11-17 | 2023-03-21 | Koska Family Limited | Systems and methods for fluid delivery manifolds |
| USD992110S1 (en) | 2021-08-10 | 2023-07-11 | Koska Family Limited | Sealed fluid container |
| CN117357468A (en) * | 2023-11-27 | 2024-01-09 | 宁波慈溪生物医学工程研究所 | Probiotic gel preparation capable of being stored for long time, and use method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013113767A1 (en) * | 2012-01-31 | 2013-08-08 | Bioclin Bv | Method for administration of a probiotic |
-
2016
- 2016-06-28 BE BE20165484A patent/BE1023895B1/en not_active IP Right Cessation
-
2017
- 2017-06-28 WO PCT/EP2017/065954 patent/WO2018002113A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013113767A1 (en) * | 2012-01-31 | 2013-08-08 | Bioclin Bv | Method for administration of a probiotic |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11607369B2 (en) | 2017-11-17 | 2023-03-21 | Koska Family Limited | Systems and methods for fluid delivery manifolds |
| CN109674828A (en) * | 2019-02-18 | 2019-04-26 | 深圳汉朔建元健康管理有限公司 | A kind of preparation and preparation method thereof for rebuilding vaginal flora balance |
| WO2020249734A1 (en) * | 2019-06-13 | 2020-12-17 | Lactobio Aps | A gel composition comprising viable microorganisms |
| USD992110S1 (en) | 2021-08-10 | 2023-07-11 | Koska Family Limited | Sealed fluid container |
| CN117357468A (en) * | 2023-11-27 | 2024-01-09 | 宁波慈溪生物医学工程研究所 | Probiotic gel preparation capable of being stored for long time, and use method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| BE1023895B1 (en) | 2017-09-06 |
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