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WO2023195570A1 - Composition anticancéreuse comprenant de la superoxyde dismutase - Google Patents

Composition anticancéreuse comprenant de la superoxyde dismutase Download PDF

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Publication number
WO2023195570A1
WO2023195570A1 PCT/KR2022/005558 KR2022005558W WO2023195570A1 WO 2023195570 A1 WO2023195570 A1 WO 2023195570A1 KR 2022005558 W KR2022005558 W KR 2022005558W WO 2023195570 A1 WO2023195570 A1 WO 2023195570A1
Authority
WO
WIPO (PCT)
Prior art keywords
present
cancer
sod
superoxide dismutase
composition
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/KR2022/005558
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English (en)
Korean (ko)
Inventor
이왕재
이상윤
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.)
Lee Wangjae Bio Laboratory Co Ltd
Original Assignee
Lee Wangjae Bio Laboratory Co Ltd
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 Lee Wangjae Bio Laboratory Co Ltd filed Critical Lee Wangjae Bio Laboratory Co Ltd
Publication of WO2023195570A1 publication Critical patent/WO2023195570A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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 an anti-cancer composition containing superoxide dismutase, and more specifically, to a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD). It may be provided.
  • SOD superoxide dismutase
  • Superoxide dismutase is an enzyme found in all cells of the human body. Superoxide decomposes radicals, is toxic to living cells and causes DNA mutations. Peroxide is a harmless component made up of oxygen and hydrogen. The theory of taking SOD as a supplement is that it provides additional protection against cell and DNA damage, but this is not true because SOD is not absorbed into the bloodstream when taken orally. The enzyme catalyzes the breakdown of superoxide radicals, which are toxic to living cells.
  • One object of the present invention is to provide a composition having an anticancer effect by introducing conventional superoxide dismutase (SOD) to the surface of exosomes.
  • SOD superoxide dismutase
  • the present invention in one embodiment, can provide a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD).
  • SOD superoxide dismutase
  • the superoxide dismutase may further include any one or more peptides of SEQ ID NOs: 1 to 2.
  • the composition may further include an organic acid, D-mannitol, and D-sorbitol.
  • the D-mannitol may be present in an amount of 5 to 15 parts by weight, and the D-sorbitol may be contained in an amount of 5 to 15 parts by weight.
  • the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid.
  • composition according to the present invention can have an anti-cancer effect by inhibiting angiogenesis of cancer cells.
  • Figure 1 shows the results of confirming the anticancer effect of a composition according to an embodiment of the present invention by MTT assay.
  • the present invention in one embodiment, can provide a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD).
  • SOD superoxide dismutase
  • the superoxide dismutase may further include any one or more peptides of SEQ ID NOs: 1 to 2.
  • the composition may further include an organic acid, D-mannitol, and D-sorbitol.
  • the D-mannitol may be present in an amount of 5 to 15 parts by weight, and the D-sorbitol may be contained in an amount of 5 to 15 parts by weight.
  • the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid.
  • a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD) can be provided.
  • the exosome is an extracellular vesicle (EV) produced in the endosomal compartment of most eukaryotic cells, and its production method may be included without limitation.
  • the superoxide dismutase may further include any one or more peptides of SEQ ID NOs: 1 to 2, or may further include any one or more peptides of SEQ ID NOs: 1 to 3. There is, and this can be expressed as Table 1 below.
  • the composition may further include an organic acid, D-mannitol, and D-sorbitol.
  • the D-mannitol may be 5 parts by weight to 15 parts by weight and the D-sorbitol may be 5 parts by weight to 15 parts by weight.
  • the cancer angiogenesis inhibitory effect of superoxide dismutase can be effectively demonstrated.
  • the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid.
  • ascorbic acid has antioxidant properties and is an organic compound with a lactone structure
  • citric acid is an intermediate product of the citric acid cycle that occurs in the metabolic process of all organisms that breathe aerobically.
  • the pyruvic acid is an alpha-keto acid with carboxylic acid and ketone functional groups
  • the mannitol is a type of sugar alcohol that can be used as an osmotic diuretic drug
  • the sorbitol is a hexose such as glucose. It is a type of hexahydric alcohol obtained by reducing , and has a sweet taste similar to sugar.
  • the “cancer” refers to a disease characterized by rapid and uncontrolled growth of mutant cells, such as melanoma, fallopian tube cancer, brain cancer, small intestine cancer, esophageal cancer, lymph node cancer, gallbladder cancer, blood cancer, thyroid cancer, endocrine cancer, Oral cancer, liver cancer, biliary tract cancer, colon cancer, rectal cancer, cervical cancer, ovarian cancer, kidney cancer, stomach cancer, duodenal cancer, prostate cancer, breast cancer, brain tumor, lung cancer, undifferentiated thyroid cancer, uterine cancer, colon cancer, bladder cancer, ureter cancer, pancreatic cancer, A group consisting of bone/soft tissue sarcoma, skin cancer, non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic mye
  • mutant cells
  • the "prevention" of the present invention may be included without limitation as long as it is an act of blocking diseases and symptoms caused by cancer or angiogenesis thereof using the composition of the present invention, or suppressing or delaying the symptoms.
  • improvement of the present invention may include, without limitation, any action that improves or benefits symptoms caused by cancer or angiogenesis by using the composition of the present invention.
  • the "treatment” of the present invention may include without limitation any action that improves or benefits symptoms caused by cancer by using the composition of the present invention, and may particularly include suppressing angiogenesis caused by cancer.
  • the pharmaceutical composition of the present invention may be in the form of capsules, tablets, granules, injections, ointments, powders, or beverages, and may be intended for use on humans or animals.
