WO2022265447A1 - Composition comprising lacticaseibacillus sp. or lactobacillus sp. strain as active ingredient for diagnosis, prevention, or treatment of cancer - Google Patents

Composition comprising lacticaseibacillus sp. or lactobacillus sp. strain as active ingredient for diagnosis, prevention, or treatment of cancer Download PDF

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WO2022265447A1
WO2022265447A1 PCT/KR2022/008602 KR2022008602W WO2022265447A1 WO 2022265447 A1 WO2022265447 A1 WO 2022265447A1 KR 2022008602 W KR2022008602 W KR 2022008602W WO 2022265447 A1 WO2022265447 A1 WO 2022265447A1
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cancer
lactobacillus
composition
strain
curvatus
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PCT/KR2022/008602
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French (fr)
Korean (ko)
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박승환
최승현
이정숙
이주혁
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한국생명공학연구원
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Publication of WO2022265447A1 publication Critical patent/WO2022265447A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • 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
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • a composition for cancer diagnosis a kit comprising the composition; cancer prevention or treatment method using the pharmaceutical composition; And it relates to a method for diagnosing cancer using the composition for diagnosis and a method for providing information for diagnosing cancer.
  • Viral vectors A variety of agents for treating cancer have been developed, and non-viral vectors using viral vectors and nano-particles as gene carriers to deliver drugs into cancer tissues.
  • Viral vectors bacterial vectors using aerobic, anaerobic, and anaerobic strains are used.
  • Viral vectors showing high drug delivery efficiency are being used not only for anticancer treatment but also for gene therapy for other diseases.
  • the recently reported side effects of viral vectors clearly show the limitations of viral vectors (wide range of host cells, causing side effects on immunity upon repeated administration), and thus the development of safer gene delivery systems is required.
  • the present inventors have made diligent efforts to develop strains that are safe and have excellent anticancer effects without pathogenicity . ), and Lactobacillus brevis ( Lactobacillus brevis ) By confirming that the strain has a cancer targeting effect and cancer growth inhibitory effect, the strain can be used as an active ingredient in a composition for diagnosing, preventing or treating cancer By revealing that completed the present invention.
  • One object of the present invention is to provide a Lactobacillus paracasei strain deposited under accession number KCTC 14228BP.
  • Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or to provide a pharmaceutical composition for the prevention or treatment of cancer, comprising a culture thereof as an active ingredient.
  • Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or it relates to a food composition for preventing or improving cancer, comprising a culture thereof as an active ingredient.
  • Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or it relates to a feed composition for preventing or improving cancer, comprising a culture thereof as an active ingredient.
  • Another object of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis; Or to provide a composition for diagnosing cancer comprising a culture thereof as an active ingredient.
  • Another object of the present invention is to provide a kit for diagnosing cancer including the composition for diagnosing cancer.
  • Another object of the present invention is to provide a method for diagnosing cancer or providing information for diagnosing cancer, including administering the composition for diagnosing cancer to a subject.
  • Another object of the present invention is to provide a method for preventing or treating cancer, comprising administering the pharmaceutical composition to a subject.
  • Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or to provide a cancer prevention, treatment, or improvement use of a composition containing a culture thereof.
  • Another object of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis; Or to provide a cancer diagnosis use of the culture thereof.
  • the strain of the present invention itself can be used for diagnosis, prevention, improvement, or treatment of cancer without toxicity, and can be used as a carrier for a cancer therapeutic agent according to loading of an anticancer agent.
  • Lactobacillus paracasei Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis confirming the cancer targeting effect of strains in a mouse model of colorectal cancer. This is the diagram showing the result.
  • Figure 2 is a diagram showing the results of confirming the cancer-targeting effect of the Lactobacillus paracasei strain in a colorectal cancer animal model.
  • Figure 3 is a diagram showing the results of confirming the cancer-targeting effect of the Lactobacillus paracasei strain in breast cancer animal models.
  • Figure 4 shows the anticancer effects of Lactobacillus paracasei KCTC 14228BP, Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis strains in a mouse model of colorectal cancer. It is a diagram showing the result of checking.
  • Lactobacillus paracasei KCTC 14228BP alone and in combination with Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis in a mouse model of colorectal cancer. It is a diagram showing the results of quantifying the anticancer effect.
  • Figure 6 is a diagram showing the results of confirming the anticancer effect of Lactobacillus paracasei KCTC 14228BP strain and Salmonella strain ( Salmonella - ⁇ ppGpp) in a breast cancer mouse model.
  • FIG. 7 is a diagram showing the results of quantifying the anticancer effect of Lactobacillus paracasei KCTC 14228BP strain and Salmonella strain ( Salmonella - ⁇ ppGpp) in a breast cancer mouse model.
  • FIG. 8 is a diagram showing the anticancer effect of the Lactobacillus paracasei KCTC 14228BP strain against various carcinoma types.
  • FIG. 9 is a diagram showing that the anticancer effect of the Lactobacillus paracasei KCTC 14228BP strain is excellent compared to other Lactobacillus paracasei.
  • One aspect of the present invention provides a Lactobacillus paracasei strain deposited with accession number KCTC 14228BP.
  • Lactobacillus paracasei is one of microorganisms belonging to the Lactobaciilus casei group, and is one of the microorganisms inhabiting the human intestine. According to the recent reclassification of the genus Lactobacillus by genetic analysis, Lactobacillus paracasei can be used interchangeably with Lactobacillus paracasei belonging to the genus Lacticaseibacillus.
  • the Lactobacillus paracasei may be a strain deposited as KCTC 14228BP, but is not limited thereto.
  • the strain may be a live strain or an attenuated strain (killed strain).
  • "Attenuation” means modifying a strain to reduce its pathogenicity. Attenuation is done for the purpose of reducing toxicity and other side effects when the strain is administered to a subject.
  • Attenuated strains can be prepared through various methods known in the art. For example, attenuation can be achieved by deleting or destroying virulence factors that allow the strain to survive in host cells. Such deletions and disruptions are well known in the art and are performed by methods such as homologous recombination, chemical mutagenesis, irradiation mutagenesis, or transposon mutagenesis.
  • the culture of the present invention refers to a culture solution obtained by culturing a specific microorganism in a culture medium, a concentrated culture solution, a dried product of a culture solution, a culture filtrate, a concentrated culture filtrate, a dried product of a culture filtrate, a diluted solution, a concentrated solution, and collecting cells of the strain It means a lysate, a fermented product, etc., which have been disrupted, and the culture medium means that it contains a specific bacterium, and the culture filtrate is substantially excluding a specific bacterium separated by filtration or the like. It does not mean that bacteria are completely excluded from the filtrate.) It means not included.
  • the fermentation product of a specific strain is not only the fermented material itself, but also the culture medium of the strain in which the strain and the culture coexist, the fermentation product obtained by filtering the strain from the culture medium, and the strain being sterilized from the culture medium and filtered.
  • fermented product an extract obtained by extracting the fermentation product or a culture medium containing the same, a diluent obtained by diluting the fermentation product or its extract, a concentrated solution, a dried product obtained by drying the fermentation product or its extract, and collecting and crushing the cells of the strain Lysates, etc., include all kinds of materials including fermented products generated from the above strains.
  • the Lactobacillus paracasei strain deposited under accession number KCTC 14228BP of the present invention may have cancer targeting.
  • Lactobacillus paracasei deposited under accession number KCTC 14228BP has a cancer target, enabling cancer diagnosis, and having significantly superior anticancer effect compared to other Lactobacillus paracasei strains (Example 3 and 6).
  • Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer, including a Lactobacillus paracasei strain or a culture thereof deposited under accession number KCTC 14228BP.
  • the culture and the like are as described above.
  • the pharmaceutical composition is any one or more selected from the group consisting of Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis , or a culture thereof It may further include.
  • Lactobacillus reuteri is known as one of the most widely inhabited intestinal microorganisms in mammals.
  • Lactobacillus curvatus is one of non-starter (NSLAB) microorganisms, and has two subspecies of curvatus and melibiosus.
  • Lactobacillus brevis in the present invention can be found in fermented food, human intestines, feces, and vagina, and is the main Lactobacillus found in tibicos cereals that make kefir. one of the species
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis are all Gram-positive microorganisms belonging to the Lactobaciilaceae family, and have the advantage of being non-toxic to humans.
  • Lactobacillus paracasei and Lactobacillus reuteri are microorganisms included in the Ministry of Food and Drug Safety Notice 19, and have excellent stability.
  • the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains of the present invention may all be derived from the human body, specifically, from the microbiome of the human intestine, but are limited thereto. It doesn't work.
  • all of the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains can be isolated from feces, etc., but the method of origin and separation is not limited as long as each strain has its own characteristics. don't
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains may be live strains or attenuated strains (dead strains). Attenuation is as described above.
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains of the present invention are derived from the human body and are safe, so they can be used in the form of live strains.
  • cancer refers to cells having characteristics of cancer-causing cells such as uncontrolled proliferation, immortality, metastatic potential, rapid growth and proliferation rate, and characteristic morphological characteristics known in the art. speaks of existence.
  • the cancer may be used in the same sense as "tumor".
  • the cancer is not limited as long as it can be targeted by Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis, but specifically colorectal cancer, breast cancer, and prostate cancer.
  • lung cancer non-small cell lung cancer, colon cancer, bone cancer, pancreatic cancer, gallbladder cancer, skin cancer, head or neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, perianal cancer, colon cancer, fallopian tube carcinoma, endometrium Carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, chronic or acute leukemia, It may be lymphocytic lymphoma, bladder cancer, renal or ureteric cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system (CNS) tumor, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma or pituitary adenoma, etc.
  • CNS central nervous system
  • pancreatic cancer gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, bladder cancer, and stomach cancer, but is not limited thereto.
  • Cancer can also include pre-malignant cancer as well as malignant cancer.
  • Lactobacillus paracasei Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis may be a genetically engineered strain to additionally express a gene having an anticancer effect.
  • the gene is not limited in type as long as it has anticancer activity, but specifically p53, rb1 (retinoblastoma susceptibility gene), wt1 (Wilms' tumors), nf1 (neurofibromatosis type-1), fap (familial adenomatosis polyposis) coli), vhl (von Hippel-Lindau syndrome), Cytolysin A (toxin gene), and antibody mimics.
  • p53 retinoblastoma susceptibility gene
  • wt1 Wide tumors
  • nf1 neurofibromatosis type-1
  • fap familial adenomatosis polyposis
  • vhl von Hippel-Lindau syndrome
  • Cytolysin A toxin gene
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains or cultures thereof contain components known to have anticancer effects (eg, anticancer drugs) or metabolites of the strains. It may be further included, and for the purpose of the present invention, the component or metabolite is not limited in kind.
  • the component having the anticancer effect examples include doxorubicin, cyclophosphamide, mecholrethamine, uramustine, melphalan, chlorambucil, Ifosfamide, bendamustine, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide ), thiotepa, altretamine, duocarmycin, cisplatin, carboplatin, nedaplatin, oxaliplatin, satrapl Satraplatin, triplatin tetranitrate, 5-fluorouracil, 6-mercaptopurine, capecitabine, cladribine , clofarabine, cystarbine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, pemetrexed (pemetrexed), pentostatin, thioguanine, camptothecin, topotecan, irinote
  • prevention refers to any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis or a culture thereof as an active ingredient. It means any action that inhibits or delays the onset or progression of cancer by administration of the composition.
  • treatment refers to clinically intervening to alter the natural process of a subject or cell to be treated, which can be performed during the course of a clinical pathological condition or to prevent it. Desired therapeutic effects include preventing occurrence or recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, and alleviating the disease state. or providing temporary relief, remission or improving prognosis.
  • all actions that improve the course of cancer by administering a composition containing Lactobacillus paracasei or its culture as an active ingredient, deposited under accession number KCTC 14228BP, are included.
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis of the present invention have excellent cancer targeting, the efficiency of anticancer drug delivery is high, and the cancer prevention or treatment effect is excellent.
  • Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis of the present invention may be an active ingredient of a pharmaceutical composition, and a component having an anticancer effect by targeting cancer (eg, an anticancer agent) or It can be used as a carrier for the metabolite of the strain and used as a pharmaceutical composition.
  • a component having an anticancer effect by targeting cancer eg, an anticancer agent
  • a carrier for the metabolite of the strain can be used as a pharmaceutical composition.
  • composition of the present invention can be formulated in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, etc. according to conventional methods for the administration.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
  • excipient for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
  • Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, in addition to water and liquid paraffin, which are commonly used simple diluents, may be used.
  • Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
  • composition of the present invention may further include a carrier, excipient or diluent.
  • Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydrogel Mineral oils such as hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and silicon dioxide may be used.
  • Another aspect of the present invention provides a method for preventing or treating cancer, comprising administering the pharmaceutical composition for preventing or treating cancer to a subject.
  • the pharmaceutical composition for preventing or treating cancer, prevention, treatment, and cancer is as described above.
  • Another aspect of the present invention provides a food composition for preventing or improving cancer, comprising Lactobacillus paracasei or a culture thereof deposited under accession number KCTC 14228BP as an active ingredient.
  • the food composition of the present invention may further include any one or more selected from the group consisting of Lactobacillus reuteri, Lactobacillus, Curvatus, and Lactobacillus brevis, or a culture thereof.
  • Lactobacillus paracasei Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, cancer, prevention, etc. are as described above.
  • the term "improvement” refers to any one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, or a culture thereof, as an active ingredient. It refers to any activity in which cancer is improved or beneficially changed by administration of the composition.
  • the food composition for preventing or improving cancer of the present invention includes pills, powders, granules, precipitates, tablets, capsules or liquids, and the food to which the composition of the present invention can be added includes, for example, various foods. , For example, there are beverages, gum, tea, vitamin complexes, and health supplements.
  • supplementary food additives may be further added, and the supplementary food additives include conventional food supplement additives in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. .
  • natural carbohydrates examples include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavors for example, rebaudioside A, glycyrrhizin, etc.
  • synthetic flavors sacharin, aspartame, etc.
  • the food composition for preventing or improving cancer of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like.
  • it may include fruit flesh for the manufacture of natural fruit juice, fruit juice beverages, and vegetable beverages. These components may be used independently or in combination.
