KR20160131448A - SCHISANDRAE Chinensis Extracts For Preventing OR Treating CANCER And Manufacturing Method reof - Google Patents
SCHISANDRAE Chinensis Extracts For Preventing OR Treating CANCER And Manufacturing Method reof Download PDFInfo
- Publication number
- KR20160131448A KR20160131448A KR1020150063851A KR20150063851A KR20160131448A KR 20160131448 A KR20160131448 A KR 20160131448A KR 1020150063851 A KR1020150063851 A KR 1020150063851A KR 20150063851 A KR20150063851 A KR 20150063851A KR 20160131448 A KR20160131448 A KR 20160131448A
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- cells
- omija
- cancer
- drying
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 156
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 61
- 201000011510 cancer Diseases 0.000 title claims abstract description 60
- 238000004519 manufacturing process Methods 0.000 title description 11
- 230000000694 effects Effects 0.000 claims abstract description 65
- 239000000203 mixture Substances 0.000 claims abstract description 60
- 230000006907 apoptotic process Effects 0.000 claims abstract description 27
- 208000032839 leukemia Diseases 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 12
- YEFOAORQXAOVJQ-RZFZLAGVSA-N schisandrol a Chemical compound C1[C@H](C)[C@@](C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-RZFZLAGVSA-N 0.000 claims description 79
- 241001400472 Omiza Species 0.000 claims description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- YEFOAORQXAOVJQ-UHFFFAOYSA-N wuweizischun A Natural products C1C(C)C(C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-UHFFFAOYSA-N 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 18
- 239000000843 powder Substances 0.000 claims description 14
- 102000004091 Caspase-8 Human genes 0.000 claims description 13
- 108090000538 Caspase-8 Proteins 0.000 claims description 13
- 238000004108 freeze drying Methods 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 235000013305 food Nutrition 0.000 claims description 9
- 102000004039 Caspase-9 Human genes 0.000 claims description 7
- 108090000566 Caspase-9 Proteins 0.000 claims description 7
- 230000006698 induction Effects 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000000341 volatile oil Substances 0.000 claims description 5
- 230000001737 promoting effect Effects 0.000 claims description 4
- 238000010298 pulverizing process Methods 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 230000000698 schizophrenic effect Effects 0.000 claims description 3
- 241000235346 Schizosaccharomyces Species 0.000 claims description 2
- 230000009702 cancer cell proliferation Effects 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 abstract description 13
- 108090000623 proteins and genes Proteins 0.000 abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 9
- 230000035755 proliferation Effects 0.000 abstract description 8
- 231100000957 no side effect Toxicity 0.000 abstract description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 abstract description 2
- 239000005445 natural material Substances 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 89
- 238000011282 treatment Methods 0.000 description 34
- 102000011727 Caspases Human genes 0.000 description 21
- 108010076667 Caspases Proteins 0.000 description 21
- 239000003814 drug Substances 0.000 description 14
- 230000030833 cell death Effects 0.000 description 13
- 238000000684 flow cytometry Methods 0.000 description 13
- 238000009472 formulation Methods 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 9
- 239000000796 flavoring agent Substances 0.000 description 9
- 235000019634 flavors Nutrition 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000036962 time dependent Effects 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 230000002438 mitochondrial effect Effects 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 108090000397 Caspase 3 Proteins 0.000 description 7
- 102100029855 Caspase-3 Human genes 0.000 description 7
- 102100021008 Endonuclease G, mitochondrial Human genes 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 108010047964 endonuclease G Proteins 0.000 description 7
- 210000003470 mitochondria Anatomy 0.000 description 7
- 230000002265 prevention Effects 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 6
- 235000013361 beverage Nutrition 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 102000004121 Annexin A5 Human genes 0.000 description 5
- 108090000672 Annexin A5 Proteins 0.000 description 5
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 210000000805 cytoplasm Anatomy 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000004940 nucleus Anatomy 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 102000055102 bcl-2-Associated X Human genes 0.000 description 4
- 108700000707 bcl-2-Associated X Proteins 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 235000019640 taste Nutrition 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- 102100030497 Cytochrome c Human genes 0.000 description 3
- 108010075031 Cytochromes c Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000001640 apoptogenic effect Effects 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 235000019629 palatability Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 3
- 235000005282 vitamin D3 Nutrition 0.000 description 3
- 239000011647 vitamin D3 Substances 0.000 description 3
- 229940021056 vitamin d3 Drugs 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- 108700000712 BH3 Interacting Domain Death Agonist Proteins 0.000 description 2
- 102000055105 BH3 Interacting Domain Death Agonist Human genes 0.000 description 2
- 241000255789 Bombyx mori Species 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000207199 Citrus Species 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 102000040104 IAP family Human genes 0.000 description 2
- 108091069885 IAP family Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 2
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000005775 apoptotic pathway Effects 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940099596 manganese sulfate Drugs 0.000 description 2
- 235000007079 manganese sulphate Nutrition 0.000 description 2
- 239000011702 manganese sulphate Substances 0.000 description 2
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 229940127255 pan-caspase inhibitor Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- SUUHZYLYARUNIA-YEWWUXTCSA-N (3s)-5-fluoro-3-[[(2s)-2-[[(2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoic acid Chemical compound OC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 SUUHZYLYARUNIA-YEWWUXTCSA-N 0.000 description 1
- UUTKICFRNVKFRG-WDSKDSINSA-N (4R)-3-[oxo-[(2S)-5-oxo-2-pyrrolidinyl]methyl]-4-thiazolidinecarboxylic acid Chemical compound OC(=O)[C@@H]1CSCN1C(=O)[C@H]1NC(=O)CC1 UUTKICFRNVKFRG-WDSKDSINSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- XKWQNWOHLZAFPS-UHFFFAOYSA-N 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloroimidacarbocyanine Chemical compound CCN1C2=CC(Cl)=C(Cl)C=C2N(CC)C1=CC=CC1=[N+](CC)C2=CC(Cl)=C(Cl)C=C2N1CC XKWQNWOHLZAFPS-UHFFFAOYSA-N 0.000 description 1
- PXEZTIWVRVSYOK-UHFFFAOYSA-N 2-(3,6-diacetyloxy-2,7-dichloro-9h-xanthen-9-yl)benzoic acid Chemical compound C1=2C=C(Cl)C(OC(=O)C)=CC=2OC2=CC(OC(C)=O)=C(Cl)C=C2C1C1=CC=CC=C1C(O)=O PXEZTIWVRVSYOK-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 235000009604 Chrysanthemum X morifolium Nutrition 0.000 description 1
- 244000189548 Chrysanthemum x morifolium Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100037024 E3 ubiquitin-protein ligase XIAP Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000001483 Initiator Caspases Human genes 0.000 description 1
- 108010054031 Initiator Caspases Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010021101 Lamin Type B Proteins 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000006404 Mitochondrial Proteins Human genes 0.000 description 1
- 108010058682 Mitochondrial Proteins Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 240000006322 Sambucus chinensis Species 0.000 description 1
- 241000222480 Schizophyllum Species 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 108700031544 X-Linked Inhibitor of Apoptosis Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000010428 chromatin condensation Effects 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 102000038905 cytochrome c family Human genes 0.000 description 1
- 108091065115 cytochrome c family Proteins 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012137 double-staining Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- -1 ethyl oleate Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000034725 extrinsic apoptotic signaling pathway Effects 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 238000007602 hot air drying Methods 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 238000007603 infrared drying Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000034727 intrinsic apoptotic signaling pathway Effects 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000005776 mitochondrial apoptotic pathway Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000006540 mitochondrial respiration Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 235000019991 rice wine Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000019614 sour taste Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 235000016804 zinc Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2300/00—Processes
- A23V2300/14—Extraction
Abstract
Description
The present invention relates to a pharmaceutical composition for preventing or ameliorating leukemia containing an extract of Omija and a method for producing the same.
