EP3772986A1 - Mikroverkapselte probiotische und diese enthaltende zusammensetzungen mit geringer wasseraktivität - Google Patents

Mikroverkapselte probiotische und diese enthaltende zusammensetzungen mit geringer wasseraktivität

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Publication number
EP3772986A1
EP3772986A1 EP19777860.8A EP19777860A EP3772986A1 EP 3772986 A1 EP3772986 A1 EP 3772986A1 EP 19777860 A EP19777860 A EP 19777860A EP 3772986 A1 EP3772986 A1 EP 3772986A1
Authority
EP
European Patent Office
Prior art keywords
probiotic
microencapsulated
chosen
composition
polymer
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.)
Withdrawn
Application number
EP19777860.8A
Other languages
English (en)
French (fr)
Other versions
EP3772986A4 (de
Inventor
Brain P. ARGO
Sara R. CARLSON
Reynee W. KACHUR
Jenna FOTH
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GPCP IP Holdings LLC
Original Assignee
GPCP IP Holdings LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GPCP IP Holdings LLC filed Critical GPCP IP Holdings LLC
Publication of EP3772986A1 publication Critical patent/EP3772986A1/de
Publication of EP3772986A4 publication Critical patent/EP3772986A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/11—Encapsulated compositions
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
    • A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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
    • A61K2800/10—General cosmetic use
    • 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
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives
    • 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
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/84—Products or compounds obtained by lyophilisation, freeze-drying
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars

Definitions

  • the present disclosure relates to a microencapsulated probiotic. More particularly, the present disclosure relates to a probiotic that comprises a polymeric slurry of freeze-dried probiotic(s) encased with a nutrient composition in a protective barrier layer. Still more particularly, the disclosure relates to a probiotic particulate that can be incorporated in a large variety or products without being compromised by the chemistry within the carrier compositions.
  • the present disclosure further relates to products containing the
  • microencapsulated probiotic and methods of making and using the same.
  • Probiotics are live bacteria and yeast that are known to provide a variety of health benefits, particularly in the digestive system.
  • the digestive system being such a harsh environment, has spurred much research on ways to deliver probiotics to a host. Because probiotics are living cells, they must be protected if they are to remain viable until they reach the host that can receive the expected health benefit.
  • Probiotics have found many uses outside of the digestive system. Recently, it has been discovered that an imbalance in the human biome can be a substantial cause of conditions, including for example, skin irritations and eczema. Adding beneficial bacteria back to the skin through contact with probiotics has shown to improve skin barrier function, counteract inflammatory diseases such as eczema, and reduce the microbes that cause acne.
  • compositions that can kill the probiotic. Worse yet, even if the probiotic is protected and does remain viable until application, the contact between the probiotic and the surrounding carrier composition results in the same
  • the high level of preservatives that are required for adequate shelf-life of a cosmetic can also damage the human biome by killing naturally occurring microbes.
  • the residual activity of preservatives found in products like skin care lotions can kill large numbers of beneficial bacteria that are naturally found on the skin.
  • areas with a dearth of healthy bacteria provide an opportunity for pathogens like Clostridium difficille, Methicillin Resistant Staphylococcus aureus (MRSA), or Vancomycin-Resistant Enterococci (VRE) to grow.
  • MRSA Methicillin Resistant Staphylococcus aureus
  • VRE Vancomycin-Resistant Enterococci
  • the probiotic that is added to the cosmetic is in a lysed form. Lysed probiotics are those that have been chemically cleaved into many pieces and accordingly, they are not alive, so the issue of viability would seem less urgent. Without comment on whether or not there are benefits derived from bacteria parts, the cellular parts delivered to the host will likely also be compromised by the preservatives or other ingredients in the carrier cosmetic formulation.
  • Probiotic encapsulation has been contemplated for a number of years, to improve the survival of living probiotics in a range of formulations.
  • Probiotic survival can be affected by a number of factors including, by way of example, pH and temperature. Encapsulation of the probiotic creates a physical barrier between the living probiotic and its surroundings, be they stomach acid, or pharmaceutical excipients.
  • Current probiotic encapsulation technology PET includes encapsulation, entrapment and immobilization within a variety of biocompatible materials. While substantial research has been conducted on ways to maintain the viability of a living probiotic until it can reach the point of release and benefit, the currently available solutions remain wholly inadequate.
  • the present disclosure provides a method for producing
  • microencapsulated, living probiotics that remain alive until they are delivered to the area of the host in need of the health benefit.
  • the bioencapsulated, living probiotics that remain alive until they are delivered to the area of the host in need of the health benefit.
