WO2020213938A1 - Composition pharmaceutique pour le traitement du cancer comprenant une saponine utilisée comme principe actif - Google Patents

Composition pharmaceutique pour le traitement du cancer comprenant une saponine utilisée comme principe actif Download PDF

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WO2020213938A1
WO2020213938A1 PCT/KR2020/005064 KR2020005064W WO2020213938A1 WO 2020213938 A1 WO2020213938 A1 WO 2020213938A1 KR 2020005064 W KR2020005064 W KR 2020005064W WO 2020213938 A1 WO2020213938 A1 WO 2020213938A1
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cancer
pharmaceutical composition
carcinoma
ginsenoside
methylsulfonyl
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PCT/KR2020/005064
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English (en)
Korean (ko)
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김홍렬
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주식회사 진센
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Publication of WO2020213938A1 publication Critical patent/WO2020213938A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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 pharmaceutical composition for cancer treatment comprising saponin as an active ingredient.
  • Cancer is one of the most common causes of death worldwide. About 10 million new cases occur every year, accounting for about 12% of all causes of death, making it the third-most cause of death. Therefore, efforts to develop effective anticancer agents have been continued, but anticancer drugs developed until recently are mostly targeting general cancer cells, and are not effective in killing cancer stem cells, which play an important role in treatment resistance and recurrence of cancer patients.
  • the cancer stem cells described above are cancer cells that have unlimited regenerative ability similar to general stem cells. They proliferate slowly differently from general cancer cells, have self-renewal or differentiation ability, which is a unique ability of stem cells, and Although it is known to have a different mechanism, the development of a drug for treating cancer stem cells targeting cancer stem cells is still insufficient (Korean Patent Application No. 10-2011-0066035). If cancer stem cells remain in the body even after cancer treatment, recurrence and/or metastasis of cancer occurs actively, so the development of cancer stem cell therapeutics is an urgent task.
  • saponin is a glycoside of steroids, steroid alkaloids, or triterpene, and is a generic term for substances that dissolve in water and exhibit the foaming action of a soap type. It is present in various plants and is known to be included in the body of some echinoderms (starfish, sea cucumber), but ginsenoside and eleutheroside, which are saponin types contained in ginseng, are particularly famous. Ginsenosides reach over 34 species such as Rg1, Rb1, Rb2, Rh2, and Rg3, and the effects of each component are different. For example, Korean Patent No. KR 101539574 B1 describes “the retinal regeneration effect by ginsenoside Rg1”, and Korean Patent Publication No. KR 2015-0099043 A describes “the effect of improving osteoporosis of red ginseng enhanced with Rg2”. have.
  • the present invention relates to a pharmaceutical composition for cancer treatment comprising the above ginsenosides, in particular Rg3 and Rh2 as active ingredients. Since the pharmaceutical composition of the present invention has a remarkable killing effect of cancer cells, particularly cancer stem cells, it is expected to be widely used in the fields of medicine and health.
  • the present invention was conceived to solve the problems of the prior art as described above, and relates to a pharmaceutical composition for cancer treatment comprising saponin as an active ingredient.
  • cancer is characterized by uncontrolled cell growth, and by such abnormal cell growth, a mass of cells called a tumor is formed and penetrates into surrounding tissues, and in severe cases, to other organs of the body. It refers to something that can be transferred. In academic terms, it is sometimes referred to as a neoplasm. Cancer is an intractable chronic disease that in many cases cannot be cured by surgery, radiation, and chemotherapy, causes pain to the patient, and ultimately leads to death.There are various causes of cancer, but internal factors Classify by external factors. The mechanism by which normal cells are transformed into cancer cells has not been accurately identified, but it is known that a significant number of cancers are affected by external factors such as environmental factors.
  • Cancer Internal factors include genetic factors and immunological factors, and external factors include chemicals, radiation, and viruses. Genes involved in the occurrence of cancer include oncogenes and tumor suppressor genes, and cancer occurs when the balance between them is broken by the internal or external factors described above. Cancer is oral cancer, liver cancer, stomach cancer, colon cancer, breast cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, cervical cancer, skin cancer, cervical cancer, ovarian cancer, colon cancer, small intestine cancer, rectal cancer, fallopian tube carcinoma, anus.
  • Peripheral cancer endometrial carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, lymph node cancer, bladder cancer, gallbladder cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, Prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphoma, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma. It is not limited to this.
