KR20230077635A - Probiotic composition comprising novel Bifidobacterium bifidum 193 strain - Google Patents

Abstract

In the present invention, the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) isolated from cabbage kimchi, a traditional Korean fermented food, has an excellent effect on relieving intestinal inflammation compared to the existing Bifidobacterium bifidum 193 strain, so it is a probiotic It can be used in products, health food for immune enhancement, or treatment for inflammatory bowel disease.

Description

Probiotic composition comprising novel Bifidobacterium bifidum 193 strain {Probiotic composition comprising novel Bifidobacterium bifidum 193 strain}

The present invention relates to a probiotic composition comprising a novel Bifidobacterium bifidum 193 strain, and more particularly, to a probiotic composition containing a Bifidobacterium bifidum 193 strain derived from Chinese cabbage kimchi (Accession No. KCTC14782BP), a culture thereof and/or Or it relates to a probiotic composition containing an extract thereof, a pharmaceutical composition and a functional food composition for preventing or treating inflammatory bowel disease.

Probiotics are live microorganisms that, when ingested in adequate amounts, provide health benefits to the host. Recently, as the awareness of domestic consumers that probiotics exhibit various health functionalities has increased, the number of items and annual sales of probiotics among domestic health functional foods are increasing every year.

Most probiotics products in Korea are imported and used, but the imported strains are strains isolated from foreign feces and are tailored to the intestinal and dietary characteristics of foreigners, so the effect on Koreans is limited. In addition, research results have been reported that Korean lactobacillus extracted from domestic traditional food has more than twice the intestinal viability of Koreans compared to imported lactobacillus. Furthermore, since genetically modified strains are difficult to use in food, there is a need for strains effective in alleviating intestinal inflammation without genetic manipulation.

Accordingly, the present invention found that the Bifidobacterium bifidum 193 strain (accession number KCTC14782BP) isolated from cabbage kimchi, a traditional Korean fermented food, was much more effective in relieving intestinal inflammation than the existing Bifidobacterium bifidum strain. By confirming, the present invention was completed.

An object of the present invention is to provide a probiotic composition comprising a novel Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP).

In order to achieve the above object, the present invention provides a probiotic composition comprising a Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

In the present invention, the probiotic composition may be characterized in that it is for improving inflammatory bowel disease.

In the present invention, the inflammatory bowel disease may be characterized as Crohn's disease and/or ulcerative colitis.

The present invention also provides a pharmaceutical composition for preventing or treating inflammatory bowel disease comprising a Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

In the present invention, the inflammatory bowel disease may be characterized as Crohn's disease and/or ulcerative colitis.

The present invention also provides a functional food composition comprising the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and/or extract as an active ingredient.

The Bifidobacterium bifidum 193 strain isolated from cabbage kimchi in the present invention is a probiotic product and immune-enhancing health food in that it has much better anti-inflammatory and immunomodulatory functions than the existing Bifidobacterium bifidum 193 strain. Or it has the advantage that it can be used for the treatment of inflammatory bowel disease.

1 is a schematic diagram of an inflammatory bowel disease (IBD) mouse model experiment.
Figure 2 relates to body weight change in inflammatory bowel disease (IBD) mouse model.
Figure 3 relates to the intestinal length of the inflammatory bowel disease (IBD) mouse model.
Figure 4 relates to the intestinal immune cytokine IL-6 in inflammatory bowel disease (IBD) mouse model.
Figure 5 relates to the intestinal immune cytokine IL-1β in inflammatory bowel disease (IBD) mouse model.
Figure 6 relates to the intestinal immune cytokine IL-10 in inflammatory bowel disease (IBD) mouse model.
Figure 7 relates to the spleen weight of inflammatory bowel disease (IBD) mouse model.
8 relates to genetic information of strain Bifidobacterium bifidum 193 isolated from cabbage kimchi.

Hereinafter, the present invention will be described in detail.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is one well known and commonly used in the art.

The present invention relates to a probiotic composition comprising a Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

In the present invention, the term "probiotics" refers to live bacteria that have a beneficial effect on the health of humans and animals.

In the present invention, the Bifidobacterium bifidum 193 strain was isolated from cabbage kimchi, a traditional fermented food, and the Bifidobacterium bifidum 193 strain, its culture or its extract may be characterized as having immune modulating ability, Not limited to this.