  • microencapsulated delivery vehicle allows living microbes to be delivered to the skin in a cosmetic or pharmaceutical composition, without the microbe death experienced by prior art products.
  • the present disclosure relates to a composite material comprising a freeze-dried probiotic and a low-water-activity carrier.
  • the present disclosure further relates to a microencapsulated probiotic including a core containing a freeze-dried probiotic and a polymer; a nutrient layer surrounding the freeze-dried core; and a protective layer surrounding the nutrient layer.
  • the present disclosure further relates to a microencapsulated probiotic including a core comprising a freeze-dried probiotic, a polymer and a nutritive composition; and a protective layer surrounding the core.
  • the present disclosure relates to a composition for delivering a probiotic to a host including a freeze-dried probiotic suspended in a polymeric core and further including a probiotic nutrient; and an excipient having a low-water-activity (or water activity below 0.3).
  • the disclosure relates to a method for making an encapsulated probiotic comprising, freeze drying a probiotic, mixing the freeze-dried probiotic and a prebiotic sugar with a polymer or oil to create a composite, and encapsulating the composite in a protective coating.
  • the instant disclosure relates to skin and skin care products that comprise microencapsulated probiotics
  • FIGURE 1 illustrates one embodiment of a microencapsulated probiotic according to the disclosure.
  • FIGURE 2 illustrates another embodiment of a microencapsulated probiotic according to the disclosure.
  • the present disclosure relates to a probiotic microcapsule, a process for microencapsulating the probiotic, compositions containing the probiotic microcapsule, and uses and treatments using the probiotic
  • the probiotic microcapsule as described herein includes a probiotic material that is encased in a manner that prevents death of the live probiotic material before it can be delivered to a host in need of the probiotic.
  • the microcapsule is made up of a number of layers, each of which serves a different purpose in protecting the probiotic material.
  • the microcapsule may include all or a subset of a polymeric core that contains the probiotic material, a nutritive composition dispersed in the core or as a layer around the core, an
  • the moisture protective layer and fugitive layers are optional and may or may not be used in combination with all of the embodiments.
  • encapsulation layer As used herein,“encapsulation layer,”“encapsulation coating,” “encapsulation layers,”“shell,” and“encapsulate shell” are interchangeable and refer to the protective layer that surrounds the probiotic and nutritive composition.
  • each of the layers may be a single distinct coating or layer or may be made up of a number of layers.
  • the term“layer” or“layers” is used, it should be understood that all embodiment can include either the plural and singular.
  • the probiotic microcapsule of the instant disclosure 10 comprises a probiotic that has been freeze-dried. Freeze drying is a multi-step dehydration process in which a material is frozen and water is minimized by sublimation, leaving a dehydrated and preserved product. In the instant product, this preservation technique puts the probiotic into a state of stasis.
  • Probiotics for use in the instant disclosure can be chosen from any art recognized probiotic that one would want to protect until administration of the probiotic to the appropriate host.
  • Such probiotics include one or more of
  • Staphylococcus Streptocococcus, Cadida, Bacillus, and combinations thereof.
  • exemplary probiotics may include Staphylococcus, including S. epidermidis and S hominis; Propionibacterium including P. acnes, P. australiense, P. avidum, P. cyclohexanicum, P. granulosum, P. jensenii, PI. microaerophilum, P.
  • probiotics include those that can grow on, adhere to, or release beneficial proteins or DNA to the skin.
  • Appropriate probiotics and prebiotics for use in the instant disclosure can be found, for example, in the Handbook or Probiotics and Prebiotics by Yuan Kun Lee and Seppo Alminen, second edition.
  • Some probiotics can be analogized to small biochemical manufacturing facilities where each microbe is a biochemical plant that keeps producing beneficial biochemicals. Microbes that naturally grow on the skin are those most often thought of in this way. According to one embodiment, the biochemicals of the probiotic can safely and naturally disinfect the skin. According to another embodiment, the biochemicals can reduce the inflammation response and reduce or eliminate eczema or skin irritation. According to yet another embodiment, the biochemicals of the probiotics can strengthen the skin and induce natural ceramide production - which is to say that skin is rejuvenated, made younger, and made more resistant to the effects of pollution and aging.
  • probiotics can be understood as delivery vehicles that drop off the beneficial ingredients and then move on to deliver the ingredients somewhere else. These are generally the microbes that cannot grow on the skin. Instead they release beneficial peptides and DNA delivering unique benefits to the skin.
