WO2006011495A1 - Remede pour l'hypercholesterolemie et/ou l'hypertriglyceridemie - Google Patents
Remede pour l'hypercholesterolemie et/ou l'hypertriglyceridemie Download PDFInfo
- Publication number
- WO2006011495A1 WO2006011495A1 PCT/JP2005/013693 JP2005013693W WO2006011495A1 WO 2006011495 A1 WO2006011495 A1 WO 2006011495A1 JP 2005013693 W JP2005013693 W JP 2005013693W WO 2006011495 A1 WO2006011495 A1 WO 2006011495A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- fenofibrate
- pitapastatin
- hypertriglyceridemia
- hyperlipidemia
- blood
- Prior art date
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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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- 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
Definitions
- the present invention relates to a therapeutic agent for hyperlipidemia and Z or hypertriglyceridemia containing pitapastatin and fenofibrate as active ingredients, and a preparation thereof.
- Hyperlipidemia is a symptom in which lipoproteins in the blood are abnormally increased and is strongly related to diseases such as arteriosclerosis and myocardial infarction. Being
- statin-type HMG-CoA reductase inhibitors such as oral pastatin, simpastatin, pravastatin, flupastatin, atorvastatin, rospastatin, pitapastatin, etc. It is the center of the therapeutic agent.
- the main components of blood lipoproteins are cholesterol triglycerides and the like, and hyperlipidemia patients not only have an increase in blood cholesterol but may also have an increase in blood triglycerides. Many. When HMG-CoA reductase inhibitor is administered to hyperlipidemic patients, blood cholesterol can be lowered.
- HMG-CoA reductase inhibitor In hyperlipidemic patients with high levels of both blood cholesterol and blood triglycerides, increasing the dose of HMG-CoA reductase inhibitor to treat both sufficiently is a safety issue. Etc. Not recommended.
- HMG—CoA reductase inhibitor and fibric acid derivative represented by fenofibrate This combination has been reported.
- Phenofibrate (2- [4 benzoyl) phenoxy] 2-methylpropionic acid (1-methylethyl) is a fibrate antihyperlipidemic agent, and blood cholesterol And has an action of lowering blood triglyceride, and its blood triglyceride lowering action is known to be strong (see Non-patent Document 1).
- Patent Document 1 describes a specific test example in humans regarding the combined use of cerivastatin and fenofibrate, but the combined use of both drugs reduces blood triglycerides. The effect is said to be additively enhanced.
- Non-Patent Document 2 states that blood glyceride lowering action is additively enhanced by the combined use of atorvastatin and fenofibrate in diabetic patients.
- Patent Document 1 US Pat. No. 6511985
- Non-Patent Document 1 New Current, 7 (6), 9 19 (1996)
- Non-Patent Document 2 Diabetes Care, 25, 1198-1202 (2002)
- the present invention provides a concomitant drug capable of efficiently reducing both blood cholesterol and blood triglycerides.
- the present invention provides a therapeutic agent for hyperlipidemia or hypertriglyceridemia containing pitapastatin and fenofibrate as active ingredients, and a high fat composition containing pitapastatin and fenofibrate as active ingredients.
- the present invention relates to a therapeutic agent for blood glucose and hypertriglyceridemia.
- the present invention relates to a preparation for a therapeutic agent for hyperlipidemia or a therapeutic agent for hypertriglyceridemia, comprising pitapastatin and fenofibrate as active ingredients, and pitavastatin and fenofib.
- the present invention relates to a preparation for a therapeutic agent for hyperlipidemia and a therapeutic agent for hypertriglyceridemia comprising lato as an active ingredient.
- the present invention provides a pharmaceutical thread and composition for the treatment of hyperlipidemia and Z or hypertriglyceridemia, comprising pitapastatin and fenofibrate, and a pharmaceutically acceptable carrier. Is to provide.
- the present invention also provides a method for treating patients with hyperlipidemia and Z or hypertriglyceridemia.
- the present invention provides the use of pitapastatin and fenofibrate for the manufacture of a pharmaceutical composition for the treatment of hyperlipidemia and Z or hypertriglyceridemia.
- the hyperlipidemic agent of the present invention is excellent in the effect of lowering blood cholesterol and blood triglycerides, and is also effective in the treatment of lib type and type IV hyperlipidemia.
- the pitapastatin in the present invention may be in the form of a pitanostatin latatotone or ring-opened form, or may be a prodrug or a salt thereof that can be a precursor of pitapastatin. Furthermore, the pitapastatin in the present invention may be a hydrate or a solvate acceptable as a pharmaceutical product.
- the fenofibrate in the present invention may be a hydrate or a pharmaceutically acceptable solvate as well as itself.
- the present invention relates to a therapeutic agent for hyperlipidemia or hypertriglyceridemia containing pitapastatin and funofibrate as active ingredients, and hyperlipidemia containing pitapastatin and fenofibrate as active ingredients, and
- the therapeutic agents (including prophylactic agents) of the present invention will be described as “pharmaceutical compositions”.
- the pharmaceutical composition of the present invention comprises pitapastatin and fenofibrate as active ingredients, but other drugs are further added within a range that does not excessively affect the action and side effects of these drugs. Can be used together.
- “combination” refers to hyperlipidemia and Z or hypertriglyceridemia patients who are at risk of developing vascular events in blood vessels such as cardiovascular and cerebrovascular. Above all Hyperlipidemic patients with hypertriglyceridemia are used to prevent and / or treat hyperlipidemia and Z or hypertriglyceridemia in patients at extremely high risk of developing vascular events such as coronary artery disease. Mean that pitapastatin and fenofibrate are administered at the same time.
- Such administration means may include not only a form in which both pitapastatin and fenofibrate are administered as a single preparation, but also a form in which each preparation is administered separately at the same time.
- each drug is formulated separately and may be from separate products.
- they can be combined into a kit to produce a product.
- the present invention can reduce the dose of each drug by using both "pitapastatin” and “fenofibrate” "in combination” as compared with the case where they are administered alone. It can effectively prevent and treat hyperlipidemia and Z or hypertriglyceridemia. This can improve patient compliance. As long as the effects of the present invention can be exhibited, any formulation or product may be used.
- the pharmaceutical composition of the present invention may be in a dosage form once a day, or in divided dosage forms 2-6 times a day, preferably 3 times a day. Which dosage form is to be used can be appropriately determined according to the patient's condition and symptoms.
- the dosage of the pharmaceutical composition of the present invention is selected as pitanostatin in the range of 0.1 to 50 mg per day for adults, usually 1 to 20 mg, and 1 to 10 mg per day for adults as fenofibrate. Usually, it is selected in the range of 100 to 300 mg. However, this effective amount is not necessarily limited and will be determined by the attending physician depending on factors such as the patient's age, weight, health status and symptoms.
- the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier.
- pharmaceutically acceptable carriers include various known excipients, binders (eg, starch), disintegrants, buffers, preservatives, antioxidants, lubricants, fragrances, thickeners. , Coloring agents, milking agents and the like.
- the amount of these carriers added is preferably selected in the range of about 0.1 to about 95% by weight and about 10 to 90% by weight of the total weight of the pharmaceutical composition of the present invention.
- the pharmaceutical composition of the present invention can be formulated into various dosage forms for oral administration and parenteral administration. For example, capsules, tablets, powders, suspensions, solutions, etc. can be formulated as needed. These preparations can be prepared by conventional preparation techniques in pharmacy.
- the present invention provides a pharmaceutical preparation for hyperlipidemia and a therapeutic agent for Z or hypertriglyceridemia comprising pitapastatin and fenofibrate as active ingredients, thus formulated. Is to provide.
- the rate of decrease in blood triglyceride was 14.7% in the group administered with pitapastatin calcium salt alone, and 23.8% in the group administered with fenofibrate alone, whereas it was 23.8%.
- salt and fenofibrate were used in combination, it was 37.3%, and there was a significant difference in the p ⁇ 0.01 test.
- this result is expressed as a relative index when the non-administration group is 1.0, the pitapastatin calcium salt single administration group is 0.853, the fenofibrate single administration group is 0.762, and pitapastatin When calcium salt and fenofibrate are used in combination, it is 0.627.
- the drug of the present invention is extremely effective in the treatment of symptoms accompanied by a high triglyceride state by the combined use of not only the treatment of hyperlipidemia with pitapastatin.
- the doses of pitapastatin and fenofibrate can be reduced compared to each drug alone. became.
- the present invention enhances the blood triglyceride-lowering action of pitapastatin and enables treatment of hyperlipidemic patients with high levels of both blood cholesterol and triglycerides.
- the combined use of pitapastatin and fenofibrate has been found to have a synergistic effect on the reduction of blood tridalylide, and in a smaller amount, not only treatment and prevention of hyperlipidemia but also hypertriglyceridemia Therefore, the present invention provides a combination therapy of extremely effective drugs and a preparation for the same.
- FIG. 1 is a graph showing the effect of reducing blood triglycerides by the combined administration of pitapastatin calcium salt and fenofibrate.
- the vertical axis in FIG. 1 shows blood triglyceride concentration (mgZ dL), and the horizontal axis shows, from the left, the control, the pitanostatin calcium salt alone administration group, the fenofibrate alone administration group, and the combination administration group of both.
- Wistar male rats (Nippon Medical Science Experimental Animal Co., Ltd.) 6 weeks old were used. Throughout the experimental period, the light-dark cycle (bright period with room light: 7 am to 7 pm), temperature 23 ⁇ 3 ° C, humidity 55 persons, maintained at 15%, solid feed (CE— 2; Nippon Claire Co., Ltd.) and tap water were given freely.
- 32 rats were divided into the following 4 groups (8 patients in each group): control group, pitapastatin calcium salt alone (10 mg / kg) group, fenofibrate alone (10 mg / kg) group, and pitapastatin strength lucum salt (1 Omg / kg) and fenofibrate (1 Omg / kg) combined groups were grouped so that total cholesterol and triglycerides were averaged. Both drugs were orally administered once a day (4 pm) repeatedly for 14 days, and the control group was orally administered 2 mL / kg of a 0.5% by weight aqueous solution of sodium carboxymethylcellulose. In all groups, blood was collected after fasting for 18 hours from the final administration, and blood triglyceride concentration was measured.
- a multigroup comparison between the control group and the drug-administered group was performed using Bartlett's analysis of variance—Dmrnett's multiple comparison test, and a risk rate of less than 5% was determined to be significant.
- the blood triglyceride reduction rate (%) is ((control blood triglyceride average value in each group blood triglyceride average value) / (control group blood triglyceride average value)) X 100, relative index is ((each Mean blood triglyceride value) Z (control blood triglyceride average value))).
- the present invention provides a therapeutic agent for hyperlipidemia and Z or hypertriglyceridemia containing pitapastatin and fenofibrate as active ingredients, and a preparation for the same.
- hypertriglyceridemia can be treated or prevented at the same time, and the use of both can be reduced by the synergistic effect of the combination of both. is there. Therefore, the present invention is extremely useful not only in the medical field but also in the pharmaceutical field and has industrial applicability.
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- Health & Medical Sciences (AREA)
- Public Health (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)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006527814A JPWO2006011495A1 (ja) | 2004-07-30 | 2005-07-27 | 高コレステロール血症及び/又は高トリグリセリド血症治療剤 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004-223695 | 2004-07-30 | ||
JP2004223695 | 2004-07-30 |
Publications (1)
Publication Number | Publication Date |
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WO2006011495A1 true WO2006011495A1 (fr) | 2006-02-02 |
Family
ID=35786245
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/013693 WO2006011495A1 (fr) | 2004-07-30 | 2005-07-27 | Remede pour l'hypercholesterolemie et/ou l'hypertriglyceridemie |
Country Status (2)
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JP (1) | JPWO2006011495A1 (fr) |
WO (1) | WO2006011495A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007008923A (ja) * | 2005-05-31 | 2007-01-18 | Aska Pharmaceutical Co Ltd | フィブラート系薬剤を含有する製剤及びその製造方法 |
WO2008015763A1 (fr) | 2006-08-04 | 2008-02-07 | Aska Pharmaceutical Co., Ltd. | Formulation médicamenteuse contenant un médicament fibrate et procédé pour la produire |
WO2010098482A1 (fr) * | 2009-02-27 | 2010-09-02 | 興和株式会社 | Préparation de capsules stable et son procédé de fabrication |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002067901A1 (fr) * | 2001-02-22 | 2002-09-06 | Skyepharma Canada Inc. | Combinaisons statine et fibrate presentant des effets secondaires alimentaires indesirables « a jeun-nourri » reduits |
WO2003026573A2 (fr) * | 2001-09-24 | 2003-04-03 | Merck & Co., Inc. | Methodes d'analyse et de selection d'associations de medicaments a base de statines |
WO2005034908A2 (fr) * | 2003-10-10 | 2005-04-21 | Lifecycle Pharma A/S | Forme posologique solide comprenant une fibrate et une statine |
-
2005
- 2005-07-27 WO PCT/JP2005/013693 patent/WO2006011495A1/fr active Application Filing
- 2005-07-27 JP JP2006527814A patent/JPWO2006011495A1/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002067901A1 (fr) * | 2001-02-22 | 2002-09-06 | Skyepharma Canada Inc. | Combinaisons statine et fibrate presentant des effets secondaires alimentaires indesirables « a jeun-nourri » reduits |
WO2003026573A2 (fr) * | 2001-09-24 | 2003-04-03 | Merck & Co., Inc. | Methodes d'analyse et de selection d'associations de medicaments a base de statines |
WO2005034908A2 (fr) * | 2003-10-10 | 2005-04-21 | Lifecycle Pharma A/S | Forme posologique solide comprenant une fibrate et une statine |
Non-Patent Citations (1)
Title |
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MATHEW P.: "Pitavastatin (NK-104) no Fibrate Yakuzai (Fenofibrate, Gemfibrozil) Heiyoji ni Okeru Yakubutsu Dotai Shiken", SHINRYO TO SHIN'YAKU, vol. 40, no. 9, September 2003 (2003-09-01), pages 779 - 785, XP002999374 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007008923A (ja) * | 2005-05-31 | 2007-01-18 | Aska Pharmaceutical Co Ltd | フィブラート系薬剤を含有する製剤及びその製造方法 |
WO2008015763A1 (fr) | 2006-08-04 | 2008-02-07 | Aska Pharmaceutical Co., Ltd. | Formulation médicamenteuse contenant un médicament fibrate et procédé pour la produire |
WO2010098482A1 (fr) * | 2009-02-27 | 2010-09-02 | 興和株式会社 | Préparation de capsules stable et son procédé de fabrication |
Also Published As
Publication number | Publication date |
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JPWO2006011495A1 (ja) | 2008-05-01 |
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