WO2023243856A1 - Composition de prévention, d'amélioration ou de traitement de la dyscrasie sanguine comprenant un micro-organisme du genre euglène - Google Patents

Composition de prévention, d'amélioration ou de traitement de la dyscrasie sanguine comprenant un micro-organisme du genre euglène Download PDF

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WO2023243856A1
WO2023243856A1 PCT/KR2023/005907 KR2023005907W WO2023243856A1 WO 2023243856 A1 WO2023243856 A1 WO 2023243856A1 KR 2023005907 W KR2023005907 W KR 2023005907W WO 2023243856 A1 WO2023243856 A1 WO 2023243856A1
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euglena gracilis
composition
present
preventing
cancer
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Korean (ko)
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강희
이석찬
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경희대학교 산학협력단
성균관대학교산학협력단
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/202—Algae extracts

Definitions

  • the present invention relates to the use of Euglena genus microorganisms to prevent, improve or treat hematopoietic disorders; and for use in preventing, improving or treating cancer.
  • Anticancer drugs act on proliferating cells, such as hematopoietic stem cells and intestinal stem cells, in addition to target cancer cells. Therefore, some of the side effects of chemotherapy are leukopenia and mucositis. Moreover, dysbiosis of the intestinal microbial ecosystem occurs after chemotherapy. A healthy gut microbiome is necessary to maintain the intestinal barrier, colonization resistance, immunity and hematopoiesis. Defects in the stable microbial ecosystem in the intestines impair the physiological functions of the host, resulting in the invasion of endogenous bacteria and inhibition of hematopoiesis. Additionally, the use of antibiotics in cancer patients with leukopenia and mucositis after chemotherapy may worsen immunosuppression. Due to the role of intestinal bacteria in hematopoiesis, interest in non-drug supplements to restore intestinal microorganisms, such as prebiotics and probiotics, has recently increased.
  • the present inventors completed the present invention by confirming that microorganisms of the Euglena genus restore the blood cell count reduced by anticancer drugs.
  • an object of the present invention is to provide a composition for preventing, improving or treating blood dyscrasia containing Euglena gracilis .
  • Another object of the present invention is to provide a composition for preventing, improving or treating cancer containing Euglena gracilis and an anticancer agent.
  • Another object of the present invention is to provide an anticancer adjuvant composition containing Euglena gracilis.
  • Another object of the present invention is to provide a method for promoting hematopoiesis, comprising administering Euglena gracilis to an individual in need thereof.
  • Another object of the present invention is to provide a method of treating hematopoietic disorders comprising administering Euglena gracilis to an individual in need thereof.
  • Another object of the present invention is to provide a method of treating cancer comprising administering Euglena gracilis and an anticancer agent to an individual in need thereof.
  • the present invention provides a pharmaceutical composition for preventing or treating hematopoietic disorders containing Euglena gracilis.
  • the present invention provides a food composition for preventing or improving hematopoietic disorders containing Euglena gracilis.
  • the present invention provides a health functional food composition for preventing or improving hematopoietic disorders containing Euglena gracilis.
  • the present invention provides a pharmaceutical composition for preventing or treating cancer containing Euglena gracilis and an anticancer agent.
  • the present invention provides a food composition for preventing or improving cancer containing Euglena gracilis and an anticancer agent.
  • the present invention provides a health functional food composition for preventing or improving cancer containing Euglena gracilis and an anticancer agent.
  • the present invention provides an anti-cancer adjuvant composition containing Euglena gracilis.
  • the present invention provides a method for promoting hematopoiesis, comprising administering Euglena gracilis to an individual in need thereof.
  • the present invention also provides a method of treating hematopoietic disorders, comprising administering Euglena gracilis to an individual in need thereof.
  • the present invention also provides a method of treating cancer comprising administering Euglena gracilis and an anticancer agent to an individual in need thereof.
  • the Euglena genus microorganism according to the present invention restores blood cells reduced by anticancer drug administration to a normal level without affecting the spleen immune cell population.
