WO2004002474A1 - 糖尿病性合併症の予防又は進展阻止用医薬組成物 - Google Patents
糖尿病性合併症の予防又は進展阻止用医薬組成物 Download PDFInfo
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- WO2004002474A1 WO2004002474A1 PCT/JP2003/008084 JP0308084W WO2004002474A1 WO 2004002474 A1 WO2004002474 A1 WO 2004002474A1 JP 0308084 W JP0308084 W JP 0308084W WO 2004002474 A1 WO2004002474 A1 WO 2004002474A1
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- diabetic
- pharmaceutical composition
- mitiglinide
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- hydrate
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- 229940125396 insulin Drugs 0.000 description 1
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- 229960002198 irbesartan Drugs 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
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- 229960004329 metformin hydrochloride Drugs 0.000 description 1
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- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- VLPIATFUUWWMKC-UHFFFAOYSA-N mexiletine Chemical compound CC(N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-UHFFFAOYSA-N 0.000 description 1
- 229960001070 mexiletine hydrochloride Drugs 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
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- 235000019426 modified starch Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229960002827 pioglitazone hydrochloride Drugs 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
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- 229920002689 polyvinyl acetate Polymers 0.000 description 1
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- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D7/00—Compositions of detergents based essentially on non-surface-active compounds
- C11D7/22—Organic compounds
- C11D7/32—Organic compounds containing nitrogen
- C11D7/3281—Heterocyclic compounds
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D17/00—Detergent materials or soaps characterised by their shape or physical properties
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/26—Organic compounds containing nitrogen
- C11D3/28—Heterocyclic compounds containing nitrogen in the ring
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/26—Organic compounds containing nitrogen
- C11D3/30—Amines; Substituted amines ; Quaternized amines
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D7/00—Compositions of detergents based essentially on non-surface-active compounds
- C11D7/22—Organic compounds
- C11D7/32—Organic compounds containing nitrogen
- C11D7/3209—Amines or imines with one to four nitrogen atoms; Quaternized amines
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D7/00—Compositions of detergents based essentially on non-surface-active compounds
- C11D7/22—Organic compounds
- C11D7/36—Organic compounds containing phosphorus
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D2111/00—Cleaning compositions characterised by the objects to be cleaned; Cleaning compositions characterised by non-standard cleaning or washing processes
- C11D2111/10—Objects to be cleaned
- C11D2111/12—Soft surfaces, e.g. textile
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D2111/00—Cleaning compositions characterised by the objects to be cleaned; Cleaning compositions characterised by non-standard cleaning or washing processes
- C11D2111/10—Objects to be cleaned
- C11D2111/14—Hard surfaces
Definitions
- composition for preventing or preventing progress of diabetic complications (Technical field)
- the present invention relates to a pharmaceutical composition containing mitiglinide or a pharmacologically acceptable salt thereof, or a hydrate thereof, prepared for administration before meals, for preventing or preventing the progression of diabetic complications. is there. Further, the present invention provides a method for preventing or preventing the development of diabetic complications, which comprises administering a pre-meal mitiglinide or a pharmacologically acceptable salt thereof, or a hydrate thereof, and a diabetic complication. The present invention relates to the use of mitiglinide, a pharmacologically acceptable salt thereof, or a hydrate thereof for producing a pharmaceutical composition for preventing or preventing the progression of mitiglinide.
- Diabetic complications are mainly chronic complications that result from long-standing chronic mild to severe hyperglycemia.
- Mild hyperglycemia includes impaired glucose tolerance (IGT) and impaired fasting blood glucose (IFG), which progress to lead to diabetes.
- IIG impaired glucose tolerance
- IGF impaired fasting blood glucose
- diabetic complications accompanying these include, for example, diabetic retinopathy, diabetic nephropathy, diabetic microvascular complications such as diabetic neuropathy, and ischemic heart disease, cerebrovascular disease, Arteriosclerotic diseases such as arteriosclerosis obliterans are mentioned.
