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WO2024245585A1 - Formulation topique comprenant une substance déliquescente - Google Patents

Formulation topique comprenant une substance déliquescente Download PDF

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Publication number
WO2024245585A1
WO2024245585A1 PCT/EP2023/082735 EP2023082735W WO2024245585A1 WO 2024245585 A1 WO2024245585 A1 WO 2024245585A1 EP 2023082735 W EP2023082735 W EP 2023082735W WO 2024245585 A1 WO2024245585 A1 WO 2024245585A1
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WO
WIPO (PCT)
Prior art keywords
anhydrous
substance
deliquescent
composition
weight
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
PCT/EP2023/082735
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English (en)
Inventor
Anders Bech Bruntse
Søren Kjærulff
Charlotte VEDEL
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LOreal SA
Original Assignee
LOreal SA
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Filing date
Publication date
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Publication of WO2024245585A1 publication Critical patent/WO2024245585A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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Classifications

    • 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
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • 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
    • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous

Definitions

  • the present invention is related to a new composition, a new method of making stable formulations and a new use of deliquescent substances. Products based thereon are stable over prolonged periods of time and maintain the viability of microorganisms in the product.
  • the invention has particular advantage when stabilizing live microorganisms in an anhydrous substance or essential anhydrous substance for topical application of microorganisms.
  • the present invention relates to water free or essential water free systems comprising viable microorganisms.
  • the present invention relates to compositions for topical use on skin or mucous membranes comprising at least one viable microorganism.
  • the present invention relates to stability of viable microorganisms in cosmetic or pharmaceutical products for topical application.
  • Probiotics are live microorganisms that confer health benefits to the host when administered at adequate levels (FAO WHO, 2006).
  • FAO WHO a live microorganism that confer health benefits to the host when administered at adequate levels
  • the microorganisms must remain viable during the processing and storage of the product containing live probiotics.
  • Considerable amount of research has been done to stabilize probiotics for oral consumption and ensure resistance to gastrointestinal fluids.
  • Topical formulations and products for pharmaceutical or cosmetic purposes are developed to have a long shelf life at room temperature and to be stable towards contamination and spoilage caused by microorganisms.
  • the stability of viable probiotics in these topical formulations are very limited, however, the use of probiotics in topical formulations could have a huge potential if viability can be maintained in the formulation.
  • Topical formulations like creams, lotions, gels, and mists inherently contain a high degree of water, i.e. in order to be suitably formulated into a gel, cream, foam, lotion, ointment etc.
  • the presence of such high degrees of water in these formulations poses a problem for the storage of probiotics in their metabolically inactive condition.
  • a second problem occurring in such topical formulations is that these generally contain agents, which are not compatible with the survival of microorganisms; such as preservatives, surfactants, emulsifiers and other ingredients in order to protect such formulations against the growth of unwanted microorganisms as well as for forming stable emulsions.
  • agents which are not compatible with the survival of microorganisms; such as preservatives, surfactants, emulsifiers and other ingredients in order to protect such formulations against the growth of unwanted microorganisms as well as for forming stable emulsions.
  • an object of the present invention relates to anhydrous topical compositions with increased stability comprising viable microorganisms and a deliquescent substance, preferably an inorganic salt, use of such composition and a method of preparing such composition.
  • an object of the present invention to provide an anhydrous topical composition where stability of live microorganisms, in particular added live microorganisms, may be improved.
  • An aspect of the present invention relates to a topical anhydrous composition
  • a topical anhydrous composition comprising an anhydrous substance, at least one viable microorganism and a deliquescent substance.
  • a further aspect of the present invention relates to a topical anhydrous composition
  • a topical anhydrous composition comprising at least one viable microorganism and a deliquescent substance wherein the weight ratio of the deliquescent substance to the viable microorganism is in the range from 10:1 to 1 : 10.
  • compositions according to the present invention relate to the use of a composition according to the present invention on skin or mucous membranes or genitals of a mammal.
  • a further aspect of the present invention relates to a composition comprising the topical anhydrous composition according to the present invention in a cosmetic, in a prophylaxis medicament or in a medicament, for the treatment of a disease, dysfunction or disorder.
  • Still a further aspect of the present invention relates to the use of a deliquescent substance to stabilize viable microorganisms in an anhydrous topical composition.
  • Still a further aspect of the present invention relates to a method for providing a topical anhydrous composition comprising an anhydrous substance, at least one viable microorganism and a deliquescent substance wherein the deliquescent substance is subjected to a step of dehydration or partly dehydration before being mixed into the anhydrous substance providing the anhydrous composition.
  • an aspect of the present invention relates to a process for producing an anhydrous composition, the method comprises the steps of:
  • a further aspect of the present invention relates to an anhydrous composition may be used for topical application to human skin.
  • a further aspect of the present invention relates to an anhydrous composition may be used for topical application to human mucous membranes.
  • a further aspect of the present invention relates to an anhydrous composition may be used for application to mucous membranes of the genitals.
  • a further aspect of the present invention relates to an anhydrous composition may be used for topical cosmetic applications.
  • a further aspect of the present invention relates to an anhydrous composition may be used for topical pharmaceutical applications.
  • a further aspect of the present invention relates to an anhydrous composition may be used for a cosmetic, a prophylaxis medicament or a medicament for the treatment of a disease, dysfunction, or disorder.
  • a further aspect of the present invention relates to an anhydrous composition may be used for a cosmetic for anti-age treatment.
  • Inorganic salts are well known to be antimicrobial and are traditionally used for preservation and inhibition of microorganisms, especially with a long history as preservatives being used in the food industry. It was therefore unexpected to find that these water-soluble salts have a stabilizing effect on viable microorganisms in anhydrous compositions, thus being able to significantly extend the viability of microorganisms and prolong the storage stability of such products.
  • Water-soluble inorganic salts are used in the cosmetic and pharmaceutical industry in multiple water-based topical products as a binder, mild abrasive, thickener and preservative, e.g. as viscosity increasing agents to enhance texture of cosmetic products, often combined with guar-based, cellulose, or gum-based thickeners.
  • Water-soluble salts are typically not used in anhydrous (water free) products e.g. oils and fats used as topical cosmetic.
  • the antimicrobial activity of inorganic salt was not observed in anhydrous compositions and even more surprisingly it was observed that the inorganic salt was able to stabilize the viable (live) microorganisms and improve long term viability of the microorganisms.
  • MgCh magnesium chloride
  • NaCI sodium chloride
  • KCI potassium chloride
  • Hygroscopic substances are substances that attract water molecules from the air without necessarily dissolving in the absorbed water and reach a state of equilibrium with the humidity around them. This is due to the presence of hydrophilic groups on the surface of the solid. Deliquescent substances are substances that absorb and dissolve in water to form a liquid. This is due to the absorption of water molecules by the solid.
  • Deliquescence like hygroscopy, is also characterized by a strong affinity for water and tendency to absorb moisture from the atmosphere or the surrounding environment if exposed to it. Unlike hygroscopy, however, deliquescence involves absorbing sufficient water to form an aqueous solution.
  • “Deliquescent substance”, within the meaning of the invention, is a salt characterized by the dehydrated substance ability to adsorb water below 35°C, more preferably below 30°C, more preferably below 25°C, more preferably between 15°C and 25°C.
  • the deliquescent substance is a salt that adsorbs water at 25°C.
  • the absorption of water increases the weight of deliquescent substance by at least 5% (w/w), calculated as by weight of the total weight of the adsorbed deliquescent substance (deliquescent substance including absorbed water) by the weight of the deliquescent substance (w/w), more preferably by at least 15% (w/w), more preferably by at least 30% (w/w), more preferably by at least 50% (w/w).
  • Absorption of water can be determined by standard procedures for water absorption.
