CN1332657C - Composition containing lovastatin and use thereof - Google Patents
Composition containing lovastatin and use thereof Download PDFInfo
- Publication number
- CN1332657C CN1332657C CNB200510049300XA CN200510049300A CN1332657C CN 1332657 C CN1332657 C CN 1332657C CN B200510049300X A CNB200510049300X A CN B200510049300XA CN 200510049300 A CN200510049300 A CN 200510049300A CN 1332657 C CN1332657 C CN 1332657C
- Authority
- CN
- China
- Prior art keywords
- lovastatin
- compositions
- pantethine
- blood
- flavonoid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 title claims abstract description 51
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960004844 lovastatin Drugs 0.000 title claims abstract description 49
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 claims abstract description 35
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 claims abstract description 35
- 235000008975 pantethine Nutrition 0.000 claims abstract description 35
- 239000011581 pantethine Substances 0.000 claims abstract description 35
- 229960000903 pantethine Drugs 0.000 claims abstract description 35
- 210000004369 blood Anatomy 0.000 claims abstract description 24
- 239000008280 blood Substances 0.000 claims abstract description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229930003935 flavonoid Natural products 0.000 claims abstract description 12
- 150000002215 flavonoids Chemical class 0.000 claims abstract description 12
- 235000017173 flavonoids Nutrition 0.000 claims abstract description 12
- 150000002632 lipids Chemical class 0.000 claims abstract description 12
- 239000000654 additive Substances 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 26
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 claims description 18
- 235000008696 isoflavones Nutrition 0.000 claims description 18
- 235000010469 Glycine max Nutrition 0.000 claims description 16
- 244000068988 Glycine max Species 0.000 claims description 16
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 claims description 16
- 241000218628 Ginkgo Species 0.000 claims description 10
- 235000011201 Ginkgo Nutrition 0.000 claims description 10
- 235000008100 Ginkgo biloba Nutrition 0.000 claims description 10
- 229930003944 flavone Natural products 0.000 claims description 9
- 150000002213 flavones Chemical class 0.000 claims description 9
- 235000011949 flavones Nutrition 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 8
- 235000012000 cholesterol Nutrition 0.000 claims description 5
- 230000000996 additive effect Effects 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 15
- 201000005577 familial hyperlipidemia Diseases 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 238000011160 research Methods 0.000 abstract description 2
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 abstract 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 15
- 102000007330 LDL Lipoproteins Human genes 0.000 description 15
- 238000000034 method Methods 0.000 description 11
- -1 2-mercaptoethyl Chemical group 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 102000015779 HDL Lipoproteins Human genes 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- SQGLUEWZRKIEGS-UHFFFAOYSA-N Ginkgetin Natural products C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(OC)C(C=3C(=CC=C(C=3)C=3OC4=CC(O)=CC(O)=C4C(=O)C=3)O)=C2O1 SQGLUEWZRKIEGS-UHFFFAOYSA-N 0.000 description 3
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000002547 new drug Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 108700022737 rat Fat1 Proteins 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 201000002481 Myositis Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- AIFCFBUSLAEIBR-UHFFFAOYSA-N ginkgetin Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C(C=1)=CC=C(OC)C=1C1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=C(O)C=C1 AIFCFBUSLAEIBR-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940055726 pantothenic acid Drugs 0.000 description 2
- 235000019161 pantothenic acid Nutrition 0.000 description 2
- 239000011713 pantothenic acid Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 208000031288 Combined hyperlipidaemia Diseases 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000009429 Ginkgo biloba extract Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 229920002752 Konjac Polymers 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010039020 Rhabdomyolysis Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- UNLRVSBRNJYNHN-UHFFFAOYSA-N [cyano-(3-phenoxyphenyl)methyl] 2-(4-chlorophenyl)-3-methylbutanoate;dimethoxy-(4-nitrophenoxy)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1.C=1C=C(Cl)C=CC=1C(C(C)C)C(=O)OC(C#N)C(C=1)=CC=CC=1OC1=CC=CC=C1 UNLRVSBRNJYNHN-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 150000004645 aluminates Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- KYIDJMYDIPHNJS-UHFFFAOYSA-N ethanol;octadecanoic acid Chemical compound CCO.CCCCCCCCCCCCCCCCCC(O)=O KYIDJMYDIPHNJS-UHFFFAOYSA-N 0.000 description 1
