WO2015068940A1 - Pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as active ingredient - Google Patents
Pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as active ingredient Download PDFInfo
- Publication number
- WO2015068940A1 WO2015068940A1 PCT/KR2014/007719 KR2014007719W WO2015068940A1 WO 2015068940 A1 WO2015068940 A1 WO 2015068940A1 KR 2014007719 W KR2014007719 W KR 2014007719W WO 2015068940 A1 WO2015068940 A1 WO 2015068940A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- artemisinin
- osteoporosis
- preventing
- pharmaceutical composition
- pharmaceutically acceptable
- Prior art date
Links
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 title claims abstract description 87
- 229960004191 artemisinin Drugs 0.000 title claims abstract description 87
- 229930101531 artemisinin Natural products 0.000 title claims abstract description 86
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 50
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 22
- 239000004480 active ingredient Substances 0.000 title claims abstract description 21
- 210000000963 osteoblast Anatomy 0.000 claims abstract description 23
- 210000002997 osteoclast Anatomy 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 20
- 230000004069 differentiation Effects 0.000 claims description 18
- 235000013402 health food Nutrition 0.000 claims description 9
- 235000001405 Artemisia annua Nutrition 0.000 claims 1
- 240000000011 Artemisia annua Species 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 38
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000011282 treatment Methods 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 18
- -1 artehaninin B Chemical compound 0.000 description 16
- 210000000988 bone and bone Anatomy 0.000 description 16
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 13
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- 210000002798 bone marrow cell Anatomy 0.000 description 11
- 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 9
- 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 241000254158 Lampyridae Species 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 230000004072 osteoblast differentiation Effects 0.000 description 6
- 229940011871 estrogen Drugs 0.000 description 5
- 239000000262 estrogen Substances 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 4
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000228212 Aspergillus Species 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108090000445 Parathyroid hormone Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 230000000996 additive effect Effects 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PLQMEXSCSAIXGB-SAXRGWBVSA-N (+)-artemisinic acid Chemical compound C1=C(C)CC[C@H]2[C@H](C)CC[C@@H](C(=C)C(O)=O)[C@H]21 PLQMEXSCSAIXGB-SAXRGWBVSA-N 0.000 description 2
- VWGPQZZLIAQJCE-DWIPZSBTSA-N (1R,4S,5S,8R,9S,12R,14R)-4,8,12-trimethyl-2,13-dioxatetracyclo[7.5.0.01,5.012,14]tetradecan-3-one Chemical compound C([C@H]1[C@H](C)CC2)C[C@@]3(C)O[C@H]3[C@@]31[C@@H]2[C@H](C)C(=O)O3 VWGPQZZLIAQJCE-DWIPZSBTSA-N 0.000 description 2
- 102000013563 Acid Phosphatase Human genes 0.000 description 2
- 108010051457 Acid Phosphatase Proteins 0.000 description 2
- 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 2
- 241000208838 Asteraceae Species 0.000 description 2
- 229940122361 Bisphosphonate Drugs 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 2
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102100036893 Parathyroid hormone Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000004663 bisphosphonates Chemical class 0.000 description 2
- 210000002805 bone matrix Anatomy 0.000 description 2
- 230000010478 bone regeneration Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000001848 dysentery Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000009245 menopause Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000013599 spices Nutrition 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
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000002303 tibia Anatomy 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- KPCRYSMUMBNTCK-UHFFFAOYSA-N 3',5-dihydroxy-3,4',7-trimethoxyflavone Chemical compound C=1C(OC)=CC(O)=C(C(C=2OC)=O)C=1OC=2C1=CC=C(OC)C(O)=C1 KPCRYSMUMBNTCK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- ITZMJCSORYKOSI-AJNGGQMLSA-N APGPR Enterostatin Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N1[C@H](C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CCC1 ITZMJCSORYKOSI-AJNGGQMLSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 229940078581 Bone resorption inhibitor Drugs 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000219357 Cactaceae Species 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 244000180278 Copernicia prunifera Species 0.000 description 1
- 235000010919 Copernicia prunifera Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 208000008924 Femoral Fractures Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 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
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 206010027304 Menopausal symptoms Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 102000004067 Osteocalcin Human genes 0.000 description 1
- 108090000573 Osteocalcin Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 229920002230 Pectic acid Polymers 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 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 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940070021 anabolic steroids Drugs 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- PLQMEXSCSAIXGB-UHFFFAOYSA-N artemisininic acid Natural products C1=C(C)CCC2C(C)CCC(C(=C)C(O)=O)C21 PLQMEXSCSAIXGB-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 235000020964 calcitriol Nutrition 0.000 description 1
- 239000011612 calcitriol Substances 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- JYGAZEJXUVDYHI-DGTMBMJNSA-N dihydroartemisinic acid Chemical compound C1CC(C)=C[C@@H]2[C@H]([C@@H](C)C(O)=O)CC[C@@H](C)[C@@H]21 JYGAZEJXUVDYHI-DGTMBMJNSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 241001233957 eudicotyledons Species 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001375 lactose Drugs 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
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000005088 multinucleated cell Anatomy 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 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
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940124595 oriental medicine Drugs 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 206010041569 spinal fracture Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 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 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Definitions
- composition for the prevention and treatment of osteoporosis comprising artemisinin as an active ingredient
- the present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemisinin (artemisinin) as an active ingredient.
- artemisinin artemisinin
- Bone is a specialized tissue that combines a hardened calcified surface with an internal cellular component called the bone marrow.
- the combination of these two physiologically different structures is due to the life-long process of bone remodeling, which causes osteoclasts in the bone marrow It is explained by the bone formation of bone matrix by osteoblasts that gathered at the site where bone resorption occurred by gathering and destroying bones on the surface (Park JS, Natl. Nutr., 215, ⁇ 25). -31, 2000).
- Osteoblasts located on the bone surface have alkaline phosphatase (ALP), a glycoprotein enzyme in the cell membrane, type I collagen (Col), osteocalcin (0CN), and osteopontin (0PN). And secrete and calcify bone matrix substances such as bone sialoprotein (BSP) (Collier FM et al., Endocrinology, 139 (3), ⁇ 1258-1267, 1998). Bone maintains a constant call volume by balancing osteoblast and osteoclast activity, and bone regeneration occurs continuously due to their activity. However, when osteoclast activity is increased than osteoblasts, bone mass decreases to induce osteoporosis, and postmenopausal women cause osteoporosis due to a decrease in blood estrogen concentration.
- ALP alkaline phosphatase
- Col type I collagen
- osteocalcin CN
- osteopontin osteopontin
- BSP bone sialoprotein
- Osteoporosis is one of the most important social problems at present, and various fractures, especially femoral fractures or vertebral fractures, which are easily caused by the weakening of bones rather than the symptoms themselves, limit the long-term activity and lead to a healthy life. It is known to provide a cause for 15% of cases. Bone mass is influenced by several factors, including genetic factors, nutrition, hormone changes, differences in exercise and lifestyle, and the causes of osteoporosis include old age, lack of exercise, low weight, smoking, low calcium diet, menopause, Ovarian ablation is known.
- the bones are higher than the whites due to lower bone resorpt ion levels, which is usually the highest at 14 to 18 years of age and decreases by about 1% per year in old age.
- bone reduction continues after 30 years of age, and when menopause reaches bone growth rapidly due to hormonal changes.
- osteoporosis is unavoidable for elderly people, especially postmenopausal women, and as the population ages in developed countries, interest in osteoporosis and its treatments is gradually increasing. It is also known that around $ 130 billion of market is formed around the world for the treatment of bone diseases and is expected to increase further. And the development of a bone resorption inhibitor is currently in progress.
- ER a relatively high distribution of bone estrogen receptor subtypes
- drugs that inhibit bone resorption and include SERMs and fluoride are effective for short-term ( ⁇ 5 years) treatment of bone mineral density but increase bone mass with long-term administration.
- long-term administration is expected to result in a sustained increase in bone mineral density and development of safe prophylactic and therapeutic agents with fewer side effects.
- Bone regeneration unit by inhibiting or proliferating osteoblasts As a drug to increase the activity and the like l, 25 (0H) 2D3 (calcitriol) (calcitonin), PTH (parathyroid hormone, PTH), bisphosphonates (bisphosphonate) formulation.
- Cactus C4rie7? / S / a annua L. is an annual herb of a dicotyledon plant, Asteraceae, which belongs to Asteraceae and is distributed in Korea, Japan, Thailand, Taiwan, Siberia, etc. .
- the plant is about lm tall and has a hairy, peculiar smell throughout the grass.
- oriental medicine it is used to treat fever, cold, child's game, dyspepsia, dysentery, etc. It has been used as a fragrance in spices, spices and vinegar.
- the present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemisinin (artemisinin).
- the present invention provides a pharmaceutical composition for osteoporosis prevention and treatment comprising artemisinin (artemi sinin) or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present invention also provides a health food for osteoporosis prevention and improvement comprising artemisinin or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present invention also provides a method for treating osteoporosis comprising administering an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof to an individual suffering from osteoporosis.
- the present invention also provides a method for preventing osteoporosis comprising administering to a subject an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof.
- the present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a pharmaceutical composition for the prevention and treatment of osteoporosis.
- the present invention provides artemisinin or a pharmaceutically acceptable salt thereof for use as a health food for preventing and improving osteoporosis.
- the present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemi sinin as an active ingredient, artemisinin proliferates osteoblasts and significantly inhibits the formation and activity of osteoclasts.
- artemisinin can be usefully used as an active ingredient of the pharmaceutical composition for preventing and treating osteoporosis.
- [Brief Description of Drawings] 1 is a diagram showing the effect of artemisinin on TRA tartrate-resi stant acid phosphatase (TRAP) activity.
- FIG. 2 is a diagram showing the effect of artemisinin on osteoclast differentiation.
- 3 is a diagram showing the effect of artemisinin on ALP (alkal ine phosphatase, ALP) activity.
- ALP alkal ine phosphatase
- FIG. 4 is a diagram showing the effect of artemisinin on osteoblast differentiation.