  • the health supplements include health functional foods and health foods.
  • the health functional food is the same term as food for special health use (FoSHU), and is a medicine processed to efficiently display bioregulatory functions in addition to nutrient supply, and has high medical effect.
  • “function (sex)” means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions.
  • the food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the preparation.
  • the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food.
  • the food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material, and has excellent portability, so that the composition of the present invention
  • the food composition can be ingested as an adjuvant to enhance the effect of preventing or improving cancer.
  • Another aspect of the present invention provides a feed composition for preventing or improving cancer comprising a Lactobacillus paracasei strain or a culture thereof deposited under accession number KCTC 14228BP.
  • Lactobacillus paracasei prevention, improvement, and cancer are as described above.
  • the feed composition may include known carriers, stabilizers, or additives acceptable for pharmaceutical, food, or feed use.
  • binders for example, there are binders, emulsifiers, and preservatives added to prevent quality deterioration, and amino acids, vitamins, enzymes, flavors, non-protein nitrogen compounds, silicates, and buffers added to feed to increase efficacy.
  • extractants, oligosaccharides, etc. may further include a feed mixture and the like, but is not limited thereto.
  • the feed composition may contain various nutrients such as vitamins, amino acids, and minerals, antioxidants, and other additives as needed, and may be in a suitable state such as powder, granule, pellet, or suspension.
  • the feed composition of the present invention can be supplied alone or mixed with feed for unit animals.
  • the feed of the present invention is not particularly limited, and is not particularly limited as long as it is for animals such as dogs, cats, horses, and cattle. Powder feed, solid feed, dry feed, wet feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet ) Feed, raw food, etc., any feed is fine.
  • Another aspect of the present invention is selected from the group consisting of Lactobacillus paracasei , Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis It provides a composition for diagnosing cancer, comprising any one or more or a culture thereof as an active ingredient.
  • Lactobacillus paracasei Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis are as described above.
  • Lactobacillus paracasei may be deposited under accession number KCTC 14228BP, but is not limited thereto.
  • the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curbatus, and Lactobacillus brevis of the present invention can target cancer, the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curbatus, or Lactobacillus brevis strains It may include a means capable of detecting, and for example, the strain may be a genetically engineered strain to express a luminescent protein.
  • the type of the luminescent protein is not limited as long as it emits light of a wavelength that can be detected by a device capable of detecting light.
  • the luminescent protein may be green fluorescent protein, red fluorescent protein, blue fluorescent protein, yellow fluorescent protein, near-infrared fluorescent protein, or luciferase derived from prokaryotic or eukaryotic organisms.
  • the luciferase may be bacterial-derived luciferase, firefly ( Photinus pyralis ) luciferase, sea pansy ( Renilla ) luciferase, or Metridia luciferase.
  • the strain is a strain-specific gene known in the art in addition to the expression of a luminescent protein. It may include mutations, markers, and the like.
  • diagnosis means a process of confirming the presence or characteristics of a pathological state.
  • diagnosis may be interpreted as confirming whether cancer progresses or develops.
  • the diagnostic composition of the present invention is administered to a subject to determine whether or not cancer has occurred, and the level of the strain contained in the composition is measured at a specific location (tissue) of the subject to determine whether or not cancer has occurred at the location (tissue).
  • tissue a specific location of the subject to determine whether or not cancer has occurred at the location (tissue).
  • the term “individual” of the present invention refers to all animals, such as rats, mice, livestock, and the like, including humans who have or are likely to develop cancer. Specifically, it may be mammals including humans.
  • the "administration” means introducing the composition of the present invention to a subject by any suitable method, and the route of administration of the composition may be administered through various routes, oral or parenteral.
  • an injection method such as external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection may be selected.
  • composition of the present invention can be formulated in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, etc. according to conventional methods for the administration.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
  • excipient for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
  • Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, in addition to water and liquid paraffin, which are commonly used simple diluents, may be used.
  • Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
  • composition of the present invention may further include a carrier, excipient or diluent.
  • Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydrogel Mineral oils such as hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and silicon dioxide may be used.
  • kits for diagnosing cancer including the composition for diagnosing cancer.
  • composition for diagnosing cancer and cancer are as described above.
  • the kit can measure the presence level of the strain in an individual or sample and the strain in normal tissue with the kit. After measuring and comparing the presence level, if the object or sample has a higher level of strain than normal tissue, it can be diagnosed as having cancer.
  • the kit treats a subject suspected of having cancer or a composition containing one or more strains selected from Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, or a culture thereof, to a sample of the subject. And, it can be used to diagnose cancer by measuring the level of presence of one or more of the strains present in the subject or a sample of the subject, as long as it is suitable for a luminometer, primer or probe as well as an analysis method for measuring the level of existence
  • One or more other component compositions, solutions or devices may also be included.
  • a diagnostic kit for measuring the presence level of the strain of the present invention may be a kit including a luminometer.
  • the strain since the strain may be a strain genetically engineered to express a luminescent protein, the measuring instrument is not limited to that type as long as it can measure the luminescence of the expressed protein.
  • a diagnostic kit for specifically measuring the presence level of the strain may be a kit including essential elements required to perform RT-PCR.
  • the RT-PCR kit contains, in addition to each primer pair for the strain-specific gene, a test tube or other suitable container, reaction buffer (with varying pH and magnesium concentration), deoxynucleotides (dNTPs), Taq-polymerase and reverse transcriptase. enzymes such as enzymes, DNase, RNAse inhibitors, DEPC-water, sterile water, and the like.
  • a primer pair specific to a gene used as a quantitative control may be included.
  • the diagnostic kit for specifically measuring the levels of the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains may be a kit including a probe.
  • the probe refers to a nucleic acid fragment such as RNA or DNA corresponding to as short as several bases to as long as several hundred bases, capable of specific binding with the strain-specific gene, and labeled with a fluorescent marker or a radioactive marker, etc. (labeled), it is possible to confirm the presence or absence of a specific gene region.
  • the probe may be in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, or an RNA probe.
  • Another aspect of the present invention is cancer diagnosis comprising the step of detecting any one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis in a sample.
  • the sample may be a sample isolated from a subject treated with the composition for diagnosing cancer, or a sample isolated from a subject to which the composition for diagnosing cancer is administered.
  • Lactobacillus paracasei Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, the composition for diagnosing cancer, and the subject are as described above.
  • the step of detecting one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis may include measuring the level of the strain in a tissue. However, it is not limited thereto. The detection or level measurement may be performed through biopsy biopsy, measurement of luminescent protein, etc., but is not limited thereto. A step of diagnosing cancer or providing information for diagnosing cancer when a strain of a certain level or higher (eg, the strain detection level of the normal control group) is detected may be further included, but is not limited thereto.
  • the sample may be a cell or tissue of an individual, but is not limited thereto.
  • administering the composition for diagnosing cancer to a subject; and/or measuring the level of detection in the tissue, but is not limited thereto.
  • composition for diagnosing cancer, diagnosing cancer, and the like are as described above.
  • composition for diagnosing cancer of the present invention has an effect of targeting cancer, it is possible to track the occurrence of cancer and the location of a tumor by administering the composition, and by providing such information, information for diagnosing cancer is provided. can do.
  • compositions comprising a Lactobacillus paracasei strain and/or a culture thereof deposited under Accession No. KCTC 14228BP for use in preventing, treating, or improving cancer.
  • the composition may be a pharmaceutical composition, food composition, and / or feed composition, but is not limited thereto.
  • the composition is any one or more selected from the group consisting of Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis; And / or may further include a culture thereof, but is not limited thereto.
  • Another aspect of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis; Or it provides a cancer diagnostic use of its culture.
  • Lactobacillus paracasei may be deposited under accession number KCTC 14228BP, but is not limited thereto.
  • Lactobacillus paracasei Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, cancer, prevention, treatment, improvement, diagnosis, and the like are as described above.
  • Example 1 Production of colon cancer and breast cancer animal models by injecting colon cancer or breast cancer cells into normal mice
  • a colorectal cancer animal model was prepared by subcutaneously administering CT26 cell line 1x10 6 cells/50 ⁇ L, a colorectal cancer cell line, to the thigh of a known BALB/c (male) mouse.
  • a breast cancer animal model was prepared by subcutaneously administering 4T1 cell line 1 ⁇ 10 6 cells/50 ⁇ L, a breast cancer cell line, to the thigh of a known BALB/c (male) mouse.
  • Example 2 Preparation of an anticancer composition comprising Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains
  • Example 2-1 Obtaining Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis
  • Lactobacillus paracasei In order to obtain Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, known Lactobacillus reuteri from KGMB, a strain bank derived from Korean intestinal microbiome banking business, Lactobacillus curvatus , and Lactobacillus brevis strains were distributed.
  • the present inventors newly discovered a Lactobacillus paracasei strain, and the first Lactobacillus strain discovered by the present inventors is Lactobacillus paracasei subsp.
  • KGMB04157 or V1bio04157, BCT04157 is the same
  • KCTC Korea Center for Biological Resources
  • Example 2-2 Preparation of anti-cancer composition for administration to cancer animal models
  • a composition containing Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis obtained in Example 2-1 was prepared as follows.
  • the composition contained only microorganisms or PBS, and the composition is classified according to the type of microorganisms included as shown in [Table 2].
  • Example 3 Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains
  • Example 3-1 Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis
  • the microorganism has a cancer target, it suggests that cancer can be diagnosed based on this and suggests the possibility of an excellent cancer treatment effect, so the cancer target of the microorganism of the genus Lactobacillus of the present invention was analyzed.
  • composition No. 2 of [Table 2] was administered to the cancer animal model, and 5 days later, the tumor was extracted from the animal model. After each strain, the number of strains per tumor mass was measured. As a result, it was confirmed that all of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis have cancer targets (FIG. 1).
  • Example 3-2 Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP)
  • Lactobacillus paracasei KGMB04157 or V1bio04157, BCT04157, KCTC 14228BP was further specifically confirmed.
  • the Lactobacillus paracasei (1x10 9 CFU) was injected into the colorectal cancer animal model, and 5 days later, the colorectal Tumors were extracted from cancer animal models, smeared on MRS agar, and the resulting colonies were finally confirmed. Colonies were identified by 16S rRNA sequencing.
  • Lactobacillus paracasei (KCTC 14228BP) has excellent colorectal cancer tumor targeting (FIG. 2).
  • Lactobacillus paracasei injection, tumor extraction, smearing, and colony confirmation were performed in the same manner as in the colorectal cancer animal model described above.
  • Lactobacillus paracasei The targeting properties of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis suggest that they have cancer diagnostic effects.
  • Example 4 Confirmation of anticancer effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains (in vivo)
  • Example 4-1 Confirmation of the effect of reducing the volume of colorectal cancer tumors by the Lactobacillus strain mixture (in vivo)
  • the mixed composition including Lactobacillus paracasei and Lactobacillus paracasei It was confirmed that significantly reduced the volume of cancer (FIG. 4).
  • Example 4-3 Confirmation of breast cancer tumor volume reduction effect by Lactobacillus paracasei (KCTC 14228BP) (in vivo)
  • Lactobacillus paracasei (KCTC 14228BP) is more cancerous than Salmonella- ⁇ ppGpp (Park SH et al., Theranostics 2016; 6(10):1672-1682.), which is known to have anticancer effects, as well as the PBS group. It was confirmed that the volume was greatly reduced (FIG. 6).
  • Example 4-4 Confirmation of breast cancer tumor volume reduction effect by Lactobacillus paracasei (KCTC 14228BP) (in vivo)
  • Lactobacillus paracasei (KCTC 14228BP) significantly reduced the volume of cancer than not only the PBS group but also Salmonella - ⁇ ppGpp known to have anticancer effects (FIG. 7).
  • Example 5 Confirmation of anticancer effect of Lactobacillus paracasei KCTC 14228BP strain against various cancer types
  • the anticancer effect was confirmed by treating the Lactobacillus paracasei KCTC 14228BP strain of the present invention with various types of carcinoma.
  • each cancer cell was cultured in a 37°C CO 2 incubator using DMEM or RPMI medium supplemented with 10% FBS and 1% Antibiotic solution, and then the number of cancer cells in a 96 well plate was prepared to be 1x10 4 cells/well. After overnight culture, Lactobacillus paracasei KCTC 14228BP was treated at an MOI of 10 with DMEM or RPMI medium supplemented with 2% FBS. After 48 hours, absorbance was measured using LDH assay reagent.
  • Lactobacillus paracasei KCTC 14228BP strain of the present invention has excellent anticancer effects against pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, and stomach cancer (FIG. 8).
  • Example 6 Comparison of anticancer effects of Lactobacillus paracasei KCTC 14228BP strain and other Lactobacillus paracasei strains
  • Lactobacillus paracasei KCTC 3189 and KCTC 3510 were distributed, and the cancer cell inhibition levels of Lactobacillus paracasei KCTC 14228BP (KGMB04157), KCTC 3189, and KCTC 3510 were measured.
  • a colorectal cancer cell line in a 37°C CO 2 incubator using DMEM or RPMI medium supplemented with 10% FBS and 1% Antibiotic solution
  • the number of cancer cells in a 96 well plate is 1x10 4 cells/well.
  • Lactobacillus paracasei was treated at an MOI of 10 with DMEM or RPMI medium supplemented with 2% FBS. After 48 hours, absorbance was measured using LDH assay reagent.
  • Lactobacillus paracasei KCTC 14228BP (KGMB04157) significantly reduced the survival rate of cancer cells, but Lactobacillus paracasei KCTC 3189 and KCTC 3510 had little effect of reducing cancer cell viability (FIG. 9).
  • Lactobacillus paracasei KCTC 14228BP has a significantly superior anticancer effect compared to other Lactobacillus paracasei.

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Abstract

The present invention relates to: a (Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; a pharmaceutical composition for prevention or treatment of cancer and a food composition for prevention or alleviation of cancer, each comprising the strain or a culture thereof as an active ingredient; a composition comprising at least one selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis as an active ingredient for diagnosis of cancer; a kit comprising the composition; a method for prevention or treatment of cancer, using the pharmaceutical composition; a method for diagnosis of cancer, using the diagnostic composition; and a method for providing information for cancer diagnosis.

