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    • 专利摘要:
    The present invention relates to a germanium composite mineral having an anticancer active ingredient and its use as an anticancer agent. According to the present invention, a germanium composite mineral containing 36 ppm germanium, biotite, dolomite, gold mica, feldspar, tourmaline, zircon, garnet, apatite and opaque minerals, to which iodine, cobalt, selenium and vanadium are added as auxiliary minerals It provides a useful use as an anticancer agent.
    公开号:KR20030077503A
    申请号:KR1020030061580
    申请日:2003-09-03
    公开日:2003-10-01
    发明作者:정연권
    申请人:(주)서봉바이오베스텍；
    IPC主号:
    专利说明:

    GERMANIUM MIXED MINERAL HAVING ANTI-CANCER ACTIVATING INGREDIENT AND ITS USE AS ANTI-CANCER MEDICINE}
    [4] The present invention relates to an anticancer agent, and more particularly, to the use of an anticancer agent of a germanium complex mineral having an anticancer active ingredient.
    [5] The global cancer incidence is increasing by more than 5% every year due to the increase in elderly population and environmental degradation. According to the 1997 statistics, 6 million people died of cancer, accounting for 12% of the global mortality rate.
    [6] In South Korea, according to statistics, about 100,000 new cancer cases and 50,000 deaths occur each year. In 1997, 120,000 cancer patients included gastric cancer (21%), liver cancer (12%), and lung cancer (11). In women, cervical cancer (20%), gastric cancer (16%), and breast cancer (13%) occurred in the order of cancer patients.
    [7] Representative cancer treatments of modern medicine include surgical surgery, chemotherapy, biological therapy, and radiotherapy, and these are applied alone or in combination, but there is no perfect treatment. Therefore, cancer is recognized as one of the top tasks to overcome in order to extend the life span of humans in the 21st century.
    [8] An anticancer agent is a generic term for drugs that act on various metabolic pathways of cancer cells and exhibit cytotoxicity or cytostatic effects on cancer cells. The anticancer agents developed so far are metabolic antagonists depending on their mechanism of action and chemical structure. , Plant alkaloids, topoisomerase inhibitors, alkylating agents, anticancer antibiotics, hormones, and other drugs.
    [9] Anticancer drugs vary in intracellular targets, depending on the drug, blocking the DNA replication, transcription, and translation processes of the cell or disrupting the action of proteins important for cell survival. The effects on these intracellular targets are then necrotic or internal Apoptosis kills cancer cells. In general, the metabolic pathways in which these anticancer drugs work are not specific to cancer cells and are also the same for normal cells. Thus, when the anticancer drug is administered, normal tissue damage (ie, toxicity) is inevitable.
    [10] However, there is a significant quantitative difference between the metabolism of cancer cells and normal cells, and based on these differences, anticancer drugs are more toxic to cancer tissues. Thus, by utilizing the selective toxicity of such anticancer drugs, Chemotherapy is possible. Therefore, the greater the specific therapeutic index (therapeutic index) that can eliminate cancer cells while avoiding the toxicity of normal tissue, the safer the cancer drug.
    [11] The inventors continued various experiments related to the anticancer effect, and germanium, an off-white antimetallic element, emits far-infrared rays, and has the function of strengthening immunity, interferon generation and stimulation, and protecting cancer cells from toxic substances, viruses, etc. After confirming the fact that it protects the living body, it obtained Korean Patent No. 043367 regarding the germanium complex mineral as an antibiotic replacement agent having the ability to improve digestion rate and to suppress the occurrence of Salmonella and food poisoning bacteria.
    [12] In other words, biotite gneiss has a porous structure and black spots are embedded on a gray background. Specific components include silicon dioxide (SiO 2 ), aluminum oxide (A1 2 O 3 ), iron oxide (Fe 2 O 3 ), calcium oxide (CaO), magnesium oxide (MgO), titanium oxide (TiO 2 ), phosphorus pentoxide (P 2 O 5 ), potassium oxide (K 2 O), sodium oxide (Na 2 O), manganese trioxide (MnO 3 ), such as oxides and the like has a high far-infrared emissivity of about 93%. At the same time, it absorbs odors, purifies water by ion exchange, absorbs moisture in the room, and especially absorbs and removes harmful heavy metals such as cadmium, mercury, and lead in the body through ion adjustment. It is known to have the effect of detoxification.