  • the DNA and peptides carried by these probiotics are proteins, and as such, they interact with the chemistry of the surrounding delivery vehicle or composition base. Specifically, proteins cannot function properly when they chemically attach to cationic ingredients or become misshapen due to acids or bases. The only way to successfully deliver these proteins to a host is to deliver the proteins in a viable bacteria that naturally breaks when exposed to air.
  • probiotic bacteria e.g. anaerobic bacteria
  • microcapsule that is, according to the described invention, then
  • anaerobic bacteria delivered to the skin may enter the pores and survive naturally, delivering the beneficial proteins to the host.
  • the freeze-dried probiotic is suspended in a polymer to form the composite 40 making up the core of the microcapsule.
  • Any art recognized polymer(s) or combination of polymers useful for pharmaceutical applications can be used for suspending the freeze-dried probiotic including, but not limited to, polyethylene glycols (PEGs), polyvinyl pyrrolidone ((PVPs)- preferably with molecular weights between about 40,000 to about 360,0000), polyvinyl alcohol (PVAs), polyacrylamides, N-(2-hydroxypropyl) methacrylamide (HPMA), xanthan gum, guar gum, pectins, dextran, carrageenan, sodium carboxyethyl cellulose, polyacrylic acid polymers, hyaluronic acid, carboxyvinyl polymers, hydroxyethyl cellulose, cellulose, hydroxypropylmethyl cellulose, carboxyvinyl polymer.
  • polyacrylic acid polymers for example, Carbopol® Ultrez 20, Carbopol® Ultrez 21 , both from Lubrizol, as well as HivisWako® a carboxyl vinyl polymer, from Wako Chemicals Ltd, can be used to suspend the freeze-dried probiotic.
  • the microcapsule core 40 has a low- water-activity.
  • Water activity is a measure of how much water is available to hydrate materials. Maintaining a low-water-activity minimizes the need for preservatives, keeps the freeze-dried probiotic from becoming hydrated, and improves the long term survival of the probiotic.
  • the polymer is treated with a hygroscopic agent to bind and remove free water.
  • a hygroscopic agent can be any material that will bind free water and not interfere with the stasis or release of the probiotic.
  • the hygroscopic material may be chosen from prebiotic sugars (e.g. dried (glucose corn syrup, fructose, manose, mannitol, maltodextrin, lactulose, treehalos, and sorbitol) oligosaccharides (e.g.
  • Fructo-oliosaccharides - Raftilose P95 Orafti, Belgium), galactooligosaccharises, resistant starch-rich whole grains (e.g. oat b-glucan, flaxseed gum, fenugreek gum, and matured gum Arabic), and mannan oligosaccharide-rich yeast cell wall material is demonstrated to be a valuable prebiotic, and certain proteins (e.g. lactoferrin), certain plant extracts (e.g. luteins and black current extract powered).
  • Prebiotic sugars or sugar alcohols have the advantage that they can not only reduce the water activity, but also act as a nutritive composition 20 for the probiotics since they include compounds such as glucose, fructose, oligosaccharides, mannose,
  • glucomannans hydrolyzate xylitol, erythitol, or sorbitol, all of which encourage the growth of the probiotic microbes.
  • the water activity may be modified by adding a humectant (miscible solvent) such as glycerin, propylene glycol, butylene glycol, and the like.
  • a humectant miscible solvent
  • the nutritive composition 20 may be coated around the core 40.
  • the coating 20 is made from any material that can provide nutritive compounds, e.g., glucose, fructose, etc. to the probiotic microbes.
  • Appropriate coatings 20 can be made, for example, from combinations of fat and sugar. Such coatings are well known and are most often found in the candy industry, for example, the coating on an M&M. This coating can be from about 0.1 pm to about 10 pm, for example, from about 0.5 pm to about 5 pm, for example, from about 1 pm to about 5 pm, for example from about 1.5 pm to 5 pm.
  • prebiotic sugars may be added to the core to scavenge water and provide some nutritive benefit, while a nutritive coating layer is also applied around the microcapsule core (not shown).
  • the core may be a non-active around which a probiotic containing polymer layer, a nutritive layer can be created.
  • the non-active core may be chosen from any material that is compatible and capable of being coated with the probiotic material.
  • Appropriate cores may be made of materials such as cellulose or other filling agents.
  • the polymer core 40 with the incorporated nutritive composition 30 of FIG. 1 or the polymer core 40 with the nutritive coating 30 of FIG. 2 further includes a protective encapsulation coating 20.
  • the encapsulation coating 20 may be from 1 to 30 layers thick, for example, from about 1 to about 20 layers thick, for example, from about 1 to about 10 layers thick.
