JP2003501385A5 - - Google Patents
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- JP2003501385A5 JP2003501385A5 JP2001501212A JP2001501212A JP2003501385A5 JP 2003501385 A5 JP2003501385 A5 JP 2003501385A5 JP 2001501212 A JP2001501212 A JP 2001501212A JP 2001501212 A JP2001501212 A JP 2001501212A JP 2003501385 A5 JP2003501385 A5 JP 2003501385A5
- Authority
- JP
- Japan
- Prior art keywords
- carnitine
- alkanoyl
- acid
- hmg
- composition according
- 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.)
- Pending
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- 239000002253 acid Substances 0.000 description 16
- -1 alkanoyl L-carnitine Chemical compound 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 10
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 10
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- 125000002252 acyl group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- 229960002855 simvastatin Drugs 0.000 description 5
- 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
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 229940095064 tartrate Drugs 0.000 description 4
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-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-NRFPMOEYSA-M 0.000 description 3
- 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 description 3
- 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 description 3
- 229960003765 fluvastatin Drugs 0.000 description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group 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 description 3
- 229960004844 lovastatin Drugs 0.000 description 3
- 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 description 3
- 229960002965 pravastatin Drugs 0.000 description 3
- 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 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 description 2
- QWYFHHGCZUCMBN-SECBINFHSA-N O-butanoyl-L-carnitine Chemical compound CCCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C QWYFHHGCZUCMBN-SECBINFHSA-N 0.000 description 2
- VSNFQQXVMPSASB-SNVBAGLBSA-N O-valeroyl-L-carnitine Chemical compound CCCCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C VSNFQQXVMPSASB-SNVBAGLBSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- IGQBPDJNUXPEMT-SNVBAGLBSA-N isovaleryl-L-carnitine Chemical compound CC(C)CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C IGQBPDJNUXPEMT-SNVBAGLBSA-N 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 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
Description
【特許請求の範囲】
【請求項１】
解毒量のＬ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつを含有し、２０ｍｇ／日を超える治療有効量のＨＭＧ−ＣＯＡレダクターゼ阻害剤を含有する、医薬組成物。
【請求項２】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤がロバスタチン、シンバスタチン、プラバスタチン、およびフルバスタチンからなる群から選択される、請求項１記載の医薬組成物。
【請求項３】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤がシンバスタチンである、請求項２記載の組成物。
【請求項４】
アルカノイルＬ−カルニチンが、アセチルＬ−カルニチン、プロピオニルＬ−カルニチン、ブチリルＬ−カルニチン、バレリルＬ−カルニチン、およびイソバレリルＬ−カルニチンからなる群より選択される、請求項１から３いずれかに記載の組成物。
【請求項５】
アルカノイルＬ−カルニチンがプロピオニルＬ−カルニチンである、請求項４記載の組成物。
【請求項６】
Ｌ−カルニチンが含まれている、請求項１から５いずれかに記載の組成物。
【請求項７】
Ｌ−カルニチンまたはアルカノイルＬ−カルニチンの薬学上許容される塩が、クロライド、ブロマイド、オロテート、酸アスパルテート、酸シトレート、酸ホスフェート、フマレートおよび酸フマレート、マレエートおよび酸マレエート、ムケート、酸オキサレート、酸スルフェート、グルコースホスフェート、タートレートおよび酸タートレートからなる群から選択される、請求項１から６いずれかに記載の組成物。
【請求項８】
解毒量のＬ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつを含有し、２０ｍｇ／日を超える治療有効量のＨＭＧ−ＣＯＡレダクターゼ阻害剤を含有する、脂質代謝不全に起因する疾患の治療のための医薬組成物。
【請求項９】
Ｌ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつを含有する、ＨＭＧ−ＣＯＡレダクターゼ阻害剤誘導性の毒性もしくは副作用の治療のための医薬組成物。
【請求項１０】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤がロバスタチン、シンバスタチン、プラバスタチン、およびフルバスタチンからなる群から選択される請求項８または９記載の医薬組成物。
【請求項１１】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤がシンバスタチンである請求項１０記載の医薬組成物。
【請求項１２】
アルカノイルＬ−カルニチンが、アセチルＬ−カルニチン、プロピオニルＬ−カルニチン、ブチリルＬ−カルニチン、バレリルＬ−カルニチン、およびイソバレリルＬ−カルニチンからなる群より選択される、請求項８または９記載の医薬組成物。
【請求項１３】
アルカノイルＬ−カルニチンがプロピオニルＬ−カルニチンである、請求項８または９記載の医薬組成物。
【請求項１４】
Ｌ−カルニチンが存在している、請求項８または９記載の医薬組成物。
【請求項１５】