  • the Euglena genus microorganisms significantly increased the production of granulocyte/macrophage-colony stimulating factor, which is the basis of hematopoietic reaction. This means that the Euglena genus microorganism of the present invention promotes hematopoiesis, and can be used in various fields of treatment related to hematopoietic disorders and cancer.
  • Figure 1a is a diagram showing the schedule of blood analysis experiments in mice administered a single dose of gemcitabine.
  • Figure 1b is a diagram showing the results of confirming the white blood cell count following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 1c is a diagram showing the results of confirming the number of neutrophils following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 1d is a diagram showing the results of confirming the number of lymphocytes following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 1e is a diagram showing the results of confirming the number of red blood cells following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 2a is a diagram showing the schedule of the spleen immune cell analysis experiment in mice administered a single dose of gemcitabine.
  • Figure 2b is a diagram showing the results of analyzing the number of CD11b (myeloid) and CD49b (NK cell) positive cells following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 2c is a diagram showing the results of analyzing the number of CD4 and CD8 positive cells following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 2d is a diagram showing the results of analyzing the expression of Dectin-1 following a single administration of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 3 shows the results of analyzing granulocyte/macrophage-colony-stimulating factor (GM-CSF) secretion following a single administration of gemcitabine in mice orally administered Euglena gracilis. .
  • GM-CSF granulocyte/macrophage-colony-stimulating factor
  • Figure 4a is a diagram showing the schedule of blood analysis experiments in mice administered multiple doses of gemcitabine.
  • Figure 4b is a diagram showing the results of analyzing the number of white blood cells following multiple administrations of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 4c is a diagram showing the results of analyzing the number of lymphocytes following multiple administrations of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 4d is a diagram showing the results of analyzing the number of neutrophils following multiple administrations of gemcitabine in mice orally administered Euglena gracilis.
  • Figure 4e is a diagram showing the results of analyzing the number of red blood cells following multiple administrations of gemcitabine in mice orally administered Euglena gracilis.
  • the present invention provides a composition for preventing, improving or treating hematopoietic disorders (blood dyscrasia) containing Euglena gracilis .
  • the composition of the present invention is a pharmaceutical composition for preventing or treating hematopoietic disorders; Food composition for preventing or improving hematopoietic disorders; Or it may be a health functional food composition for preventing or improving hematopoietic disorders.
  • the present invention provides a composition for preventing, improving or treating cancer containing Euglena gracilis and an anticancer agent. More specifically, the composition of the present invention is a pharmaceutical composition for preventing or treating cancer; Food compositions for preventing or improving cancer; Or it may be a health functional food composition for preventing or improving cancer.
  • Euglena gracilis is a single-celled eukaryote with flagella and chloroplasts, which are characteristic of plants and animals. As a food supplement, it is rich in essential amino acids, lipids, vitamins and beta glucans. Unlike the beta-glucans of bacteria, fungi, and plants, which are found in cell walls, the beta-glucans of Euglena gracilis are stored in granules called paramylons in the cytoplasm. This paramylon is a very pure beta-glucan composed of 100% glucose with linear beta-1,3 glycosidic linkages. It has high crystallinity and a molecular weight of 100 to 500 kDa. Euglena gracilis can accumulate large amounts of paramylon (more than 90% of dry weight) under dark conditions using glucose as a carbon source. Euglena is easy to culture, making it an inexpensive source of glucan.
  • hematopoietic disorder refers to a disorder occurring in hematopoietic function in the bone marrow.
  • Hematopoietic disorders are disorders in the production of blood cells, causing various blood cell-related diseases.
  • the hematopoietic disorder includes leukopenia, neutropenia, lymphopenia, monocytopenia, granulocytopenia, aplastic anemia, malignant lymphoma, leukemia,
  • leukopenia leukopenia
  • neutropenia neutropenia
  • lymphopenia lymphopenia
  • monocytopenia granulocytopenia
  • aplastic anemia malignant lymphoma
  • leukemia leukemia
  • diseases selected from the group consisting of chronic liver failure, renal failure, severe infections, myelopathogenic thrombocytopenia, idiopathic thrombocytopenic purpura (ITP), thrombocytopenia, myelodysplastic syndrome, and myeloproliferative disease It is not limited to this.