  • the coating weight of the encapsulation coating 20 may be from about 1 % to about 50% of the microcapsule 10 weight, for example, from about 1 % to about 40% of the microcapsule 10 weight, for example, from about 1 % to about 30% of the microcapsule 10 weight, for example, from about 1 % to about 20% of the microcapsule 10 weight, for example, less than 15% of the microcapsule 10 weight.
  • the probiotic core may be further coated with an oil layer before being subjected to encapsulation.
  • the oil layer may provide insulation between the probiotic core and the encapsulation layer allowing higher temperature materials to be used during the microencapsulation process.
  • freeze-dried probiotic may be dispersed in oil.
  • the oil may be thickened with a polymer or copolymer (e.g. Adjinimoto AJK-OD2046 (Octyl Dodecanol and Dibutyl Lauroyl Glutamide and Dibutyl ethylhexanoly Glutamide).
  • Adjinimoto AJK-OD2046 Octyl Dodecanol and Dibutyl Lauroyl Glutamide and Dibutyl ethylhexanoly Glutamide.
  • the slurry can be dispersed in water and encapsulated with gelatin.
  • Suitable materials for the encapsulation coating 20 include those appropriate for application at about 120°C or less, for example, less than about 100°C, for example, less than about 90°C, to facilitate the coating of the freeze- dried probiotic slurry.
  • Waxes may be chosen from organic esters and waxy compounds derived from animal, vegetable, and mineral sources including modifications of such compounds in addition to synthetically produced materials having similar properties.
  • hydrophobic wax materials include for use in the instant disclosure include DynasanTM 110, 114, 116, and 118 (commercially available from DynaScan Technology Inc., Irvine, Calif.),
  • SterotexTM (commercially available from ABITEC Corp., Janesville, Wisconsin.
  • the encapsulation coating layer 20 may be comprised of a polymeric material, a crosslinked polymeric material, a metal, such as Ca 2+ , a ceramic or a combination thereof, that results in a shell material that may be formed during manufacturing.
  • the encapsulation coating layer may be comprised of crosslinked sodium alginate, anionic dispersed latex emulsions, crosslinked polyacrylic acid, crosslinked polyvinyl alcohol, crosslinked polyvinyl acetate, silicates, carbonates, sulfates, phosphates, borates, polyvinyl pyrollidone, PLA/PGA, thermionic gels, urea formaldehyde, melamine
  • the crosslinked polymeric system is crosslinked sodium alginate.
  • the encapsulation coating layer 20 generally has a thickness of from about 0.1 micrometers to about 500 micrometers, for example, from about from about 1 micrometer to about 100 micrometers, for example, from about 1 micrometer to about 50 micrometers, for example, from about 1 micrometer to about 20 micrometers, for example, from about 10 micrometers to about 20 micrometers.
  • Suitable methods for measuring the thickness of the encapsulation layer 20 (once fractured), and the other optional layers described herein, include Scanning Electron Microscopy (SEM) and Optical Microscopy.
  • the encapsulation coating layer 20 has a sufficient thickness to achieve its intended function.
  • the barrier coating can serve one or more functions.
  • the barrier can act to protect the contents of the microcapsule from low water pressure.
  • the water activity inside the microcapsule should be approximately equal to water activity outside the microcapsule.
  • the balance is usually not perfect, and the microcapsule coating layer will protect the capsule contents against small osmotic pressure differences. In this way, the encapsulation coating protects the bacteria from being prematurely activated due to water exposure.
  • the encapsulation coating protects the live bacteria from low levels of preservative. Although low water systems many not need a preservative, it is likely that a minimal level of preservative may be needed to maintain shelf stability. If a small amount of preservative is used, the
  • the encapsulation coating would protect the probiotic bacteria.
  • the preservative would be present in low enough level either to disappear during storage or to be insufficient to cause any damage to the bacterial during dispersion.
  • the encapsulation coating layer is a single discrete layer. According to another embodiment, the encapsulation coating 20 comprises multiple layers added in one or more steps.
  • a moisture protective layer (not shown) may also be included.
  • the moisture protective layer generally surrounds the encapsulation coating 20.
  • the moisture protective layer can comprise one or more of the following compositions, alone or in combination.