Cancer is one of the incurable diseases. In Korea, about 100,000 people are diagnosed with cancer annually, and about 60,000 people die from cancer. Cancer inducers vary in genetic and environmental factors, and there are difficulties in the development of therapeutic agents due to the different effects of therapeutic agents depending on the site of occurrence. In addition, most of the substances currently used as medicines for treatment have significant toxicity, do not selectively remove cancer cells, and cause many side effects.
Among cancers, white blood cells, white blood cells, red blood cells, platelets, and other white blood cells among blood cells, called bone marrow, are called leukemia. Abnormal white blood cells (leukemia cells) are overproduced and the production of normal white blood cells, red blood cells and platelets is suppressed. When the normal white blood cell count is decreased, immunity deterioration may cause septicemia due to bacterial infection, , Dyspnea, etc., and platelet reduction causes hemorrhagic tendency. In addition, hypertrophic leukemia cells may cause high fever, fatigue, bone pain, diarrhea, decreased consciousness, dyspnea, etc. Leukemia cells may not be able to stop growth, restrict proliferation, Do.
Although the combination of cytarabine and anthracycline is commonly used in the treatment of leukemia, these drugs have limited treatment capacity and recurrence of the disease is frequent. Therefore, there is a strong demand for the development of new therapeutic agents that can overcome drug resistance and utilize apoptosis potency.
Ochiza (S chisandrae chinensis ) is distributed over 200-1,600m above sea level and is a deciduous deciduous broad-leaved tree that grows widely in Mt. Jiri, Mt. The leaves are 6 ~ 9m long, 7 ~ 10㎝ long, 3 ~ 5㎝ wide, with hairs on the back vein, small teeth on the edge, and wide oval shape. The flower is slightly reddish yellowish white with a diameter of about 1.5㎝. It blooms one by one on the axil of the short branch of newly emerged 3-5. The fruit is strong in sour taste and ripen in red color from August to September, and its length is 0.6 ~ 1.2㎝, and several dogs are hanging down with grape clusters. It is used for ornamental purposes, and the fruit is used for medicinal purposes.
As for the specific prior art, Prior Art 1 (KR 10-2010-0072390 A, published on July 01, 2010) discloses a composition for raw rice wine containing an extract of Omija. However, this is based on the taste and aroma of Omija, and since it is a natural fruit extract, the beneficial ingredients of Omija are said to promote health, and it can be said that research on specific effects or characteristics other than taste has not been made.
Therefore, the prior art of the prior art is not enough to study the new effects of Omija besides the food composition based on the unique flavor and texture of Omija. Therefore, the present invention has been completed on the basis of the characteristics of the cancer effect of Omiza while studying the new effect features of Omiza.
It is an object of the present invention to provide a pharmaceutical composition for preventing or ameliorating cancer.
Another object of the present invention is to provide a method for producing an omiza composition having an effect of preventing, ameliorating or treating cancer.
It is still another object of the present invention to provide a food composition for preventing or ameliorating cancer and a composition for inhibiting cancer metastasis.
In order to achieve the above object, the pharmaceutical composition for preventing or ameliorating cancer according to an embodiment of the present invention comprises an extract of Omija.
The Schizandra chinensis extract may be Essential oil.
The cancer may be leukemia.
The leukemia may be selected from the group consisting of acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia and chronic lymphocytic leukemia.
The above-mentioned Omiza extract may have the effect of promoting the activity of caspase-8 and caspase-9 to inhibit apoptosis and cancer cell proliferation.
The Schizandra chinensis extract may be one obtained by extracting Schizosaccharomyces cerevisiae which has been dried and pulverized and lyophilized at 150 to 210 ° C and having 1 to 4 carbon atoms and then distilled at 160 to 190 ° C for 1 to 5 hours.
According to another aspect of the present invention, there is provided a method for preparing an omija extract, which comprises drying omija at 150 to 210 ° C to produce dried omija; Crushing the dried omiza to produce an omija powder; A freeze-drying step of freeze-drying the above-mentioned schizophrenic powder; Drying the lyophilized Schizandra chinensis powder with a 1 to 4 carbon atoms lower alcohol aqueous solution at 20 to 40 ° C for 10 to 30 hours; And separating the extract by distillation at 160 to 190 ° C for 1 to 5 hours.
According to another aspect of the present invention, there is provided a food composition for preventing or ameliorating cancer, which comprises an extract of Schizandrae chinensis .
In order to achieve still another object of the present invention, the composition for inhibiting cancer metastasis according to an embodiment includes an extract of Schizandrae chinensis .
Hereinafter, the present invention will be described in more detail. The following description is intended to assist in a clear understanding of the present invention only and does not limit the scope of the present invention to the following contents.
The term "prophylactic" in the present invention means any action that inhibits or delays the onset of leukemia upon administration of the composition.
The term "improvement" or "treatment" in the present invention means any action that alleviates or alleviates the symptoms of leukemia upon administration of the composition.
The present invention relates to a composition for preventing or ameliorating cancer comprising an extract of Omija.
The present invention also relates to a composition for inhibiting cancer metastasis comprising an extract of Schizandrae chinensis .
The composition may be a pharmaceutical composition.
