KR101721780B1 - Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis - Google Patents
Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis Download PDFInfo
- Publication number
- KR101721780B1 KR101721780B1 KR1020150167290A KR20150167290A KR101721780B1 KR 101721780 B1 KR101721780 B1 KR 101721780B1 KR 1020150167290 A KR1020150167290 A KR 1020150167290A KR 20150167290 A KR20150167290 A KR 20150167290A KR 101721780 B1 KR101721780 B1 KR 101721780B1
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- cancer
- angiogenesis
- aqueous solution
- tumor
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 63
- 241001632410 Eleutherococcus senticosus Species 0.000 title claims abstract description 12
- 239000000203 mixture Substances 0.000 title abstract description 32
- 230000003527 anti-angiogenesis Effects 0.000 title abstract description 3
- 230000033115 angiogenesis Effects 0.000 claims abstract description 40
- 235000013399 edible fruits Nutrition 0.000 claims abstract description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 90
- 239000007864 aqueous solution Substances 0.000 claims description 47
- 201000001441 melanoma Diseases 0.000 claims description 18
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 17
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 claims description 14
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 8
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 5
- 208000030381 cutaneous melanoma Diseases 0.000 claims description 4
- 201000003708 skin melanoma Diseases 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 abstract description 57
- 201000011510 cancer Diseases 0.000 abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 19
- 201000010099 disease Diseases 0.000 abstract description 18
- 230000036541 health Effects 0.000 abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 12
- 235000013376 functional food Nutrition 0.000 abstract description 9
- 230000002265 prevention Effects 0.000 abstract description 4
- 230000006872 improvement Effects 0.000 abstract description 3
- 210000001519 tissue Anatomy 0.000 description 44
- 241000699666 Mus <mouse, genus> Species 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 21
- 230000002401 inhibitory effect Effects 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 206010033128 Ovarian cancer Diseases 0.000 description 11
- 206010061535 Ovarian neoplasm Diseases 0.000 description 11
- 229920000297 Rayon Polymers 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 206010027476 Metastases Diseases 0.000 description 6
- 244000171263 Ribes grossularia Species 0.000 description 6
- 235000002357 Ribes grossularia Nutrition 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000009401 metastasis Effects 0.000 description 6
- 239000008055 phosphate buffer solution Substances 0.000 description 6
- 241000223221 Fusarium oxysporum Species 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 241000251511 Holothuroidea Species 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 208000000453 Skin Neoplasms Diseases 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 201000000849 skin cancer Diseases 0.000 description 4
- 235000014347 soups Nutrition 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 235000011511 Diospyros Nutrition 0.000 description 3
- 244000055850 Diospyros virginiana Species 0.000 description 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 244000184734 Pyrus japonica Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000010411 cooking Methods 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 201000003908 endometrial adenocarcinoma Diseases 0.000 description 3
- 201000003914 endometrial carcinoma Diseases 0.000 description 3
- 208000029382 endometrium adenocarcinoma Diseases 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 235000015203 fruit juice Nutrition 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 230000007954 hypoxia Effects 0.000 description 3
- 238000007654 immersion Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- -1 methyl-6,8-dimethylcoumarine glycoside Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 208000003120 Angiofibroma Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 240000006439 Aspergillus oryzae Species 0.000 description 2
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 2
- 206010006143 Brain stem glioma Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 2
- 208000002471 Penile Neoplasms Diseases 0.000 description 2
- 206010034299 Penile cancer Diseases 0.000 description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 2
- 201000005746 Pituitary adenoma Diseases 0.000 description 2
- 206010061538 Pituitary tumour benign Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 201000007737 Retinal degeneration Diseases 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- 206010046431 Urethral cancer Diseases 0.000 description 2
- 206010046458 Urethral neoplasms Diseases 0.000 description 2
- 201000003761 Vaginal carcinoma Diseases 0.000 description 2
- 208000009443 Vascular Malformations Diseases 0.000 description 2
- 206010047741 Vulval cancer Diseases 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 201000007455 central nervous system cancer Diseases 0.000 description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 239000000469 ethanolic extract Substances 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 2
- 239000000401 methanolic extract Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 201000003142 neovascular glaucoma Diseases 0.000 description 2
- 235000012149 noodles Nutrition 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 208000021310 pituitary gland adenoma Diseases 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004258 retinal degeneration Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 206010062261 spinal cord neoplasm Diseases 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- QJVXKWHHAMZTBY-GCPOEHJPSA-N syringin Chemical compound COC1=CC(\C=C\CO)=CC(OC)=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 QJVXKWHHAMZTBY-GCPOEHJPSA-N 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 230000006459 vascular development Effects 0.000 description 2
- 235000015192 vegetable juice Nutrition 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 238000004017 vitrification Methods 0.000 description 2
- 201000004916 vulva carcinoma Diseases 0.000 description 2
- 208000013013 vulvar carcinoma Diseases 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- NPNUFJAVOOONJE-ZIAGYGMSSA-N β-(E)-Caryophyllene Chemical compound C1CC(C)=CCCC(=C)[C@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-ZIAGYGMSSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 1