    [13] The present inventors have completed the present invention for the purpose of overcoming the side effects and clinical usefulness of conventional chemotherapy by confirming that germanium complex minerals have selective toxicity to cancer cells in a continuous study.
    [14] The present invention has no side effects and is intended to provide a use as an anticancer agent having selective toxicity against cancer cells exhibiting higher protein synthesis ability than normal cells.
    [15] Another object of the present invention, to determine the anticancer effect of the germanium complex minerals to provide an anticancer agent using these.
    [1] 1 and 2 are graphs showing far-infrared emissivity and radiation energy of a germanium-containing composite mineral according to the present invention.
    [2] 3 is a weight change graph.
    [3] 4 and 5 are tumor size change graphs.
    [16] According to the present invention, there is provided the use of germanium complex minerals as anticancer agents, and accordingly the present invention provides germanium complex mineral compositions as anticancer agents.
    [17] The germanium composite mineral for anticancer drug use according to the present invention was obtained from the mine of Seobong Biovestec.
    [18] Such germanium composite mineral contains 36 ppm of germanium, biotite, dolomite, gold mica, feldspar, tourmaline, zecon, garnet, apatite, and opaque minerals, to which iod, cobalt, selenium and vanadium are added as auxiliary minerals. As a result, it is pulverized into a fine particle state alone or dissolved in DMSO (dimethyl sulfoxide), which is a pharmaceutically acceptable solvent, and treated with cancer cell lines and normal cells, thereby inducing cancer cell death by showing selective toxicity to cancer cell lines. It will have a useful pharmacological effect as an anticancer agent.
    [19] The component added to the auxiliary mineral is characterized in that 0.05 ppm of iodine, 10 ppm of cobalt, 5 ppm of selenium and 74.2 ppm of vanadium.
    [20] The germanium complex minerals on normal cells reported so far have been found to have little toxicity at concentrations of 625 nmol or less against mononuclear cells isolated from human blood.
    [21] An anticancer composition comprising a germanium complex mineral according to the present invention or an anticancer composition containing a germanium complex mineral as an active ingredient may be parenterally or orally administered as desired. The germanium complex mineral can be prepared as an anticancer composition alone or in admixture with a pharmaceutically acceptable carrier. The germanium composite mineral anticancer composition of the present invention may include conventionally used excipients, disintegrants, lubricants and the like in a conventional manner.
    [22] In addition, the germanium composite mineral anticancer agent according to the present invention may be a unit dosage form or a multi-dose preparation such as tablets, capsules, powders, granules, suspensions, emulsifiers, syrups, solutions or parenteral preparations by well-known conventional methods. It can be formulated as.
    [23] The effective dose of the germanium composite mineral anticancer agent according to the present invention is approximately 0.6 µg to 6 µg per day, per kg of patient weight, preferably 3-6 µg / KG per day.
    [24] The germanium composite mineral is preferably a pulverized powder having a particle size of 800 to 5000 mesh. To this end, the heat treatment is performed at 500 to 1300 ° C. This heat treatment process is to remove the organic impurities remaining in the mineral, because it is possible to polymerize by inducing component activation and induction of oxidation.
    [25] Of course, the powder method using the laser and nano technology together with the powder method by heat treatment can be effectively used, but the heat treatment method is most suitable for economic and stabilization.
    [26] (Example)
    [27] Hereinafter, the effectiveness of the germanium complex mineral as an anticancer agent will be described in detail based on a test report of KemOn Co., Ltd., a preclinical research institution approved by the KFDA.
    [28] The germanium composite mineral according to the present invention was determined based on the germanium composite mineral (product name "SolToBio V") containing the components shown in Table 1 below.