In the present invention, the probiotic composition may be characterized in that it is for improving inflammatory bowel disease, but is not limited thereto.

In the present invention, the inflammatory bowel disease may be characterized as Crohn's disease and/or ulcerative colitis, but is not limited thereto.

In another aspect, the present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease comprising a Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

In the present invention, the inflammatory bowel disease may be characterized as Crohn's disease and/or ulcerative colitis, but is not limited thereto.

In another aspect, the present invention relates to a functional food composition comprising a Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

In the present invention, the term “pharmaceutical composition” refers to the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) of the present invention, its culture and/or its extract, and pharmaceutically acceptable pharmaceutically acceptable ingredients such as diluents or carriers. It means a mixture containing an excipient to be. Pharmaceutical compositions include compositions for therapeutic use as well as cosmetic compositions. According to some embodiments, a method of administering a pharmaceutical composition comprising a composition of the present invention to a subject in need thereof is provided. In some embodiments, compositions of the present invention can be administered to humans.

In the context of the present invention, the description of a pharmaceutical composition principally relates to a pharmaceutical composition for administration to humans, but the skilled person will understand that such compositions are generally suitable for administration to animals of all kinds. Modifications of pharmaceutical compositions for administration to a variety of animals are well understood, and a skilled veterinary pharmacologist can design and/or perform such modifications, if necessary, with simply routine experimentation.

In the present invention, the pharmaceutical composition may be prepared by any method known in the field of pharmacology or developed in the following text. Generally, such methods for purification include the step of associating the active ingredient with an excipient and/or one or more other auxiliary ingredients, followed by shaping and/or packaging the product into desired single- or multi-dose units, if necessary or desired. Include steps.

In the present invention, the pharmaceutical composition may be manufactured, packaged, and/or sold unpackaged as a single unit dose and/or a plurality of single unit doses. A "unit dose" is a discrete amount of a pharmaceutical composition comprising a predetermined amount of an active ingredient. The amount of active ingredient is generally equal to the dosage of active ingredient administered to a subject and/or a convenient fraction of such dosage such as, for example, 1/2 or 1/3 of the dosage.

In the present invention, the relative amounts of the active ingredient, pharmaceutically acceptable excipients, and/or any additional ingredients in the pharmaceutical composition depend on the identity, size, and/or disorder of the subject to be treated and on the route by which the composition is administered. will change By way of example, the composition may contain from 0.1% to 100% (w/w) active ingredient.

In the present invention, pharmaceutically acceptable excipients are any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, tonicity agents, thickening or emulsifying agents, preservatives, solids suitable for the purpose of the particular dosage form. binders, lubricants, and the like. Remington, The Science and Practice of Pharmacy, 21st Edition, A. R. Gennaro, (Lippincott, Williams & Wilkins, Baltimore, MD, 2006) describes various excipients used in the formulation of pharmaceutical compositions and known methods for their preparation. Any conventional carrier medium is incompatible with the substance or its derivatives, for example by providing any undesirable biological effect or otherwise interacting in a detrimental manner with any other component of the pharmaceutical composition. Pharmaceutically acceptable excipients are at least 95%, 96%, 97%, 98%, 99%, or 100% pure.

The excipients are approved for human and veterinary use. In some embodiments, an excipient is approved by the US Food and Drug Administration. In some embodiments, an excipient is pharmaceutical grade. In some embodiments, an excipient meets the standards of the United States Pharmacopoeia (USP), European Pharmacopeia (EP), British Pharmacopoeia, and/or International Pharmacopoeia (EP).

In some embodiments, an excipient is approved for human and veterinary use. In some embodiments, an excipient is approved by the US Food and Drug Administration. In some embodiments, an excipient is pharmaceutical grade. In some embodiments, an excipient meets the standards of the United States Pharmacopoeia (USP), European Pharmacopeia (EP), British Pharmacopoeia, and/or International Pharmacopoeia (EP).

Pharmaceutically acceptable excipients used in the preparation of pharmaceutical compositions include, but are not limited to, inert diluents, dispersing and/or granulating agents, surface active and/or emulsifying agents, disintegrating agents, binders, preservatives, buffers, lubricants, and/or oils. Not limited.