  • the materials are chosen from polyols in combination with isocynate, styrene-acrylate, vinyl tolueneacrylate, styrene-butadiene, vinyl-acrylate, polyvinylbutyral, polyvinyl acetate, polyethylene terephthalate, polypropylene, polystyrene, polymethyl methacrylate, polylactic acid, polyvinylidene chloride, polyvinyldichloride, polyethylene, alkyd polyester, carnauba wax, hydrogenated plant oils,
  • the moisture protective layer may be from about 5% to about 35% of the microcapsule weight, for example, from about 5% to about 30% of the capsule weight, for example, from about 5% to about 20%, for example, from about 5% to about 15%.
  • one or more fugitive layers may be added to protect the microcapsule from process damage.
  • the fugitive layer may be comprised of any one of several suitable materials including polylactic acid, polymers of dextrose, hydrocolloids, alginate, zein, and
  • the fugitive layer is starch.
  • the fugitive layer protects the microcapsule during production.
  • the layer may be applied to any of the layers of the microcapsule.
  • the fugitive layer may be something that is eliminated during processing or something that may remain as part of the end product.
  • the probiotic microcapsules 10 of the instant disclosure can be produced using any art recognized methods.
  • the first step in the production of the encapsulated probiotic 10 is to select and freeze dry the probiotic materials.
  • the probiotic is selected from a combination of bacteria and/or yeast. To decrease production losses, the probiotic can be cooled to a temperature of 5°C to 15°C and dried by sublimation of the water from the organism.
  • the probiotic may be added to an excipient before being cooled. Such an excipient may contain an oil and/or a prebiotic sugar.
  • Probiotics can be freeze-dried using any art recognized process.
  • the probiotic powder is produced using standard freeze drying, spray drying, or chemical drying.
  • the freeze-dried probiotic is next encapsulated in a polymeric material to form the core of the microcapsule 40.
  • the polymer is dissolved in water at a high enough concentration to suspend the freeze-dried probiotic, but at a low enough concentration to allow the solution to flow through the microencapsulation process equipment.
  • concentrations are generally between 5 % and 60%, for example, from about 40 % to about 60%, when using a sugar/protein or wax matrix, and for example, from about 5% to about 15% when using a polymeric matrix.
  • the polymer While the polymer is diluted with water to form a slurry, the polymer is highly hygroscopic so it quickly reduces the water activity by absorbing the water preventing the probiotic materials from being hydrated. Hydration of the freeze-dried probiotic will interfere with the probiotic and reduce its ability to survive long-term. According to one embodiment, after addition of the probiotic to the slurry, the water activity of the polymer slurry is then lowered as low as possible, preferably below 0.1. Measurement of water activity is taught in U.S. Patent 4,886,664, which is incorporated herein by reference.
  • low-water-activity means a water activity of 0.6 or less measured using a standard water activity monitor, for example, Goldenwall Model HD-3A, available from Great Wall Instruments.
  • the material can be heat dried at low temperature, sealed and subjected to heat and/or vacuum with a desiccant, spray dried or dried in a fluidized bed at appropriate temperatures, and/or combined with hygroscopic materials.
  • Other drying techniques will be readily apparent to the skilled artisan.
  • a hygroscopic composition that scavenges water can be added.
  • the hygroscopic scavenging composition is a prebiotic sugar.
  • the water activity of the composition can approach zero.
  • the amount of hygroscopic material needed can be calculated based upon the measured water activity of the system. Once the polymer solution has achieved a low-water-activity, care should be taken to prevent the reintroduction of water to the system before, during or after the encapsulation coating.
  • the freeze-dried probiotic slurry can be blended with a wax.
  • the freeze-dried probiotic slurry is hydrophilic and would form droplets inside the wax at an elevated temperature.
  • the selected temperature should be sufficient to melt the hydrophobic wax material, but maintained for a sufficiently short time to keep the freeze-dried probiotic viable. Temperatures can range from 80°F to about 150°F. To maintain the viability of the freeze-dried probiotics, the temperature should not be maintained at or above 140°F, for longer than required to create the desired thickness of microcapsule. Appropriate times are based upon the specific materials being used and would be well understood by the skilled artisan.
  • the mixture is cooled to room temperature to allow the wax to solidify on the freeze-dried probiotic slurry.
  • the coated particles can be ground to the desired size prior to incorporation into a carrier composition.
  • Suitable after processes include, for example, spheroidization (high heat fluidization slightly below the melt temperature of the hydrophobic wax material) and ball milling. These after processes should cause the hydrophobic wax material to coat the freeze-dried probiotic slurry particles in a substantially continuous manner.
  • the core 40 may be
  • the encapsulating activator may be any activator capable of initiating a crosslinking reaction in the presence of a crosslinkable compound.
  • Suitable encapsulating activators include polyvalent ions of calcium, polyvalent ions of copper, polyvalent ions of barium, silanes, aluminum, titanates, chelators, acids, or combinations of these.