- Diabetes includes type 1 diabetes (formerly known as juvenile-onset diabetes and insulin-dependent diabetes mellitus (IDDM)), type 2 diabetes (formerly adult-onset diabetes and non-insulin-dependent diabetes mellitus (NIDDM)), and others Specific mechanism ⁇ It is broadly divided into diabetes and gestational diabetes due to diseases. Diabetes can be judged as follows: 1) If the blood glucose level is 20 OmgZdL or more at any time,
- FPG fasting fasting blood glucose
- ITT impaired glucose tolerance
- IGF impaired fasting glucose
- Abnormal glycemia is determined when the fasting blood glucose (F PG) in the early morning is 110 to 125 mgZdL and the 2-hour value is less than 140 mgZdL in a 75 g glucose tolerance test (see Reference 1 below).
- Glycemic control is set as a treatment goal for these diabetic patients, and by maintaining good glycemic control, maintenance of quality of life (QOL) that is the same as that of healthy people and life expectancy that is no different from that of healthy people
- QOL quality of life
- diabetic microvascular complications diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, etc.
- arteriosclerotic diseases ischemic heart disease, cerebrovascular disease, obstructive atherosclerosis
- Etc. ischemic heart disease, cerebrovascular disease, obstructive atherosclerosis
- the HbA1C value is used as a main criterion for the above-mentioned glycemic control, and it is desirable that the HbA1C value is 7% or less, more preferably less than 6.5%.
- 2-hour postprandial blood glucose or fasting blood glucose level is shown as a reinforcing index of HbA lc value, less than 20 OmgZdL a 2-hour postprandial blood glucose, also the target value is from 100 to 14 Omg / dL in a fasting blood glucose (See references 2 and 3 below).
- HbAlc reduced diabetes-related mortality by 10%, reduced myocardial infarction by 16%, and significantly reduced microvascular complications by 25%. It has been effective for the onset and progression of diabetic complications (see Reference 4 below). Furthermore, if the HbA lc value exceeds 7.5%, the incidence of overt diabetic nephropathy increases, and diabetic retinopathy frequently occurs in patients with fasting blood glucose levels of 14 OmgZ d L or more. It has been reported to develop.
- glycemic control is important for preventing or preventing the development of diabetes and diabetic complications.However, maintaining good glycemic control depends on the type of drug used, its effects, pharmacokinetics, etc. However, it is necessary to administer appropriate doses and dosages under a careful regimen. A point to be noted in glycemic control is that blood glucose levels during the day, including postprandial and fasting blood glucose levels, should be reliably controlled without prolonged hypoglycemia.
- Mitiglinide calcium salt hydrate (Chemical name: (+)-monocalcimn bis [(2S, 3a, 7a-c / 5) -Q! -Benzylhexahydro-r-oxo-2-isoindolinebutyrate] dihydrate has the following chemical structural formula It is a rapid-acting short-acting insulin secretagogue and is known to be a promising compound as a drug that corrects postprandial hyperglycemia (see Reference 5 below.) However, the pharmacokinetics of mitiglinide and glycemic control There is no report on how to use this tool.
- immediate-release preparations containing mitiglinide calcium salt hydrate as an active ingredient have been reported (see Reference 6 below). However, these are merely immediate-release preparations, and they are only effective in mitiglinide pharmacokinetics and its glycemic control. It is not prescribed based on use.
- Reference 1 Japan Diabetes Association, edited by The Diabetes Society of Japan, 2002-2003, 1st edition, Bunkodo, May 9, 2002, p. 14-15;
- Reference 2 Japan Diabetes Academic Society, "Diabetes Treatment Guide 2002-2003", 1st edition, Bunkodo Co., Ltd., May 9, 2002, p.18-19;
- Reference 3 Hiroshi Mizushima, "Today's therapeutic drugs Handbook ", 24th edition, Nankodo Co., Ltd., March 15, 2002, p.297;
- Reference 4 “Lancet", September 12, 1998, Vol. 352, No. 9131, pp. 837-853;
- the present inventors conducted intensive studies on the activity and pharmacokinetics of mitiglinide or a pharmacologically acceptable salt thereof, or a hydrate thereof, established a suitable dose and usage, and Using the pharmaceutical composition prepared below, a clinical test is performed as follows, and by taking mitiglinide calcium salt hydrate as described below, excellent blood sugar control can be achieved, and postprandial hyperglycemia can be effectively suppressed. It has been found that it can be controlled, and that it suppresses fasting hyperglycemia in the early morning, and that the incidence of hypoglycemic symptoms and gastrointestinal disorders that are of concern are low, preventing or progressing diabetic complications. The inventor has found that it is extremely effective in preventing the occurrence, and has accomplished the present invention.
- the present invention provides a pharmaceutical composition excellent in preventing or preventing the progress of diabetic complications and a method for using the same.
- the present inventors have found that dosage requirements Mi Chigurinido or a pharmaceutically acceptable salt, or hydrate thereof for reducing significantly the HbA lc values as a single dose 5 mg or more and a pharmacokinetic half-life of about 1.5 hours.Based on the findings, the appropriate dose and usage were examined.As a result, a single dose of 5 to 45 mg was preferred.
- the present invention comprises a single dose of 5-45 mg of mitiglinide or a pharmacologically acceptable salt thereof, or a hydrate thereof, and is prepared for diabetic complications.
- the present invention relates to a pharmaceutical composition for preventing or inhibiting the progress of the drug.
- the present invention provides a method for preventing or progressing diabetic complications, which comprises administering a 5-mg dose of mitiglinide or a pharmacologically acceptable salt thereof or a hydrate thereof as a single dose before meals. It relates to a blocking method.
- the present invention relates to the use of mitiglinide or a pharmaceutically acceptable salt thereof or a hydrate thereof for producing the pharmaceutical composition for pre-prandial administration for preventing or preventing the progress of diabetic complications. is there.
- the postprandial hyperglycemia means that the postprandial blood glucose (PPG) 1 hour value and / or the 2 hour value is 20 Omg / dL or more, and the 2 hour value of the blood glucose level and the 75 g glucose tolerance test as needed. Is 20 OmgZdL or more.
- Fasting hyperglycemia means fasting blood glucose (FPG) in the early morning of 126 mgZdL or more.
- the target patients in the present invention are type 2 diabetic patients with diabetic complications, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) at risk of developing diabetic complications. Or a patient with type 2 diabetes. Suitable cases include patients with postprandial hyperglycemia, and are also suitable for patients with postprandial hyperglycemia concurrent with fasting hyperglycemia.
- ITT impaired glucose tolerance
- IGF impaired fasting glucose
- Examples of diabetic complications include diabetic retinopathy, diabetic nephropathy, diabetic microvascular complications such as diabetic neuropathy, ischemic heart disease (myocardial infarction, angina pectoris, etc.), cerebrovascular disease ( Cerebral infarction, etc.), arteriosclerotic diseases such as arteriosclerosis obliterans, diabetic gangrene and the like.
- Examples of pharmacologically acceptable salts of mitiglinide include salts with inorganic bases such as sodium salt, potassium salt and calcium salt, and organic or amino acids such as morpholine, piperidine and phenylalaninol. And preferably a calcium salt.
- the most preferable active ingredient is mitiglinide calcium salt hydrate.
- mitiglinide Or a pharmacologically acceptable salt thereof or a hydrate thereof is preferably administered orally in a single dose of 5 to 45 mg. Improves 1-hour and post-prandial 2-hour values and fasting fasting glucose in the early morning.
- the single dose is preferably 5 to 22 mg, and more preferably 10 to 1 mg of mitiglinide calcium salt hydrate.
- the method of administration is, in principle, three times a day before a meal (within 10 minutes before the start of a meal), preferably immediately before a meal (within 5 minutes before the start of a meal), and the administration period is preferably at least 4 weeks.
- the meal before the meal (within 10 minutes before the start of meal), preferably immediately before the meal (within 5 minutes before the start of meal) in a single dose of 10 to 1 lmg of mitiglinide calcium salt hydrate (increase or decrease appropriately considering the symptoms) ) Is most preferably administered 3 times a day for 4 weeks or more.
- Mitiglinide a pharmacologically acceptable salt thereof, or a hydrate thereof, which is an active ingredient of the present invention, is disclosed in Japanese Patent Application Laid-Open Nos. It can be easily produced by the method described in Japanese Patent Application Laid-Open Publication No. Hei.
- Examples of the pharmaceutical composition used in the present invention include oral pharmaceutical compositions such as granules, fine granules, powders, tablets, and capsules.
- compositions may be formulated into appropriate excipients, binders, surfactants, lubricants, glidants, coating agents, plasticizers, coloring agents, and the like, depending on the formulation used, depending on the formulation. It can be produced by appropriately mixing with a pharmaceutical additive such as a flavor and dispensing according to a conventional method.
- excipients include cellulose or cellulose derivatives such as crystalline cellulose, starch or starch derivatives such as corn starch, wheat starch, cyclodextrin, sugar or sugar alcohol such as lactose, D-mannitol, and dry aluminum hydroxide.
- excipients include inorganic excipients such as gel, precipitated calcium carbonate, magnesium metasilicate aluminate, and calcium hydrogen phosphate.
- binder examples include hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, povidone, dextrin, and pullula. , Hydroxypropyl starch, polyvinyl alcohol, gum arabic, stainless steel, gelatin, tragacanth, macrogol and the like.
- surfactants include sucrose fatty acid esters, polyoxystearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypyrene pyrene glycol, sorbitan sesquioleate, sorbitan trioleate, sorbitan monostearate Sorbitan monopalmitate, sorbitan monolaurate, polysorbate, glyceryl monostearate, sodium lauryl sulfate, lauromacrogol, and the like.
- lubricant examples include stearic acid, calcium stearate, magnesium stearate, and talc.
- Examples of the fluidizing agent include dried aluminum hydroxide gel and magnesium silicate.
- the coating agent examples include hydroxypropyl methylcellulose 2910, aminoalkyl methacrylate copolymer E, polyvinyl acetate lejtyl amino acetate, McGol 600, titanium oxide and the like. .
- plasticizer examples include triethyl quenate, triacetin, macrogol 600, and the like.
- an immediate-release preparation is preferable.
- the preparation can be prepared according to the method described in WO 00/71111 pamphlet or a method analogous thereto.
- composition of the present invention besides mitiglinide or a pharmacologically acceptable salt thereof or a hydrate thereof as an active ingredient, other therapeutic drugs for diabetic complications are appropriately combined (combined). You can also. In addition, they can be used simultaneously (at the same time) or at different intervals (combined use) in combination with other therapeutic agents for diabetic complications as appropriate.
- Examples of the therapeutic agent for diabetic complications that can be used in combination with the compound of the present invention include aldose reductase inhibitors (epalrestat, etc.), sodium channel antagonists (mexiletine hydrochloride, etc.), angiotensin modification Examples thereof include an enzyme inhibitor (imidabril hydrochloride, lisinopril, etc.), angiotensin II receptor antagonist (oral sultan potassium, irbesartan, etc.) and the like. Further, a hypoglycemic drug may be appropriately blended or used in the same manner.
- hypoglycemic agents examples include insulin sensitivity enhancers (such as pioglitazone hydrochloride and oral siglisunesone maleate), sugar absorption inhibitors (such as podalipose, acarpoise, and miglitol), and biguanide drugs (Such as metformin hydrochloride and buformin hydrochloride); insulin secretagogues (such as torptami, acetohexamide, tolazamide, glicloviramide, dalibazole, glyburide / daribenclamide, daliclazide, glimepiride), and insulin preparations.
- insulin sensitivity enhancers such as pioglitazone hydrochloride and oral siglisunesone maleate
- sugar absorption inhibitors such as podalipose, acarpoise, and miglitol
- biguanide drugs Such as metformin hydrochloride and buformin hydrochloride
- insulin secretagogues such as torptami
- Example 1 The content of the present invention will be described in more detail in the following Test Examples and Examples, but the present invention is not limited to the content.
- Example 1 The content of the present invention will be described in more detail in the following Test Examples and Examples, but the present invention is not limited to the content.