  • An example hereof is:
  • the deliquescent substance is dried in an oven for a specified time and temperature to remove water;
  • the deliquescent substance is then placed in open air or at a chosen relative humidity, and water absorption is measured and followed over time until the weight increase stabilizes at a stationary level;
  • the weight is measured, and the weight increase is calculated as percentage increase of the weight measured in point 3.
  • the deliquescent substance absorbs water below 99% relative humidity, more preferably below 90% relative humidity, more preferably below 80% relative humidity, more preferably below 60% relative humidity, more preferably below 40% relative humidity at 25 °C.
  • Humidity can be measured using a hygrometer, i.e. a tool that utilizes various materials and measurements to gauge a room or spaces level of water vapor.
  • Relative humidity is the amount of water vapor in air compared to the amount of water vapor that the air can hold. The amount of water vapor that air can hold depends on the temperature; the warmer the air, the more water vapor it can hold. Air is said to be saturated when it cannot hold any more water. Multiple standard instruments are available to determine relative humidity.
  • the deliquescent substance may be a salt selected from a water soluble inorganic salt or a water soluble organic salt, preferably, the salt may be a water soluble inorganic salt.
  • the deliquescent substance may be a deliquescent salt.
  • the deliquescent salt may be selected from the group consisting of calcium chloride (CaCL), magnesium chloride (MgCh), zinc chloride (ZnCL), ferric chloride (FeCh), lithium chloride (LiCI), carnallite (KCl.MgCh), potassium carbonate (K2CO3), sodium acetate anhydrous (CHsCOONa), ammonium nitrate (NH4NO3), potassium hydroxide (KOH), dipotassium phosphate (K2HPO4), magnesium nitrate (MgfNOsh), sodium formate (NaCHO2), sodium acetate (NaC2H3O2), trisodium phosphate (Na3PO 4 ), magnesium sulfate (MgSO 4 ), sodium sulfate (Na2SO 4 ), aluminum potassium sulfate (CH3NH2AI(SO 4 )2), Manganese(I), calcium chloride (Ca
  • the deliquescent salt may be a water soluble salt selected from magnesium chloride (MgCL), calcium chloride (CaCL), carnallite (KCl.MgCh), potassium carbonate (K2CO3), sodium acetate anhydrous (CHsCOONa), and dipotassium phosphate (K2HPC ) and any combinations hereof.
  • MgCL magnesium chloride
  • CaCL calcium chloride
  • KCl.MgCh carnallite
  • K2CO3 potassium carbonate
  • CHsCOONa sodium acetate anhydrous
  • K2HPC dipotassium phosphate
  • the deliquescent substances may be a partly deliquescent substance and have deliquescent behaviour when applied to skin.
  • partly deliquescent substance may be sodium chlorite (NaCIC ) or ozalic acid (H 2 C 2 O 4 ).
  • NaCIC sodium chlorite
  • ozalic acid H 2 C 2 O 4
  • the present invention relates to deliquescent substances for anhydrous topical compositions for mammals, therefore some of the listed deliquescent substances e.g. zinc chloride, lithium chloride and ferric chloride may not be suited or desired due to toxicity.
  • the deliquescent substances may be selected from the group comprising of calcium chloride (CaCL), magnesium chloride (MgCL), carnallite (KCl.MgCh), potassium carbonate (K2CO3), sodium acetate anhydrous (CHsCOONa), potassium hydroxide (KOH), dipotassium phosphate (K2HPO4) and sodium hydroxide (NaOH) or any combinations thereof.
  • CaCL calcium chloride
  • MgCL magnesium chloride
  • KCl.MgCh carnallite
  • K2CO3 potassium carbonate
  • CHsCOONa sodium acetate anhydrous
  • KOH potassium hydroxide
  • K2HPO4 dipotassium phosphate
  • NaOH sodium hydroxide
  • the human skin has an acid pH, and therefore most topical compositions intent to have an acidic or slightly acidic pH, a deliquescent substance supporting the natural pH of healthy skin will be advantageous.
  • the deliquescent substance may be selected from calcium chloride (CaCL), magnesium chloride (MgCL), carnallite (KCl.MgCh), potassium carbonate (K2CO3), sodium acetate anhydrous (CHsCOONa), dipotassium phosphate (K2HPO4), or a combination hereof.
  • the deliquescent substances may be selected from calcium chloride (CaCh), magnesium chloride (MgCL), carnallite (KCl.MgCh), potassium carbonate (K2CO3), sodium acetate anhydrous (CHsCOONa), dipotassium phosphate (K2HPO4), or any combinations hereof.
  • CaCh calcium chloride
  • MgCL magnesium chloride
  • KCl.MgCh carnallite
  • K2CO3 potassium carbonate
  • CHsCOONa sodium acetate anhydrous
  • K2HPO4 dipotassium phosphate
  • the deliquescent substance is selected from from calcium chloride (CaCL), magnesium chloride (MgCL), carnallite (KCl.MgCh), potassium carbonate (K2CO3), dipotassium phosphate (K2HPO4) and their combinations.
  • CaCL calcium chloride
  • MgCL magnesium chloride
  • KCl.MgCh carnallite
  • K2CO3 potassium carbonate
  • K2HPO4 dipotassium phosphate
  • the deliquescent substance may comprise a magnesium salt, in particular magnesium chloride (MgCL).
  • MgCL magnesium chloride
  • the deliquescent substance may be a salt hydrate which can be dehydrated to form an unstable hydration level in the salt at temperature from 5-40°c.
  • the deliquescent substance may be a salt hydrate which at standard atmospheric pressure and relative humidity between 45% and 75% will be fully hydrated or partly hydrated.
  • the deliquescent salt according to the present invention may dehydrate at a temperature above 20°C. More preferably the deliquescent salt according to the present invention may dehydrate at a temperature above 25°C. More preferably the deliquescent salt according to the present invention may dehydrate at a temperature above 30°C. More preferably the deliquescent salt according to the present invention may dehydrate at a temperature above 40°C. More preferably the deliquescent salt according to the present invention may dehydrate at a temperature above 50°C.
  • the deliquescent substance according to the present invention may be a dry deliquescent substance.
  • the dry deliquescent substance comprises a moisture content below 8% (w/w), e.g. below 6% (w/w), such as below 4% (w/w), e.g. below 2% (w/w), such as below 1% (w/w), e.g. below 0.5% (w/w), such as below 0.1% (w/w), e.g. below 0.05% (w/w), such as below 0.01% (w/w),
  • the deliquescent substance and the viable microorganisms may be added to the anhydrous substance providing the anhydrous composition.
  • a preferred embodiment of the present invention relates to a topical anhydrous composition
  • a topical anhydrous composition comprising an anhydrous substance, at least one viable microorganism, and a deliquescent substance.
  • the deliquescent substance may be placed in the anhydrous substance.
  • the deliquescent substance may be distributed in the anhydrous substance.
  • the deliquescent substance may be homogenously, or substantially homogenously, distributed in the anhydrous substance.
  • the deliquescent substance may be represent in the range of 0.05 to 5% (w/w) of the anhydrous composition, more preferable in the in the range of 0.075 to 4% (w/w), more preferable in the in the range of 0.1 to 2% (w/w), more preferable in the in the range of 0.15 to 1.75% (w/w), more preferable in the range of 0.2 to 1.5% (w/w).
  • the deliquescent substance e.g. the deliquescent salt may be dried and distributed in the anhydrous substance as crystals, e.g. salt crystals.
  • the salt crystals may have a size less than 500 pm, such as less than 400 pm, e.g. less than 300 pm, such as less than 200 pm, e.g. less than 100 pm, such as less than 75 pm, e.g. less than 50 pm, e.g. less than 30 pm, e.g. less than 10 pm.
  • the weight ratio of the deliquescent substance to the viable microorganism is in the range from 10: 1 to 1 : 10, such as in the range of 8: 1 to 1 :8, e.g. in the range of 6: 1 to 1 :6, such as in the range of 4: 1 to 1 :4, e.g. in the range of 2: 1 to 1 :2, e.g. in the range of 2:3 to 1 :3, such as about 1 : 1.