- BEGBSFPALGFMJI-UHFFFAOYSA-N ethene;sodium Chemical group [Na].C=C BEGBSFPALGFMJI-UHFFFAOYSA-N 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 229940068052 ginkgo biloba extract Drugs 0.000 description 1
- 235000020686 ginkgo biloba extract Nutrition 0.000 description 1
- SYKWLIJQEHRDNH-KRPIADGTSA-N glutaryl-coa Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSC(=O)CCCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SYKWLIJQEHRDNH-KRPIADGTSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229940080794 lovastatin 20 mg Drugs 0.000 description 1
- 108010030696 low density lipoprotein triglyceride Proteins 0.000 description 1
- QXUAFCKBYYPTPQ-ZWKAXHIPSA-L magnesium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.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 QXUAFCKBYYPTPQ-ZWKAXHIPSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000003687 soy isoflavones Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a composition containing lovastatin and the use thereof. The composition contains lovastatin, pantethine, and/or medicinally acceptable coating material or additives in the class of flavonoid. The composition can be applied to prepare medicine for improving the content of cholesterin in blood and prepare an agent for improving the lipid in blood. The composition of the present invention can obviously reduce the content of cholesterin in blood by proved by research; compared with the effect of respectively using each component, the effect is better; the dosage of the lovastatin can be reduced; consequently, the adverse reactions caused by long-term and a large amount of medicine administration can be greatly reduced; the composition provides medicine with an outstanding curative effect of treating hyperlipemia for clinical application.
Description
Technical field
The present invention relates to lipid ameliopant composition in a kind of blood, relate in particular to the compositions that contains lovastatin, and improve in preparation in the medicine of accent blood fat such as blood middle cholesterol content and use.
Background technology
Raise with low density lipoprotein, LDL and very low density lipoprotein (VLDL) be that the hyperlipemia of feature can cause that atherosclerotic endotheliocyte obstacle, platelet aggregation are hyperfunction, foam cell formation etc., be one of main hazard factor of human tuinga cardiopathia early, so blood lipid ameliopant have vast market prospect.
Lovastatin (Lovastatin) is a kind of complete synthesis novel hydroxyl first glutaryl CoA reductase inhibitor.It is the most effective one of lipid lowering agent at present.This product oral absorption is good, but absorbs minimizing 30% on an empty stomach.This product is extensive first pass metabolism in liver, is hydrolyzed to multiple metabolite, comprises three kinds of active metabolites based on the b-hydroxy acid.The protein binding rate of this product and b-hydroxy acid metabolite is up to 95%, and peak time is 2～4 hours, T
1/2It is 3 hours.83% from the feces discharge, and 10% from the urine discharge.Drug withdrawal after the long-term treatment, effect continued for 4～6 weeks.It also has certain reduction effect to triglyceride.For the combined hyperlipidemia familial that low-density lipoprotein cholesterol and triglyceride all raise, the effect of lovastatin is particularly evident.But the heavy dose of use of patient can cause that liver transaminase raises, and causes myalgia and myositis.If share with other fat-reducing medicaments such as nicotinic acid or the special class of shellfish needs SC, in case myositis and rhabdomyolysis and acute renal failure takes place.In addition, though the lovastatin high medicine that is safety threshold owing to be the medicine of taking for a long time, thereby wishes to reduce T-CHOL amount in the blood with still less dose.
Pantethine is the analog of pantothenic acid, more is similar to coenzyme A than pantothenic acid, can reduce blood cholesterol, improves lipid metabolism, also can suppress thrombocytopenia, promotes the platelet recovery effect.Clinically be mainly used in blood fat reducing, effect is not as statins, but side effect is little, and idol has the gastrointestinal upset reaction.
On the other hand, can bring into play effect for reducing fat by number of ways for the flavones ingredient that extracts the plant of representative, prevention and treatment hyperlipemia are had certain meaning from Semen sojae atricolor, Semen Ginkgo, Radix Puerariae etc.
Still there is not the medicine listing of similar preparation of compositions so far.