Such excipients may optionally be included in the formulations of the present invention. Excipients such as cocoa butter and suppository wax, colorants, coatings, sweeteners, flavors, and perfumes may be present in the composition at the discretion of the formulator.

Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium lactose phosphate, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dried starch, corn starch, powdered sugar, and combinations thereof.

Exemplary granulating and/or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clay, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, natural sponges, cation-exchange resins. , calcium carbonate, silicate, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethylstarch (sodium starch glycolate), carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose ( croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Vegum), sodium lauryl sulfate, quaternary ammonium compounds, and these Combinations of, but not limited to.

Exemplary surface active agents and/or emulsifiers include natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, waxes, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and veegum [aluminum magnesium silicate]), long chain amino acid derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol) , triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymers, and carboxyvinyl polymers), carrageenan, cellulose derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxy Ethylene Sorbitan Monolaurate [Tween 20], Polyoxyethylene Sorbitan [Tween 60], Polyoxyethylene Sorbitan Monooleate [Tween 80], Sorbitan Monopalmitate [Span 40], Sorbitan Monostearate [ span 60], sorbitan tristearate [span 65], glyceryl monooleate, sorbitan monooleate [span 80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [myrz 45] , polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and solutol), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g. Cremophor), polyoxyethylene ethers, ( for example polyoxyethylene lauryl ether [breeze 30]), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laureate, sodium lauryl sulfate, pluronic F 68, poloxamer 188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, and/or combinations thereof. don't

Exemplary binders include starches (eg corn starch and starch paste); gelatin; sugars (eg sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol); Natural and synthetic gums (e.g. acacia, sodium alginate, extract of Irish moss, fanwar gum, shatty gum, mucilage of Ispaul Husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (veegum), and lachi arabogalactan); alginate; polyethylene oxide; polyethylene glycol; inorganic calcium salts; silicic acid; polymethacrylate; wax; water; Alcohol; and combinations thereof, but are not limited thereto.

Exemplary preservatives may include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and other preservatives. Exemplary antioxidants are alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, bisulfite but is not limited to sodium sulfate, sodium metabisulfite, and sodium sulfite. Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA), citric acid monohydrate, disodium edetate, dipotassium edetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid, and trisodium edetate. . Exemplary antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal. Exemplary antifungal preservatives include, but are not limited to, butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. Exemplary alcohol preservatives include, but are not limited to, ethanol, polyethylene glycol, phenols, phenolic compounds, bisphenols, chlorobutanol, hydroxybenzoates, and phenylethyl alcohol. Exemplary acidic preservatives include, but are not limited to, vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid. Other preservatives include tocopherol, tocopherol acetate, deteroxymesylate, cetrimide, butylated hydroxyanisole (BHA), butylated hydroxytoluend (BHT), ethylenediamine, sodium lauryl sulfate (SLS), Sodium Lauryl Ether Sulfate (SLES), Sodium Bisulfite, Sodium Metabisulfite, Potassium Sulfite, Potassium Metabisulfite, Glidant Plus, Fenonib, Methylparaben, Low Mol 115, Germaben II, Neolon, Carton, and Including, but not limited to, oxalic acid. In certain embodiments, the preservative is an anti-oxidant. In another embodiment, the preservative is a chelating agent.

Exemplary buffers include citrate buffer solution, acetate buffer solution, phosphate buffer solution, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium globionate, calcium gluceptate, calcium gluconate, D-gluconic acid, glycero Calcium phosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, calcium phosphate dibasic, phosphoric acid, calcium phosphate tribasic, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixture, dibasic potassium phosphate, one Basic potassium phosphate, potassium phosphate mixture, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixture, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen -free water, isotonic saline, Ringer's solution, ethyl alcohol, and combinations thereof.

Exemplary lubricants include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oil, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and combinations thereof.

Exemplary oils are almond, apricot kernel, avocado, babasu palm, bergamot, black currant seed, borage, caade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee , corn, cottonseed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, pumpkin, grapeseed, hazelnut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea ku Beba, Macadamia Nut, Mallow, Mango Seed, Meadowfoam Seed, Mink, Nutmeg, Olive, Orange Raffi with Orange, Palm, Palm Kernel, Peach Kernel, Peanut, Poppy Seed, Pumpkin Seed, Rapeseed, Rice Bran, Rosemary, Safflower , sandalwood, sasquana, savory, sea buckthorn, sesame, shea butter, silicon, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary oils are butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil , and combinations thereof, but are not limited thereto.

