[go: up one dir, main page]

WO2023013963A1 - Composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer - Google Patents

Composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer Download PDF

Info

Publication number
WO2023013963A1
WO2023013963A1 PCT/KR2022/011062 KR2022011062W WO2023013963A1 WO 2023013963 A1 WO2023013963 A1 WO 2023013963A1 KR 2022011062 W KR2022011062 W KR 2022011062W WO 2023013963 A1 WO2023013963 A1 WO 2023013963A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer
pharmaceutical composition
extract
preventing
betel nut
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/KR2022/011062
Other languages
English (en)
Korean (ko)
Inventor
이재형
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.)
Individual
Original Assignee
Individual
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
Priority claimed from KR1020210158697A external-priority patent/KR102559079B1/ko
Application filed by Individual filed Critical Individual
Publication of WO2023013963A1 publication Critical patent/WO2023013963A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • 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)
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/285—Aucklandia
    • 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)
    • A61K36/577—Malvaceae (Mallow family)
    • A61K36/5775—Hibiscus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/89—Cyperaceae (Sedge family)
    • A61K36/8905—Cyperus (flatsedge)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8966—Fritillaria, e.g. checker lily or mission bells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • 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 the prevention or treatment of cancer comprising a composite extract of herbal medicine as an active ingredient, and specifically, a composite extract of sage, baekbokryeong, paemo, hyangbuja, mokhyang, maize root, betel nut and betel nut as an active ingredient. It relates to a pharmaceutical composition and health functional food for preventing or treating cancer comprising.
  • cancer is still one of the diseases that are difficult to conquer completely.
  • treatment is performed through surgery, radiation therapy, chemotherapy, etc., but there is a problem in that it is difficult to completely remove microscopic lesions that have infiltrated into surrounding tissues or metastasized to lymph nodes.
  • the present invention exhibits cytotoxicity against liver cancer cell lines, induces intracellular reactive oxygen species to induce apoptosis, suppresses substances that induce inflammation in serum and increases substances that regulate immune responses, Sain, Baekbokryeong, It is intended to provide a pharmaceutical composition and health functional food for the prevention or treatment of cancer containing a complex extract of shellfish, fragrant buckwheat, cedar root, maize root, betel nut and horse chestnut as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cancer comprising a composite extract of coine, baekbokryeong, clams, hyangbuja, cedar, maize, betel nut, and hemp seed as an active ingredient.
  • the Sain, Baekbokryeong, Paemo, Hyangbuja, Mokhyang, Gyegeun, Betel nut and Majain complex extract is characterized in that it is a hot water extract.
  • the sign, baekbokryeong, paemo, hyangbuja, mokhyang, gyegeun, betel nut and betel nut are characterized in that they are mixed in the same ratio.
  • the composite extract is characterized by dissolving a mixed powder of coine, baekbokryeong, paemo, hyangbuja, mokhyang, gyegeun, betel nut, and manjain hot water extraction in distilled water at a concentration of 1 to 10% (w / v).
  • extracts of gyegeun, betel nut and horse chestnut are lactic acid bacteria fermented extracts.
  • the lactic acid bacteria may be selected from the group consisting of Steptococcus sp., Lactobascillus sp., and Bifidobacterium sp., but is not limited thereto.
  • the cancers include colorectal cancer, hematoma cancer, blood cancer, laryngeal cancer, esophageal cancer, oral cancer, basal cell cancer, biliary tract cancer, thyroid cancer, rectal cancer, stomach cancer, prostate cancer, breast cancer, kidney cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, and bladder cancer. and pancreatic cancer, but is not limited thereto.
  • the composite extract exhibits an apoptotic effect on liver cancer cells, but does not show an apoptotic effect on normal hepatocytes and lung fibroblasts.
  • the composite extract is characterized by increasing the level of ROS in liver cancer cells.
  • the composite extract is characterized by lowering mitochondrial membrane potential in liver cancer cells.
  • the complex extract is characterized in that it has an effect of increasing IL-22 and INF- ⁇ in serum and reducing TNF- ⁇ in healthy individuals.
  • the complex extract is characterized in that it has an effect of increasing TNF- ⁇ and INF- ⁇ in serum in individuals suffering from cancer.
