CA2007643A1 - Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination - Google Patents

Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination

Info

Publication number: CA2007643A1
Authority: CA; Canada
Prior art keywords: inhibitor; combination; enzyme; hmg coa; coa reductase
Prior art date: 1989-02-01
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.): Abandoned

Application number

CA002007643A

Other languages

English (en)

French (fr)

Inventor

Donald S. Karanewsky

Scott A. Biller

Eric M. Gordon

William A. Scott

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1989-02-01

Filing date

1990-01-12

Publication date

1990-08-01

1990-01-12 Application filed by Individual filed Critical Individual

1990-08-01 Publication of CA2007643A1 publication Critical patent/CA2007643A1/en

Status Abandoned legal-status Critical Current

Links

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 title claims abstract description 31
238000000034 method Methods 0.000 title claims abstract description 11
229940121710 HMGCoA reductase inhibitor Drugs 0.000 title abstract description 14
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title abstract description 14
239000004059 squalene synthase inhibitor Substances 0.000 title description 21
229940123495 Squalene synthetase inhibitor Drugs 0.000 title description 16
239000003112 inhibitor Substances 0.000 claims abstract description 32
TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims abstract description 24
229960002965 pravastatin Drugs 0.000 claims abstract description 24
TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims abstract description 24
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 claims abstract description 21
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 claims abstract description 19
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 claims abstract description 19
108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 claims abstract description 17
229960004844 lovastatin Drugs 0.000 claims abstract description 17
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims abstract description 12
230000015572 biosynthetic process Effects 0.000 claims abstract description 10
102000004190 Enzymes Human genes 0.000 claims abstract description 8
108090000790 Enzymes Proteins 0.000 claims abstract description 8
102000004316 Oxidoreductases Human genes 0.000 claims abstract description 7
108090000854 Oxidoreductases Proteins 0.000 claims abstract description 7
230000002401 inhibitory effect Effects 0.000 claims abstract description 7
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-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@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 claims abstract description 5
102000003960 Ligases Human genes 0.000 claims abstract description 4
108090000364 Ligases Proteins 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 15
-1 2,3-di-substituted pyrrole Chemical class 0.000 claims description 11
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims description 10
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 10
JYVXNLLUYHCIIH-ZCFIWIBFSA-N R-mevalonolactone, (-)- Chemical compound C[C@@]1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-ZCFIWIBFSA-N 0.000 claims description 9
JYVXNLLUYHCIIH-UHFFFAOYSA-N (+/-)-mevalonolactone Natural products CC1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-UHFFFAOYSA-N 0.000 claims description 7
229940057061 mevalonolactone Drugs 0.000 claims description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 4
AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical group C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 4
229950009116 mevastatin Drugs 0.000 claims description 4
BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 4
RIZIYJOVNPJCDN-UHFFFAOYSA-N 3-hydroxy-4-phosphonobutanoic acid Chemical class OC(=O)CC(O)CP(O)(O)=O RIZIYJOVNPJCDN-UHFFFAOYSA-N 0.000 claims description 2
150000002460 imidazoles Chemical class 0.000 claims description 2
125000000468 ketone group Chemical group 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
150000003217 pyrazoles Chemical class 0.000 claims description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
FJLGEFLZQAZZCD-JUFISIKESA-N (3S,5R)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@H](O)C[C@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-JUFISIKESA-N 0.000 claims 1
POPHMOPNVVKGRW-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydronaphthalene Chemical compound C1CCC2CCCCC2=C1 POPHMOPNVVKGRW-UHFFFAOYSA-N 0.000 claims 1
ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 claims 1
230000000055 hyoplipidemic effect Effects 0.000 claims 1
230000000871 hypocholesterolemic effect Effects 0.000 claims 1
125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 claims 1
229930192474 thiophene Natural products 0.000 claims 1
SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 37
150000004702 methyl esters Chemical class 0.000 description 21
150000001875 compounds Chemical class 0.000 description 18
239000004305 biphenyl Substances 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 10
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 10
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 10
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 10
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 9
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 9
239000002775 capsule Substances 0.000 description 9
239000002552 dosage form Substances 0.000 description 9
239000008101 lactose Substances 0.000 description 9
229960001375 lactose Drugs 0.000 description 9
235000002639 sodium chloride Nutrition 0.000 description 9
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 7
235000012000 cholesterol Nutrition 0.000 description 7
235000011180 diphosphates Nutrition 0.000 description 7
102000007330 LDL Lipoproteins Human genes 0.000 description 6
108010007622 LDL Lipoproteins Proteins 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 6
229920002261 Corn starch Polymers 0.000 description 5
ATZKAUGGNMSCCY-VVFNRDJMSA-N [(1r,2r,3r)-2-[(3e)-4,8-dimethylnona-3,7-dienyl]-2-methyl-3-[(1e,5e)-2,6,10-trimethylundeca-1,5,9-trienyl]cyclopropyl]methyl phosphono hydrogen phosphate Chemical class CC(C)=CCC\C(C)=C\CC\C(C)=C\[C@@H]1[C@@H](COP(O)(=O)OP(O)(O)=O)[C@]1(C)CC\C=C(/C)CCC=C(C)C ATZKAUGGNMSCCY-VVFNRDJMSA-N 0.000 description 5
239000013543 active substance Substances 0.000 description 5
235000010290 biphenyl Nutrition 0.000 description 5
239000008120 corn starch Substances 0.000 description 5
229940099112 cornstarch Drugs 0.000 description 5
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical group [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 5
238000009472 formulation Methods 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
239000000126 substance Substances 0.000 description 5
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
229920000168 Microcrystalline cellulose Polymers 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
239000008108 microcrystalline cellulose Substances 0.000 description 4
235000019813 microcrystalline cellulose Nutrition 0.000 description 4
229940016286 microcrystalline cellulose Drugs 0.000 description 4
239000006186 oral dosage form Substances 0.000 description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
229920002785 Croscarmellose sodium Polymers 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
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 3
229960001681 croscarmellose sodium Drugs 0.000 description 3
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
150000001942 cyclopropanes Chemical class 0.000 description 3
239000000463 material Substances 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
ZGGHKIMDNBDHJB-RPQBTBOMSA-M (3S,5R)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@H](O)C[C@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-RPQBTBOMSA-M 0.000 description 2
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YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
241000271566 Aves Species 0.000 description 2
241000167854 Bourreria succulenta Species 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
GVVPGTZRZFNKDS-YFHOEESVSA-N Geranyl diphosphate Natural products CC(C)=CCC\C(C)=C/COP(O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-YFHOEESVSA-N 0.000 description 2
102000015779 HDL Lipoproteins Human genes 0.000 description 2
108010010234 HDL Lipoproteins Proteins 0.000 description 2
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WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
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ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
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229930006000 Sucrose Natural products 0.000 description 2
BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
COPCBKSWBBSTPU-UHFFFAOYSA-M [O-2].[Mg+2].[Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O Chemical compound [O-2].[Mg+2].[Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O COPCBKSWBBSTPU-UHFFFAOYSA-M 0.000 description 2
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
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PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
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GVVPGTZRZFNKDS-JXMROGBWSA-N geranyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-JXMROGBWSA-N 0.000 description 2
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NUHSROFQTUXZQQ-UHFFFAOYSA-N isopentenyl diphosphate Chemical compound CC(=C)CCO[P@](O)(=O)OP(O)(O)=O NUHSROFQTUXZQQ-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
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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
- A61K31/66—Phosphorus compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics

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Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002007643A 1989-02-01 1990-01-12 Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination Abandoned CA2007643A1 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US30534389A	1989-02-01	1989-02-01
US305,343		1989-02-01

Publications (1)

Publication Number	Publication Date
CA2007643A1 true CA2007643A1 (en)	1990-08-01

Family

ID=23180410

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002007643A Abandoned CA2007643A1 (en)	1989-02-01	1990-01-12	Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination

Country Status (6)

Country	Link
JP (1)	JPH02235821A (ja)
CA (1)	CA2007643A1 (ja)
DE (1)	DE4002836C2 (ja)
FR (1)	FR2642311B1 (ja)
GB (1)	GB2227662B (ja)
IT (1)	IT1238080B (ja)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH05239075A (ja) *	1991-08-27	1993-09-17	Eisai Co Ltd	含リンイソプレノイド誘導体
HUT72307A (en)	1993-03-08	1996-04-29	Eisai Co Ltd	Phosphonic acid derivatives
AU4988100A (en) *	1999-05-07	2000-11-21	Brigham And Women's Hospital	Use of hmgcoa reductase inhibitors in the prevention of diseases whose pathogenesis is dependent on neovascularization
DE10038043B4 (de) *	2000-08-02	2006-09-07	Walter, Michael, Dr.	Phamakologisch wirksame Substanz zur Behandlung kardiovaskulärer Erkrankungen
AUPR549901A0 (en)	2001-06-06	2001-07-12	Vital Health Sciences Pty Ltd	Topical formulation containing tocopheryl phosphates
BR0211673A (pt)	2001-07-27	2004-07-13	Vital Health Sciences Pty Ltd	Terapia dermal utilizando derivados de fosfato de agentes de transferência de elétrons
AU2002950713A0 (en)	2002-08-09	2002-09-12	Vital Health Sciences Pty Ltd	Carrier
AU2003901812A0 (en) *	2003-04-15	2003-05-01	Vital Health Sciences Pty Ltd	Phosphates of secondary alcohols
JP4847437B2 (ja)	2004-03-03	2011-12-28	バイタルヘルスサイエンシズプロプライアタリーリミティド	アルカロイド製剤
AR054368A1 (es) *	2005-06-01	2007-06-20	Takeda Pharmaceutical	Metodo para tratar hiperlipidemia
US9168216B2 (en)	2005-06-17	2015-10-27	Vital Health Sciences Pty. Ltd.	Carrier comprising one or more di and/or mono-(electron transfer agent) phosphate derivatives or complexes thereof
EP2531047B1 (en)	2010-02-05	2024-11-13	Phosphagenics Limited	Carrier comprising non-neutralised tocopheryl phosphate
ES2829386T3 (es)	2010-03-30	2021-05-31	Phosphagenics Ltd	Parche de administración transdérmica
WO2012122586A1 (en)	2011-03-15	2012-09-20	Phosphagenics Limited	New composition
MX383940B (es)	2015-12-09	2025-03-14	Phosphagenics Ltd	Formulación farmacéutica que contiene tocol fosfato.
IL267006B2 (en)	2016-12-21	2024-11-01	Phosphagenics Ltd	Process for phosphorylation of a complex alcohol with p4o10 at high temperatures, and products thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2009918A6 (es) *	1987-05-22	1989-10-16	Squibb & Sons Inc	Procedimiento para preparar inhibidores de hmg-coa-reductasa que contienen fosforo.
US4871721A (en) *	1988-01-11	1989-10-03	E. R. Squibb & Sons, Inc.	Phosphorus-containing squalene synthetase inhibitors
CA2003478A1 (en) *	1988-12-12	1990-06-12	Leonard G. Dennick	Combination of an hmg coa reductase inhibitor and other type of serum cholesterol reducing agent and method for lowering serum cholesterol using such combination