    [29] Mineral Composition and Chemical Composition of Germanium Composite Minerals divisionMineral compositionChemical composition (%) Main composition mineralTrace component mineralSiO 2 Al 2 O 3 Fe 2 O 3 CaO MgO K 2 O Na 2 O TiO 2 P 2 O 5 Other contentQuartzWhite MicaMica MicaFeldspar Tourmaline Cone Garnet76.7 10.8 2.01 0.12 0.47 1.69 0.79 0.45 0.11 6.56
    [30] Other chemical components in Table 1 include iodine, cobalt, selenium, and vanadium, which were analyzed by the ICP method by the Korea Institute of Science and Technology, and have the contents shown in Table 2.
    [31] Other Nutrition Facts of Germanium Complex Minerals (Unit: ppm) divisionOther Nutrition Facts ICoSeV content0.0510574.2
    [32] Anticancer Activity Test Using Nude Mouse Implanted with Human Colon Cancer Cell, HCT-15 of "SoiToBio V"
    [33] In order to investigate the anticancer activity of the test substance "solToBio V", a test was performed using a regression model among xenograftmodels in which HCT15, a human rectal cancer cell line, was transplanted to nude mice of the balb / c strain.
    [34] The test group consisted of 50 mg / kg of test substance each and orally administered for 14 days. In the negative control group, a group in which physiological saline was injected was used to observe general symptoms, weight change, and tumor size change. The result of this test was as follows.
    [35] (1) No death or abnormal symptoms of animals were observed.
    [36] (2) Compared with the negative control group, the test substance-administered group showed a decrease of about 15% in the average of the tumor volume as a whole.
    [37] From the above results, the anticancer effect of "SolToBio V" under these test conditions was observed with the naked eye and decreased in the tumor volume.
    [38] Test substance and media control substance
    [39] (1) Test substance
    [40] Name: SolToBio "V"
    [41] Lot number: STB-V-303523
    [42] Supplier: Seobong Bio Best Tech Co., Ltd.
    [43] Appearance: Gray Stone Flour
    [44] Quantity of water: 1,055g
    [45] Date of Acquisition: June 3, 2003
    [46] Storage condition: room temperature
    [47] (2) excipients (negative controls)
    [48] Physiological saline for injection
    [49] Materials and methods
    [50] (1) Test system
    [51] 1) Species and strains
    [52] Nucleotide-free (SPF) nude mice in the BALB / C strain
    [53] 2) Source
    [54] Source: Daehan Biolink
    [55] Producer: Harlan Co. Ltd. (United States of America)
    [56] 3) Reason for selection of test system
    [57] Nude mice used in this study are animal systems commonly used for anticancer activity tests, and a lot of data have been accumulated in connection with anticancer activity tests. Therefore, it is possible to use these data when interpreting the test results.
    [58] 4) Age and number of animals
    [59] Age at acquisition: 5 weeks
    [60] Number of Animals: 12
    [61] Age at cancer cell transplantation: 6 weeks
    [62] Age at start of administration: 8 weeks
    [63] Number of animals at start of administration: 10
    [64] 5) Quarantine and Purification
    [65] When the animals were visually inspected at the time of obtaining the animals, the normal symptoms were observed in the animal room to be tested for 7 days, and only healthy animals were selected for the test.
    [66] 6) Transplantation of Cancer Cells
    [67] (A) Type of cancer cell: Rectal cancer cell line: HCT-15
    [68] (B) Source of cancer cells: Cancer Cell Bank, Korea Research Institute of Bioscience and Biotechnology
    [69] (C) Culture of cancer cells: Cultured cells were cultured in the cancer cell bank. The culture was incubated in a CO₂incubator (Forma, USA) at a temperature of 37 ℃ and a CO₂ concentration of 5%. The culture medium was finally RPMI-1640 with 10% FBS (Gibco BRL, 16000-044) and 10% Penicillin-Streptomycin solution (Gibco BRL, 15140-122). Cells isolated from the culture medium for transplantation were refrigerated. Stored in the state.
    [70] (D) Transplantation of cancer cells: On the last day of culture, all cells were harvested and counted, and the cell concentration was adjusted to 1 × 10 cells / ml using PBS. The regulated cell culture solution was injected at 0.3 x 10 cells / head into healthy mice that passed through the circulation.