- UYIWPVOKZZKUMC-UHFFFAOYSA-N 4-(3,4-diaminophenyl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1.C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 UYIWPVOKZZKUMC-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- NVEQFIOZRFFVFW-UHFFFAOYSA-N 9-epi-beta-caryophyllene oxide Natural products C=C1CCC2OC2(C)CCC2C(C)(C)CC21 NVEQFIOZRFFVFW-UHFFFAOYSA-N 0.000 description 1
- 244000015329 Aeginetia indica Species 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- FFDULTAFAQRACT-JSGUJALWSA-N Eleutheroside E Chemical compound COC1=CC([C@@H]2[C@@H]3[C@H]([C@@H](OC3)C=3C=C(OC)C(O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)=C(OC)C=3)CO2)=CC(OC)=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FFDULTAFAQRACT-JSGUJALWSA-N 0.000 description 1
- FFDULTAFAQRACT-MWBGVTEFSA-N Eleutheroside E Natural products COc1cc(cc(OC)c1O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)[C@@H]3OC[C@H]4[C@H]3CO[C@@H]4c5cc(OC)c(O[C@@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)c(OC)c5 FFDULTAFAQRACT-MWBGVTEFSA-N 0.000 description 1
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 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
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 102000042092 Glucose transporter family Human genes 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 201000002154 Pterygium Diseases 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 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
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046392 Ureteric cancer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- FAMPSKZZVDUYOS-UHFFFAOYSA-N alpha-Caryophyllene Natural products CC1=CCC(C)(C)C=CCC(C)=CCC1 FAMPSKZZVDUYOS-UHFFFAOYSA-N 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- NPNUFJAVOOONJE-UHFFFAOYSA-N beta-cariophyllene Natural products C1CC(C)=CCCC(=C)C2CC(C)(C)C21 NPNUFJAVOOONJE-UHFFFAOYSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000015190 carrot juice Nutrition 0.000 description 1
- 229940117948 caryophyllene Drugs 0.000 description 1
- NPNUFJAVOOONJE-UONOGXRCSA-N caryophyllene Natural products C1CC(C)=CCCC(=C)[C@@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-UONOGXRCSA-N 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 229930182483 coumarin glycoside Natural products 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 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 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 150000002148 esters 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
- 230000003203 everyday effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 201000001343 fallopian tube carcinoma Diseases 0.000 description 1
- 238000009313 farming Methods 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 150000008195 galaktosides Chemical class 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 235000019674 grape juice Nutrition 0.000 description 1
- 235000013882 gravy Nutrition 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000007602 hot air drying Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 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
- ZOLPMMWNCLHKPX-UHFFFAOYSA-N ligustrin Natural products CC1=CCC2C1C3OC(=C)C(=O)C3C(O)CC2=C ZOLPMMWNCLHKPX-UHFFFAOYSA-N 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 208000029559 malignant endocrine neoplasm Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000020874 response to hypoxia Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 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
- 239000003765 sweetening agent Substances 0.000 description 1
- QJVXKWHHAMZTBY-KSXIZUIISA-N syringin Natural products COc1cc(C=CCO)cc(OC)c1O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O QJVXKWHHAMZTBY-KSXIZUIISA-N 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 201000011294 ureter cancer Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000003817 vacuum liquid chromatography Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 238000007879 vasectomy Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/254—Acanthopanax or Eleutherococcus
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
The present invention relates to a composition for inhibiting angiogenesis containing a fruit extract of Acanthopanax senticosus. More particularly, the present invention relates to a composition for inhibiting angiogenesis, which comprises a C1-C4 alcohol or an aqueous solution extract thereof.
The term angiogenesis refers to a series of processes in which a new blood vessel is created in an existing blood vessel. The term "angiogenesis" refers to a process in which a new blood vessel is created in an existing blood vessel, and includes not only normal conditions such as fetal development and women's menstruation and wound healing, but also cancer cell growth and metastasis, (Folkman, J., 1976; Folkman, J., M., 1987), which is also required for various diseases such as sexual dysfunction. This is a very tightly controlled phenomenon that rarely occurs under normal conditions. Therefore, in a normal state, living organisms are equilibrated with factors that induce angiogenesis and inhibitory factors. However, in the situation where the disease is induced, angiogenesis promoting factors increase, inhibitory factors do not work properly, and angiogenesis is not regulated autonomously, so that the disease develops as a disease.
Up to now, more than 20 angiogenesis promoting factors have been known, among which vascular endothelial growth factor (VEGF) is secreted in many types of tumor cells and at the same time is known as the most potent angiogenesis promoting factor (Fox , SB et al ., 1996). VEGF is also known as a vascular permeability factor and binds to its receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1 / KDR) to induce endothelial cell proliferation and increase vascular permeability (Leung, DW et al ., 1989), which is known to be involved in tumor growth and metastasis. VEGFR-2 is overexpressed under hypoxia, which is known to be involved in the regulation of neovascularization to inhibit tumor growth. In addition, HIF-1 acts as a transcription factor that increases the expression of genes such as VEGF in a variety of stimulus situations such as hypoxia, reactive oxygen and stress.
The angiogenesis of cancer, especially malignant tumors, is an important determinant of tumor cell growth and metastasis, and the degree of angiogenesis in many types of malignant tumors is known to be related to tumor progression and metastasis (Folkman, J., 1995, Fidler, IJ et al ., 1994, Hanahan, D. et al ., 1996, Weidner, N., 1995). In addition to cancer, chronic diseases such as various adult diseases are known to occur as abnormalities in angiogenesis, including diabetic retinopathy, rheumatoid arthritis, hemangioma, psoriasis, and atherosclerosis (Folkman, J., 1976).