Liquid dosage forms for oral and parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage form may contain an inert diluent commonly used in the art such as, for example, water or other solvents, solubilizers and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed, peanut, corn, sprout, olive, castor, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions may include adjuvants such as wetting, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In a specific embodiment for parenteral administration, the Bifidobacterium bifidum 193 strain of the present invention (Accession No. KCTC14782BP), its culture and/or its extract may contain a solubilizing agent such as Cremophor, alcohol, oil, denatured oil, It is mixed with glycols, polysorbates, cyclodextrins, polymers, and combinations thereof.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active ingredient may contain one or more inert pharmaceutically acceptable excipients or carriers such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid, b) ) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrants such as agar, calcium carbonate, potato or tapioca starch , alginic acid, certain silicates, and sodium carbonate, e) dissolution retardants such as paraffin, f) absorption enhancers such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof.

In the case of capsules, tablets and pills, dosage forms may contain a buffering agent. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using lactose or milk sugar as well as high molecular weight polyethylene glycols and the like as such excipients. Solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They may optionally contain opacifying agents and may be of a composition that they release the active ingredient only, or preferentially, in a specific part of the intestinal tract, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric materials and waxes. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using lactose or milk sugar as well as high molecular weight polyethylene glycols and the like as such excipients.

The active ingredient may be in micro-encapsulated form with one or more excipients as described above. Solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings, and other coatings well known in the pharmaceutical formulation art. In such solid dosage forms the active ingredient may be mixed with one or more inert diluents such as sucrose, lactose or starch. Such dosage forms may contain additional substances other than inert diluents, as is usually practiced, for example tablet lubricants and other tablet aids such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, dosage forms may also contain a buffering agent. They may optionally contain opacifying agents and may be of a composition that they release the active ingredient only, or preferentially, in a specific part of the intestinal tract, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric materials and waxes.

In the present invention, the dosage form for topical and / or transdermal administration of the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and / or its extract is an ointment, paste, cream, lotion, gel, Powders, solutions, sprays, inhalants and/or patches may also be included. Generally, the active ingredient is mixed with a pharmaceutically acceptable carrier and/or any necessary preservatives and/or buffers as may be required under sterile conditions. Additionally, the present invention contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of active ingredients to the body. Such dosage forms can be prepared, for example, by dissolving and/or dispersing the active ingredient in a suitable medium. Alternatively or additionally, the ratio may be controlled by providing a ratio controlling membrane and/or dispersing the active ingredient in a polymer matrix and/or gel.

Formulations for topical administration include, but are not limited to, liquid and/or semi-liquid preparations such as liniments, lotions, oil-in-water and/or water-in-oil emulsions such as creams, ointments/or pastes, and/or solutions and/or suspensions. A topically-administerable formulation may contain, for example, from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient may be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further include one or more of the additional ingredients described herein.

In the present invention, the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and/or its extract are typically prepared in dosage unit form for easy and uniform administration. It will be appreciated, however, that the total daily usage of the compositions of the present invention will be determined by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dosage level for any particular subject depends on a variety of factors including the disease, disorder, or disorder being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the subject's age, weight, general health, sex, and diet; the administration time, administration route, and excretion rate of the specific active ingredient employed; duration of treatment; drugs used in combination or coincidental with the specific active ingredient employed; and factors well known in the medical arts.

The pharmaceutical composition comprising the Bifidobacterium bifidum 193 strain of the present invention (Accession No. KCTC14782BP), its culture and/or its extract may be administered by any route. In some embodiments, a pharmaceutical composition comprising Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof is administered orally, intravenously, intramuscularly, intraarterially, intramedullarily, intrathecally. , subcutaneous, intraventricular, transdermal, intradermal, rectal, intravaginal, intraperitoneal, topical (by powder, ointment, cream, and/or droplets), mucosal, nasal, buccal, enteral, sublingual; intratracheal instillation, bronchial instillation, and/or inhalation; and/or by various routes including oral spray, nasal spray, and/or aerosol. Routes specifically contemplated are permeable intravenous injection, local administration via blood and/or lymphatic supply, and/or administration directly to the affected site. In general, the most suitable route of administration will depend on a variety of factors, including the nature of the agent (eg, stability in the environment of the gastrointestinal tract), and the disorder of the subject (eg, whether the subject can tolerate oral administration). will be. Currently, oral and/or nasal spray and/or aerosol routes are most commonly used to deliver therapeutic agents directly to the lungs and/or respiratory system. However, the present invention includes delivery of a pharmaceutical composition according to the present invention by any suitable route taking into account advances in the field of drug delivery.