  • the present invention relates to and anhydrous composition comprising live microorganisms including any bacteria, archaea, phages, viruses, yeast or fungi or any combinations thereof.
  • the live microorganism may be a probiotic live microorganism.
  • suitable probiotic microorganisms include bacteria such as the genera Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Streptococcus, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus, Cutibacterium, Lactobacillus, Lactiplantbacillus, Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacillus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus,
  • the most commonly used probiotics are strains of the lactic acid bacteria (LAB). These LAB are considered non-pathogenic and are used as probiotic bacteria in general to improve gastrointestinal flora and in the treatment of gastrointestinal symptoms.
  • the present invention may relate to stabilization of any viable microorganisms in an anhydrous composition for topical application.
  • the bacteria are preferably selected among the genera Lactobacillus, Lactiplantbacillus, Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacillus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus, Furfurilactobacillus, Paucilactobacillus, Limosilactobacillus, Fructilactobacillus, Acetilactobacillus, Apilactobacillus, Levilactobacillus, Secundilactobacillus, Lentilactobacillus, Leuconostoc, Bifidobacterium, Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carnobacter
  • the preferred microorganisms may be bacteria, in particular probiotic bacteria.
  • the probiotic bacteria may preferably be selected from the group comprising Lactococcus lactis, Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lactobacillus helveticus, Lactobacillus jensenii, Lactobacillus acidophilus, Lactobacillus buigaricus, Lactobacillus amyiovorus, Lactobacillus amyioiyticus, Lactobacillus alimentarius, Lactobacillus aviaries, Lactobacillus delbrueckii, Lactobacillus diolivorans, Lactobacillus farciminis, Lactobacillus gaHinarum, Lacticaseibacillus easel, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus hilgardii, Lactobacill
  • the probiotic microorganism may be selected from the genera related to the natural healthy skin microbiome including genera Lactobacillus, Lactiplantbacillus, Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacillus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus, Furfurilactobacillus, Paucilactobacillus, Limosilactobacillus, Fructilactobacillus, Acetilactobacillus, Apilactobacillus, Levilactobacillus, Secundilactobacillus, Lentilactobacillus, Leuconostoc, Probionibacterium, Cutibacterium, Staphylococcus
  • the probiotic strain may be Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes (Probionibacterium acnes), Nitrosomonas eutropha or any combinations thereof.
  • the probiotic strain may be a Gram-positive bacteria.
  • the anhydrous composition according to the present invention may comprise at least one bacterial strain selected from the group consisting of Lactiplantibacillus plantarum LB356R. (DSM 33094), Lactiplantibacillus plantarum LB244R. (DSM 32996), Lactobacillus crispatus LB714R. (DSM 33732), Pediococcus pentosaceus LB606R. (DSM 33730), Weissella viridescens LB10G (DSM 32906), Lacticaseibacillus paracasei LB113R. (DSM 32907), Lacticaseibacillus paracasei LB116R.
  • DSM 33094 Lactiplantibacillus plantarum LB356R.
  • DSM 32996 Lactobacillus crispatus LB714R.
  • DSM 33732 Lactobacillus crispatus LB714R.
  • DSM 32908 Levilactobacillus brevis LB152G (DSM 32995), Lacticaseibacillus paracasei LB28R. (DSM 32994), Enterococcus faecium LB276R. (DSM 32997), Leuconostoc mesenteriodes LB349R. (DSM 33093), Lactiplantibacillus plantarum LB316R. (DSM 33091), Lactiplantibacillus plantarum LB312R. (DSM 33098), Lactiplantibacillus plantarum LB679R. (DSM 33731), Lactobacillus gasseri LB905R.
  • DSM 34094 Lactobacillus crispatus LB912R.
  • DSM 34095 Lactobacillus crispatus LB919R.
  • DM 34097 Lactobacillus jensenii LB918R.
  • DM 34096 Lacticaseibacillus paracasei LB555R.
  • DSM 34249 Lactiplantibacillus plantarum LB681R.
  • DSM 34250 Lactiplantibacillus plantarum LB948R.
  • DM 34251 Lactiplantibacillus plantarum LB958R.
  • DM 34252 Lactiplantibacillus plantarum LB721R.
  • DSM 34491 Lactiplantibacillus plantarum LB760R.
  • DSM 34492 Lactiplantibacillus plantarum LB990R.
  • DSM 34494 Lacticaseibacillus paracasei LB857R. (DSM 34493); and/or any combinations hereof and/or any mutant strains.
  • the probiotic microorganism may be selected from the group consisting of Bifidobacterium lactis DSM10140, B. lactis LKM512, B. lactis DSM 20451, Bifidobacterium bifidum BB-225, Bifidobacterium adolescentis BB-102, Bifidobacterium breve BB-308, Bifidobacterium longum BB-536 from Zaidanhojin Nihon Bifizusukin Senta (Japan Bifidus Bacteria Center), Bifidobacterium NCIMB 41675 described in EP2823822.
  • lactis Bi-07 Bifidobacterium bifidum Bb-02, Bifidobacterium bifidum Bb-06, Bifidobacterium longum KC-1, Lactobacillus paracasei Lpc-37 , Lactobacillus rhamnosus HN001 (Howaru), Streptococcus thermophilus 715, Streptococcus thermophilus ST21, Bifidobacterium longum 913, Lactobacillus acidophilus NCFM, Lactobacillus buigaricus 1260 (International Flavors & Fragrances Inc.), Bifidobacterium breve M-16V (Morinaga) and/or a Lactobacillus having a probiotic effect and may be any of the following strains; Lactobacillus rhamnosus LGG (Chr.
  • Lactobacillus paracasei subsp. paracasei CR.L431 ATCC 55544
  • Lactobacillus paracasei strain F-19 from Medipharm, Inc.
  • L. paracasei LAFTI L26 DSM Food Specialties
  • Lactobacillus plantarum 299v available from Probi, L. paracasei CR.L 431 (Chr. Hansen)
  • Lactobacillus acidophilus PTA-4797, L. salivarius Ls-33 and L. curvatus 853 International Flavors & Fragrances Inc.
  • rhamnosus LC705 is described in Fl Patent 92498, Valio Oy, Lactobacillus DSM 15527 (Bifodan), Lactobacillus DSM15526 (Bifodan), Lactobacillus rhamnosus GG (LGG) (ATCC 53103) is described in US Patent 5,032,399 and Lactobacillus rhamnosus LC705 (DSM 7061), Lactobacillus reuteri strains available from BioGaia e.g. Lactobacillus reuteri ATCC PTA 6475, Propionic acid bacterium eg. Propionibacterium freudenreichii ssp.
  • DSM 33094 Lactiplantibacillus plantarum LB244R.
  • DSM 32996 Weissella viridescens LB10G
  • DSM 32906 Weissella viridescens LB10G
  • DSM 32907 Lacticaseibacillus paracasei LB116R.
  • DSM 32908 Levilactobacillus brevis LB152G
  • DM 32994 Enterococcus faecium LB276R.
  • DSM 32997 Leuconostoc mesenteriodes LB349R.
  • DSM 33093 Lactiplantibacillus plantarum LB316R.
  • DSM 33091 Lactiplantibacillus plantarum LB312R.
  • DM 33098 Pediococcus pentosaceus LB606R.
  • DM 33730 Lactiplantibacillus plantarum LB679R.
  • DSM 33731 Lactobacillus crispatus LB714R.
  • DM 33732 Lactobacillus gasseri LB905R.
  • DM 34094 Lactobacillus crispatus LB912R.
  • DM 34095 Lactobacillus crispatus LB919R.
  • DSM 34097 Lactobacillus jensenii LB918R.
  • DSM 34096 Lacticaseibacillus paracasei LB555R.
  • DSM 34249 Lactiplantibacillus plantarum LB681R.
  • DSM 34250 Lactiplantibacillus plantarum LB948R.
  • DSM 34251 Lactiplantibacillus plantarum LB958R.