The Schizandrae chinensis of the present invention is a deciduous deciduous broad-leaved tree. The fruit is sour and strong in sour color in August-September, and the length is about 0.6 to 1.2 cm. It is used for ornamental purposes, and the fruit is medicinal. Omija is known to have unique flavor and excellent antimicrobial power.
The above-mentioned Omija may preferably be an Omija seed, more preferably a dried Omija seed, and most preferably a dried Omija seed may be pulverized and lyophilized again.
The above-mentioned Schizosaccharum can be lyophilized after drying at 150 to 210 ° C. Particularly, when drying is carried out at a temperature of less than 150 ° C, the above-mentioned effect is hardly obtained. When the temperature exceeds 210 ° C, the effect of preventing the cancer of Omija seed extract is rather reduced. Respectively.
More preferably, the Schizosacchis seeds may be lyophilized after drying at 170 to 190 ° C. In the case of drying the omija seeds in the above-mentioned temperature range, the omija seed extract has the most effect to prevent cancer, so that the active ingredient for preventing cancer can be contained the most.
There is an advantage in commercialization when the omija is dried, and preferably, when the omija seed is dried, the active ingredient having the effect of improving the cancer is more activated. In other words, there is a more advantageous effect on the prevention or treatment of cancer than in the case of extracting omija seeds, as compared with the case of producing the extract by freeze-drying the omija seed without drying.
In the present invention, "cancer" includes all diseases caused by overgrowth of cells or abnormal proliferation, preferably blood cancer, more preferably leukemia. The leukemia may be selected from the group consisting of acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia and chronic lymphocytic leukemia, most preferably acute myelogenous leukemia. It was experimentally confirmed that the extract of Omija of the present invention is involved in the expression of the proteins caspase-3, -8 and -9 involved in apoptosis, inducing apoptosis and inhibiting cell proliferation.
As used herein, the term "extract " means an active ingredient isolated from a natural product. The extract can be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, and includes an extract, a dry powder thereof, or all the forms formulated with it.
The extraction solvent of the Omiza extract may be extracted using water, an organic solvent, or a mixed solvent thereof. Preferably, the aqueous solution is extracted with an organic solvent, particularly ethanol. The aqueous solution may be any one selected from the group consisting of water, C1-4 alcohols, and combinations thereof, preferably 90-100% ethanol have.
The Schizandra chinensis extract may be obtained by treating Schizandra chinensis and an extraction solvent at a volume ratio of 1: 2 to 1: 3. When the alcohol content is lower than the above range, the extraction amount of the effective substance effective for the improvement of the cancer contained in the Omija seed is decreased rapidly. When the alcohol content is larger than the above range, There is a problem that an effective substance effective for the improvement of cancer contained in the extract of the present invention is lost.
The extracted liquid may be used directly or by concentrating and / or drying. Concentration of the extract can be carried out by reduced-pressure concentration, reverse osmosis concentration, or the like. The post-concentration drying step includes, but is not limited to, freeze drying, vacuum drying, hot air drying, spray drying, vacuum drying, foam drying, high frequency drying, infrared drying and the like. In some cases, a step of pulverizing the final dried extract may be added.
The extraction method is not particularly limited, and examples thereof include cold extraction, ultrasonic extraction, and reflux cooling extraction. Filtration is a process of removing suspended solid particles from an extract, and may be performed by filtering particles using a cotton, nylon, or the like, or by ultrafiltration, freezing filtration, centrifugation, and the like.
The above-mentioned Omiza extract is preferably an essential oil extracted from Omiza seed, more preferably, it is obtained by extracting the dried and lyophilized Omiza seeds after drying at 150 to 210 DEG C with the above-mentioned lower alcohol having 1 to 4 carbon atoms, Lt; RTI ID = 0.0 > 160-190 C < / RTI > for 1 to 5 hours. It was experimentally confirmed that the above-mentioned Schizandra chinensis extract had better cell death induction and cell proliferation inhibitory effect than Schizandra chinensis.
The pharmaceutical composition for prevention and improvement of cancer of the present invention comprises 0.1 to 50% by weight of the above extract or compound based on the total weight of the composition. In addition, the composition does not increase the efficacy, but may contain additional ingredients that are commonly used in pharmaceutical compositions to improve odor, taste, visual appearance, and the like. In addition, the composition may further include inorganic and organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folic acid pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, As shown in FIG. In addition, the composition may contain a substance that has therapeutic activity against leukemia alone or in a previously used form.
The pharmaceutical composition for preventing or improving may further comprise a pharmaceutically acceptable carrier, salt or diluent.
The term "pharmaceutically acceptable carrier" is intended to encompass pharmaceutically acceptable substances, such as liquid or solid fillers, diluents, excipients or solvents, which serve to transport the active ingredient from one or more parts of the body to other organs or parts of the body , Composition, or vehicle.
In the present invention, the term "pharmaceutically acceptable salt" means salts derived from pharmacologically or physiologically acceptable inorganic acids, organic acids and bases. Examples of suitable acids include hydrochloric, hydrobromic, sulfuric, nitric, perchloric, fumaric, maleic, phosphoric, glycolic, lactic, salicylic, succinic, toluene- Formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Salts derived from suitable bases may include alkali metals, such as sodium, alkaline earth metals, such as magnesium, ammonium, and the like.
The composition for improving leukemia of the present invention may be prepared by adding a pharmaceutically acceptable carrier and at least one pharmaceutically acceptable carrier. Such carriers include, but are not limited to, saline, buffered saline, water, glycerol, and ethanol, and any suitable formulation known in the art may be used (Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA).
The formulation for pharmacological treatment of the extract of Omiza of the present invention can be administered orally at the time of clinical administration and can be used in the form of a general pharmaceutical preparation. In the case of formulation, a filler, an extender, a binder, a wetting agent, A surfactant, or the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. Examples of liquid formulations for oral use include suspensions, solutions, emulsions and syrups. Common diluents such as water, In addition to liquids and paraffins, various excipients such as wetting agent sweetening agents, perfumes, preservatives and the like may be included.
The composition of the present invention can be administered in various forms of parenteral administration at the time of actual clinical administration. Solid formulations include tablets, pills, powders, granules, capsules and the like. Examples of the liquid formulations include suspensions, , Syrups, and the like. Various excipients such as wetting agent sweeteners, fragrances, preservatives, etc. may be included in addition to simple diluents commonly used in water, liquids and paraffins. Specifically, formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like. Calcium or vitamin D3 may also be added to enhance the efficacy of the therapeutic agent. Such compositions may be presented in unit-dose (one-time) or multi-dose (several-dose) containers, such as sealed ampoules and vials, and may be presented in a sterile liquid carrier, Lt; RTI ID = 0.0 > freeze-drying < / RTI > Immediate injectable solutions and suspensions may be prepared from sterile powders, granules and tablets.
