WO2024155158A1 - Composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires dérivées de cultures comestibles - Google Patents

Composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires dérivées de cultures comestibles Download PDF

Info

Publication number
WO2024155158A1
WO2024155158A1 PCT/KR2024/000995 KR2024000995W WO2024155158A1 WO 2024155158 A1 WO2024155158 A1 WO 2024155158A1 KR 2024000995 W KR2024000995 W KR 2024000995W WO 2024155158 A1 WO2024155158 A1 WO 2024155158A1
Authority
WO
WIPO (PCT)
Prior art keywords
exosomes
cancer
oxaliplatin
extracellular vesicles
radish
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2024/000995
Other languages
English (en)
Korean (ko)
Inventor
이예지
양상화
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nextab Inc
Original Assignee
Nextab Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nextab Inc filed Critical Nextab Inc
Priority claimed from KR1020240008911A external-priority patent/KR20240116412A/ko
Publication of WO2024155158A1 publication Critical patent/WO2024155158A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a composition for preventing or treating cancer containing extracellular vesicles (EV) derived from edible crops.
  • EV extracellular vesicles
  • EVs are classified according to their size into exosomes (30-150 nm in diameter), microvesicles (microvesicle/MV, 100-1,000 nm in diameter), ectosomes, and apoptotic bodies (>1,000 nm in diameter). They contain DNA, RNA, small RNA, peptides, and metabolites (secondary metabolites) derived from the originating cell, and move and penetrate into surrounding cells or cells located over long distances and carry out internal genetic and biological functions. By transferring the possessed substances, changes in the characteristics of the recipient cells occur as a result. In other words, EV is a third signaling substance, a carrier of useful materials, and a diagnostic material for disease-specific phenomena. EVs secreted during bacterial culture and EVs isolated from human urine are exosomes, EVs derived from seaweed are microvesicles, and in terrestrial edible crops, exosomes and microvesicles appear to coexist.
  • EVs including exosomes and microvesicles, are released out of the cell through the fusion of multivesicular bodies (MVBs) and the cell membrane, and contain DNA, RNA, peptide/protein, and metabolites that represent the characteristics of the discharged cell of origin.
  • MVBs multivesicular bodies
  • EVs The primary function of EVs is long-distance intercellular material transport. EVs are released out of the cell containing genetic material (genomic DNA, messenger/micro/long non-coding RNA), metabolites (lipid/metabolite), and proteins of the cell of origin, and deliver these to target cells.
  • genetic material for example, mRNA
  • mRNA it is synthesized into protein through transcription, so it shows the effect of introducing new proteins, and in the case of miRNA, it regulates gene expression, causing a variety of problems, including tumor formation. It can also induce changes in cellular function.
  • EVs are excreted from all living cells, including land and sea microorganisms, animals and plants, and as such, research on the usefulness of EVs derived from various organisms is actively underway.
  • Non-patent Document 1 SCIENCE 7 Feb 2020, Vol 367, Issue 6478
  • the present invention relates to a composition for preventing or treating cancer containing extracellular vesicles (EV) derived from edible crops.
  • EV extracellular vesicles
  • the purpose of the present invention is to provide a quasi-drug composition for improving cancer, comprising extracellular vesicles derived from edible crops.
  • Another object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer, comprising extracellular vesicles derived from edible crops.
  • Another object of the present invention is to provide a health functional food for improving cancer, containing extracellular vesicles derived from edible crops.
  • the extracellular vesicle of the present invention not only exhibits an inherent anti-cancer effect, but can also be used as DDS, so it can be usefully used in the prevention, improvement, and treatment of cancer.
  • Figure 1 shows the results of confirming the exosome size distribution using DLS.
  • Figure 2 shows the results of confirming the shapes of radish exosomes (A) and potato exosomes (B) under a transmission electron microscope.
  • Figure 3 shows the results of confirming exosome-free cell permeability through confocal microscopy.
  • Figure 4 shows the intrinsic anticancer efficacy of radish exosomes (A), the results of confirming the anticancer efficacy by loading oxaliplatin into radish exosomes (B), and the results of confirming the efficacy of oxaliplatin alone as a control (C).
  • Figure 5 shows the results confirming the intrinsic anticancer efficacy of potato and soybean exosomes.
  • Figure 6 shows the results of confirming the shapes of radish exosomes and radish exosomes loaded with oxaliplatin using a transmission electron microscope.
  • Figure 7 shows the IC50 comparison results between oxaliplatin loaded on radish exosomes and oxaliplatin alone.
  • Figure 8 shows the results of treating oxaliplatin (OxPt) and oxaliplatin (ExoR-OxP) loaded on exosomes and confirming the cancer cell growth inhibition rate.
  • Figure 9 shows the comparison results between the case of loading oxaliplatin in exosomes and the case of simply mixing exosomes and oxaliplatin.
  • One aspect of the present invention is a quasi-drug composition for preventing or improving cancer, comprising extracellular vesicles derived from edible crops.