  • DM 34252 Lactiplantibacillus plantarum LB721R.
  • DM 34491 Lactiplantibacillus plantarum LB760R.
  • DM 34492 Lactiplantibacillus plantarum LB990R.
  • DM 34494 Lacticaseibacillus paracasei LB857R.
  • the at least one viable microorganism according to the present invention may be provided in a crystal of a cryoprotectant.
  • the crystals comprising the microorganism may further comprise at least one further probiotic microorganism selected from the group consisting of bacteria, archaea, phages, virus, yeasts or molds or any combinations thereof.
  • the at least one further probiotic microorganism may be a bacterium.
  • compositions for topical applications are typically to be stable for months at room temperature, this is a major problem for maintaining viability of live probiotic microorganisms in skin care products.
  • the present invention solves the problem of stabilizing the live microorganisms, in particular the probiotic strains, in a composition for topical use on skin or mucous membranes.
  • the anhydrous substance disclosed herein remain essentially water free and contain no more than a trace of water.
  • the invention relates to anhydrous topical compositions comprising only anhydrous ingredients and no added water. Examples of such compositions based on lipids, oils and fats. Such anhydrous composition is directly applicable as a cosmetic or pharmaceutical formulation.
  • the anhydrous substance may comprise a vegetable lipid.
  • anhydrous substance may comprise a vegetable oil and/or a vegetable fat and/or a hydrogenated oil and/or a vegetable wax and/or a fatty pasty compound (in particular a vegetable fatty pasty compound), or any combination hereof.
  • the anhydrous topical composition comprises less than 10% (w/w) water relative to the anhydrous topical composition, such as less than 8% (w/w) water, e.g. less than 6% (w/w) water, such as less than 4% (w/w) water, e.g. less than 2% (w/w) water, such as less than 1.5% (w/w) water, e.g. less than 1% (w/w) water, such as less than 0.5% (w/w) water.
  • the anhydrous composition comprises no added water.
  • Some anhydrous substances e.g. anhydrous vegetable oils, may comprise traces of water and may be essentially water free.
  • the anhydrous substances (or other anhydrous ingredients) used in the anhydrous composition may comprise less than 3% water, more preferable the anhydrous composition may comprise less than 1% water, more preferable the anhydrous composition may comprise less than 0.5% water, more preferable the anhydrous composition may comprise less than 0.1% water, more preferable the anhydrous composition may comprise less than 0.05% water.
  • the anhydrous composition may be an oil.
  • the "oil" according to the present invention may relate to an oil being liquid at storage temperature, thus the liquid oil has a freezing point below 25°C.
  • the freezing point of the oil may relate to the temperature at which the oil may change between liquid phase and solid phase.
  • the oil may be a vegetable oil which can be absorbed by the skin or the mucous membrane.
  • the oil may be a vegetable oil selected from the group consisting of almond oil, sunflower oil, hemp oil, CBD oil, cannabis oil, Evening prim rose, Borage oil, baobab oil, acai oil, Almond sweet oil, Rose Hip oil, jojoba oil, Jojoba Golden oil, Camomile oil, shea oil, coconut oil, calendula oil, sea buck-thorn oil, Jafflower oil, castor oil, olive oil, corn oil, soya bean oil, cotton seed oil, wheat oil, linseed oil, apricot kernel oil, argan oil, camelina oil, comfrey oil, grape seed oil, kiwi seed oil, mullein oil, rapeseed oil, peach kernel oil, thistle oil, sesame oil, and a combination hereof.
  • a vegetable oil selected from the group consisting of almond oil, sunflower oil, hemp oil, CBD oil, cannabis oil, Evening prim rose, Borage oil, baobab oil, acai oil, Almond sweet oil, Rose
  • the anhydrous composition may also comprises an oil selected from the group consisting of acai, acai berry, almond, almond sweet, aloes vera, andiroba, apricot kernel, arnica, argan, avocado, babassu, baobab, black berry seed, black cumin, black currant seed, blueberry, borage, brazil nut, brocoli seed, buriti, calendula, camellia seed, cannabis oil including CBD and THC, canola, copaiba balsam, cape chestnut (yangu), carrot (daucus carrota), castor, Chardonnay grape, chaulmoogra, cherry Kernel, chia seed, chickweed, coconut, coconut fractionated, cotton seed, comfrey, corn, crambe seed, cranberry seed, cucumber seed, echium seed, evening primrose, emu, flax seed, grape seed, hazelnut, hemp seed, horsechest nut seed,
  • an oil selected from the group
  • the anhydrous composition may comprise an oil selected from sunflower oil, jojoba oil, olive oil, rapeseed oil and/or almond oil or any combinations hereof.
  • Anhydrous ingredients which may suitably be used in the anhydrous composition according to the invention may include waxes, such as beeswax, paraffin wax, animal stearates, glycol esters, mono and diglycerides and wax mixtures; oils, such as olive oil, sunflower oil, canola oil, coconut oil, corn oil, palm oil, sesame oil, peanut oil, along with medium chain triglycerides; an emulsifier, for example a phospholipid such as lecithin; a glyceride such as a mono- or di-glyceride or a combination thereof, for example a stearate, for example glycerol monostearate, such as an animal or vegetable stearate, and/or a palmitate such as glycerol monopalmitate, a dispersant or a surfactant such as polyethylene glycols.
  • waxes such as beeswax, paraffin wax, animal stearates, glycol esters, mono and
  • the anhydrous composition comprises anhydrous ingredients including lipids, oils, fats, waxes and water-free organogelators. Structuring the anhydrous composition as a formulation suitable for topical applications can be done by using a water-free organogelator and be used to create a partly liquid two-phase water-free system (oil-gel).
  • An organogel also called oleogel, may be a class of gel made of oils, fats and waxes in a three-dimensional network formed by an organogelator.
  • anhydrous organogelators include vegetable waxes and hydrogenated vegetable oils such as Rapeseed wax (hydrogenated rapeseed oil), candelilla wax (Euphorbia cerifera cera), rice bran wax (Oryza Sativa Bran Cera), berry wax (Rhus Verniciflua peel cera/Rhus Succedanea fruit cera), Oliwax (hydrogenated olive oil), Tea wax (camellia sinensis cera), Myrica fruit wax (myrica cerifera fruit wax), sunflower wax (Hydrolyzed sunflower seed wax), Sunflower seed wax (Helianthus Annuus Seed cera, ascorbyl palmitate, tocopherol), Castor wax (Hydrogenated castor oil), carnauba wax (Copernicia cerifera cera), or any other vegetable based wax (hydrogenated vegetable oil).
  • Non vegan natural waxes which can be used as organogelator is bee's wax.
  • composition according to the invention can comprise at least one solid compound (solid at ambient temperature and atmospheric pressure) selected more particularly from waxes, pasty compounds and mixtures thereof.
  • “Wax”, within the meaning of the invention, designates a lipophilic compound solid at ambient temperature (25°C), having a melting temperature greater than or equal to 40°C and less than or equal to 120°C, more particularly less than or equal to 90°C.
  • the melting temperature is the temperature of the most endothermic peak observed in thermal analysis (DSC), as described in ISO 11357-3 : 1999.
  • the melting point of a solid fat can be measured using a differential scanning calorimeter (DSC), for example the calorimeter sold under the trade name "DSC 2000” by TA Instruments with the “TA Universal Analysis” software.
  • DSC differential scanning calorimeter
  • the measurement protocol is as follows:
  • a 5 mg sample of wax may be placed in a crucible and subjected to a first temperature rise from -20°C to 120°C, at a heating rate of 10°C I minute, and is then cooled from 120°C to -20°C at a cooling rate of 10°C I minute and finally subjected to a second temperature rise from -20°C to 120°C at a heating rate of 5°C I minute.
  • the melting point of the solid fat is measured, corresponding to the temperature of the most endothermic peak of the melting curve observed.
