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WO2006048457A1 - Probiotiques et polyphenol - Google Patents

Probiotiques et polyphenol Download PDF

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Publication number
WO2006048457A1
WO2006048457A1 PCT/EP2005/055787 EP2005055787W WO2006048457A1 WO 2006048457 A1 WO2006048457 A1 WO 2006048457A1 EP 2005055787 W EP2005055787 W EP 2005055787W WO 2006048457 A1 WO2006048457 A1 WO 2006048457A1
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Prior art keywords
composition according
composition
lactobacillus
product
group
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PCT/EP2005/055787
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English (en)
Inventor
Karl Anders Olof Henriksson
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DSM IP Assets BV
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DSM IP Assets BV
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/20—Bacteria; Substances produced thereby or obtained therefrom
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23B—PRESERVATION OF FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES; CHEMICAL RIPENING OF FRUIT OR VEGETABLES
    • A23B2/00—Preservation of foods or foodstuffs, in general
    • A23B2/70—Preservation of foods or foodstuffs, in general by treatment with chemicals
    • A23B2/725—Preservation of foods or foodstuffs, in general by treatment with chemicals in the form of liquids or solids
    • A23B2/729—Organic compounds; Microorganisms; Enzymes
    • A23B2/733—Compounds of undetermined constitution obtained from animals or plants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23B—PRESERVATION OF FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES; CHEMICAL RIPENING OF FRUIT OR VEGETABLES
    • A23B2/00—Preservation of foods or foodstuffs, in general
    • A23B2/70—Preservation of foods or foodstuffs, in general by treatment with chemicals
    • A23B2/725—Preservation of foods or foodstuffs, in general by treatment with chemicals in the form of liquids or solids
    • A23B2/729—Organic compounds; Microorganisms; Enzymes
    • A23B2/783—Microorganisms; Enzymes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives

Definitions

  • the present invention relates to the field of infection caused among others by Gram positive Bacteria and associated diseases, and in particular to compositions comprising probiotica and polyphenol, which have the capacity to prevent and/or treat these infections and that may also be used as a preservative.
  • Microbial pathogens remain a serious threat to human health despite the availability of traditional anti-microbial therapies.
  • Such pathogens are known to be both Gram positive and Gram negative bacteria.
  • Staphylococci are a group of Gram positive bacteria that are known to cause numerous infections, including neonatal infections, mastitis, post-operative infections, furuncles and carbuncles, pneumonia, bacteremia, endocarditis and enterocolitis (1).
  • Pathogenic streptococci, including Streptococcus pyrogenes are commonly associated with the skin and nasopharynx where they may cause disease.
  • Streptococcus pneumoniae is another human pathogen that causes infection in the lower respiratory tract (2).
  • Streptococci such as Streptococcus mutans
  • Gram positive bacteria such as staphylococci and to some extent streptococci often carry multiple antibiotic resistances, which makes successful treatment difficult and in some cases impossible.
  • Certain Gram negative bacteria are also known to cause prolonged and even chronic infections due to a lack of effective treatments.
  • Helicobacter pylori is an example on such an pathogen. Gastric infection by this pathogen would mostly lead to peptic ulcer, in some cases (1%) developing to gastric cancer. Gastric infection with H. pylori is often treated with a combination therapy. However, emerging strains with resistance to such therapies are a problem (3).
  • EGCG Epigallocatechin gallate
  • prebiotic compounds For a probiotic culture to be active, it needs to compete with other microorganisms, in the targeted area. Therefore, prebiotic compounds have been useful in stimulating growth and activity of probiotics in specific targeted areas to maximize the beneficial effect of probiotic cultures.
  • the drawback with such prebiotics is that they may also stimulate growth and activity of certain undesirable bacteria.
  • the invention relates to a composition comprising a probiotic and a polyphenol.
  • a probiotic is defined herein as a live microbial strain, which beneficially affects the human host cell by improving its microbial balance.
  • the probiotic is selected from the group consisting of a Lactobacillus, a Bifidobacterium species and mixture thereof.
  • the Lactobacillus is selected from the group consisting of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus helveticus, Lactobacillus fermentum and mixtures thereof and the Bifidobacterium is selected from the group consisting of
  • the probiotica is selected from the group consisting of the Lactobacillus acidophilus CBS 116411, the Lactobacillus casei CBS 116412, and the Bifidobacterium lactis B94 CBS 118529 all three protected by the trademark LAFTITM (DSM, The Netherlands), a Bifidobacterium species.