Description

락티카제이바실러스 속 또는 락토바실러스 속 균주를 유효성분으로 포함하는 암 진단, 예방 또는 치료용 조성물A composition for diagnosing, preventing or treating cancer comprising a strain of the genus Lactasei bacillus or a strain of the genus Lactobacillus as an active ingredient
수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이(Lactobacillus paracasei) 균주; 상기 균주 또는 이의 배양물을 유효성분으로 포함하는, 암 예방 또는 치료용 약학적 조성물, 암 예방 또는 개선용 식품 조성물, 사료 조성물; 락토바실러스 파라카제이(Lactobacillus paracasei), 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상을 유효성분으로 포함하는, 암 진단용 조성물; 상기 조성물을 포함하는 키트; 상기 약학적 조성물을 이용한 암 예방 또는 치료방법; 및 상기 진단용 조성물을 이용한 암 진단방법 및 암 진단을 위한 정보제공방법에 관한 것이다. Lactobacillus paracasei strain deposited under accession number KCTC 14228BP; A pharmaceutical composition for preventing or treating cancer, a food composition for preventing or improving cancer, and a feed composition comprising the strain or its culture as an active ingredient; Contains at least one selected from the group consisting of Lactobacillus paracasei , Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis as an active ingredient To, a composition for cancer diagnosis; a kit comprising the composition; cancer prevention or treatment method using the pharmaceutical composition; And it relates to a method for diagnosing cancer using the composition for diagnosis and a method for providing information for diagnosing cancer.
암을 치료하기 위한 제제는 다양하게 개발되어 왔으며, 암 조직의 내부로 약물을 전달하기 위한 유전자 전달체로 바이러스 벡터(viral vector), 나노입자(nano-particle)를 사용하는 비-바이러스 벡터(non-viral vector), 호기성, 통혐기성, 및 혐기성 균주를 사용하는 박테리아 벡터(bacterial vector)가 사용되고 있다. 이중 높은 약물전달 효율을 보여주는 바이러스 벡터는 항암치료뿐만 아니라 다른 질병의 유전자 치료에도 활용되고 있다. 하지만, 최근 보고되고 있는 바이러스 벡터의 부작용 사례들은 바이러스 벡터가 가지는 한계점(숙주세포의 범위가 넓고, 반복투여 시 면역부작용을 일으킴)을 여실히 보여주고 있어, 더욱 안전한 유전자 전달체의 개발이 요구된다.A variety of agents for treating cancer have been developed, and non-viral vectors using viral vectors and nano-particles as gene carriers to deliver drugs into cancer tissues. Viral vectors), bacterial vectors using aerobic, anaerobic, and anaerobic strains are used. Viral vectors showing high drug delivery efficiency are being used not only for anticancer treatment but also for gene therapy for other diseases. However, the recently reported side effects of viral vectors clearly show the limitations of viral vectors (wide range of host cells, causing side effects on immunity upon repeated administration), and thus the development of safer gene delivery systems is required.
이러한 실정에 맞추어, 약 100여 년 전 세균에 의한　암　억제현상이 보고된 후, 많은 연구진들에 의해 항암효과를 가지는 균주들이 개발되고 있으며 일부 연구 그룹에서는 이미 임상단계가 진행 중에 있다.In line with this situation, after the phenomenon of suppressing cancer by bacteria was reported about 100 years ago, strains with anticancer effects have been developed by many researchers, and some research groups are already in the clinical stage.
암 조직의 특성인 낮은 산소 분압, 풍부한 영양분 및 면역반응의 결핍 등은 세포환경에서 증식하는 병원성 균주가 선호하는 서식지의 특징이기도 하다. 특히　암 조직의 중심에 위치한 괴사 영역(necrotic region)은 약물전달이 효율적으로 이루어지지 않고,　암의 전이 등을 유발한다고 알려져 있다. 클로스트리듐(Clostridium), 비피도박테리움(Bifidobacterium),　살모넬라(Salmonella), 리스테리아(Listeria) 등은　암 조직 중심에 있는 괴사 영역의 풍부한 영양분에 집적하여 증식하며, 이 과정에서　암 조직의 축소 및 성장억제 등이 관찰되어 예로부터 항암치료를 위한 생 균주로 사용되고 있다(Nicholas J Roberts et al, Science Translational Medicine, 2014, Vol. 6, Issue 249, pp. 249ra111).Low oxygen partial pressure, abundant nutrients, and lack of immune response, which are characteristics of cancer tissue, are also characteristics of the habitat that pathogenic strains proliferating in the cellular environment prefer. In particular, it is known that a necrotic region located in the center of cancer tissue does not efficiently deliver drugs and induces cancer metastasis. Clostridium , Bifidobacterium , Salmonella , Listeria , etc. accumulate and proliferate in rich nutrients in the necrotic area in the center of cancer tissue, and in this process, cancer tissue shrinks and Growth inhibition has been observed and has been used as a live strain for anticancer treatment since ancient times (Nicholas J Roberts et al, Science Translational Medicine, 2014, Vol. 6, Issue 249, pp. 249ra111).
그러나, 상기 균주들은 병원성이 있어 항암치료를 위해 사용할 때 주의가 요구된다. 암 세포 사멸 후 제거되지 않고 남은 잔존 균주에 의해 부작용이 발생할 수 있기 때문이다. 예를 들어, 잔존　살모넬라에 의한 만성 감염 시 보균자로서 다른 주변인에게로의 감염 우려가 있고, 면역 기능이 약화된 환자나 노약자는 병원성이 약화된　살모넬라에 의해 치명적인 패혈증이 발생할 수 있으며, 만성 감염 시 생성된 항체는 자가면역질환(autoimmune disease)을 일으킬 가능성, 예를 들면, 관절염, 안염, 요도염 등이 발생할 우려가 있다.However, since these strains are pathogenic, caution is required when using them for anticancer treatment. This is because side effects may occur due to remaining strains that are not removed after cancer cell death. For example, in the case of chronic infection by residual 　Salmonella, there is a risk of infection to other people as a carrier, and patients with weakened immune function or the elderly may develop fatal sepsis due to 　Salmonella whose pathogenicity is weakened. Antibodies may cause autoimmune diseases, such as arthritis, blepharitis, and urethritis.
본 발명자들은 병원성이 없어 안전하고 항암효과가 뛰어난 균주를 개발하기 위해 예의 노력한 결과, 인체에서 유래한 락토바실러스 파라카제이(Lactobacillus paracasei), 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis) 균주에 암 표적화(targeting) 효과 및 암 성장 억제 효과가 있는 것을 확인하여, 상기 균주를 암 진단, 예방 또는 치료용 조성물의 유효성분으로 사용할 수 있음을 밝힘으로써 본 발명을 완성하였다.The present inventors have made diligent efforts to develop strains that are safe and have excellent anticancer effects without pathogenicity . ), and Lactobacillus brevis ( Lactobacillus brevis ) By confirming that the strain has a cancer targeting effect and cancer growth inhibitory effect, the strain can be used as an active ingredient in a composition for diagnosing, preventing or treating cancer By revealing that completed the present invention.
본 발명의 하나의 목적은 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주를 제공하는 것이다.One object of the present invention is to provide a Lactobacillus paracasei strain deposited under accession number KCTC 14228BP.
본 발명의 다른 하나의 목적은 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주; 또는 이의 배양물을 유효성분으로 포함하는, 암 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or to provide a pharmaceutical composition for the prevention or treatment of cancer, comprising a culture thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주; 또는 이의 배양물을 유효성분으로 포함하는, 암 예방 또는 개선용 식품 조성물에 관한 것이다.Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or it relates to a food composition for preventing or improving cancer, comprising a culture thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주; 또는 이의 배양물을 유효성분으로 포함하는, 암 예방 또는 개선용 사료 조성물에 관한 것이다.Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or it relates to a feed composition for preventing or improving cancer, comprising a culture thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 또는 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물을 유효성분으로 포함하는, 암 진단용 조성물을 제공하는 것이다.Another object of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis; Or to provide a composition for diagnosing cancer comprising a culture thereof as an active ingredient.
본 발명의 또 다른 하나의 목적은 상기 암 진단용 조성물을 포함하는 암 진단용 키트를 제공하는 것이다.Another object of the present invention is to provide a kit for diagnosing cancer including the composition for diagnosing cancer.
본 발명의 또 다른 하나의 목적은 상기 암 진단용 조성물을 개체에 투여하는 단계를 포함하는, 암 진단방법 또는 암 진단을 위한 정보제공 방법을 제공하는 것이다.Another object of the present invention is to provide a method for diagnosing cancer or providing information for diagnosing cancer, including administering the composition for diagnosing cancer to a subject.
본 발명의 또 다른 하나의 목적은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는, 암 예방 또는 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating cancer, comprising administering the pharmaceutical composition to a subject.
본 발명의 또 다른 하나의 목적은 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주; 또는 이의 배양물을 포함하는 조성물의 암 예방, 치료, 또는 개선 용도를 제공하는 것이다.Another object of the present invention is the Lactobacillus paracasei strain deposited with accession number KCTC 14228BP; Or to provide a cancer prevention, treatment, or improvement use of a composition containing a culture thereof.
본 발명의 또 다른 하나의 목적은 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 또는 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물의 암 진단 용도를 제공하는 것이다.Another object of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis; Or to provide a cancer diagnosis use of the culture thereof.
본 발명의 균주는 그 자체로 독성 없이 암 진단, 예방, 개선, 또는 치료에 이용될 수 있으며, 항암제 탑재에 따른 암 치료제의 담체로 활용될 수 있다.The strain of the present invention itself can be used for diagnosis, prevention, improvement, or treatment of cancer without toxicity, and can be used as a carrier for a cancer therapeutic agent according to loading of an anticancer agent.
도 1은 대장암 마우스 모델에서 락토바실러스 파라카제이(Lactobacillus paracasei), 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis) 균주의 암 표적화 효과를 확인한 결과를 나타낸 도이다.1 is Lactobacillus paracasei , Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis confirming the cancer targeting effect of strains in a mouse model of colorectal cancer. This is the diagram showing the result.
도 2는 대장암 동물모델에서 락토바실러스 파라카제이(Lactobacillus paracasei) 균주의 암 표적화 효과를 확인한 결과를 나타낸 도이다.Figure 2 is a diagram showing the results of confirming the cancer-targeting effect of the Lactobacillus paracasei strain in a colorectal cancer animal model.
도 3은 유방암 동물모델에서 락토바실러스 파라카제이(Lactobacillus paracasei) 균주의 암 표적화 효과를 확인한 결과를 나타낸 도이다.Figure 3 is a diagram showing the results of confirming the cancer-targeting effect of the Lactobacillus paracasei strain in breast cancer animal models.
도 4는 대장암 마우스 모델에서 락토바실러스 파라카제이(Lactobacillus paracasei) KCTC 14228BP, 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis) 균주의 항암효과를 확인한 결과를 나타낸 도이다.Figure 4 shows the anticancer effects of Lactobacillus paracasei KCTC 14228BP, Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis strains in a mouse model of colorectal cancer. It is a diagram showing the result of checking.
도 5는 대장암 마우스 모델에서 락토바실러스 파라카제이(Lactobacillus paracasei) KCTC 14228BP 단독 및, 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스 (Lactobacillus brevis)와의 조합의 항암효과를 정량한 결과를 나타낸 도이다.5 is Lactobacillus paracasei KCTC 14228BP alone and in combination with Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis in a mouse model of colorectal cancer. It is a diagram showing the results of quantifying the anticancer effect.
도 6은 유방암 마우스 모델에서 락토바실러스 파라카제이 KCTC 14228BP 균주 및 살모넬라 균주(Salmonella-△ppGpp)의 항암효과를 확인한 결과를 나타낸 도이다.Figure 6 is a diagram showing the results of confirming the anticancer effect of Lactobacillus paracasei KCTC 14228BP strain and Salmonella strain ( Salmonella -ΔppGpp) in a breast cancer mouse model.
도 7은 유방암 마우스 모델에서 락토바실러스 파라카제이 KCTC 14228BP 균주 및 살모넬라 균주(Salmonella-△ppGpp)의 항암효과를 정량한 결과를 나타낸 도이다.7 is a diagram showing the results of quantifying the anticancer effect of Lactobacillus paracasei KCTC 14228BP strain and Salmonella strain ( Salmonella -ΔppGpp) in a breast cancer mouse model.
도 8은 다양한 암종에 대한 락토바실러스 파라카제이 KCTC 14228BP 균주의 항암효과를 나타낸 도이다.8 is a diagram showing the anticancer effect of the Lactobacillus paracasei KCTC 14228BP strain against various carcinoma types.
도 9는 다른 락토바실러스 파라카제이에 대비하여 락토바실러스 파라카제이 KCTC 14228BP 균주의 항암효과가 우수함을 나타낸 도이다.9 is a diagram showing that the anticancer effect of the Lactobacillus paracasei KCTC 14228BP strain is excellent compared to other Lactobacillus paracasei.
이하, 본 발명 내용에 대하여 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시한 일 양태의 설명 및 실시형태는 공통된 사항에 대하여 다른 양태의 설명 및 실시 형태에도 적용될 수 있다. 또한, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 더불어, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.Hereinafter, the contents of the present invention will be described in detail. On the other hand, the description and embodiment of one aspect disclosed in the present invention can also be applied to the description and embodiment of another aspect with respect to common matters. Additionally, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.
본 발명의 일 양태는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이(Lactobacillus paracasei) 균주를 제공한다.One aspect of the present invention provides a Lactobacillus paracasei strain deposited with accession number KCTC 14228BP.
본 발명에서 용어 "락토바실러스 파라카제이(Lactobacillus paracasei)" 는 락토바실러스 카제이(Lactobaciilus casei) 군에 속하는 미생물 중 하나로서, 인체 장 내에 서식하는 미생물 중 하나이다. 최근 유전자 분석에 의해 락토바실러스 속이 재분류됨에 따라, 락토바실러스 파라카제이는 락티카제이바실러스(Lacticaseibacillus) 속에 속하는 락토카제이바실러스 파라카제이와 혼용될 수 있다.In the present invention, the term " Lactobacillus paracasei " is one of microorganisms belonging to the Lactobaciilus casei group, and is one of the microorganisms inhabiting the human intestine. According to the recent reclassification of the genus Lactobacillus by genetic analysis, Lactobacillus paracasei can be used interchangeably with Lactobacillus paracasei belonging to the genus Lacticaseibacillus.