- the present invention provides a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemi sinin or an acceptable salt thereof as an active ingredient.
- the present invention also provides a method for treating osteoporosis comprising administering an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof to an individual suffering from osteoporosis.
- the present invention also provides a method for preventing osteoporosis comprising administering to a subject an effective amount of artemisinin or a pharmaceutically acceptable salt thereof.
- the present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a pharmaceutical composition for the prevention and treatment of osteoporosis.
- the artemisinin is isolated from the firefly extract.
- the artemisinin is preferably represented by the following [Formula 1]:
- the artemisinin preferably inhibits the differentiation of osteoclasts, but is not limited thereto.
- the artemisinin preferably promotes differentiation of osteoblasts, but is not limited thereto.
- the present inventors obtained bone marrow cells by separating the tibia and the femur in 5 to 6 week old C57BL / 6 mice.
- the effect of artemisinin using a tartrate-resistant acid phosphatase (TRAP) staining method was used.
- TRIP tartrate-resistant acid phosphatase
- artemisinin according to the invention of the osteoblasts By proliferating and significantly inhibiting the formation and activity of osteoclasts, the artemisinin or a pharmaceutically acceptable salt thereof can be usefully used as an active ingredient of a pharmaceutical composition for preventing and treating osteoporosis.
- the composition containing artemisinin of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the above components.
- composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additive may include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone colloidal silicon dioxide, calcium hydrogen phosphate, Lactose, Manni, Peel, Arabian Rubber, Pregelatinized Starch, Corn Starch, Powdered Salose, Hydroxypropyl Cellulose, Opadry, Sodium Starch Glycolate, Carnauba Lead, Synthetic Aluminum Silicate, Stearic Acid, Stearic Acid Magnesium, aluminum stearate, calcium stearate, sucrose, textose, sorbbi and talc can be used.
- the pharmaceutically acceptable additive according to the present invention is preferably included 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
- composition of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, the fillers, extenders, binders, wetting agents, disintegrating agents, and the diluents or excipients of surfactants are commonly used. It can be prepared using.
- Solid form preparations for oral administration include tablets, pills, powders, granules, capsulants, etc. These solid form preparations contain at least one excipient such as starch, Calcium carbonate, sucrose, etc. ), Lactose or gelatin, and the like.
- lubricants such as magnesium styrate talc may also be used.
- Oral liquid preparations include suspensions, solvents, emulsions and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, Suspensions, emulsions, lyophilized preparations, suppositories may be included.
- the non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl acrylate, etc. may be used.
- As a base of suppositories wi tepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
- composition of the present invention can be administered orally or parenterally according to the desired method, the external or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intramuscular injection It is desirable to choose all. Dosage varies according to the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, and severity of disease.
- the dosage of the composition of the present invention varies depending on the patient's weight, age, sex, health status, diet, time of administration, administration method, excretion rate and severity of the disease, the daily dosage is Aspergillus terius extract It is 0.0001 to 100 mg / kg, preferably 0.0 to 10 mg / kg based on the amount of can be administered 1 to 6 times a day.
- composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of inflammatory diseases.
- Artemisinin of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful.
- Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and Non-toxic organic acids such as alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids, acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-lluenesulfonic acid, tartaric acid and fumaric acid.
- inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates
- These pharmaceutically harmless salts include sulfate, pyrosulfate, bisulfate, sulfite, Bisulfite, nitrate, phosphate, monohydrogen phosphate 0 dihydrogen phosphate, metaphosphate, pyrophosphate chlora bromide, iodide, fluoride, acetate, propione ⁇ decanoate, caprylate, Acrylate, Formate, Isobutyre 0 Caprate, Heptanoate, Propylate, Oxalate, Malone 0 Succinate, Suberate, Sebacate, Fumarate, Mali 0 Butyne-1, 4-Diate, Nucleic Acid -1, 6-dioate, benzoate, chlorobenzo 0 methylbenzoate, dinatro benzoate, hydroxybenzoate o methoxybenzoate, phthalate, terephthalate, benzene sulfone.
- Acid addition salt according to the present invention is a conventional method, for example, by dissolving a derivative of formula (1) in an organic solvent, such as methanol, ethanol, acetone, methylene chloride, acetonitrile and the like, and the organic acid or inorganic acid is added to filter the precipitate produced It may be prepared by drying, or the solvent and the excess acid may be prepared by distillation under reduced pressure, followed by drying or crystallization under an organic solvent.
- an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile and the like
- Bases can also be used to make pharmaceutically acceptable metal salts.
- Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the compound salt at no cost, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt.
- Silver salts are also obtained by reacting alkali or alkaline earth metal salts with a suitable negative salt (eg, silver nitrate).
- the present invention is artemisinin (ar temi s inin) or pharmaceutically thereof It provides a health food for preventing and improving osteoporosis comprising an acceptable salt as an active ingredient.
- the present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a health food for preventing and improving osteoporosis.
- the artemisinin is isolated from the firefly extract.
- the artemisinin is preferably represented by the following [Formula 1]:
- the artemisinin preferably inhibits the differentiation of osteoclasts, but is not limited thereto.
- -Artemisinin is preferred to promote the differentiation of osteoblasts, but is not limited thereto.
- Artemisinin according to the present invention exhibits an effect of proliferating osteoblasts and significantly inhibiting the formation and activity of osteoclasts, such artemisinin or a pharmaceutically acceptable salt thereof prevents osteoporosis. And it can be usefully used as an active ingredient of the improved health food composition.
- Examples of the food to which the substance may be added include various foods such as confectionery, bread and noodles, drinks such as water, soft drinks and fruit drinks, gums, teas, vitamin complexes, seasonings, and health functional foods. And includes all of the health functional foods in the ordinary sense.
- the terrain of the present invention can be added as is to foods or used with other foods or food ingredients, and can be suitably used according to conventional methods.
- the combined amount of the active ingredient can be suitably determined depending on the purpose of use (prevention or improvement).
- the amount of the compound in the health food can be added to 0.01 to 15% by weight, preferably from 0.01 to 5% by weight of the total food weight, and 0 to 5.0 g, preferably from 100 to 100 in the health beverage composition Preferably 0.01 to 1.0 g.
- the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
- the health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the compound as essential ingredients in the ratios indicated, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, such as ordinary drinks.
- natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, and the like, and polysaccharides, such as conventional sugars such as textine, cyclotextine, and sugar alcohols such as Xyl, Sorbi, Erisli, etc. to be.
- natural flavoring agents tacumakin, stevia extract, etc.
- synthetic flavoring agents sacharin, aspartan, etc.
- the proportion of natural carbohydrates is generally from about 0.01 to 2.0 g, preferably from about 0.01 to 1.0 g per 100 compositions of the present invention.
- the Aspergillus terius extract of the present invention or a fraction thereof may be used for the preparation of natural fruit juices and fruit juice beverages and vegetable beverages. It may contain pulp. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of about 20 parts by weight per 100 parts by weight of the Aspergillus terius extract or fractions thereof.
- the present invention will be described in detail by way of examples.
- Example 1 Isolation of Artemisinin from Extract from Firefly
- Artemisinin isolated from the firefly extract was purchased from Enzo Li fe Sciences (Cat #: ALX-350-219-G001).
- Bone marrow cells were obtained by separating tibia and femur from 5 to 6 week old C57BL / 6 mice. The isolated bone marrow cells were cultured for 3 days in ⁇ — minimum essential medium ( ⁇ MEM) containing K »fetal bovine serum (FBS) and 50 ng / ml M— CSF. The cells were removed and the attached cells were used as bone marrow macrophages (mils). The macrophages were then incubated for 4 days in a medium containing 50 ng / ml M-CSF and 100 ng / ml RANKL. Staining was performed using tartrate-resistant acid phosphatase (TRAP) and TRAP-positive multinucleated cells were used as osteoclasts.
- TRAP tartrate-resistant acid phosphatase
- the bone marrow cells cultured by the method described in Example ⁇ 2-1> were treated with M-CSF and RANKLE and treated with artemisinin by concentration during differentiation into osteoclasts, followed by culturing for 4 days. After incubation, the medium was removed and the cells were washed with PBS. Then, the cells were fixed with 10% formalin for 5 minutes and washed three times with distilled water. Chromogenic substrate was added to the cells in 50 ⁇ and stained at 37 0 C for 30 minutes and observed under a microscope ( Figure 2).
- TRAP activity was added to the culture supernatant s by adding chromogenic substrate / tartrate-containing buffer at 170 ⁇ in culture supernatant s and reacting at 37 ° C for 3 hours. Absorbance was measured at 540 nm using an EUSA reader (Molecular Devices, Calif., USA).
- FBS fetal bovine serum, Gibco Invi trogen, Grand Island
- DMEM medium DMEM, Hyclone, Logan, UT, USA. Then C2C12 cells were placed in a 96-well plate.
- ALP Alkaline phosphatase
- Alkaline phosphatase a serum enzyme, is an enzyme that is an indicator of bone formation and is produced during the differentiation of osteoblasts (Zhao Yet al., Biol. Pharm. Bull., 28 (8), ppl371-1376, 2005).
- the present invention relates to a pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as an active ingredient, the artemisinin proliferates osteoblasts, osteoclast formation and active ol significantly By showing the inhibitory effect, the artemisinin can be usefully used as an active ingredient of the pharmaceutical composition for preventing and treating osteoporosis.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as an active ingredient, wherein the artemisinin increases osteoblast and exhibits an effect of significantly inhibiting the formation and activity of osteoclast, and thus the artemisinin may be usefully used as an active ingredient in a pharmaceutical composition for preventing or treating osteoporosis.