  • the wax can be selected from polar waxes in particular alcohol waxes; esters such as waxes of animal or plant origin, such as beeswax, lanolin, sunflower, candelilla, carnauba, rice bran, montan, hydrogenated jojoba oil; waxes resulting from the hydrogenation of esters obtained from C6-C22 fatty alcohols of plant origin and vegetable oil; waxes having the formula R.1COOR.2 wherein Ri and R.2 are aliphatic linear, branched or cyclic chains wherein the number of atoms varies from 10 to 50, that can contain a heteroatom, in particular oxygen, and the melting temperature of which varies from 40 to 120°C; partial or total, preferably total, esters of a C16-C30 carboxylic acid, saturated, with glycerol, such as glyceryl tristearate or tribehenate, and mixtures thereof.
  • esters such as waxes of animal or plant origin, such as beeswax,
  • non-polar hydrocarbon waxes in other words consisting solely of carbon and hydrogen atoms
  • resulting from the transformation of petroleum such as for example polyethylene waxes, polymethylene waxes (synthetic wax, Fischer- Tropsch waxes), alone or in mixtures.
  • the composition comprises 10 to 40% (w/w) of at least one wax by weight of the total weight of the composition, preferably 12 to 30% (w/w) by weight.
  • Pasty compound within the meaning of the present invention, means a lipophilic compound, which at a temperature of 25°C has a liquid fraction and a solid fraction.
  • a pasty compound can have a commencing melting point of less than 25°C.
  • the melting point of the fatty pasty compound may be determined according to the same principle as that detailed previously for waxes.
  • the measurement protocol is however as follows:
  • a 5 mg sample of pasty fat placed in a crucible may be subjected to a first temperature rise from -20°C to 100°C, at a heating rate of 10°C I minute, and is then cooled from 100°C to -20°C at a cooling rate of 10°C I minute and finally subjected to a second temperature rise from -20°C to 100°C at a heating rate of 5°C I minute.
  • the melting point of the pasty fat is the value of the temperature equivalent to the top point of the peak of the curve representing the variation in the difference in power absorbed as a function of temperature.
  • the liquid fraction by weight of the pasty fat at ambient temperature is equal to the ratio of the enthalpy of fusion consumed at ambient temperature to the enthalpy of fusion of the pasty fat.
  • the enthalpy of fusion of the pasty fat is the enthalpy consumed by the latter to change from the solid state to the liquid state.
  • the pasty fat is said to be in the solid state when the entire mass thereof is in solid crystalline form.
  • the pasty fat is said to be in the liquid state when the entire mass thereof is in liquid form.
  • the enthalpy of fusion of the pasty fat is the quantity of energy required to change the pasty fat from the solid state to the liquid state. It is expressed in J/g .
  • the enthalpy of fusion of the pasty fat is equal to the area under the curve of the thermogram obtained.
  • this or these pasty hydrocarbon compounds may be selected from vaseline; plant butters, such as in particular mango, shea, cupuacu, murumuru, cocoa, babassu and jojoba butters; completely or partially hydrogenated vegetable oils, such as for example hydrogenated soya oil, hydrogenated copra oil, hydrogenated rapeseed oil, mixtures of hydrogenated vegetable oils such as products with the INCI name hydrogenated vegetable oil, partially hydrogenated olive oil; esters of hydrogenated castor oil and of C16-C22 fatty acids, bis-diglyceryl polyacyladipate-2; products with the INCI name Hydrogenated Coco- Glycerides; esters of dilinoleic alcohol dimer and/or of dilinoleic acid such as for example products with the following INCI names: Bis-Behenyl I Isostearyl I Phytosteryl Dimer Dilinoleyl Dimer Dilinoleate, Phytosteryl I Isostearyl I Cetyl/
  • the composition comprises 10 to 50% (w/w) of at least one pasty fatty compound by weight of the total weight of the composition, preferably 20 to 40% by weight.
  • Organogelator may be used in concentrations up to 40% (w/w) of the anhydrous substance. More preferable the concentration of the organogelator may be less than 20% (w/w) and even more preferable the concentration may be less than 17% (w/w).
  • the organogelator in the anhydrous composition may be a hydrogenated vegetable oil.
  • the anhydrous organogelator may be hydrogenated olive oil, hydrogenated rapeseed oil or hydrogenated sunflower oil.
  • Water free polymers and synthetic waxes can also be used to gel the anhydrous substance.
  • the polymer suited for the present invention may be hydrogenated oils and polyurethane polymers and co-polymers being able to gel oils. Examples of such polyurethane polymers are disclosed in WO18185432.
  • the polyurethane polymers may be selected from Oilkemia 5S polymer from Lubrisol and EstoGel M polymer from Polymerexpert or the like.
  • the polyurethane polymers according to the present invention comprises caprylic/capric triglycerides (e.g. castor oil) and may typically be co-polymers of castor oil and polyurethane.
  • the polymer of the invention may be a polyurethane based on vegetable oils. Some vegetable oils used for production of polyurethane may need chemical modifications before polymerization.
  • the polyurethane polymer may be based on Castor oil.
  • the polymer may comprise more than 10% w/w castor oil, in a more preferred embodiment of the present invention the polyurethane polymer may comprise more than 15% w/w castor oil, an even more preferred embodiment of the present invention the polyurethane polymer may comprise more than 20% w/w castor oil, an even more preferred embodiment of the present invention the polyurethane polymer may comprise more than 20% w/w castor oil.
  • the anhydrous substance may comprise a polyurethane polymer obtained from (based on) caster oil.
  • the anhydrous substance may comprise more than 10% (w/w) polyurethane polymer obtained from (based on) caster oil, such as more than 15% (w/w) polyurethane polymer obtained from (based on) caster oil, e.g. more than 15% (w/w) polyurethane polymer obtained from (based on) caster oil, such as more than 20% (w/w) polyurethane polymer obtained from (based on) caster oil, e.g.
  • more than 25% (w/w) polyurethane polymer obtained from (based on) caster oil such as more than 30% (w/w) polyurethane polymer obtained from (based on) caster oil, e.g. more than 35% (w/w) polyurethane polymer obtained from (based on) caster oil, such as more than 40% (w/w) polyurethane polymer obtained from (based on) caster oil, e.g. more than 45% (w/w) polyurethane polymer obtained from (based on) caster oil, such as more than 50% (w/w) polyurethane polymer obtained from (based on) caster oil.
  • the invention may not be limited to commercially available water free polyurethane products but to any water free polyurethane polymer/co-polymer product being able to gel anhydrous carriers.
  • the caprylic/capric triglyceride and polyurethane polymers may be used in the oil in a concentration from 0.1% (w/w) to 20% (w/w). Preferable in the concentration from 0.3% (w/w) to 10% (w/w) and more preferable from 0.5% (w/w) to 6% (w/w).
  • Synthetic anhydrous waxes may include microcrystalline wax which may be produced by de-oiling petrolatum as part of its refining process.
  • Parafin wax may be derived from petroleum.
  • Ozokerite, ceresin, and montan waxes may originally be mineral waxes which are derived from coal and shale.
  • Ozokerite for cosmetics may also be synthesized from petroleum, exactly like microcrystalline waxes.
  • topical may relate to formulations that are adapted for application to body surfaces (e.g. the skin or mucous membranes).
  • Mucous membranes may include the mucosa of the vagina, the penis, the urethra, the bladder, the anus, the mouth, the nose and/or the ear.
  • the present invention relates to new methodologies and compositions for stabilization of live probiotic strains in a composition for topical use to skin and/or mucous membranes.
  • compositions comprising probiotic bacteria further facilitate the probiotic effects on skin of both humans and animals.
  • the present invention relates to methodologies for preparing an anhydrous composition comprising an anhydrous substance, at least one viable microorganism and a deliquescent substance, preferably a deliquescent salt.
  • the present invention provides a topical therapeutic composition for the treatment or prevention of a skin disorder.