In a specific embodiment, a pharmaceutical composition comprising the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof of the present invention is about 0.001 mg/kg to about 100 mg of the subject's body weight daily. /kg, about 0.01 mg/kg to about 50 mg/kg, about 0.1 mg/kg to about 40 mg/kg, about 0.5 mg/kg to about 30 mg/kg, about 0.01 mg/kg to about 10 mg/kg , about 0.1 mg/kg to about 10 mg/kg, or about 1 mg/kg to about 25 mg/kg at dosage levels sufficient to deliver one or more times per day to achieve the desired therapeutic effect. The target dosage may be delivered three times a day, twice a day, every day, every two days, every three days, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage may be delivered via multiple administrations (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more administrations). .

In the context of the present invention, it will be appreciated that the dosage ranges provide guidance for the administration of a given pharmaceutical composition to an adult. For example, the amount to be administered to a child or adolescent can be determined by a physician or a person skilled in the art, and may be less than or equal to that administered to an adult. The exact amount of a peptide according to the present invention required to achieve an effective amount will vary from subject to subject, depending, for example, on the subject's species, age, and overall disability, severity of side effects or disorders, identity of the particular compound, mode of administration, and the like.

In the present invention, it will be understood that the pharmaceutical composition comprising the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and/or its extract can be used as a combination therapy. The particular combination of treatments (therapeutic agents or procedures) to be used in combination therapy will take into account the desired therapeutic effect to be achieved and the suitability of the desired therapeutic agent and/or procedure.

A pharmaceutical composition of the present invention may be administered alone or in combination with one or more therapeutically active agents. By “combination,” the following delivery methods are within the scope of this invention, but are not intended to imply that the agents must be administered at the same time and/or formulated for co-delivery. The composition may be administered concurrently with, prior to, or after one or more other desired therapeutic agents or medical procedures. Generally, each agent will be administered at the dosage and/or time schedule defined for that agent. Additionally, the present invention relates to the pharmaceutical use of the present invention in combination with an agent capable of improving its bioavailability, reducing and/or modifying its metabolism, inhibiting its secretion, and/or modifying its distribution in the body. It encompasses delivering the composition. The Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and/or its extract and therapeutically active agent of the present invention used in this combination can be administered together in a single composition or separately administered in different compositions. It will be understood.

The specific combination used in the combination therapy is a desired therapeutic effect to be achieved and/or a procedure comprising the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), a culture thereof and/or an extract thereof and/or a therapeutically active agent of the present invention. will consider the suitability of The combination used can achieve the desired effect for the same disorder (for example, the Bifidobacterium bifidum 193 strain of the present invention (Accession No. KCTC14782BP), its culture and / or its extract treats the same disorder It will be appreciated that they may be administered in combination with another therapeutically active agent used to achieve different effects (eg, control of any side effects).

In the present invention, "therapeutic active agent" refers to any substance used as a medicine to treat, prevent, delay, reduce or ameliorate a disorder, and refers to a substance used for treatment, including prophylactic and curative treatment. .

In some embodiments, a pharmaceutical composition of the present invention treats, alleviates, ameliorates, alleviates, delays the onset, inhibits progression, reduces the severity of one or more symptoms or features of inflammatory bowel disease, and/or or in combination with any therapeutically active agent or procedure useful for reducing its incidence (eg, surgery, radiation therapy).