  • the probiotic used in the composition of the invention comprises a biologically pure culture of said deposited strain.
  • the probiotic used in the composition of the invention comprises a biologically pure culture of said deposited strain in combination with any other valuable probiotic strain.
  • the polyphenol present in the composition of the invention derives preferably from a tea extract or is preferably a tea extract.
  • the tea extract is a green tea extract.
  • the polyphenol is or comprises catechins.
  • the major catechins present in green tea extract are epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC).
  • the green tea extract comprises EGCG.
  • EGCG is a polyphenol derived from the green tea plant Camellia sinensis.
  • EGCG preparations are already known. A process for preparing EGCG preparations has already been described for example in EP 1 ,077,211.
  • EGCG is highly enriched starting from any green tea extract, e.g. green tea leaves are typically extracted with hot or cold water to form a solution containing tea catechins and caffeine.
  • This green tea solution can be further concentrated to form either a concentrated extract solution or a dry powder.
  • Tea extract powders are commercially available e.g. from Guizhou Highyin Biological Product Co., Guiyang, P. R. China, or Zhejang Zhongke Plant Technical Co. Ltd., Hangzhou, Zhejang, P. R. China.
  • the green tea extract comprises as major compound EGCG.
  • Major compound means that the green tea extract comprises at least 90% w/w, preferably at least 93 %, more preferably at least 95 % EGCG.
  • the green tea extract is TeavigoTM (DSM Nutritional products Ltd., Kaiseraugst, Switzerland) or is EGCG.
  • the composition comprises EGCG and a probiotica is selected from the group consisting of the Lactobacillus acidophilus CBS 116411, the Lactobacillus casei CBS 116412, and the Bifidobacterium lactis B94 CBS 118529
  • Green tea extract is a powerful antioxidant and is known to have some anti ⁇ microbial activities, against undesirable bacteria such as Gram positive and Gram negative bacteria. Gram positive bacteria appear to be particularly sensitive to polyphenol.
  • Gram positive bacteria appear to be particularly sensitive to polyphenol.
  • probiotic strains Lactobacilli and Bifidobacteria strains
  • These strains grow at concentrations that are close to 10 times higher than the minimum concentrations that inhibit other Gram positive bacteria and some Gram negative bacteria. Therefore, the composition of the invention could be used in any types of applications wherein the undesirable agent is among others a Gram positive bacteria: the green tea extract would act as an anti-microbial agent which would allow the probiotic to colonize the treated human, animal or product.
  • the composition of the invention has a synergistic action on the modulation of the immune system.
  • the composition of the invention has the capacity to kill an undesirable bacterium or to inhibit its growth, or to prevent the germination of its spores in vitro in a given medium and/or in vivo in a given food product matrix, crop protection application, pharmaceutical or cosmetic product.
  • Undesirable bacteria are defined as being either a Gram positive or a Gram-negative bacterium.
  • undesirable bacteria are bacteria, which are not defined as probiotic.
  • Undesirable Gram-negative bacteria that are selectively targeted by the composition of the invention are a.o. Helicobacter pylori.
  • undesirable Gram-positive bacteria that are susceptible and are targeted by the composition of the invention are selected from the group consisting of a Streptococcus, Staphylococcus species and mixture thereof. The effect of killing undesirabie bacteria or inhibiting their growth is preferably measured using the following in vitro assay: 10 7 of
  • probiotic Lactobacillus acidophilus L10 CBS 116411 and/or Lactobacillus casei L26 iTM i ,:TM TM serve as controls: (1 ) 10 7 cfu of the chosen undesirable bacteria as defined above are
  • the composition is said to have the capacity to kill undesirable bacteria if the reduction that is at least 20% greater
  • the composition is said to have to prevent the growth of the undesirabie bacteria if in the /n v/fro test d « undesirabie bacteria at the end of the assays is the same
  • composition of the composition of the present disclosure is a pharmaceutically acceptable salt.
  • the two components may be first 1 as a smq ⁇ e to the human or to the product to
  • the composition of the invention comprises as probiotic any of the strains as defined earlier, preferably the strain Lactobacillus acidophilus CBS 116411 and/or the strain Lactobacillus casei CBS 116412 and/or Bifidobacterium lactis CBS 118529 and mixtures thereof with polyphenol or EGCG or preferably TeavigoTM in combination with at least one of the following ingredients in order to get a synergistic combination on the human being treated.