  • the composite extract is characterized by increasing the expression of Bax and Caspase 7 proteins in cells.
  • the present invention provides a health functional food for preventing or improving cancer containing a composite extract of coine, baekbokryeong, scallop, fragrant japonica, cedar, maize root, betel nut and hemp seed as an active ingredient.
  • the composite extract of the present invention exhibits cytotoxicity against liver cancer cell lines, induces intracellular active oxygen to induce apoptosis, suppresses substances that induce inflammation in serum, and increases substances that regulate immune responses, thereby preventing cancer. It can be usefully used for prevention or treatment.
  • FIGS. 1A-D are graphs showing the results of measuring the effect of the herbal medicine complex extract of the present invention on cell activity;
  • A liver cancer cell line Hep3B cells
  • B liver cancer cell line Huh 7 cells
  • C normal liver cells WRL 6
  • D human lung fibroblasts IMR-90.
  • Figure 1E shows the results of Calcein-AM staining of Hep3B cells treated with the herbal composite extract of the present invention
  • Figure 1F shows the results of lactate dehydrogenase (LDH) in Hep3B cells treated with the herbal composite extract of the present invention. It is a graph showing the result of measuring the amount of emission.
  • FIG. 2A-C are images observed by staining Hep3B cells treated with the herbal composite extract of the present invention with DHE in order to measure the effect of the herbal composite extract of the present invention on ROS in Hep3B cells
  • FIG. 2D is an image of the present invention It is a graph showing the total antioxidant capacity (T-AOC) test results of Hep3B cells treated with herbal medicine composite extracts.
  • Figure 3 is a graph showing changes in the expression of bax, pro-Casepase 3, and c-Casepase 7, which are proteins related to apoptosis activity, after treatment with the herbal medicine composite extract of the present invention in Hep3B cells.
  • Figure 4 is a graph measuring the changes in cytokines in the serum of laboratory rats (BALB / c) after treatment with the herbal medicine complex extract of the present invention; (A) IL-17 (B) IL-22 (C) TNF- ⁇ (D) IFN- ⁇ .
  • Figure 5 is a graph showing the results of observing the effect of the herbal medicine complex extract of the present invention on the health of laboratory rats (BALB / c);
  • A Changes in water intake
  • B Changes in body temperature
  • C Changes in body weight.
  • Figure 6 is an image showing the effect on the tissues of experimental rats (BALB / c) after treatment with the herbal medicine composite extract of the present invention (heart, liver, spleen, lungs, kidneys).
  • Figure 7 is a graph analyzing the effect on the physiological activity of tumor transplantation model rats after processing the herbal medicine complex extract of the present invention.
  • Figure 8 is a graph analyzing the effect of the herbal medicine composite extract of the present invention on tumor formation in tumor transplantation model rats.
  • FIG. 9 is a graph analyzing the effect of the herbal medicine complex extract of the present invention on the immunity of tumor transplantation model rats.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cancer comprising a composite extract of coine, baekbokryeong, clams, hyangbuja, cedar, maize, betel nut, and hemp seed as an active ingredient.
  • Amomum xanthioides Wallich is a perennial herb belonging to the family Zingiberaceae, and is distributed abroad in southern China, Southeast Asia and India.
  • the shape of the medicinal material forms an oval or oval shape with three dull edges, 15 ⁇ 20 mm in length and 10 ⁇ 15 mm in diameter.
  • Donguibogam it is recorded that it is used when the stomach hurts and bulges, and the food does not go down and is nauseated and vomited.
  • Baekbongryeong Poria cocas
  • the medicinal use is the sclerotium that this mushroom makes on the roots of pine trees in the ground, and fruiting bodies are rarely formed on the surface of the sclerotium when it is exposed to the surface.
  • the sclerotium is a potato-shaped or oval lump with a diameter of 10 to 30 cm, and the surface is dark brown, covered with a hard wrinkled shell.
  • As a diuretic, sedative, and tonic it is used to treat edema, mental anxiety, palpitations, and indigestion.
  • it has effects of detoxification, freckles prevention, and skin protection (stabilization).
  • Fritillaria thunbergii belongs to the lily family (Lilaceae) and is a plant.
  • the bulbs of thunbergii have anticancer effects such as tumors and breast cancer and lowering hypertension, and are effective for cough, sputum, pneumonia, tonsillitis, sore throat, bronchitis, and dry mouth It is known to be effective for cuts, boils, and insect bites.