  • the present invention provides a topical therapeutic anhydrous composition for the treatment or prevention of a skin disorder, comprising a therapeutically-effective concentration of one or more viable microorganisms, e.g. live probiotic species or probiotic strains or live biotherapeutic products (LBP), within a pharmaceutically-acceptable anhydrous substance suitable for topical administration on the skin or mucous membranes of a mammal.
  • a topical therapeutic anhydrous composition for the treatment or prevention of a skin disorder, comprising a therapeutically-effective concentration of one or more viable microorganisms, e.g. live probiotic species or probiotic strains or live biotherapeutic products (LBP), within a pharmaceutically-acceptable anhydrous substance suitable for topical administration on the skin or mucous membranes of a mammal.
  • the probiotic strain possesses the ability to maintain viable in the anhydrous composition at room temperature.
  • the invention relates to an anhydrous composition according to the present invention further comprising a cosmetically acceptable anhydrous ingredient.
  • the anhydrous composition may be provided in an anhydrous liquid, anhydrous fluid, or anhydrous ointment form for topical application.
  • the anhydrous composition may advantageously further comprise other probiotics, prebiotics, or other active substances and/or may preferably also contain one or more of the following substances selected from antioxidants, vitamins, coenzymes, fatty acids, amino acids, and cofactors.
  • the antioxidant may be Vitamin E or a variant thereof (wherein the variants may be selected from alfa, beta, gamma, delta tocopherol, tocotrienols and tocomonoenols).
  • the antioxidant is present at a concentration below 5% (w/w) of the anhydrous composition, preferably below 4% (w/w), preferably below 3% (w/w), preferably in the range of 0.01-5% (w/w), preferably in the range of 0.02-4% (w/w), preferably in the range of 0.03-3% (w/w), preferably in the range of 0.06 to 1% (w/w).
  • the antioxidant may be tocopherol.
  • the tocopherol may be provided in the anhydrous substance, or in the anhydrous composition.
  • tocopherol may represent a concentration below 5% (w/w) of the anhydrous substance or composition, such as a concentration below 4% (w/w), e.g. a concentration below 3% (w/w), such as in the range of 0.01-5% (w/w), e.g. in the range of 0.1-4% (w/w), such as in the range of 0.5-3% (w/w), preferably in the range of 0.06 to 1% (w/w) or in the range of 1-2% (w/w).
  • Vegetable oils may contain natural antioxidants, in an embodiment of the invention further antioxidants may be incorporated into the composition.
  • Antioxidants preferably added to a vegetable oil may be tocopherol (added in a range between 0.25 to 2.5% (w/w)) and/or Rosemary extract (added in a range between 0.1 to 0.75 % (w/w)).
  • composition according to the invention preferably comprises, by weight of the total weight of the composition:
  • At least one anhydrous substance preferably chosen from vegetable oils, vegetable waxes, vegetable pasty fatty compounds and their mixtures;
  • Viability of microorganisms may be measured as Colony Forming Units CFU.
  • a "decrease" in viability of microorganisms may be determined as the difference in CFU/g or CFU/ml as compared to the CFU/g or CFU/ml at the time of formulating the composition.
  • a “decrease” in viability may be "statistically significant” as compared to the viability determined at the time of formulating the composition. Decrease may be measured as a log reduction and may include a log reduction of 0.1 or more, such as of 0.5 or more, e.g. of 1.0 or more, such as of 1.5 or more, e.g. of 2.0 or more, such as of 2.5 or more, e.g. of 3.0 or more, such as of 3.5 or more, e.g. of 4.0 or more, such as of 4.5 or more, e.g. of 5.0 or more.
  • microorganisms according to the invention may be provided in isolated or purified form.
  • isolated may mean that the microorganism is cultivated as a monoculture and may be derived from the culture medium including their natural medium.
  • purified is not restricted to absolute purity.
  • the microorganisms may advantageously be present in viable dried form.
  • the dried viable microorganism may be spray-dried or lyophilized or vacuum dried.
  • the probiotic strain may be used as a live isolated microorganism in a dried form.
  • the at least one viable microorganism may be a lyophilized microorganism, preferably a lyophilized microorganism comprising a cryoprotective agent.
  • the probiotic strain may be used as a viable isolated probiotic strain dried into a crystal of cryoprotectant.
  • the crystal may comprise at least 2% cryoprotectant, such as at least 5% cryoprotectant, e.g. at least 10% cryoprotectant, such as at least 15% cryoprotectant.
  • the cryoprotectant may be selected from maltodextrin, trehalose, saccharose, lactose, mannitol, sucrose, glycerol, sorbitol, dextran, inulin, citrate, ascorbate, calcium chloride or a combination hereof.
  • the dried microorganism prefferably be present in the anhydrous composition in an amount by weight of 0.001% (w/w) to 20% (w/w), preferably 0.005% to 10% (w/w), especially preferably 0.01% to 5% (w/w).
  • the anhydrous composition according to the present invention may be formulated for the administration of from approximately lxl0 2 to lxl0 14 CFU of viable bacteria per gram anhydrous composition, more preferably from approximately lxlO 3 to lxlO 10 CFU/g, and most preferably from approximately lxlO 4 to lxlO 9 CFU of viable bacteria per gram of anhydrous composition.
  • the anhydrous composition according to the present invention wherein the at least one microorganism may be present in the anhydrous composition in a concentration above 10 4 CFU per gram anhydrous composition, such as above 10 5 CFU per gram anhydrous composition, e.g. above 10 5 CFU per gram anhydrous composition, such as above 10 7 CFU per gram anhydrous composition, such as above 10 8 CFU per gram anhydrous composition.
  • the dosage of live probiotic microorganisms in the anhydrous composition may be above approximately lxlO 3 CFU of viable bacteria per gram of the anhydrous composition, preferably above approximately lxlO 4 CFU/g, even more preferably above approximately lxlO 5 CFU/g, even more preferably above approximately lxlO 5 CFU/g.
  • an effective amount may be the number of viable microorganisms determined as CFU/gram which may have a probiotic effect on skin or mucous membranes.
  • anhydrous topical compositions according to the present invention surprisingly showed an increased stability on the microbial viability when providing an anhydrous composition comprising an anhydrous substance, at least one viable microorganism and a deliquescent substance, preferably an inorganic salt.
  • the increased stability may be measured as a log reduction in CFU/g per month of storage at 25 degrees Celsius.
  • the increased stability may be a log reduction in CFU/g of less than 0.3 log per month of storage at 25 degrees Celsius, more preferably a log reduction in CFU/g of 0.2 log per month of storage at 25 degrees Celsius, more preferably a log reduction in CFU/g of 0.1 log per month of storage at 25 degrees Celsius.
  • Crystals comprising microorganisms may be less than 2 mm in diameter, more preferable less than 1 mm in diameter, typically in the interval from 5 pm to 1 mm in diameter. More preferable in the interval 10 pm to 0.5 mm, such as in the range of 50-250 pm, e.g. in the range of 100-150 pm.
  • the crystal size may be determined by sieving using predefined mesh sizes.
  • the at least one microorganism may be a single microorganism or a mixture of microorganisms, such as a single bacterium or a mixture of bacterial strains.
  • a "mammal” include, but are not limited to, humans, primates, farm animals, sport animals, rodents, and pets.
  • Non-limiting examples of non-human mammal subjects may include rodents such as hamsters, and guinea pigs; rabbits; dogs; cats; sheep; pigs; piglets; sows; poultry; turkeys; broilers; minks; goats; cattle; horses; and non-human primates such as apes and monkeys.
  • anhydrous composition may be used for topical application to human skin.
  • anhydrous composition may be used for topical application to human mucous membranes.
  • the anhydrous composition may be used for application to mucous membranes of the genitals.
  • anhydrous composition may be used for topical cosmetic applications.
  • anhydrous composition may be used for topical pharmaceutical applications.
  • the anhydrous composition may be used for a cosmetic, a prophylaxis medicament or a medicament for the treatment of a disease, dysfunction, or disorder.