  • Preferred ingredients are: vitamin A, vitamin C, vitamin D3, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, nicotinamide, folic acid, beta carotene, lutein, Zinc, Copper, selenium, and prebiotic.
  • the composition of the invention comprises a probiotic, a polyphenol and a prebiotic. It has been surprisingly found that the combination of these three components together (polyphenol, probiotic and prebiotic) works synergistically such that the combination is more effective against undesirable bacteria than each agent taken separately. Surprisingly, the composition of the invention has a synergistic action on the modulation of the immune system.
  • Prebiotic is defined as a component, which has a favourable influence on the growth of certain beneficial intestinal bacteria, preferably probiotic.
  • the prebiotic is selected from the group consisting of pentosans (or arabinoxylans), b glucans, pectins, and pectic polysaccharides, mannans, arabinans, galactans, fructo- oligosaccharides, resistant starch and mixture thereof.
  • pentosans or arabinoxylans
  • pectins pectic polysaccharides
  • mannans arabinans
  • galactans fructo- oligosaccharides
  • resistant starch and mixture thereof.
  • Most preferred fructo-oligosaccharides are selected among the group consisting of inulin, banana fiber, and soy fructo-oligosaccharides or soy oligosaccharides.
  • mannans are selected among the group consisting of guar gum, locust bean gum, konjac and ad xanthan gum.
  • Resistant starch as used in the context of this invention includes tiose forms defined as RS1 , RS2, RS3, and RS4 as defined in Brown et al (Brown, Mc Knaught and Moloney (1995) Food Australia 47:272- 275). Resistant starch and modified resistant starch have been both extensively described in US 6,348,452.
  • the Composition of the invention is preferably for use as a medicament.
  • the invention relates to the use of the composition of the invention for the preparation of a medicament for preventing and/or treating infections caused by undesirable bacteria and associated diseases in a human being in a need thereof.
  • the medicament, which comprises the composition of the invention is preferably used for preventing and/or treating infections caused by undesirable bacteria and associated diseases in a human being in a need thereof.
  • the undesirable bacterium is among other a Gram positive bacteria.
  • a human being in the need of the composition of the invention is preferably defined as follows: human subjects that experience some form of fatigue and/or stress, bed sores, gingivitis, nose, throat infection and peptic ulcer.
  • Stress and fatigue can have any origin but could have a professional origin: shiftwork, international travel, academic stress in students, over-training in sport (athletes). Alternatively and/or in combination with stress having a professional origin, stress could also have a domestic origin: family stress, stress caused by children. Alternatively and/or in combination with previous mentioned possible origins of stress, stress is caused by mid-life crisis and/or diet-related stress. More preferably, the stress and/or fatigue cause impaired physical performance in human over-training in sport such as athletes.
  • Humans, In a need of the composition of the invention are preferably individuals that have been subjected to physical stress, e.g. afhietes or other individuals that are susceptible to infections caused by among other
  • the undesirable bacterium Is preferably a Streptococcus or a Staphylococcus species.
  • the undesirable bacterium is defected by Nutrient agar.
  • the biomarker is the Cross Reactive Protein (CRP), which is measured as described by (15).
  • CRP Cross Reactive Protein
  • a norma! level of CRP is iess than 7mg/L blood as measured by this assay. More
  • composition of the invention can be used to prevent and/or treat gingivitis (mouthwash), skin infection (skin cream), nose and throat infections (tablet, capsule, spray), Helicobacter infections (tablet, capsule).
  • gingivitis mouthwash
  • skin infection skin cream
  • nose and throat infections tablet, capsule, spray
  • Helicobacter infections tablet, capsule
  • composition of invention may be in any galenic form that is suitable for administrating to the animal body including the human body, especially in any form that is conventional for oral administration, e.g. in solid form such as (additives/supplements for) food or feed, food or feed premix, fortified food or feed, tablets, pills, granules, dragees, capsules, and effervescent formulations such as powders and tablets, or in liquid form such as solutions, emulsions or suspensions as e.g. beverages, pastes and oily suspensions.
  • the pastes may be filled into hard or soft shell capsules, whereby the capsules feature e.g. a matrix of plant proteins or ligninsulfonate for example.
  • compositions of the invention may be in the form of controlled (delayed) release formulations.