The formulations of the present invention may be applied differently depending on the age, sex, condition of the subject, the degree of absorption of the active ingredient in the body, the rate of inactivation and the rate of excretion, and the drugs used in combination. The present invention also includes formulations of dosage units. The formulations are presented in separate dosage forms, such as tablets, coated tablets, capsules, pills, suppositories, and ampoules, and the content of active compound in the drug is a fraction or multiple of the individual dosage. Dosage units may contain, for example, 1, 2, 3 or 4 times, or 1/2, 1/3 or 1/4 times the individual doses. The individual doses preferably contain amounts in which the active compound is administered in a single dose, which usually corresponds to the full, half, one-third or one-fourth of the daily dose.
The term "administering" in the present invention means introducing a predetermined substance into a patient in any appropriate manner, and the administration route of the composition of the present invention may be oral or parenteral ≪ / RTI > The composition may also be administered by any device capable of transferring the active agent to the target cell.
The composition of the present invention is administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the sex of the patient, age, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts.
The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. May be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. The method for administration of the composition comprising the extract or the compound prepared according to the preparation method of the present invention is preferably oral or intravenous. Generally, the effective dose is usually 1 to 10 times, 500 mg / kg is preferable, and in case of intravenous administration, 1 to 100 mg / kg is preferable, and it can be administered 2-3 times a day. The dosage level for a particular patient can be varied depending on the sex, age, health condition, diet, time of administration, method of administration, drug mix, patient condition, and severity of neurological disease.
Another aspect of the present invention relates to a method for producing omiza, which comprises drying an omija at 150 to 210 ° C to produce a dried omija; Crushing the dried omiza to produce an omija powder; A freeze-drying step of freeze-drying the above-mentioned schizophrenic powder; Drying the lyophilized Schizandra chinensis powder with a 1 to 4 carbon atoms lower alcohol aqueous solution at 20 to 40 ° C for 10 to 30 hours; And separating the extract by distillation at 160 to 190 ° C for 1 to 5 hours to separate and isolate the extract.
In the pulverizing step, the average particle diameter of the ground powder of omija or omija may be 0.03 mm to 1 mm. When the average particle diameter is less than 0.03 mm, the pulverized material clumps and the extraction efficiency of the effective component decreases. When the average particle diameter exceeds 1 mm, there is a problem that the extraction efficiency of an effective component for improving the cancer existing in the endothelium of Omija is low.
When the temperature is lower than 15 ° C, the yield of the effective substance against the improvement of cancer among the active ingredients contained in the omija may be lowered. When the osmotic pressure exceeds 35 ° C, the alcohol is partially volatilized, There is a problem that an effective substance effective for improving the cancer contained in the extract is lost. Therefore, it is preferable to slowly extract for 10 to 30 hours in the above temperature range to obtain an Omija extract. More preferably at 19 to 28 DEG C for 20 to 28 hours. The yield of the effective substance is the highest in the above range.
Preferably, the composition for preventing or ameliorating cancer further comprises 100 parts by weight of the above-mentioned Omija extract, 20-40 parts of the bumudaceae extract and 30-50 parts by weight of the extract of the family Chrysanthemum morifolium extract. When the above range is used, the sour flavor of the omija is neutralized, and the flavor is excellent as a whole, so that high palatability can be maintained, so that it can be utilized as a food composition.
Preferably, the composition for preventing or ameliorating cancer further comprises 100 parts by weight of the above-mentioned Omiza extract, 30-50 parts by weight of the above extract of Bombyx mori, and 40-60 parts by weight of an extract of a potato extract. By the above range, antioxidative activity is increased and the activity of caspase-8 is further promoted, so that cancer prevention and improvement effect is enhanced and high antioxidative effect can be maintained.
More preferably, the composition for preventing or improving cancer may further comprise 100 parts by weight of the above-mentioned Omiza extract, 30-40 parts by weight of the above extract of Bombyx mori, and 40-50 parts by weight of the extract of the family pot. According to the above range, the activity of antioxidant and caspase-8 is further promoted to further enhance the effect of preventing and / or improving cancer, and it can be provided as a functional food with excellent palatability.
The extract of Omiza produced by the above method has excellent effect of inducing apoptosis in a small amount and is excellent in the effect of inhibiting proliferation of cells, and thus can be used for prevention, improvement or treatment of cancer. Since the toxicity is low, there is no side effect and it can be effectively used for the treatment of cancer.
Another aspect of the present invention is a food composition for preventing or ameliorating cancer comprising an extract of Schizandrae chinensis .
The food composition may further comprise a pharmaceutically acceptable food-aid additive.
The food composition may preferably contain 0.1 to 0.17% by weight of the Omija extract. By the above range, it is possible to exhibit an improvement effect on the cancer in various patient groups as a range without cytotoxicity. In particular, when the above range is applied, the absorption rate of the Omija extract is the most excellent, It can be the most excellent.
The food composition for prevention or amelioration of cancer including the extract of Omiza induces the death of cancer cells and inhibits the proliferation of cancer, thereby preventing or improving cancer.
The above-mentioned cancer is as described above.
The above-mentioned Omiza extract is as described above.
The use of the extract of Omiza of the present invention is experimentally confirmed that it has an effect of inducing the death of cancer cells and inhibiting proliferation without side effects and toxic action on normal cells and is useful as a composition for prevention, Can be used.
The extract of Omija according to the present invention is useful as a composition for prevention, improvement or treatment of cancer by experimentally confirming that it has an effect of inducing the death of cancer cells by participating in the activity of proteins involved in apoptosis and inhibiting proliferation Can be used. Accordingly, the present invention relates to a pharmaceutical composition for treating cancer, a functional food composition, a composition for cancer metastasis, and a composition for preventing or treating cancer, Yes.
FIG. 1 is a graph showing cell activity according to the treatment with Schizophyllum sinensis extract (SSeo) in U93 cells. The abscissa of the graph represents the SSeo treatment time (h), and the ordinate axis represents the relative cell activity (%) when SSeo treatment is not performed.
