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WO2023195570A1 - Anticancer compositoin comprising superoxide dismutase - Google Patents

Anticancer compositoin comprising superoxide 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
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present
cancer
sod
superoxide dismutase
composition
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PCT/KR2022/005558
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French (fr)
Korean (ko)
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이왕재
이상윤
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이왕재바이오연구소 주식회사
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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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Abstract

The present invention relates to an anticancer composition comprising superoxide dismutase (SOD) and, more specifically, may provide a pharmaceutical composition for preventing or treating cancer which comprises exosomes surface-modified with SOD.

Description

슈퍼옥시드 디스무타아제를 포함하는 항암 조성물 Anticancer composition containing superoxide dismutase
본 발명은 슈퍼옥시드 디스무타아제를 포함하는 항암 조성물에 관한 것으로, 보다 상세하게는 슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공하는 것일 수 있다.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.
슈퍼옥시드 디스무타아제(Superoxide dismutase; SOD)는 인체의 모든 세포에서 발견되는 효소이다. 슈퍼옥사이드 라디칼을 분해하고, 살아있는 세포에 독성이 있고 DNA 돌연변이를 일으켜 산소와 수소로 이루어진 무해한 성분으로 과산화물. SOD를 보충제로 섭취하는 이론은 세포 및 DNA 손상에 대한 추가 보호를 제공한다는 것이지만, SOD는 경구 복용 시 혈류에 흡수되지 않기 때문에 사실이 아니다. 상기 효소는 살아있는 세포에 유독한 슈퍼옥사이드 라디칼의 분해를 촉매한다.Superoxide dismutase (SOD) 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.
이에 슈퍼옥시드 디스무타아제(SOD)를 엑소좀 표면에 도입할 경우, 항암효과가 있음을 보일 수 있음을 확인하여, 본 발명을 완성하였다.Accordingly, it was confirmed that when superoxide dismutase (SOD) is introduced to the surface of exosomes, it can be shown to have an anti-cancer effect, and the present invention was completed.
본 발명의 일 목적은 종래의 슈퍼옥시드 디스무타아제(SOD)를 엑소좀 표면에 도입하여 항암 효과를 가지는조성물을 제공하는데 있다. 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.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다. However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the description below.
상기한 목적을 달성하기 위하여, 본 발명은 일 실시예에서, 슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공할 수 있다.In order to achieve the above object, the present invention, in one embodiment, can provide a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD).
또한 본 발명에서, 상기 슈퍼옥시드 디스무타아제(SOD)는 서열번호 1 내지 2 중 어느 하나 이상의 펩타이드를 더 포함하는 것일 수 있다.Additionally, in the present invention, the superoxide dismutase (SOD) may further include any one or more peptides of SEQ ID NOs: 1 to 2.
또한 본 발명에서, 상기 조성물은 유기산, D-만니톨 및 D-소르비톨을 더 포함하는 것일 수 있다.Additionally, in the present invention, the composition may further include an organic acid, D-mannitol, and D-sorbitol.
또한 본 발명에서, 상기 유기산 100 중량부에 대하여, 상기 D-만니톨은 5 중량부 내지 15 중량부 및 D-소르비톨은 5 중량부 내지 15 중량부인 것일 수 있다.Additionally, in the present invention, based on 100 parts by weight of the organic acid, 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.
또한 본 발명에서, 상기 유기산은 아스코르브산, 구연산, 및 피루브산이 포함된 군에서 선택된 어느 하나 이상인 것일 수 있다.Additionally, in the present invention, the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid.
본 발명에 따른 조성물의 경우, 암 세포의 혈관신생을 억제하여 항암 효과를 가질 수 있게 한다.In the case of the composition according to the present invention, it can have an anti-cancer effect by inhibiting angiogenesis of cancer cells.
본 발명의 효과들은 이상에서 언급된 효과로 제한되지 않으며, 언급되지 않은 또 다른 효과들은 아래의 기재로부터 통상의 기술자에게 명확하게 이해될 수 있을 것이다.The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description below.
도 1은 본 발명의 일 실시예에 따른 조성물의 항암 효과를 MTT assay로 확인한 결과이다.Figure 1 shows the results of confirming the anticancer effect of a composition according to an embodiment of the present invention by MTT assay.
상기한 목적을 달성하기 위하여, 본 발명은 일 실시예에서, 슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공할 수 있다.In order to achieve the above object, the present invention, in one embodiment, can provide a pharmaceutical composition for preventing or treating cancer containing exosomes surface-modified with superoxide dismutase (SOD).