  • anhydrous composition may be used for a cosmetic for anti-age treatment.
  • the anhydrous composition comprising the microorganism further comprises a prebiotic.
  • Prebiotics are components that increase the growth of specific microorganisms.
  • Synbiotics are compositions comprising at least one probiotic and at least one prebiotic. Such compositions may be understood to encourage the growth of beneficial microorganisms (e.g. the probiotic).
  • beneficial microorganisms e.g. the probiotic.
  • powerful synbiotics may be based on a combination of specific strains of probiotic microorganisms with carefully selected prebiotics. They can lead to an important health benefit to a mammal.
  • a probiotic composition comprising the probiotic microorganism and at least one more active ingredient, like a prebiotic.
  • Prebiotics may refer to chemical products that induce the growth and/or activity of commensal microorganisms of the microbiota (e.g., bacteria and fungi) that contribute to the well-being of their host. Prebiotics stimulate the growth and/or activity of advantageous bacteria that colonize the skin.
  • Prebiotics may include one or more oligosaccharides.
  • Some oligosaccharides that may be used as prebiotics are fructooligosaccharides (FOS), xylooligosaccharides (XOS), polydextrose, pectins, galactooligosaccharides (GOS) or human milk oligo saccharides (HMO).
  • FOS fructooligosaccharides
  • XOS xylooligosaccharides
  • polydextrose polydextrose
  • pectins pectins
  • GOS galactooligosaccharides
  • HMO human milk oligo saccharides
  • disaccharides like lactulose, lactose or some monosaccharides such as or tagatose may also be used as prebiotics.
  • the other active ingredient may not be limited in any way.
  • at least one prebiotic compound may be added to the anhydrous composition of the invention, i.e. as other ingredient.
  • Prebiotics according to the present invention may include all those compounds which can be metabolized by probiotics. Prebiotics can thus serve as a food source for probiotics. Prebiotics are well known in the art and when used in the present invention there is no particular limitation of the prebiotic as such.
  • the at least one prebiotic in the anhydrous composition may be selected from the following group of compounds and compositions carbohydrates, glucans, alpha-glucans, beta-glucans, mannan-oligosaccharides, inulin, oligofructose, human milk oligosaccharides (HMO), galactooligosaccharides (GOS), lactulose, lactosucrose, galactotriose, fructooligosaccaride (FOS), cellobiose, cellodextrins, cylodextrins, maltitol, lactitol, glycosilsucrose, betaine, Vitamin E or a variant thereof (wherein the variants are selected from alfa, beta, gamma, delta tocoferols, tocotrienols and tocomonoenols).
  • mannanoligosaccharides and/or inulin may be preferred.
  • HMOs may include lacto-N-tetraose, lacto-N-fucopentaose, lacto-N-triose, 3 '-sialyllactose, lacto-N-neofucopentaose, sialic acid, L-fucose, 2-fucosyllactose, 6 '-sialyllactose, lacto-N- neotetraose, 3-fucosyllactose, or any combination hereof.
  • At least one of the following prebiotic compounds may be used in the topical anhydrous composition of the present invention lactose, beta-glucans, mannanoligosaccharides, inulin, oli-gofructose, galactooligosaccharides (GOS), lactulose, lactose, lactosucrose, galactotriose, fructo-oligosaccaride (FOS), cellobiose, cellodextrins, cylodextrins, maltitol, lactitol, glycosilsucrose, betaine, lacto-N-tetraose, lacto-N- fucopentaose, lac-to-N-triose, 3 '-sialyllactose, lacto-N-neofucopentaose, sialic acid, 2- fucosyllactose, 6 '-sialyllactose, lacto
  • Fucose in particular L-fucose, may be believed to strengthen natural defence of skin, stimulate epidermis immune defence and/or prevent and/or treat cutaneous autoimmune disease.
  • the anhydrous composition comprises L-fucose and/or D-fucose.
  • the anhydrous composition further comprises L-fucose and/or D-fucose in a concentration in the anhydrous composition in the range of 10 mM to 500 mM, such as in the range of 50-400 mM, e.g. in the range of 100-300 mM, e.g. in the range of 150-250 mM.
  • the present invention provides several advantages.
  • viability of the microorganisms is kept in the composition even at storage at room temperature (about 20°C).
  • the microorganisms may be activated by the temperature and moisture of the skin releasing the microorganisms from the anhydrous composition as it is absorbed by the skin.
  • compositions for topical use are not able to maintain the viability of the microorganisms at room temperature for long term storage.
  • a preferred embodiment of the present invention relates to a deliquescent substance, such as a deliquescent salt, to stabilize viable microorganisms in an anhydrous topical composition.
  • anhydrous composition comprising a viable microorganism and a deliquescent substance, e.g. a water soluble deliquescent salt for topical use.
  • a deliquescent substance e.g. a water soluble deliquescent salt for topical use.
  • a preferred embodiment of the present invention relates to a process for producing an anhydrous composition, the method comprises the steps of:
  • the anhydrous substance may be mixed and homogenized with the microorganism before the deliquescent substance is added; the anhydrous substance is mixed and homogenized with the deliquescent substance before the microorganism is added; or the anhydrous substance may be mixed with the microorganism and the deliquescent substance before being homogenized, providing the anhydrous product.
  • a preferred embodiment of the present invention relates to a process for producing an anhydrous composition, the method comprises the steps of:
  • a Further preferred embodiment relates to a method for providing a topical anhydrous composition
  • a topical anhydrous composition comprising an anhydrous substance, at least one viable microorganism and a deliquescent substance, such as a deliquescent salt, wherein the deliquescent substance may be subjected to a step of dehydration or partly dehydration before being mixed into the anhydrous substance providing the anhydrous composition.
  • the anhydrous substance or the mixture of the anhydrous substance and the deliquescent substance may be cooled to a temperature below 40°C before the at least one microorganism may be added, such as below 35°C, e.g. a temperature below 30°C, such as to a temperature below 25°C, e.g. a temperature below 20°C, such as in the range of 10-40°C, e.g. in the range of 15-35°C, such as in the range of 18-30°C, e.g. in the range of 20-25°C.
  • the deliquescent substance e.g. the deliquescent salts
  • the drying of the deliquescent substance may be provided by heating at a temperature of 100-200°C, such as a temperature of 125-175°C, e.g. for about 150°C for a period of at least 30 minutes, such as for at least 1 hour, e.g. for at least l 1 /2 hours, such as for at least 2 hours, e.g. for at least 3 hours, such as for at least 4 hours, e.g. for at least 5 hours, such as for at least 6 hours, e.g.
  • the drying of the deliquescent substance may be done in a Binder Model ED 23 drying chamber.
  • the anhydrous composition according to the present invention may not comprise a coated or a microencapsulated microorganism, and/or a coated or a microencapsulated deliquescent substance.
  • Coating and microencapsulation may relate to tiny particles or droplets of a material (the core material) which are surrounded by a protective shell, forming small capsules.
  • This shell acts as a barrier between the core material and its environment.
  • the shell material is typically a polymeric substance.
  • the anhydrous composition comprises a mixture of the microorganisms, the deliquescent substance, and the anhydrous substance.
  • a mixture may be a combination of two or more substances (the anhydrous substance and the deliquescent substances and the microorganisms) in which each substance may retains its own chemical properties. Mixtures may be homogeneous (uniformly mixed) or heterogeneous (non-uniformly mixed).
  • the deliquescent substances, the microorganisms, and the anhydrous substance may form a homogenous or a heterogeneous mixture in which the deliquescent substances and/or the microorganisms may be dispersed within the anhydrous substance.
  • the anhydrous composition according to the present invention may be provided according to the one of the following procedures.
