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WO2008058358A2 - Combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires - Google Patents

Combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires Download PDF

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Publication number
WO2008058358A2
WO2008058358A2 PCT/BR2007/000349 BR2007000349W WO2008058358A2 WO 2008058358 A2 WO2008058358 A2 WO 2008058358A2 BR 2007000349 W BR2007000349 W BR 2007000349W WO 2008058358 A2 WO2008058358 A2 WO 2008058358A2
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WO
WIPO (PCT)
Prior art keywords
insulin
metformin
rosuvastatin
cardiovascular diseases
medicament
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.)
Ceased
Application number
PCT/BR2007/000349
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English (en)
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WO2008058358A3 (fr
Inventor
Walter Santos Junior
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Individual
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Individual
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Application filed by Individual filed Critical Individual
Publication of WO2008058358A2 publication Critical patent/WO2008058358A2/fr
Publication of WO2008058358A3 publication Critical patent/WO2008058358A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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

Definitions

  • BJORNTORP E COLS who first related the relation between central obesity with augmented risk of diabetes and cardiovascular disease (DCD) in both men and women.
  • DCD cardiovascular disease
  • the relation between the degree of obesity and the incidence of heart disease was established in 1983 when were published the results of evolution of 5.209 men and women who took part in Framingham study.
  • the resistance to insulin can be defined whit a condition in which occurs lesser glucose utilization in reply to the insulin action in the peripheral tissues.
  • VLDL very low density lipoproteins
  • HDL high density lipoproteins
  • the hyperinsulinemia acts rising the activity of the sympathetic nervous system, generating a hyperadrenergico state that promotes vasoconstriction in the musculature contributing for the elevation of the arterial pressure levels.
  • either the insulin or the rise of the sympathetic activity can estimulate the renal reabsorption of sodium, which, in turn also contributes for the elevation of arterial pressure.
  • the metformin (drawing 01 picture 01) is a compound of the biguanides group which augments the sensitivity of insulin in the peripheral tissues, mainly the liver.
  • the reduction of glycemic provoked by metformin (drawing 01 figure 01) is due specially to the diminution of the glucose hepatic production. It is not associated to the rise of weight, being able, inclusively to determine the reduction from two to three kilos during the first six months of treatment. It reduces the triglycerides from 10 to 15% and also from the plasminogen activator inhibitor 1 In the UKPDS, the metformin ( drawing 01 picture 01) was the only medication that determined significative reduction of incidence of cardiovascular complications in obese patients, inclusively myocardial infarction and death.
  • the metformin ( figure 01 picture 01) is counter-indicated in patients with renal insufficiency ( creatinine > 1 ,5 mg/dl in men and >1 ,4 mg/dl in women). Congestive cardiac insufficiency, chronic hepatic illness ( transaminases > 3 times the superior limit of normality) and abusive use of alcohol.
  • the medicament must be interrupted during the surgical procedures, radiographies with use of serious medical contrast and I intercurrence.
  • estatinas-inhibitors of the 3 - hydroxy -3 - methylglutaryl coenzyme A reductase rosuvastatin (drawing 01 figure 02) is beneficial for treatment of the lipoproteins anormalities and for primary and secondary prevention of DAC in patients DM type , even in subjects with normal plasmatic levels of LDL-c since the plasmatic levels of HDL - c are below the normal and are present hypertrigliceridemia.
  • apolipoprotein B diminishe by the treatment with estatinas because of the reduction in the synthesis in combination with the augment of the depuration of the plasmatic LDL, resulting in subsequent lipoproteic degration. Consequently, the number of particles of LDL diminishe by the augment by the synthesis of cholesterol particles of cholesterol of the lipoproteins of very low density reduces.
  • the rosuvastatin demonstrated to reduce the normal and elevated concentrations of LDL - c.
  • the LDL that are formed from the very low density lipoprotein (VDL) and its catabolism occurs predominantly by the receptor of high afinity LDL.
  • the mechanism of reductor effect of LDL of the rosuvastatin (drawing 01 figure 02) can involve the reduction of VLDL - c cholesterol concentration and the reduction of the LDL receptor, which leads to the reduction of production and the rise of the LDL - c catabolism.
  • the counter-indications consist of hypersensitivity to active principles or to any of the excipients, active hepatic dysfunction or persistent and unexplainable elevation of the serum transaminases, pregnancy and lactation.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne la combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires. Cette combinaison de deux médicaments est utilisée pour lutter contre les maladies cardiovasculaires qui sont la principale cause de mortalité dans le monde. Une nette corrélation est établie entre la prise de poids et l'excès de poids et un risque de maladies cardiovasculaires. L'excès de poids prédispose à ces maladies en raison des anomalies du métabolisme des lipides, du glucose et de la pression artérielle. La résistance à l'insuline/l'hyperinsulinémie semble être un facteur de risque indépendant d'autres facteurs de risque associés, tels que l'obésité, l'hyperlipidémie et l'hypertension, que ce soit chez l'homme ou chez la femme. L'insuline et les facteurs de croissance similaires à l'insuline stimulent l'activité des cellules des muscles lisses et sont impliqués dans l'athérogénèse et même dans la resténose suivant une réparation coronarienne par angioplastie. D'autres effets de l'insuline sont liés à des mécanismes qui contribuent au développement d'une hypertension ou d'une dyslipidémie. La combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires selon cette invention permet de réduire la résistance à l'insuline, la pression artérielle et la prise de poids et d'améliorer le profil lipidique de ces patients, réduisant ainsi proportionnellement la probabilité d'un accident cardiovasculaire et par conséquent la mortalité qui en résulte.
PCT/BR2007/000349 2006-11-16 2007-11-14 Combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires Ceased WO2008058358A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BRMU8602999-1U BRMU8602999U (pt) 2006-11-16 2006-11-16 medicamento "rosuvastatina + metformina" em forma combinada para doenças cardiovasculares
BRMU8602999-1 2006-11-16