  • the composition comprises: - at least 100 ⁇ g/ml polyphenol or EGCG or 200 ⁇ g/ml polyphenol or EGCG or at least 300 ⁇ g/ml polyphenol or EGCG associated with at least 10 6 cfti/ml probiotic or at least 10 7 cfti/ml probiotic or at least 10 8 cfu/ml probiotic.
  • the preparation comprises:
  • - at least 10 mg polyphenol or EGCG as the daily dose or at least 200 mg polyphenol or EGCG as the daily dose or at least 500mg polyphenol or EGCG as the daily dose, or at least 1000 mg polyphenol or EGCG as the daily dose associated with - at least 10 8 cfu probiotic or at least 10 1 ° cfu probiotic at least 10 1 1 cfu probiotic.
  • the polyphenol is as defined earlier a green tea extract or derived thereof or ECGC or TEAVIGOTM.
  • the probiotic is one of the probiotic strain defined earlier on.
  • the invention further relates to a product comprising the composition of the invention.
  • the product is preferably selected from the group consisting of a medicament, a feed product, a food product, a cosmetic, an oral hygiene product and an agricultural product.
  • the composition of the invention is a medicament or for use in the preparation of a medicament or is a food product or part thereof. According to a preferred embodiment, the composition of the invention is used for the manufacture of said medicament or food product.
  • the medicament of the invention may comprise any physiologically or pharmacologically acceptable excipient and/or diluent. If the composition of the invention is part of a food product, the composition of the invention can be present as a dry formulation, e.g. granule, powder, tablet or the like. Alternatively, the composition of the invention may be formulated in a liquid form.
  • the food product of the invention comprising the composition of the invention may comprise any physiologically or acceptable excipient and/or diluent.
  • Preferred food products are cultured milk, yoghurt, cheese, milk drink, milk powder, sport drink, coveratures (defined as mixtures of oil, sugar(s) and milk protein (whey)), infant formulas and fermented meat products. Since the composition of the invention may be incorporated into a (food) product, which already contains endogenous probiotic and/or polyphenol, all amounts of probiotic and/or polyphenol given in the description relates to added amounts of these components.
  • a Lactobacillus strain as defined before preferably the Lactobacillus acidophilus strain CBS 116411 and/or the Lactobacillus casei CBS 116412 and/or Bifidobacterium lactis CBS 118529 and mixtures thereof and a polyphenol, preferably EGCG as defined before are used in the preparation of a food product for preventing and/or combating infections associated with undesirable bacteria and associated diseases in a human being in a need thereof.
  • the undesirable bacteria is a Gram positive bacteria as defined before.
  • the product (medicament or food product) of the invention comprises a probiotic, preferably a Lactobacillus strain as defined earlier, preferably the Lactobacillus acidophilus strain CBS 116411 and/or the Lactobacillus casei CBS 116412 and/or Bifidobacterium lactis CBS 118529 and a polyphenol, preferably EGCG as defined before in an effective amount to prevent and or treat infections associated with undesirable bacteria and associated diseases.
  • the food product or medicament comprises at least 10 6 to 10 8 cfu probiotic per gram product and at least 2 to 5 mg polyphenol or EGCG per gram product.
  • the food product or medicament comprises at least 10 6 to 10 8 cfu probiotic and at least 2 to 5 mg TEAVIGOTM or EGCG per gram product.
  • the composition and the product of the invention is in the form of tablet, capsule, powder or granule, orally liquid administered liquid preparations, or suppositories, or dry preparations.
  • the probiotic present in the composition and the product of the invention is in the form of an enteric tablet, capsule, powder or granule, meaning it will survive the stomach and arrive intact in the intestine. All these forms can be prepared by known means, using food grade, respectively pharmaceutically acceptable carriers, excipients, solvents or adjuvants.
  • standard ingredients and method of preparation as already described in Remington: The science and practice of pharmacy, 1995, Mack Publishing, Co Easton, PA 18042, USA can be used, which content is herewith incorporated by reference.
  • the invention therefore also relates to a method wherein the composition of the invention, comprising a probiotic and a polyphenol preferably EGCG and/or preferably a Lactobacillus strain as defined earlier, more preferably the Lactobacillus acidophilus strain CBS 116411 and/or the Lactobacillus casei CBS 116412 and/or Bifidobacterium lactis CBS 118529 are formulated in a food product or in a medicament, and said food product or medicament is administered to a given human being in an amount effective for preventing and/or treating diseases associated with undesirable bacterial infections. Therefore, the invention further relates to a method for preventing and/or treating infections associated with undesirable bacteria, preferably Gram positive bacteria and associated diseases in a given human being.