  • Another aspect of the present invention is a pharmaceutical composition for preventing or treating cancer, comprising extracellular vesicles derived from edible crops.
  • Another aspect of the present invention is a health functional food for preventing or improving cancer, comprising extracellular vesicles derived from edible crops.
  • edible crops refer to crops that can serve as food for humans, and include both horticultural plants and craft crops grown for the purpose of eating.
  • the edible crop of the present invention may be selected from radishes, potatoes, beans, oranges, apples, tomatoes, olives, garlic, berries, and herbs.
  • the edible crop of the present invention may be selected from radish, potato, and soybean.
  • the edible parts of the above edible crops can be used.
  • the part of the radish excluding the leaves can be used.
  • the tuber portion of the potato may be used.
  • the fruit portion of the soybean may be used.
  • Extracellular vesicles of the present invention are circular bodies with a double lipid membrane structure naturally secreted from cells of the edible crop of the present invention, and refer to nano-vesicles with a diameter of 50 to 1000 nm.
  • nano-vesicles with a diameter of 50 to 150 nm can be referred to as exosomes.
  • the exosome is a third signaling substance containing biologically active substances such as metabolites, DNA, RNA, and proteins.
  • the extracellular vesicles of the present invention may have a diameter of 200 nm or less.
  • the extracellular vesicles of the present invention may have a diameter of 50 to 150 nm.
  • Cancer of the present invention refers to aggressive characteristics in which cells divide and grow by ignoring normal growth limits, invasive characteristics that infiltrate surrounding tissues, and metastatic characteristics that spread to other parts of the body. It is a general term for diseases caused by cells with metastatic characteristics. As used herein, the term cancer may also be used in the same sense as malignant tumor or malignant ascites.
  • the cancers of the present invention include gastric cancer, breast cancer, lung cancer, liver cancer, blood cancer, bone cancer, and pancreatic cancer.
  • cancer skin cancer, head or neck cancer, cutaneous or intraocular melanoma, uterine sarcoma, ovarian cancer, rectal cancer , anal cancer, colon cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, small intestine cancer, endocrine cancer cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue tumor, urethral cancer, prostate cancer, bronchogenic cancer ) and bone marrow tumor.
  • An example would be prostate cancer.
  • the extracellular vesicle of the present invention may be loaded with an anticancer agent.
  • Extracellular vesicles loaded with the anticancer agent of the present invention can be produced by culturing the extracellular vesicles with the anticancer agent at low temperature.
  • extracellular vesicles loaded with the anticancer agent of the present invention can be produced by mixing extracellular vesicles and the anticancer agent at a temperature of 0°C or lower. The incubation time may be 1 hour or more.
  • one aspect of the present invention provides a method for producing extracellular vesicles derived from edible crops loaded with anticancer agents. Edible crops and extracellular vesicles are as described above.
  • the type of anticancer agent loaded into the extracellular vesicle of the present invention is not particularly limited, but may be classified as a cytotoxic anticancer agent, for example, cisplatin, Carboplatin, Oxaliplatin, Mechlorethamine (nitrogen mustard), Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil , Thiotepa, Altretamine, Procarbazine, Busulfan, Carmustine (BCNU), Lomustine (CCNU), dacarbazine (DTIC) It may be selected among: An example of this may be oxaliplatin.
  • a cytotoxic anticancer agent for example, cisplatin, Carboplatin, Oxaliplatin, Mechlorethamine (nitrogen mustard), Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil , Thiotepa, Altretamine, Procarbazine, Busulfan, Car
  • the present inventors have confirmed that extracellular vesicles derived from specific edible crops have anti-cancer activity in themselves and can be used as a drug delivery system by efficiently delivering anti-cancer drugs, thereby providing the present invention. was completed.
  • prevention used herein may refer to any action that inhibits or delays the development of cancer by administering the composition of the present invention to an individual.
  • treatment refers to any action in which the symptoms of an individual suspected or affected by a disease are improved or beneficially changed by using the composition of the present invention.
  • the term “improvement” can mean any action that reduces at least the severity of a parameter associated with the condition being treated, such as a symptom.
  • Quasi-drugs of the present invention refer to products that have a milder effect than pharmaceuticals among products used for the purpose of diagnosing, treating, improving, alleviating, treating, or preventing diseases in humans or animals.
  • quasi-drugs exclude products used for medicinal purposes and include products used to treat or prevent diseases in humans and animals, and products that have a mild or no direct effect on the human body.
  • the pharmaceutical composition of the present invention may further include appropriate carriers, excipients, or diluents commonly used in the preparation of pharmaceutical compositions.
  • the pharmaceutical composition may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. You can.
  • carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, Examples include calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the extract and its fractions with at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used.
  • Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups, and may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives in addition to the commonly used simple diluents such as water and liquid paraffin. there is.
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
  • Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
  • a base for suppositories witepsol, macrogol, tween 61, cacao, laurin, glycerogenatin, etc. can be used.
  • composition of the present invention is not particularly limited thereto, but is administered through routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, and intrarectal administration, depending on the purpose. can be administered.
  • routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, and intrarectal administration, depending on the purpose.
  • routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, and intrarectal administration, depending on the purpose.
  • routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, intrapulmonary administration, and intrarectal administration, depending on the purpose.
  • the oral composition may be formulated to coat the active agent or protect
  • the health functional food of the present invention is the same term as food for special health use (FoSHU), and refers to food with high medical and medical effects that has been processed to efficiently exhibit bioregulatory functions in addition to nutritional supply.
  • “function” means adjusting nutrients to the structure and function of the human body or obtaining useful effects for health purposes, such as physiological effects.
  • the food of the present invention can be manufactured by methods commonly used in the industry, and can be manufactured by adding raw materials and ingredients commonly added in the industry. Additionally, the food formulation can be manufactured without limitation as long as it is a formulation recognized as a food.
  • the food composition of the present invention can be manufactured in various types of formulations, and unlike general drugs, it is made from food as a raw material and has the advantage of not having any side effects that may occur when taking the drug for a long time. It is also highly portable, and can be used to prevent cancer or prevent cancer. It can be taken as a supplement to enhance the improvement effect.
  • Another aspect of the present invention provides the use of the composition for preventing, improving or treating cancer.
  • Another aspect of the present invention provides a method for preventing, improving, or treating cancer, comprising administering the composition to a subject.
  • the composition, prevention, improvement, and treatment containing the edible crop-derived extracellular vesicles are as described above.
  • Example 1-1 Isolation of radish exosomes
  • the thick part of the radish excluding the leaves was used and ground using a blender.
  • the juice was sequentially centrifuged at 5,000 to 40,000 g at 4°C, and the supernatant was filtered through a 0.8 ⁇ m filter. Next, the filtrate was subjected to ultra-high-speed centrifugation at 100,000-180,000 g at 4°C, and the precipitated pellet containing exosomes was taken and dissolved in PBS (phosphate buffer, pH 6.5-7.5).
  • PBS phosphate buffer, pH 6.5-7.5
  • the stem part (tuber) of potatoes which is the part mainly used for food, was used, and after washing, the skin was removed and ground using a blender.
  • the juice was sequentially centrifuged at 5,000 to 40,000 g at 4°C, and the supernatant was filtered through a 0.8 ⁇ m filter. Next, the filtrate was subjected to ultra-high-speed centrifugation at 100,000-180,000 g at 4°C, and the precipitated pellet containing exosomes was taken and dissolved in PBS (phosphate buffer, pH 6.5-7.5).
  • the skin was removed and ground using a blender.
  • the juice was sequentially centrifuged at 5,000 to 40,000 g at 4°C, and the supernatant was filtered through a 0.8 ⁇ m filter. Subsequently, the filtrate was subjected to ultra-high-speed centrifugation at 100,000-180,000 g at 4°C, and the precipitated pellet containing exosomes was taken and dissolved in PBS (phosphate buffer, pH 6.5-7.5).
  • PBS phosphate buffer, pH 6.5-7.5
  • the size of exosomes derived from edible crops such as radish and potato using DLS has an average diameter of 66.8 nm, and ranges from a minimum of 30 nm to a maximum of 150 nm ( Figure 1).
  • Potato exosome samples were stained with 1% uranyl acetate for 15 seconds, dried under an infrared lamp for 10 minutes, and photographed using a transmission electron microscope (HT7800, Hitachi, Japan).
  • Example 1-1 the radish exosomes isolated in Example 1-1 were mixed with ExoSparkler Exsome Membrane Labeling Kit-Deep Red (EX03, Dojindo, Japan), and after removing the unbound fluorescence, only the labeled exosomes were isolated. . Fluorescently labeled exosomes were added to the PC3 cell line at a concentration of 3x10 5 cells/1ml, and cultured for 24 hours at 37°C and 5% CO 2. The cell line was photographed using a confocal microscope (LSM980, Carl Zeiss, Germany). did.
  • EX03 ExoSparkler Exsome Membrane Labeling Kit-Deep Red
  • Example 3-1 Intrinsic anti-cancer efficacy of radish exosomes