  • the activator is calcium chloride or calcium combined with any number of anions.
  • freeze-dried probiotic/polymer slurry in the presence of an activator in the core composition allows for almost instantaneous crosslinking when the core composition is introduced into the solution containing the crosslinkable compound. This immediate crosslinking reduces the potential for unwanted freeze-dried probiotic hydration.
  • the freeze-dried probiotic/polymer slurry may be added dropwise into the liquid containing the crosslinkable compound and the beads that form when the drops contact the liquid will form an encapsulating coating. Stirring can provide sufficient disruption to maintain the individual beads separate during the crosslinking reaction. Agglomerated masses can be susceptible to numerous defects and while they may be physically separated, it is preferable that they not be formed.
  • the drops added to the liquid solution may have a diameter of from about 0.05 millimeters to about 1 millimeter, for example from about 0.1 millimeters to about 1 millimeter.
  • encapsulating activator migrates to the interface between the core composition and the liquid solution and initiates the crosslinking reaction on the surface of the core composition to allow the encapsulation layer to grow outward toward the liquid solution.
  • the thickness of the resulting encapsulation layer 20 surrounding the core 40 composition can be controlled by (1 ) controlling the amount of encapsulating activator included in the core composition; (2) controlling the amount of time the core composition including the encapsulating activator is exposed to the liquid solution including the crosslinkable compound; and/or (3) controlling the amount of crosslinkable compound in the liquid solution.
  • a solution including alginate in a range of from about 1 to about 500 mg/ml, CaCL in a range of from about 0.1 to about 100 mg/ml level and at a temperature between about 4°C and about 37°C would produce a thickness of between 1 -20pm of alginate.
  • the core composition may be introduced or poured into a liquid solution including the crosslinkable compound and then subjected to shear sufficient to break the paste into small beads for crosslinking. Any art recognized method of applying the shear may be used.
  • the liquid solution includes a crosslinkable compound that can be crosslinked in the presence of the crosslinkable compound
  • the surfactant can be chosen from one or more sugar or sugar-based surfactants, e.g., Tween 20, or amino acid or protein-based materials
  • the encapsulation coating 20 may can be formed using a process known as coacervation, which may not require a chemical encapsulating activator to be present in the core composition.
  • Coacervation processes can utilize a change in pH, a change in temperature, and/or a change in ionic strength of the liquid solution to initiate the formation of the encapsulating layer around the core composition.
  • the encapsulating activator may be in the liquid solution.
  • the encapsulating activator chemically reacts with the crosslinkable compound also contained in the liquid solution.
  • the resulting microencapsulated freeze-dried probiotic slurry may be free from any encapsulating activator or it may contain a small amount of encapsulating activator not consumed in the crosslinking reaction.
  • microencapsulated freeze-dried probiotics are subjected to a process to impart a moisture protective layer that surrounds the encapsulated layer that comprises the crosslinked compound.
  • This moisture protective layer provides the microencapsulated freeze-dried probiotic with increased protection from water; that is, it makes the microencapsulated freeze-dried probiotic substantially fluid impervious and allows the microencapsulated freeze-dried probiotic to survive long term in an aqueous environment and not degrade until the moisture protective layer is ruptured by mechanical action.
  • the moisture protective layer may be a single layer applied onto the microencapsulated freeze-dried probiotic, or may comprise several layers one on top of the other.
  • the moisture protective layer may be applied to the
  • the solids content of the solution is generally from about 5% to about 40%, for example, from about 5% to about 30%, for example from about 5% to about 20%, for example from about 10% to about 20%.
  • the viscosity of the solution is from about 20 cp to about 500 cp, for example from about 20 cp to about 80 cp, for example, from about 30 cp to about 70 cp.
  • a fluidized bed process can be utilized to impart the moisture protective layer on the microencapsulated freeze- dried probiotic.
  • the fluidized bed is a bed or layer of microencapsulated freeze- dried probiotic through which a stream of heated or unheated carrier gas is passed at a rate sufficient to set the microencapsulated freeze-dried probiotic in motion and cause them to act like a fluid as the microcapsules are fluidized, a spray of a solution comprising a carrier solvent and the moisture protective material is injected into the bed and contacts the vehicles imparting the moisture protective material to the outside of the microcapsule.
  • microcapsules 10 are collected when the desired moisture protective layer thickness is achieved.
  • the microencapsulated freeze-dried probiotic 10 can be subjected to one or more fluidized bed processes to impart the desired level of moisture protective layer.