  • This method comprises the step of administering the medicament or food product of the invention to said human being.
  • the exact dosage of both essential active ingredients which are the probiotic and the polyphenol, constituting an amount effective for preventing and/or treating infections associated with undesirable bacteria and associated diseases in a human being in a need thereof may vary depending on the specific nature of the clinical conditions being treated, severity of the condition, age of human being treated, weight and condition of the human being treated, mode of administration of the dosage form, and the specific formulation being administered.
  • administrating the composition or the product of the invention preferably means ingesting said product to give a daily dose of at least 10 8 cfu probiotic and 10 mg polyphenol or EGCG per day. More preferably, an amount of the product that corresponds to 10 10 cfu probiotic and 800 mg polyphenol or EGCG per day.
  • the preservative composition of the invention may additionally comprise an anti-fungal agent selected from the group consisting of a weak acid preservative, a polyene anti-fungal compound, sulphur dioxide, sulphites, nitrate, nitrite, dimethyl dicarbonate, biphenyl, diphenyl, orthophenylphenol, thiobendazole, an inorganic acid, an imidazole and mixture thereof.
  • an anti-fungal agent selected from the group consisting of a weak acid preservative, a polyene anti-fungal compound, sulphur dioxide, sulphites, nitrate, nitrite, dimethyl dicarbonate, biphenyl, diphenyl, orthophenylphenol, thiobendazole, an inorganic acid, an imidazole and mixture thereof.
  • a weak acid preservative such as sorbic acid, propionic acid, benzoic acid, a p- hydroxybenzoic acids, lactic acid, citric acid, acetic acid or an alkali metal or alkali earth metal salt thereof;
  • a polyene anti-fungal compound preferably natamycin
  • an inorganic acid such as hydrochloric acid
  • imidazole such as imazalil
  • the present invention further relates to the use of the composition of the invention comprising a probiotic and a polyphenol for killing among other undesirable bacateria such as Gram-positive bacteria or for inhibiting their growth or for preventing the germination of their spores.
  • the composition of the invention can be used for the preparation of any types of products such as a food product or a medicament for preventing and/or treating infections caused by undesirable bacteria and associated diseases in a human being in a need thereof.
  • the Gram-positive bacteria, the human being in need of the composition and the type of food products are as defined above including the preferences as described.
  • the composition of the invention can be used as a preservative for the preparation of a product.
  • the objectives of this study were to (i) assess the antimicrobial activity of TEAVIGOTM against pathogenic bacteria, Staphylococcus aureus and Streptococcus pyogenes in liquid medium, (ii) assess the effect of TEAVIGOTM on growth of probiotic strains Lactobacillus acidophilus LAFTI ® L10, Bifidobacteria lactis LAF ⁇ P B94 and Lactobacillus casei LAF ⁇ P L26 in liquid medium and (iii) explore the possibility of combined therapy for infectious diseases using TEAVIGOTM and probiotics together.
  • strains S. aureus ATCC 25923 and S. Pyogenes ATCC 10389 were obtained from the UNSW Microbiology Culture Collection.
  • Three probiotic strains, L. acidophilus LAFTp L10 (CBS 116411 ), ⁇ . lactis YAFTf B94 (CBS 118529) and L. casei YAFTf L26 (CBS 116412) were supplied by DSM Food Specialties, Australia.
  • S. aureus was grown on nutrient agar medium under aerobic conditions.
  • L. acidophilus, B. lactis and L. casei were grown in anaerobic jars under CO 2 + N 2 atmosphere (AnaroGenTM, Oxoid) at 37 0 C on reinforced clostridial medium (RCM) agar media.
  • S. pyogenes was grown on blood agar media under microaerophilic conditions. The susceptibility tests were carried out in RCM broth. All media were purchased from Oxoid, England.
  • Example 1 In vitro growth responses of probiotic strains and pathogenic bacteria to TEAVIGOTM
  • TEAVIGOTM Antimicrobial effect and MIC of TEAVIGOTM in liquid medium TEAVIGOTM was obtained from DSM Nutritional Products Ltd. Kaiseraugst Switzerland.