Description
【명세서】 【Specification】
[발명의 명칭】 [Name of invention]
아르테미시닌을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물 Pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemisinin as an active ingredient
【기술분야】 Technical Field
본 발명은 아르테미시닌 (artemisinin)을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물에 관한 것이다. 【배경기술】 The present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemisinin (artemisinin) as an active ingredient. Background Art
골은 석회화된 견고한 표면과 골수로 불리는 내부의 세포 성분이 결합된 특수조직이다. 생리적으로 상이한 이 두 구조의 결합은 일생을 두고 지속되는 골의 재형성 (bone remodeling) 과정에 기인한 것인데, 이는 골에 가해지는 호르몬이나 물리적 자극에 의해 골수에 있는 파골세포 (osteoclast)들이 골의 표면으로 모여 골을 파들어가면서 파괴하는 골흡수 (bone resorption)가 일어난 자리에 모여든 조골세포 (osteoblast)에 의한 골기질의 합성 (bone formation)으로 설명된다 (Park JS, Natl. Nutr. , 215, ρρ25-31, 2000) . Bone is a specialized tissue that combines a hardened calcified surface with an internal cellular component called the bone marrow. The combination of these two physiologically different structures is due to the life-long process of bone remodeling, which causes osteoclasts in the bone marrow It is explained by the bone formation of bone matrix by osteoblasts that gathered at the site where bone resorption occurred by gathering and destroying bones on the surface (Park JS, Natl. Nutr., 215, ρρ25). -31, 2000).
골표면에 위치하는 조골세포는 세포막에 당단백 효소인 알칼리 포스파타제 (alkaline phosphatase, ALP)를 가지고 있으며 I형 콜라겐 (type I Collagen, Col), 오스테오칼신 (osteocalcin, 0CN), 오스테오폰틴 (osteopontin, 0PN), 뼈 시알로단백 (bone sialoprotein, BSP)과 같은 골기질 물질을 분비하고 석회화시키는 역할을 한다 (Collier FM et al. , Endocrinology, 139(3), ρρ1258-1267, 1998). 골은 조골세포와 파골세포 활성의 균형을 유지함으로 콜량이 일정하게 유지되며 이들의 활성으로 골의 재생이 지속적으로 일어난다. 그러나 조골세포보다 파골세포의 활성이 증가할 때 골량이 감소하여 골다공증을 유발하고, 폐경기 이후의 여성은 혈중 에스트로겐농도 감소로 골다공증을 유발한다.
골다공증은 현재 가장 중요한 사회적 문제 중 하나로 그 증세 자체보다는 골의 약화에 따라 용이하게 초래되는 각종 골절, 특히 대퇴골 골절 또는 척추골절 등이 장기간 활동을 제한하여 건강한 생활을 영위할 수 없고, 결과적으로 노인층 사망의 15%에 대한 원인제공을 하는 것으로 알려져 있다. 골량은 유전적 요인, 영양 섭취, 호르몬의 변화, 운동 및 생활 습관의 차이 등 여러 가지 요인들에 의해 영향을 받으며, 골다공증의 원인으로는 노령, 운동 부족, 저체중, 흡연, 저칼슘 식이, 폐경, 난소 절제 둥이 알려져 있다. 한편 개인차는 있지만 백인보다는 혹인이 골 재흡수 수준 (bone resorpt ion level )이 낮아 골량이 더 높으며 , 대개 골량은 14~18세에 가장 높고 노후에는 1년에 약 1%씩 감소한다. 특히 여성의 경우 30세 이후부터 골 감소가 지속적으로 진행되며, 폐경기에 이르면 호르몬 변화에 의해 골 감소가 급격히 진행된다. 이와 같이 골다공증은 정도에 차이는 있으나 노년층, 특히 폐경기 이후의 여성에게 있어서는 피할 수 없는 증상으로, 선진국에서는 인구가 노령화됨에 따라 골다공증 및 그 치료제에 대한 관심이 점차 증가되고 있다. 또한, 전세계적으로 골질환 치료와 관련되어 약 1 ,300억 달러의 시장이 형성되어 있는 것으로 알려져 있으며 앞으로 더 증가할 것으로 예상되기 때문에, 세계적인 각 연구 기관과 제약회사에서는 골 질환 치료제 개발에 많은 투자를 하고 있고 현재 골 흡수 억제제의 개발이 활발히 진행되고 있다. 골다공증과 관련하여 과거에는 주로 골의 무기질, 즉 칼슘과 인의 대사이상을 중심으로 그 연구가 진행되어 왔으나, 이의 발병 기전 규명에는 큰 진전을 보지 못하였다. 현재 골다공증 치료제로 사용되고 있는 물질로는 에스트로겐 (estrogen) , 남성화 스테로이드 호르몬 (androgenic anabol ic steroid) , 칼슘 제제, 인산염, 불소 제제, 이프리플라본 ( Ipr i f lavone) , 비타민 D3 등이 있다. 에스트로겐은 조골세포의 세포고사를 억제하여 세포의 생존기간을 증가시키고 파골세포의 세포고사를 촉진하여 세포의 생존기간을 감소시켜 폐경증상의 치료와 골밀도 유지에 어느 정도 효과적인 방법이나 유방암, 자궁내막 증식증 ^을 유발하는 부작용이 있다. 따라서 세계적으로 에스트로겐의 긍정적인 치료 효과만을
갖는 선택적인 에스트로겐 수용체 조절자 (selective estrogen receptor modulators, sERMs)를 개발하여 에스트로겐 대체 치료에 이용하려는 연구가 활발히 진행되고 있고 같은 맥락에서 최근에 상대적으로 골에 분포도가 높은 에스트로겐 수용체 아형 (subtype)인 ER(5에 대한 관심이 집중되고 있다. 골의 재흡수를 억제하는 약물이고 SERMs, fluoride 등이 있는데 이들 약물은 단기간 (~ 5년 정도)의 치료에는 골밀도 증가에 효과적이나 장기간의 투여시 골량의 증가가 촉진되지 않으며 오히려 장기간의 투여에 따른 부작용을 초래한다. 따라서 장기간의 투여에도 지속적인 골밀도 증가 효과를 나타내고 부작용이 적은 안전한 예방 및 치료제 개발이 요구되고 있다. 이외에도 골다공증 파골세포의 활성을 억제하여 골파괴를 억제시키거나 조골세포의 증식을 통해 골재생 단위의 활성을 증가시키는 약물로 l,25(0H)2D3(calcitriol) (칼시토닌), 부갑상선호르몬 (parathyroid hormone, PTH), 비스포스포네이트 (bisphosphonate) 제제 등이 있다. Osteoblasts located on the bone surface have alkaline phosphatase (ALP), a glycoprotein enzyme in the cell membrane, type I collagen (Col), osteocalcin (0CN), and osteopontin (0PN). And secrete and calcify bone matrix substances such as bone sialoprotein (BSP) (Collier FM et al., Endocrinology, 139 (3), ρρ1258-1267, 1998). Bone maintains a constant call volume by balancing osteoblast and osteoclast activity, and bone regeneration occurs continuously due to their activity. However, when osteoclast activity is increased than osteoblasts, bone mass decreases to induce osteoporosis, and postmenopausal women cause osteoporosis due to a decrease in blood estrogen concentration. Osteoporosis is one of the most important social problems at present, and various fractures, especially femoral fractures or vertebral fractures, which are easily caused by the weakening of bones rather than the symptoms themselves, limit the long-term activity and lead to a healthy life. It is known to provide a cause for 15% of cases. Bone mass is influenced by several factors, including genetic factors, nutrition, hormone changes, differences in exercise and lifestyle, and the causes of osteoporosis include old age, lack of exercise, low weight, smoking, low calcium diet, menopause, Ovarian ablation is known. On the other hand, although there are individual differences, the bones are higher than the whites due to lower bone resorpt ion levels, which is usually the highest at 14 to 18 years of age and decreases by about 1% per year in old age. Especially in women, bone reduction continues after 30 years of age, and when menopause reaches bone growth rapidly due to hormonal changes. As described above, osteoporosis is unavoidable for elderly people, especially postmenopausal women, and as the population ages in developed countries, interest in osteoporosis and its treatments is gradually increasing. It is also known that around $ 130 billion of market is formed around the world for the treatment of bone diseases and is expected to increase further. And the development of a bone resorption inhibitor is currently in progress. In the past, the study was mainly focused on the minerals of bone, that is, metabolic abnormalities of calcium and phosphorus, but no significant progress has been made in determining the pathogenesis. Current substances used in the treatment of osteoporosis include estrogen, androtic anabolic steroids, calcium preparations, phosphates, fluoride preparations, Ipr if lavone, and vitamin D3. Estrogens inhibit osteoblastic cell death, increase cell survival, and promote osteoclast cell death to decrease cell survival, which is somewhat effective in treating menopausal symptoms and maintaining bone mineral density. There are side effects that cause ^. Therefore, the only positive therapeutic effect of estrogen worldwide There are active studies to develop selective estrogen receptor modulators (sERMs) for use in the treatment of estrogen replacement. In the same vein, ER, a relatively high distribution of bone estrogen receptor subtypes, (Attention has been focused on 5) drugs that inhibit bone resorption and include SERMs and fluoride. These drugs are effective for short-term (~ 5 years) treatment of bone mineral density but increase bone mass with long-term administration. In addition, long-term administration is expected to result in a sustained increase in bone mineral density and development of safe prophylactic and therapeutic agents with fewer side effects. Bone regeneration unit by inhibiting or proliferating osteoblasts As a drug to increase the activity and the like l, 25 (0H) 2D3 (calcitriol) (calcitonin), PTH (parathyroid hormone, PTH), bisphosphonates (bisphosphonate) formulation.