본 발명의 목적상 상기 락토바실러스 파라카제이는 KCTC 14228BP로 기탁된 균주일 수 있으나, 이에 제한되지 않는다. 또한, 본 발명자들은 KCTC 14228BP 미생물은 KGMB04157, V1bio04157, 및 BCT04157와 같이 여러 종류의 명칭으로 명명 하였는 바, 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주는 KGMB04157, V1bio04157, 및 BCT04157 균주 또는 미생물과 혼용될 수 있다.For the purposes of the present invention, the Lactobacillus paracasei may be a strain deposited as KCTC 14228BP, but is not limited thereto. In addition, the present inventors named KCTC 14228BP microorganisms by various names such as KGMB04157, V1bio04157, and BCT04157, and the Lactobacillus paracasei strain deposited under accession number KCTC 14228BP is KGMB04157, V1bio04157, and BCT04157 strains or microorganisms may be mixed.
상기 균주는 생 균주 또는 약독화 균주(사균주)일 수 있다. "약독화"는 균주의 병원성을 감소시키도록 변형시키는 것을 의미한다.　약독화는 균주를 대상체에 투여할 경우 독성 및 다른 부작용을 감소시킬 목적으로 이루어진다.　약독화 균주는 당업계에 공지된 다양한 방법을 통하여 제조될 수 있다. 예를 들어,　약독화는 균주가 숙주세포에서 생존하도록 하는 독성인자(virulence factor)을 결실시키거나 파괴하여 달성될 수 있다. 상기 결실 및 파괴는 당업계에 잘 알려져 있으며, 예컨대, 상동성 재조합, 화학적 변이유발, 조사 변이유발, 또는 트랜스포존 변이유발 등과 같은 방법에 의해 실시된다. The strain may be a live strain or an attenuated strain (killed strain). "Attenuation" means modifying a strain to reduce its pathogenicity. Attenuation is done for the purpose of reducing toxicity and other side effects when the strain is administered to a subject. Attenuated strains can be prepared through various methods known in the art. For example, attenuation can be achieved by deleting or destroying virulence factors that allow the strain to survive in host cells. Such deletions and disruptions are well known in the art and are performed by methods such as homologous recombination, chemical mutagenesis, irradiation mutagenesis, or transposon mutagenesis.
본 발명의 배양물이란 특정 미생물을 배양 배지에서 배양하여 수득한 배양액, 농축 배양액, 배양액의 건조물, 배양 여과액, 농축 배양 여과액, 배양 여과액의 건조물, 희석액, 농축액, 상기 균주의 균체를 포집해서 파쇄시킨 용해물, 발효물 등을 의미하며, 상기 배양액은 특정 균을 포함하는 것을 의미하고, 상기 배양 여과액은 특정 균을 실질적으로(여기서, 실질적으로는 여과등에 의해 분리되는 특정 균을 배제한다는 것을 의미하는 것으로서 여과액에 균이 완전히 배제된다는 것을 의미하지는 않는다.) 포함하지 않는 것을 의미한다. The culture of the present invention refers to a culture solution obtained by culturing a specific microorganism in a culture medium, a concentrated culture solution, a dried product of a culture solution, a culture filtrate, a concentrated culture filtrate, a dried product of a culture filtrate, a diluted solution, a concentrated solution, and collecting cells of the strain It means a lysate, a fermented product, etc., which have been disrupted, and the culture medium means that it contains a specific bacterium, and the culture filtrate is substantially excluding a specific bacterium separated by filtration or the like. It does not mean that bacteria are completely excluded from the filtrate.) It means not included.
본 발명에서, 특정 균주의 발효물은 발효된 물질 자체뿐만 아니라, 균주 및 배양물이 공존하는 균주의 배양 배지, 상기 배양 배지로부터 균주를 여과시킨 발효물, 상기 배양 배지로부터 균주을 멸균처리하고 이를 여과시킨 발효물, 상기 발효물 또는 이를 포함하는 배양 배지를 추출한 추출물, 상기 발효물 또는 이의 추출물을 희석시킨 희석액, 농축액, 상기 발효물 또는 이의 추출물을 건조시킨 건조물, 상기 균주의 균체를 포집해서 파쇄시킨 용해물 등, 상기 균주로부터 발생한 발효물을 포함하는 모든 종류의 물질을 포함한다.In the present invention, the fermentation product of a specific strain is not only the fermented material itself, but also the culture medium of the strain in which the strain and the culture coexist, the fermentation product obtained by filtering the strain from the culture medium, and the strain being sterilized from the culture medium and filtered. fermented product, an extract obtained by extracting the fermentation product or a culture medium containing the same, a diluent obtained by diluting the fermentation product or its extract, a concentrated solution, a dried product obtained by drying the fermentation product or its extract, and collecting and crushing the cells of the strain Lysates, etc., include all kinds of materials including fermented products generated from the above strains.
본 발명의 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주는 암 표적성을 갖는 것일 수 있다.The Lactobacillus paracasei strain deposited under accession number KCTC 14228BP of the present invention may have cancer targeting.
본 발명의 일 실시예에서는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이가 암 표적성이 있어 암 진단이 가능하며 다른 락토바실러스 파라카제이 균주에 비해 항암효과가 현저히 우수함을 확인하였다(실시예 3 및 6).In one embodiment of the present invention, it was confirmed that Lactobacillus paracasei deposited under accession number KCTC 14228BP has a cancer target, enabling cancer diagnosis, and having significantly superior anticancer effect compared to other Lactobacillus paracasei strains (Example 3 and 6).
본 발명의 다른 하나의 양태는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이(Lactobacillus paracasei) 균주 또는 이의 배양물을 포함하는, 암 예방 또는 치료용 약학적 조성물을 제공한다.Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer, including a Lactobacillus paracasei strain or a culture thereof deposited under accession number KCTC 14228BP.
상기 배양물 등은 앞서 설명한 바와 같다.The culture and the like are as described above.
하나의 구체예로, 상기 약학적 조성물은 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상 또는 이의 배양물을 더 포함하는 것일 수 있다.In one embodiment, the pharmaceutical composition is any one or more selected from the group consisting of Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis , or a culture thereof It may further include.
본 발명에서 용어 "락토바실러스 루테리(Lactobacillus reuteri)"는 포유류에서 가장 널리 서식하고 있는 장내 미생물 중 하나로 알려져 있다.In the present invention, the term " Lactobacillus reuteri " is known as one of the most widely inhabited intestinal microorganisms in mammals.
본 발명에서 용어 "락토바실러스 커바투스(Lactobacillus curvatus)" 비스타터(NSLAB) 미생물 중 하나이며, curvatus 및 melibiosus의 두가지 아종을 갖는다.In the present invention, the term " Lactobacillus curvatus " is one of non-starter (NSLAB) microorganisms, and has two subspecies of curvatus and melibiosus.
본 발명에서 용어 "락토바실러스 브레비스(Lactobacillus brevis)"는 발효된 음식, 인체의 장내, 분변, 및 질 등에서 발견될 수 있으며, 케피어(kefir)를 만드는 티비코스(tibicos)곡류에서 발견되는 주된 Lactobacillus 종 중의 하나이다.The term " Lactobacillus brevis " in the present invention can be found in fermented food, human intestines, feces, and vagina, and is the main Lactobacillus found in tibicos cereals that make kefir. one of the species
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 모두 Lactobaciilaceae 과에 속하는 그람 양성 미생물이며, 인체에 독성이 없는 장점이 있다. 특히, 그 중에서도 락토바실러스 파라카제이 및 락토바실러스 루테리는 식약처 고시 19에 포함되는 미생물로서, 안정성이 우수하다. The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis are all Gram-positive microorganisms belonging to the Lactobaciilaceae family, and have the advantage of being non-toxic to humans. In particular, among them, Lactobacillus paracasei and Lactobacillus reuteri are microorganisms included in the Ministry of Food and Drug Safety Notice 19, and have excellent stability.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 균주는 모두 인체에서 유래한 것일 수 있고, 구체적으로 인체 장내의 마이크로바이옴에서 유래한 것일 수 있으나, 이에 제한되지 않는다. 또한, 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 균주는 모두 분변 등에서 분리될 수 있으나, 상기 균주의 각각의 특징을 갖는 한 유래 및 분리되는 방법 등은 제한되지 않는다.The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains of the present invention may all be derived from the human body, specifically, from the microbiome of the human intestine, but are limited thereto. It doesn't work. In addition, all of the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains can be isolated from feces, etc., but the method of origin and separation is not limited as long as each strain has its own characteristics. don't
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 균주는 생 균주 또는 약독화 균주(사균주)일 수 있다. 약독화에 대해서는 앞서 설명한 바와 같다.The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains may be live strains or attenuated strains (dead strains). Attenuation is as described above.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 균주는 인체에서 유래한 것으로서 안전하므로 생 균주 형태로 사용될 수 있다. The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains of the present invention are derived from the human body and are safe, so they can be used in the form of live strains.
본 발명에서 용어, "암"은 조절되지 않은 증식, 불멸성, 전이 잠재성, 신속한 성장 및 증식 속도, 및 당해 분야에 공지된 특징적인 형태학적 특성과 같은 암-유발 세포의 특징을 지니는 세포의 존재를 말한다. 상기 암은 "종양"과 동일한 의미로 사용될 수 있다. 본 발명의 목적상 상기 암은 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스에 의해 표적화 될 수 있는 암이라면 제한이 없으나, 구체적으로 대장암, 유방암, 전립선암, 폐암, 비소세포성 폐암, 결장암, 골암, 췌장암, 담낭암, 피부암, 두부 또는 경부 암, 피부 또는 안구내 흑색종, 자궁암, 난소암, 직장암, 위암, 항문부근암, 결장암, 나팔관암종, 자궁내막암종, 자궁경부암종, 질암종, 음문암종, 호지킨병(Hodgkin's disease), 식도암, 소장암, 내분비선암, 갑상선암, 부갑상선암, 부신암, 연조직 육종, 요도암, 음경암, 만성 또는 급성 백혈병, 림프구 림프종, 방광암, 신장 또는 수뇨관암, 신장세포 암종, 신장골반 암종, 중추신경계(CNS; central nervous system) 종양, 1차 중추신경계 림프종, 척수 종양, 뇌간 신경교종 또는 뇌하수체 선종 등일 수 있으며, 더욱 구체적으로 췌장암, 담낭암, 신장암, 대장암, 폐암, 간암, 피부암, 유방암, 방광암, 및 위암으로 구성되는 군에서 선택되는 어느 하나 이상일 수 있으나, 이에 제한되지 않는다. 또한, 암은 악성 암 뿐만 아니라 전-악성 암도 포함할 수 있다. As used herein, the term "cancer" refers to cells having characteristics of cancer-causing cells such as uncontrolled proliferation, immortality, metastatic potential, rapid growth and proliferation rate, and characteristic morphological characteristics known in the art. speaks of existence. The cancer may be used in the same sense as "tumor". For the purposes of the present invention, the cancer is not limited as long as it can be targeted by Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis, but specifically colorectal cancer, breast cancer, and prostate cancer. , lung cancer, non-small cell lung cancer, colon cancer, bone cancer, pancreatic cancer, gallbladder cancer, skin cancer, head or neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, stomach cancer, perianal cancer, colon cancer, fallopian tube carcinoma, endometrium Carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, chronic or acute leukemia, It may be lymphocytic lymphoma, bladder cancer, renal or ureteric cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system (CNS) tumor, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma or pituitary adenoma, etc. It may be any one or more selected from the group consisting of pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, bladder cancer, and stomach cancer, but is not limited thereto. Cancer can also include pre-malignant cancer as well as malignant cancer.
이때, 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 또는 락토바실러스 브레비스는 항암 효과를 갖는 유전자를 추가로 발현하도록 유전자 조작된 균주일 수 있다.　본 발명의 목적 상 상기 유전자는 항암 활성이 있는 것이라면 종류에 제한이 없으나, 구체적으로 p53, rb1(retinoblastoma susceptibility gene), wt1(Wilms' tumors), nf1(neurofibromatosis type-1), fap(familial adenomatosis polyposis coli), vhl(von Hippel-Lindau syndrome), Cytolysin A(toxin gene), 및 antibody mimics 일 수 있다. In this case, the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis may be a genetically engineered strain to additionally express a gene having an anticancer effect. For the purpose of the present invention, the gene is not limited in type as long as it has anticancer activity, but specifically p53, rb1 (retinoblastoma susceptibility gene), wt1 (Wilms' tumors), nf1 (neurofibromatosis type-1), fap (familial adenomatosis polyposis) coli), vhl (von Hippel-Lindau syndrome), Cytolysin A (toxin gene), and antibody mimics.