  • Example 1-1 When the human prostate cancer cell line PC3 was cultured and treated with radish-derived exosomes (indicated as “ExoR” in FIG. 4) purified in Example 1-1 into the culture medium, cancer cells were treated with 1ug/ml of radish exosomes. While there was no effect on growth (Figure 4A), when radish exosomes were added to the cell culture medium at concentrations of 10, 20, and 50 ug/ml, the cancer cell growth rate was 61.5%, respectively, compared to the control group without exosome treatment. decreases to 53.2% and 38.1%. Through this, it was shown that exosomes extracted from radish exhibit anticancer efficacy.
  • Example 3-2 Intrinsic anticancer efficacy of potato and soybean exosomes
  • PC3 human-derived prostate cancer cells
  • RPMI1640 LM 011-03 with 10% FBS, 1% penicillin, and streptomycin was added.
  • welgene, Republic of Korea welgene, Republic of Korea medium at 37°C and 5% CO 2 conditions.
  • PC3 culture medium was treated with potato and exosomes at a concentration of 50 and 20 ⁇ g/ml, and soybean exosomes at a concentration of 20 ⁇ g/ml, and after 72 hours, cell death was measured using the WST-1 assay.
  • the human prostate cancer cell line PC3 was cultured, and exosomes derived from potato and soybean, which are pure isolated land plants, were treated with the culture medium. The results are shown in Figure 5.
  • Radish exosomes and the drug to be added were mixed in PBS and incubated at 0°C or lower for more than 1 hour. To remove drugs that were not loaded into the exosomes, they were washed several times using a column.
  • the radish exosome of the present invention and the radish exosome loaded with oxaliplatin each exhibit a typical exosome size of 50-100 nm (FIG. 6).
  • Example 4-4 Confirmation of cancer cell death effect by radish exosome loaded with oxaliplatin
  • Oxaliplatin (abbreviated as OxPt in the graph, Comparative Example 1) has no effect on the growth of the cancer cell line PC3 when treated in cell culture medium at a concentration of 0.5ug/ml.
  • oxaliplatin (ExoR-OxPt, Example 4-2) loaded into radish exosomes showed a cancer cell growth rate of 87% at the same concentration of 0.5ug/ml, showing a superiority in cancer cell growth inhibition rate of about 13%.
  • oxaliplatin When the concentration of oxaliplatin (Comparative Example 1) is increased to 1ug/ml, oxaliplatin (OxPt) shows a cancer cell growth rate of 88.4%, while oxaliplatin (ExoR-OxPt) loaded on radish exosomes shows a cell growth rate of 59.9%, showing a cancer cell growth rate of 59.9%. There was a large difference in efficacy, inhibiting cell growth by 11.6% (OxPt) and 40% (ExoR-OxPt), respectively.
  • IC50 Insultory Concentration 50
  • IC50 represents the minimum concentration of a substance required to reduce the maximum biological or biochemical activity of a target to 50% in in vitro experiments. Inhibitors with lower IC50 show 50% inhibitory ability (efficacy) even at that concentration, so their inhibitory ability is that much better than substances with high IC50 that require higher concentrations. In other words, the IC50 value indicates pharmacological effect, and the lower the value, the higher the pharmacological efficacy.
  • the IC50 value of oxaliplatin (OxPt) against the prostate cancer cell line PC3 varies between laboratories, but is reported to be 29 uM in some reports.
  • Example 4-6 Comparison of efficacy of delivered and residual amounts in cancer cells by oxaliplatin-loaded radish exosomes
  • Oxaliplatin (OxPt, Comparative Example 1) and oxaliplatin (ExoR-OxPt, Example 4-2) loaded on exosomes were added to the PC3 cell line (human-derived prostate cancer cells) in each 96 well plate, 1x10 4 cells/ After dispensing at a concentration of 100 ⁇ l, the cells were cultured in RPMI1640 medium supplemented with 10% FBS, 1% penicillin, and streptomycin at 37°C and 5% CO 2 conditions. PC3 culture medium was treated with 10 ⁇ M of control oxaliplatin and radish exosomes loaded with oxaliplatin so that the amount was the same at 10 ⁇ M based on the oxaliplatin concentration. After each culture time (3, 6, 24, 30 hours), all medium containing the drug was removed, and after a total time of 72 hours in the same RPMI1640 medium, cell death was measured using the WST-1 assay ( Figure 8).
  • the PC3 prostate cancer cell line treated with oxaliplatin showed a relative growth rate equivalent to 93.5% of that of the untreated control PC3, and was loaded into exosomes.
  • oxaliplatin ExoR-OxPt
  • a cell growth rate of 71% was observed.
  • exosomes are interpreted to significantly aid the delivery of oxaliplatin into cell lines. This pattern is effectively observed even in 6- and 24-hour incubations, and is even effective in incubation conditions for an additional 72 hours after simultaneous drug removal after 30-hour incubation.
  • Example 4-1 In order to reconfirm the active drug loading technology of exosome-free exosomes, the same exosomes and the same amount of drug as in Example 4-1 were incubated at room temperature under the same conditions except for the temperature, and then incubated in the same manner as those that were not loaded using the same method. Removes drugs.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Botany (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention concerne une composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires (VE) dérivées de cultures comestibles.
PCT/KR2024/000995 2023-01-19 2024-01-19 Composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires dérivées de cultures comestibles Ceased WO2024155158A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2023-0008154 2023-01-19
KR20230008154 2023-01-19
KR1020240008911A KR20240116412A (ko) 2023-01-19 2024-01-19 식용작물에서 유래된 세포 외 소포(tracellular vesicle, EV)를 포함하는 암 예방 또는 치료용 조성물
KR10-2024-0008911 2024-01-19