FIG. 2 is a graph showing the induction of cell death by treatment with Omine extract (SSeo) in U937 cells. FIG. 2A is a graph showing a fluorescence microscopic observation of stained cells, FIG. 2B is a graph showing the amount of sub-G1 DNA measured, and FIG. 2C is a graph showing flow cytometric analysis results.
3 is a graph showing the activity of caspase and the decrease of PARP according to the treatment with Schizosacral extract (SSeo) in U937 cells. FIG. 3A is a graph showing the results of SDS-polyacrylamide gel electrophoresis, FIG. 3B is a graph showing activity of each of
Figure 4 shows the effect of Omiza extract on IAP family and DR-related protein levels in U937 cells.
Figure 5 shows the effect of Omiza extract on cytochrome c and Bcl-2 family protein levels and MMP value in U937 cells. FIG. 5A is a flow cytometry analysis result of JC-1 fluorescence intensity measurement, FIG. 5B is a graph showing protein expression in cytosolic and mitochondria with time, FIG. 5C is a graph showing the expression of total cell protein to be. In the figure, actin and lamin B were used as internal control in cytosol and mitochondrial fractions, respectively.
FIG. 6 is a graph showing the migration of EndoG and AIF by treatment with Schizosacral extract (SSeo) in U937 cells.
FIG. 7 is a graph showing the induction of ROS-dependent cell death by treatment with Schizosacral extract (SSeo) in U937 cells. FIG. 7A is a flow cytometry analysis result for ROS generation, FIG. 7B is a flow cytometric analysis result of apoptotic cells, and FIG. 7C is a flow cytometric analysis result of mitochondrial membrane potential (MMP) value.
Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.
[Experimental Example 1] Preparation of Schizosaccharomyces pombe extract (SSeo)
The dried seeds of S. chinensis Turcz. Were collected at Mungyeong, Korea and then completely dried at 180 ° C using a furnace (Korean Scientific, Korea), followed by pulverization and freeze-drying (
[Experimental Example 2] Cell culture and cell viability assay]
Human acute myelogenous leukemia U937 cell line was purchased from American Type Culture Collection (Manassas, USA). The cells were stored at 37 ℃, 5% carbon dioxide (CO 2), RPMI 1640 medium (Gibco-BRL, Rockville, MD , USA). The medium contained 2 mM L-glutamine, 1.5 g / L sodium bicarbonate, 4.5 g / L glucose, 10 mM HEPES, 1.0 mM sodium pyruvate, 10% fetal bovine serum, 100 units / mL penicillin, and 100 μg / mL streptomycin (Gibco-BRL). The cells were treated with different concentrations of Omija extract for cell activity analysis. The treatment time was each treated according to the time and 0.5 mg / ml of 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide (3- -dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolium bromide, MTT, Sigma-Aldrich Chemicals, USA), followed by incubation at 37 ° C for 2 hours under dark conditions, Respectively. After formazan precipitate was dissolved in dimethyl sulfoxide (Sigma-Aldrich), the formazan product was subjected to an enzyme-linked immunosorbent assay (ELISA) reader (Molecular Devices, Sunnyvale, Calif., USA).
The results of the above experiment are shown in FIG. 1 and FIG.
[Experimental Example 3: DAPI nuclear staining]
To confirm morphological changes in apoptosis, cells were washed with phosphate-buffered saline (PBS) and resuspended in PBS with 7% paraformaldehyde (Sigma-Aldrich) for 10 min at room temperature Respectively. The fixed cells were washed with PBS and incubated with a solution of 4,6-diamidino-2-phenylindile (DAPI, Sigma-Aldrich) at 2.5 μg / Lt; / RTI > The cells were washed twice with PBS and the stained nuclei were observed with a fluorescence microscope (Carl Zeiss, Oberkochen, Germany).
In order to confirm the involvement of caspase in apoptosis, tripeptide pan-caspase inhibitor z-Val-Ala-Asp-fluoromethyl ketone (z-Val) -Ala-Asp-fluoromethyl ketone, z-VAD-fmk, Calbiochem, USA).
The results are shown in Figures 2 and 3
[Experimental Example 4: Analysis of apoptosis by DNA flow cytometry]
After treatment with Omiza extract, the cells were pooled and fixed with 70% ethanol at 4 ° C for 30 minutes. Cell DNA was stained with propidium iodide (PI) using a DNA staining kit (CycleTEST PLUS Kit, Becton Dickinson, USA) according to the manufacturer's manual. The cells were then flow cytometry analyzed from a DNA bar graph to determine cell rates at different stages of the cell cycle. The cells in the sub-G1 DNA stage were considered dead cells. To count the number of cells in different stages of apoptosis in each sample, the cells were stained with 5 μl of Annexin V-fluorescein isothiocyanate (R & D Systems, USA) and 1 μl of PI Respectively. After 15 min of incubation at room temperature, cell death was quantified by flow cytometry using the ratio of Annexin V-positive and PI-negative cells (Annexin V + / PI - cells).
[Experimental Example 5: Protein extraction and Western blot analysis]
The harvested cells were treated with lysis buffer (20 mM sucrose, 1 mM EDTA, 20 μM Tris-Cl, pH 7.2, 1 mM dithiothreitol, 10 mM KCl, 1.5 mM MgCl 2 , 5 μg / ml pepstatin A, ml leupeptin, and 2 μg / ml aprotinin) for 30 min at 4 ° C. In parallel with the experiment, the nuclear / cytosol and mitochondrial / cytosolic fractions were separated according to the user manual using a commercial fractionation kit (Biovision, Milpitas, Calif., USA) The same amount of protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the nitrocellulose membrane (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) The membrane was then incubated with PBST buffer (containing 0.05% Triton X-100) containing 5% non-fat milk to block non-specific binding. PBS for 1 hour and probed with complementary antibodies to specific proteins for 2 hours at 37 ° C or overnight at 4 ° C. Washed with PBST buffer and incubated with appropriate peroxidase-conjugated secondary antibody for 1 hour. After the final wash, the specific protein was incubated with a chemiluminescence kit (Amersham Corp.). Primary antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, USA), Chemicon (Temecula, USA), and Sigma-Aldrich Peroxidase-labeled donkey anti-rabbit and sheep anti-mouse immunoglobulin were purchased from Amersham Corp. (Piscataway, USA) and used .
[Experimental Example 6: Caspase activity assay]
Measurement of caspase activity was performed using a colorimetric assay kit (R & D Systems) based on the ability of the active caspase to cleave the chromophore from the enzyme-substrate. Omiza extract-treated and untreated cells were dissolved in a lysis buffer and the lysate was mixed with a reaction buffer and incubated with a caspase-specific substrate (Caspase-3 is Asp-Glu-Val-Asp, caspase-8 is Ile-Glu-Thr-Asp, caspase-9 is Leu -Glu-His-Asp) at 37 < 0 > C for 3 hours. The pNA release was measured at 405 nm using an ELISA reader. The results are shown in Fig.