  • the microencapsulated freeze- dried probiotic 10 can be subjected to a process for imparting a fugitive layer surrounding the outermost layer.
  • the fugitive layer could be applied on the freeze-dried probiotic 10 such that it substantially completely covered the moisture protective layer.
  • the fugitive layer may be applied to the
  • microencapsulated freeze-dried probiotic 10 utilizing any number of suitable processes including, atomizing, or dripping a fugitive material onto the
  • the solids content of the solution is from about 10% to about 60%, for example, from about 10% to about 50%, for example, from about 20% to about 50%.
  • the pH of the solution is from about 2.5 to about 11.
  • the viscosity of the solution may be from about 20 cp to about 100 cp, for example from about 20 cp to about 80 cp, for example, from about 30 cp to about 70 cp.
  • the preferred method of applying the fugitive layer utilizes a fluidized bed reactor. Alternatively, any art recognized coating process may be used, including a Wurster coating process.
  • an alternative method of producing a preserved encapsulated probiotic may comprise microencapsulating the live microbes that have not been freeze-dried into a slurry with prebiotic materials and, optionally, a polymer, and then coating the microcapsules with alginate or another crosslinked system. After those microcapsules are formed, they would be subjected to freeze drying to preserve the probiotics. Further, the freeze-dried microcapsule may then be coated with a water impermeable coating.
  • probiotic microcapsules can be used in a vast number of ways and in a variety of compositions. For example, they can be used to 1 ) deliver living probiotic microbes to the skin to improve skin barrier function, 2) deliver living probiotic microbes to the skin to reduce inflammation associated with acne, eczema, rosacea, or contact dermatitis, 3) strengthen the human biome so pathogenic bacteria do not have a chance to colonize, 4) deposit probiotics on skin that produce anti-pathogenic peptides which kill pathogens; 5) improve the skins ability to ward off pathogen colonization near medical devices such as insulin pumps or catheters; 6) reduce or eliminate the need for preservatives in cosmetic products; 7) reduce skin ulcers on bedridden, diabetic, or otherwise compromised individuals, 8) protects skin from and fights cancer.
  • microencapsulated probiotics that remain viable will allow further development of 1 ) cosmetic formulations that are hospitable to probiotic microcapsules; 2) a prebiotic media that encourages the growth of probiotics after deposition on the skin: 3) a prebiotic media that extends the shelf- life of encapsulated probiotic bacteria; 4) microcapsules that increase the shelf- life of consumer products.
  • the system as described herein further comprises a method for determining suitable microbes for use in the disclosed microencapsulation process.
  • the process comprises testing microbes for their ability to withstand freezing, testing microbes to ascertain their ability to withstand temperatures up to 140°F; and testing microbes for their ability to survive at various water activities.
  • Appropriate microbes will be those that can handle the extremes of freezing and the encapsulation temperature. Further preferred microbes will remain viable even if the water activity of the composition is increased.
  • Preferred microbes for use in health and beauty products may be tested for their ability to adhere to human skin, their ability to produce peptides that are anti-pathogenic, their ability to grow on human skin, their ability to respond to probiotic media, and, for commercial purposes, their ability to be grown on a macro scale.
  • Micro-encapsulated probiotics can be used in compositions including, for example, moisturizing lotion, sunscreen, lip balm, oral care product, shampoo, soap, hair conditioner, baby wipes, perineal wipes, facial cleaning wipes, feminine hygiene pad or tampon, diaper or adult incontinence product, deodorant (roll-on liquid, spray, or stick), pet food, food additives, food
  • the microcapsules are broken by physical forces that are applied to the capsules. Accordingly, depending upon the end use, the size and thickness of the microcapsules can play a big role in the release of the probiotics. Thinner capsule walls would generally result in more delicate capsules.
  • applications such as lotion, sunscreen, deodorants, lip balm or hair conditioners may be made in systems with low-water-activity.
  • the water activity is reduced not only in the microencapsulated probiotic, but also in the surrounding carrier composition or cosmetic product.
  • the carrier composition has low-water-activity, the osmotic pressure on the microcapsules is minimized which would allow microcapsules to be smaller, thinner, and less noticeable.
  • the microcapsules could be undetectable by the by the consumer.
  • Low preservative levels are likely to increase the shelf life of the cosmetic or health product.
  • decreasing the water activity of the cosmetic decreases through the incorporation of prebiotic sugars in the carrier composition. Adding sufficient prebiotic sugar may reduce the water activity to nearly 0, or undetectable levels.
  • preservatives can have a significant impact on the functions of cosmetic and/or health products.