Acanthopanax Senticosus is a dried deciduous shrub ( Acanthopanax senticosus Harms) root and rootstock and dried bark. It contains carotene, ligustrin, 7-methyl-6,8-dimethyl coumarin glycoside (7- such as flavonoids, essential oils, polysaccharides, and the like, such as methyl-6,8-dimethylcoumarine glycoside, galactoside, caryophyllene, Eleutheroside B or E , And in recent years, various studies have been conducted on the pharmacological effects on leaves, stems,
Accordingly, the inventors of the present invention have studied various physiological activities possessed by the astringent gut, and confirmed that the astringent fruit extract has an angiogenesis inhibitory effect and thus can be used as a therapeutic agent for various diseases related to angiogenesis.
As a prior art to the present invention, a methanol extract of a medicinal herb having a sea cucumber as a component is disclosed (Korean Patent Laid-Open No. 10-2009-0094637), an anticancer drug containing a water extract of sea cucumber (Korean Patent Laid-Open No. 10-2005-0022945), a technique relating to a therapeutic agent for skin cancer or head and neck cancer containing water extract of Rhizoma roots as an active ingredient (Korean Patent No. 10-0588651), Ogaki fruit extract (Korean Patent Laid-Open Publication No. 10-2012-0085048) and an anticancer drug-containing technique (Korean Patent Laid-Open No. 10-2003-0091760) containing a polysaccharide derived from Ogaki fruit.
It is an object of the present invention to provide a composition for inhibiting angiogenesis containing an extract of Acanthopanax senticosus fruit. More specifically, it is an object of the present invention to provide a composition for inhibiting angiogenesis, which comprises an extract of C1-C4 alcohol or an aqueous solution thereof, which is a viscous fruit.
The present invention relates to a composition for inhibiting angiogenesis containing a C1-C4 alcohol or an aqueous solution extract thereof of Acanthopanax senticosus fruit. Preferably, the present invention may be directed to a composition for inhibiting angiogenesis, which comprises an aqueous solution of 50 to 90% (v / v) ethanol in water.
The present invention also relates to a method for the treatment and / or prophylaxis of angiogenesis, angiofibroma, vascular malformation, arteriosclerosis, vascular adhesion, edema sclerosis, corneal graft angiogenesis, angiogenesis glaucoma, macular degeneration, Retinopathy, retinal degeneration, posterior lens fibrosis, granular conjunctivitis, arthritis, psoriasis, capillary dilatation, purulent granulomas, seborrheic dermatitis, acne, acne, retinopathy, retinopathy of prematurity, neovascular glaucoma, Ovarian cancer, rectal cancer, stomach cancer, anal cancer, colon cancer, ovarian cancer, ovarian cancer, ovarian cancer, ovarian cancer, ovarian cancer, ovarian cancer, Breast cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small bowel cancer, endocrine cancer, thyroid cancer, parathyroid cancer, Cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, spinal cord tumor, brainstem glioma and pituitary adenoma The present invention relates to a pharmaceutical composition for preventing or treating diseases caused by angiogenesis selected from the group consisting of The disease caused by angiogenesis may preferably be a skin melanoma.
The present invention also relates to a health functional food for inhibiting angiogenesis containing the extract of C1-C4 alcohol or its aqueous solution of the above-mentioned Acanthopanax senticosus fruit and a health function for preventing or ameliorating diseases caused by angiogenesis containing the same Provide food.
Hereinafter, the present invention will be described in detail.
The present invention provides a composition for inhibiting angiogenesis, which comprises an extract of C1-C4 alcohol or aqueous solution thereof of a viscera fruit. The C1 to C4 alcohols may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol. The C1-C4 alcohol or the aqueous solution thereof may be an aqueous 50 to 90% (v / v) C1-C4 alcohol aqueous solution, more preferably a 50 to 90% (v / v) aqueous ethanol solution. At this time, the soluble component (various glycoside materials) of the viscose fruit is best extracted under the above-mentioned 50 to 90% (v / v) ethanol aqueous solution solvent condition.
The C1-C4 alcohol or its aqueous solution used in the production of the C1-C4 alcohol or its aqueous solution of the above-mentioned viscose fruit is preferably 1 to 40 times the volume or weight (1 to 40 liters or 1 kg Standard 1 to 40 kg) may be used, preferably 5 to 40 times. The extraction conditions of the Fusarium oxysporum fructus extract may be 1 to 48 hours at 20 to 90 ° C. The above process can be repeated 1 to 4 times.
As a conventional method in the art, the C1-C4 alcohol or an aqueous solution extract thereof is dissolved in water, and then a solution of 1 < RTI ID = 0.0 > The fractions may be further fractionated using more than one species of solvent.
The production temperature of the extract may be 20 to 90 ° C, but is not limited thereto. The extraction time is not particularly limited, but it is preferable to perform extraction within 1 to 48 hours. As the extraction apparatus, a conventional extraction apparatus, an ultrasonic pulverization extractor or a fractionator may be used. The thus prepared dried fruit extract can be removed by hot air drying, vacuum drying or freeze drying. In addition, the C1-C4 alcohol or its aqueous solution extract of the above-mentioned viscose fruit can be purified and used by using column chromatography.