    [71] (2) Breeding environment
    [72] 1) Environmental conditions
    [73] In this test, temperature 23 ± 3 ℃, relative humidity 55 ± 15% lighting time 12 hours (8 am-8 pm), ventilation times 10-20 times / hr. And Chem-on-Suk Preclinical Research Center Co., Ltd., set at a roughness of 150 to 300 Lux.
    [74] 2) Identification of breeding box, breeding density and breeding box
    [75] During the purifying and quarantine periods, 10 animals were housed in polycarbonate shoeboxes (260W x 420L x 180H mm). During the administration and observation period, three animals were housed in polycarbonate shoeboxes (200W × 260L × 130H mm). During the trial period, breeding boxes were identified by labeling with test and animal numbers.
    [76] 3) feed and water
    [77] 급여 Feeding method
    [78] Feed was freely ingested by radiation sterilized solid feed for experimental animals (Supplier: Daehan Biolink, Producer: Harlan Co.).
    [79] 급여 How to feed water
    [80] Water was freely ingested by using a water bottle after the groundwater went through a UV-flow sterilizer and a microfiltration device.
    [81] (3) Dosage and composition of test group
    [82] Dose setting, the composition of the test group, and the concentration and dose of the dose were used in the test as the dose set by the doctor. The composition of the test group and the dosage were as shown in Table 3 below.
    [83] groupgenderAnimal count (mari)Animal NumberDosage amount (ml / Kg)Dose (mg / Kg) G1 (V.C) G2FemaleFemale551-621-261010050
    [84] G1 (V.C): control group using normal animals
    [85] G2: Oral administration after cancer cell transplantation (the dose setting is equivalent to 1% of the daily feed intake of mice (5 g / day))
    [86] 1) Group separation and animal identification
    [87] Group separation of animals was performed as follows. First, the tumor size of the nude mouse transplanted with cancer cells was measured using Vernier calipers. The tumor size was calculated and ranked for each cancer cell. First of all, 10 animals of 50-100mm³ tumor size were selected and used for the test. Individual identification was marked on the axle wheel using an individual identification label attached to the front of the breeding box and a car punch.
    [88] (4) Administration of test substance
    [89] 1) Method of preparing test substance to be administered
    [90] While freezing the test material provided by the client side was dissolved in the refrigerator when necessary, a test material to be diluted and administered to the 50 mg / kg administration group was prepared.
    [91] 2) Route of administration and method of administration
    [92] The test substance was fixed orally and administered once a day by the dorsal skin fixation method.
    [93] 3) Reason for selection of route of administration
    [94] Oral administration was chosen because the test substance is easy to apply to large amounts of animals.
    [95] 4) Frequency and period of administration
    [96] Test substance was repeatedly administered daily for 14 days once / day.
    [97] 5) Calculation of the amount of liquid to be administered
    [98] The amount to be administered was again selected and administered based on the weight changed at a weekly price. The dose was administered at 50 mg / kg for the negative control group and the administration group.
    [99] (5) Observation and Inspection Items
    [100] 1) General Symptom Observation: All animals were observed at least once every day. Animals whose abnormalities were observed in general symptoms were recorded with animal numbers and their status in detail. General symptom observation was performed daily for one week before autopsy. If the growth inhibition effect of the tumor appeared only later in the test, the test period was extended.
    [101] 2) Tumor size measurement: Tumor size of all animals was measured on days 1,3,5,7,9,12 and 14 until the start of administration and subsequent necropsy. Tumor size was measured using Vernier calipers in the order of long axis, short axis and height, and the volume was calculated using the following formula.
    [102] Long axis x short axis x thickness / 2 ..... (calculated)
    [103] 3) Body weight measurement: All animals were measured on the start of administration, on days 2, 3 and 7 of administration.
    [104] 4) Necropsy: At the end of the observation period, all living animals underwent CO₂ inhalation anesthesia, followed by open abdominal artery bleeding, and autopsy findings were observed for abdominal and thoracic organs.
    [105] (6) statistical method
    [106] The mean and standard deviation of body weight, tumor size, and tumor weight for each group were calculated and compared with the media control group using the student-t test.