그러나 기존 골다공증 치료약제들은 골흡수만을 차단시키거나 골형성을 촉진시키는 효능만을 갖으며 장기간 투여시 많은 부작용을 유발하고 있다. 따라서 장기간 투여에도 지속적인 골밀도 증가 효과를 나타내고 부작용이 적은 안전한 예방 및 치료제 개발이 요구되고 있다. 한편, 개똥쑥 C4rie7?/s/a annua L.)은 쌍떡잎식물 초통꽃목 국화과의 한해살이풀로서, 국화과에 속하며 한국 ·일본ᅳ타이완꽁골.시베리아 등지 분포되어 있는 것으로, 잔잎쑥ᅳ개땅쑥이라고도 한다. 길가나 빈터, 강가에서 자라는 것으로 높이가 약 lm이며, 풀 전체에 털이 없고 특이한 냄새가 나는 식물로서, 한방에서는 발열 감기 ·학잘 ·소아경기.소화불량.이질 등의 치료에 사용되며, 서양에서는 마취제, 양념, 식초의 방향제로 쓰여져 왔다. 개똥쑥 G4r a7//s/a annua L.)에 포함되어 있는 성분으로는
아르테미시닌 (Artemi sinin) , 아르테아뉴인 B(arteannuin B) , 아르테미신닌 산 (artemi sininic acid) , 디하이드로아테미신닌 산 (Dihydroartmisinic acid) , 알파ᅳ에폭시디하이드로아르테미신닌 산 (a-Epoxydihydroartemisinic acid) , 아르테아뉴인 UArteannuin L) , 아테아뉴인 N(ArteannuinN), 디하이드로아르테아뉴인 B(Dihydroarteannuin B) ,However, existing osteoporosis therapeutics have only the effect of blocking bone resorption or promoting bone formation and causing many side effects when administered for a long time. Therefore, there is a need for the development of safe prophylactic and therapeutic agents that have a long-term effect of increasing bone mineral density and have fewer side effects. On the other hand, Cactus C4rie7? / S / a annua L.) is an annual herb of a dicotyledon plant, Asteraceae, which belongs to Asteraceae and is distributed in Korea, Japan, Thailand, Taiwan, Siberia, etc. . Growing on the side of a road, on a vacant land, or on a river, the plant is about lm tall and has a hairy, peculiar smell throughout the grass. In oriental medicine, it is used to treat fever, cold, child's game, dyspepsia, dysentery, etc. It has been used as a fragrance in spices, spices and vinegar. The ingredients included in the firefly G4r a7 // s / a annua L.) Artemi sinin, artehaninin B, artemi sininic acid, dihydroartmisinic acid, alpha ᅳ epoxydihydroartemisinin acid (a- Epoxydihydroartemisinic acid), Artaeanin UArteannuin L), Arteanin N (ArteannuinN), Dihydroarteanin B (Dihydroarteannuin B),
3,3' ,7-트리메틸케르세틴 (3,3' , 7-Tr imethylquercet in) , 3,3 ', 7-trimethylquecetin (3,3', 7-Tr imethylquercet in),
3,4',7-트리메틸케르세틴 (3,4' -Tr imethylquercet in)이 있으며, 개똥쑥이 함유하고 있는 아르테미시닌 (artemisinin) 물질은 항암효과가 매우 뛰어나 기존의 항암제보다도 1200 배나 효능이 있다고 보고되어 있다 (Choi SR et al . , 2008; Xu Q et al . , 1989) . 또한, 고혈압, 당뇨 등 성인병에도 효과가 있다고 알려져 있으며, 말라리아나 결핵, 이질 등을 치료하는데에도 효능이 있다고 보고되고 있다 (Klayman DL et al . , 1984) . 아울러, 허혈을 다스리거나 종기, 가려움증, 설사, 기생충 제거 , 체력개선 및 면역력 (Han HS et al . , 2008; Singh ΝΡ et al . , 2001) 강화에 효능이 있다고 보고되고 있으나, 아르테미시닌을 포함하는 개똥숙이 골다공증 예방 및 치료에 어떠한 영향을 미치는지는 알려진 바 없다. 이에, 본 발명자들은 아르테미시닌의 골다공증 예방 및 치료 효과에 대하여 규명하고자 노력한 결과, 아르테미시닌은 조골세포를 증식시키고, 파골세포의 형성 및 활성을 유의적으로 억제하는 효과를 나타냄을 확인함으로써, 상기 아르테미시닌을 골다공증 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용될 수 있음을 밝힘으로써, 본 발명을 완성하였다. 3,4 ', 7-trimethyl quercetin (3,4'-Tr imethylquercet in), and Artemisinin (artemisinin) substance contained in the firefly is very effective anti-cancer effect, 1200 times more effective than conventional anticancer drugs Have been reported (Choi SR et al., 2008; Xu Q et al., 1989). In addition, it is known to be effective in adult diseases such as hypertension and diabetes, and has been reported to be effective in treating malaria, tuberculosis and dysentery (Klayman DL et al., 1984). In addition, it has been reported to be effective in treating ischemia, boils, itching, diarrhea, parasite removal, physical improvement and strengthening immunity (Han HS et al., 2008; Singh ΝΡ et al., 2001). It is not known what affects the treatment and prevention of osteoporosis. Accordingly, the present inventors have tried to clarify the effects of artemisinin on the prevention and treatment of osteoporosis, by confirming that artemisinin has the effect of proliferating osteoblasts and significantly inhibiting the formation and activity of osteoclasts, By revealing that the artemisinin can be usefully used as an active ingredient of the pharmaceutical composition for preventing and treating osteoporosis, the present invention has been completed.
[발명의 상세한 설명; I Detailed description of the invention; I
【기술적 과제】 [Technical problem]
본 발명 목적은 아르테미시닌 (artemisinin)을 포함하는 골다공증 예방 및 치료용 약학적 조성물에 관한 것이다.
【기술적 해결방법】 The present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemisinin (artemisinin). Technical Solution
상기 목적을 달성하기 위하여, In order to achieve the above object ,
본 발명은 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물을 제공한다. The present invention provides a pharmaceutical composition for osteoporosis prevention and treatment comprising artemisinin (artemi sinin) or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 아르테미시닌 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 개선용 건강식품을 제공한다. The present invention also provides a health food for osteoporosis prevention and improvement comprising artemisinin or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 유효한 양의 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 골다공증에 걸린 개체에 투여하는 단계를 포함하는 골다공증 치료 방법을 제공한다. The present invention also provides a method for treating osteoporosis comprising administering an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof to an individual suffering from osteoporosis.
또한, 본 발명은 유효한 양의 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 개체에 투여하는 단계를 포함하는 골다공증 예방 방법을 제공한다. The present invention also provides a method for preventing osteoporosis comprising administering to a subject an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof.
또한, 본 발명은 골다공증 예방 및 치료용 약학적 조성물의 용도로 사용하기 위한 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 제공한다. The present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a pharmaceutical composition for the prevention and treatment of osteoporosis.
아울러, 본 발명은 골다공증 예방 및 개선용 건강 식품의 용도로 사용하기 위한 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 제공한다. In addition, the present invention provides artemisinin or a pharmaceutically acceptable salt thereof for use as a health food for preventing and improving osteoporosis.
【유리한 효과】 Advantageous Effects
본 발명은 아르테미시닌 (artemi sinin)을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물에 관한 것으로, 아르테미시닌은 조골세포를 증식시키고, 파골세포의 형성 및 활성을 유의적으로 억제하는 효과를 나타냄으로써, 상기 아르테미시닌을 골다공증 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용할 수 있다. The present invention relates to a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemi sinin as an active ingredient, artemisinin proliferates osteoblasts and significantly inhibits the formation and activity of osteoclasts. By showing the effect, the artemisinin can be usefully used as an active ingredient of the pharmaceutical composition for preventing and treating osteoporosis.
【도면의 간단한 설명】
도 1은 아르테미시닌이 TRA tartrate-resi stant acid phosphatase , TRAP) 활성에 미치는 영향을 나타낸 도이다. [Brief Description of Drawings] 1 is a diagram showing the effect of artemisinin on TRA tartrate-resi stant acid phosphatase (TRAP) activity.
도 2는 아르테미시닌이 파골 세포 분화에 미치는 영향을 나타낸 도이다. 도 3은 아르테미시닌이 ALP( alkal ine phosphatase , ALP) 활성에 미치는 영향을 나타낸 도이다. 2 is a diagram showing the effect of artemisinin on osteoclast differentiation. 3 is a diagram showing the effect of artemisinin on ALP (alkal ine phosphatase, ALP) activity.
도 4는 아르테미시닌이 조골 세포 분화에 미치는 영향을 나타낸 도이다. 4 is a diagram showing the effect of artemisinin on osteoblast differentiation.
【발명의 실시를 위한 최선의 형태】 [Best form for implementation of the invention]
이하, 본 발명을 상세히 설명한다. 본 발명은 아르테미시닌 (artemi sinin) 또는 이의 약학작으로 허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물을 제공한다. Hereinafter, the present invention will be described in detail. The present invention provides a pharmaceutical composition for the prevention and treatment of osteoporosis comprising artemi sinin or an acceptable salt thereof as an active ingredient.
또한, 본 발명은 유효한 양의 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 골다공증에 걸린 개체에 투여하는 단계를 포함하는 골다공증 치료 방법을 제공한다. The present invention also provides a method for treating osteoporosis comprising administering an effective amount of artemi sinin or a pharmaceutically acceptable salt thereof to an individual suffering from osteoporosis.
또한, 본 발명은 유효한 양의 아르테미시닌 (artemisinin) 또는 이의 약학적으로 허용가능한 염올 개체에 투여하는 단계를 포함하는 골다공증 예방 방법을 제공한다. The present invention also provides a method for preventing osteoporosis comprising administering to a subject an effective amount of artemisinin or a pharmaceutically acceptable salt thereof.
또한, 본 발명은 골다공증 예방 및 치료용 약학적 조성물의 용도로 사용하기 위한 아르테미시닌 (artemi s inin) 또는 이의 약학적으로 허용가능한 염을 제공한다. The present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a pharmaceutical composition for the prevention and treatment of osteoporosis.
상기 아르테미시닌을 개똥쑥 추출물로부터 분리된 것이 바람직하다. 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것이 바람직하다: It is preferable that the artemisinin is isolated from the firefly extract. The artemisinin is preferably represented by the following [Formula 1]:
[화학식 1]
[Formula 1]
상기 아르테미시닌은 파골세포의 분화를 억제하는 것이 바람직하나, 이에 한정되지 않는다. The artemisinin preferably inhibits the differentiation of osteoclasts, but is not limited thereto.