[Experimental Example 7: Detection of MMP (占 m)]
Dyes having cell permeability, cationic and lipophilic properties are internalized by mitochondrial respiration, accumulate, and reflect the change of MMP in living cells, so that the mitochondrial potential sensor, 5,5 ', 6,6'-tetrachloro -1,1 ', 3,3'-tetraethyl-imidacarbocyanine iodide (5,5', 6,6'-tetrachloro-1,1 ', 3,3'- 1, Sigma-Aldrich) was used to measure the mitochondrial transmembrane electrochemical gradient. Specifically, the collected cells were cultured for 20 minutes in a dark condition with 10 μM of JC-1 at 37 ° C. After the cells were cultured, the cells were washed with PBS to remove unbound dye, and then analyzed by flow cytometry using JC -1 was measured. The amount of JC-1 containing about 10,000 cells per sample was measured using a flow cytometer at 488 nm and 575 nm.
[Experimental example 8] Measurement of intracellular ROS [
2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA, Molecular Probes, USA) was used to test the effect of the extract of Orimida on the production of active oxygen. Cells from each treatment were harvested, washed twice with PBS, resuspended in 10 μM DCFH-DA, and maintained at 37 ° C for 30 min. The active oxygen production of the cells was immediately observed by flow cytometry using Cell-Quest pro software.
In order to confirm the association of high concentration of active oxygen in the extract of Omija-induced cell death, the cells were treated with N-acetylcysteine (NAC, Calbiochem), which is conventionally used as an antioxidant, for 2 hours before treatment with Omiza extract ) Were used for pre-culture.
[Experimental Example 9: Preparation of mixed extract]
(Unit: parts by weight)
- Buchoeson extract: Buchoeson was prepared by hot water extraction.
- Citrus extract: Citrus extract was prepared by hot water extraction.
[Experimental example 10: Statistical analysis]
Experimental results were expressed as mean ± standard deviation (SD) of three independent experiments. Changes in single analysis were statistically significant. The significance level is p < 0.05.
Test Example 1. Identification of Anti-proliferative Activity and Apoptosis-inducing Effect of Omiza Extract in U937 Cells [
To examine the effect of Omiza extract on U937 cell proliferation, 1 × 10 5 cells / ml were each seeded and cultured for 24 hours. The cells were treated with 60 μg / ml of Omija extract for 0, 3, 6, 12, 18, and 24 hours, respectively, and cell activity was confirmed by MTT assay. The results are shown in FIG.
To confirm whether the inhibitory effect of Omiza extract on cells was related to induction of apoptosis, DNA was stained with DAPI and confirmed by fluorescence microscopy. The chromatin concentration of the nucleus, which is characteristic of apoptotic cells, and the number of sub-G1 stage and the number of Annexin V-positive cells were measured, and the results are shown in FIG.
As shown in Fig. 1, in U937 cells, Omija extract caused a significant decrease in cell activity in a time-dependent manner. As shown in FIG. 2 A, it was found that the number of chromatin condensation and cell killing was significantly increased in the cells treated with Omija extract in a time-dependent manner, while it was confirmed that these characteristics were not observed in the control cells. In addition, as shown in FIG. 2B, cell cycle analysis by flow cytometry showed that the accumulation of sub-G1 phase cells was increased in a time-dependent manner after treatment with Omija extract. As shown in Fig. 2C, the Annexin-V and PI double-staining revealed increased cell death rates in cells treated with Omija extract (Fig. 2C).
Therefore, it was confirmed that when treated with the extract of Omija, the activity of the cells was lowered and the cell death was increased, and that the Omija extract was effective in inhibiting cell proliferation and inducing apoptosis.
[Test Example 2: Examination of the activity of caspase and the degradation effect of PARP in U937 cells of Omiza extract]
(-3, -8 and -9) and poly (ADP-ribose) -polymerase, to confirm the relevance of caspase activity in Omiza extract-induced cell death. PARP) was measured, and the results are shown in Fig. 3A.
In order to demonstrate that caspase activity is associated with Omija extract-induced apoptosis in U937 cells, the cells were pretreated with 50 [mu] M pan-caspase inhibitor z-VAD-fmk, / ml for 24 hours, and the results of the observation are shown in Fig.
As shown in Figure 3A, western blot analysis showed that the expression levels of pro-caspase-8, -9, the initiator caspases of extrinsic and intrinsic apoptotic pathways, Were down-regulated, whereas their active forms were up-regulated in a time-dependent manner. As shown in FIG. 3B, the activity of caspase-3, -8 and -9 was remarkably increased by 4.3-, 2.7-, and 3.1-fold, respectively, when Schizo extract (SSeo) was treated at 60? / Ml for 24 hours (Fig. 3B). Treatment of U937 cells with Omiza extract resulted in a time-dependent increase in the effector caspase, caspase-3, segmented fragment, and the caspase-3 substrate to produce an 85 kDa segmented fragment Leading to a gradual protein hydrolysis segment of the known PARP (116 kDa). Accordingly, the activity of this caspase was measured through quantitative detection of colorimetric tetrapeptide substrates, and as a result, it was found that the Omija extract stimulates caspase-3, -8 and -9 activity in a time-dependent manner Respectively.
In addition, as shown in Figs. 3C and 3D, it was confirmed that pretreatment with z-VED-fmk remarkably prevented accumulation of sub-G1 cells and apoptosis. This means that apoptosis induced by Omiza extract in U937 cells will be regulated through a caspase-dependent extrinsic and intrinsic pathways (Fig. 3C and D).
In addition, the SSeo treatment reduced down-regulated proteins of the apoptosis protein (IAP) family, such as XIAP, cIAP-1, cIAP-2 and survivin, which bind to caspases and cause inactivation (Fig. 4), which means that the activity of Omija extract-induced caspase is associated with a decrease in IAP family protein in U937 cells.
Therefore, it was confirmed that the treatment with Omiza extract increased cell death, and that the effect of Omiza extract on cell proliferation inhibition and death induction was related to caspase activity.
[Test Example 3: Effect of Omiza extract on recovery of mitochondrial apoptosis pathway in U937 cells]
In order to confirm whether or not the Omiza extract activates the mitochondrial apoptotic pathway, the MMP value was analyzed by staining with JC-1, and the result is shown in FIG.