In the present invention, functional foods or health functional foods can be prepared in various forms according to conventional methods known in the art. Functional foods or health functional foods are not limited thereto, but for example, the Bifidobacterium bifidum 193 strain of the present invention (accession number KCTC14782BP), its culture and / or its extract in the form of tea, juice and drink It can be consumed by liquefying, granulating, encapsulating, and powdering so that it can be manufactured and consumed (health drink). In addition, nutritional supplements are not limited thereto, but may be prepared by adding the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) of the present invention, its culture and/or its extract to capsules, tablets, pills, etc. In addition, in order to use the Bifidobacterium bifidum 193 strain (accession number KCTC14782BP), its culture and/or its extract of the present invention in the form of a food additive, it can be prepared and used in the form of a powder or concentrate. In addition, the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) of the present invention, its culture and / or its extract, and a known active ingredient known to have an effect of preventing or improving inflammatory bowel disease are mixed together in the form of a composition. can be manufactured

In the present invention, when the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP), its culture and/or its extract are used as a health drink, the health drink composition is prepared with various flavors or natural ingredients like conventional drinks. It may contain carbohydrates and the like as additional ingredients. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

In the present invention, the Bifidobacterium bifidum 193 strain (accession number KCTC14782BP), its culture and / or its extract may be contained as an active ingredient of a food composition for preventing or improving inflammatory bowel disease, the amount of which is inflammatory bowel disease It is not particularly limited to an effective amount to achieve disease prevention or amelioration, but is preferably 0.01 to 100% by weight based on the total weight of the total composition.

In the present invention, the functional food composition or health functional food composition is a Bifidobacterium bifidum 193 strain (accession number KCTC14782BP), its culture and / or its extract together with other activities known to be effective in inflammatory bowel disease. It can be prepared by mixing together the ingredients.

In the present invention, in addition to the above, the food of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, and stable It may contain an agent, preservative, glycerin, alcohol or carbonation agent, and the like. In addition, the food of the present invention may contain fruit flesh for producing natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for exemplifying the present invention, and it is obvious to those skilled in the art that the scope of the present invention is not construed as being limited by these examples.

[Example]

Production of Inflammatory Bowel Disease (IBD) mouse model

An inflammatory bowel disease mouse model was prepared by mixing DSS in drinking water at a concentration of 3% (w/v) and drinking C57BL6/N mice for 5 days.

Experimental method for inflammatory bowel disease (IBD) mouse model

After making an inflammatory bowel disease (IBD) mouse model, sterile PBS (phosphate buffered saline), Bifidobacterium bifidum ATCC 29521 strain and Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) were ingested for 14 days, and the intestinal The degree of relief of inflammation was compared. At 9 weeks, male C57BL6/N mice were mixed with untreated healthy mice (negative control), DSS ((Dextran Sulfate Sodium)) 3% in negative water, and then 14 days after ingestion of PBS, 3% DSS in negative water. Mice that ingested Bifidobacterium bifidum 193 (Accession No. KCTC14782BP) for 14 days after mixing and ingestion, and mice that ingested Bifidobacterium bifidum ATCC 29521 strain for 14 days after mixing 3% DSS in drinking water, respectively. The experiment was conducted for a total of 3 weeks with 4 animals per group (FIG. 1). Mice that ingested each strain ingested 10 9 CFU/kg/day of the strain.

Body weight change in inflammatory bowel disease (IBD) mouse model

When intestinal inflammation is induced, diarrhea and bloody stools occur and rapid weight loss occurs, so the relief of inflammation was evaluated based on these indicators.

As a result, while the weight of the negative control group was constant for 3 weeks, it was confirmed that the weight of the group with intestinal inflammation was severely reduced. The ingested strain tended to recover weight loss (FIG. 2).

As a result, it was confirmed that the Bifidobacterium bifidum strain (Accession No. KCTC14782BP) is effective in regulating inflammation.

Intestinal Length in Inflammatory Bowel Disease (IBD) Mouse Model

When intestinal inflammation is induced, the length of the colon is reduced, so the relief of inflammation was evaluated based on the recovery of the length of the colon.

As a result, the average length of the colon in the negative control group was 7.9 cm, whereas in the case of the group with intestinal inflammation, the length of the colon was severely reduced to an average of 5.1 cm (FIG. 3). In addition, the intestinal length of the group ingesting the Bifidobacterium bifidum ATCC 29521 strain tended to decrease to an average of 4.9 cm (FIG. 3). In contrast, in the case of Bifidobacterium bifidum strain 193 (accession number KCTC14782BP), it was confirmed that the average length of the large intestine increased to 5.3 cm (FIG. 3).