상기 아르테미시닌은 조골세포의 분화를 촉진하는 것이 바람직하나ᅳ 이에 한정되지 않는다. 본 발명의 구체적인 실시예에서, 본 발명자들은 5 내지 6주령 C57BL/6 마우스에서 경골과 대퇴골을 분리하여 골수 세포를 수득하였다. 상기 수득된 골수세포로부터 파골세포로 분화 유도하는 동안 아르테미시닌의 효과를 확인하기 위하여, 주석산염저항산성인산분해효소 (tartrate-resistant acid phosphatase , TRAP)염색 방법을 이용하여 아르테미시닌의 효과를 확인한 결과, 아르테미시닌을 처리한 골수세포에서 농도의존적으로 파골세포로의 분화를 억제하는 것을 확인하였고 (도 1 참조), 현미경 관찰에서도 아르테미시닌을 농도의존적으로 골수세포를 파골세포로의 분화를 유의적으로 억제하는 것을 확인하였다 (도 2참조) . The artemisinin preferably promotes differentiation of osteoblasts, but is not limited thereto. In a specific embodiment of the present invention, the present inventors obtained bone marrow cells by separating the tibia and the femur in 5 to 6 week old C57BL / 6 mice. In order to confirm the effect of artemisinin during induction of differentiation from the obtained bone marrow cells into osteoclasts, the effect of artemisinin using a tartrate-resistant acid phosphatase (TRAP) staining method was used. As a result, it was confirmed that the myeloid cells treated with artemisinin inhibited the differentiation of osteoclasts in a concentration-dependent manner (see FIG. 1). Was significantly inhibited (see FIG. 2).
또한, C2C12세포에 BMP-2를 처리하여 조골세포로 분화를 유도하는 동안, 아르테미시닌 (artemisinin)이 미치는 영향을 알칼리 포스파타제 활성 측정 및 염색을 통해 확인한 결과, 각각 0.3 μΜ, 1 μΜ, 3 μΜ 및 10 μΜ 아르테미시닌을 처리한 골수세포에서 농도의존적으로 조골세포로 분화하는 것을 확인하였고 (도 3 참조), 현미경 관찰에서도 아르테미시닌을 농도의존적으로 골수세포를 조골세포의 분화를 유의적으로 촉진하는 것을 확인하였다 (도 4 참조) . In addition, the effects of artemisinin on the treatment of BMP-2 on C2C12 cells induced osteoblast differentiation through alkaline phosphatase activity measurement and staining, respectively, 0.3 μΜ, 1 μΜ, 3 μΜ, respectively. And 10 μΜ artemisinin-treated bone marrow cells were found to differentiate into osteoblasts in a concentration-dependent manner (see FIG. 3), and microscopic observation also significantly differentiated osteoblast differentiation of artemisinin in bone marrow cells. It was confirmed to promote (see FIG. 4).
따라서, 본 발명의 에 따른 아르테미시닌 (artemisinin)은 조골세포를
증식시키고, 파골세포의 형성 및 활성을 유의적으로 억제하는 효과를 나타냄으로, 상기 아르테미시닌 또는 이의 약학적으로 허용가능한 염은 골다공증 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용할 수 있다. 본 발명의 아르테미시닌을 함유하는 조성물은 상기 성분에 추가로 동일 또는 유사한 기능을 나타내는 유효성분올 1종 이상 함유할 수 있다. Therefore, artemisinin according to the invention of the osteoblasts By proliferating and significantly inhibiting the formation and activity of osteoclasts, the artemisinin or a pharmaceutically acceptable salt thereof can be usefully used as an active ingredient of a pharmaceutical composition for preventing and treating osteoporosis. . The composition containing artemisinin of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the above components.
본 발명의 조성물은 약제학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약제학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀를로오스, 유당, 포비돈 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니를, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말샐를로오스, 히드특시프로필셀를로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 텍스트로스, 소르비를 및 탈크 둥이 사용될 수 있다. 본 발명에 따른 약제학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 ~ 90 중량부 포함되는 것이 바람직하나 이에 한정되는 것은 아니다. The composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additive may include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone colloidal silicon dioxide, calcium hydrogen phosphate, Lactose, Manni, Peel, Arabian Rubber, Pregelatinized Starch, Corn Starch, Powdered Salose, Hydroxypropyl Cellulose, Opadry, Sodium Starch Glycolate, Carnauba Lead, Synthetic Aluminum Silicate, Stearic Acid, Stearic Acid Magnesium, aluminum stearate, calcium stearate, sucrose, textose, sorbbi and talc can be used. The pharmaceutically acceptable additive according to the present invention is preferably included 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
즉, 본 발명의 조성물은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 둥의 회석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡술제 등이 포함되몌 이러한 고형 제제는 아르테시미닌에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슴카보네이트 (Calcium carbonate) , 수크로스 (Sucrose) , 락토오스 (Lactose)또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제,
현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜 (Propylene glycol ) , 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸을레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위템솔 (wi tepsol ) , 마크로골, 트원 ( tween) 61 , 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. In other words, the composition of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, the fillers, extenders, binders, wetting agents, disintegrating agents, and the diluents or excipients of surfactants are commonly used. It can be prepared using. Solid form preparations for oral administration include tablets, pills, powders, granules, capsulants, etc. These solid form preparations contain at least one excipient such as starch, Calcium carbonate, sucrose, etc. ), Lactose or gelatin, and the like. In addition to simple excipients, lubricants such as magnesium styrate talc may also be used. Oral liquid preparations include suspensions, solvents, emulsions and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, Suspensions, emulsions, lyophilized preparations, suppositories may be included. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl acrylate, etc. may be used. As a base of suppositories, wi tepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사ᅳ 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식올 선택하는 것이 바람직하다. 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다. The composition of the present invention can be administered orally or parenterally according to the desired method, the external or intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intramuscular injection It is desirable to choose all. Dosage varies according to the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, and severity of disease.
본 발명의 조성물의 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하며, 일일 투여량은 아스퍼질러스 테리우스 추출물의 양을 기준으로 0.0001 내지 100 mg/kg이고, 바람직하게는 0.0이내지 10 mg/kg이며, 하루 1 ~ 6회 투여될 수 있다. The dosage of the composition of the present invention varies depending on the patient's weight, age, sex, health status, diet, time of administration, administration method, excretion rate and severity of the disease, the daily dosage is Aspergillus terius extract It is 0.0001 to 100 mg / kg, preferably 0.0 to 10 mg / kg based on the amount of can be administered 1 to 6 times a day.
본 발명의 조성물은 염증성 질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다. 본 발명의 아르테미시닌은 약학적으로 허용 가능한 염의 형태로 사용할 수 있으며, 염으로는 약학적으로 허용 가능한 유리산 ( free acid)에 의해 형성된 산 부가염이 유용하다. 산 부가염은 염산, 질산, 인산, 황산, 브름화수소산, 요드화수소산, 아질산 또는 아인산과 같은 무기산류와 지방족 모노 및 디카르복실레이트, 페닐-치환된 알카노에이트, 하이드록시 알카노에이트 및 알칸디오에이트, 방향족 산류, 지방족 및 방향족 설폰산류와 같은 무독성 유기산, 아세트산, 안식향산, 구연산, 젖산, 말레인산, 글루콘산, 메탄설폰산, 4-를루엔설폰산, 주석산, 푸마르산과 같은 유기산으로부터 얻는다. 이러한 약학적으로 무독한 염류로는 설페이트, 피로설페이트, 바이설페이트, 설파이트,
바이설파이트, 니트레이트, 포스페이트, 모노하이드로겐 포스페 0 디하이드로겐 포스페이트, 메타포스페이트, 피로포스페이트 클로라 Ο 브로마이드, 아이오다이드, 플루오라이드, 아세테이트, 프로피오네 ο 데카노에이트, 카프릴레이트, 아크릴레이트, 포메이트, 이소부티레 0 카프레이트, 헵타노에이트, 프로피을레이트, 옥살레이트, 말로네 0 석시네이트, 수베레이트, 세바케이트, 푸마레이트, 말리에 0 부틴 -1 , 4-디오에이트, 핵산 -1, 6-디오에이트, 벤조에이트, 클로로벤조에 0 메틸벤조에이트, 디나트로 벤조에이트, 하이드톡시벤조에 o 메톡시벤조에이트, 프탈레이트, 테레프탈레이트, 벤젠설포네。 The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of inflammatory diseases. Artemisinin of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and Non-toxic organic acids such as alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids, acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-lluenesulfonic acid, tartaric acid and fumaric acid. These pharmaceutically harmless salts include sulfate, pyrosulfate, bisulfate, sulfite, Bisulfite, nitrate, phosphate, monohydrogen phosphate 0 dihydrogen phosphate, metaphosphate, pyrophosphate chlora bromide, iodide, fluoride, acetate, propione ο decanoate, caprylate, Acrylate, Formate, Isobutyre 0 Caprate, Heptanoate, Propylate, Oxalate, Malone 0 Succinate, Suberate, Sebacate, Fumarate, Mali 0 Butyne-1, 4-Diate, Nucleic Acid -1, 6-dioate, benzoate, chlorobenzo 0 methylbenzoate, dinatro benzoate, hydroxybenzoate o methoxybenzoate, phthalate, terephthalate, benzene sulfone.
를루엔설포네이트, 클로로벤젠설포네이트, 크실렌설포네이트, 페닐아세테 0 페닐프로피오네이트, 페닐부티레이트, 시트레이트, 락테 o β -하이드록시부티레이트,글리콜레이트,말레이트,타트레이트, 메탄설포네이트, 프로판설포네이트, 나프탈렌 -1-설포네이트, 나프탈렌 -2—설포네이트 또는 만델레이트를 포함한다. Toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacete 0 phenylpropionate, phenylbutyrate, citrate, lacte o β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, Propanesulfonate, naphthalene-1-sulfonate, naphthalene-2—sulfonate or mandelate.