  • TEAVIGOTM is a green tea extract and contains minimum 90% of EGCG, a tea polyphenol.
  • TEAVIGOTM was dissolved at a concentration of 10 mg /ml in milli-Q water, and was sterilised by passing through a 0.45 ⁇ M filter.
  • the minimum inhibitory concentrations (MICs) of TEAVIGOTM were determined by the broth microdilution method, at an inoculum of about 1 x 10 7 cfu per well.
  • TEAVIGOTM The anti-microbial effect of TEAVIGOTM was assessed using seven bacterial strains in RCM broth containing 0, 25, 50, 100, 200, 400 and 800 ⁇ g/ml TEAVIGOTM. Visible growth of bacteria is illustrated in table 1.
  • TEAVIGOTM Minimum inhibitory concentrations of TEAVIGOTM on seven bacteria MICs were calculated from Table 1. As shown in table 2, the seven tested strains showed quite different susceptibility to TEAVIGOTM. Compared to the MICs of TEAVIGOTM against S. aureus and S. pyogenes (100-200 ⁇ g/ml), the MICs of TEAVIGOTM against probiotic LAFTI ® strains were higher than 800 ⁇ g/ml. Table 2. Comparison of TEAVIGOTM MICs against four strains of pathogenic bacteria and three probiotic LAF ⁇ P strains
  • Test strain MIC ( ⁇ g/ml) Test strain MIC ( ⁇ g/ml)
  • Gram-positive bacteria Gram-positive bacteria
  • probiotic strains and pathogenic strains defined in general experimental conditions were used in this example and cultivated the same way as defined in general experimental conditions and in example 1 unless otherwise indicated.
  • Lactobacillus acidophilus L10 was inoculated at 0 h at 5% (v/v). For other conditions see legends of Table 3.
  • Bifidobacterium lactis B94 was inoculated at 0 h at 5% (v/v). For other conditions see legends of Table 3.
  • Lactobacillus casei L26 was inoculated at 0 h at 5% (v/v). For other conditions see legends of Table 3.
  • Lactobacillus acidophilus L10 was inoculated at 0 h at 5% (v/v). For other conditions see legends of Table 3.
  • Lactobacillus casei L26 was inoculated at 0 h at 5% (v/v). For other conditions see Legends of Table 3.

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Abstract

La présente invention se rapporte au domaine des infections causées par des bactéries indésirables et des maladies associées. Elle concerne en particulier des compositions comprenant des probiotiques et des polyphénols, qui peuvent prévenir ou traiter ces infections, ou être utilisées comme agents de préservation.
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Cited By (16)

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WO2007009187A1 (fr) * 2005-07-22 2007-01-25 Tarac Technologies Pty Ltd Complement nutritionnel contenant un polyphenol et un probiotique
EP1955702A1 (fr) * 2006-11-28 2008-08-13 GenMont Biotech Inc. Produit à base de Lactobacillus paracasei
WO2009021585A1 (fr) * 2007-08-13 2009-02-19 Dsm Ip Assets B.V. Bactéries probiotiques pour réduire l'occurrence de symptômes d'infections hivernales
US20090060879A1 (en) * 2007-09-04 2009-03-05 The Procter & Gamble Company Oral Compositions, Products and Methods Of Use
WO2009100331A3 (fr) * 2008-02-06 2009-12-17 The Procter & Gamble Company Compositions, méthodes et kits de stimulation de la réponse immunitaire à une maladie respiratoire
US7666407B2 (en) 2006-08-09 2010-02-23 Genmont Biotech Inc. Lactobacillus paracasei-containing product
US20150174087A1 (en) * 2013-12-25 2015-06-25 China Medical University Method for Alleviating Disturbance of Bile Acid Metabolism, Amino Acid Metabolism, and/or Gut Microbiota Metabolism
US9277763B2 (en) 2013-06-27 2016-03-08 Starbucks Corporation Biopreservation methods for beverages and other foods
WO2018142101A1 (fr) * 2017-02-03 2018-08-09 Vornagain Ltd Compositions pharmaceutiques et de nettoyage et leur utilisation en traitement