As shown in FIG. 5A, treatment of U937 cells with Omiza extract resulted in a time-dependent reduction in MMP levels, suggesting that depolarization of mitochondria occurs by the extract of Omija. Furthermore, in order to characterize the mitochondria - regulated apoptotic effect of the extract of Omija in U937 cells, the dislocation of Bax and the release of cytochrome c were analyzed using cytoplasmic and mitochondrial classifications. As shown in Figure 5B, the immunoblot results confirmed that the Schizo extract treatment (SSeo) induces a time-dependent increase in the release of cytochrome c from the mitochondria to the cytoplasm. In particular, the total levels of pro-apoptotic Bax and anti-apoptotic Bcl-2 protein remained unchanged despite treatment with Omija extract (Fig. 5C); However, increasing the concentration of Omiza extract significantly increased mitochondrial levels, whereas treatment with Omine extract (SSeo) reduced the cellular level of Bax (Fig. 5B). These results are generated by inducing translocation of Bax to the mitochondria, and the loss of MMP and the release of cytokine c to the cytoplasm of Omija extract-induced apoptosis are responsible for the apoptosis of caspase-9 and -3 Resulting in activation.
From the above results, it was experimentally confirmed that cell death was caused by caspase activity when treated with an extract of Omija.
Test Example 4. Confirmation of induction effect of cleavage of Bid and expression of DR-related proteins in U937 cells of Omiza extract [
In order to confirm the signaling mechanism of cell death by treatment with Omija extract, the effect of Omiza extract on the level of DR-related protein and Bid expression was further observed.
As a result, levels of DR ligands such as tumor necrosis factor-associated apoptosis inducing ligands and Fas ligands were relatively unchanged for treatment with Omija extract;
However, as shown in FIG. 4, DR4, DR5, and Fas levels increased significantly in a time-dependent manner (FIG. 4). Western blot analysis then showed a gradual downward regulation of total Bid protein and the accumulation of tBid (Figure 5C) resulting from cleavage by caspase-8 produced in the cells.
These results indicate that the cytotoxic effect of the Schizandra chinensis extract could be controlled through DR-regulated apoptosis and that it would thus emphasize crosstalk between internal and external apoptotic pathways , And the pathway of apoptosis mechanism to the extract of Omija was experimentally confirmed.
Test Example 5. Confirmation of nuclear potential enhancement effect of EndoG and AIF in U937 cells [
In addition to cytochrome c , the release of other mitochondrial proteins such as endonuclease G (EndoG) and AIF is a major event that occurs during apoptosis. These proteins release into the cytoplasm and into the nucleus when the MMP is lost, leading to apoptosis through a caspase-independent mechanism.
In this regard, western blotting was performed to compare levels of endogenous G (EndoG) and AIF using mitochondria, cytoplasm and nuclear fragments, and the results are shown in FIG.
Western blot analysis revealed that treatment of Omiza extract induced the dislocation of EndoG to the nucleus (Fig. 6B), although control cells showed a significant lack of nuclear expression of EndoG. Similarly, the level of AIF in U937 cells exposed to Omiza extract was further enhanced in the cytoplasm and nuclear fraction and decreased in the mitochondrial fraction, indicating the promotion of migration to the nucleus (Fig. 6A).
Taken together, these results demonstrate that both the caspase-dependent and non-caspase-induced apoptosis of U937 cells are induced by Omija extract.
Test Example 6. Confirmation of Promoting Effect of ROS Generation on Extract of Omiza in U937 Cells [
To determine if Omija extract-induced cell death is regulated by oxidative stress; The level of intracellular reactive oxygen (ROS) was measured using a ROS-detecting fluorescent dye DCFH-DA, and the results are shown in FIG.
As shown in Fig. 7A, the flow cytometry analysis showed that the Schizandra chinensis extract produced active oxygen within 15 minutes, and the level continued to increase until 30 minutes. In addition, pretreatment with 10 mM NAC (a commonly used ROS abolisher) completely blocked ROS production in U937 cells treated with Omija extract as well as in control cells.
U937 cells were pretreated with NAC and then treated with Omija extract to determine whether the oxidative burst induced by Omiza extract was the most important factor for pro-apoptotic activity.
As shown in FIGS. 7B and 7C, the number of Omija extract-induced Annexin-V + cells was completely removed by pretreatment with NAC (FIG. 7B). In addition, treatment of the cells with NAC significantly reduced the loss of Omija extract-induced MMP (Fig. 7C).
These results confirmed that the production of reactive oxygen species (UO) in U937 cells is an important factor in the pathogenesis of Omiza extract-regulated mitochondria-dependent cell death signaling pathways.
Test Example 7. Confirmation of Promoting Effect of ROS Generation on Extract of Omiza in U937 Cells [
1. Sensory evaluation of mixed extracts
Examples 1 to 5 and Comparative Examples 1 and 2 were dried to prepare a beverage, and the beverage and the comparative example were included in the beverage in an amount of 1 wt%. The beverage is prepared by diluting an appropriate amount of the composition with water, and the composition is prepared by a person skilled in the art. In addition to the above examples and comparative examples, the beverages prepared by the same method were tasted to 30 persons to check palatability including flavor and texture. As a result, the beverage was expressed as an index of 1 to 10 on the basis of Comparative Example 5, Lt; / RTI > The larger the number, the better the degree of preference.
In the case of Example 1, there was a disadvantage in that the taste of Omija remained and the flavor of the mixture did not match. In Example 5, there was a disadvantage that the unique flavor of Omija was reduced and it was difficult to feel Omija flavor.
2. Caspase-8 activity of the mixed extract
The activity of caspase-8 was confirmed in the same manner as in Test Example 2, and the results are shown in Table 3 below, in comparison with the results obtained by treating Omiza extract (SSeo) at 60? / Ml for 24 hours.
(fold induction)
Referring to Table 3, it can be confirmed that caspase-8 activity is promoted by the mixed extract, and in particular, the effects of Examples 3 to 5 are enhanced.
[Production example. Preparation of Cancer Therapeutics Containing Schizandra chinensis Extract]
The inventors of the present invention confirmed the excellent therapeutic effect of the cancer of the Schizandra chinensis extract by the above examples and prepared a cancer treatment agent containing the extract as an active ingredient as follows.