  • cancer stem cell refers to a cancer cell in a comprehensive sense that has a self-renewal or differentiation ability, which is a unique ability of stem cells, for example, in a sphere shape. It may include cancerous tissues of unclear form and poor prognosis, such as cancer cell populations or hypodifferentiated cancers.
  • the normal tumor growth conditions refers to a state in which nutrients (glucose) required for cell growth are sufficient and the growth conditions of the tumor microenvironment are sufficient and there is no cellular stress.
  • the expression of transcriptional regulators such as PGC-1a is controlled unlike normal tumor cells.
  • the functions of major metabolic modulators may be different compared to normal cancer cells. These different metabolic regulatory abilities and mechanisms linked thereto, through the regulation of the cell signaling system, obtain resistance to apoptosis in a nutrient-deficient state, and collectively refer to cells with invasion and/or metastasis. .
  • any cell capable of differentiating into a general cancer cell is not limited thereto.
  • "saponin” is a glycoside of steroids, steroid alkaloids, or triterpene, and is a generic term for a substance that dissolves in water and exhibits the foaming action of a soap type. It is present in various plants and is known to be included in the body of some echinoderms (starfish, sea cucumber), but ginsenoside and eleutheroside, which are saponin types contained in ginseng, are particularly famous. Ginsenosides reach over 34 species such as Rg1, Rb1, Rb2, Rh2, and Rg3, and the effects of each component are different. For example, Korean Patent No.
  • KR 101539574 B1 describes “the retinal regeneration effect by ginsenoside Rg1”, and Korean Patent Publication No. KR 2015-0099043 A describes “the effect of improving osteoporosis of red ginseng enhanced with Rg2”. have.
  • the active ingredient of the pharmaceutical composition for cancer treatment is saponin
  • the type is not limited, but ginsenoside Rg3 or Rh2 is preferred.
  • the "aldehyde inhibitor” means a substance that suppresses the oxidation or reduction reaction of aldehyde.
  • Aldehyde is a generic term for a chemical substance in which a formyl group is added to a hydrocarbon group, and is expressed by the molecular formula RCHO. It is caused by insufficient oxidation of alcohol and has an irritating odor. Due to the nature of the formyl group, it is easy to oxidize, causing silver mirror reaction or Pelling reaction, and after oxidation, it becomes carboxylic acid.
  • aldehyde inhibitor examples include benomyl, cis-diamminedichloridoplatinum (CDDP), chlorpropamide, citral, CVT-10216(3-[[[3-[4-[ (Methylsulfonyl)amino]phenyl]-4-oxo-4H-1-benzopyran-7-yl]oxy]methyl]-benzoic acid, 3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4 -oxo-4H-chromen-7-yl]oxy]methyl]benzoic acid), cyanamide, daidzin, diethylaminobenzaldehyde (DEAB), disulfiram, notice Gossypol, morinate, N-acetyl-N-acetoxy-4-chlorobenzenesulfonamide, pargyline hydrochloride, phospho( Enol) pyruvic acid monosodium salt
  • biguanide-based compound is preferably a biguanide-based diabetes treatment agent, more preferably metformin, phenformin, buformine ) Or the like, but is not limited thereto if it is a biguanide-based compound that induces a nutrient-deficiency-like state by interfering with the generation of energy in cells.
  • treatment means a series of activities performed to alleviate or/and ameliorate a desired disease.
  • treatment is to inhibit the numerical or quantitative proliferation of cancer cells including cancer stem cells, kill cancer cells, inhibit the growth of cancer tissues, reduce the size of cancer tissues, or It includes activities that inhibit the development of new blood vessels within the body.
  • cancer means that cancer cells leave the primary organ and go to other organs
  • cancer means including “cancer stem cells”.
  • the spread of cancer to other parts of the body is largely divided into the growth of cancerous tissues in primary cancer and directly infiltrating the surrounding organs, and distant metastasis along blood vessels or lymphatic vessels to other organs far away. Metastasis can be regulated through inhibition of expression of genes related to cancer development or inhibition of protein activity of the gene.
  • the "pharmaceutical composition” means a composition administered for a specific purpose.
  • the pharmaceutical composition of the present invention further comprises an aldehyde inhibitor in Rg3 or Rh2, and treats or inhibits metastasis of cancer cells or cancer stem cells, and compounds involved therein and pharmaceutically acceptable carriers , Excipients or diluents.
  • the pharmaceutical composition according to the present invention contains 0.1 to 50% by weight of the active ingredient of the present invention based on the total weight of the composition.
  • Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil may be mentioned, but are not limited thereto.
  • administration means introducing the composition of the present invention to a patient by any suitable method, and the route of administration of the composition of the present invention is through any general route as long as it can reach the target tissue.
  • the effective amount is the type of disease, the severity of the disease, the type and content of the active ingredient and other ingredients contained in the composition, the type of formulation and the age, weight, general health condition, sex and diet, administration time, route of administration And the secretion rate of the composition, duration of treatment, and drugs used simultaneously.
  • the therapeutic pharmaceutical composition can be administered in the body in an amount of 50ml ⁇ 500ml once, 0.1ng/kg-10mg/kg in the case of a compound, 0.1ng/kg-10mg in the case of a monoclonal antibody It can be administered at a dose of /kg.
  • the administration interval may be 1 to 12 times a day, and in the case of administration 12 times a day, it may be administered once every 2 hours.
  • the pharmaceutical composition of the present invention may be administered alone or with other treatments known in the art, such as chemotherapeutic agents, radiation, and surgery, for the treatment of desired cancer stem cells.
  • the pharmaceutical composition of the present invention may be administered in combination with other treatments designed to enhance the immune response, for example, adjuvants or cytokines (or nucleic acids encoding cytokines) as well known in the art.
  • Other standard delivery methods may be used such as biolistic delivery or ex vivo treatment.
  • antigen presenting cells APCs
  • dendritic cells dendritic cells
  • peripheral blood mononuclear cells or bone marrow cells
  • bone marrow cells can be obtained from a patient or a suitable donor, activated in vitro with this pharmaceutical composition, and then administered to the patient. have.
  • ginsenoside Rg3 or Rh2 is included as an active ingredient, and an aldehyde inhibitor is further included, and the aldehyde inhibitor is benomyl, cis-diamminedichloridoplatinum (CDDP), chlorpro Chlorpropamide, citral, CVT-10216(3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-1-benzopyran-7-yl]oxy ]methyl]-benzoic acid, 3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-chromen-7-yl]oxy]methyl]benzoic acid), cyanamide ( cyanamide), daidzin, diethylaminobenzaldehyde (DEAB), disulfiram, gossypol, morinate, N-acetyl-N-ace
  • the ginsenoside Rg3, or Rh2 is preferably a red ginseng or ginseng-derived extract, but is not limited thereto.
  • composition further comprising a biguanide-based compound in the pharmaceutical composition, wherein the biguanide-based compound is selected from the group consisting of metformin, phenformin, and buformine. It provides any one or more pharmaceutical compositions.
  • the cancer provides a pharmaceutical composition comprising cancer stem cells, wherein the cancer is oral cancer, liver cancer, gastric cancer, colon cancer, breast cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, neck cancer, Skin cancer, cervical cancer, ovarian cancer, colon cancer, small intestine cancer, rectal cancer, fallopian tube carcinoma, anal cancer, endometrial carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, lymph adenocarcinoma, bladder cancer, gallbladder cancer, Endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphoma, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, It provides a pharmaceutical composition of any one or more selected from the group consisting of primary central nervous system lymphoma, spinal cord tumor,
  • ginsenoside Rg3 or Rh2 is included as an active ingredient, and an aldehyde inhibitor is further included, and the aldehyde inhibitor is benomyl, cis-diamminedichloridoplatinum (CDDP), chlorpro Chlorpropamide, citral, CVT-10216(3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-1-benzopyran-7-yl]oxy ]methyl]-benzoic acid, 3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-chromen-7-yl]oxy]methyl]benzoic acid), cyanamide ( cyanamide), daidzin, diethylaminobenzaldehyde (DEAB), disulfiram, gossypol, morinate, N-acetyl-N-ace
  • the ginsenoside Rg3, or Rh2 is preferably a red ginseng or ginseng-derived extract, but is not limited thereto.
  • composition further comprising a biguanide-based compound in the pharmaceutical composition, wherein the biguanide-based compound is selected from the group consisting of metformin, phenformin, and buformine. It provides any one or more pharmaceutical compositions.