Accordingly, it was confirmed that intake of the Bifidobacterium bifidum 193 strain (Accession No. KCTC14782BP) has a superior effect on recovery from inflammatory bowel disease compared to intake of the Bifidobacterium bifidum ATCC 29521 strain.

Measurement of intestinal immune cytokines in inflammatory bowel disease (IBD) mouse model

When intestinal inflammation is induced, inflammatory cytokines IL-6 and IL-1β are increased and intestinal inflammation is induced due to the activation of immune cells. Excessive secretion of inflammatory cytokines intensifies inflammation, resulting in tissue damage and, when more severe, causes cancer. To control this, the secretion of inflammatory cytokines is regulated by the anti-inflammatory cytokine IL-10. When inflammatory bowel disease is induced by DSS, inflammatory cytokines increase. By evaluating how well they are controlled in mice ingesting the strain, it was confirmed that there is a recovery effect for inflammatory bowel disease.

As a result, IL-6 and IL-1β, which are inflammatory cytokines in the colon, were significantly increased in inflammatory bowel disease model mice fed DSS compared to the negative control group. It was confirmed that IL-6 and IL-1β cytokines were greatly reduced compared to mice fed the Bifidobacterium bifidum ATCC 29521 strain (FIGS. 4 and 5).

In addition, in the case of IL-10, an anti-inflammatory cytokine, it was confirmed that the Bifidobacterium bifidum 193 (Accession No. KCTC14782BP) or Bifidobacterium bifidum ATCC 29521 strain was significantly increased in the mouse group fed (FIG. 6). .

As a result, it was confirmed that the Bifidobacterium bifidum strain 193 (Accession No. KCTC14782BP) has excellent ability to regulate inflammation.

Measurement of Spleen Weight in Inflammatory Bowel Disease (IBD) Mouse Model

The weight of the spleen increases as it increases in size when infected or inflamed. When inflammatory bowel disease is induced by DSS, the weight of the spleen increases due to inflammation. It was confirmed that there is a recovery effect of inflammatory bowel disease by evaluating how well the spleen weight is controlled in mice ingesting the strain.

As a result, compared to the negative control group, the spleen weight of the inflammatory bowel disease model mice fed with DSS was significantly increased to 188 mg (FIG. 7). In the case of mice ingesting the Bifidobacterium bifidum 193 strain (accession number KCTC14782BP), the intake decreased to 180 mg, whereas in the case of mice ingesting the ATCC 29521 strain, the intake increased to 197.5 mg (FIG. 7).

As a result, it was confirmed that the inflammation of the mice ingested the Bifidobacterium bifidum strain 193 (Accession No. KCTC14782BP) was alleviated.

Confirmation of genome information of Bifidobacterium bifidum 193 strain

Genomic information of the Bifidobacterium bifidum 193 strain isolated from cabbage kimchi was confirmed (FIG. 8). Bifidobacterium bifidum 193 strain has a size of 2,228,015 bp. As a result of comparison with the genomes of various probiotics registered in the NCBI Database, it was confirmed that the nucleotide sequence of the genome of the Bifidobacterium bifidum 193 strain was different from that of other bifidobacterium bifidum. Specifically, it was confirmed that the Bifidobacterium bifidum genome was grouped with each other to confirm that the strain of the present invention was Bifidobacterium bifidum. It was confirmed that there was a lot of difference from Gamterium bifidum 193 strain.

[Accession number]

Name of depositor: Korea Research Institute of Bioscience and Biotechnology Biological Resources Center (KCTC)

Accession number: KCTC14782BP

Entrusted date: 20211118

Claims (6)

A probiotic composition comprising a Bifidobacterium bifidum 193 strain (accession number: KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.
According to claim 1,
The probiotic composition is characterized in that for improving inflammatory bowel disease, the composition.
According to claim 2,
The composition, characterized in that the inflammatory bowel disease is Crohn's disease and / or ulcerative colitis.
A pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a Bifidobacterium bifidum 193 strain (accession number: KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.
According to claim 4,
The composition, characterized in that the inflammatory bowel disease is Crohn's disease and / or ulcerative colitis.
A functional food composition comprising a Bifidobacterium bifidum 193 strain (accession number: KCTC14782BP), a culture thereof and/or an extract thereof as an active ingredient.

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