  • the hematopoietic disorder may be a hematopoietic disorder caused by a side effect of an anticancer drug.
  • the anticancer agent is Doxorubicin, Epirubicin, Gemsitabin, Cisplatin, Carboplatin, Procarbazine, and Cyclophos. Cyclophosphamide, Dactinomycin, Daunorubicin, Etoposide, Tamoxifen, Mitomycin, Bleomycin, Plicomycin , Transplatinum, Vinblastine, and Methotrexate, and most preferably gemcitabine, but the scope of the present invention is not limited thereto.
  • Euglena gracilis of the present invention may be included in various forms such as its culture medium, dried product, or cell free supernatant, and may preferably be included in the form of Euglena gracilis dry powder, but is not limited thereto.
  • the Euglena gracilis dry powder may contain Carbohydrate, Crude Protein, Crude Fat, Ash, Fiber, Beta-glucan, and Pheophorbide, and exemplary contents are shown in Table 1 of the present specification.
  • prevention refers to all actions that inhibit or delay the onset of hematopoietic disorders or cancer by administering the composition according to the present invention.
  • treatment refers to any action that improves or beneficially changes the symptoms of a hematopoietic disorder or cancer by administering the composition according to the present invention.
  • improvement refers to any action that improves the bad condition of hematopoietic disorder or cancer by administering or ingesting the composition of the present invention to an individual.
  • the pharmaceutical composition of the present invention can be formulated and used in various forms according to conventional methods.
  • it can be formulated into oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., and can be formulated and used in the form of external preparations, suppositories, and sterile injection solutions.
  • composition of the present invention may contain one or more known active ingredients that have a preventive or therapeutic effect on hematopoietic disorders or cancer along with Euglena gracilis.
  • composition of the present invention may further include pharmaceutically acceptable additives, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, and lactose. , mannitol, taffy, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, Opadry, sodium starch glycolate, carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, calcium stearate, White sugar, etc. may be used.
  • the pharmaceutically acceptable additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
  • composition of the present invention can be administered in various oral or parenteral formulations during actual clinical administration.
  • diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants are used. It can be prepared by doing so, and it is preferable to use suitable preparations known in the art that are disclosed in the literature.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient, such as starch, calcium carbonate, sucrose, or It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium styrate talc are also used.
  • the liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. This may be included.
  • Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
  • injectable ester such as ethyl oleate.
  • As a base for suppositories witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.
  • the dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, and/or administration route of the pharmaceutical composition, and the type and degree of response to be achieved by administration of the pharmaceutical composition. , various factors including the type, age, weight, general health condition, symptoms or degree of disease, gender, diet, excretion, drugs used simultaneously or simultaneously with the subject, other components of the composition, etc. of the subject to be administered, and It may vary depending on similar factors well known in the pharmaceutical field, and a person skilled in the art can easily determine and prescribe an effective dosage for the desired treatment.
  • the dosage of the pharmaceutical composition of the present invention is preferably administered at a concentration of, for example, 0.05 to 5 mg/kg, more preferably 0.1 to 0.4 mg/kg, and even more preferably 0.2 to 0.35 mg/kg. , and even more preferably 0.25 mg/kg, but the dosage does not limit the scope of the present invention in any way.
  • the administration route and administration method of the pharmaceutical composition of the present invention may be independent, and are not particularly limited, and any administration route and administration method may be used as long as the pharmaceutical composition can reach the desired area. can be followed.
  • the pharmaceutical composition can be administered orally or parenterally.
  • the parenteral administration method includes, for example, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration, or subcutaneous administration.
  • composition of the present invention can be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response regulators for the prevention or treatment of hematopoietic disorders.
  • food refers to food that has a bioregulatory function and is a concept that includes health functional foods.