  • Cyperi Rhizoma is a tuberous root of a perennial plant belonging to the Cyperaceae family. It has a warm and spicy taste and has the effect of spreading energy in all directions. It is being utilized.
  • Aucklandia lappa Decne is a perennial plant belonging to the Asteraceae/Compositae family, with a flowering period of July to September and a fruiting period of August to October. Because the scent of wood is warm, it shows good therapeutic effects on abdominal pain caused by cold stomach, flatulence, vomiting, diarrhea, etc., and is also effective for dysentery, enhancing the function of the large intestine, urinating well, and reducing pain. It is known to have a stopping effect.
  • Cirsii Radix is the root of Cirsium japonicum DC.; Greater thistle, which is a plant of the family Cirsii, and is used for the treatment of boils and hemostasis such as uterine bleeding, hematemesis, and nosebleeds.
  • Betel Palm (Betel Palm) is a kind of herbal medicine, and in oriental medicine, it has the effect of strengthening, passing, and dihydrating. Therefore, it is used for parasite control, glaucoma treatment, mouthwash, dysentery, skin disease, etc. by mixing with dammi and various herbal medicines for abdominal pain caused by alluvium, phlegm caused by dampness, aftercare, dietary carrier, chest and stomach intestines, and various herbal medicines.
  • Cannabis Semen is a dried seed of Cannabis sativa L. of the Moraceae family.
  • the origin plant, Cannabis Semen is an annual plant native to Central Asia. am. Majain enriches the intestines, and Majainhwan mixed with Passenger, Peony, Jisil, Rhubarb, and Zucchini is used to treat constipation.
  • the Sain, Baekbokryeong, Paemo, Hyangbuja, Mokhyang, Gyegeun, Betel nut and Majain complex extract is characterized in that it is a hot water extract. According to the experiments of the present inventors, it was confirmed that when the extracts of Daegyeun, betel nut, and horse chestnut were mixed with the composite extracts of Sain, Baekbokryeong, Paemo, Hyangbuja, and Mokhyang, they exhibited excellent cell killing effects on liver cancer cells.
  • baekbokryeong paemo
  • hyangbuja mokhyang
  • gyegeun betel nut and majain may be mixed in equal proportions, but are not limited thereto.
  • extracts of gyegeun, betel nut and horse chestnut are lactic acid bacteria fermented extracts.
  • the lactic acid bacteria may be selected from the group consisting of Steptococcus sp., Lactobacillus sp. and Bifidobacterium sp., but is not limited thereto, and preferably Lactobacillus Plantarum ( Lactobacillus plantarum ).
  • the liver cancer cell killing effect was not improved, and therefore, the present invention complex extract prevents or treats liver cancer.
  • the cancers include colorectal cancer, hematoma cancer, blood cancer, laryngeal cancer, esophageal cancer, oral cancer, basal cell cancer, biliary tract cancer, thyroid cancer, rectal cancer, stomach cancer, prostate cancer, breast cancer, kidney cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, and bladder cancer. And it may be selected from the group consisting of pancreatic cancer, but is not limited thereto, preferably liver cancer.
  • the composite extract exhibits an apoptotic effect on liver cancer cells, but does not show an apoptotic effect on normal hepatocytes and lung fibroblasts. According to the experiment of the present inventors, the composite extract showed an apoptotic effect on liver cancer cell lines Hep3B and Huh 7 cells, but did not show an apoptotic effect on normal hepatocytes WRL 6 and human lung fibroblasts IMR-90 cells.
  • the composite extract is characterized by increasing the ROS level of liver cancer cells and mitochondria of liver cancer cells. It is known that cancer cells produce higher levels of ROS than normal cells to induce continuous proliferation, and it has recently been reported that ROS-generating derivatives induce specific ROS stress in cancer cells to induce apoptosis of cancer cells. there is a bar Therefore, the complex extract of the present invention can effectively induce apoptosis of liver cancer cells by increasing the specific ROS level of liver cancer cells and liver cancer cell mitochondria.
  • the composite extract is characterized by lowering the mitochondrial membrane potential in liver cancer cells, and the composite extract of the present invention can induce apoptosis of cancer cells through the generation of ROS as well as the disruption of the mitochondrial membrane potential. .
  • the composite extract is characterized in that it has an effect of increasing interleukin-22 (IL-22) and interferon- ⁇ (INF- ⁇ ) in serum in healthy individuals and has an effect of reducing TNF- ⁇ .
  • IL-22 interleukin-22
  • INF- ⁇ interferon- ⁇
  • the complex extract is characterized in that it has an effect of increasing TNF- ⁇ and INF- ⁇ in serum in individuals suffering from cancer.