  • Preservatives can do significantly more damage to the skin biome than antimicrobial soaps.
  • the same preservatives that give hand lotion a long shelf life, will kill both the microbes in the skin’s biome, as well as any probiotics that may be delivered to the skin biome in a viable state.
  • the encapsulated microbes may be chosen from those that can produce peptides that kill pathogenic bacteria. When such a product is applied to the skin, it provides anti-bacterial properties that may extend beyond the point of first application.
  • Tables 1 provides a description of probiotic materials that can be used in the processes described herein. Many are preferred for use on the skin.
  • Table 2 lists probiotics that are not harmful to skin, but that create peptides that target non-native bacteria (pathogens). Besides targeting C. difficile, MRSA, and VRE, probiotics can be used to target other pathogens of concern are listed below: Table 2: Pathogenic Skin Microorganisms.
  • oxygen transmissive packaging may allow the microencapsulated probiotics to remain viable without refrigeration.
  • Containers for the products described herein may be any standard art recognized packaging. Packaging compositions with the described microencapsulated probiotic in packages with low oxygen transmission may reduce shelf-like, but would not otherwise interfere with the product.
  • compositions comprising the microencapsulated probiotic(s) are packaged in high oxygen transmission packaging which can improve both shelf-like and/or bacterial viability without refrigeration.
  • Oxygen transmission rate OTR
  • high OTR packaging is used for products that require substantial oxygen concentrations, such as contact lenses. See, for example, U.S. Patent No. US 9,062,180.
  • the probiotic container could be a single layer of any number of materials including:
  • LDPE packaging could be used for oxygen loving microbes.
  • the packaging could be selected with lower OTR per the list above.
  • the oxygen transmission should not be so high that the probiotic leaves stasis.
  • a non-encapsulated freeze-dried probiotic can be incorporated into a carrier composition that has low-water-activity and is free from microbial contamination and is free from preservatives.
  • the carrier composition for example, a lotion, sunscreen, deodorant, could be irradiated to assure it was free from microbial contamination.
  • the low-water-activity of the composition would prevent the growth or reintroduction of microbes.
  • the irradiated product could be blended with freeze-dried probiotic.
  • the product could them be packaged in an appropriate OTR material and sold.
  • the freeze- dried probiotic should stay in stasis until water is introduced at the time of use of the product.
  • probiotic microcapsules Formulations and uses for the probiotic microcapsules will be discussed below.
  • the described microencapsulated probiotics are particularly useful in low- water-activity compositions.
  • Examples of low-water-activity skin care lotions are set forth below in Tables 4 to 7.
  • Examples of hand cleaner, hand soap and shampoo can be found in Tables 8, 9, and 10, respectively.
  • the encapsulated probiotic product as described can be delivered to the gut of a user by incorporation of the encapsulated probiotic into or onto a food source.
  • microencapsulated probiotic is sprinkled onto a food, such as bread or pastry and is consumed by the user.
  • the microcapsules should protect the probiotic until it can be released and provide benefit to the user.

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EP19777860.8A 2018-03-27 2019-03-27 Mikroverkapselte probiotische und diese enthaltende zusammensetzungen mit geringer wasseraktivität Withdrawn EP3772986A4 (de)

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EP3871653A1 (de) * 2020-02-27 2021-09-01 MicroCen Trans s.r.o Zusammensetzung mit einer vitalen probiotischen kultur zur menschlichen oder tierärztlichen verwendung als deodorant
CN112094419B (zh) * 2020-09-16 2022-08-19 青岛迦南美地家居用品有限公司 一种玻尿酸微胶囊、包含其的纤维、制备方法及应用
CN112890202A (zh) * 2021-02-01 2021-06-04 绍兴同创生物科技有限公司 一种益生菌微囊及其制备方法
FR3136672A1 (fr) * 2022-06-15 2023-12-22 Basf Beauty Care Solutions France Sas Nouvelle composition cosmétique ou dermatologique contenant une souche de bactérie vivante probiotique.
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CN116283418B (zh) * 2023-05-25 2023-08-11 地康食安(北京)农业科技有限公司 一种固载微生物的植物生长促进剂及其制备方法

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CA2570126C (en) * 2004-07-01 2014-08-12 General Mills, Inc. Cultures encapsulated with chocolate food products coated with chocolate and methods of preparation
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US9210945B2 (en) 2009-07-31 2015-12-15 The Iams Company Animal food having low water activity
US20140065210A1 (en) 2012-08-29 2014-03-06 David W. Koenig Protein stabilized probiotics and personal care products
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