또한, 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스 균주 또는 이의 배양물은 항암효과를 갖는 것으로 알려진 성분(예를 들어, 항암제) 또는 균주의 대사산물을 추가로 포함할 수 있으며, 본 발명의 목적상 상기 성분 또는 대사산물은 종류에 제한이 없다. 상기 항암효과를 갖는 성분의 예로는 독소루비신(doxorubicin), 사이클로포스파아마이드(cyclophosphamide), 메클로레타민(mecholrethamine), 우라무스틴(uramustine), 멜파란(melphalan), 클로라부실(chlorambucil), 이포스파미드(ifosfamide), 벤다무스틴(bendamustine), 카르무스틴(carmustine), 로무스틴(lomustine), 스트렙토조신(streptozocin), 부설판(busulfan), 다카바진(dacarbazine), 테모졸로마이드(temozolomide), 티오테파(thiotepa), 알트레타민(altretamine), 듀오카르마이신(duocarmycin), 시스플라틴(cisplatin), 카르보플라틴(carboplatin), 네다플라틴(nedaplatin), 옥사리플라틴(oxaliplatin), 사트라플라틴(satraplatin), 트리플라틴 테트라나이트레이트(triplatin tetranitrate), 5-플루오로우라실(5-fluorouracil), 6-머캅토퓨린(6-mercaptopurine), 카페시타빈(capecitabine), 클라드리빈(cladribine), 클로파라빈(clofarabine), 시스타르빈(cystarbine), 플록스유리딘(floxuridine), 플루다라빈(fludarabine), 겜시타빈(gemcitabine), 하이드록시우레아(hydroxyurea), 메토트렉세이트(methotrexate), 페메트렉세드(pemetrexed), 펜토스타틴(pentostatin), 티오구아닌(thioguanine), 캠토테신(camptothecin), 토포테칸(topotecan), 이리노테칸(irinotecan), 에토포사이드(etoposide), 테니포시드(teniposide), 미토산트론(mitoxantrone), 파클리탁셀(paclitaxel), 도세탁셀(docetaxel), 이자베필론(izabepilone), 빈블라스틴(vinblastine), 빈크리스틴(vincristine), 빈데신(vindesine), 비노렐빈(vinorelbine), 에스트라머스틴(estramustine), 메이탄신(maytansine), DM1 (mertansine, 메르탄신), DM4, 돌라스타틴(dolastatin), 아우리스타틴 E(auristatin E), 아우리스타틴 F(auristatin F), 모노메틸 아우리스타틴 E(monomethyl auristatin E), 모노메틸 아우리스타틴 F(monomethyl auristatin F) 및 이들의 유도체로 이루어진 군에서 선택되는 것일 수 있으나, 이에 제한되지 않는다.In addition, the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains or cultures thereof contain components known to have anticancer effects (eg, anticancer drugs) or metabolites of the strains. It may be further included, and for the purpose of the present invention, the component or metabolite is not limited in kind. Examples of the component having the anticancer effect are doxorubicin, cyclophosphamide, mecholrethamine, uramustine, melphalan, chlorambucil, Ifosfamide, bendamustine, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide ), thiotepa, altretamine, duocarmycin, cisplatin, carboplatin, nedaplatin, oxaliplatin, satrapl Satraplatin, triplatin tetranitrate, 5-fluorouracil, 6-mercaptopurine, capecitabine, cladribine , clofarabine, cystarbine, floxuridine, fludarabine, gemcitabine, hydroxyurea, methotrexate, pemetrexed (pemetrexed), pentostatin, thioguanine, camptothecin, topotecan, irinotecan, etoposide, teniposide, mitoxantrone ( mitoxantrone), paclitaxel, docetaxel, izabepilone, vinblastine, Vincri vincristine, vindesine, vinorelbine, estramustine, maytansine, DM1 (mertansine), DM4, dolastatin, auristatin E It may be selected from the group consisting of (auristatin E), auristatin F, monomethyl auristatin E, monomethyl auristatin F, and derivatives thereof. , but not limited thereto.
본 발명에서 용어, "예방"은 본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 이루어진 군에서 선택되는 어느 하나 이상 또는 이의 배양물을 유효성분으로 포함하는 조성물의 투여로 암의 발병 또는 진행을 억제 또는 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" refers to any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis or a culture thereof as an active ingredient. It means any action that inhibits or delays the onset or progression of cancer by administration of the composition.
본 발명에서 용어, "치료"는 치료하고자 하는 대상체 또는 세포의 천연 과정을 변경시키기 위해 임상적으로 개입하는 것을 지칭하고, 이는 임상 병리 상태가 진행되는 동안 또는 이를 예방하기 위해 수행할 수 있다. 목적하는 치료 효과에는 질병의 발생 또는 재발을 예방하고, 증상을 완화시키며, 질병에 따른 모든 직접 또는 간접적인 병리학적 결과를 저하시키며, 전이를 예방하고, 질병 진행 속도를 감소시키며, 질병 상태를 경감 또는 일시적 완화시키며, 차도시키거나 예후를 개선시키는 것이 포함된다. 본 발명에서는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 또는 이의 배양물을 유효성분으로 포함하는 조성물의 투여로 암의 경과를 호전시키는 모든 행위를 포함한다. As used herein, the term "treatment" refers to clinically intervening to alter the natural process of a subject or cell to be treated, which can be performed during the course of a clinical pathological condition or to prevent it. Desired therapeutic effects include preventing occurrence or recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, and alleviating the disease state. or providing temporary relief, remission or improving prognosis. In the present invention, all actions that improve the course of cancer by administering a composition containing Lactobacillus paracasei or its culture as an active ingredient, deposited under accession number KCTC 14228BP, are included.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 우수한 암 표적성을 가지므로, 항암 약물 전달의 효율성이 높아 암 예방 또는 치료효과가 우수하다.Since the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis of the present invention have excellent cancer targeting, the efficiency of anticancer drug delivery is high, and the cancer prevention or treatment effect is excellent.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 약학적 조성물의 유효성분일 수 있으며, 암 표적성에 의해 항암효과가 있는 성분(예를 들어, 항암제) 또는 균주의 대사산물의 담체로 사용되어 약학적 조성물로 이용될 수 있다.Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis of the present invention may be an active ingredient of a pharmaceutical composition, and a component having an anticancer effect by targeting cancer (eg, an anticancer agent) or It can be used as a carrier for the metabolite of the strain and used as a pharmaceutical composition.
본 발명의 조성물은 상기 투여를 위해 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제 등의 형태로 제제화가 가능하다.The composition of the present invention can be formulated in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, etc. according to conventional methods for the administration.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스, 젤라틴 등을 섞어 제조될 수 있다. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 포함되며, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제 등이 사용될 수 있다.Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, in addition to water and liquid paraffin, which are commonly used simple diluents, may be used.
비경구투여를 위한 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등을 포함할 수 있다. 비수성용제와 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일 등과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
또한, 본 발명의 조성물은 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 담체, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오즈, 메틸 셀루로오즈, 하이드록시 프로필 메틸 셀룰로오즈, 미정질 셀룰로오즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 플로필히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 이산화규소 등의 광물유 등이 사용될 수 있다.In addition, the composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydrogel Mineral oils such as hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and silicon dioxide may be used. can
본 발명의 또 다른 하나의 양태는 상기 암 예방 또는 치료용 약학적 조성물을 개체에 투여하는 단계를 포함하는, 암 예방 또는 치료방법을 제공한다.Another aspect of the present invention provides a method for preventing or treating cancer, comprising administering the pharmaceutical composition for preventing or treating cancer to a subject.
상기 암 예방 또는 치료용 약학적 조성물, 예방, 치료, 및 암 등에 대해서는 앞서 설명한 바와 같다.The pharmaceutical composition for preventing or treating cancer, prevention, treatment, and cancer is as described above.
본 발명의 또 다른 하나의 양태는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 또는 이의 배양물을 유효성분으로 포함하는, 암 예방 또는 개선용 식품 조성물을 제공한다.Another aspect of the present invention provides a food composition for preventing or improving cancer, comprising Lactobacillus paracasei or a culture thereof deposited under accession number KCTC 14228BP as an active ingredient.
하나의 구체예로, 본 발명의 식품 조성물은 락토바실러스 루테리, 락토바실러스, 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상 또는 이의 배양물을 더 포함할 수 있다.In one embodiment, the food composition of the present invention may further include any one or more selected from the group consisting of Lactobacillus reuteri, Lactobacillus, Curvatus, and Lactobacillus brevis, or a culture thereof.
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 락토바실러스 브레비스, 암, 예방 등에 대해서는 앞서 설명한 바와 같다. The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, cancer, prevention, etc. are as described above.
본 발명에서 용어 "개선"은 본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 이루어진 군에서 선택되는 어느 하나 이상의 균주 또는 이의 배양물을 유효성분으로 포함하는 조성물의 투여로 암이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.In the present invention, the term "improvement" refers to any one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, or a culture thereof, as an active ingredient. It refers to any activity in which cancer is improved or beneficially changed by administration of the composition.
본 발명의 암 예방 또는 개선용 식품 조성물은 환제, 분말, 과립, 침제, 정제, 캡슐 또는 액제 등의 형태를 포함하며, 본 발명의 조성물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조식품류 등이 있다.The food composition for preventing or improving cancer of the present invention includes pills, powders, granules, precipitates, tablets, capsules or liquids, and the food to which the composition of the present invention can be added includes, for example, various foods. , For example, there are beverages, gum, tea, vitamin complexes, and health supplements.
본 발명의 암 예방 또는 개선용 식품 조성물에서 포함할 수 있는 필수 성분으로 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스 균주 또는 이의 배양물을 포함하는 암 예방 또는 치료 활성을 갖는 조성물 또는 그의 유효 성분, 또는 그의 생리학적으로 허용 가능한 염을 포함하는 외에는 다른 성분에는 특별히 제한이 없으며 통상의 식품과 같이 여러 가지 생약추출물, 식품 보조 첨가제 또는 천연 탄수화물 등을 추가 성분으로 포함할 수 있다.Prevention of cancer comprising the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strain or a culture thereof as an essential ingredient that can be included in the food composition for preventing or improving cancer of the present invention. Or, there is no particular limitation on other ingredients except for the composition having therapeutic activity, its active ingredient, or its physiologically acceptable salt, and various herbal extracts, food supplement additives, or natural carbohydrates are added as in conventional foods. can be included as
또한, 상기 언급한 바와 같이 식품 보조 첨가제를 추가로 첨가할 수도 있는바 식품 보조 첨가제는 당업계에 통상적인 식품 보조 첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함한다.In addition, as mentioned above, supplementary food additives may be further added, and the supplementary food additives include conventional food supplement additives in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. .
상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 다이사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외에 향미제로서 천연 향미제 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.Examples of the natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the above, natural flavors (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can advantageously be used as flavoring agents.
상기 외에 본 발명의 암 예방 또는 개선용 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 포함할 수 있다. 그밖에 천연 과일쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 포함할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.In addition to the above, the food composition for preventing or improving cancer of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, it may include fruit flesh for the manufacture of natural fruit juice, fruit juice beverages, and vegetable beverages. These components may be used independently or in combination.
상기 건강보조식품은 건강기능식품 및 건강식품 등을 포함한다.The health supplements include health functional foods and health foods.
상기 건강 기능(성) 식품 (functional food)이란, 특정보건용 식품(food for special health use, FoSHU)와 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 "기능(성)"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 식품 조성물은 암의 예방 또는 개선의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The health functional food (functional food) is the same term as food for special health use (FoSHU), and is a medicine processed to efficiently display bioregulatory functions in addition to nutrient supply, and has high medical effect. means food. Here, "function (sex)" means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. The food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the preparation. In addition, the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food. The food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material, and has excellent portability, so that the composition of the present invention The food composition can be ingested as an adjuvant to enhance the effect of preventing or improving cancer.
본 발명의 또 다른 하나의 양태는 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주 또는 이의 배양물을 포함하는 암 예방 또는 개선용 사료 조성물을 제공한다.Another aspect of the present invention provides a feed composition for preventing or improving cancer comprising a Lactobacillus paracasei strain or a culture thereof deposited under accession number KCTC 14228BP.
상기 락토바실러스 파라카제이, 예방, 개선, 및 암 등에 대해서는 앞서 설명한 바와 같다.The Lactobacillus paracasei, prevention, improvement, and cancer are as described above.
상기 사료 조성물에는 상기 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주 또는 이의 배양물 외에도 약학적, 식품학적 또는 사료용으로 허용되는 공지의 담체, 안정화제, 또는 첨가제가 포함될 수 있다. 예를 들어, 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 있고, 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 향미제, 비단백질태질소화합물, 규산염제, 완충제, 추출제, 올리고당 등이 있다. 그 외에도 사료 혼합제 등을 추가로 포함할 수 있으며 이에 한정된 것은 아니다. 상기 사료 조성물은 필요에 따라 비타민, 아미노산류, 미네랄 등의 각종 양분, 항산화제 및 기타의 첨가제 등을 포함할 수도 있으며, 그 형상으로서는 분체, 과립, 펠릿, 현탁액 등의 적당한 상태일 수 있다. 본 발명의 사료 조성물은 단위 동물에 대하여 단독으로 또는 사료에 혼합하여 공급할 수 있다. 본 발명의 사료는 특별히 한정되는 것은 아니고, 개, 고양이, 말, 소 등 동물용이면 제한이 없으며, 분말 사료, 고형 사료, 건사료, 습식사료, 모이스트 펠릿 사료, 드라이 펠릿 사료, EP(Extruder Pellet) 사료, 날먹이 등 어떠한 사료라도 무방하다. In addition to the Lactobacillus paracasei strain or culture thereof deposited under the accession number KCTC 14228BP, the feed composition may include known carriers, stabilizers, or additives acceptable for pharmaceutical, food, or feed use. For example, there are binders, emulsifiers, and preservatives added to prevent quality deterioration, and amino acids, vitamins, enzymes, flavors, non-protein nitrogen compounds, silicates, and buffers added to feed to increase efficacy. , extractants, oligosaccharides, etc. In addition, it may further include a feed mixture and the like, but is not limited thereto. The feed composition may contain various nutrients such as vitamins, amino acids, and minerals, antioxidants, and other additives as needed, and may be in a suitable state such as powder, granule, pellet, or suspension. The feed composition of the present invention can be supplied alone or mixed with feed for unit animals. The feed of the present invention is not particularly limited, and is not particularly limited as long as it is for animals such as dogs, cats, horses, and cattle. Powder feed, solid feed, dry feed, wet feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet ) Feed, raw food, etc., any feed is fine.
본 발명의 또 다른 하나의 양태는 락토바실러스 파라카제이(Lactobacillus paracasei), 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis) 로 구성되는 군에서 선택되는 어느 하나 이상 또는 이의 배양물을 유효성분으로 포함하는, 암 진단용 조성물을 제공한다.Another aspect of the present invention is selected from the group consisting of Lactobacillus paracasei , Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis It provides a composition for diagnosing cancer, comprising any one or more or a culture thereof as an active ingredient.
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 전술한 바와 같다.The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis are as described above.