  • health functional food refers to a food group or food composition that provides added value to a food by using physical, biochemical, biotechnological methods, etc. to function and express the function of the food for a specific purpose, or a food group that regulates the biological defense rhythm and diseases. It refers to food that has been designed and processed to fully express the body's regulatory functions related to prevention and recovery in the living body.
  • the health functional food is intended to enhance the activity of preventing or improving hematopoietic disorders or cancer.
  • the food composition can be manufactured by a method commonly used in the art, and can be manufactured by adding raw materials and components commonly added in the art. Additionally, the formulation of the food composition can be manufactured without limitation as long as it is a formulation recognized as a food composition.
  • Foods according to the present invention include, for example, various foods, beverages, gum, tea, vitamin complexes, functional foods, etc. Additionally, foods include special nutritional foods (e.g., milk formula, infant and baby food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g., ramen, noodles, etc.), breads, health supplements, seasonings (e.g., soy sauce) , soybean paste, red pepper paste, mixed paste, etc.), sauces, confectionery (e.g., snacks), candy, chocolate, gum, ice cream, dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various types of kimchi) , pickles, etc.), beverages (e.g., fruit drinks, vegetable drinks, soy milk, fermented drinks, etc.), natural seasonings (e.g., ramen soup, etc.), food additives, etc., but are not limited thereto.
  • the food, beverage or food additive can
  • the composition of the present invention When using the composition of the present invention as a health functional food additive, the composition can be added as is or used together with other health functional food ingredients, and can be used appropriately according to conventional methods.
  • the mixing amount of the active ingredient can be appropriately determined depending on the purpose of use.
  • the composition of the present invention can be added in an amount of preferably 50 parts by weight or less, more preferably 25 parts by weight or less, based on the raw materials.
  • the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • the food or health functional food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients like a typical food composition.
  • natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • the above-described flavoring agents include natural flavoring agents (thaumatin), stevia extracts (e.g. rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
  • the food composition contains, in addition to Euglena gracilis, various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and the like. It may contain salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the food composition of the present invention may contain pulp for the production of natural fruit juice and fruit juice drinks and vegetable drinks.
  • the present invention provides an anticancer adjuvant composition containing Euglena gracilis.
  • the anti-cancer adjuvant according to the present invention may be in the form of a pharmaceutical composition or food composition, and more specifically, may be an anti-cancer pharmaceutical adjuvant or an anti-cancer food adjuvant.
  • anti-cancer adjuvant refers to an agent that can be used as an auxiliary agent to enhance the effect of a cancer treatment agent commonly used in the art, and the effect of a cancer treatment or anti-cancer treatment can be improved by using the adjuvant according to the present invention. It can improve or alleviate the side effects of cancer treatment or anti-cancer treatment.
  • the term “food” refers to all foods that people consume on a daily basis, and includes health functional foods.
  • Euglena gracilis of the present invention can be added to food compositions as an anti-cancer supplement, and can be added as the active ingredient or used together with other foods or food ingredients, and can be used appropriately according to conventional methods.
  • the mixing amount of the active ingredient can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment).
  • the type of anticancer agent that can be used with the anticancer adjuvant of the present invention is not particularly limited.
  • Anticancer drugs can be selected based on general principles that are considered when selecting anticancer drugs, such as the type of cancer cell, the absorption rate of the anticancer drug (treatment period and route of anticancer drug administration), the location of the tumor, and the size of the tumor.
  • the present invention provides a method for promoting hematopoiesis comprising administering Euglena gracilis to an individual in need thereof.
  • the subject may be an individual in need of blood cell formation, examples of which include individuals with reduced hematopoiesis and individuals with reduced blood cell counts due to various hematopoietic disorders.
  • the entity may be an insect, fish, bird, or mammal, including humans, and may be a single cell or colony, but is not limited thereto.
  • the present invention provides a method of treating hematopoietic disorders comprising administering Euglena gracilis to an individual in need thereof.
  • the present invention also provides a method of treating cancer comprising administering Euglena gracilis and an anticancer agent to an individual in need thereof.
  • the individual is an individual expected to develop a hematopoietic disorder; invented entity; It may be, but is not limited to, an entity that has been judged to be fully cured.
  • Redundant content is omitted in consideration of the complexity of the present specification, and terms not otherwise defined in this specification have meanings commonly used in the technical field to which the present invention pertains.
  • Euglena gracilis was provided in powder form from Daesang Co., Ltd.'s R&D Center (Icheon, Korea). The composition of Euglena gracilis powder was analyzed by the Korea Institute of Health Functional Foods (Seongnam, Korea), and the results are shown in Table 1.
  • Euglena gracilis powder consists of 69.41% carbohydrates, which is approximately twice that reported elsewhere.
  • the amount of paramylon (average molecular weight, 500 kDa) in Euglena gracilis was 597.88 mg/g.
  • mice Male BALB/c mice aged 6–7 weeks were purchased from Coretech (Pyeongtaek, Korea). Animals were housed in a pathogen-free animal facility with temperature control (23°C ⁇ 3°C) and humidity control (55% ⁇ 15%), with sufficient ventilation and a 12-hour light/dark cycle. Mice were housed in polypropylene cages containing up to 5 mice each. Additionally, mice were provided with a commercial diet (Cargill Agri Purina Inc., Pyeongtaek, Korea) and water. The commercial diet contains 20% protein, 4.5% fat, 6% fiber, 0.5% calcium, 1% phosphorus, and 7% ash. All animals had a 1-week adjustment period prior to the experiment and were randomly assigned to the control or test group.
  • mice For blood cell analysis, 8-10 animals per group were used, and for spleen isolation, 3-6 animals were used.
  • the oral dose of Euglena gracilis was set at 3 g per kg body weight, which was set based on previous studies. Euglena gracilis suspended in saline solution was administered orally once a day until the mice were euthanized. Gemcitabine (120 mg/kg; Merck, Germany) dissolved in saline solution was administered intraperitoneally 2 weeks after the first oral administration of Euglena gracilis. Gemcitabine treatment was applied 1 to 4 times at 3-day intervals. Untreated mice received the same volume of saline. All experimental protocols were approved by the Sungkyunkwan University Animal Ethics Committee (SKKUIACUC2019-04-34-3). Animals were cared for in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals (1996).
  • Blood cells were collected at various time points after gemcitabine treatment.
  • the specific administration schedule and blood collection schedule are as shown in Figure 1A.
  • blood was collected on days 0, 3, 5, and 7 after a single dose of gemcitabine.
  • mice were euthanized using Zoletil 50 (Virbac, Carros, France) and Rompen (Bayer Healthcare, Leverkusen, Germany), and blood was collected using cardiac puncture.
  • the collected blood was collected in K2 EDTA tubes, and the number of white blood cells and cells was calculated using a ProCyte Dx hematology analyzer (IDEXX, Westbrook, ME, USA).
  • IDEXX ProCyte Dx hematology analyzer
  • the results of calculating the number of white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), and red blood cells (RBC) are shown in Figures 1b and 1d, respectively.
  • Example 4 Analysis of spleen immune cells in mice administered a single dose of gemcitabine
  • spleens were obtained 7 days after a single dose of gemcitabine was administered to mice.
  • Splenocytes were prepared by dissociating spleen tissue using a glass mill under sterile conditions. Cells were collected in RPMI 1640 medium containing 1% fetal bovine serum (FBS) (HyClone, Logan, UT, USA) and 1% penicillin-streptomycin (WelGene, Gyeongsan, Korea), and filtered through a cell strainer (70 ⁇ m). filtered through. After centrifugation, red blood cells contained in the filtrate were lysed using BD PharmLyse lysis buffer (BD Biosciences, San Diego, CA, USA) to obtain only spleen cells. The obtained splenocytes were resuspended in RPMI 1640 containing 10% FBS and 1% penicillin-streptomycin to obtain a cell suspension.
  • FBS fetal bovine serum
  • penicillin-streptomycin WelGen
  • a cell pellet was obtained from the cell suspension containing the spleen cells obtained in Example 4-1.
  • the cell pellet was resuspended in FACS buffer (PBS/0.1% NaN 3 /1% FBS). Splenocytes were blocked with rat anti-mouse CD16/CD32 antibody (BD Biosciences) at 4°C for 5 minutes.
  • splenocytes were stained with fluorescein isothiocyanate (FITC)-conjugated CD11b, phycoerythrin-conjugated CD49b, FITC-conjugated CD19, phycoerythrin-conjugated CD3, FITC-conjugated anti-mouse CD4, phycoerythrin-conjugated anti-mouse CD8a, and phycoerythrin-conjugated anti.
  • FITC fluorescein isothiocyanate
  • the proportion of bone marrow cells was confirmed to be increased after chemotherapy such as gemcitabine ( Figure 4b ).
  • the ratio of NK cells in the gemcitabine-treated group (GEM) was higher than the control group, but the gemcitabine + Euglena gracilis-treated group (G+E) was confirmed to be lowered to the control group (CON) level ( Figure 4b). It was confirmed that there was no difference in subtypes of T cells, CD4 cells, and CD8 T cells ( Figure 4c).
  • the gemcitabine-treated group (GEM) was also confirmed to have increased expression of Dectin-1.
  • the gemcitabine treatment group (GEM) and gemcitabine + Euglena gracilis treatment group (G+E) were higher than the control group (CON) and Euglena gracilis treatment group (EUG), and there was a difference in Dectin-1 expression between groups. There was no.
  • GM-CSF granulocyte/macrophage-colony-stimulating factor
  • GM-CSF concentrations were determined using the mouse GM-CSF DuoSet ELISA kit (R&D Systems, Minneapolis, MN, USA). The results of analyzing GM-CSF secretion from splenocytes after a single administration of gemcitabine are shown in Figure 3.
  • each group produced an almost undetectable amount of GM-CSF, and there was no difference between the groups.
  • GM-CSF in the gemcitabine + Euglena gracilis group (G + E) was higher than that in the control group (CON) and gemcitabine (GEM) groups.
  • GM-CSF in the gemcitabine + Euglena gracilis group (G+E) was higher than that in the control group (CON) and gemcitabine (GEM) groups, but there was a statistically significant difference between the groups. There was no.
  • mice following multiple administrations of gemcitabine was analyzed.
  • the specific administration schedule and blood collection schedule are shown in Figure 4A.
  • gemcitabine was administered, and blood was collected on days 0, 1, 3, 5, and 7 after four administrations.
  • mice were administered four doses of gemcitabine three days apart. Blood cells were obtained on days 1, 3, 5, and 7 after gemcitabine administration.
  • Blood analysis was performed in the same manner as in Example 3 above.
  • the control group in this experiment was the normal group (i.e., the group that did not receive gemcitabine).
  • the results of analyzing blood collected 1 day after the last administration of gemcitabine are shown in Figures 4b to 4e, respectively.
  • the gemcitabine + Euglena gracilis group had an increase in total white blood cells compared to the gemcitabine group (GEM), and in particular, there was a statistically significant increase in lymphocytes. There was no significant difference in neutrophil counts between the gemcitabine group (GEM) and the gemcitabine + Euglena gracilis group (G+E). Additionally, administration of Euglena gracilis to healthy mice (CON) had no significant effect on the white blood cell count.
  • Euglena gracilis and the anticancer drug gemcitabine were administered to experimental animals, Euglena gracilis did not affect the spleen immune cell population and increased the number of white blood cells to the level of normal groups. Additionally, it was confirmed that Euglena gracilis improves the production of granulocyte/macrophage-colony stimulating factor. This means that Euglena gracilis has a significant effect of improving leukopenia, and Euglena gracilis of the present invention can be used in various fields in the field of treating anticancer drug side effects and leukopenia.