본 발명에 따른 산 부가염은 통상의 방법, 예를 들면, 화학식 1의 유도체를 유기용매, 예를 들면 메탄올, 에탄올, 아세톤, 메틸렌클로라이드, 아세토니트릴 등에 녹이고 유기산 또는 무기산을 가하여 생성된 침전물을 여과, 건조하여 제조되거나, 용매와 과량의 산을 감압 증류한 후 건조하거나 유기용매 하에서 결정화시켜셔 제조할 수 있다. Acid addition salt according to the present invention is a conventional method, for example, by dissolving a derivative of formula (1) in an organic solvent, such as methanol, ethanol, acetone, methylene chloride, acetonitrile and the like, and the organic acid or inorganic acid is added to filter the precipitate produced It may be prepared by drying, or the solvent and the excess acid may be prepared by distillation under reduced pressure, followed by drying or crystallization under an organic solvent.
또한, 염기를 사용하여 약학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리 토금속 염은 예를 들면 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해하고, 비용해 화합물 염을 여과하고, 여액을 증발, 건조시켜 얻는다. 이때, 금속 염으로는 나트륨, 칼륨 또는 칼슘염올 제조하는 것이 제약상 적합하다. 또한, 이에 대웅하는 은 염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 음염 (예, 질산은)과 반웅시켜 얻는다. 또한, 본 발명은 아르테미시닌 ( ar temi s inin) 또는 이의 약학적으로
허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 개선용 건강식품을 제공한다. Bases can also be used to make pharmaceutically acceptable metal salts. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the compound salt at no cost, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt. Silver salts are also obtained by reacting alkali or alkaline earth metal salts with a suitable negative salt (eg, silver nitrate). In addition, the present invention is artemisinin (ar temi s inin) or pharmaceutically thereof It provides a health food for preventing and improving osteoporosis comprising an acceptable salt as an active ingredient.
또한, 본 발명은 골다공증 예방 및 개선용 건강 식품의 용도로 사용하기 위한 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염을 제공한다. The present invention also provides artemisinin or a pharmaceutically acceptable salt thereof for use as a health food for preventing and improving osteoporosis.
상기 아르테미시닌을 개똥쑥 추출물로부터 분리된 것이 바람직하다. 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것이 바람직하다: It is preferable that the artemisinin is isolated from the firefly extract. The artemisinin is preferably represented by the following [Formula 1]:
[화학식 1] [Formula 1]
상기 아르테미시닌은 파골세포의 분화를 억제하는 것이 바람직하나, 이에 한정되지 않는다. - 상기 아르테미시닌은 조골세포의 분화를 촉진하는 것이 바람직하나, 이에 한정되지 않는다. 본 발명의 에 따른 아르테미시닌 (artemi sinin)은 조골세포를 증식시키고 파골세포의 형성 및 활성을 유의적으로 억제하는 효과를 나타냄으로, 상기 아르테미시닌 또는 이의 약학적으로 허용가능한 염은 골다공증 예방 및 개선용 건강식품 조성물의 유효성분으로 유용하게 사용할 있다. The artemisinin preferably inhibits the differentiation of osteoclasts, but is not limited thereto. -Artemisinin is preferred to promote the differentiation of osteoblasts, but is not limited thereto. Artemisinin according to the present invention exhibits an effect of proliferating osteoblasts and significantly inhibiting the formation and activity of osteoclasts, such artemisinin or a pharmaceutically acceptable salt thereof prevents osteoporosis. And it can be usefully used as an active ingredient of the improved health food composition.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 과자류, 빵류 면류 등과 같은 각종 식품류, 물, 청량음료, 과실음료 등의 드링크류, 껌, 차, 비타민 복합제, 조미료류, 건강기능 식품류
등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다. There is no particular limitation on the kind of food. Examples of the food to which the substance may be added include various foods such as confectionery, bread and noodles, drinks such as water, soft drinks and fruit drinks, gums, teas, vitamin complexes, seasonings, and health functional foods. And includes all of the health functional foods in the ordinary sense.
본 발명의 테레인은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 흔합량은 그의 사용 목적 (예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 화합물의 양은 전체 식품 중량의 0.01 내지 15 중량 %, 바람직하게는 0. 1 내지 5 중량 %로 가할 수 있으며 건강음료 조성물에는 100을 기준으로 0.이내지 5.0 g, 바람직하게는 0.01내지 1.0 g의 비율로 첨가할 수 있다. 그러나 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다. The terrain of the present invention can be added as is to foods or used with other foods or food ingredients, and can be suitably used according to conventional methods. The combined amount of the active ingredient can be suitably determined depending on the purpose of use (prevention or improvement). In general, the amount of the compound in the health food can be added to 0.01 to 15% by weight, preferably from 0.01 to 5% by weight of the total food weight, and 0 to 5.0 g, preferably from 100 to 100 in the health beverage composition Preferably 0.01 to 1.0 g. However, in the case of long-term intake for health control purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 화합물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어, 말토스, 수크로즈 등 및 폴리사카라이드, 예를 들어, 텍스트린, 사이클로텍스트린 등과 같은 통상적인 당, 및 자일리를, 소르비를, 에리스리를 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마킨, 스테비아 추출물 등), 및 합성 향미제 (사카린, 아스파르탄 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 당 일반적으로 약 0. 1 내지 2.0 g, 바람직하게는 약 0. 1 내지 1.0 g이다. The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the compound as essential ingredients in the ratios indicated, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, and the like, and polysaccharides, such as conventional sugars such as textine, cyclotextine, and sugar alcohols such as Xyl, Sorbi, Erisli, etc. to be. As flavoring agents other than those mentioned above, natural flavoring agents (tauumakin, stevia extract, etc.), and synthetic flavoring agents (saccharin, aspartan, etc.) can be advantageously used. The proportion of natural carbohydrates is generally from about 0.01 to 2.0 g, preferably from about 0.01 to 1.0 g per 100 compositions of the present invention.
상기 외에 본 발명의 테레인은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 중점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코을, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 아스퍼질러스 테리우스 추출물 또는 이의 분획물은 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한
과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 아스퍼질러스 테리우스 추출물 또는 이의 분획물 100중량부 당 약 20증량부의 범위에서 선택되는 것이 일반적이다. 이하, 본 발명은 실시예에 의하여 상세히 설명한다. In addition to the above-mentioned terane of the present invention, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and It may contain a salt thereof, an organic acid, a protective colloidal thickener, a pH adjuster, a stabilizer, a preservative, a glycerin, an alcohol, a carbonation agent used in a carbonated beverage, and the like. In addition, the Aspergillus terius extract of the present invention or a fraction thereof may be used for the preparation of natural fruit juices and fruit juice beverages and vegetable beverages. It may contain pulp. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of about 20 parts by weight per 100 parts by weight of the Aspergillus terius extract or fractions thereof. Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다. <실시예 1> 개똥쑥 추출물로부터 아르테미시닌 (artemisinin) 분리 However, the following examples are merely to illustrate the present invention, and the content of the present invention is not limited to the following examples. Example 1 Isolation of Artemisinin from Extract from Firefly
개똥쑥 추출물로부터 분리된 아르테미시닌을 Enzo Li fe Sciences (Cat #: ALX-350-219-G001) 에서 구입하였다. Artemisinin isolated from the firefly extract was purchased from Enzo Li fe Sciences (Cat #: ALX-350-219-G001).
<실시예 2> 아르테미시닌 (artemisinin)에 의한파골세포 분화 억제 효과 확인 <2-1>파골세포 배양 Example 2 Confirmation of Inhibitory Effects of Osteoblast Differentiation by Artemisinin (2-1) Osteoclast Cell Culture
5 내지 6주령 C57BL/6 마우스에서 경골과 대퇴골을 분리하여 골수 세포를 수득하였다. 상기 분리된 골수세포는 K» fetal bovine serum(FBS) 및 50 ng/ml M— CSF가 포함된 α—최소 필수 배지 ( α _ minimum essent ial medium, α一 MEM)에서 3일 동안 배양한 후 부유 세포는 제거하고 부착된 세포를 대식세포 (bone marrow macrophages , mils)로 사용하였다. 그런 다음,상기 대식 세포를 50 ng/ml M-CSF 및 100 ng/ml RANKL이 포함된 배지에 4일 동안 배양하였다. 주석산염저항산성인산분해효소 (tartrate-resistant acid phosphatase , TRAP)를 이용하여 염색하고, TRAP 양성 다핵 형 세포를 파골세포로 간주하여 사용하였다. Bone marrow cells were obtained by separating tibia and femur from 5 to 6 week old C57BL / 6 mice. The isolated bone marrow cells were cultured for 3 days in α— minimum essential medium (α MEM) containing K »fetal bovine serum (FBS) and 50 ng / ml M— CSF. The cells were removed and the attached cells were used as bone marrow macrophages (mils). The macrophages were then incubated for 4 days in a medium containing 50 ng / ml M-CSF and 100 ng / ml RANKL. Staining was performed using tartrate-resistant acid phosphatase (TRAP) and TRAP-positive multinucleated cells were used as osteoclasts.
<2-2> T APCtartrate-resistant acid phosphatase) 활성 측정 <2-2> Determination of T APCtartrate-resistant acid phosphatase activity
상기 실시예 <2-1>에 기재된 방법으로 골수세포로부터 파골세포로 분화 유도하는 동안 아르테미시닌의 효과를 확인하기 위하여,
주석산염저항산성인산분해효소 (tart rate-res i st ant acid phosphatase , TRAP) 염색 방법올 이용하여 아르테미시닌의 효과를 확인하였다. In order to confirm the effect of artemisinin during induction of differentiation from bone marrow cells to osteoclasts by the method described in Example <2-1>, The effect of artemisinin was confirmed using the method of staining the tartarate-resistant ant acid phosphatase (TRAP).