Preparation Example 1. Preparation of soft capsules containing Omija extract (% by weight)
Omija extract 20%
Vitamin C 4.5%
Vitamin D3 0.001%
Manganese sulfate 0.1%
palm oil 25%
Safflower oil 30.399%
Production Example 2. Preparation of intravenous formulation containing Omija extract (% by weight)
Omija extract 0.2%
Mannitol 0.3%
Saline solution
Preparation Example 3. Preparation of tablet containing Omija extract (% by weight)
Omija extract 35%
Vitamin D3 0.001%
Manganese sulfate 0.1%
Crystalline cellulose 25.0%
Lactose 17.999%
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.
Claims (9)
Wherein the Schizandra chinensis extract is an essential oil extracted from Schizandra chinensis.
Wherein the cancer is a leukemia.
Wherein said leukemia is selected from the group consisting of acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia and chronic lymphocytic leukemia.
The above Omiza extract has an effect of promoting the activity of caspase-8 and caspase-9 to inhibit apoptosis induction and cancer cell proliferation. Composition.
Wherein the Schizandra chinensis extract is obtained by extracting the Schizandra chinensis after drying at 150 to 210 ° C and pulverizing and freeze-drying the Schizosaccharomyces cerevisiae with 1 to 4 carbon atoms and distilling the mixture at 160 to 190 ° C for 1 to 5 hours. Or a pharmaceutically acceptable salt thereof.
Crushing the dried omiza to produce an omija powder,
A freeze-drying step of freeze-drying the above-mentioned schizophrenic powder;
Drying the lyophilized Schizandra chinensis powder with a 1 to 4 carbon atoms lower alcohol aqueous solution at 20 to 40 ° C for 10 to 30 hours; And
And separating the extract by distillation at 160 to 190 ° C for 1 to 5 hours and separating the extract.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150063851A KR101809933B1 (en) | 2015-05-07 | 2015-05-07 | Schisandrae chinensis extracts for preventing or treating leukemia and manufacturing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150063851A KR101809933B1 (en) | 2015-05-07 | 2015-05-07 | Schisandrae chinensis extracts for preventing or treating leukemia and manufacturing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160131448A true KR20160131448A (en) | 2016-11-16 |
| KR101809933B1 KR101809933B1 (en) | 2017-12-18 |
Family
ID=57540956
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150063851A KR101809933B1 (en) | 2015-05-07 | 2015-05-07 | Schisandrae chinensis extracts for preventing or treating leukemia and manufacturing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101809933B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100072390A (en) | 2008-12-22 | 2010-07-01 | 홍승희 | Enhanced health functional schizandra fruit(schizandra chinensis fructus) makgeolli(squash rice wine) and process for preparation thereof |
-
2015
- 2015-05-07 KR KR1020150063851A patent/KR101809933B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100072390A (en) | 2008-12-22 | 2010-07-01 | 홍승희 | Enhanced health functional schizandra fruit(schizandra chinensis fructus) makgeolli(squash rice wine) and process for preparation thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| KR101809933B1 (en) | 2017-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101382400B1 (en) | Composition comprising Protaetia brevitarsis for preventing and treating Inflammatory Disorder | |
| KR100769654B1 (en) | Composition comprising the extract of Houttuynia cordata for treating or prevening cancer disease | |
| KR101392204B1 (en) | Composition comprising herbal extract of red ginseng, Angelicae gigantis Radix, citrus peel and green tea leaves for treating or preventing vascular diseases | |
| US20180153852A1 (en) | Composition for preventing and treating muscle diseases or improving muscular function, containing morusin, kuwanon g, or mori cortex radicis | |
| KR20170007637A (en) | Compositions for preventing or treating bladder cancer comprising citrus fermentd broth with Kombucha as an active ingredient | |
| KR20160050108A (en) | Compositions for Improving Oral Hygiene comprising extracts derived from natural materials and Uses Thereof | |
| Abusamra et al. | Evaluation of putative cytotoxic activity of crude extracts from Onopordum acanthium leaves and Spartium junceum flowers against the U-373 glioblastoma cell line. | |
| KR101776001B1 (en) | Composition for treating, preventing or improving born loss containing panduratin or fingerroot(boesenbergia pandurata) extract | |
| US20040219233A1 (en) | Composition comprising the extract of cistanche deserticola Y.C. MA showing enhancing activity of the neurite outgrowth and neurotrophic effects | |
| KR101851167B1 (en) | Pharmaceutical composition containing extract of Spiraea prunifolia for prevention and treatment of allergic diease | |
| KR20040107853A (en) | Dendropanax morbifera Lev. extract having inhibitory effect of liver injury induced by ethanol | |
| KR20150010923A (en) | Composition for prevention, improvement or treatment of osteoporosis comprising kirenol or extract of Sigesbeckia spp. | |
| KR100623972B1 (en) | Composition comprising the extract of Cinnamomum camphora Sieb. for preventing and treating inflammatory disease | |
| Elkomy et al. | Renal protective effect of cardamom against nephrotoxicity induced by gentamicin in rats | |
| KR101809933B1 (en) | Schisandrae chinensis extracts for preventing or treating leukemia and manufacturing method thereof | |
| KR20170109703A (en) | A pharmaceutical composition for preventing or treating cancer comprising fractions of herbal mixture extract | |
| Ly et al. | Anti-urolithic, anti-inflammatory and antibacterial properties of various extracts from Musa balbisiana Colla fruits. | |
| KR20160060504A (en) | Composition comprising the extract of Lygodii Spora for preventing and treating calculus | |
| KR101838379B1 (en) | Composition for increasing salivary secretion, or prevention, improvement or treatment of xerostomia of disorder of salivation comprising curcuma xanthorrhiza extract or xanthorrhizol | |
| KR101497818B1 (en) | Pharmaceutical composition comprising the organic solvent fraction of achyranthis radix as an effective component for prevention or treatment of thrombosis and health functional food comprising the same | |
| KR101060909B1 (en) | Composition comprising plantain extract comprising brain neuronal cell protective material | |
| KR101711397B1 (en) | Pharmaceutical compositions and health functional foods comprising Persicaria fauriei extracts for preventing or treating anticancer agent-induced of hematopoietic toxicity | |
| KR101684574B1 (en) | Pharmaceutical compositions and health functional foods comprising Cibotium barometz J. Smith extracts for preventing or treating anticancer agent-induced of hematopoietic toxicity | |
| KR101839186B1 (en) | Use of Aplysia kurodai extract having retinal cell regeneration effect | |
| KR102214014B1 (en) | Antioxidant or anticancer composition comprising extract of Osmanthus heterophylla leaf |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E90F | Notification of reason for final refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |