WO2008026668A1 - Composition médicale contenant un agent d'amélioration de la résistance à l'insuline - Google Patents

Composition médicale contenant un agent d'amélioration de la résistance à l'insuline Download PDF

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Publication number
WO2008026668A1
WO2008026668A1 PCT/JP2007/066836 JP2007066836W WO2008026668A1 WO 2008026668 A1 WO2008026668 A1 WO 2008026668A1 JP 2007066836 W JP2007066836 W JP 2007066836W WO 2008026668 A1 WO2008026668 A1 WO 2008026668A1
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Prior art keywords
insulin
pharmaceutical composition
composition according
methoxy
insulin secretagogue
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PCT/JP2007/066836
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English (en)
Japanese (ja)
Inventor
Shoichi Kanda
Ryutaro Nakashima
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Daiichi Sankyo Company, Limited
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Publication of WO2008026668A1 publication Critical patent/WO2008026668A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • 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
    • 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
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a medicament (preferably a medicament for treating and / or preventing diabetes) comprising a combination of an insulin secretagogue (preferably sulfonylurea) and an insulin resistance ameliorating agent.
  • a medicament preferably a medicament for treating and / or preventing diabetes
  • an insulin secretagogue preferably sulfonylurea
  • an insulin resistance ameliorating agent preferably sulfonylurea
  • the present invention relates to the use of the above-mentioned drug for producing the above-mentioned medicine, or a method for preventing or treating the above-mentioned disease wherein the above-mentioned medicine is administered to a warm-blooded animal (preferably a human).
  • Insulin resistance improving agents are administered to patients as antidiabetic agents in order to lower blood glucose levels by improving insulin dysfunction.
  • insulin sensitizers can be used for diabetic strength, glucose tolerance, hypertension, hyperlipidemia, diabetic complications (eg, retinopathy, nephropathy, neuropathy), gestational diabetes, polycystic ovary. It is known that diseases caused by insulin resistance such as syndrome are also effective for cardiovascular diseases such as atherosclerosis.
  • Examples of insulin resistance improvers currently on the market include thiazolidinedione insulin resistance improvers such as piodaritazone and rosiglitazone. It is said that the amelioration of insulin dysfunction by these drugs is due to activation of PPAR (peroxisome proliferator activated receptor) 7 .
  • PPAR peroxisome proliferator activated receptor
  • sulfonylurea agents (hereinafter referred to as SU agents), fast-acting insulin secretion promoters, and the like are administered to diabetic patients as therapeutic agents for diabetes.
  • SU agents sulfonylurea agents
  • fast-acting insulin secretion promoters and the like are administered to diabetic patients as therapeutic agents for diabetes.
  • side effects such as hypoglycemia and weight gain occur and secondary inefficiency occurs due to long-term administration, sufficient caution is required during use.
  • Patent Document 1 International Publication No. 98/36755 Pamphlet Disclosure of the invention
  • the present inventors have conducted extensive research on anti-diabetic and / or therapeutic agents that have few side effects even in long-term administration of drugs and are effective for many diabetic patients.
  • the inventors have found that the object can be achieved by combining an insulin secretagogue and an insulin resistance improving agent, and have completed the present invention.
  • the present invention provides:
  • the present invention is a.
  • a pharmaceutical composition comprising a combination of an insulin resistance improver and an insulin secretion promoter
  • Insulin resistance-improving drug power A pharmaceutical composition according to any one of the above (1) to sol (3), which is pioglitazone or rosiglitazone,
  • Insulin secretion promoter power Use according to (18) above, which is glimepiride, darivenclamide or darliclazide,
  • Insulin resistance improver S 5- ⁇ 4-[(6_methoxy-1-methyl-1H-benzimidazol-2-yl) methoxy] benzylto 1,3-thiazolidine-2,4-dione Or a pharmacologically acceptable salt thereof, the use according to any one of (18) to (20) above,
  • the “insulin resistance improving agent” is a general term for drugs that improve insulin resistance and enhance insulin sensitivity.