Ｌ−カルニチンまたはアルカノイルＬ−カルニチンの薬学上許容される塩が、クロライド、ブロマイド、オロテート、酸アスパルテート、酸シトレート、酸ホスフェート、フマレートおよび酸フマレート、マレエートおよび酸マレエート、ムケート、酸オキサレート、酸スルフェート、グルコースホスフェート、タートレートおよび酸タートレートからなる群から選択される、請求項８または９記載の医薬組成物。
【請求項１６】
ロバスタチン、シンバスタチン、プラバスタチン、およびフルバスタチンからなる群から選択される２０ｍｇ／日を超える治療有効量のＨＭＧ−ＣＯＡレダクターゼ阻害剤と、Ｌ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつの解毒量との、ＨＭＧ−ＣＯＡレダクターゼ阻害剤の治療有効性を維持しつつＨＭＧ−ＣＯＡレダクターゼ阻害剤誘導性毒性作用を減ずるための組合せ。
【請求項１７】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤とＬ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつが連続的に投与される、請求項１６記載の組合せ。
【請求項１８】
ＨＭＧ−ＣＯＡレダクターゼ阻害剤とＬ−カルニチンまたは２〜６炭素原子の直鎖または分岐鎖状アルカノイル基を有するアルカノイルＬ−カルニチン、もしくはこれらの薬学上許容される塩のひとつが実質的に同時に投与される、請求項１６記載の組合せ。
【請求項１９】
請求項１の医薬組成物に、各薬物を同時に摂取せよ、または各薬物を予め定められた用量基準に基づき摂取せよとの使用説明書が添付されている製品。
[Claims]
(1)
Contains a detoxifying amount of L-carnitine or an alkanoyl L-carnitine having a linear or branched alkanoyl group of 2 to 6 carbon atoms, or one of pharmaceutically acceptable salts thereof , and has a therapeutic effect of more than 20 mg / day A pharmaceutical composition comprising an amount of an HMG-COA reductase inhibitor .
(2)
The pharmaceutical composition according to claim 1, wherein the HMG-COA reductase inhibitor is selected from the group consisting of lovastatin, simvastatin, pravastatin, and fluvastatin .
(3)
3. The composition according to claim 2 , wherein the HMG-COA reductase inhibitor is simvastatin.
(4)
The composition according to any one of claims 1 to 3 , wherein the alkanoyl L-carnitine is selected from the group consisting of acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine, and isovaleryl L-carnitine. object.
(5)
The composition according to claim 4 , wherein the alkanoyl L-carnitine is propionyl L-carnitine.
6.
The composition according to any one of claims 1 to 5 , wherein L-carnitine is contained.
7.
Pharmaceutically acceptable salts of L-carnitine or alkanoyl L-carnitine are chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, maleate and acid maleate, mukate, acid oxalate, acid sulfate The composition according to any one of claims 1 to 6, wherein the composition is selected from the group consisting of: glucose phosphate, tartrate, and acid tartrate.
Claim 8.
Contains a detoxifying amount of L-carnitine or alkanoyl L-carnitine having a linear or branched alkanoyl group of 2 to 6 carbon atoms, or one of pharmaceutically acceptable salts thereof, and has a therapeutic effect of more than 20 mg / day A pharmaceutical composition for treating a disease caused by lipid metabolism deficiency, which comprises an amount of an HMG-COA reductase inhibitor .
9.
HMG-COA reductase inhibitor- induced toxicity containing L-carnitine or alkanoyl L-carnitine having a linear or branched alkanoyl group of 2 to 6 carbon atoms, or one of their pharmaceutically acceptable salts Or a pharmaceutical composition for the treatment of side effects .
10.
The pharmaceutical composition according to claim 8 or 9, wherein the HMG-COA reductase inhibitor is selected from the group consisting of lovastatin, simvastatin, pravastatin, and fluvastatin .
11.
The pharmaceutical composition according to claim 10, wherein the HMG-COA reductase inhibitor is simvastatin .
12.
10. The pharmaceutical composition according to claim 8 , wherein the alkanoyl L-carnitine is selected from the group consisting of acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine, and isovaleryl L-carnitine.
Claim 13
The pharmaceutical composition according to claim 8 or 9 , wherein the alkanoyl L-carnitine is propionyl L-carnitine.
14.
The pharmaceutical composition according to claim 8 or 9 , wherein L-carnitine is present.
15.
Pharmaceutically acceptable salts of L-carnitine or alkanoyl L-carnitine are chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, maleate and acid maleate, mukate, acid oxalate, acid sulfate The pharmaceutical composition according to claim 8 or 9 , wherein the pharmaceutical composition is selected from the group consisting of glucose phosphate, tartrate and acid tartrate.
16.
A therapeutically effective amount of an HMG-COA reductase inhibitor in excess of 20 mg / day selected from the group consisting of lovastatin, simvastatin, pravastatin and fluvastatin, and L-carnitine or a linear or branched alkanoyl of 2 to 6 carbon atoms The HMG-COA reductase inhibitor- induced toxic effect while maintaining the therapeutic efficacy of the HMG-COA reductase inhibitor with a detoxifying amount of the alkanoyl L-carnitine having one or a pharmaceutically acceptable salt thereof. Combination to reduce .
17.
HMG-COA reductase inhibitor and L-carnitine or alkanoyl L-carnitine having a linear or branched alkanoyl group of 2 to 6 carbon atoms, or one of their pharmaceutically acceptable salts are continuously administered , 16. the combination according.
18.
HMG-COA reductase inhibitor and L-carnitine or alkanoyl L-carnitine having a linear or branched alkanoyl group of 2 to 6 carbon atoms, or one of pharmaceutically acceptable salts thereof are administered substantially simultaneously. 17. The combination according to claim 16, wherein
(19)
A product, wherein the pharmaceutical composition according to claim 1 is accompanied by instructions for ingesting each drug simultaneously or ingesting each drug based on a predetermined dose standard.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13800899P | 1999-06-08 | 1999-06-08 | |
| US60/138,008 | 1999-06-08 | ||
| EP99830415.8 | 1999-06-30 | ||
| EP99830415A EP1064943B1 (en) | 1999-06-30 | 1999-06-30 | Combination having antilipemic activity substantially free from toxic or side effects due to antilipemic drugs |
| PCT/EP2000/005091 WO2000074675A1 (en) | 1999-06-08 | 2000-06-05 | Antilipemic combinations comprising hmg-coa reductase inhibitors and carnitines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003501385A JP2003501385A (en) | 2003-01-14 |
| JP2003501385A5 true JP2003501385A5 (en) | 2007-07-05 |
Family
ID=26153794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001501212A Pending JP2003501385A (en) | 1999-06-08 | 2000-06-05 | Anti-hyperlipidemic combination comprising HMG-COA reductase inhibitor and carnitines |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JP2003501385A (en) |
| KR (1) | KR100725263B1 (en) |
| AU (1) | AU782188B2 (en) |
| CA (1) | CA2375378C (en) |
| CZ (1) | CZ20014218A3 (en) |
| HU (1) | HUP0201597A3 (en) |
| MX (1) | MXPA01012644A (en) |
| PL (1) | PL197899B1 (en) |
| SK (1) | SK285900B6 (en) |
| WO (1) | WO2000074675A1 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0721333A8 (en) * | 2007-02-27 | 2017-12-26 | Sigma Tau Ind Farmaceuti | COMPOSITION USEFUL FOR THE TREATMENT OF TYPE 2 DIABETES |
| EP2136798B1 (en) * | 2007-03-21 | 2015-07-29 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Composition useful for the prevention of type 2 diabetes and its complications in pre-diabetic patients with insulin resistance |
| US20110052556A1 (en) | 2008-02-29 | 2011-03-03 | Biolab Sanus Farmaceutical Ltda | Pharmaceutical composition comprising racetam and carnitine and process for its preparation |
| US20120130202A1 (en) * | 2010-11-24 | 2012-05-24 | Fujitsu Limited | Diagnosis and Monitoring of Musculoskeletal Pathologies |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0667833B2 (en) * | 1985-11-28 | 1994-08-31 | 雪印乳業株式会社 | Enteral nutrition |
| EP0383432B1 (en) * | 1989-01-18 | 1993-03-24 | Merck & Co. Inc. | Coenzyme q10 with hmg-coa reductase inhibitors |
| IT1293067B1 (en) * | 1997-07-01 | 1999-02-11 | Sigma Tau Ind Farmaceuti | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF PATHOLOGIES CAUSED BY ALTERED LIPID METABOLISM |
-
2000
- 2000-06-05 CA CA002375378A patent/CA2375378C/en not_active Expired - Fee Related
- 2000-06-05 JP JP2001501212A patent/JP2003501385A/en active Pending
- 2000-06-05 CZ CZ20014218A patent/CZ20014218A3/en unknown
- 2000-06-05 KR KR1020017015675A patent/KR100725263B1/en not_active Expired - Fee Related
- 2000-06-05 SK SK1715-2001A patent/SK285900B6/en not_active IP Right Cessation
- 2000-06-05 MX MXPA01012644A patent/MXPA01012644A/en active IP Right Grant
- 2000-06-05 WO PCT/EP2000/005091 patent/WO2000074675A1/en not_active Ceased
- 2000-06-05 HU HU0201597A patent/HUP0201597A3/en unknown
- 2000-06-05 AU AU59697/00A patent/AU782188B2/en not_active Ceased
- 2000-06-05 PL PL352106A patent/PL197899B1/en unknown
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