Summary of the invention
The purpose of this invention is to provide a kind of compositions that contains lovastatin, said composition comprises adjuvant or the additive that lovastatin, pantethine and/or flavonoid, pharmaceutics allow.Lovastatin be meant (S)-2-Methyl Butyric Acid-(1S, 3S, 7S, 8S, 8aR)-1,2,3,7,8,8a-six hydrogen-3,7-dimethyl-8-{2-[(2R, 4R)-4-hydroxyl-6 oxos-2-THP trtrahydropyranyl]-ethyl-1-naphthalene ester; Pantethine is meant 2,4-dihydroxy-N-[3-[(2-mercaptoethyl) amino]-the 3-oxopropyl]-3, the 3-amide dimethyl butyrate; Flavonoid is meant soybean isoflavone or Ginkgo total flavones.
The form of the pharmaceutical preparation of present composition preparation is solid preparation or liquid preparation.
Compositions of the present invention is in the occasion of solid preparation, the weight percentage of the lovastatin that contains is generally 0.005%～3%, preferred 0.03～2%, the weight percentage of pantethine is generally 0.3～47%, preferred 1.0～20%, the weight percentage of flavonoid is generally 0.3～50%, and preferred 1～25%.
Compositions of the present invention is in the occasion of liquid preparation, in g/ml, the weight percentage of the lovastatin that contains is generally 0.03%～0.1%, preferred 0.005%～0.05%, pantethine is generally 0.05%～2%, preferred 0.1%～1%, flavonoid is generally 0.1%～5%, and preferred 0.2%～3.5%.
Solid preparation as the present composition comprises tablet, granule, powder, capsule etc.
Compositions provided by the invention, adjuvant that allows with pharmaceutics or additive can be used in preparation improves the medicine of blood middle cholesterol content.Also can in preparation blood, use in the lipid ameliopant.
" improvement " of lipid ameliopant is meant significant clinically improvement in the blood of the present invention, can cholesterol reducing, triglyceride, low density lipoprotein, LDL, and can raise high density lipoprotein.
When giving compositions of the present invention, can adopt the various compositions that give compositions simultaneously respectively, perhaps certain hour gives the mode of the various compositions of compositions respectively at interval.
Above-mentioned " simultaneously " administration, so long as can get final product in simultaneously the mode of time administration almost, there is no particular limitation, preferably as single compositions administration.
In addition, above-mentioned " certain hour is respectively at interval " administration, so long as can get final product at the administering mode of different time difference administrations, there is no particular limitation, for example gives a kind of composition, then after the time that process is determined, gives the method for other composition.Comprise the method that gives all these compositions simultaneously, difference interval certain hour is the method for independent administration separately, gives 2 kinds simultaneously, and certain hour gives the method for residual drug at interval.
The present composition is through transferring the experimentation of blood fat, and confirmation can significantly reduce blood cholesterol, triglyceride, low density lipoprotein, LDL, and can raise hdl concentration.Its effect is singly used better effects if than each component, and because the minimizing of lovastatin consumption, thereby can significantly reduce the untoward reaction of taking medicine.
The compositions that lovastatin provided by the invention and pantethine or lovastatin, pantethine and flavonoid combine (the i.e. lovastatin of 0.075% (g/ml), the pantethine of 0.675% (g/ml), the soybean isoflavone of 0.3% (g/ml)) has good effects such as accent blood fat, and can alleviate the untoward reaction that long-term prescription brings, therefore can in preparation improves the medicine of blood middle cholesterol content, use, also can use in as the blood fat and improving agent in preparation.
The specific embodiment
Exemplify case study on implementation below and further describe the present invention, but the present invention is not subjected to the qualification of these embodiment.
Embodiment 1 tablet
(1) composition
| In 4 (1400mg) | In 4 (1400mg) | In 4 (1400mg) | |
| Lovastatin pantethine isoflavones GINKGO BILOBA EXTRACT avicel cellulose metasilicic acid magnesium aluminate sucrose fatty ester hydroxypropyl cellulose dolomol PVPP lactose | 20mg 550mg--170mg 60mg 200mg 48mg 24mg 48mg is an amount of | 20mg 500mg 225mg-120mg-140mg 48mg 24mg 48mg is an amount of | 20mg 500mg-225mg 120mg-140mg 48mg 24mg 48mg is an amount of |
(2) method for making
By the amount of above-mentioned each composition, measure mentioned component, according to a preparation of Chinese Pharmacopoeia preparation general provisions " tablet " tablet.
Embodiment 2 granules
(1) composition
| In 4 bags (5g) | In 4 bags (5g) | In 4 bags (5g) | |
| Lovastatin pantethine soybean isoflavone Ginkgo total flavones | 20mg 1100mg - - | 20mg 1000mg 300mg - | 20mg 1000mg - 300mg |
| Refined sucrose starch polysorbate80 metasilicic acid magnesium aluminate magnesium stearate lactose | 1650mg 1300mg-50mg 24mg is an amount of | 1600mg 1200mg 48mg-24mg is an amount of | 1600mg 1200mg 48mg-24mg is an amount of |
(2) method for making: by the amount of above-mentioned each composition, measure mentioned component, according to a preparation of Chinese Pharmacopoeia preparation general provisions " granule " granule.
Embodiment 3 capsules
(1) composition
| In 4 capsules | In 4 capsules | In 4 capsules | |
| Lovastatin | 20mg | 20mg | 20mg |
| Pantethine | 550mg | 500mg | 500mg |
| Soybean isoflavone | - | 300mg | - |
| Ginkgo total flavones | - | - | 300mg |
| Starch | 1210mg | 960mg | 960mg |
| Polysorbate80 | - | 48mg | 48mg |
| The metasilicic acid magnesium aluminate | 50mg | - | - |
| Magnesium stearate | 24mg | 24mg | 24mg |
| Lactose | In right amount | In right amount | In right amount |
(2) method for making: by the amount of above-mentioned each composition, measure mentioned component, according to a preparation of Chinese Pharmacopoeia preparation general provisions " capsule " capsule.
Embodiment 4 liquid preparations (oral liquid)
(1) composition
| Among the 100mL | Among the 100mL | Among the 100mL | |
| The lovastatin pantethine | 20mg 550mg | 20mg 500mg | 20mg 500mg |
| Isoflavones Total Ginkgo Flavone-Glycoides D-glucitol liquid honey sodium ethylene diamine tetracetate ethanol stearic acid polyoxyethylene hardened castor oil 60 Sodium Benzoate spices distilled water | --6g 8g 20mg 2ml 100mg 60mg trace is an amount of | 300mg-6g 8g 20mg 2mL 100mg 60mg trace is an amount of | -300mg 6g 8g 20mg 2mL 100mg 60mg trace is an amount of |
(2) method for making
By the amount of above-mentioned each composition, measure mentioned component, according to a preparation of Chinese Pharmacopoeia preparation general provisions " liquid preparation " oral liquid.
The pharmaceutical composition of embodiment 5 lovastatins, pantethine and soybean isoflavone improves the blood fat pharmacodynamics test
(1) experiment purpose
Observe lovastatin, pantethine compositions or lovastatin, pantethine, soybean isoflavone compositions prevention curative effect to the high fat rat model of bait.
(2) experimental drug thing
Lovastatin is Zhejiang Rui Bang pharmaceutcal corporation, Ltd product, lot number 040205.
Pantethine is Xinfu Pharmaceutical Ind Co., Ltd., Hangzhou's product, lot number 20040401.
Soybean isoflavone is Zhejiang Xinxin Bio-tech Co., Ltd.'s product, lot number: 20040611.
(3) laboratory animal
60 of SD rats, male, body weight 150-170g is provided the quality certification by Zhejiang University's Experimental Animal Center: No. 20010014, the moving word of Zhejiang doctor.
(4) experimental technique
60 of SD rats, male, body weight 150-170g, give normal diet earlier under the environment of experiment, observed 5 days, water 12h is can't help in fasting then, cut tail and get blood 1.0～1.5ml, centrifugal 5000rpm, 10min, get serum 0.3～0.5ml, measure the normal value of its T-CHOL (TC), triglyceride (TG), low density lipoprotein, LDL (LDL), high density lipoprotein (HDL) respectively, and, adopt the stratified random method according to blood lipid level, animal is divided into 6 groups, 10 every group.Be grouped as follows: 1. group of solvents (0.8% sodium carboxymethyl cellulose, CMC-Na); 2. lovastatin group 15mg/kg (A); 3. pantethine group 90mg/kg (B); 4. lovastatin 7.5mg/kg+ pantethine 67.5mg/kg; 5. lovastatin 7.5mg/kg+ pantethine 67.5mg/kg+ Ginkgo total flavones 30mg/kg; 6. lovastatin 7.5mg/kg+ pantethine 67/5mg/kg+ soybean isoflavone 30mg/kg.
Begin from formal experiment, each treated animal is used high lipid food instead and is fed, administration respectively.Administration capacity 1ml/100g, one month administration cycle.Get hematometry for the same method of medicamental pulverata.
(5) experimental result
High lipid food was fed in continuous 30 days, and each lipid level of organizing rat blood serum significantly raises.Lovastatin 7.5mg/kg+ pantethine 67.5mg/kg group; Lovastatin 7.5mg/kg+ pantethine 67.5mg/kg+ soybean isoflavone 30mg/kg group is all good than lovastatin or the independent Use Limitation fruit of pantethine.Compare with group of solvents, lovastatin 7.5mg/kg+ pantethine 67.5mg/kg+ soybean isoflavone 30mg/kg prescription can prevent the rising of T-CHOL, low density lipoprotein, LDL, C-VLDL level, and significant difference (P＜0.05) is arranged.Simultaneously, significant difference (P＜0.05) is also arranged with lovastatin group comparison T-CHOL, low density lipoprotein, LDL, C-VLDL level, T-CHOL and high density lipoprotein ratio, and the liver toxicity of antagonism lovastatin, the results are shown in Table 1.
Table 1 lovastatin, pantethine share soybean isoflavone or Ginkgo total flavones to rat fat level and toxic influence
(n＝10)
| Group | Serum lipids lift-off value (mg/dl) | Toxicity (U/L) | |||||||
| T-CHOL | Triglyceride | High density lipoprotein | Low density lipoprotein, LDL | Very low density lipoprotein (VLDL) | T-CHOL/high density lipoprotein | Alanine aminotransferase (ALT) | Creatine kinase | Aspartate aminotransferase enzyme (AST) | |
| Solvent | 204±42 | 61±20 | 12±9 | 180±45 | 21±17 | 2.23±0.72 | 42±9 | 609±150 | 175±35 |
| Lovastatin 7.5mg/kg | 177±25 | 62±17 | 17±15 | 168±23 | 23±13 | 2.23±0.59 | 62±28 * | 611±203 | 174±32 |
| Pantethine 67.5mg/kg | 198±88 | 63±26 | 21±8 * | 174±58 | 26±13 | 1.94±0.76 | 46±9 # | 633±234 | 194±35 |
| Lovastatin | 166±97 | 63±29 | 19±13 | 154±62 | 15±14 | 1.99±0.81 | 56±28 | 629±162 | 183±27 |
| 7.5mg/kg+pantethine 67.5mg/kg | |||||||||
| Lovastatin 7.5mg/kg+pantethine 67.5mg/kg+Ginkgo total flavones 30mg/kg | 126±35 *# | 49± 20 *# | 24±11 * | 127±29 *# | 11±9 *# | 2.62±0.83 | 41±13 # | 606±183 | 188±48 |
| Luo Tating 7.5 mg/kg+ pantethine 67.5mg/kg+soybean isoflavone 30mg/kg | 118± 27 *## | 47± 18 *# | 24±7 * | 125±20 *# | 8±8 *# | 1.54±031 # | 39±11 # | 602±133 | 177±32 |
*P＜0.05, vs group of solvents, t check
#P＜0.05,
##P＜0.01, vs lovastatin group, t check
(6) experiment conclusion
By every day 7.5mg/kg lovastatin+67.5mg/kg pantethine+soybean isoflavone 30mg/kg and every day 7.5mg/kg lovastatin+67.5mg/kg pantethine+ginkgetin 30mg/kg prescription the drug composition oral administration, prevention rat fat other group that raises in this experiment is more effective.
List of references:
1, punishment is prosperous emerging. transfer the pharmacological action and the clinical practice of blood fat new drug atorvastatin. and " foreign medical science pharmacy fascicle " the 25th the 6th phase of volume of December in 1998.
2, wear big, Chen Xuezhi, Wang Xiaoli, Haibo Liu, Li Nan. Fructus Pruni extract and ginkgetin are regulated the effect research of rat fat. " Shanghai preventive medicine magazine " .Sh J Prev Med, Vol 15, No.6.
3. among the Xiao Li, Jiang Zhiping, Xu Xin: soybean isoflavone influences clinical department of internal medicine magazine 2004 to the serum lipid with coronary heart disease compliance rate; 21 (6): 393-394.
4, appoint quiet, He Jiaqing, Chen Qin Konjaku plucosidopolyose and ginkgetin compound are to the experimentation of hyperlipemia. " Zhongshan University's journal (natural science edition) " Vol.42 Suppl Jun.2003.
5, PANG Xiao-yun, YAO Ming-hui, LU Ying-qing, GONG Qin-yan.Effectof soy isoflavones on malondialdehyde and superoxide dismutase of bloodandliver in hypercholesterolemia rats. Chinese Journal of New Drugs and Clinical Remedies (Chin J NewDrugs Clin Rem), in May, 2002, the 21st volume, the 5th phase 257-262.
Claims (4)
1. compositions that contains lovastatin, lovastatin is meant: (S)-and 2-Methyl Butyric Acid-(1S, 3S, 7S, 8S, 8aR)-1,2,3,7,8,8a-six hydrogen-3,7-dimethyl-8-{2-[(2R, 4R)-4-hydroxyl-6-oxo-2-THP trtrahydropyranyl]-ethyl }-1-naphthalene ester, it is characterized in that: compositions comprises lovastatin, pantethine, adjuvant or additive that flavonoid and pharmaceutics allow, flavonoid is selected soybean isoflavone or Ginkgo total flavones for use, and compositions is the solid preparation form, and the weight percentage of the lovastatin that compositions contains is 0.005～3%, the weight percentage of pantethine is 0.3～47%, and the weight percentage of flavonoid is 0.3～50%.
2. compositions that contains lovastatin, lovastatin is meant: (S)-and 2-Methyl Butyric Acid-(1S, 3S, 7S, 8S, 8aR)-1,2,3,7,8,8a-six hydrogen-3,7-dimethyl-8-{2-[(2R, 4R)-4-hydroxyl-6-oxo-2-THP trtrahydropyranyl]-ethyl }-1-naphthalene ester, it is characterized in that: compositions comprises lovastatin, pantethine, flavonoid, adjuvant or additive with the pharmaceutics permission, flavonoid is selected soybean isoflavone or Ginkgo total flavones for use, and compositions is the liquid preparation form, and the weight percentage of the lovastatin that contains in g/ml in the compositions is 0.03～0.1%, the weight percentage of pantethine is 0.05～2.0%, and the weight percentage of flavonoid is 0.1～5.0%.
3. the compositions that contains lovastatin according to claim 1 and 2 is improved application in the medicine of blood middle cholesterol content in preparation.
4. the compositions application in the lipid ameliopant in preparation blood that contains lovastatin according to claim 1 and 2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510049300XA CN1332657C (en) | 2005-01-31 | 2005-01-31 | Composition containing lovastatin and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510049300XA CN1332657C (en) | 2005-01-31 | 2005-01-31 | Composition containing lovastatin and use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1679548A CN1679548A (en) | 2005-10-12 |
| CN1332657C true CN1332657C (en) | 2007-08-22 |
Family
ID=35066571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510049300XA Expired - Fee Related CN1332657C (en) | 2005-01-31 | 2005-01-31 | Composition containing lovastatin and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1332657C (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1304724A (en) * | 2001-01-19 | 2001-07-25 | 郭兴华 | Composition for preventing and treating osteoporosis and cancer and decreasing blood fat and its application |
| WO2004004774A2 (en) * | 2002-07-03 | 2004-01-15 | Esperion Therapeutics, Inc. | Compositions comprising panthetine for the treatment of dyslipidemia |
| CN1539475A (en) * | 2003-10-27 | 2004-10-27 | 张文高 | Combination of natural products for curing hyperlipemia, atherosclerosis and relevant disease |
-
2005
- 2005-01-31 CN CNB200510049300XA patent/CN1332657C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1304724A (en) * | 2001-01-19 | 2001-07-25 | 郭兴华 | Composition for preventing and treating osteoporosis and cancer and decreasing blood fat and its application |
| WO2004004774A2 (en) * | 2002-07-03 | 2004-01-15 | Esperion Therapeutics, Inc. | Compositions comprising panthetine for the treatment of dyslipidemia |
| CN1539475A (en) * | 2003-10-27 | 2004-10-27 | 张文高 | Combination of natural products for curing hyperlipemia, atherosclerosis and relevant disease |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1679548A (en) | 2005-10-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Orsi et al. | Simvastatin‐associated memory loss | |
| AU732465B2 (en) | Combination therapy for reducing the risks associated with cardiovascular disease | |
| US8895079B2 (en) | Combinations of botanical extracts for promoting cardiovascular health | |
| US6673831B1 (en) | Combination therapy for reducing the risks associated with cardiovascular disease | |
| US7977378B1 (en) | Compositions and methods for enhancing weight-loss by cyclical administration of compounds | |
| JP2007530688A (en) | Composition with reduced hepatotoxicity | |
| RU2003122061A (en) | ANTIATEROSCLEROTIC COMPOSITION CONTAINING CAROTINOIDS AND METHOD FOR INHIBITING OXIDATION OF LOW DENSITY Lipoprotein (LDL) | |
| CN106659755A (en) | Methods, drugs and drug formula for processing mammal sexual dysfunction | |
| US9642860B2 (en) | Combinations of corroles and statins | |
| AU726822B2 (en) | Pharmaceutical compositions comprising alkanoyl L-carnitine in combination with a statine for treating pathologies brought about by an altered lipid metabolism | |
| CN1332657C (en) | Composition containing lovastatin and use thereof | |
| US20110117070A1 (en) | Compositions and methods for treating headache | |
| JP4741581B2 (en) | Composition for the treatment of hyperlipidemia | |
| CN1329031C (en) | Blood-fat regulating medicinal composition and use thereof | |
| US20090214682A1 (en) | Composition and methods for weight loss in a subject | |
| CN1274302C (en) | Blood fat reducing composition containing avatatin and its use | |
| KR100725263B1 (en) | Antilipemic combinations comprising HMG-CoA reductase inhibitors and carnitines | |
| CN113271931A (en) | New application of carbamate beta phenylethanolamine analogue in enhancing clearance of intracellular LDL cholesterol and combination with statins | |
| CN100566716C (en) | The compositions of treatment hyperlipidemia | |
| CN113134086B (en) | Pharmaceutical composition for reducing blood fat | |
| CN100358526C (en) | Composite for treating hyperlipidemia | |
| KR20090027383A (en) | Composition for preventing or treating hyperlipidemia | |
| Zeb | Hepatoprotective effects of various solvent extracted samples of paeonia emodi (wall) in mice with paracetamol-induced hepatotoxicity | |
| Sarangi et al. | PIPERINE: A NATURAL BIOENHANCER. | |
| EP2958627A1 (en) | Composition for the treatment of metabolic disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG HANGZHOU XINFU PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: XINFU PHARMACEUTICAL IND CO., LTD., HANGZHOU Effective date: 20080222 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20080222 Address after: Ling'an Economic Development Zone, Zhejiang Patentee after: ZHEJIANG HANGZHOU XINFU PHARMACEUTICAL Co.,Ltd. Address before: Economic Development Zone, Lin'an City, Zhejiang Province (Qingshanhu Street) Post code: 311305 Patentee before: ZHEJIANG HANGZHOU XINFU PHARMACEUTICAL Co.,Ltd. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 311300 Ling'an Economic Development Zone, Zhejiang Patentee after: YIFAN XINFU PHARMACEUTICAL Co.,Ltd. Address before: 311300 Ling'an Economic Development Zone, Zhejiang Patentee before: ZHEJIANG HANGZHOU XINFU PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20160720 Address after: Hangzhou City, Zhejiang province 311300 Ling'an City Kam South Street No. 9 Gua fan Patentee after: HANGZHOU XINFU SCIENCE & TECHNOLOGY Co.,Ltd. Address before: 311300 Ling'an Economic Development Zone, Zhejiang Patentee before: YIFAN XINFU PHARMACEUTICAL Co.,Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070822 Termination date: 20210131 |