  • the subject with cancer may be an animal with cancer, specifically a mammal with cancer, and more specifically a human with cancer.
  • IL-22 is associated with T helper 17 (Th17) cells and can simultaneously induce inflammatory and protective effects in tissues depending on the inflammatory environment.
  • INF- ⁇ is a pleiotropic cytokine that is a key regulator of innate and acquired immunity and inflammatory responses, and affects various immune cells including macrophages, dendritic cells, and T cells. Therefore, the complex extract of the present invention can exhibit the effect of increasing the immune function in vivo by increasing IL-22 and INF- ⁇ in serum.
  • TNF- ⁇ Tumor necrosis factor- ⁇
  • the composite extract of the present invention may exhibit an effect of relieving inflammation by reducing TNF- ⁇ in serum.
  • the composite extract is characterized by increasing the expression of Bax and Caspase 7 (caspase 7) proteins in cells.
  • caspase 7 caspase 7
  • the expression of Bax and Caspase 7 proteins in cells increased when the complex extract of the present invention was treated.
  • the expression level of Caspase 7 protein increased about 20 to 35 times.
  • caspase 7 exists as an inactive proenzyme, but is cleaved by caspase-8 or caspase-9, which is activated by apoptosis signal stimulation, and changes to an active form.
  • Caspase 7 is an enzyme that directly degrades substrate proteins while being activated at the final stage of apoptosis, so an increase in intracellular Caspase 7 protein can be seen as promoting apoptosis.
  • the complex extracts of coine, baekbokryeong, clams, hyangbuja, mokhyang, gyegeun, betel nut and horse chestnut of the present invention can also be used as an anti-inflammatory pharmaceutical composition.
  • the pharmaceutical composition of the present invention may further include a carrier, an excipient or a diluent in addition to the complex extracts of cognac, baekbokryeong, shellfish, hyangbuja, mokhyang, gyegeun, betel nut and horse chestnut.
  • composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection method.
  • the pharmaceutical composition of the present invention may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in one or more compounds, for example, starch, calcium carbonate, sucrose or lactose ( lactose) and gelatin.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc.
  • Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending solvents.
  • witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used as a base for the suppository.
  • the present invention relates to a health functional food for the prevention or improvement of cancer, comprising a complex extract of sage, baekbokryeong, shellfish, hyangbuja, mokhyang, gyegeun, betel nut and hemp seed as an active ingredient.
  • the characteristics of the active ingredient of the health functional food are the same as those of the active ingredient of the pharmaceutical composition, and detailed descriptions are omitted to avoid redundant description.
  • the health functional food for preventing or improving cancer containing the coine, baekbokryeong, paemo, hyangbuja, mokhyang, gyegeun, betel nut and hemp seed complex extract as an active ingredient is a beverage, pill, tablet, capsule, It can be prepared with any one selected from powders, or can be prepared by adding it as a food component, and can be appropriately prepared according to conventional methods.
  • the health functional food composition of the present invention may contain various flavoring agents or natural carbohydrates as additional components.
  • Example 2 Manufacture of Sain, Baekbokryeong, Paemo, Hyangbuja, Mokhyang, Daegyeun, Betel nut, Manjain Complex Extract
  • the present inventors marked the composite extract of Sain, Baekbokryeong, Paemo, Hyangbuja, Mokhyang, Gyegeun, Betel nut and Hemp seed as ERM211 and used it in the following experiments.
  • the Lactobacillus plantarum strain used in the present invention was distributed from the Korea Culture Center of Microorganisms (KCCM) and used in the experiment.
  • the pre-sale strain was inoculated into a slanted medium and cultured in a 37 ° C incubator for 24 hours, and then inoculated into a liquid medium when a colony was formed.
  • Sufficiently dried maize root, betel nut, and betel nut were ground, respectively, distilled water (DW) was added at 0 times the capacity of each ground, extracted in an autoclave for 2 hours, and filtered three times. 100 mL of each extract was mixed, and Lactobacillus plantarum was inoculated with 1.0% (v/v) of the mixed extract, fermented at 35° C. for 48 hours, filtered, and freeze-dried. The mixed fermentation complex extract powder of asmarseine was isolated.
  • DW distilled water
  • Human liver cancer cell lines Hep3B and Huh 7 cells distributed from the American Type Culture Collection, normal hepatocyte WRL 6 cells, and human lung fibroblasts IMR-90 cells were used in the experiments.