  • the pharmaceutical composition of the present invention is not limited to these, but is formulated into oral dosage forms such as powders, granules, capsules, tablets, and aqueous suspensions, external preparations, suppositories, and sterile injection solutions according to conventional methods. can be used
  • the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, colorants, flavorings, etc. for oral administration, and for injections, buffers, preservatives, Analgesics, solubilizers, isotonic agents, stabilizers, etc. can be mixed and used, and for topical administration, bases, excipients, lubricants, preservatives, etc. can be used.
  • the formulation of the pharmaceutical composition of the present invention can be prepared in various ways by mixing it with a pharmaceutically acceptable carrier as described above.
  • a pharmaceutically acceptable carrier for example, for oral administration, it can be manufactured in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and in the case of injections, it can be manufactured in the form of unit dose ampoules or multiple doses. there is.
  • it can be formulated into solutions, suspensions, tablets, capsules, sustained-release preparations, etc.
  • Examples of carriers, excipients and diluents suitable for the formulation of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium. Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil may be used.
  • fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives, etc. may be additionally included.
  • the route of administration of the pharmaceutical composition of the present invention is not limited to these, but is oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, and topical. , sublingual or rectal. Oral or parenteral administration is preferred.
  • parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
  • the pharmaceutical composition of the present invention depends on several factors, including the activity of the specific compound used, age, body weight, general health, gender, diet, administration time, administration route, excretion rate, drug formulation, and the severity of the specific disease to be prevented or treated.
  • the dosage of the pharmaceutical composition may vary depending on the patient's condition, weight, degree of disease, drug form, route and period of administration, but may be appropriately selected by a person skilled in the art, and is 0.0001 to 50 doses per day. It can be administered at mg/kg or 0.001 to 50 mg/kg. Administration may be administered once a day, or may be administered several times. The above dosage does not limit the scope of the present invention in any way.
  • the pharmaceutical composition according to the present invention can be formulated into pills, dragees, capsules, solutions, gels, syrups, slurries, and suspensions.
  • a method for preventing or treating diseases caused by free radicals comprising administering to an individual a composition containing superoxide dismutase or a derivative thereof in a pharmaceutically effective amount.
  • the term “administration” refers to the process of introducing the active ingredient of the present invention into an individual by any appropriate method.
  • the administration method is through various routes such as oral or parenteral. may be administered.
  • the specific pharmaceutically effective amount for the subject of interest is the type and degree of response to be achieved, the composition containing the active ingredient, the patient's age, and whether other agents are used as the case may be.
  • Various factors well known in the medical field including body weight, general health condition, gender and diet, administration time, administration route and secretion rate of the composition containing the active ingredient, treatment period, and drugs used together or simultaneously with the specific composition. It is desirable to apply it differently depending on similar factors.
  • a method for preventing or treating diseases caused by free radicals comprising administering to an individual a composition containing ascorbic acid or a derivative thereof in a pharmaceutically effective amount.
  • the term “administration” refers to the process of introducing the active ingredient of the present invention into an individual by any appropriate method.
  • the administration method is through various routes such as oral or parenteral. may be administered.
  • the specific pharmaceutically effective amount for the subject of interest is the type and degree of response to be achieved, the composition containing the active ingredient, the patient's age, and whether other agents are used as the case may be.
  • Various factors well known in the medical field including body weight, general health condition, gender and diet, administration time, administration route and secretion rate of the composition containing the active ingredient, treatment period, and drugs used together or simultaneously with the specific composition. It is desirable to apply it differently depending on similar factors.
  • Exosomes with superoxide dismutase (SOD) modified on the surface were prepared, and sodium citrate (KP), calcium pyruvate, D-mannitol, and D-sorbitol were quantified as shown in Table 2 below, respectively.
  • KP sodium citrate
  • a mixture was prepared by dissolving in a solvent, and the compositions of Preparation Examples 1 to 7 were prepared by adding peptides.
  • composition without adding exosomes to the prepared mixture was prepared as shown in Table 3 below.
  • Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 exosome Exosome-free SOD-free exosomes SOD-free exosomes sodium citrate 10 10 10 10 10 10 Calcium pyruvate salt 20 20 20 20 D-mannitol 10 10 10 5 D-Sorbitol 10 10 10 20 menstruum Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount
  • the expression of angiogenic factors in cancer cell lines according to treatment with each composition was evaluated. Specifically, the stabilized cancer cell line (PC-14) was treated with each composition, and the relative expression levels of VEGF mRNA, an angiogenic factor, were compared and the results are shown in Figure 1. However, the control group was set to the VEGF expression level in the exosome-free composition of Comparative Example 1.
  • the present invention relates to an anti-cancer composition containing superoxide dismutase, and more specifically, to a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD). It may be provided.
  • SOD superoxide dismutase