상기 락토바실러스 파라카제이는 수탁번호 KCTC 14228BP로 기탁된 것일 수 있으나, 이에 제한되지 않는다.The Lactobacillus paracasei may be deposited under accession number KCTC 14228BP, but is not limited thereto.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 암을 표적화할 수 있으므로 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 또는 락토바실러스 브레비스 균주를 검출할 수 있는 수단을 포함할 수 있으며, 그 예로 상기 균주는 발광단백질을 발현하도록 유전자 조작된 균주일 수 있다. 본 발명의 목적 상 상기 발광단백질은 광을 검출할 수 있는 기기에 의해 검출 될 수 있는 파장의 빛을 발하는 것이면 종류가 제한되지 않는다. 상기 발광단백질은 녹색형광단백질, 적색형광단백질, 청색형광단백질, 황색형광단백질, 근적외광형광단백질, 또는 원핵 또는 진핵생물 유래의 루시퍼라제 일 수 있다. 상기 루시퍼라제는 박테리아 유래의 루시퍼라제 또는 반딧불(Photinus pyralis) 루시퍼라제, 바다팬지(Renilla) 루시퍼라제, 메트리디아(Metridia) 루시퍼라제일 수 있다. Since the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curbatus, and Lactobacillus brevis of the present invention can target cancer, the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curbatus, or Lactobacillus brevis strains It may include a means capable of detecting, and for example, the strain may be a genetically engineered strain to express a luminescent protein. For the purposes of the present invention, the type of the luminescent protein is not limited as long as it emits light of a wavelength that can be detected by a device capable of detecting light. The luminescent protein may be green fluorescent protein, red fluorescent protein, blue fluorescent protein, yellow fluorescent protein, near-infrared fluorescent protein, or luciferase derived from prokaryotic or eukaryotic organisms. The luciferase may be bacterial-derived luciferase, firefly ( Photinus pyralis ) luciferase, sea pansy ( Renilla ) luciferase, or Metridia luciferase.
본 발명의 목적상 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 또는 락토바실러스 브레비스 균주의 존재 수준을 확인할 수 있다면, 상기 균주는 발광단백질의 발현 외에 당업계에 알려진 상기 균주 특이적인 유전자 변이, 표지 물질 등을 포함할 수 있다.For the purpose of the present invention, if the presence level of a Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, or Lactobacillus brevis strain can be confirmed, the strain is a strain-specific gene known in the art in addition to the expression of a luminescent protein. It may include mutations, markers, and the like.
본 발명에서 용어 "진단"이란, 병리 상태의 존재 또는 특징을 확인하는 과정을 의미한다. 본 발명에 있어서, 상기 진단은 암의 진행 또는 발병 여부를 확인하는 것으로 해석될 수 있다.In the present invention, the term "diagnosis" means a process of confirming the presence or characteristics of a pathological state. In the present invention, the diagnosis may be interpreted as confirming whether cancer progresses or develops.
본 발명의 진단용 조성물은 암 발병 여부를 확인하고자 하는 개체에 투여하고 개체의 특정 위치(조직)에서 상기 조성물에 포함된 균주의 존재 수준을 측정하여 상기 위치(조직)에서의 암 발병 여부를 판별하는데 이용될 수 있으나, 본 발명의 진단용 조성물을 이용하여 암을 진단할 수 있는 한 본 발명의 범주에 포함되는 것은 자명하다.The diagnostic composition of the present invention is administered to a subject to determine whether or not cancer has occurred, and the level of the strain contained in the composition is measured at a specific location (tissue) of the subject to determine whether or not cancer has occurred at the location (tissue). However, as long as cancer can be diagnosed using the diagnostic composition of the present invention, it is obvious that it is included in the scope of the present invention.
본 발명의 용어 "개체"는 암이 발병하였거나 발병할 가능성이 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적으로, 인간을 포함한 포유동물일 수 있다.The term “individual” of the present invention refers to all animals, such as rats, mice, livestock, and the like, including humans who have or are likely to develop cancer. Specifically, it may be mammals including humans.
이때, 상기 "투여"는 어떠한 적절한 방법으로 개체에게 본 발명의 조성물을 도입하는 것을 의미하며, 조성물의 투여 경로는 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다. 구체적으로, 비경구 투여 시 피부 외용 또는 복강 내 주사, 직장 내 주사, 피하주사, 정맥 내 주사, 근육 내 주사 또는 흉부 내 주사 등의 주입방식을 선택할 수 있다.At this time, the "administration" means introducing the composition of the present invention to a subject by any suitable method, and the route of administration of the composition may be administered through various routes, oral or parenteral. Specifically, for parenteral administration, an injection method such as external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection may be selected.
본 발명의 조성물은 상기 투여를 위해 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제 등의 형태로 제제화가 가능하다.The composition of the present invention can be formulated in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, etc. according to conventional methods for the administration.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제, 예를 들면, 전분, 탄산칼슘, 수크로스, 락토오스, 젤라틴 등을 섞어 제조될 수 있다. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. It can be.
경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 포함되며, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면, 습윤제 등이 사용될 수 있다.Liquid preparations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, in addition to water and liquid paraffin, which are commonly used simple diluents, may be used.
비경구투여를 위한 제제는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제 등을 포함할 수 있다. 비수성용제와 현탁용제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일 등과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
또한, 본 발명의 조성물은 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 담체, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오즈, 메틸 셀루로오즈, 하이드록시 프로필 메틸 셀룰로오즈, 미정질 셀룰로오즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 플로필히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 이산화규소 등의 광물유 등이 사용될 수 있다.In addition, the composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydrogel Mineral oils such as hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and silicon dioxide may be used. can
본 발명의 또 다른 하나의 양태는 상기 암 진단용 조성물을 포함하는, 암 진단용 키트를 제공한다.Another aspect of the present invention provides a kit for diagnosing cancer including the composition for diagnosing cancer.
상기 암 진단용 조성물 및 암 등에 대해서는 앞서 설명한 바와 같다.The composition for diagnosing cancer and cancer are as described above.
본 발명의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 암 특이적인 표적화 효과가 있으므로, 상기 키트로 개체 또는 시료 내 상기 균주의 존재 수준과 정상 조직내 상기 균주의 존재 수준을 측정 후 비교하여, 개체 또는 시료가 정상조직보다 균주 존재 수준이 높으면 암이 존재하는 것으로 진단할 수 있다. Since the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis of the present invention have a cancer-specific targeting effect, the kit can measure the presence level of the strain in an individual or sample and the strain in normal tissue with the kit. After measuring and comparing the presence level, if the object or sample has a higher level of strain than normal tissue, it can be diagnosed as having cancer.
상기 키트는 암의 발병이 의심되는 개체 또는 개체의 시료에 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스에서 선택되는 하나 이상의 균주 또는 이의 배양물을 포함하는 조성물을 처리하고, 상기 개체 또는 개체의 시료에 존재하는 상기 균주 중 어느 하나 이상의 존재 수준을 측정함으로써 암을 진단하는데 사용될 수 있는데, 상기 존재 수준을 측정하기 위한 발광 측정기, 프라이머 또는 프로브 뿐만 아니라 분석 방법에 적합한 한 종류 또는 그 이상의 다른 구성 성분 조성물, 용액 또는 장치가 포함될 수도 있다. The kit treats a subject suspected of having cancer or a composition containing one or more strains selected from Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, or a culture thereof, to a sample of the subject. And, it can be used to diagnose cancer by measuring the level of presence of one or more of the strains present in the subject or a sample of the subject, as long as it is suitable for a luminometer, primer or probe as well as an analysis method for measuring the level of existence One or more other component compositions, solutions or devices may also be included.
구체적으로, 본 발명의 균주의 존재 수준을 측정하기 위한 진단 키트는 발광 측정기를 포함하는 키트일 수 있다. 전술한대로, 상기 균주는 발광단백질을 발현하도록 유전자 조작된 균주 일 수 있으므로 발현되는 단백질의 발광을 측정할 수 있으면 상기 측정기는 그 종류에 제한되지 않는다.Specifically, a diagnostic kit for measuring the presence level of the strain of the present invention may be a kit including a luminometer. As described above, since the strain may be a strain genetically engineered to express a luminescent protein, the measuring instrument is not limited to that type as long as it can measure the luminescence of the expressed protein.
또한, 구체적으로 상기 균주의 존재 수준을 측정하기 위한 진단 키트는 RT-PCR을 수행하기 위해 필요한 필수 요소를 포함하는 키트일 수 있다. RT-PCR 키트는, 상기 균주 특이적인 유전자에 대한 각각의 프라이머 쌍 외에도 테스트 튜브 또는 다른 적절한 컨테이너, 반응 완충액(pH 및 마그네슘 농도는 다양), 데옥시뉴클레오타이드(dNTPs), Taq-폴리머라아제 및 역전사효소와 같은 효소, DNase, RNAse 억제제, DEPC-수(DEPC-water), 멸균수 등을 포함할 수 있다. 또한, 정량 대조군으로 사용되는 유전자에 특이적인 프라이머 쌍을 포함할 수 있다. 　 In addition, a diagnostic kit for specifically measuring the presence level of the strain may be a kit including essential elements required to perform RT-PCR. The RT-PCR kit contains, in addition to each primer pair for the strain-specific gene, a test tube or other suitable container, reaction buffer (with varying pH and magnesium concentration), deoxynucleotides (dNTPs), Taq-polymerase and reverse transcriptase. enzymes such as enzymes, DNase, RNAse inhibitors, DEPC-water, sterile water, and the like. In addition, a primer pair specific to a gene used as a quantitative control may be included.
또한, 구체적으로 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 균주의 존재 수준을 측정하기 위한 진단 키트는 프로브(probe)를 포함하는 키트일 수 있다. 상기 프로브는 상기 균주 특이적인 유전자와 특이적 결합을 이룰 수 있는, 짧게는 수 염기 내지 길게는 수백 염기에 해당하는 RNA 또는 DNA 등의 핵산 단편을 의미하며, 형광 표지인자 또는 방사선 표지인자 등으로 라벨링(labeling) 되어 있어 특정 유전자 부위의 존재 유무를 확인할 수 있다. 프로브는 올리고 뉴클레오타이드(oligonucleotide) 프로브, 단일 사슬 DNA(single stranded DNA) 프로브, 이중 사슬 DNA(double stranded DNA) 프로브, RNA 프로브 등의 형태일 수 있다. In addition, the diagnostic kit for specifically measuring the levels of the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis strains may be a kit including a probe. The probe refers to a nucleic acid fragment such as RNA or DNA corresponding to as short as several bases to as long as several hundred bases, capable of specific binding with the strain-specific gene, and labeled with a fluorescent marker or a radioactive marker, etc. (labeled), it is possible to confirm the presence or absence of a specific gene region. The probe may be in the form of an oligonucleotide probe, a single stranded DNA probe, a double stranded DNA probe, or an RNA probe.
본 발명의 또 다른 하나의 양태는 샘플의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상의 균주를 검출하는 단계를 포함하는 암 진단방법 및 암 진단을 위한 정보제공 방법을 제공한다. 상기 샘플은 개체에서 분리된 샘플에 상기 암 진단용 조성물이 처리된 것이거나, 상기 암 진단용 조성물이 투여된 개체에서 분리된 샘플인 것일 수 있다.Another aspect of the present invention is cancer diagnosis comprising the step of detecting any one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis in a sample Methods and methods for providing information for cancer diagnosis are provided. The sample may be a sample isolated from a subject treated with the composition for diagnosing cancer, or a sample isolated from a subject to which the composition for diagnosing cancer is administered.
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 락토바실러스 브레비스, 암 진단용 조성물, 및 개체 등은 앞서 전술한 바와 같다.The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, the composition for diagnosing cancer, and the subject are as described above.
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상의 균주를 검출하는 단계는 상기 균주의 조직 내 수준을 측정하는 단계를 포함할 수 있으나, 이에 제한되지 않는다. 상기 검출 또는 수준 측정은 생검조직검사, 발광 단백질 측정 등을 통해 이루어질 수 있으나, 이에 제한되지 않는다. 일정 수준 이상(예를 들어, 정상 대조군의 균주 검출 수준)의 균주가 검출되면 암으로 진단 또는 암으로 진단하기 위한 정보를 제공하는 단계를 더 포함할 수 있으나, 이에 제한되지 않는다.The step of detecting one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis may include measuring the level of the strain in a tissue. However, it is not limited thereto. The detection or level measurement may be performed through biopsy biopsy, measurement of luminescent protein, etc., but is not limited thereto. A step of diagnosing cancer or providing information for diagnosing cancer when a strain of a certain level or higher (eg, the strain detection level of the normal control group) is detected may be further included, but is not limited thereto.
상기 샘플은 개체의 세포 또는 조직일 수 있으나, 이에 제한되지 않는다. The sample may be a cell or tissue of an individual, but is not limited thereto.
다른 구체적인 양태로는 상기 암 진단용 조성물을 개체에 투여하는 단계; 및/또는 조직 내 검출 수준을 측정하는 단계를 포함할 수 있으나, 이에 제한되지 않는다.In another specific aspect, administering the composition for diagnosing cancer to a subject; and/or measuring the level of detection in the tissue, but is not limited thereto.
상기 암 진단용 조성물, 암 진단, 및 암 등에 대해서는 앞서 설명한 바와 같다.The composition for diagnosing cancer, diagnosing cancer, and the like are as described above.
본 발명의 상기 암 진단용 조성물은 암을 표적화하는 효과를 가지므로, 상기 조성물의 투여로 암의 발병여부 및 종양 위치추적 등이 가능하고, 이와 같은 정보를 제공함으로써 암을 진단할 수 있는 정보를 제공할 수 있다.Since the composition for diagnosing cancer of the present invention has an effect of targeting cancer, it is possible to track the occurrence of cancer and the location of a tumor by administering the composition, and by providing such information, information for diagnosing cancer is provided. can do.
본 발명의 또 다른 하나의 양태는 본 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주 및/또는 이의 배양물을 포함하는 조성물의 암 예방, 치료, 또는 개선 용도를 제공한다.Another aspect of the present invention provides a composition comprising a Lactobacillus paracasei strain and/or a culture thereof deposited under Accession No. KCTC 14228BP for use in preventing, treating, or improving cancer.