또한 본 발명에서, 상기 슈퍼옥시드 디스무타아제(SOD)는 서열번호 1 내지 2 중 어느 하나 이상의 펩타이드를 더 포함하는 것일 수 있다.Additionally, in the present invention, the superoxide dismutase (SOD) may further include any one or more peptides of SEQ ID NOs: 1 to 2.
또한 본 발명에서, 상기 조성물은 유기산, D-만니톨 및 D-소르비톨을 더 포함하는 것일 수 있다.Additionally, in the present invention, the composition may further include an organic acid, D-mannitol, and D-sorbitol.
또한 본 발명에서, 상기 유기산 100 중량부에 대하여, 상기 D-만니톨은 5 중량부 내지 15 중량부 및 D-소르비톨은 5 중량부 내지 15 중량부인 것일 수 있다.Additionally, in the present invention, based on 100 parts by weight of the organic acid, 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.
또한 본 발명에서, 상기 유기산은 아스코르브산, 구연산, 및 피루브산이 포함된 군에서 선택된 어느 하나 이상인 것일 수 있다.Additionally, in the present invention, the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid.
이하, 본 발명에 대하여 상세히 설명하기로 한다. 이에 앞서, 본 명세서 및 특허청구범위에 사용된 용어 또는 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 아니되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다. 따라서, 본 명세서에 기재된 실시예에 기재된 구성은 본 발명의 가장 바람직한 일 실시예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 염 및 유도체 등과 같은 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.Hereinafter, the present invention will be described in detail. Prior to this, the terms or words used in this specification and patent claims should not be construed as limited to their usual or dictionary meanings, and the inventor must appropriately use the concept of the term to explain his or her invention in the best way. It must be interpreted as meaning and concept consistent with the technical idea of the present invention based on the principle that it can be defined clearly. Therefore, the configuration described in the examples described in this specification is only one of the most preferred embodiments of the present invention and does not represent the entire technical idea of the present invention, so salts, derivatives, etc. that can replace them at the time of filing the present application. It should be understood that there may be various equivalents and variations.
한편, 본 명세서에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 명세서에서 개시된 다양한 요소들의 모든 조합이 본 출원의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.Meanwhile, each description and embodiment disclosed in this specification may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present application. Additionally, the scope of the present invention cannot be considered limited by the specific description described below.
본 발명의 일 구현예에서, In one embodiment of the present invention,
슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공할 수 있다. 상기 엑소좀은 대부분의 진핵 세포의 엔도솜 구획에서 생성되는 세포외 소포체(Extracellular vesicle; EV)로, 그 제조 방법은 제한없이 포함될 수 있다.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.
본 발명에서, 상기 슈퍼옥시드 디스무타아제(SOD)는 서열번호 1 내지 2 중 어느 하나 이상의 펩타이드를 더 포함하는 것일 수 있고, 또는 서열번호 1 내지 3 중 어느 하나 이상의 펩타이드를 더 포함하는 것일 수 있고, 이를 하기 표 1 과 같이 나타낼 수 있다.In the present invention, the superoxide dismutase (SOD) 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.
서열번호sequence number 서열order
1One MLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGTLHAACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGDLSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVVHAGEDDLGRG GNQASVENGN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAAMALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQPRGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVLMLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGTLHAACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGDLSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVVHAGEDDLGRG GNQASVEN GN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAAMALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQPRGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVL
22 MATKAVCVLK GDGPVQGIIN FEQKESNGPV KVWGSIKGLT EGLHGFHVHE FGDNTAGCTSAGPHFNPLSR KHGGPKDEER HVGDLGNVTA DKDGVADVSI EDSVISLSGD HCIIGRTLVVHEKADDLGKG GNEESTKTGN AGSRLACGVI GIAQGGGGSI YIWAPLAGTC GVLLLSLVITLYCGGGGSMATKAVCVLK GDGPVQGIIN FEQKESNGPV KVWGSIKGLT EGLHGFHVHE FGDNTAGCTSAGPHFNPLSR KHGGPKDEER HVGDLGNVTA DKDGVADVSI EDSVISLSGD HCIIGRTLVVHEKADDLGKG GNEESTKTGN AGSRLACGVI GIAQGGGGSI YIWAPLAGTC GVLLLSLVITLYCGGGGS
33 MLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGTLHAACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGDLSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVVHAGEDDLGRG GNQASVENGN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAAGGGGSIYIWA PLAGTCGVLL LSLVITLYCG GGGSMLALLCSCLL LAAGASDAWT GEDSAEPNSD SAEWIRDMYA KVTEIWQEVM QRRDDDGTLHAACQVQPSAT LDAAQPRVTG VVLFRQLAPR AKLDAFFALE GFPTEPNSSS RAIHVHQFGDLSQGCESTGP HYNPLAVPHP QHPGDFGNFA VRDGSLWRYR AGLAASLAGP HSIVGRAVVVHAGEDDLGRG GNQASVEN GN AGRRLACCVV GVCGPGLWER QAREHSERKK RRRESECKAAGGGGSIYIWA PLAGTCGVLL LSLVITLYCG GGGS
본 발명에서, 상기 조성물은 유기산, D-만니톨 및 D-소르비톨을 더 포함하는 것일 수 있다. In the present invention, the composition may further include an organic acid, D-mannitol, and D-sorbitol.