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne une composition anticancéreuse comprenant de la superoxyde dismutase (SOD) et peut fournir, plus spécifiquement, une composition pharmaceutique pour prévenir ou traiter le cancer qui comprend des exosomes modifiés en surface par SOD.
PCT/KR2022/005558 2022-04-08 2022-04-18 Composition anticancéreuse comprenant de la superoxyde dismutase Ceased WO2023195570A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR20220043686 2022-04-08
KR10-2022-0043686 2022-04-08

Publications (1)

Publication Number Publication Date
WO2023195570A1 true WO2023195570A1 (fr) 2023-10-12

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PCT/KR2022/005558 Ceased WO2023195570A1 (fr) 2022-04-08 2022-04-18 Composition anticancéreuse comprenant de la superoxyde dismutase

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200037366A (ko) * 2017-08-11 2020-04-08 제넨테크, 인크. 항-cd8 항체 및 이의 용도
KR20200108275A (ko) * 2017-12-28 2020-09-17 코디악 바이오사이언시즈, 인크. 면역-종양학 및 항-염증 요법을 위한 엑소좀
US20200297631A1 (en) * 2016-03-30 2020-09-24 The University Of North Carolina At Chapel Hill Biological agent-exosome compositions and uses thereof
KR20210066005A (ko) * 2018-10-25 2021-06-04 가톨릭대학교 산학협력단 Sod3를 과발현시킨 줄기세포 유래 세포외 소낭의 신규한 용도
KR20210126501A (ko) * 2020-04-10 2021-10-20 한국과학기술연구원 신규 재조합 엑소좀 및 그의 용도

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200297631A1 (en) * 2016-03-30 2020-09-24 The University Of North Carolina At Chapel Hill Biological agent-exosome compositions and uses thereof
KR20200037366A (ko) * 2017-08-11 2020-04-08 제넨테크, 인크. 항-cd8 항체 및 이의 용도
KR20200108275A (ko) * 2017-12-28 2020-09-17 코디악 바이오사이언시즈, 인크. 면역-종양학 및 항-염증 요법을 위한 엑소좀
KR20210066005A (ko) * 2018-10-25 2021-06-04 가톨릭대학교 산학협력단 Sod3를 과발현시킨 줄기세포 유래 세포외 소낭의 신규한 용도
KR20210126501A (ko) * 2020-04-10 2021-10-20 한국과학기술연구원 신규 재조합 엑소좀 및 그의 용도

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