상기 조성물은 약학적 조성물, 식품 조성물, 및/또는 사료 조성물일 수 있으나, 이에 제한되지 않는다.The composition may be a pharmaceutical composition, food composition, and / or feed composition, but is not limited thereto.
상기 조성물은 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상; 및/또는 이의 배양물을 더 포함하는 것일 수 있으나, 이에 제한되지 않는다.The composition is any one or more selected from the group consisting of Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis; And / or may further include a culture thereof, but is not limited thereto.
본 발명의 또 다른 하나의 양태는 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물의 암 진단 용도를 제공한다.Another aspect of the present invention is any one or more selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis; Or it provides a cancer diagnostic use of its culture.
상기 암 진단 용도에서 락토바실러스 파라카제이는 수탁번호 KCTC 14228BP로 기탁된 것일 수 있으나, 이에 제한되지 않는다.In the cancer diagnosis use, Lactobacillus paracasei may be deposited under accession number KCTC 14228BP, but is not limited thereto.
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 락토바실러스 브레비스, 암, 예방, 치료, 개선, 및 진단 등은 전술한 바와 같다.The Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, Lactobacillus brevis, cancer, prevention, treatment, improvement, diagnosis, and the like are as described above.
이하, 본 발명을 실시예를 들어 상세히 설명하고자 하나, 이는 본 발명의 이해를 돕기 위한 것일 뿐, 본 발명의 범위가 이에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by way of example, but this is only to aid understanding of the present invention, and the scope of the present invention is not limited thereto.
실시예Example 1. 정상 마우스에 대장암 또는 유방암 세포를 주사하여 대장암 및 유방암 동물 모델 제작1. Production of colon cancer and breast cancer animal models by injecting colon cancer or breast cancer cells into normal mice
공지된 BALB/c (male) 마우스의 허벅지쪽에 대장암 세포주인 CT26 cell line 1x106 cells/50μL을 피부 밑으로 투여하여 대장암 동물모델을 제작하였다.A colorectal cancer animal model was prepared by subcutaneously administering CT26 cell line 1x10 6 cells/50μL, a colorectal cancer cell line, to the thigh of a known BALB/c (male) mouse.
또한, 공지된 BALB/c (male) 마우스의 허벅지쪽에 유방암 세포주인 4T1 cell line 1Х106 cells/50μL 을 피부 밑으로 투여하여 유방암 동물모델을 제작하였다.In addition, a breast cancer animal model was prepared by subcutaneously administering 4T1 cell line 1Х10 6 cells/50 μL, a breast cancer cell line, to the thigh of a known BALB/c (male) mouse.
실시예 2. 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스 균주를 포함하는 항암용 조성물의 제조Example 2. Preparation of an anticancer composition comprising Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains
실시예 2-1. 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 수득Example 2-1. Obtaining Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis
락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스를 수득하기 위해, 한국인 장내 마이크로바이옴 뱅킹 사업에서 유래된 균주은행인 KGMB으로부터, 공지된 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis) 균주를 분양 받았다.In order to obtain Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, known Lactobacillus reuteri from KGMB, a strain bank derived from Korean intestinal microbiome banking business, Lactobacillus curvatus , and Lactobacillus brevis strains were distributed.
또한, 본 발명자들은 락토바실러스 파라카제이(Lactobacillus paracasei) 균주를 새로이 발굴하였으며, 본 발명자들이 최초로 발굴한 락토바실러스 균주는 Lactobacillus paracasei subsp. tolerance KGMB04157(또는 V1bio04157, BCT04157도 동일함)로 명명한 후 부다페스트 조약 하에 국제기탁기관인 한국생물자원센터(KCTC)에 2020년 7월 6일자로 기탁하여 수탁번호 KCTC 14228BP를 부여 받았다. In addition, the present inventors newly discovered a Lactobacillus paracasei strain, and the first Lactobacillus strain discovered by the present inventors is Lactobacillus paracasei subsp. After naming tolerance KGMB04157 (or V1bio04157, BCT04157 is the same), it was deposited with the Korea Center for Biological Resources (KCTC), an international depositary under the Budapest Treaty, on July 6, 2020, and was given accession number KCTC 14228BP.
구체적인 각각의 균주 명은 하기 [표 1]에 나타내었다.The specific names of each strain are shown in [Table 1] below.
균주명strain name KGMB No.KGMB No.
Lactobacillus paracaseiLactobacillus paracasei KGMB04157 (KCTC 14228BP)KGMB04157 (KCTC 14228BP)
Lactobacillus reuteriLactobacillus reuteri KGMB08543KGMB08543
Lactobacillus curvatusLactobacillus curvatus KGMB04289KGMB04289
Lactobacillus brevisLactobacillus brevis KGMB05945KGMB05945
실시예 2-2. 암 동물 모델에 투여하기 위한 항암용 조성물의 제조Example 2-2. Preparation of anti-cancer composition for administration to cancer animal models
실시예 2-1에서 수득한 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스를 포함하는 조성물을 다음과 같이 제조하였다. 상기 조성물에는 미생물 또는 PBS 만을 포함하였으며, 포함되는 미생물의 종류에 따라 조성물을 구분하면 하기 [표 2]와 같다.A composition containing Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis obtained in Example 2-1 was prepared as follows. The composition contained only microorganisms or PBS, and the composition is classified according to the type of microorganisms included as shown in [Table 2].
조성물 종류composition type 투여 균주 세포 수(CFU)Administered strain Cell count (CFU) 실험군 수number of experimental groups
1One PBS PBS -- n=4n=4
22 Lactobacillus sp.(4종 혼합) Lactobacillus sp. (mix of 4 types) 1x109 cells1x10 9 cells n=8n=8
33 Lactobacillus sp.(4종 혼합) Lactobacillus sp. (mix of 4 types) 1x108 cells1x10 8 cells n=8n=8
44 Lactobacillus paracasei KGMB04157 (KCTC 14228BP) Lactobacillus paracasei KGMB04157 (KCTC 14228BP) 1x109 cells1x10 9 cells n=6n=6
실시예 3. 락토바실러스 파라카제이(KCTC 14228BP), 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스 균주의 암 표적성 및 진단 효과 확인Example 3. Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains
실시예 3-1. 락토바실러스 파라카제이(KCTC 14228BP), 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스의 암 표적성 및 진단 효과 확인Example 3-1. Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis
미생물이 암 표적성이 있다면 이를 기반으로 암을 진단할 수 있음을 시사하며 우수한 암 치료 효과의 가능성을 시사하므로, 본원발명의 락토바실러스 속 미생물의 암 표적성을 분석하였다.If the microorganism has a cancer target, it suggests that cancer can be diagnosed based on this and suggests the possibility of an excellent cancer treatment effect, so the cancer target of the microorganism of the genus Lactobacillus of the present invention was analyzed.
실시예 1에서 제작한 대장암 동물모델의 종양 부피가 약 100 mm3이 되었을 때, 상기 [표 2]의 2번 조성물을 암 동물모델에 투여하여, 5일 후 상기 동물모델로부터 종양을 적출한 후 균주 별로 종양의 질량 당 균주의 수를 측정하였다. 그 결과, 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스 모두 암 표적성이 있음을 확인하였다(도 1). When the tumor volume of the colorectal cancer animal model prepared in Example 1 reached about 100 mm 3 , composition No. 2 of [Table 2] was administered to the cancer animal model, and 5 days later, the tumor was extracted from the animal model. After each strain, the number of strains per tumor mass was measured. As a result, it was confirmed that all of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis have cancer targets (FIG. 1).
실시예 3-2. 락토바실러스 파라카제이(KCTC 14228BP)의 암 표적성 및 진단 효과 확인Example 3-2. Confirmation of cancer targeting and diagnostic effects of Lactobacillus paracasei (KCTC 14228BP)
락토바실러스 파라카제이 KGMB04157 (또는 V1bio04157, BCT04157, KCTC 14228BP)의 암 표적성을 더욱 구체적으로 확인하고자 하였다.The cancer target of Lactobacillus paracasei KGMB04157 (or V1bio04157, BCT04157, KCTC 14228BP) was further specifically confirmed.
이를 위해, 실시예 1에서 제작한 대장암 동물모델의 종양 부피가 약 100 mm3이 되었을 때, 상기 락토바실러스 파라카제이(1x109 CFU)를 대장암 동물모델에 주입하고, 5일 후 상기 대장암 동물모델로부터 종양을 적출하여 MRS agar에 도말하고 생성된 콜로니를 최종 확인하였다. 콜로니는 16S rRNA 시퀀싱을 통해 확인하였다.To this end, when the tumor volume of the colorectal cancer animal model prepared in Example 1 reached about 100 mm 3 , the Lactobacillus paracasei (1x10 9 CFU) was injected into the colorectal cancer animal model, and 5 days later, the colorectal Tumors were extracted from cancer animal models, smeared on MRS agar, and the resulting colonies were finally confirmed. Colonies were identified by 16S rRNA sequencing.
그 결과, 락토바실러스 파라카제이(KCTC 14228BP)의 대장암 종양 표적성이 매우 우수함을 확인하였다(도 2).As a result, it was confirmed that Lactobacillus paracasei (KCTC 14228BP) has excellent colorectal cancer tumor targeting (FIG. 2).
한편, 실시예 1에서 제작한 유방암 동물모델에도 전술한 대장암 동물모델에서 수행한 방식과 동일하게 락토바실러스 파라카제이 주입, 종양 적출, 도말, 및 콜로니 확인을 수행하였다.Meanwhile, in the breast cancer animal model prepared in Example 1, Lactobacillus paracasei injection, tumor extraction, smearing, and colony confirmation were performed in the same manner as in the colorectal cancer animal model described above.
그 결과, 락토바실러스 파라카제이(KCTC 14228BP)의 유방암 종양 표적성이 매우 우수함을 확인하였다(도 3).As a result, it was confirmed that the breast cancer tumor targeting of Lactobacillus paracasei (KCTC 14228BP) was very good (FIG. 3).
상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스의 표적성은 이들의 암 진단 효과가 있음을 시사하는 것이다.The targeting properties of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis suggest that they have cancer diagnostic effects.
실시예 4. 락토바실러스 파라카제이(KCTC 14228BP), 락토바실러스 루테리, 락토바실러스 커바투스, 및/또는 락토바실러스 브레비스 균주의 항암 효과 확인(in vivo)Example 4. Confirmation of anticancer effects of Lactobacillus paracasei (KCTC 14228BP), Lactobacillus reuteri, Lactobacillus curvatus, and/or Lactobacillus brevis strains (in vivo)
실시예 4-1. 락토바실러스 균주 혼합물에 의한 대장암 종양의 부피 감소 효과 확인(in vivo)Example 4-1. Confirmation of the effect of reducing the volume of colorectal cancer tumors by the Lactobacillus strain mixture (in vivo)
실시예 1에서 제작한 대장암 동물모델의 종양 부피가 약 100 mm3이 되었을 때, 상기 [표 2]의 조성물을 각각 대장암 동물모델(n=10 per group)에 투여한 후 0일, 2일, 4일, 6일, 8일, 10일, 13일, 16일, 및 19일차에 상기 동물모델에서의 종양 부피를 확인한 결과, 락토바실러스 파라카제이를 포함한 혼합 조성물 및 락토바실러스 파라카제이가 암의 부피를 크게 감소시켰음을 확인하였다(도 4).When the tumor volume of the colorectal cancer animal model prepared in Example 1 reached about 100 mm 3 , the composition of [Table 2] was administered to the colorectal cancer animal model (n = 10 per group), respectively, on day 0 and 2 As a result of confirming the tumor volume in the animal model on days 1, 4, 6, 8, 10, 13, 16, and 19, the mixed composition including Lactobacillus paracasei and Lactobacillus paracasei It was confirmed that significantly reduced the volume of cancer (FIG. 4).
실시예 4-2. 락토바실러스 균주에 의한 대장암 종양의 부피 감소 효과 확인(in vivo)Example 4-2. Confirmation of the volume reduction effect of colorectal cancer tumors by Lactobacillus strains (in vivo)
상기 실시예 4-1와 동일한 방식으로 실험하여, 암의 부피를 정량화 및 도식화한 결과, 상기 [표 2]의 조성물 모두 암의 부피를 크게 감소시켰음을 확인하였다(도 5).As a result of quantifying and plotting the cancer volume in the same manner as in Example 4-1, it was confirmed that all of the compositions in [Table 2] greatly reduced the cancer volume (FIG. 5).
실시예 4-3. 락토바실러스 파라카제이(KCTC 14228BP)에 의한 유방암 종양의 부피 감소 효과 확인(in vivo)Example 4-3. Confirmation of breast cancer tumor volume reduction effect by Lactobacillus paracasei (KCTC 14228BP) (in vivo)
유방암 동물모델(n=10 per group)에서, 실시예 1에서 제작한 유방암 동물모델의 종양 부피가 약 100 mm3이 되었을 때, PBS, Salmonella-△ppGpp (5×107 CFU) 및 L. paracasei (1×109 CFU)를 각각의 군에 투여하였다. 투여 후 0일, 2일, 4일, 6일, 8일, 및 10일차에 상기 유방암 동물모델에서의 종양 부피를 확인하였다.In the breast cancer animal model (n = 10 per group), when the tumor volume of the breast cancer animal model prepared in Example 1 reached about 100 mm 3 , PBS, Salmonella- ΔppGpp (5×10 7 CFU) and L. paracasei (1×10 9 CFU) was administered to each group. On days 0, 2, 4, 6, 8, and 10 after administration, the tumor volume in the breast cancer animal model was confirmed.
그 결과, PBS군 뿐만 아니라 항암효과가 있는 것으로 알려진 Salmonella-△ppGpp(Park SH et al., Theranostics　2016; 6(10):1672-1682.)보다도 락토바실러스 파라카제이(KCTC 14228BP)가 암의 부피를 크게 감소시켰음을 확인하였다(도 6).As a result, Lactobacillus paracasei (KCTC 14228BP) is more cancerous than Salmonella- ΔppGpp (Park SH et al., Theranostics 2016; 6(10):1672-1682.), which is known to have anticancer effects, as well as the PBS group. It was confirmed that the volume was greatly reduced (FIG. 6).