- the dissolution test was performed on the following tablets at 50 rpm using 90 mL of the Japanese Pharmacopoeia first solution as a test solution in accordance with the second paddle method of the dissolution test method [Table 1]
- Example 2 The test results for the dissolution rate 20 minutes after the start of the test are shown in Table 1 above. It was confirmed that the tablets of Examples 1 and 2 had a 75% elution time of 20 minutes or less in drug elution with the Japanese Pharmacopoeia First Solution.
- Example 3 The test results for the dissolution rate 20 minutes after the start of the test are shown in Table 1 above. It was confirmed that the tablets of Examples 1 and 2 had a 75% elution time of 20 minutes or less in drug elution with the Japanese Pharmacopoeia First Solution.
- Example 3 The test results for the dissolution rate 20 minutes after the start of the test are shown in Table 1 above. It was confirmed that the tablets of Examples 1 and 2 had a 75% elution time of 20 minutes or less in drug elution with the Japanese Pharmacopoeia First Solution.
- a clinical test was conducted on type 2 diabetes patients using the pharmaceutical composition described in Example 1 under the following conditions.
- Investigational drug and administration method (1) Tablet containing 1 Omg of mitiglinide calcium salt hydrate, (2) Podalipose (chemical name: (+)-lL- [l (OH), 2,4,5 / 3] -5- [2 -Hydroxy-l- (hydroxymethyl) ethyl] amino-lC- (hydroxyinethyl) -l, 2,3,4-cyclohexane-terol) 0.2mg tablet, 3Mitiglinide calcium salt hydrate without active ingredient
- the following combinations (1 tablet each) selected from the placebo tablets (1) and (2) the pogose placebo tablets containing no active ingredient were orally administered 3 times a day immediately before meals (within 5 minutes before the start of meals).
- Observation items The following items were measured before administration, after a certain period of initiation of administration, and at the end of administration to calculate the amount of change, or to calculate and evaluate the incidence of side effects.
- Table 2 shows the test results of the change in the HbA1C value.
- Michiguri two de calcium salt hydrate compared to Poguriposu and placebo positive control to reduce the 4-week or we significantly HbA lc values after administration, also Poguriposu significantly H bA lc values compared to placebo Decreased.
- mitiglinide calcium salt hydrate showed lowering effect of strong H'b A 1C values, Les Rukoto was confirmed with a improvement of good glycemic control state.
- Postprandial blood glucose 1 hour value Postprandial blood glucose 2 hour value Inventive group -53.1-50.1 Positive control group -24.8-5.1 Placebo group 7.1.9.9
- Postprandial blood glucose (PPG) 1 hour value and 2 Table 4 shows the test results of the amount of change with time (the average values in the table are the values at the time of the final evaluation).
- Mitiglinide calcium salt hydrate significantly reduced one-hour and two-hour postprandial blood glucose (PPG) values compared to the positive controls pogliose and placebo. Therefore, it was confirmed that mitidalinide calcium salt hydrate exhibited a potent postprandial blood glucose (PPG) lowering effect.
- Table 5 shows the test results of the incidence of side effects of hypoglycemic symptoms and gastrointestinal tract disorders.
- Mitiglidide calcium salt hydrate reduced the incidence of gastrointestinal disorders such as hypoglycemia and increased flatus as compared to the positive control voglipose. Therefore, it was confirmed that mitiglinide calcium salt hydrate was a highly safe drug with a low incidence of these side effects.
- Example 4 Clinical studies on administration timing
- the timing of administration before eating meals was studied in healthy adult males.
- the investigational drug is a tablet or placebo tablet containing 10 mg of mitiglinide calcium salt hydrate, and the tablet containing 1 O mg of mitiglinide calcium salt hydrate is 0.5 minutes, 5 minutes, 10 minutes before starting meals. Minutes or 30 minutes (positive group), placebo tablets were taken 0.5 minutes before the start of meal (placebo group). After taking the drug, blood glucose was measured and evaluated at the start of meal.
- Mitiglinide calcium salt hydrate maintained good blood sugar levels when taken within 10 minutes before the start of the meal, but significantly decreased when taken 30 minutes before the start of the meal. Therefore, it was confirmed that the risk of hypoglycemia can be avoided by taking mitiglinide calcium salt hydrate within 10 minutes before starting a meal. Also, from the viewpoint of medication compliance, taking the drug within 5 minutes before the start of meal was preferred.
- ADVANTAGE OF THE INVENTION By this invention, a favorable glycemic control state can be achieved, hyperglycemia after a meal and fasting hyperglycemia in the early morning can be corrected, Furthermore, the incidence rate of hypoglycemia and the side effect of gastrointestinal tract disorder is low.
- the present invention can provide an excellent clinically effective pharmaceutical composition for preventing or preventing progress of diabetic complications.
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Abstract
Description
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Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003244083A AU2003244083A1 (en) | 2002-06-28 | 2003-06-26 | Drug composition for prevention or inhibition of advance of diabetic complication |
EP03761816A EP1552830A4 (en) | 2002-06-28 | 2003-06-26 | DRUG COMPOSITION FOR PREVENTING OR INHIBITING PROGRESSION OF DIABETES COMPLICATIONS |
CA002489660A CA2489660A1 (en) | 2002-06-28 | 2003-06-26 | Drug composition for prevention or inhibition of advance of diabetic complication |
US10/519,155 US20050215607A1 (en) | 2002-06-28 | 2003-06-26 | Drug composition for prevention or inhibition of advance of diabetic complication |
KR1020047021405A KR100709531B1 (ko) | 2002-06-28 | 2003-06-26 | 당뇨병성 합병증의 예방 또는 진전저지용 의약조성물 |
JP2004517287A JPWO2004002474A1 (ja) | 2002-06-28 | 2003-06-26 | 糖尿病性合併症の予防又は進展阻止用医薬組成物 |
US12/212,244 US20090018181A1 (en) | 2002-06-28 | 2008-09-17 | Drug composition for prevention or inhibition of advance of diabetic complication |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002-189559 | 2002-06-28 | ||
JP2002189559 | 2002-06-28 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/212,244 Continuation US20090018181A1 (en) | 2002-06-28 | 2008-09-17 | Drug composition for prevention or inhibition of advance of diabetic complication |
Publications (1)
Publication Number | Publication Date |
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WO2004002474A1 true WO2004002474A1 (ja) | 2004-01-08 |
Family
ID=29996854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/008084 WO2004002474A1 (ja) | 2002-06-28 | 2003-06-26 | 糖尿病性合併症の予防又は進展阻止用医薬組成物 |
Country Status (9)
Country | Link |
---|---|
US (2) | US20050215607A1 (ja) |
EP (1) | EP1552830A4 (ja) |
JP (1) | JPWO2004002474A1 (ja) |
KR (1) | KR100709531B1 (ja) |
CN (1) | CN1665499A (ja) |
AU (1) | AU2003244083A1 (ja) |
CA (1) | CA2489660A1 (ja) |
TW (1) | TW200403054A (ja) |
WO (1) | WO2004002474A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006003907A1 (ja) * | 2004-07-01 | 2006-01-12 | Kissei Pharmaceutical Co., Ltd. | 血管内膜過増殖疾患の予防または治療剤 |
CN1976696B (zh) * | 2004-05-11 | 2010-10-06 | 橘生药品工业株式会社 | 用于预防或治疗脂质代谢异常的医药组合物 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103565764B (zh) * | 2013-11-26 | 2016-08-31 | 重庆科瑞南海制药有限责任公司 | 米格列奈钙组合物片剂及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000026292A (ja) * | 1998-01-29 | 2000-01-25 | Kissei Pharmaceut Co Ltd | 速放性経口医薬品組成物 |
WO2001062295A1 (fr) * | 2000-02-24 | 2001-08-30 | Takeda Chemical Industries, Ltd. | Medicaments contenant des ingredients actifs combines |
EP1179342A1 (en) * | 1999-05-21 | 2002-02-13 | Kissei Pharmaceutical Co., Ltd. | Immediate release medicinal compositions for oral use |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5428066A (en) * | 1989-03-08 | 1995-06-27 | Larner; Joseph | Method of reducing elevated blood sugar in humans |
JP2686863B2 (ja) * | 1991-04-25 | 1997-12-08 | キッセイ薬品工業株式会社 | 新規なベンジルコハク酸誘導体 |
FR2765578B1 (fr) * | 1997-07-03 | 1999-09-10 | Adir | Procede de preparation d'un perhydroisoindole substitue |
JP4917712B2 (ja) * | 2000-02-24 | 2012-04-18 | 武田薬品工業株式会社 | 併用医薬 |
CN1234414C (zh) * | 2000-03-17 | 2006-01-04 | 味之素株式会社 | 糖尿病性合并症和神经障碍用的药剂及其应用 |
FR2834892B1 (fr) * | 2002-01-23 | 2004-02-27 | Servier Lab | Composition pharmaceutique orodispersible de mitiglinide |
US6830759B2 (en) * | 2002-06-28 | 2004-12-14 | Ajinomoto Co., Inc. | Antidiabetic preparation for oral administration |
-
2003
- 2003-06-26 AU AU2003244083A patent/AU2003244083A1/en not_active Abandoned
- 2003-06-26 US US10/519,155 patent/US20050215607A1/en not_active Abandoned
- 2003-06-26 EP EP03761816A patent/EP1552830A4/en not_active Withdrawn
- 2003-06-26 CA CA002489660A patent/CA2489660A1/en not_active Abandoned
- 2003-06-26 WO PCT/JP2003/008084 patent/WO2004002474A1/ja active Application Filing
- 2003-06-26 KR KR1020047021405A patent/KR100709531B1/ko active IP Right Grant
- 2003-06-26 CN CN038152452A patent/CN1665499A/zh active Pending
- 2003-06-26 JP JP2004517287A patent/JPWO2004002474A1/ja active Pending
- 2003-06-27 TW TW092117572A patent/TW200403054A/zh unknown
-
2008
- 2008-09-17 US US12/212,244 patent/US20090018181A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000026292A (ja) * | 1998-01-29 | 2000-01-25 | Kissei Pharmaceut Co Ltd | 速放性経口医薬品組成物 |
EP1179342A1 (en) * | 1999-05-21 | 2002-02-13 | Kissei Pharmaceutical Co., Ltd. | Immediate release medicinal compositions for oral use |
WO2001062295A1 (fr) * | 2000-02-24 | 2001-08-30 | Takeda Chemical Industries, Ltd. | Medicaments contenant des ingredients actifs combines |
Non-Patent Citations (3)
Title |
---|
"Mitiglinide calcium hydrate", DRUGS OF THE FUTURE, vol. 20, no. 10, 2000, pages 1034 - 1042, XP002972238 * |
HIDETAKA KOMATSU: "Sokko.tanjikangata insulin bunpitsu sokushinzai KAD-1229", JAPANESE JOURNAL OF CLINICAL MEDICINE, vol. 55, 1997, pages 171 - 179, XP002972237 * |
See also references of EP1552830A4 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1976696B (zh) * | 2004-05-11 | 2010-10-06 | 橘生药品工业株式会社 | 用于预防或治疗脂质代谢异常的医药组合物 |
WO2006003907A1 (ja) * | 2004-07-01 | 2006-01-12 | Kissei Pharmaceutical Co., Ltd. | 血管内膜過増殖疾患の予防または治療剤 |
JPWO2006003907A1 (ja) * | 2004-07-01 | 2008-04-17 | キッセイ薬品工業株式会社 | 血管内膜過増殖疾患の予防または治療剤 |
JP4955392B2 (ja) * | 2004-07-01 | 2012-06-20 | キッセイ薬品工業株式会社 | 血管内膜過増殖疾患の予防または治療剤 |
Also Published As
Publication number | Publication date |
---|---|
US20090018181A1 (en) | 2009-01-15 |
KR20050016936A (ko) | 2005-02-21 |
JPWO2004002474A1 (ja) | 2005-10-27 |
US20050215607A1 (en) | 2005-09-29 |
AU2003244083A1 (en) | 2004-01-19 |
EP1552830A4 (en) | 2007-07-18 |
CA2489660A1 (en) | 2004-01-08 |
TW200403054A (en) | 2004-03-01 |
EP1552830A1 (en) | 2005-07-13 |
KR100709531B1 (ko) | 2007-04-23 |
CN1665499A (zh) | 2005-09-07 |
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