  • the cancer provides a pharmaceutical composition comprising cancer stem cells, wherein the cancer is oral cancer, liver cancer, gastric cancer, colon cancer, breast cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, neck cancer, Skin cancer, cervical cancer, ovarian cancer, colon cancer, small intestine cancer, rectal cancer, fallopian tube carcinoma, anal cancer, endometrial carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, lymph adenocarcinoma, bladder cancer, gallbladder cancer, Endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphoma, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, It provides a pharmaceutical composition of any one or more selected from the group consisting of primary central nervous system lymphoma, spinal cord tumor,
  • a method for preventing or treating cancer comprising administering to an individual a composition comprising a ginsenoside Rg3, or Rh2, and an aldehyde inhibitor as an active ingredient, the aldehyde inhibitor Benomyl, cis-diamminedichloridoplatinum (CDDP), chlorpropamide, citral, CVT-10216(3-[[[3-[4-[(Methylsulfonyl)amino]phenyl) ]-4-oxo-4H-1-benzopyran-7-yl]oxy]methyl]-benzoic acid, 3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-chromen -7-yl]oxy]methyl]benzoic acid), cyanamide, daidzin, diethylaminobenzaldehyde (DEAB), disulfiram, gossypol, Mori
  • the ginsenoside Rg3, or Rh2 is preferably a red ginseng or ginseng-derived extract, but is not limited thereto.
  • the composition provides a method for preventing or treating cancer, further comprising a biguanide-based compound in the composition, wherein the biguanide-based compound is metformin, phenformin, and buformine. Any one or more selected from the group consisting of.
  • the cancer includes cancer stem cells, and the cancer is oral cancer, liver cancer, gastric cancer, colon cancer, breast cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, cervical cancer, skin cancer, cervical cancer, ovarian cancer, Colon cancer, small intestine cancer, rectal cancer, fallopian tube carcinoma, anal muscle cancer, endometrial carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, lymphatic cancer, bladder cancer, gallbladder cancer, endocrine cancer, thyroid cancer, parathyroid cancer, Adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphoma, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, spinal cord tumor It provides a method for preventing or treating cancer, which is any one or more selected from the group consisting of brainstem
  • a composition for preventing or treating cancer comprising a ginsenoside Rg3, or Rh2, and an aldehyde inhibitor, wherein the aldehyde inhibitor is benomyl, cis-diamminedichloridoplatinum (CDDP) , Chlorpropamide, citral, CVT-10216(3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-1-benzopyran-7- yl]oxy]methyl]-benzoic acid, 3-[[[3-[4-[(Methylsulfonyl)amino]phenyl]-4-oxo-4H-chromen-7-yl]oxy]methyl]benzoic acid), between Anamide, daidzin, diethylaminobenzaldehyde (DEAB), disulfiram, gossypol, morinate, N-acetyl-N-
  • the ginsenoside Rg3, or Rh2 is preferably a red ginseng or ginseng-derived extract, but is not limited thereto.
  • compositions for preventing or treating cancer further comprising a biguanide-based compound in the composition, and the biguanide-based compound is metformin, phenformin, and buformine Any one or more selected from the group consisting of.
  • the cancer includes cancer stem cells, and the cancer is oral cancer, liver cancer, gastric cancer, colon cancer, breast cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head cancer, cervical cancer, skin cancer, cervical cancer, ovarian cancer, Colon cancer, small intestine cancer, rectal cancer, fallopian tube carcinoma, anal muscle cancer, endometrial carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, lymphatic cancer, bladder cancer, gallbladder cancer, endocrine cancer, thyroid cancer, parathyroid cancer, Adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic leukemia, acute leukemia, lymphocytic lymphoma, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, spinal cord tumor It provides a composition for preventing or treating cancer, which is any one or more selected from the group consisting of brainstem
  • the present invention relates to a pharmaceutical composition for treating cancer comprising saponin as an active ingredient, and the pharmaceutical composition of the present invention has a remarkable effect on killing cancer cells or cancer stem cells, and is expected to be widely used in the fields of medicine and health. .
  • ginsenoside Rg3 shows the effect of killing cancer cells when ginsenoside Rg3 is administered at different concentrations to cancer cells according to an embodiment of the present invention.
  • FIG. 2 shows the effect of killing cancer cells when ginsenoside Rh2 is administered by concentration to cancer cells according to an embodiment of the present invention.
  • FIG. 3 is a diagram illustrating the effect of killing cancer cells when various aldehyde inhibitors are administered to cancer cells according to an embodiment of the present invention.
  • Figure 4 shows the cancer cell killing effect when the ginsenoside Rg3 concentration, which had no killing effect on cancer cells, and the aldehyde inhibitor concentration are administered in combination according to an embodiment of the present invention.