실시예 4-4. 락토바실러스 파라카제이(KCTC 14228BP)에 의한 유방암 종양의 부피 감소 효과 확인(in vivo)Example 4-4. Confirmation of breast cancer tumor volume reduction effect by Lactobacillus paracasei (KCTC 14228BP) (in vivo)
유방암 동물모델(n=10 per group)에서, 실시예 1에서 제작한 유방암 동물모델의 종양 부피가 약 100 mm3이 되었을 때, PBS, Salmonella-△ppGpp (5×107 CFU) 및 L. paracasei (1×109 CFU)를 각각의 군에 투여하였다. 투여 후 0일, 2일, 4일, 6일, 8일, 및 10일차에 상기 유방암 동물모델에서 종양 부피를 확인하였다.In the breast cancer animal model (n = 10 per group), when the tumor volume of the breast cancer animal model prepared in Example 1 reached about 100 mm 3 , PBS, Salmonella- ΔppGpp (5×10 7 CFU) and L. paracasei (1×10 9 CFU) was administered to each group. On days 0, 2, 4, 6, 8, and 10 after administration, the tumor volume was confirmed in the breast cancer animal model.
암의 부피를 정량화 및 도식화한 결과, PBS군 뿐만 아니라 항암효과가 있는 것으로 알려진 Salmonella-△ppGpp보다도 락토바실러스 파라카제이(KCTC 14228BP)가 암의 부피를 크게 감소시켰음을 확인하였다(도 7).As a result of quantifying and plotting the volume of cancer, it was confirmed that Lactobacillus paracasei (KCTC 14228BP) significantly reduced the volume of cancer than not only the PBS group but also Salmonella -ΔppGpp known to have anticancer effects (FIG. 7).
실시예 5: 락토바실러스 파라카제이 KCTC 14228BP 균주의 다양한 암종에 대한 항암 효과 확인Example 5: Confirmation of anticancer effect of Lactobacillus paracasei KCTC 14228BP strain against various cancer types
본 발명의 락토바실러스 파라카제이 KCTC 14228BP 균주를 다양한 암종에 처리하여 항암효과를 확인하였다.The anticancer effect was confirmed by treating the Lactobacillus paracasei KCTC 14228BP strain of the present invention with various types of carcinoma.
이를 위하여, 각각의 암세포들을 10% FBS와 1% Antibiotic solution을 첨가한 DMEM 또는 RPMI 배지를 이용하여 37℃ CO2 incubator에서 배양 후, 96 well plate에 암세포수가 1x104 cells/well 가 되도록 준비하였다. Overnight 배양 후, 2 % FBS를 첨가한 DMEM 또는 RPMI 배지와 함께 락토바실러스 파라카제이 KCTC 14228BP를 MOI 10 농도로 처리하였다. 48시간 후 LDH assay 시약을 이용하여 흡광도를 측정하였다. To this end, each cancer cell was cultured in a 37°C CO 2 incubator using DMEM or RPMI medium supplemented with 10% FBS and 1% Antibiotic solution, and then the number of cancer cells in a 96 well plate was prepared to be 1x10 4 cells/well. After overnight culture, Lactobacillus paracasei KCTC 14228BP was treated at an MOI of 10 with DMEM or RPMI medium supplemented with 2% FBS. After 48 hours, absorbance was measured using LDH assay reagent.
세포주(cell line)cell line 종류Kinds
MRC-5MRC-5 정상폐세포normal lung cells
ASPC-1ASPC-1 췌장암pancreatic cancer
SNU-308SNU-308 담낭암gallbladder cancer
Caki-1Caki-1 신장암kidney cancer
HCT116HCT116 대장암colorectal cancer
A549A549 폐암lung cancer
Hep3BHep3B 간암liver cancer
A431A431 피부암cutaneous cancer
MDA-MB-231MDA-MB-231 유방암breast cancer
AGSAGS 위암stomach cancer
CT26CT26 대장암 colorectal cancer
4T-14T-1 유방암breast cancer
그 결과, 본 발명의 락토바실러스 파라카제이 KCTC 14228BP 균주는 췌장암, 담낭암, 신장암, 대장암, 폐암, 간암, 피부암, 유방암, 및 위암에 대한 항암효과가 우수함을 확인하였다(도 8).As a result, it was confirmed that the Lactobacillus paracasei KCTC 14228BP strain of the present invention has excellent anticancer effects against pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, and stomach cancer (FIG. 8).
실시예 6: 락토바실러스 파라카제이 KCTC 14228BP 균주 및 다른 락토바실러스 파라카제이 균주의 항암효과 비교Example 6: Comparison of anticancer effects of Lactobacillus paracasei KCTC 14228BP strain and other Lactobacillus paracasei strains
다른 락토바실러스 파라카제이에 대비하여 락토바실러스 파라카제이 KCTC 14228BP 균주의 항암 효과를 평가하였다.Compared to other Lactobacillus paracasei, the anticancer effect of the Lactobacillus paracasei KCTC 14228BP strain was evaluated.
이를 위하여, 락토바실러스 파라카제이 KCTC 3189 및 KCTC 3510를 분양 받았으며, 락토바실러스 파라카제이 KCTC 14228BP (KGMB04157), KCTC 3189, KCTC 3510의 암세포 억제 정도를 측정하였다.To this end, Lactobacillus paracasei KCTC 3189 and KCTC 3510 were distributed, and the cancer cell inhibition levels of Lactobacillus paracasei KCTC 14228BP (KGMB04157), KCTC 3189, and KCTC 3510 were measured.
구체적으로, 대장암 세포주인 CT26 세포를 10% FBS와 1% Antibiotic solution을 첨가한 DMEM 또는 RPMI 배지를 이용하여 37℃ CO2 incubator에서 배양 후, 96 well plate에 암세포 수가 1x104 cells/well가 되도록 준비하였다. Overnight 배양 후, 2% FBS를 첨가한 DMEM 또는 RPMI 배지와 함께 락토바실러스 파라카제이를 MOI 10 농도로 처리하였다. 48시간 후 LDH assay 시약을 이용하여 흡광도를 측정하였다.Specifically, after culturing CT26 cells, a colorectal cancer cell line, in a 37°C CO 2 incubator using DMEM or RPMI medium supplemented with 10% FBS and 1% Antibiotic solution, the number of cancer cells in a 96 well plate is 1x10 4 cells/well. prepared. After overnight culture, Lactobacillus paracasei was treated at an MOI of 10 with DMEM or RPMI medium supplemented with 2% FBS. After 48 hours, absorbance was measured using LDH assay reagent.
그 결과, 락토바실러스 파라카제이 KCTC 14228BP(KGMB04157)는 암세포의 생존률을 현저히 감소시켰으나, 락토바실러스 파라카제이 KCTC 3189 및 KCTC 3510는 암세포의 생존률 감소 효과가 미미함을 확인하였다(도 9).As a result, it was confirmed that Lactobacillus paracasei KCTC 14228BP (KGMB04157) significantly reduced the survival rate of cancer cells, but Lactobacillus paracasei KCTC 3189 and KCTC 3510 had little effect of reducing cancer cell viability (FIG. 9).
상기 결과는 락토바실러스 파라카제이 KCTC 14228BP는 다른 락토바실러스 파라카제이에 대비하여 항암 효과가 현저히 우수함을 시사하는 것이다.The above results suggest that Lactobacillus paracasei KCTC 14228BP has a significantly superior anticancer effect compared to other Lactobacillus paracasei.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not limiting. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described later and equivalent concepts rather than the detailed description above are included in the scope of the present invention.
Figure PCTKR2022008602-appb-img-000001
Figure PCTKR2022008602-appb-img-000001

Claims (19)

  1. 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이(Lactobacillus paracasei) 균주. Lactobacillus paracasei strain deposited with accession number KCTC 14228BP.
  2. 제1항에 있어서, 상기 균주는 암 표적성을 갖는 것인, 균주.The strain according to claim 1, wherein the strain has cancer targeting.
  3. 제1항의 균주 또는 이의 배양물을 포함하는, 암 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating cancer, comprising the strain or culture thereof of claim 1.
  4. 제3항에 있어서, 상기 약학적 조성물은 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물을 더 포함하는, 약학적 조성물.The method of claim 3, wherein the pharmaceutical composition is Lactobacillus reuteri , Lactobacillus curvatus ( Lactobacillus curvatus ), and Lactobacillus brevis ( Lactobacillus brevis ) Any one or more selected from the group consisting of; Or, a pharmaceutical composition further comprising a culture thereof.
  5. 제4항에 있어서, 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 인체에서 유래한 것인, 약학적 조성물.The pharmaceutical composition according to claim 4, wherein the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis are of human origin.
  6. 제4항에 있어서, 상기 암은 췌장암, 담낭암, 신장암, 대장암, 폐암, 간암, 피부암, 유방암, 방광암, 및 위암으로 구성되는 군에서 선택되는 어느 하나 이상인 것인, 약학적 조성물.The pharmaceutical composition according to claim 4, wherein the cancer is any one or more selected from the group consisting of pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, bladder cancer, and stomach cancer.
  7. 제1항의 균주 또는 이의 배양물을 포함하는, 암 예방 또는 개선용 식품 조성물.A food composition for preventing or improving cancer, comprising the strain of claim 1 or its culture.
  8. 제7항에 있어서, 상기 식품 조성물은 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물을 더 포함하는, 식품 조성물.The method of claim 7, wherein the food composition is Lactobacillus reuteri ( Lactobacillus reuteri ), Lactobacillus curvatus ( Lactobacillus curvatus ), and Lactobacillus brevis ( Lactobacillus brevis ) Any one or more selected from the group consisting of; Or, a food composition further comprising a culture thereof.
  9. 제1항의 균주 또는 이의 배양물을 포함하는, 암 예방 또는 개선용 사료 조성물.A feed composition for preventing or improving cancer, comprising the strain of claim 1 or its culture.
  10. 제9항에 있어서, 상기 사료 조성물은 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물을 더 포함하는, 사료 조성물.10. The method of claim 9, wherein the feed composition is Lactobacillus reuteri ( Lactobacillus reuteri ), Lactobacillus curvatus ( Lactobacillus curvatus ), and Lactobacillus brevis ( Lactobacillus brevis ) Any one or more selected from the group consisting of; Or further comprising a culture thereof, feed composition.
  11. 락토바실러스 파라카제이(Lactobacillus paracasei), 락토바실러스 루테리(Lactobacillus reuteri), 락토바실러스 커바투스(Lactobacillus curvatus), 및 락토바실러스 브레비스(Lactobacillus brevis)로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물을 유효성분으로 포함하는, 암 진단용 조성물.At least one selected from the group consisting of Lactobacillus paracasei , Lactobacillus reuteri , Lactobacillus curvatus , and Lactobacillus brevis ; Or a composition for diagnosing cancer comprising a culture thereof as an active ingredient.
  12. 제11항에 있어서, 상기 락토바실러스 파라카제이는 수탁번호 KCTC 14228BP로 기탁된 것인, 암 진단용 조성물.The composition for diagnosing cancer according to claim 11, wherein the Lactobacillus paracasei is deposited under accession number KCTC 14228BP.
  13. 제11항에 있어서, 상기 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스는 암 표적성을 갖는 것인, 암 진단용 조성물.The composition for diagnosing cancer according to claim 11, wherein the Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis have cancer targets.
  14. 제11항에 있어서, 상기 암은 췌장암, 담낭암, 신장암, 대장암, 폐암, 간암, 피부암, 유방암, 방광암, 및 위암으로 구성되는 군에서 선택되는 어느 하나 이상인 것인, 암 진단용 조성물.The composition for diagnosing cancer according to claim 11, wherein the cancer is at least one selected from the group consisting of pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, bladder cancer, and stomach cancer.
  15. 샘플의 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상의 균주를 검출하는 단계를 포함하는 암 진단을 위한 정보제공 방법으로서,An information providing method for cancer diagnosis comprising the step of detecting any one or more strains selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis in a sample,
    상기 샘플은 개체에서 분리된 샘플에 제11항 내지 제14항 중 어느 한 항의 암 진단용 조성물이 처리된 것이거나, 상기 암 진단용 조성물이 투여된 개체에서 분리된 샘플인 것인, 암 진단을 위한 정보제공 방법.The sample is a sample isolated from a subject treated with the composition for diagnosis of cancer according to any one of claims 11 to 14, or a sample isolated from a subject to which the composition for diagnosis of cancer is administered, information for diagnosis of cancer How to provide.
  16. 수탁번호 KCTC 14228BP로 기탁된 락토바실러스 파라카제이 균주 또는 이의 배양물을 포함하는 조성물의 암 예방 또는 치료 용도.Use of a composition comprising a Lactobacillus paracasei strain or a culture thereof deposited under Accession No. KCTC 14228BP for preventing or treating cancer.
  17. 제16항에 있어서, 상기 조성물은 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상의 균주 또는 이의 배양물을 더 포함하는 것인, 암 예방 또는 치료 용도.The method of claim 16, wherein the composition further comprises any one or more strains or cultures thereof selected from the group consisting of Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis, cancer prevention or treatment use.
  18. 락토바실러스 파라카제이, 락토바실러스 루테리, 락토바실러스 커바투스, 및 락토바실러스 브레비스로 구성되는 군에서 선택되는 어느 하나 이상; 또는 이의 배양물의 암 진단 용도.at least one selected from the group consisting of Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus curvatus, and Lactobacillus brevis; Or a cancer diagnostic use of a culture thereof.
  19. 제18항에 있어서, 상기 락토바실러스 파라카제이는 수탁번호 KCTC 14228BP로 기탁된 것인, 암 진단 용도.The method of claim 18, wherein the Lactobacillus paracasei is deposited under accession number KCTC 14228BP, cancer diagnostic use.
PCT/KR2022/008602 2021-06-18 2022-06-17 Composition comprising lacticaseibacillus sp. or lactobacillus sp. strain as active ingredient for diagnosis, prevention, or treatment of cancer WO2022265447A1 (en)

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