The C.sub.1-C.sub.4 alcohol or its aqueous solution extract of the viscose fruit is subjected to extraction by extraction with an organic solvent (alcohol, ether, acetone, etc.), distillation with hexane and water, and column chromatography, The known methods to be used may be used alone or in a suitable combination and fractionated or purified.
The chromatography can be carried out using silica gel column chromatography, LH-20 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography chromatography, thin layer chromatography (TLC), silica gel vacuum liquid chromatography, and high performance liquid chromatography.
The present invention provides a pharmaceutical composition for inhibiting angiogenesis or a pharmaceutical composition for the prevention or treatment of diseases caused by angiogenesis, which comprises an extract of C1-C4 alcohol or an aqueous solution thereof, which is a fruit of Persimmon juice. The C 1 -C 4 alcohol or its aqueous solution extract of the viscose fruit may be added to the pharmaceutical composition of the present invention in an amount of 0.001 to 100% by weight.
The pharmaceutical composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method have. Examples of carriers, excipients and diluents that can be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose, Lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
The dosage of the pharmaceutical composition of the present invention will depend on the age, sex, body weight of the subject to be treated, the particular disease or condition to be treated, the severity of the disease or condition, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.
The pharmaceutical composition of the present invention can be administered to mammals such as rats, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. Since the compound of the present invention has little toxicity and side effects, it can be safely used even for long-term administration for preventive purposes.
The present invention also relates to a method for preventing or preventing angiogenesis-induced health functional food for inhibiting angiogenesis, comprising a C 1 to C 4 alcohol or an aqueous solution extract thereof and a pharmaceutically acceptable food-aid additive, And provides a health functional food for improvement. The C1-C4 alcohol or its aqueous solution extract of the viscera fruit may be added to the health functional food of the present invention in an amount of 0.001 to 100% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the extract of the present invention can be added include various kinds of drinks, meat, sausage, bread, Snacks, noodles, ice cream, dairy products, soups, ionic drinks, beverages, alcoholic beverages, gums, tea and vitamin complexes.
The composition containing the C1-C4 alcohols or aqueous solution extracts thereof of the present invention is preferably selected from the group consisting of hemangiomas, angiofibromas, vascular malformations, arteriosclerosis, vascular adhesion, edema sclerosis, corneal graft angiogenesis, Macular degeneration, diabetic retinopathy, retinopathy of prematurity, neovascular glaucoma, corneal disease caused by neovascularization, denaturation of spots, pterygium, retinal degeneration, posterior capsular hyperplasia, granular conjunctivitis, arthritis, psoriasis, capillary Cancer, skin cancer, skin melanoma, intra-ocular melanoma, uterine cancer, ovarian cancer, ovarian cancer, ovarian cancer, colon cancer, ovarian cancer, pancreatic cancer, Endometrial carcinoma, cervical cancer, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, endometrial carcinoma, gastric cancer, Renal cell carcinoma, renal pelvic carcinoma, central nervous system tumor, primary central nervous system lymphoma, renal cell carcinoma, endometrial adenocarcinoma, endometrial adenocarcinoma, endometrial adenocarcinoma, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, , A spinal cord tumor, a brain stem glioma, and a pituitary adenoma, and can be used as a pharmaceutical composition or a health functional food for these diseases because it has an effect of preventing, treating or improving diseases induced by angiogenesis.
The present invention relates to a composition for inhibiting angiogenesis, which comprises a fruit extract of Persimmonia japonica, wherein the pharmaceutical composition or the health food containing the extract of Persimmonia japonica is a composition for the treatment of diseases associated with angiogenesis such as cancer, And can be easily used as a health functional food for improvement.
As a prior art to the present invention, a methanol extract of a medicinal herb having a sea cucumber as a component is disclosed (Korean Patent Laid-Open No. 10-2009-0094637), an anticancer drug containing a water extract of sea cucumber (Korean Patent Laid-Open No. 10-2005-0022945), a technique relating to a therapeutic agent for skin cancer or head and neck cancer containing water extract of Rhizoma roots as an active ingredient (Korean Patent No. 10-0588651), Ogaki fruit extract (Korean Patent Laid-Open Publication No. 10-2012-0085048) and an anticancer drug-containing technology (Korean Patent Laid-Open No. 10-2003-0091760) containing a polysaccharide derived from Ogaki fruit, , There is no known prior art which confirms that the aqueous alcoholic solution extract of A. japonica has an inhibitory effect on angiogenesis.
1 is a graph showing changes in size of melanoma cancer tissues in a mouse to which melanoma cancer cells are administered.
FIG. 2 is a photograph of H & E staining obtained by confirming the degree of tumor tissue vascularization in a mouse administered with melanoma cancer cells. FIGS. 2A and 2B are photographs showing tumor tissues of control mice, and FIGS. 2C and 2D are photographs showing tumor tissues of mouse group treated with 60% (v / v) ethanol aqueous solution extract of viscose fruit. FIG. 2B is an enlarged photograph of the tumor tissue of FIG. 2A, and FIG. 2D is an enlarged photograph of the tumor tissue of FIG. 2C.