구체적으로, 상기 실시예 <2-1>에 기재된 방법으로 배양한 골수세포에 M-CSF 및 RANKLE을 처리하여 파골세포로 분화하는 동안 아르테미시닌을 농도별로 처리한 후, 4일 동안 배양하였다. 배양 후, 배지를 제거하고 PBS를 사용하여 상기 세포를 세척하였다. 그런 다음, 상기 세포를 10 %포르말린으로 5분 동안 고정시킨 후, 증류수로 3번 세척하였다. 발색반웅 물질 (Chromogenic substrate)을 상기 세포에 50 μΐ씩 첨가하고 37 0C에서 30분 동안 염색한 후 현미경을 통해 관찰하였다 (도 2) . 또한, TRAP 활성은 배양 상측액 (culture supernatant s)에 170 μΐ씩 발색반웅 물질 /테트라를 포함한 버퍼 (chromogenic substrate/ tartrate-containing buffer)를 첨가하고 37 °C에서 3 시간 동안 반웅시킨 후, 엘라이저 리더기 (EUSA reader) (Molecular Devices , CA, USA)를 이용하여 540 nm에서 흡광도를 측정하였다. Specifically, the bone marrow cells cultured by the method described in Example <2-1> were treated with M-CSF and RANKLE and treated with artemisinin by concentration during differentiation into osteoclasts, followed by culturing for 4 days. After incubation, the medium was removed and the cells were washed with PBS. Then, the cells were fixed with 10% formalin for 5 minutes and washed three times with distilled water. Chromogenic substrate was added to the cells in 50 μΐ and stained at 37 0 C for 30 minutes and observed under a microscope (Figure 2). In addition, TRAP activity was added to the culture supernatant s by adding chromogenic substrate / tartrate-containing buffer at 170 μΐ in culture supernatant s and reacting at 37 ° C for 3 hours. Absorbance was measured at 540 nm using an EUSA reader (Molecular Devices, Calif., USA).
그 결과,도 1에 나타낸 바와 같이, 아르테미시닌을 처리한 골수세포에서 농도의존적으로 파골세포로의 분화를 억제하는 것을 확인하였다 (도 1) . As a result, as shown in Fig. 1, it was confirmed that differentiation into osteoclasts in a concentration-dependent manner in bone marrow cells treated with artemisinin (Fig. 1).
또한, 도 2에 나타낸 바와 같이, 현미경관찰에서도 아르테미시닌은 농도의존적으로 골수세포를 파골세포로의 분화를 유의적으로 억제하는 것을 확인하였다 (도 2) . <실시예 3>아르테미시닌 (artemisinin)에 의한조골세포 분화확인 In addition, as shown in FIG. 2, microscopic observation also confirmed that artemisinin significantly inhibited the differentiation of bone marrow cells into osteoclasts in a concentration-dependent manner (FIG. 2). Example 3 Osteoblast Differentiation by Artemisinin
<3-1>조골세포 배양 <3-1> osteoblast culture
C2C12세포를 10% FBS( fetal bovine serum, Gibco Invi trogen, Grand Island, C2C12 cells were treated with 10% FBS (fetal bovine serum, Gibco Invi trogen, Grand Island,
NY, USA) 및 항생제 ( 100 U/ml 페니실린 및 100 pg/ml 스트렙토마이신 (GibcoNY, USA) and antibiotics (100 U / ml penicillin and 100 pg / ml streptomycin (Gibco
Invi trogen) )가 포함된 DMEM 배지 (DMEM, Hyclone , Logan, UT, USA)를 사용하여 계대 배양하였다. 그런 다음, C2C12 세포를 96-웰 플레이트 (96—wel l plate)에Invi trogen)) was subcultured using DMEM medium (DMEM, Hyclone, Logan, UT, USA). Then C2C12 cells were placed in a 96-well plate.
2 X 104 세포 /ml 농도로 200 μΐ씩 분주한 후, 10% FBS가 포함된 DMEM 배지를
사용하여 24시간 동안 배양하였다. 24시간 배양 후, 배양액올 제거하고 5% DMEM배지를 첨가하였다. 그런 다음, lOOng/ml BMP-2를 상기 세포에 처리하고 4일 동안 배양하여 조골세포로 분화를 유도하였다. <3-2> Alkaline phosphatase(ALP) 활성 측정 Dispense 200 μΐ at a concentration of 2 X 10 4 cells / ml, and then use DMEM medium containing 10% FBS. Incubated for 24 hours. After incubation for 24 hours, the culture solution was removed and 5% DMEM medium was added. Then, lOOng / ml BMP-2 was treated to the cells and cultured for 4 days to induce differentiation into osteoblasts. <3-2> Alkaline phosphatase (ALP) activity measurement
상기 실시예 <3-1>에 기재된 방법으로 C2C12 세포에 BMP-2를 처리하여 조골세포로 분화를 유도하는 동안, 아르테미시닌 (artemisinin)이 미치는 영향을 알칼리 포스파타제 활성 측정 및 염색을 통해 확인하였다. 혈청효소인 알칼리 포스파타제 (alkaline phosphatase, ALP)는 골 형성의 지표가 되는 효소로써 조골세포의 분화 중기에 생성된다 (Zhao Yet al. , Biol. Pharm. Bull. , 28(8), ppl371-1376, 2005) . While inducing differentiation into osteoblasts by treating C2C12 cells with BMP-2 by the method described in Example <3-1>, the effects of artemisinin (artemisinin) were confirmed through alkaline phosphatase activity measurement and staining. . Alkaline phosphatase (ALP), a serum enzyme, is an enzyme that is an indicator of bone formation and is produced during the differentiation of osteoblasts (Zhao Yet al., Biol. Pharm. Bull., 28 (8), ppl371-1376, 2005).
구체적으로, 상기 실시예 <3_1>에 기재된 방법으로 BMP-2(10 ng/ml) 및 아르테미시닌을 처리한 후, 10 mM Tris, 0.5 mM MgCl2, 및 0.1¾> Triton X-10이 포함된 완충용액 (lysis buffer)을 사용하여 상기 세포를 용해시키고 13,000 rpm에서 20분간 원심분리를 한후 상측액올 수득하였다. 상기 수득된 상측액 Specifically, after treatment with BMP-2 (10 ng / ml) and artemisinin by the method described in Example <3_1>, 10 mM Tris, 0.5 mM MgCl 2 , and 0.1¾> Triton X-10 were included. The cells were lysed using the prepared lysis buffer and centrifuged at 13,000 rpm for 20 minutes to obtain a supernatant. Supernatant obtained above
20 μΐ를 96 웰 플레이트 (well plate)에 분주하고 60 μΐ씩 pNPP(p-nitrophenyl phosphate) 용액을 첨가한 후 370C배양기에서 1시간 동안 배양하였다. 그런 다음, 상기 세포가 노란색으로 발색한 것을 확인한 후, 405 nm에서 흡광도를 측정하였다. 또는 3.7% 포르말린 (formal in)을 사용하여 상기 세포를 고정 한 후알카리 포스파타제 키트 (alkaline phosphatase kit, Sigma; St. Louis, M0, USA)를 이용하여 염색한 후, 현비경을 통해 확인하였다. 20 μΐ was dispensed into a 96 well plate and 60 μΐ was added to pNni (p-nitrophenyl phosphate) solution, followed by incubation for 1 hour in a 37 0 C incubator. Then, after confirming that the cells developed yellow, absorbance was measured at 405 nm. Or after fixing the cells using 3.7% formalin (formal in) and stained using an alkaline phosphatase kit (alkaline phosphatase kit, Sigma; St. Louis, M0, USA), and confirmed through a microscope.
그 결과, 도 3에 나타낸 바와 같이, C2C12 세포에 BMP-2를 처리하여 조골세포로 분화하는 동안 아르테미시닌을 농도별로 처리하여 상기 세포에 대한 조골세포 분화에 미치는 영향올 확인한 결과, 각각 0.3 μΜ, 1 μΜ, 3 μΜ및 10 μΜ 아르테미시닌을 처리한 골수세포에서 농도의존적으로 조골세포로 분화하는 것을 확인하였다 (도 3).
또한, 도 4에 나타낸 바와 같이, 현미경관찰에서도 아르테미시닌은 농도의존적으로 골수세포를 조골세포의 분화를 유의적으로 촉잔하는 것을 확인하였다 (도 4) . As a result, as shown in Figure 3, the treatment of artemisinin by concentration during the differentiation into osteoblasts by treating B2-2 to C2C12 cells to confirm the effect on osteoblast differentiation of the cells, 0.3 μΜ each , 1 μΜ, 3 μΜ and 10 μΜ artemisinin-treated bone marrow cells were confirmed to differentiate into osteoblasts in a concentration-dependent manner (FIG. 3). In addition, as shown in FIG. 4, artemisinin also confirmed that artemisinin significantly accelerated the differentiation of osteoblasts into osteoblasts in a concentration-dependent manner (FIG. 4).
【산업상 이용가능성】 Industrial Applicability
상술한 바와 같이, 본 발명은 아르테미시닌을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물에 관한 것으로, 상기 아르테미시닌은 조골세포를 증식시키고, 파골세포의 형성 및 활성올 유의적으로 억제하는 효과를 나타냄으로, 상기 아르테미시닌을 골다공증 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용할 수 있다.
As described above, the present invention relates to a pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as an active ingredient, the artemisinin proliferates osteoblasts, osteoclast formation and active ol significantly By showing the inhibitory effect, the artemisinin can be usefully used as an active ingredient of the pharmaceutical composition for preventing and treating osteoporosis.
Claims
【청구항 1】 【Claim 1】
아르테미시닌 ( artemi s inin) 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 치료용 약학적 조성물. A pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin or a pharmaceutically acceptable salt thereof as an active ingredient.
【청구항 2】 【Claim 2】
제 1항에 있어서, 상기 아르테미시닌은 개똥쑥 추출물 {Artemisia annua L . )로부터 분리된 것을 특징으로 하는 골다공증 예방 및 치료용 약학적 조성물. The method of claim 1, wherein the artemisinin is Artemisia annua L. ) A pharmaceutical composition for preventing and treating osteoporosis, characterized in that it is isolated from ).
【청구항 3】 【Claim 3】
제 1항에 있어서, 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것을 특징으로 하는 골다공증 예방 및 치료용 약학적 조성물: The pharmaceutical composition for preventing and treating osteoporosis according to claim 1, wherein the artemisinin is represented by the following [Formula 1]:
[화학식 1] [Formula 1]
【청구항 4】 【Claim 4】
제 1항에 있어서, 상기 아르테미시닌은 파골세포의 분화를 억제하는 것을 특징으로 하는 골다공증 예방 및 치료용 약학적 조성물. The pharmaceutical composition for preventing and treating osteoporosis according to claim 1, wherein the artemisinin inhibits differentiation of osteoclasts.