US10542763B2 (en) 2016-12-02 2020-01-28 Fairlife, Llc Non-browning lactose-free milk powder and methods of making same
CN110915887A (zh) * 2019-12-03 2020-03-27 华南农业大学 一种复合生物保鲜剂及其应用
US20200368146A1 (en) * 2019-05-22 2020-11-26 Mary Ahern Method of cosmetic preservation
US20210299193A1 (en) * 2018-07-13 2021-09-30 Council Of Scientific & Industrial Research Synbiotic composition for improving immune response and antioxidant capacity during aging and a process for the preparation thereof
US20210369600A1 (en) * 2013-07-05 2021-12-02 Stellar Biome Inc. Oral compositions
CN115316502A (zh) * 2022-09-02 2022-11-11 吉林大学 一种表没食子儿茶素没食子酸酯复方饲料添加剂及其制备方法和应用
CN116919879A (zh) * 2023-07-20 2023-10-24 清远市望莎生物科技有限公司 一种具有调节皮肤微生态作用的生物益生素组合物及其制备方法和用途

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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007009187A1 (fr) * 2005-07-22 2007-01-25 Tarac Technologies Pty Ltd Complement nutritionnel contenant un polyphenol et un probiotique
US7666407B2 (en) 2006-08-09 2010-02-23 Genmont Biotech Inc. Lactobacillus paracasei-containing product
EP1955702A1 (fr) * 2006-11-28 2008-08-13 GenMont Biotech Inc. Produit à base de Lactobacillus paracasei
WO2009021585A1 (fr) * 2007-08-13 2009-02-19 Dsm Ip Assets B.V. Bactéries probiotiques pour réduire l'occurrence de symptômes d'infections hivernales
US20090060879A1 (en) * 2007-09-04 2009-03-05 The Procter & Gamble Company Oral Compositions, Products and Methods Of Use
WO2009100331A3 (fr) * 2008-02-06 2009-12-17 The Procter & Gamble Company Compositions, méthodes et kits de stimulation de la réponse immunitaire à une maladie respiratoire
US9277763B2 (en) 2013-06-27 2016-03-08 Starbucks Corporation Biopreservation methods for beverages and other foods
US20210369600A1 (en) * 2013-07-05 2021-12-02 Stellar Biome Inc. Oral compositions
US12226519B2 (en) * 2013-07-05 2025-02-18 Stellar Biome Inc. Oral compositions
AU2022201476B2 (en) * 2013-07-05 2025-03-06 Stellar Biome Inc. Oral compositions
US9744146B2 (en) * 2013-12-25 2017-08-29 China Medical University Method for alleviating disturbance of bile acid metabolism, amino acid metabolism, and/or gut microbiota metabolism
US20150174087A1 (en) * 2013-12-25 2015-06-25 China Medical University Method for Alleviating Disturbance of Bile Acid Metabolism, Amino Acid Metabolism, and/or Gut Microbiota Metabolism
US10542763B2 (en) 2016-12-02 2020-01-28 Fairlife, Llc Non-browning lactose-free milk powder and methods of making same
US11266158B2 (en) 2016-12-02 2022-03-08 Fairlife, Llc Non-browning lactose-free milk powder and methods of making same
WO2018142101A1 (fr) * 2017-02-03 2018-08-09 Vornagain Ltd Compositions pharmaceutiques et de nettoyage et leur utilisation en traitement
US20210299193A1 (en) * 2018-07-13 2021-09-30 Council Of Scientific & Industrial Research Synbiotic composition for improving immune response and antioxidant capacity during aging and a process for the preparation thereof
US12239676B2 (en) 2018-07-13 2025-03-04 Council Of Scientific & Industrial Research Synbiotic composition for improving immune response and antioxidant capacity during aging and a process for the preparation thereof
US20200368146A1 (en) * 2019-05-22 2020-11-26 Mary Ahern Method of cosmetic preservation
CN110915887A (zh) * 2019-12-03 2020-03-27 华南农业大学 一种复合生物保鲜剂及其应用
CN110915887B (zh) * 2019-12-03 2021-09-14 华南农业大学 一种复合生物保鲜剂及其应用
CN115316502A (zh) * 2022-09-02 2022-11-11 吉林大学 一种表没食子儿茶素没食子酸酯复方饲料添加剂及其制备方法和应用
CN116919879B (zh) * 2023-07-20 2024-05-07 宁波和草集品牌管理有限公司 一种具有调节皮肤微生态作用的生物益生素组合物及其制备方法和用途
CN116919879A (zh) * 2023-07-20 2023-10-24 清远市望莎生物科技有限公司 一种具有调节皮肤微生态作用的生物益生素组合物及其制备方法和用途

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