FIG. 3 is a photograph of the result of tissue staining for confirming the expression level of HIF-1 (Hypoxia-inducible factor-1) in tumor tissues of mice to which melanoma cancer cells were administered. FIGS. 3A and 3B are photographs showing tumor tissues of a control mouse, and FIGS. 3C and 3D are photographs showing tumor tissues of a mouse group treated with 60% (v / v) aqueous ethanol solution of gooseberry fruit. FIG. 3B is an enlarged photograph of the tumor tissue of FIG. 3A, and FIG. 3D is an enlarged photograph of the tumor tissue of FIG. 3C.
FIG. 4 is a photograph of the result of tissue staining for confirming the expression level of VEGFR-2 (vascular endothelial growth factor receptor 2) in tumor tissues of mice to which melanoma cancer cells were administered. FIGS. 4A and 4B are photographs showing tumor tissues of a control mouse, and FIGS. 4C and 4D are photographs of tumor tissues of a mouse group treated with 60% (v / v) aqueous ethanolic extract of viscose fruit. 4B is an enlarged photograph of the tumor tissue of FIG. 4A, and FIG. 4D is an enlarged photograph of the tumor tissue of FIG. 4C.
Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.
≪ Example 1: Preparation of fruit juice extract of Persimmonia japonica &
The fruit used for this experiment was purchased from Pohang Jukjang Ogphi Farming Association. The extract of Persimmon japonicus was prepared by adding 10 l of a 60% (v / v) aqueous ethanol solution to 1 kg of Persimmon juice and extracting it for 3 hours at 80 ° C. After filtration, the mixture was concentrated under reduced pressure at 80 ° C. to 43 brix. The concentrate obtained by concentration under reduced pressure was used for the experiment while being stored at 4 ° C. in a refrigerator.
≪ Example 2 > Measurement of inhibitory effect on tumor formation by extract of Fusarium oxysporum
Example 2-1. Preparation of experimental animals, administration of tumor cells and gooseberry fruit extract
Seven weeks old C57BL / 6J was purchased from Coatec Co., Ltd. and preliminary breeding for one week, then 5 rats were randomly divided into groups. Melanoma cells (B16BL6 mouse melanoma cell, 1 × 10 7 cells in 0.1 ㎖ of PBS) of the hypodermic one side on the side of the male rats 1 weeks cultivation by one group after that caused the cancer tissue is 2 weeks a phosphate buffered saline 2 groups were orally administered with 200 mg / kg of a 60% (v / v) ethanol aqueous solution extract of Example 1 in a 1 ml syringe every day for 2 weeks.
Example 2-2. Identification of the in vivo activity of carbohydrate in the extract of Fusarium oxysporum
In order to confirm the tumor size of the mouse group prepared in Example 2-1, the size of cancer tissue was measured according to the following formula (1), and the results are shown in FIG.
Equation 1
Tumor surface area (mm 3 ) = (L x S 2 ) / 2
L = long length of tumor (mm)
W = short length of tumor (mm)
As shown in FIG. 1, it can be confirmed that the mouse group treated with the aqueous solution of 60% (v / v) ethanol in water of Example 1 of the present invention has a remarkable effect of inhibiting tumor growth. Therefore, it can be seen from the above results that the aqueous solution of 60% (v / v) ethanol in water of the present invention has excellent tumor formation inhibitory effect.
≪ Example 3: Evaluation of in vivo histological efficacy of Fusarium oxysporum fructus extract >
Tumors were collected from control mice transplanted with the melanoma cells (B16BL6 mouse melanoma cells) tested in Example 2 and mice treated with a 60% (v / v) ethanol aqueous solution of gooseberry fruit, / v) paraformaldehyde solution (pH 7.4) for 48 hours. The immobilized tissues were dehydrated through sequential immersion in 70, 80, 90, 95% (v / v) ethanol aqueous solution, 100, 100 and 100% ethanol, After roughing, the sample was embedded in paraffin to prepare a sample for histological examination. To perform H & E (Hematoxylin & Eosin) staining, the embedding sample was cut to a thickness of 4 μm to prepare a section. The prepared sections were hydrated with xylenes and alcohol, and stained with hematoxylin for 5 minutes in Eosin for 1 minute, and the stained samples were observed under a microscope after sealing.
The results of the experiment are shown in Fig. 2. Figs. 2A and 2B show the tumor tissues of the control mice, Figs. 2C and 2D show the tumor tissues of mouse group treated with 60% (v / v) ethanol aqueous solution extract of viscose fruit Represents one photograph. FIG. 2B is an enlarged photograph of the tumor tissue of FIG. 2A, and FIG. 2D is an enlarged photograph of the tumor tissue of FIG. 2C.