Publications (1)

Publication Number Publication Date
WO2024155158A1 true WO2024155158A1 (fr) 2024-07-25

Family

ID=91956370

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2024/000995 Ceased WO2024155158A1 (fr) 2023-01-19 2024-01-19 Composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires dérivées de cultures comestibles

Country Status (1)

Country Link
WO (1) WO2024155158A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210137523A (ko) * 2019-03-13 2021-11-17 에보바이오테크 에스.알.엘. 식물-유래 세포외 소포(ev) 조성물 및 이의 용도
WO2022067223A2 (fr) * 2020-09-28 2022-03-31 University Of Florida Research Foundation, Incorporated Vésicules extracellulaires dérivées de plants de cannabis et méthodes thérapeutiques utilisant celles-ci
KR20220055232A (ko) * 2020-10-26 2022-05-03 인천대학교 산학협력단 배추속 식물 또는 파속 식물 유래 세포밖 소포체를 유효성분으로 포함하는 염증성 질환의 예방, 개선 또는 치료용 조성물
KR20220077578A (ko) * 2020-12-02 2022-06-09 인천대학교 산학협력단 식물 유래 세포밖 소포체를 포함하는 약물 전달체
KR20220087009A (ko) * 2020-12-17 2022-06-24 인천대학교 산학협력단 이중 약물이 봉입된 세포외 소포체의 제조방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210137523A (ko) * 2019-03-13 2021-11-17 에보바이오테크 에스.알.엘. 식물-유래 세포외 소포(ev) 조성물 및 이의 용도
WO2022067223A2 (fr) * 2020-09-28 2022-03-31 University Of Florida Research Foundation, Incorporated Vésicules extracellulaires dérivées de plants de cannabis et méthodes thérapeutiques utilisant celles-ci
KR20220055232A (ko) * 2020-10-26 2022-05-03 인천대학교 산학협력단 배추속 식물 또는 파속 식물 유래 세포밖 소포체를 유효성분으로 포함하는 염증성 질환의 예방, 개선 또는 치료용 조성물
KR20220077578A (ko) * 2020-12-02 2022-06-09 인천대학교 산학협력단 식물 유래 세포밖 소포체를 포함하는 약물 전달체
KR20220087009A (ko) * 2020-12-17 2022-06-24 인천대학교 산학협력단 이중 약물이 봉입된 세포외 소포체의 제조방법