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Abstract

La présente invention se rapporte à l'utilisation d'un micro-organisme du genre euglène destiné : à la prévention, à l'amélioration ou au traitement de la dyscrasie sanguine ; et à la prévention, à l'amélioration ou au traitement du cancer. Le micro-organisme du genre euglène selon la présente invention a été confirmé comme étant apte à restaurer les cellules sanguines réduites à un niveau normal par l'administration d'un médicament anticancéreux, sans affecter la population de cellules immunitaires de la rate. Le micro-organisme du genre euglène a également été confirmé comme étant apte à augmenter significativement la production de facteurs de stimulation de colonies de granulocytes/macrophages sous-jacents à la réponse hématopoïétique. Cela signifie que le micro-organisme du genre euglène, selon la présente invention, favorise l'hématopoïèse, et peut ainsi être utilisé dans les domaines du traitement lié au cancer et à la dyscrasie sanguine de diverses manières.
PCT/KR2023/005907 2022-06-14 2023-04-28 Composition de prévention, d'amélioration ou de traitement de la dyscrasie sanguine comprenant un micro-organisme du genre euglène WO2023243856A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016069495A (ja) * 2014-09-29 2016-05-09 株式会社ユーグレナ インドキシル硫酸産生阻害物質
CN105901714A (zh) * 2016-04-27 2016-08-31 青岛旭能生物工程有限责任公司 一种裸藻复合片剂及其制备方法
JP2017128568A (ja) * 2016-01-20 2017-07-27 株式会社ユーグレナ 抗腫瘍剤，腫瘍細胞増殖抑制剤，抗乳癌剤及び抗腫瘍剤の製造方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016069495A (ja) * 2014-09-29 2016-05-09 株式会社ユーグレナ インドキシル硫酸産生阻害物質
JP2017128568A (ja) * 2016-01-20 2017-07-27 株式会社ユーグレナ 抗腫瘍剤，腫瘍細胞増殖抑制剤，抗乳癌剤及び抗腫瘍剤の製造方法
CN105901714A (zh) * 2016-04-27 2016-08-31 青岛旭能生物工程有限责任公司 一种裸藻复合片剂及其制备方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
SONG YOUNGJU; SHIN HOCHEOL; SIANIPAR HANARY GEBY JESSICA; PARK JI YUN; LEE MIGI; HAH JIHYE; PARK HONG SHIK; LEE HYUN JEONG; LEE SU: "Oral administration of Euglena gracilis paramylon ameliorates chemotherapy-induced leukocytopenia and gut dysbiosis in mice", INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, ELSEVIER BV, NL, vol. 211, 28 April 2022 (2022-04-28), NL , pages 47 - 56, XP087085281, ISSN: 0141-8130, DOI: 10.1016/j.ijbiomac.2022.04.168 *
WATANABE TOSHIAKI ET AL: "Antitumor activity of the [beta]-glucan paramylon from Euglena against preneoplastic colonic aberrant crypt foci in mice.", FOOD & FUNCTION AUG 2015, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 4, no. 11, 1 November 2013 (2013-11-01), GB , pages 1685 - 1690, XP002791406, ISSN: 2042-650X, DOI: 10.1039/c3fo60256g *
YANG HYEONJI, CHOI KWANYONG, KIM KYEONG JIN, PARK SOO-YEON, JEON JIN-YOUNG, KIM BYUNG-GON, KIM JI YEON: "Immunoenhancing Effects of Euglena gracilis on a Cyclophosphamide-Induced Immunosuppressive Mouse Model", JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, HAN'GUG MI'SAENGMUL SAENGMYEONG GONG HAGHOE,KOREAN SOCIETY FOR MICROBIOLOGY AND BIOTECHNOLOGY, KOREA, vol. 32, no. 2, 28 February 2022 (2022-02-28), Korea, pages 228 - 237, XP093117048, ISSN: 1017-7825, DOI: 10.4014/jmb.2112.12035 *

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