Publications (2)

Publication Number Publication Date
WO2008058358A2 true WO2008058358A2 (fr) 2008-05-22
WO2008058358A3 WO2008058358A3 (fr) 2009-04-16

Family

ID=39402026

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/BR2007/000349 Ceased WO2008058358A2 (fr) 2006-11-16 2007-11-14 Combinaison médicamenteuse 'rosuvastatine + metformine' utilisée pour lutter contre les maladies cardiovasculaires

Country Status (2)

Country Link
BR (1) BRMU8602999U (fr)
WO (1) WO2008058358A2 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014011926A1 (fr) * 2012-07-11 2014-01-16 Elcelyx Therapeutics, Inc. Compositions comportant des statines, des biguanides et d'autres agents pour réduire un risque cardiométabolique
US8796338B2 (en) 2011-01-07 2014-08-05 Elcelyx Therapeutics, Inc Biguanide compositions and methods of treating metabolic disorders
US9050292B2 (en) 2011-01-07 2015-06-09 Elcelyx Therapeutics, Inc. Chemosensory receptor ligand-based therapies
US9211263B2 (en) 2012-01-06 2015-12-15 Elcelyx Therapeutics, Inc. Compositions and methods of treating metabolic disorders
US9480663B2 (en) 2011-01-07 2016-11-01 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US9572784B2 (en) 2011-01-07 2017-02-21 Elcelyx Therapeutics, Inc. Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk
US10154972B2 (en) 2011-01-07 2018-12-18 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US10668031B2 (en) 2011-01-07 2020-06-02 Anji Pharma (Us) Llc Biguanide compositions and methods of treating metabolic disorders
US11759441B2 (en) 2011-01-07 2023-09-19 Anji Pharmaceuticals Inc. Biguanide compositions and methods of treating metabolic disorders
US11974971B2 (en) 2011-01-07 2024-05-07 Anji Pharmaceuticals Inc. Compositions and methods for treating metabolic disorders

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030171407A1 (en) * 2002-03-07 2003-09-11 Upsher-Smith Laboratories, Inc. Composition for reducing blood glucose and cholesterol

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9481642B2 (en) 2011-01-07 2016-11-01 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US9572784B2 (en) 2011-01-07 2017-02-21 Elcelyx Therapeutics, Inc. Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk
US9050292B2 (en) 2011-01-07 2015-06-09 Elcelyx Therapeutics, Inc. Chemosensory receptor ligand-based therapies
US11974971B2 (en) 2011-01-07 2024-05-07 Anji Pharmaceuticals Inc. Compositions and methods for treating metabolic disorders
US11759441B2 (en) 2011-01-07 2023-09-19 Anji Pharmaceuticals Inc. Biguanide compositions and methods of treating metabolic disorders
US11065215B2 (en) 2011-01-07 2021-07-20 Anji Pharma (Us) Llc Biguanide compositions and methods of treating metabolic disorders
US8796338B2 (en) 2011-01-07 2014-08-05 Elcelyx Therapeutics, Inc Biguanide compositions and methods of treating metabolic disorders
US9463170B2 (en) 2011-01-07 2016-10-11 Elcelyx Therapeutics, Inc. Chemosensory receptor ligand-based therapies
US10201511B2 (en) 2011-01-07 2019-02-12 Elcelyx Therapeutics, Inc. Compositions and methods for treating metabolic disorders
US9480663B2 (en) 2011-01-07 2016-11-01 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US10668031B2 (en) 2011-01-07 2020-06-02 Anji Pharma (Us) Llc Biguanide compositions and methods of treating metabolic disorders
US9962344B2 (en) 2011-01-07 2018-05-08 Elcelyx Therapeutics, Inc. Chemosensory receptor ligand-based therapies
US10610500B2 (en) 2011-01-07 2020-04-07 Anji Pharma (Us) Llc Chemosensory receptor ligand-based therapies
US10028923B2 (en) 2011-01-07 2018-07-24 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US10154972B2 (en) 2011-01-07 2018-12-18 Elcelyx Therapeutics, Inc. Biguanide compositions and methods of treating metabolic disorders
US10159658B2 (en) 2011-01-07 2018-12-25 Elcelyx Therapeutics, Inc. Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk
US9211263B2 (en) 2012-01-06 2015-12-15 Elcelyx Therapeutics, Inc. Compositions and methods of treating metabolic disorders
US10603291B2 (en) 2012-01-06 2020-03-31 Anji Pharma (Us) Llc Compositions and methods for treating metabolic disorders
US9770422B2 (en) 2012-01-06 2017-09-26 Elcelyx Therapeutics, Inc. Compositions and methods for treating metabolic disorders
JP2018087214A (ja) * 2012-07-11 2018-06-07 エルセリクス セラピューティクス インコーポレイテッド スタチン、ビグアナイド、およびさらなる薬剤を含む心血管代謝性リスクを減少させるための組成物
WO2014011926A1 (fr) * 2012-07-11 2014-01-16 Elcelyx Therapeutics, Inc. Compositions comportant des statines, des biguanides et d'autres agents pour réduire un risque cardiométabolique
JP2015522080A (ja) * 2012-07-11 2015-08-03 エルセリクス セラピューティクス インコーポレイテッド スタチン、ビグアナイド、およびさらなる薬剤を含む心血管代謝性リスクを減少させるための組成物
CN104780915A (zh) * 2012-07-11 2015-07-15 埃尔舍利克斯治疗公司 包含他汀、双胍和用于减小心脏代谢风险的其它药剂的组合物

Also Published As

Publication number Publication date
WO2008058358A3 (fr) 2009-04-16
BRMU8602999U (pt) 2008-07-08

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