  • [4- [2- (4 -Ethyl-2-pyridyl) ethoxy] benzyl] -2,4-thiazolidinedione (generic name: pioglitazone, preferably pioglitazone hydrochloride), 5 _ [[4- [2- (methyl-2-pyridylamino) ethoxy Ci] phenyl] methyl] -2,4-thiazolidinedione (generic name: rosiglitazone, preferably rosiglitazone maleate), 5-[[((3,4-dihydro-3-methyl-4-oxo) 2-quinazolinyl) methoxy] benzyl] -2,4-thiazolidinedione (generic name: baraglitazone), (2S) _2-methoxy-3- [4- [3_
  • a thiazolidinedione-based insulin resistance improving agent such as 4-dione and pharmacologically acceptable salts thereof.
  • Pioglitazone is a compound described in US Pat. No. 4,687,777, and pioglitazone of the present invention includes a pharmacologically acceptable salt thereof (hydrochloride, etc.).
  • Rosiglitazone is a compound described in US Pat. No. 5,002,953, and rosiglitazone of the present invention includes pharmacologically acceptable salts thereof (such as maleate).
  • Nabedalitazal is a compound described in the pamphlet of International Publication No. 02/100813.
  • Tazar includes pharmacologically acceptable salts (hydrochlorides, etc.).
  • Balaglitazone is a compound described in WO 97/41097 pamphlet, and the balaglitazone of the present invention includes pharmacologically acceptable salts (hydrochlorides and the like) thereof.
  • Metagridacene is a compound described in US Pat. No. 6,262,118, and metaglidacene of the present invention includes pharmacologically acceptable salts thereof (hydrochlorides and the like).
  • AMG-131 is a compound described in International Publication No. 2001/579 pamphlet, International Publication No. 2001/579 pamphlet and International Publication No. 2005/33074 pamphlet. Includes acceptable salts (hydrochlorides, etc.).
  • the “insulin secretion promoter” is not particularly limited as long as it is a drug having an action of secreting insulin from ⁇ -cells, and preferably a sulfonylurea agent (SU agent) or a fast-acting agent. Type insulin secretion promoter, and SU agent is preferable.
  • “Sulfoninoreurea (SU)” is not particularly limited as long as it is an agent that acts on the SU receptor (SUR1) of prestigious Langerno and Suns 0 cells and promotes insulin secretion! / , For example, is represented by the following structural formula
  • the ⁇ rapid-acting insulin secretagogue '' is not particularly limited as long as it is an agent that acts on the SU receptor (SUR1) of the precocious islets of Langernos / 3 cells and promotes insulin secretion.
  • SUR1 SU receptor
  • Phenylalanine derivatives such as N- (trans_4-Isoprovircyclohexanecarbonyl) -D-phenylalanine (generic name: nateglinide), 2-benzyl-3_ (cis-hexahydroisoindrin-2- Ylcarbonyl) propionate (generic name: mitiglinide, preferably mitiglinide calcium hydrate), 2-ethoxy-4- [ ⁇ - [1- (2-piperidinophenyl) -3-methyl-1-butyl ] Aminocarbonylmethyl] benzoic acid (generic name: levaglinide), and nateglinide is preferred.
  • the insulin resistance improving agent and the insulin secretagogue are superior in comparison with each single agent because they are combined and used.
  • Clinically it is convenient to administer both drugs at the same time. Therefore, the insulin secretagogue and the insulin resistance ameliorating agent can be administered in the form of a combination drug.
  • Each single agent can also be administered simultaneously.
  • each single agent can be administered in succession at an appropriate interval. The interval between doses allowed to achieve the superior effects achieved by the administration of both drugs can be confirmed clinically or by animal experiments.
  • the pharmaceutical composition of the present invention is administered in various forms.
  • the dosage form depends on various dosage forms, the patient's age, sex and other conditions, the degree of disease, etc. It is determined.
  • it is orally administered in the case of tablets, pills, powders, granules, syrups, solutions, suspensions, emulsions, condyles and capsules.
  • it is a tablet.
  • conventionally known carriers can be widely used as carriers.
  • carriers for example, lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, key Excipients such as acids, water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, binders such as carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polybulurpyrrolidone, dry starch , Sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, monoglyceride stearate, starch, lactose, etc., white sugar, stearin, cacao Disintegration inhibitors such as butter and hydrogenated oil, Class 4 Absorption accelerators such as ammonium base and sodium lauryl sulfate, humectants such as g
  • a conventionally known carrier can be widely used as a carrier.
  • excipients such as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, kaolin, talc,
  • binders such as gum arabic powder, tragacanth powder, gelatin and ethanol, and disintegrants such as laminaran strength.
  • a colorant if necessary, a preservative, a fragrance, a flavoring agent, a sweetening agent, and other pharmaceuticals may be contained.
  • each antidiabetic agent used in the present invention can vary greatly depending on various conditions such as activity of individual substances, patient symptoms, age, body weight and the like.
  • an insulin resistance improving agent as an example, pioglitazone and rosiglitazone are Since in vivo activity in clinical and diabetic animal models is different, these
  • the dosage of the two drugs can vary. Moreover, each dose can be reduced by the excellent effect of the combined use of an insulin resistance improving agent and an insulin secretagogue.
  • the insulin resistance improving agent contained in the pharmaceutical preparation is not particularly limited and is appropriately selected within a wide range, but is usually 1 to 70% by weight, preferably 1 to 30% by weight in the total composition. Is appropriate.
  • the dose varies depending on symptoms, age, body weight, dosage form, etc., but is usually 0.001 mg / kg (preferably 0.001 mg / kg, moreover, 1 day for an adult) Preferably 0
  • a maximum of 30 mg / kg (preferably 3 mg / kg, more preferably 0.3 mg / kg) can be administered once or twice.
  • the amount of the insulin secretagogue contained in the pharmaceutical preparation is not particularly limited and is appropriately selected within a wide range, but is usually 1 to 70% by weight, preferably 1 to 30% by weight, based on the total composition. It is appropriate that the amount be
  • the dose varies depending on symptoms, age, body weight, dosage form, etc.
  • the lower limit is 0.0001 mg / kg (preferably 0.001 mg / kg, more preferably 0.01 mg / kg), and the upper limit is 30 mg / kg (preferably 3 mg / kg, more preferably 0.3 mg / kg). Or do it twice.
  • the dose ratio of the insulin resistance ameliorating agent and the insulin secretagogue may also be in the range of 1: 1000 to 1000: 1 in force-weight ratio that can vary significantly.
  • the insulin secretion promoter and the insulin resistance ameliorating agent each have the above dosage once or several times a day (preferably once a day or Divided into two doses, each administered at the same time or separately at different times.
  • the drug is caused by insulin resistance such as diabetes (especially type 2 diabetes), hyperglycemia, glucose intolerance, hypertension, hyperlipidemia, diabetic complications, gestational diabetes, polycystic ovary syndrome, etc. Diseases such as atherosclerosis cardiovascular system It is also effective for diseases. Furthermore, by appropriately selecting the type, administration method, and dose of each drug according to the symptoms, rapid improvement of hyperglycemia and stable hypoglycemic effect even after long-term administration are expected, and side effects are manifested. Very few! /, Which can be a prophylactic and therapeutic drug for the above diseases
  • FIG. 3 is a graph showing the effect of enhancing blood glucose lowering effect by administering a salt (compound A) and darivenclamide (compound B) in combination.
  • the control group, compound A group, and the compound B group and the combination group were administered a single dose of compound B, 6 mg / kg, as the SU agent.
  • Blood was collected from the tail vein of all individuals immediately before single oral administration of solvent or SU, 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, and 4 hours after administration.
  • the blood glucose level was measured using a sugar analyzer (Glucor 0 der-GXT, manufactured by A & T Co., Ltd.). Calculate the area under the blood glucose curve for each individual from the value obtained by subtracting the blood glucose level immediately before administration from the blood glucose level measured at each time point. The mean value and standard error of the area under the blood glucose curve were calculated and shown in FIG. The lower the area value under the blood glucose level curve, the higher the blood glucose lowering effect.
  • the compound A group to which only the solvent was administered after fasting showed an area value under the blood glucose level curve that was not different from the control group.
  • the area under the blood glucose level curve of the compound B group and the combination group to which the SU agent was administered after fasting decreased, and the compound A was administered to the combination group to which the compound A was repeatedly administered.
  • the value decreased significantly compared to the compound B group. This indicates that the combined use of Compound A and Compound B enhanced the hypoglycemic effect.
  • the medicament of the present invention lowers blood glucose more effectively than single administration of a drug, and thus is useful for the prevention and treatment of diabetes.
  • the medicament of the present invention can provide a sufficient effect even when a smaller amount is used compared to the case where each drug is administered alone, side effects that the SU agent is considered to have in the treatment of diabetes Can reduce power (eg, weight gain, hypoglycemia).
  • Capsules can be produced by thoroughly mixing the powders of the components shown above and filling the capsules.
  • the dose of active ingredient and the content of each additive are not limited to these.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Reproductive Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un procédé de traitement du diabète qui exerce un excellent effet hypoglycémiant avec peu d'effets secondaires. L'invention concerne en particulier un médicament dont le promoteur de sécrétion de l'insuline est combiné à un agent d'amélioration de résistance à l'insuline.
PCT/JP2007/066836 2006-08-31 2007-08-30 Composition médicale contenant un agent d'amélioration de la résistance à l'insuline WO2008026668A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009038107A1 (fr) * 2007-09-21 2009-03-26 Kissei Pharmaceutical Co., Ltd. Préparation pharmaceutique combinée destinée au traitement du diabète de type 2

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10167986A (ja) * 1995-06-20 1998-06-23 Takeda Chem Ind Ltd 医 薬
JP2001039976A (ja) * 1999-05-24 2001-02-13 Sankyo Co Ltd 縮合複素環化合物の塩酸塩
JP2001512478A (ja) * 1997-02-19 2001-08-21 ワーナー−ランバート・コンパニー 糖尿病のためのスルホニル尿素−グリタゾン相乗的組み合わせ物
JP2002529417A (ja) * 1998-11-09 2002-09-10 ワーナー−ランバート・カンパニー スルホニル尿素、グリタゾンおよびビグアニドを含有する糖尿病用組み合わせ薬剤
JP2002529504A (ja) * 1998-11-12 2002-09-10 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー インスリン感作物質および他の抗糖尿病薬の放出修飾のための医薬組成物
JP2003519681A (ja) * 2000-01-14 2003-06-24 ブリストル−マイヤーズ スクイブ カンパニー グルブリド組成物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10167986A (ja) * 1995-06-20 1998-06-23 Takeda Chem Ind Ltd 医 薬
JP2001512478A (ja) * 1997-02-19 2001-08-21 ワーナー−ランバート・コンパニー 糖尿病のためのスルホニル尿素−グリタゾン相乗的組み合わせ物
JP2002529417A (ja) * 1998-11-09 2002-09-10 ワーナー−ランバート・カンパニー スルホニル尿素、グリタゾンおよびビグアニドを含有する糖尿病用組み合わせ薬剤
JP2002529504A (ja) * 1998-11-12 2002-09-10 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー インスリン感作物質および他の抗糖尿病薬の放出修飾のための医薬組成物
JP2001039976A (ja) * 1999-05-24 2001-02-13 Sankyo Co Ltd 縮合複素環化合物の塩酸塩
JP2003519681A (ja) * 2000-01-14 2003-06-24 ブリストル−マイヤーズ スクイブ カンパニー グルブリド組成物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009038107A1 (fr) * 2007-09-21 2009-03-26 Kissei Pharmaceutical Co., Ltd. Préparation pharmaceutique combinée destinée au traitement du diabète de type 2

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