    [107]
    [108]
    [109]
    [110]
    [111]
    [112]
    [113]
    [114]
    [115] 4. Results
    [116] (1) general symptoms
    [117] No general symptoms associated with administration of the test substance were observed.
    [118] (2) weight change (see Fig. 3)
    [119] No change in body weight was observed with the administration of the test substance. In the administration group, the body weight remained unchanged at the initial administration, indicating that the test substance was not toxic to mice.
    [120] (3) change in tumor size (see Figure 4)
    [121] Tumor size was transplanted to the lung cancer cell line and growth was faster than expected due to the start of administration for about 14 days was observed growth. Until the end of the administration, the degree of growth inhibition was reduced by 15% in the average volume of the tumor compared to the negative control group.
    [122] 5. Discussion and conclusion
    [123] Anti-cancer activity evaluation was performed on the test substance "SolToBio V" using nude mice transplanted with HCT-15 cells, which are human-derived rectal cancer cell lines.
    [124] Increasing inhibition rate of tumor in this study was a preliminary experiment for anticancer test of test substance "Sol To Bio V", which was an experiment to see the possibility by oral administration of 50mg / kg. The overall trend up to 14 days after administration showed a decrease of about 15% in the administration group compared to the negative control group. Since the number of animals used in the solvent control group and the treatment group was about 5, it was difficult to determine the exact characteristics of the test substance, but the inhibitory activity was shown by comparing the aspects of the drug administration.
    [125] The nature of the tested model seems to be less effective because it is administered after tumor growth.
    [126] In conclusion, the anticancer effects of nude mice implanted with "Sol To Bio V" HCT-15 cells under these test conditions could be observed by comparing the average.
    [127] In this test, it is judged that the initial administration of tumor cells and the model of administration of the germanium complex mineral of the present invention by supplementing the appropriate ratio, particle size, and process solvent may maximize the effect of the test drug. It would be desirable to go to a tumor model.
    [128] As described above, the present invention is a very useful invention in the biopharmaceutical industry because it has an excellent effect of inhibiting the anticancer active ingredient in order to provide a novel use of the germanium composite mineral known as an anticancer agent.
    权利要求:
    Claims (6)
    [1" claim-type="Currently amended] Use as an anticancer agent of a germanium composite mineral containing 36 ppm of germanium, biotite, dolomite, gold mica, feldspar, tourmaline, zircon, garnet, apatite and opaque minerals, to which iodine, cobalt, selenium and vanadium are added as auxiliary minerals.
    [2" claim-type="Currently amended] It contains 36ppm of germanium, biotite, dolomite, gold mica, feldspar, tourmaline, zircon, garnet, apatite, and opaque minerals. Germanium complex minerals.
    [3" claim-type="Currently amended] The germanium complex mineral according to claim 2, wherein the germanium complex mineral exhibits selective toxicity to cancer cell lines by dissolving in dimethyl sulfoxide (DMSO), which is a pharmaceutically acceptable solvent.
    [4" claim-type="Currently amended] The germanium composite mineral according to claim 2, wherein the germanium composite mineral is a regrind whose particle size is crushed to 800 to 5000 mesh.
    [5" claim-type="Currently amended] The germanium composite mineral according to any one of claims 2 to 4, wherein the germanium composite mineral contains at least one of an excipient, a disintegrant, and a lubricant.
    [6" claim-type="Currently amended] The method of claim 5, wherein the germanium complex mineral is formulated in any one unit dosage form or several dosage forms such as tablets, capsules, powders, granules, suspensions, emulsifiers, syrups, liquids or parenteral formulations. Germanium composite mineral having an anticancer active ingredient, characterized in that.
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    同族专利:
    公开号 | 公开日
    KR100454200B1|2004-10-27|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2003-09-03|Application filed by (주)서봉바이오베스텍
    2003-09-03|Priority to KR10-2003-0061580A
    2003-10-01|Publication of KR20030077503A
    2004-10-27|Application granted
    2004-10-27|Publication of KR100454200B1
    优先权:
    申请号 | 申请日 | 专利标题
    KR10-2003-0061580A|KR100454200B1|2003-09-03|2003-09-03|Germanium mixed mineral having anti-cancer activating ingredient and its use as anti-cancer medicine|
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