  • Figure 5 shows the cancer cell killing effect when the ginsenoside Rh2 concentration, which had no killing effect on cancer cells, and the aldehyde inhibitor concentration are administered in combination according to an embodiment of the present invention.
  • FIG. 6 shows the effect of killing cancer cells when a ginsenoside Rg3, an aldehyde inhibitor, and a biguanide compound are administered in combination to cancer cells according to an embodiment of the present invention.
  • FIG. 7 shows the effect of killing cancer cells when a ginsenoside Rh2, an aldehyde inhibitor, and a biguanide-based compound are administered in combination to cancer cells according to an embodiment of the present invention.
  • FIG. 8 shows the effect of killing cancer stem cells when ginsenoside Rg3, an aldehyde inhibitor, and a biguanide compound are administered in combination to cancer stem cells according to an embodiment of the present invention.
  • FIG. 9 shows the effect of killing cancer stem cells when a ginsenoside Rh2, an aldehyde inhibitor, and a biguanide compound are administered in combination to cancer stem cells according to an embodiment of the present invention.
  • ginsenoside Rg3, ginsenoside Rh2, or various aldehyde inhibitors were administered to cancer cells or cancer stem cells by concentration.
  • ginsenoside Rg3, ginsenoside Rh2, various aldehyde inhibitors, and/or biguanide compounds were administered in combination in various combinations. As a result, it was confirmed that there was a difference in results for cancer cells or cancer stem cells according to the combination and concentration.
  • Example 1 Culture of cancer cells and cancer stem cells
  • the medium was not replaced or supplemented with cancer cells MDA-MB231 for 30 days. As time passed, the number of attached cells decreased, but a small number of cells were still alive. When there was no change in the number of cells as a result of measuring the number of cells three times at intervals of 2 days, the medium was supplemented with a fresh medium containing 5% FBS.
  • the cells produced as a result of the above were cancer stem cells, and the cells that survived were named'selected cell line MDA-MB231 (hereinafter, referred to as'S-231')'.
  • P-231 cells prepared by the method of Example 1 were seeded in a 96-well plate at a concentration of 1 ⁇ 10 4 cells/well, and cultured overnight at 37°C and 5% CO 2 . Thereafter, ginsenosides Rg3 (Embo Laboratory, Daejeon, Korea) and Rh2 (Chemfaces, Wuhan, China) were administered at the concentrations in Table 1, respectively, and cultured for 24 hours in an environment of 37°C and 5% CO 2 , and cell viability was measured.
  • Example 5 Confirmation of cancer cell killing effects of ginsenosides, aldehyde inhibitors, and biguanide compounds
  • Example 6 Confirmation of cancer stem cell killing effect of ginsenoside, aldehyde inhibitor, and biguanide compound
  • cancer stem cells have less apoptosis effect than cancer cells, but when the pharmaceutical composition of the present invention (ginsenoside, aldehyde inhibitor, and biguanide compound are administered in combination) E, cancer stem cells showed more remarkable apoptosis than cancer cells. Therefore, the pharmaceutical composition of the present invention is expected to be very useful in the treatment of cancer including cancer stem cells.
  • Cancer stem cells are cancer cells that have unlimited regenerative ability similar to general stem cells, and are known to have a different mechanism from previously known cancer cells, but are still used for cancer stem cell treatment targeting cancer stem cells.
  • the development of drugs is very poor. Since the pharmaceutical composition of the present invention has a remarkable killing effect of cancer cells, particularly cancer stem cells, it is expected to be widely used in the fields of medicine and health.

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Abstract

L'invention concerne une composition pharmaceutique pour le traitement du cancer comprenant une saponine utilisée comme principe actif. De préférence, la composition pharmaceutique comprend en outre un inhibiteur d'aldéhyde, et de préférence encore un inhibiteur d'aldéhyde et un composé biguanide, mais non exclusivement. Comme la présente invention présente comme excellent effet de tuer non seulement des cellules cancéreuses mais également des cellules souches cancéreuses, la présente invention est censée être largement utilisée dans les domaines de la médecine et des soins de santé pour le traitement du cancer.
PCT/KR2020/005064 2019-04-15 2020-04-16 Composition pharmaceutique pour le traitement du cancer comprenant une saponine utilisée comme principe actif WO2020213938A1 (fr)

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KR1020200045213A KR20200121250A (ko) 2019-04-15 2020-04-14 사포닌을 유효성분으로 포함하는 암 치료용 약학조성물

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