Similar Documents

Publication Publication Date Title
WO2020071662A1 (fr) Composition comprenant des exosomes induits destinée à la régénération des cheveux
US7078063B2 (en) Water soluble extract from plant of Solanum genus and the preparation process thereof, and pharmaceutical composition containing the water soluble extract
WO2010082798A2 (fr) Composition contenant des extraits de fuscoporia obliqua, de gonaderma lucidum et de phellinus linteus pour favoriser la prolifération de cellules souches hématopoïétiques
CN115461064A (zh) 针对移植物抗宿主病的预防或治疗用组合物
CN114940487A (zh) 一种人参碳点及其制备方法和用途
WO2024155158A1 (fr) Composition permettant de prévenir ou de traiter un cancer, comprenant des vésicules extracellulaires dérivées de cultures comestibles
WO2021125822A1 (fr) Composition destinée à soulager la gueule de bois, contenant du pediococcus inopinatus comme principe actif
US8580318B2 (en) Natural water soluble extracts for the inhibition of alpha-1-adrenergic receptors
WO2012108749A2 (fr) Composition et alimentation fonctionnelle pour traiter le cancer du cerveau comprenant un extrait de graines de pharbitis
KR20240116412A (ko) 식용작물에서 유래된 세포 외 소포(tracellular vesicle, EV)를 포함하는 암 예방 또는 치료용 조성물
KR101948407B1 (ko) 커큐민이 포집된 진세노사이드 및 인지질 기반 지질나노입자를 유효성분으로 함유하는 헬리코박터 파이로리 감염의 예방 또는 치료용 조성물
EP1096930A1 (fr) Composition therapeutique a base de flavono des destinee a etre utilisee dans le traitement des tumeurs par des agents cytotoxiques
KR20200138121A (ko) 한약 추출물을 포함하는 교모세포종 예방 또는 치료용 조성물
KR102548439B1 (ko) T 보조세포 유래의 세포외 소포체로 활성화된 세포독성 t 세포를 유효성분으로 포함하는 암 질환의 예방 또는 치료용 조성물
WO2012108747A2 (fr) Composition et composition cosmétique pour traiter le cancer du cerveau comprenant un extrait de la racine d'helena
US12453775B2 (en) Composition, for prevention or treatment of cancer disease, comprising cytotoxic T cells activated by T helper cell-derived extracellular vesicles as active ingredient
Ismeel Cytogenetic and cytotoxic studies on the effect of phytoinvestigated active compounds of Hyoscyamus niger (in vivo and ex vivo)
KR101595987B1 (ko) 오스만투스 마츠무라누스 추출물을 포함하는 항암 조성물
TWI904636B (zh) 草莓葉之經乙醇萃取的產物在治療癌症上的用途
CN110251494B (zh) 2，7，2′-三羟基-4，4′，7′-三甲氧基-1，1′-双菲的用途
WO2023113134A1 (fr) Vésicules extracellulaires dérivées de cellules immunitaires chargées de médicament, et procédé de préparation correspondant
KR102171201B1 (ko) 에우오니무스 포르피레우스 추출물을 포함하는 항산화 또는 항암용 조성물
TWI235664B (en) Extract from the leaves of Toona sinensis Roem., and the preparation process and uses thereof
US6803059B2 (en) Anti-tumor metallocomplexes of crude extracts from Canavalia ensiformis
EP1508334A1 (fr) Extrait soluble dans l'eau de solanum, procédé de préparation et composition pharmaceutique de l'extrait hydrosoluble

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24744937

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 24744937

Country of ref document: EP

Kind code of ref document: A1