Tumor is a complex disease that consists of tumor cells and host stromal cells. The substrate of the tumor consists of a basement membrane, a fibroblast, an extracellular matrix, immune cells, and vasculature. These substrates are recognized as a novel approach to tumor therapy because they affect tumor development and metastasis (Mao, Y. et al. 2013). Double-vessel development plays an important role in tumor development, and vascular development defects may lead to tumor cell growth, necrosis, apoptosis, etc. (Nishida, N. et al., 2006). Referring to Figure 2, a well-developed stroma can be observed with melanoma cells in Figure 2A (control mouse tissue). As a result of observation at a magnification of 400 times, red blood cells, one of blood vessel structures of the substrate part, are observed in Fig. 2B. In addition, apoptotic bodies due to infiltration of immune cells are observed, and these structures are confirmed as a result of active tumor proliferation. In Figure 2C (mouse tissue treated with 60% (v / v) aqueous ethanolic extract of gooseberry fruit), it is observed that the overall development of the substrate is less. As a result of observing the tissue of FIG. 2C at a magnification of 400 times, the development of the substrate supporting the tumor cells was weak in FIG. 2D, and the development of the cytoplasm was generally weaker than that of the control. Especially, the development of red blood cells and blood vessels is weak, and it can be understood that the extract of Fusarium oxysporum is effective in inhibiting tumor growth and inhibiting tumor growth.
EXAMPLE 4 Confirmation of Correlation between Expression of HIF-1 and Fruit Extract of Astragali Radix>
Hypoxia-inducible factors (HIFs) are a type of protein expressed in response to decreased oxygen saturation or hypoxia in cells. Among these, HIF-1 (Hypoxia-inducible factor-1) is expressed at high levels in oxygen-consuming animals and plays a role as a major transcriptional regulator in response to hypoxia. Thus, the expression of HIF-1 increases the expression of erythropoietin, glucose transporters, and vascular endothelial growth factor (VEGF), thereby promoting the transfer of oxygen into the cells.
Immunohistochemical staining was performed to determine the expression of HIF in tissues due to 60% (v / v) ethanol aqueous solution extract. Tumors were collected from control mice transplanted with the melanoma cells (B16BL6 mouse melanoma cells) tested in Example 2 and mice treated with a 60% (v / v) ethanol aqueous solution of gooseberry fruit, / v) paraformaldehyde solution (pH 7.4) for 48 hours. The immobilized tissue was dehydrated through sequential immersion in 70, 80, 90, 95% (v / v) ethanol aqueous solution, 100, 100 and 100% ethanol, and after vitrification through xylene treatment, Embedded in paraffin, and cut to a thickness of 10 mu m to prepare a slice. Antigen retrieval was performed using Retrievagen A (pH 6.0, BD Pharmingen) after deparaffinization with xylene. After blocking for 1 h in 3% (v: v) FBS (Fetal Bovine serum in water), the primary antibody (ab16066, Abcam) of HIF-1 was added at a ratio of 1: 500 Diluted and incubated for 1 hour. After washing with PBS (phosphate buffer solution) three times for 5 minutes, the secondary antibody was diluted at a ratio of 1: 500 (v: v) and incubated for 1 hour. After washing three times for 5 minutes in PBS, the cells were developed with 3,3'-diaminobenzidine (3,3'-diaminobenzidine). And then observed under a microscope through an inclusion process.
The results of the experiment are shown in Fig. 3. Figs. 3A and 3B show the tumor tissues of the control mice, Figs. 3C and 3D show the tumor tissues of mouse group treated with 60% (v / v) ethanol aqueous solution extract of viscose fruit Represents one photograph. FIG. 3B is an enlarged photograph of the tumor tissue of FIG. 3A, and FIG. 3D is an enlarged photograph of the tumor tissue of FIG. 3C.
Referring to FIG. 3, HIF-1 positive reactivity (brown) was observed in FIG. 3A and FIG. 3B (control mouse tissue), whereas FIG. 3C and FIG. 3D (60% / v) ethanol aqueous solution extract treated mice), the expression of HIF-1 was remarkably reduced in comparison with the control group.
Example 5 Confirmation of Correlation between Vasectomy Fruit Extract and VEGFR-2 Expression [
VEGFR-2 (vascular endothelial growth factor receptor 2) is a major factor associated with VEGF-derived vascular endothelial cells. Expression of VEGFR-2 is an essential factor in the proliferation and chemotaxis of VEGF and plays an important role in vivo in vivo.
Immunohistochemical staining was performed to determine the expression of VEGFR-2 in the tissues due to 60% (v / v) ethanol aqueous solution extract. Tumors were collected from control mice transplanted with the melanoma cells (B16BL6 mouse melanoma cells) tested in Example 2 and mice treated with a 60% (v / v) ethanol aqueous solution of gooseberry fruit, / v) paraformaldehyde solution (pH 7.4) for 48 hours. The immobilized tissue was dehydrated through sequential immersion in 70, 80, 90, 95% (v / v) ethanol aqueous solution, 100, 100 and 100% ethanol, and after vitrification through xylene treatment, Embedded in paraffin, and cut to a thickness of 10 mu m to prepare a slice. Antigen retrieval was performed using Retrievagen A (pH 6.0, BD Pharmingen) after deparaffinization with xylene. The cells were then blocked for 1 hour in 3% (v: v) FBS and incubated in a 1: 1,000 (v: v) dilution of the primary antibody (# 3791, Cell signaling) of VEGFR- Respectively. After washing three times for 5 minutes in PBS, the secondary antibody was incubated in a 1: 500 (v: v) dilution for 1 hour. After washing three times for 5 minutes in PBS, the cells were developed with 3,3'-diaminobenzidine. And then observed under a microscope through an inclusion process.