  • Cells were cultured in Dulbecco's Modified Eagles medium (DMEM) containing 10% Fetal Bovine Serum (Hyclone, South Logan, UT, USA) and 1% antibiotic-antimycotic (Gibco, Invitrogen, Carlsbad, CA, USA). ) in culture medium at 37°C 5% CO 2 conditions. Cells were passaged after reaching 80% confluency, and cells at passage 3 were used in the experiments.
  • DMEM Dulbecco's Modified Eagles medium
  • Fetal Bovine Serum Hyclone, South Logan, UT, USA
  • antibiotic-antimycotic Gibco, Invitrogen, Carlsbad, CA, USA
  • Hep3B cells were treated with ERM211 at different concentrations (0%, 2%, and 5%) for 24 h, and then stained with DHE, MitoSOX, and JC-1, respectively. Observed under a fluorescence microscope.
  • Average daily food intake was measured for 10 days, and there was no difference between each group in any week of measurement. There was no difference in average daily food intake over 10 days.
  • Tissues were collected, fixed in 10% neutral buffered formalin solution, and paraffin-embedded tissue sections were prepared. Tissues were cut to a thickness of 4 ⁇ m, deparaffinized and washed, stained with hematoxylin, separated with hydrochloric acid, and neutralized with ammonia water. It was colored in running water, stained with eoxin, dehydrated with alcohol, and sealed. On the microscope, the nucleus was stained blue and the cytoplasm was stained red.
  • Example 1 Example 2
  • Example 3 comparative example Cell viability (%) 100 84 ⁇ 1.5 20 ⁇ 4.2 11 ⁇ 2.7 23 ⁇ 3.8
  • Example 2 was more effective in killing liver cancer cells than the composite extract of Example 1. Therefore, the composite extract (ERM211) of Example 2 exhibits an excellent cell killing effect on liver cancer cell lines, and thus can be used for preventing or treating liver cancer.
  • Example 3 in which the extracts of horse chestnut, betel nut, and horse chestnut were fermented with Lactobacillus plantarum strains, a more excellent cell killing effect than that of Example 2 was shown.
  • Example 3 showed excellent cell killing effect compared to Example 2, but the difference was not large and considering the convenience of extract preparation, the present inventors proceeded with additional experiments on the complex extract (ERM211) of Example 2 below. did
  • ERM211 concentrations (w/v) of 0%, 0.5%, 1%, 2%, and 5% were administered to human liver cancer cell lines Hep3B and Huh 7 cells, normal hepatocytes WRL 6 and human lung fibroblasts IMR-90 cells for 24 hours, respectively. processed.
  • ERM211 had no significant effect on human normal hepatocytes WRL 68 and human lung fibroblasts IMR-90 cells, but it was confirmed that the apoptotic effect was particularly pronounced on human-derived liver cancer cells Hep3B and Huh 7 cells. .
  • Hep3B cells were treated with ERM211 at different concentrations (0%, 0.5%, 1%, 2%, and 5%) for 24 h, followed by DHE staining and observed under a fluorescence microscope.
  • ERM211 exhibits anti-liver cancer activity by increasing ROS levels and damaging cellular mitochondria in Hep3B liver cancer cells.
  • ERM211 suppresses TNF- ⁇ , an inflammation-inducing substance, and increases INF- ⁇ , an immune response regulator, without causing overall side effects in vivo in mice, thereby increasing the immune function in vivo.
  • mice 20 BALB/c healthy laboratory mice of the same age were selected, and then 10 animals each were divided into a control group and an ERM211 treatment group. Mice in the control group drank normal water every day, and in the ERM211 group, the ERM211 extract was suspended in distilled water and orally administered at a dose of 50 mg/kg (weight) once a day.
  • mice In order to measure the effect on the health of laboratory mice after ERM211 treatment, 10 BALB/c healthy laboratory mice of the same week were selected and 10 animals were respectively classified into a control group and an ERM211 group. After Hep3B cells were subcutaneously implanted in laboratory mice, the mice in the control group drank normal water every day, and the ERM211 group ingested ERM211.
  • ERM211 has no side effects on general physiological activities such as body weight, body temperature and water intake of mice.
  • ERM211 On tumor growth, 10 normal BALB/c mice were selected and Hep3B cells were subcutaneously transplanted into the experimental mice. After 7 days of ingestion, tumor tissue was extracted and the weight and diameter were measured. As a result of statistical analysis, it was found that tumor formation was suppressed in the ERM211 intake group compared to the control group, as the weight and size of tumors were significantly lowered (FIGS. 8A-C).
  • ERM211 increases TNF- ⁇ , an inflammation-inducing substance to induce tumor suppression, without causing overall side effects in vivo in mice, thereby increasing the content of INF- ⁇ , an immune response modulator, thereby increasing the immune function in vivo.