  • Step 1 Melt the anhydrous substance, like fats and mix with all anhydrous ingredients
  • Step 2 Cool the melted anhydrous substance (and anhydrous ingredients) to room temperature (approximately 20°C) and add at least one probiotic microorganism;
  • Step 3 Homogenize the mixture of anhydrous substance (and anhydrous ingredients) and at least one probiotic microorganism;
  • Step 4 Add a deliquescent substance, like a deliquescent salt,
  • Step 5 homogenize the mixture providing the anhydrous composition.
  • Step 1 Melt the anhydrous substance, like fats and mix with all anhydrous ingredients
  • Step 2 Add a deliquescent substance, like a deliquescent salt to the melted anhydrous substance (and anhydrous ingredients)
  • Step 3 Homogenize the mixture of anhydrous substance (and anhydrous ingredients) and deliquescent substance;
  • Step 4 Cool the melted anhydrous substance (and anhydrous ingredients) to room temperature (approximately 20°C) comprising the deliquescent substance, like a deliquescent salt:
  • Step 5 Add at least one probiotic microorganism
  • Step 6 homogenize the mixture providing the anhydrous composition.
  • Step 1 Melt the anhydrous substance, like fats or waxes and mix with all anhydrous ingredients
  • Step 2 Cool the melted anhydrous substance (and anhydrous ingredients) to room temperature (approximately 20°C) and add a deliquescent substance, like a deliquescent salt and the at least one probiotic microorganism;
  • Step 3 homogenize the mixture providing the anhydrous composition.
  • Step 1 Melt fat and waxes solid at room temperature
  • Step 2 Add liquid oil and other anhydrous ingredients e.g. Vitamine E and homogenize
  • Step 3 Add dried deliquescent salt and homogenize.
  • Step 4 Cool to a temperature of 20-30°C and add freeze-dried probiotic microorganism and homogenize.
  • compositions were produced following the procedure above.
  • Composition 1
  • Shea butter fat 10 g
  • Jojoba oil 38.5 g
  • Freeze dried microorganisms Lactiplantibacillus plantarum LB244R® (DSM 32996) : 0.5 g (correspond to approximately 10 7 CFU/ml of final composition)
  • the deliquescent salts were dried to remove water by heating at 150°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • Composition 2 is a composition of Composition 2:
  • Shea butter fat 20 g
  • Freeze dried microorganisms Lactiplantibacillus plantarum LB356R® (DSM 33094) : 1 g (correspond to approximately 10 8 CFU/ml of final composition)
  • the deliquescent salts were dried to remove water by heating at 150°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • Composition 3 is a composition of Composition 3:
  • Cocoa butter fat 80 g
  • Freeze dried microorganisms Pediococcus pentosaceus LB606R. (DSM 33730) 0.5 g and Lactiplantibacillus plantarum LB356R® (DSM 33094) 0.5 g (correspond to approximately 10 9 CFU/ml of final composition)
  • the deliquescent salts were dried to remove water by heating at 150°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • Composition 4 is a composition having Composition 4:
  • Jojoba oil 72 g
  • Freeze dried microorganisms Pediococcus pentosaceus LB606R (DSM 33730) 1 g (correspond to approximately 10 9 CFU/ml of final composition)
  • the deliquescent salts were dried to remove water by heating at 150°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • Composition 5 is a composition of Composition 5:
  • Jojoba oil 70 g
  • Lactiplantibacillus plantarum LB244R® 1 g correspond to approximately 10 9 CFU/ml of final composition
  • the deliquescent salts were dried to remove water by heating at 140°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • composition 6 is a composition of Composition 6:
  • Rapseed oil 20 g
  • Jojoba oil 20 g
  • Lactiplantibacillus plantarum LB714R® (DSM 33732) 1 g (correspond to approximately 5*10 8 CFU/ml of final composition)
  • Composition 7 is a composition of Composition 7:
  • Shea butter fat 10.5 g
  • Jojoba oil 38.5 g CaCL: 0.5 g (Sigma C3306)
  • Freeze dried microorganisms Lactiplantibacillus plantarum LB244R® (DSM 32996) : 0.5 g (correspond to approximately 10 8 CFU/ml of final composition)
  • the deliquescent salts were dried to remove water by heating at 150°C in Binder Model ED 23 drying chamber for at least 1 hour before step 3.
  • compositions were stored in airtight bottles at 25°C.
  • CFU/ml was determined after 30, 60 and 90 days and compared to the CFU/ml in the identical compositions without deliquescent salt.
  • Viability is followed by plate counting.
  • Container is opened and 1 mL of the anhydrous composition is transferred to tubes and 9 mL Maximum Recovery Diluent (Sigma 07233) is added.
  • the mixture was homogenized.
  • compositions comprising deliquescent salts were stable with a log reduction of less than 0.1 in the full test period.
  • the viability decreased with 1 log after 1 month, with about 3 log after 2 months and with about 4 log after 3 months.
  • Control is the identical composition but without the deliquescent salt.

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  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
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Abstract

La présente invention concerne une composition anhydre topique comprenant une substance anhydre, au moins un micro-organisme viable et une substance déliquescente.
PCT/EP2023/082735 2023-05-30 2023-11-22 Formulation topique comprenant une substance déliquescente Pending WO2024245585A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5032399A (en) 1985-04-17 1991-07-16 Sherwood L. Gorbach L. acidophilus strains
FI92498C (fi) 1992-06-10 1994-11-25 Valio Meijerien Uusi mikro-organismikanta, sitä sisältävät bakteerivalmisteet ja näiden käyttö hiivojen ja homeiden torjuntaan
US20090232785A1 (en) * 2005-08-01 2009-09-17 L'oreal Cosmetic and/or dermatological composition for prevention and/or treatment of sensitive or dry skin
EP2823822A1 (fr) 2009-11-11 2015-01-14 Alimentary Health Limited Souche de bifidobacterium
WO2018185432A1 (fr) 2017-04-04 2018-10-11 Polymerexpert Sa Nouveau gelifiant polyurethane
US20210393510A1 (en) * 2020-06-23 2021-12-23 Crown Laboratories, Inc. Probiotic skin formulations
WO2023025911A1 (fr) * 2021-08-25 2023-03-02 Lactobio A/S Composition de bactéries probiotiques pour inhiber la prolifération fongique

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5032399A (en) 1985-04-17 1991-07-16 Sherwood L. Gorbach L. acidophilus strains
FI92498C (fi) 1992-06-10 1994-11-25 Valio Meijerien Uusi mikro-organismikanta, sitä sisältävät bakteerivalmisteet ja näiden käyttö hiivojen ja homeiden torjuntaan
US20090232785A1 (en) * 2005-08-01 2009-09-17 L'oreal Cosmetic and/or dermatological composition for prevention and/or treatment of sensitive or dry skin
EP2823822A1 (fr) 2009-11-11 2015-01-14 Alimentary Health Limited Souche de bifidobacterium
WO2018185432A1 (fr) 2017-04-04 2018-10-11 Polymerexpert Sa Nouveau gelifiant polyurethane
US20210393510A1 (en) * 2020-06-23 2021-12-23 Crown Laboratories, Inc. Probiotic skin formulations
WO2023025911A1 (fr) * 2021-08-25 2023-03-02 Lactobio A/S Composition de bactéries probiotiques pour inhiber la prolifération fongique

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE GNPD [online] MINTEL; 13 July 2022 (2022-07-13), ANONYMOUS: "Natural Deodorant Spray", XP093125892, retrieved from https://www.gnpd.com/sinatra/recordpage/9735544/ Database accession no. 9735544 *
DATABASE GNPD [online] MINTEL; 21 May 2021 (2021-05-21), ANONYMOUS: "Deep Moist Cream", XP093125886, retrieved from https://www.gnpd.com/sinatra/recordpage/8726729/ Database accession no. 8726729 *
FAVARO-TRINDADE ET AL., CAB REVIEWS: PERSPECTIVES IN AGRICULTURE, VETERINARY SCIENCE, NUTRITION AND NATURAL RESOURCES, vol. 6, 2011, pages 1 - 8

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