【청구항 5】 【Claim 5】
제 1항에 있어서, 상기 아르테미시닌은 조골세포의 분화를 촉진하는
것을 특징으로 하는 골다공증 예방 및 치료용 약학적 조성물. The method of claim 1, wherein the artemisinin promotes differentiation of osteoblasts. A pharmaceutical composition for preventing and treating osteoporosis.
【청구항 6】 【Claim 6】
아르테미시닌 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 골다공증 예방 및 개선용 건강식품. A health food for preventing and improving osteoporosis containing artemisinin or a pharmaceutically acceptable salt thereof as an active ingredient.
【청구항 7] [Claim 7]
제 6항에 있어서, 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것을 특징으로 하는 골다공증 예방 및 개선용 건강식품: The health food for preventing and improving osteoporosis according to claim 6, wherein the artemisinin is represented by the following [Formula 1]:
[화학식 1] [Formula 1]
【청구항 8】 【Claim 8】
유효한 양의 아르테미시닌 (artemi s inin) 또는 이의 약학적으로 허용가능한 염을 골다공증에 걸린 개체에 투여하는 단계를 포함하는 골다공증 치료 방법. A method of treating osteoporosis comprising administering an effective amount of artemisinin or a pharmaceutically acceptable salt thereof to a subject suffering from osteoporosis.
[청구항 9】 [Claim 9]
제 8항에 있어서, 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것을 특징으로 하는 골다공증 치료 방법 : The method of treating osteoporosis according to claim 8, wherein the artemisinin is represented by the following [Formula 1]:
【청구항 10】 【Claim 10】
유효한 양의 아르테미시닌 (artemi s inin) 또는 이의 약학적으로 허용가능한 염을 개체에 투여하는 단계를 포함하는 골다공증 예방 방법. A method of preventing osteoporosis comprising administering an effective amount of artemisinin or a pharmaceutically acceptable salt thereof to a subject.
[청구항 11】 [Claim 11]
제 10항에 있어서, 상기 아르테미시닌을 하기 [화학식 1]로 표시되는 것을 특징으로 하는 골다공증 예방 방법: The method of claim 10, wherein the artemisinin is represented by the following [Formula 1]:
[화학식 1] [Formula 1]
【청구항 12] [Claim 12]
골다공증 예방 및 치료용 약학적 조성물의 용도로 사용하기 위한 아르테미시닌 (artemi sinin) 또는 이의 약학적으로 허용가능한 염. Artemisinin or a pharmaceutically acceptable salt thereof for use in a pharmaceutical composition for preventing and treating osteoporosis.
【청구항 13】 【Claim 13】
골다공증 예방 및 개선용 건강 식품의 용도로 사용하기 위한
아르테미시닌 (artemisinin) 또는 이의 약학적으로 허용가능한 염.
For use as a health food to prevent and improve osteoporosis Artemisinin or a pharmaceutically acceptable salt thereof.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2013-0133665 | 2013-11-05 | ||
KR20130133665A KR101487761B1 (en) | 2013-11-05 | 2013-11-05 | Pharmaceutical Composition for the prevention or treatment of osteoporosis comprising Artemisinin |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2015068940A1 true WO2015068940A1 (en) | 2015-05-14 |
Family
ID=52593029
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2014/007719 WO2015068940A1 (en) | 2013-11-05 | 2014-08-20 | Pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as active ingredient |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR101487761B1 (en) |
WO (1) | WO2015068940A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101770523B1 (en) | 2016-08-26 | 2017-08-23 | 연세대학교 산학협력단 | Pharmacological compositions comprising Arteannuin B for treating or preventing of bone disease |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101656306B1 (en) * | 2014-04-02 | 2016-09-12 | 연세대학교 산학협력단 | Composition for treating and preventing of bone disease comprising extract of Artemisia annua Linne |
KR102296780B1 (en) * | 2019-08-28 | 2021-09-01 | 전남대학교산학협력단 | Phamaceutical Composition Comprising an Extract of Artemisia scoparia for Preventing or Treating Metabolic Bone Disease-induced Bone Loss |
KR102463297B1 (en) * | 2020-12-23 | 2022-11-07 | 주식회사 생활한방연구소 | Novel use of extract of Artemisia annua |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20040083466A (en) * | 2001-12-11 | 2004-10-02 | 소시에떼 데 프로듀이 네슬레 소시에떼아노님 | Composition for promotion of bone growth and maintenance of bone health |
KR100703034B1 (en) * | 2005-06-03 | 2007-04-03 | 김자희 | Composition of the pill-type semisulcospira libertina |
CN101879158A (en) * | 2010-07-01 | 2010-11-10 | 中国科学院广州生物医药与健康研究院 | New application of artemisinin derivant |
KR101132017B1 (en) * | 2010-03-09 | 2012-04-02 | 소윤조 | A Composition Containing Hispidulin for Diseases Associated with Bones |
-
2013
- 2013-11-05 KR KR20130133665A patent/KR101487761B1/en active IP Right Grant
-
2014
- 2014-08-20 WO PCT/KR2014/007719 patent/WO2015068940A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20040083466A (en) * | 2001-12-11 | 2004-10-02 | 소시에떼 데 프로듀이 네슬레 소시에떼아노님 | Composition for promotion of bone growth and maintenance of bone health |
KR100703034B1 (en) * | 2005-06-03 | 2007-04-03 | 김자희 | Composition of the pill-type semisulcospira libertina |
KR101132017B1 (en) * | 2010-03-09 | 2012-04-02 | 소윤조 | A Composition Containing Hispidulin for Diseases Associated with Bones |
CN101879158A (en) * | 2010-07-01 | 2010-11-10 | 中国科学院广州生物医药与健康研究院 | New application of artemisinin derivant |
Non-Patent Citations (2)
Title |
---|
HAE-DONG JANG ET AL.: "Preventive effect of artemisia capillaris extract on bone loss in ovarectomized rat model", THE FASEA J., vol. 27, April 2013 (2013-04-01), pages 637.2 * |
PAMELA J. WEATHERS ET AL.: "Artemisinin production in Artemisia annua:studies in planta and results of a novel delivery method for treating malaria and other neglected diseases", PHYTOCHEM REV., vol. 10, no. 2, June 2011 (2011-06-01), pages 173 - 183 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101770523B1 (en) | 2016-08-26 | 2017-08-23 | 연세대학교 산학협력단 | Pharmacological compositions comprising Arteannuin B for treating or preventing of bone disease |
Also Published As
Publication number | Publication date |
---|---|
KR101487761B1 (en) | 2015-01-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2015068940A1 (en) | Pharmaceutical composition for preventing and treating osteoporosis comprising artemisinin as active ingredient | |
KR102334305B1 (en) | Composition for preventing or treating bon disease comprising extract of blueberry | |
KR101269208B1 (en) | Composition comprising sauchinone as an active ingredient for preventing or treating insulin resistance | |
KR100910622B1 (en) | Functional food comprising extract of Nelumbo nucifera Gaertn for the prevention and amelioration of osteoporosis | |
JP2018521003A (en) | Composition for prevention or treatment of benign prostatic hyperplasia containing sykunshi extract | |
KR101308144B1 (en) | Pharmaceutical composition for Prevention or Treatment of bone diseases comprising agelasin D | |
KR102465894B1 (en) | Composition for preventing, ameliorating or treating bone disease comprising salvianolic acid as effective component | |
KR101481709B1 (en) | Composition for preventing or treating erectile dysfunction comprising Sac-1004 compound | |
KR101265872B1 (en) | Pharmaceutical composition for preventing or treating osteoporosis, comprising praeruptorin a or pharmaceutical salt thereof as an active ingredient | |
KR20200022789A (en) | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising deoxycholic acid or pharmaceutically acceptable salt thereof | |
KR101457117B1 (en) | Pharmaceutical composition and functional food for prevention or treatment of bone disease comprising the dryopteris crassithizoma extract | |
KR101249930B1 (en) | Compositions comprising extracts of Sorbus commixta and Geranium nepalense for inhibiting osteoclastogenesis and stimulating chondrogenesis | |
KR102284907B1 (en) | Composition comprising astaxanthin as active ingredient for prevention or treatment of climacteric disorder | |
KR20200129596A (en) | Composition for Preventing or Treating of Degenerative Brain Disease Comprising Extract of Zanthoxylum piperitum Fruit | |
WO2008007880A1 (en) | A composition comprising an extract of prunus persica (l.) batsch for treating and preventing bone diseases | |
KR20150051159A (en) | Composition for preventing or treating thyroid disorders comprising phytolacca esculenta houttuyn extracts or fraction thereof | |
KR102448274B1 (en) | Composition for preventing, ameliorating or treating bone disease comprising crude polysaccharide fraction of Psoralea corylifolia extract as effective component | |
KR101320975B1 (en) | Composition for treatment and prevention of bone diseases comprising extract of magnoliae flos's active components | |
KR101320974B1 (en) | Composition for treatment and prevention of bone diseases comprising extract of magnoliae flos | |
KR20120122277A (en) | Composition for treatment and prevention of bone diseases comprising extract of magnoliae flos's active components | |
KR102141426B1 (en) | Pharmacieutical composition comprising Phloretin 4-O-glucoside for prevention and treatment of bone diseases | |
KR102122970B1 (en) | Composition for inhibiting osteoclast differentiation comprising gold compound as an active ingredient | |
KR102304966B1 (en) | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising Tolfenamic acid | |
KR101869595B1 (en) | Composition for preventing or treating bone disease comprising from sea urchin calcitonin-like peptide | |
KR101586345B1 (en) | Pharmaceutical composition for preventing or treating muscle weakness diseases comprising Estradiol benzoate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 14860477 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 14860477 Country of ref document: EP Kind code of ref document: A1 |