4A and 4B show the tumor tissues of the control mice, FIGS. 4C and 4D show the tumor tissues of mouse group treated with 60% (v / v) ethanol aqueous solution extract of viscose fruit Represents one photograph. 4B is an enlarged photograph of the tumor tissue of FIG. 4A, and FIG. 4D is an enlarged photograph of the tumor tissue of FIG. 4C.
Referring to FIG. 4, it is confirmed that the expression of VEGFR-2, which plays an important role in vascular development, is strongly expressed in mouse tumor tissues in FIG. 4A and FIG. 4B (control mouse tissue). The expression of VEGFR-2 is hardly observed in the tumor tissues of mouse group treated with the 60% (v / v) ethanol aqueous solution extract of the viscose fruit of Figs. 4C and 4D.
≪ Formulation Example 1 >
Formulation Example 1-1. Manufacture of tablets
200 g of the 60% (v / v) ethanol aqueous solution extract of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. To this mixture was added a 10% gelatin solution, which was pulverized and passed through a 14-mesh sieve. This was dried, and a mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.
Formulation Example 1-2. Injection preparation
1 g of a 60% (v / v) aqueous solution of ethanol of the present invention, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20 DEG C for 30 minutes.
<Formulation Example 2: Food Preparation>
Formulation Example 2-1. Manufacture of cooking seasonings
A 60% (v / v) ethanol aqueous solution extract of the present invention was added to the cooking seasoning at 1 wt% to prepare a cooking sauce for health promotion.
Formulation Example 2-2. Manufacture of flour food products
A food for health promotion was prepared by adding a 60% (v / v) ethanol aqueous solution extract of the present invention to 0.1% by weight of wheat flour and preparing bread, cake, cookies, crackers and noodles using the mixture .
Preparation Example 2-3. Manufacture of soups and gravies
Health enhancing soup and juice were prepared by adding 60% (v / v) ethanol aqueous solution extract of the present invention to the soup and juice at 0.1 wt%.
Formulation Example 2-4. Manufacture of dairy products
An aqueous solution of 60% (v / v) ethanol in water of the present invention was added to milk in an amount of 0.1% by weight, and various dairy products such as butter and ice cream were prepared using the milk.
Formulation Example 2-5. Vegetable juice manufacturing
A vegetable juice for health promotion was prepared by adding 0.5 g of a 60% (v / v) ethanol aqueous solution extract of the present invention to tomato juice or carrot juice 1,000 ml.
Formulation Example 2-6. Manufacture of fruit juice
Health enhancing fruit juice was prepared by adding 0.1 g of the 60% (v / v) ethanol aqueous solution extract of the present invention to apple juice or grape juice 1,000 ml.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150167290A KR101721780B1 (en) | 2015-11-27 | 2015-11-27 | Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150167290A KR101721780B1 (en) | 2015-11-27 | 2015-11-27 | Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101721780B1 true KR101721780B1 (en) | 2017-03-31 |
Family
ID=58500776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150167290A KR101721780B1 (en) | 2015-11-27 | 2015-11-27 | Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101721780B1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030091760A (en) | 2002-05-28 | 2003-12-03 | 주식회사 엠디바이오알파 | Active fraction having anti-cancer and anti-metastasis isolated from acanthopanax species and fruits |
| KR20050022945A (en) | 2003-08-27 | 2005-03-09 | 장수군 | Anticancer drug containing extract of Acanthopanax senticosus |
| KR20090094637A (en) | 2008-03-03 | 2009-09-08 | 동아대학교 산학협력단 | Anti-Cancer Composition Containing an Extract of Chinese Herb as an Effective Ingredient |
| KR20120085048A (en) | 2011-01-21 | 2012-07-31 | 경희대학교 산학협력단 | Pharmaceutical compositions for prevention and treatment of cancer diseases containing the fruits of acanthopanax sessiliflorus extracts, fractions, the isolated compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
-
2015
- 2015-11-27 KR KR1020150167290A patent/KR101721780B1/en active IP Right Grant
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030091760A (en) | 2002-05-28 | 2003-12-03 | 주식회사 엠디바이오알파 | Active fraction having anti-cancer and anti-metastasis isolated from acanthopanax species and fruits |
| KR20050022945A (en) | 2003-08-27 | 2005-03-09 | 장수군 | Anticancer drug containing extract of Acanthopanax senticosus |
| KR100588651B1 (en) | 2003-08-27 | 2006-06-12 | 장수군 | Drug containing as an effective ingredient the root extract of Acanthopanax senticosus for the prevention and treatment of skin and head-and-neck cancer |
| KR20090094637A (en) | 2008-03-03 | 2009-09-08 | 동아대학교 산학협력단 | Anti-Cancer Composition Containing an Extract of Chinese Herb as an Effective Ingredient |
| KR20120085048A (en) | 2011-01-21 | 2012-07-31 | 경희대학교 산학협력단 | Pharmaceutical compositions for prevention and treatment of cancer diseases containing the fruits of acanthopanax sessiliflorus extracts, fractions, the isolated compounds therefrom, or the pharmaceutically acceptable salts as an active ingredient |
Non-Patent Citations (14)
| Title |
|---|