본 발명에서, 상기 유기산 100 중량부에 대하여, 상기 D-만니톨은 5 중량부 내지 15 중량부 및 D-소르비톨은 5 중량부 내지 15 중량부인 것일 수 있다. 상기 중량부로 포함될 경우 슈퍼옥시드 디스무타아제의 암 혈관신생 억제 효과가 잘 발휘될 수 있다.In the present invention, based on 100 parts by weight of the organic acid, 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. When included in the above weight parts, the cancer angiogenesis inhibitory effect of superoxide dismutase can be effectively demonstrated.
본 발명에서, 상기 유기산은 아스코르브산, 구연산, 및 피루브산이 포함된 군에서 선택된 어느 하나 이상인 것일 수 있다. 여기서, 상기 아스코르브산(ascorbic acid)은 항산화 물질의 특성을 가지고 있고, 락톤 구조를 가진 유기 화합물이고, 상기 구연산(citric acid)은 산소 호흡을 하는 모든 생물의 대사 과정에서 일어나는 시트르산 회로의 중간생성물이고, 상기 피루브산(pyruvic acid)은 카복실산과 케톤 작용기를 가진 알파 케토산이며, 상기 만니톨(mannitol)은 삼투압이뇨제계 약물로 사용될 수 있는 당알코올의 일종이고, 상기 소르비톨(sorbitol)은 포도당과 같은 육탄당을 환원하여 얻는 6가 알코올의 일종으로 설탕과 유사한 단맛을 내는 것이다.In the present invention, the organic acid may be any one or more selected from the group including ascorbic acid, citric acid, and pyruvic acid. Here, ascorbic acid has antioxidant properties and is an organic compound with a lactone structure, and 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, and 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.
본 발명에서 상기 “암”은 변종 세포의 신속하고 제어되지 않은 성장을 특징으로 하는 질병으로서, 흑색종, 나팔관암, 뇌암, 소장암, 식도암, 임파선암, 담낭암, 혈액암, 갑상선암, 내분비선암, 구강암, 간암, 담도암, 대장암, 직장암, 자궁경부암, 난소암, 신장암, 위암, 십이지장암, 전립선암, 유방암, 뇌종양, 폐암, 갑상선 미분화암, 자궁암, 결장암, 방광암, 요관암, 췌장암, 뼈/연부조직 육종, 피부암, 비호지킨 림프종, 호지킨 림프종, 다발성 골수종, 백혈병, 골수이형성증후군, 급성 림프모구성 백혈병, 급성 골수성 백혈병, 만성 림프구성 백혈병, 만성 골수성 백혈병 및 고립성 골수종으로 구성되는 군으로부터 선택되는 적어도 하나인 것일 수 있다.In the present invention, 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 myeloid leukemia, and solitary myeloma. It may be at least one selected from.
본 발명의 상기 "예방"이란, 본 발명의 상기 조성물을 이용하여 암 내지 이에 의한 혈관신생에 의해 발생되는 질환 및 이의 증상을 차단하거나, 그 증상을 억제 또는 지연시키는 행위라면 제한없이 포함될 수 있다.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.
본 발명의 상기 "개선"이란, 본 발명의 상기 조성물을 이용하여 암 내지 이에 의한 혈관신생에 의해 발생되는 증상이 호전되거나 이롭게 되는 모든 행위라면 제한 없이 포함될 수 있다.The term “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.
본 발명의 상기 "치료"란, 본 발명의 상기 조성물을 이용하여 암에 의해 발생된 증상이 호전되거나 이롭게 되는 행위라면 제한 없이 포함될 수 있고, 특히 암에 의한 혈관신생을 억제하는 것일 수 있다.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.
본 발명의 상기 약학적 조성물은 캡슐, 정제, 과립, 주사제, 연고제, 분말 또는 음료 형태임을 특징으로 할 수 있으며, 상기 약학적 조성물은 인간 또는 동물을 대상으로 하는 것을 특징으로 할 수 있다. 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.
본 발명의 상기 약학적 조성물은 이들로 한정되는 것은 아니지만, 각각 통상의 방법에 따라 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사 용액의 형태로 제형화하여 사용될 수 있다. 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
본 발명의 상기 약학적 조성물은 약학적으로 허용 가능한 담체를 포함할 수 있다. 상기 약학적으로 허용되는 담체는 경구 투여 시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있고, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다.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.
본 발명의 상기 약학적 조성물의 제형은 상술한 바와 같은 약학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. 예를 들어, 경구 투여시에는 정제, 트로키, 캡슐, 엘릭서(Elixir), 서스펜션, 시럽, 웨이퍼 등의 형태로 제조할 수 있으며, 주사제의 경우에는 단위 투약 앰플 또는 다수회 투약 형태로 제조할 수 있다. 기타, 용액, 현탁액, 정제, 캡슐, 서방형 제제 등으로 제형화 할 수 있다.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. 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. In addition, it can be formulated into solutions, suspensions, tablets, capsules, sustained-release preparations, etc.
본 발명의 상기 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.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. In addition, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives, etc. may be additionally included.
본 발명의 상기 약학적 조성물의 투여 경로는 이들로 한정되는 것은 아니지만 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함된다. 경구 또는 비경구 투하가 바람직하다. 본 발명에서 상기 "비경구"는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입 기술을 포함한다.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. In the present invention, the term “parenteral” includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
본 발명의 상기 약학적 조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여 시간, 투여 경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학적 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약무 형태, 투여 경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001 내지 50 mg/kg 또는 0.001 내지 50 mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 약학적 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형화될 수 있다.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.
본 발명의 다른 구현예에서, In another embodiment of the present invention,
슈퍼옥시드 디스무타아제 또는 이의 유도체를 포함하는 조성물을 약학적 유효량으로 개체에게 투여하는 단계를 포함하는, 활성산소로 인해 발생하는 질환을 예방 또는 치료하기 위한 방법을 제공할 수 있다. A method for preventing or treating diseases caused by free radicals can be provided, comprising administering to an individual a composition containing superoxide dismutase or a derivative thereof in a pharmaceutically effective amount.
본 발명에서 용어 “투여”란, 임의의 적절한 방법으로 개체에게 본 발명의 유효성분을 도입하는 과정을 의미하는 것으로서, 본 발명의 상기 치료 방법에서 투여 방법은 경구 또는 비경구 등의 다양한 경로를 통해 투여될 수 있다.In the present invention, the term “administration” refers to the process of introducing the active ingredient of the present invention into an individual by any appropriate method. In the treatment method of the present invention, the administration method is through various routes such as oral or parenteral. may be administered.
본 발명의 목적상, 목적하는 개체에 대한 구체적인 약학적 유효량은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지의 여부를 비롯한 구체적 상기 유효성분을 포함하는 조성물, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 상기 유효성분을 포함하는 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.For the purpose of the present invention, 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.
본 발명에서, 생략된 나머지 기재들은 앞서 기재된 바와 마찬가지로 해석될 수 있다.In the present invention, the remaining omitted descriptions can be interpreted similarly to what was previously described.
본 발명의 또 다른 구현예에서, In another embodiment of the present invention,
아스코르브산 또는 이의 유도체를 포함하는 조성물을 약학적 유효량으로 개체에게 투여하는 단계를 포함하는, 활성산소로 인해 발생하는 질환을 예방 또는 치료하기 위한 방법을 제공할 수 있다. A method for preventing or treating diseases caused by free radicals can be provided, comprising administering to an individual a composition containing ascorbic acid or a derivative thereof in a pharmaceutically effective amount.
본 발명에서 용어 “투여”란, 임의의 적절한 방법으로 개체에게 본 발명의 유효성분을 도입하는 과정을 의미하는 것으로서, 본 발명의 상기 치료 방법에서 투여 방법은 경구 또는 비경구 등의 다양한 경로를 통해 투여될 수 있다.In the present invention, the term “administration” refers to the process of introducing the active ingredient of the present invention into an individual by any appropriate method. In the treatment method of the present invention, the administration method is through various routes such as oral or parenteral. may be administered.
본 발명의 목적상, 목적하는 개체에 대한 구체적인 약학적 유효량은 달성하고자 하는 반응의 종류와 정도, 경우에 따라 다른 제제가 사용되는지의 여부를 비롯한 구체적 상기 유효성분을 포함하는 조성물, 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 상기 유효성분을 포함하는 조성물의 분비율, 치료기간, 구체적 조성물과 함께 사용되거나 동시 사용되는 약물을 비롯한 다양한 인자와 의약 분야에 잘 알려진 유사 인자에 따라 다르게 적용하는 것이 바람직하다.For the purpose of the present invention, 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.
본 발명에서, 생략된 나머지 기재들은 앞서 기재된 바와 마찬가지로 해석될 수 있다.In the present invention, the remaining omitted descriptions can be interpreted similarly to what was previously described.
이하, 본 발명을 하기 실시예에 의거하여 더욱 상세히 설명하지만, 이는 본 발명을 예시하는 것일 뿐 본 발명의 범위가 이에 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail based on the following examples, but these are only illustrative of the present invention and the scope of the present invention is not limited thereto.
실시예 1. 항산화 조성물 제조Example 1. Preparation of antioxidant composition
슈퍼옥시드 디스무타아제(SOD)가 표면에 개질된 엑소좀을 제조하였고, 여기에 구연산나트륨(KP), 피루브산칼슘염, D-만니톨 및 D-소르비톨을 하기 표 2와 같이 정량한 뒤, 각각 용매에 용해시켜 혼합물을 제조하였고, 펩타이드를 추가하여 제조예 1 내지 7의 조성물을 제조하였다.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. A mixture was prepared by dissolving in a solvent, and the compositions of Preparation Examples 1 to 7 were prepared by adding peptides.
성분(단위: mg)Ingredients (unit: mg) 제조예 1Manufacturing Example 1 제조예 2Production example 2 제조예 3Production example 3 제조예 4Production example 4 제조예 5Production example 5 제조예 6Production example 6
엑소좀exosome 서열번호 1 SOD 개질된 엑소좀SEQ ID NO: 1 SOD modified exosome 서열번호 2 SOD 개질된 엑소좀SEQ ID NO: 2 SOD modified exosome 서열번호 1 SOD 개질된 엑소좀SEQ ID NO: 1 SOD modified exosome 서열번호 2 SOD 개질된 엑소좀SEQ ID NO: 2 SOD modified exosome 서열번호 1 SOD 개질된 엑소좀SEQ ID NO: 1 SOD modified exosome 서열번호 2 SOD 개질된 엑소좀SEQ ID NO: 2 SOD modified exosome
구연산나트륨sodium citrate 1010 1010 1010 1010 1010 1010
피루브산칼슘염 Calcium pyruvate salt 2020 2020 2020 2020 2020 2020
D-만니톨D-mannitol 1010 1010 55 55 2020 2020
D-소르비톨D-Sorbitol 1010 1010 2020 2020 00 00
용매menstruum 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount
또한, 제조된 혼합물에 엑소좀을 추가하지 않은 조성물을 하기 표 3과 같이 제조하였다.Additionally, a composition without adding exosomes to the prepared mixture was prepared as shown in Table 3 below.
성분(단위: mg)Ingredients (unit: mg) 비교예 1Comparative Example 1 비교예 2Comparative Example 2 비교예 3Comparative Example 3 비교예 4Comparative Example 4
엑소좀exosome 엑소좀 불포함Exosome-free SOD 불포함 엑소좀SOD-free exosomes SOD 불포함 엑소좀SOD-free exosomes SOD 불포함 엑소좀SOD-free exosomes
구연산나트륨sodium citrate 1010 1010 1010 1010
피루브산칼슘염 Calcium pyruvate salt 2020 2020 2020 2020
D-만니톨D-mannitol 1010 1010 1010 55
D-소르비톨D-Sorbitol 1010 1010 1010 2020
용매menstruum 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount 적량Appropriate amount
단, 상기 표 2, 3에서 제조된 각 조성물의 중량은 동일하도록 조절하였다.However, the weight of each composition prepared in Tables 2 and 3 was adjusted to be the same.
실시예 2. 항암능 평가Example 2. Evaluation of anticancer activity
조성물에 포함된 엑소좀의 SOD 개질화 여부에 따른 항암 효과를 확인하기 위하여, 각 조성물의 처리에 따른 암세포주의 혈관신생 인자 발현을 평가하였다. 구체적으로는, 안정화된 암세포주(PC-14)에 각 조성물을 처리하였고, 혈관신생인자인 VEGF mRNA 발현량의 상대값을 비교하여 그 결과를 도 1에 나타내였다. 단, 대조군은 비교예 1의 엑소좀 불포함 조성물에서의 VEGF 발현량으로 설정하였다.In order to confirm the anticancer effect depending on whether the exosomes contained in the composition were modified with SOD, 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.
도 1에 나타난 것처럼, 서열번호 1 또는 2의 SOD가 개질된 엑소좀을 포함하는 제조예 1 및 제조예 2의 조성물이 투여된 경우 비교예 1의 조성물이 투여된 경우에 비하여 암세포주의 VEGF 상대 감소하는 것을 확인한 바, 본 발명의 SOD 개질된 엑소좀을 포함한 조성물의 경우, 항암 효과를 가질 수 있는 것을 확인하였다.As shown in Figure 1, when the compositions of Preparation Example 1 and Preparation Example 2 containing exosomes modified with SOD of SEQ ID NO: 1 or 2 were administered, the relative decrease in VEGF of cancer cell lines compared to when the composition of Comparative Example 1 was administered. As confirmed, it was confirmed that the composition containing the SOD-modified exosomes of the present invention can have an anti-cancer effect.
이상에서 본 발명에 대하여 상세하게 설명하였지만 본 발명의 권리범위는 이에 한정되는 것은 아니고, 청구범위에 기재된 본 발명의 기술적 사상을 벗어나지 않는 범위 내에서 다양한 수정 및 변형이 가능하다는 것은 당 기술분야의 통상의 지식을 가진 자에게는 자명할 것이다. Although the present invention has been described in detail above, the scope of the present invention is not limited thereto, and it is known in the art that various modifications and variations are possible without departing from the technical spirit of the present invention as set forth in the claims. It will be self-evident to those with knowledge.
본 발명은 슈퍼옥시드 디스무타아제를 포함하는 항암 조성물에 관한 것으로, 보다 상세하게는 슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물을 제공하는 것일 수 있다.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.

Claims (5)

  1. 슈퍼옥시드 디스무타아제(SOD)가 표면 개질된 엑소좀을 포함하는 암의 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating cancer comprising exosomes surface-modified with superoxide dismutase (SOD).
  2. 제1항에 있어서, According to paragraph 1,
    상기 슈퍼옥시드 디스무타아제(SOD)는 서열번호 1 내지 2 중 어느 하나 이상의 펩타이드를 더 포함하는 것인, 약학적 조성물.A pharmaceutical composition wherein the superoxide dismutase (SOD) further comprises one or more peptides of SEQ ID NOs: 1 to 2.
  3. 제1항에 있어서, According to paragraph 1,
    상기 조성물은 유기산, D-만니톨 및 D-소르비톨을 더 포함하는 것인, 약학적 조성물.A pharmaceutical composition, wherein the composition further includes an organic acid, D-mannitol, and D-sorbitol.
  4. 제3항에 있어서, According to paragraph 3,
    상기 유기산 100 중량부에 대하여, 상기 D-만니톨은 5 중량부 내지 15 중량부 및 D-소르비톨은 5 중량부 내지 15 중량부인 것인, 약학적 조성물.A pharmaceutical composition, wherein the D-mannitol is contained in an amount of 5 to 15 parts by weight and the D-sorbitol is contained in an amount of 5 to 15 parts by weight based on 100 parts by weight of the organic acid.
  5. 제3항에 있어서,According to paragraph 3,
    상기 유기산은 아스코르브산, 구연산, 및 피루브산이 포함된 군에서 선택된 어느 하나 이상인 것인, 약학적 조성물.A pharmaceutical composition, wherein the organic acid is at least one selected from the group consisting of ascorbic acid, citric acid, and pyruvic acid.
PCT/KR2022/005558 2022-04-08 2022-04-18 Anticancer compositoin comprising superoxide dismutase WO2023195570A1 (en)

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