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
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- 239000003795 chemical substances by application Substances 0.000 abstract description 2
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- 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
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- 230000006838 adverse reaction Effects 0.000 abstract 1
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- 102000007330 LDL Lipoproteins Human genes 0.000 description 15
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- -1 2-mercaptoethyl Chemical group 0.000 description 7
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- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
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- 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
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- 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
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- 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
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- 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
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- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
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- 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
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- 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
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- 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
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- 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
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- 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
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- 210000003725 endotheliocyte Anatomy 0.000 description 1
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- 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
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- 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
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- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
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- 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
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
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 |
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 |
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 |
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 |
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 |
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Citations (3)
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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 |
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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 |
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