Landscapes

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

Abstract

La présente invention concerne une composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer et, plus spécifiquement, une composition pharmaceutique comprenant un extrait d'un mélange de graines d'Amomum villosum, de Poria cocos Wolf., de Fritalaria ussuriensis, de Cyperus rotundus, d'Aucklandia lappa Decne, de Cirsium japonicum, d'Areca catechu, et de Cannabis sativa en tant que principe actif pour la prévention ou le traitement du cancer. Grâce à son efficacité en termes de présentation d'une cytotoxicité contre les lignées cellulaires du cancer du poumon, de production d'espèces à oxygène réactif intracellulaires pour induire la mort cellulaire, de suppression de cytokines inflammatoires dans les sérums, et d'augmentation des immunomodulateurs, l'extrait composite de la présente invention peut être avantageusement utilisé pour prévenir ou traiter le cancer.
PCT/KR2022/011062 2021-08-06 2022-07-27 Composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer Ceased WO2023013963A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20210104125 2021-08-06
KR10-2021-0104125 2021-08-06
KR1020210158697A KR102559079B1 (ko) 2021-08-06 2021-11-17 한약재 복합 추출물을 유효 성분으로 포함하는 암 예방 또는 치료용 약학적 조성물
KR10-2021-0158697 2021-11-17

Publications (1)

Publication Number Publication Date
WO2023013963A1 true WO2023013963A1 (fr) 2023-02-09

Family

ID=85154537

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/011062 Ceased WO2023013963A1 (fr) 2021-08-06 2022-07-27 Composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer

Country Status (1)

Country Link
WO (1) WO2023013963A1 (fr)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20020009123A (ko) * 2000-07-24 2002-02-01 채문식 암세포에 대한 다중약제내성조절용 빈랑 추출물 및 그제조방법
KR20040110119A (ko) * 2003-06-18 2004-12-31 윤용갑 지패산 추출물을 함유하는 암 치료용 조성물
KR20060104408A (ko) * 2005-03-30 2006-10-09 정두수 암치료용 한약조성물
KR20120111125A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 마자인 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20120111123A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 대계근 추출물을 포함하는 췌장암 치료용 조성물 및 건강 기능성 식품
KR20120111122A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 대계근 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20120111126A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 마자인 추출물을 포함하는 췌장암 치료용 조성물 및 건강 기능성 식품
KR20120122410A (ko) * 2011-04-29 2012-11-07 주식회사한국전통의학연구소 목향 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20160084175A (ko) * 2015-01-05 2016-07-13 권영아 식물유래 루테리온의 암 줄기세포의 성장 및/또는 분화 억제 용도

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20020009123A (ko) * 2000-07-24 2002-02-01 채문식 암세포에 대한 다중약제내성조절용 빈랑 추출물 및 그제조방법
KR20040110119A (ko) * 2003-06-18 2004-12-31 윤용갑 지패산 추출물을 함유하는 암 치료용 조성물
KR20060104408A (ko) * 2005-03-30 2006-10-09 정두수 암치료용 한약조성물
KR20120111125A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 마자인 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20120111123A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 대계근 추출물을 포함하는 췌장암 치료용 조성물 및 건강 기능성 식품
KR20120111122A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 대계근 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20120111126A (ko) * 2011-03-31 2012-10-10 주식회사한국전통의학연구소 마자인 추출물을 포함하는 췌장암 치료용 조성물 및 건강 기능성 식품
KR20120122410A (ko) * 2011-04-29 2012-11-07 주식회사한국전통의학연구소 목향 추출물을 포함하는 신장암 치료용 조성물 및 건강 기능성 식품
KR20160084175A (ko) * 2015-01-05 2016-07-13 권영아 식물유래 루테리온의 암 줄기세포의 성장 및/또는 분화 억제 용도

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
31 July 2017 (2017-07-31), JEONG, BYUNG SEO;KIM, SEONG HOON;KIM, HYUN PYO;: "Effect of Fermented Cirsium japonicum Extract on Testosterone Deficiency Syndrome", XP053037279 *

Similar Documents

Publication Publication Date Title
KR20140147948A (ko) 항비만효과를 갖는 장수풍뎅이 유충 추출물의 제조방법 및 이를 포함하는 항비만 조성물
WO2022050516A1 (fr) Agent thérapeutique contre le coronavirus comprenant un extrait d'elaeocarpus sylvestris en tant que principe actif
WO2019103329A1 (fr) Composition antioxydante contenant un extrait de ver de farine fermenté à titre de principe actif
US20210346455A1 (en) Pharmaceutical composition comprising purple corn extract for prevention or treatment of skin disease
WO2017183902A1 (fr) Composition contenant des extraits de artemisia capillaris, sanguisorba officinalis et curcuma longa et un agent antiviral, en tant que principes actifs, destinée à prévenir ou traiter une maladie du foie
WO2021033994A1 (fr) Composition comprenant un extrait de salvia miltiorrhiza ou de paeonia lactiflora utilisé comme principe actif pour la prévention ou le traitement d'un trouble du métabolisme des lipides
KR101013527B1 (ko) 오가피-버섯 균사체 발효물을 포함하는 위염예방 및 치료용 약학 조성물과 그로부터 추출된 오가피-버섯 균사체 발효추출물을 유효성분으로 하는 위염예방 및 치료용 약제
KR102181220B1 (ko) 생약 추출물을 포함하는 항암용 약학적 조성물
WO2023013963A1 (fr) Composition pharmaceutique comprenant un extrait d'herbe médicinale composite en tant que principe actif pour la prévention ou le traitement du cancer
WO2019050123A1 (fr) Composition alimentaire pour traiter l'obésité ou l'hyperlipidémie comprenant un extrait de fruit de terminalia chebula et un extrait de phyllanthus emblica
KR102559079B1 (ko) 한약재 복합 추출물을 유효 성분으로 포함하는 암 예방 또는 치료용 약학적 조성물
WO2020085799A1 (fr) Composition pharmaceutique pour la prévention ou le traitement d'une maladie hépatique, comprenant un extrait de platycodon grandiflorum standardisé contenant de la sapopnine de platycodon grandiflorum ou un extrait de saponine de platycodon grandiflorum séparé par membrane et aliment fonctionnel de santé pour l'amélioration de la fonction hépatique
KR102551499B1 (ko) 용아초 추출물을 유효성분으로 포함하는 코로나 바이러스(SARS-CoV-2) 감염의 예방 또는 치료용 조성물
WO2011019153A2 (fr) Composition pour la prévention ou le traitement de l’arthrite, contenant un extrait d’un mélange médicinal à base de plantes de schisandra chinensis baillon, scutellaria baicalensis et kalopanax pictus nakai en tant qu’ingrédient actif
KR20230134354A (ko) 락토바실러스 가세리를 포함하는 대사성 질환 예방 또는 치료용 약학 조성물
WO2013022178A1 (fr) Composition pour prévention et traitement de l'obésité contenant un principe actif sous la forme d'un extrait de préparation végétale mélangée à base de lonicera japonica et d'aurantii nobilis pericarpium fermenté ou non fermenté, et son utilisation
Omrani et al. Sugar and insulin levels of type 2 diabetic patients
Bukit et al. In vitro and in vivo study of the red dragon fruit peel (hylocereus polyrhizus) methanolic extract gel effect on acne
KR101892381B1 (ko) 천초 추출물을 유효성분으로 포함하는 간질환의 예방 또는 치료용 조성물
KR102590151B1 (ko) 한약재 복합 추출물을 유효 성분으로 포함하는 췌장암 예방 또는 치료용 약학적 조성물
KR100839099B1 (ko) 오배자 및 목단피 추출물을 함유하는 돼지 유행성 설사바이러스의 치료 및 예방용 조성물
KR20060034879A (ko) 항당뇨 효과를 나타내는 발효구아바 조성물
KR102311887B1 (ko) 괭생이모자반 추출물을 유효성분으로 포함하는 간질환 예방 또는 치료용 약학적 조성물
WO2024219856A1 (fr) Composition pour prévenir, améliorer ou traiter des maladies oculaires
WO2023008594A1 (fr) Composition pour la prévention ou le traitement d'une infection par le coronavirus (sras-cov-2), comprenant un extrait d'agrimonia pilosa en tant que principe actif

Legal Events

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

Ref document number: 22853341

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22853341

Country of ref document: EP

Kind code of ref document: A1