1990
- 1990-01-12 CA CA002007643A patent/CA2007643A1/en not_active Abandoned
- 1990-01-30 GB GB9002016A patent/GB2227662B/en not_active Expired - Fee Related
- 1990-01-31 FR FR909001124A patent/FR2642311B1/fr not_active Expired - Fee Related
- 1990-01-31 DE DE4002836A patent/DE4002836C2/de not_active Expired - Fee Related
- 1990-02-01 IT IT01922090A patent/IT1238080B/it active IP Right Grant
- 1990-02-01 JP JP2023628A patent/JPH02235821A/ja active Pending

Also Published As

Publication number	Publication date
GB2227662B (en)	1993-03-17
DE4002836A1 (de)	1990-08-02
IT9019220A1 (it)	1991-08-01
FR2642311B1 (fr)	1991-10-25
IT9019220A0 (it)	1990-02-01
GB2227662A (en)	1990-08-08
DE4002836C2 (de)	1998-08-27
GB9002016D0 (en)	1990-03-28
FR2642311A1 (fr)	1990-08-03
IT1238080B (it)	1993-07-05
JPH02235821A (ja)	1990-09-18

Legal Events

Date	Code	Title	Description
1996-12-02	EEER	Examination request
2000-05-23	FZDE	Discontinued
2023-05-26	FZDE	Discontinued	Effective date: 20000523

Publication	Publication Date	Title
US5298497A (en)	1994-03-29	Method for preventing onset of hypertension employing a cholesterol lowering drug
USH1286H (en)	1994-02-01	Method for treating peripheral atherosclerotic disease employing a cholesterol lowering drug, an ace inhibitor, or a combination thereof
CA2040865C (en)	2002-07-23	Method for preventing, stabilizing or causing regression of atherosclerosis employing a combination of a cholesterol lowering drug and an ace inhibitor
US5622985A (en)	1997-04-22	Method for preventing a second heart attack employing an HMG CoA reductase inhibitor
CA2007643A1 (en)	1990-08-01	Combination of an hmg coa reductase inhibitor and a squalene synthetase inhibitor and method for lowering serum cholesterol using such combination
Kita et al.	1980	Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in livers of mice treated with mevinolin, a competitive inhibitor of the reductase
US5157025A (en)	1992-10-20	Method for lowering serum cholesterol employing a phosphorus containing ace inhibitor alone or in combination with a cholesterol lowering drug
CA2052014A1 (en)	1992-04-20	Method for preventing diabetic complications employing a cholesterol lowering drug alone or in combination with an ace inhibitor
EP0455042A1 (en)	1991-11-06	Combination of pravastatin and a fibric acid derivative, and method for treating dyslipidemia using such combination
IE911910A1 (en)	1991-12-18	METHOD FOR PREVENTING A SECOND HEART ATTACK EMPLOYING AN HMG¹CoA REDUCTASE INHIBITOR
CA2003478A1 (en)	1990-06-12	Combination of an hmg coa reductase inhibitor and other type of serum cholesterol reducing agent and method for lowering serum cholesterol using such combination
CA2007641A1 (en)	1990-08-01	Combination of squalene synthetase inhibitor and other type of serum cholesterol reducing agent and method for lowering serum cholesterol using such combination
US6630502B2 (en)	2003-10-07	Method for preventing, stabilizing or causing regression of atherosclerosis employing a combination of a cholesterol lowering drug and an ace inhibitor