| Fidler, I. J. et al. (1994) The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79:185~188 |
| Folkman, J. (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1:27~31 |
| Folkman, J. et al. (1976) Relation of vascular proliferation to tumor growth. Int. Rev. Exp. Path. 16:207~248. |
| Folkman, J. et al. (1987) Agiogenic factors. Science 235:442~447. |
| Fox, S. B. et al. (1996) Tumor angiogenesis. J. Pathol. 179:232~237. |
| Hanahan, D. et al. (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353~364 |
| Leung, D. W. et al. (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306~1309. |
| Mao, Y. et al.(2013). "Stromal Cells in Tumor Microenvironment and Breast Cancer", Cancer metastasis reviews 32(1-2):303-315. |
| Myong Jo Kim 외 4인. In vitro antioxidant activity and anticancer effects of the extracts from Eleutherococcus senticosus Max. Korean J. Medicinal Crop Sci, 2002, Vol. 10, No. 4, pp. 269-272 * |
| Nishida, N. et al.(2006). "Angiogenesis in Cancer", Vascular health and risk management 2(3):213-219. |
| Weidner, N. (1995) Intratumor microvessel density as a prognostic factor in cancer. Am. J. Pathol. 147:9~19. |
| 임정대 외 1인. 가시오갈피 열매 추출물의 생리활성 검정. 한국작물학회지. 2011년, 제56권, 제1호, pp. 1-7 * |
| 전윤영 외 5인. 가시오갈피 열매 추출물의 항돌연변이원성 및 세포독성 효과. 한국식품저장유통학회지. 2003년, 제10권, 제3호, pp. 394-400* * |
| 정현우 외 3인. 오가피 50% 에탄올 추출물이 면역, 항암, 뇌혈류 및 혈압에 미치는 영향. 동의생리병리학회지. 2005년, 제19권, 제5호, pp. 1213-1219 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9649351B2 (en) | Anti-angiogenic agents and anti-obesity substances applied with anti-angiogenesis from natural products | |
| KR101797813B1 (en) | Compositions for preventing or treating bladder cancer comprising citrus fermentd broth with Kombucha as an active ingredient | |
| WO2007066928A1 (en) | Use of the extract of caesalpinia sappan l. and compounds therefrom | |
| KR101872950B1 (en) | Composition for inhibiting growth or killing of brain cancer stem cells comprising a mixture extracts | |
| Reboredo-Rodriguez | Potential roles of berries in the prevention of breast cancer progression | |
| KR20110114346A (en) | Anti-cancer composition containing eriobotrya japonica extract | |
| KR101721780B1 (en) | Composition comprising extract of Acanthopanax senticosus for anti-angiogenesis | |
| KR101579820B1 (en) | Pharmaceutical compositions for the treatment of cancer metastasis or inhibition of metastasis containing Quassia undulata extracts as active fractions | |
| KR101720610B1 (en) | The pharmaceutical composition Inula helenium hexane fractions thereof or compound isolated from the fraction comprising inhibitory activity of STAT for prevention or treatment of breast cancer | |
| EP2762147B1 (en) | Pharmaceutical composition containing puerariae flos extracts as active ingredients for preventing and treating endometriosis | |
| KR102558650B1 (en) | Composition for preventing, ameliorating or treating prostate cancer comprising Hippocampus abdominalis and herbal medicine mixed extract as effective component | |
| KR102432990B1 (en) | Composition for the prevention of skin cancer of inhibition of skin cancer metastasis containing citrus unshiu peel extract | |
| KR102475985B1 (en) | Composition for preventing or treating rheumatoid arthritis comprising combination extract containing Rhei Rhizoma, Scutellariae Radix and Coptidis Rhizoma | |
| KR102633837B1 (en) | Method for preparing mixture of Scutellariae Radix extract and Coptidis Rhizoma extract having excellent improvement and treatment for rheumatoid arthritis, and composition for preventing or treating rheumatoid arthritis comprising thereof | |
| KR101185901B1 (en) | Anti-cancer composition containing eupatorium japonicum extract | |
| KR102119812B1 (en) | Composition for Preventing or Treating Uterine Myoma Comprising Rhus verniciflua Stokes Extract | |
| KR102376510B1 (en) | Composition for preventing, improving or treating prostate disease comprising extract of Allium macrostemom Bunge as effective component | |
| KR102156701B1 (en) | A composition for inhibiting cancer metastasis comprising Oenothera odorata extracts | |
| KR101636348B1 (en) | Pharmaceutical composition and functional food composition for prevention or treatment of angiogenesis-related diseases comprising Meliosma oldhamii Maxim extraction | |
| KR20090110602A (en) | The composition for the treatment of cancers and inhibition of metastasis containing extracts and fractions of the magnolia obovata | |
| KR20160129809A (en) | Pharmaceutical composition having angiogenesis inhibition activity comprising cold water based extract of Cinnamomum cassia | |
| KR101880515B1 (en) | Composition for preventing, improving or treating ischemic disease comprising extract of Tetragonia tetragonoides as effective component | |
| KR20160002068A (en) | Pharmaceutical composition having angiogenesis inhibition activity comprising cold water based extract of Cinnamomum cassia | |
| KR20210121495A (en) | Composition for the prevention of skin cancer of inhibition of skin cancer metastasis containing angelica dahurica radix extract | |
| KR20140036513A (en) | Pharmaceutical compositions for the treatment of cancer metastasis or inhibition of metastasis containing quassia undulata extracts as active fractions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant |