[go: up one dir, main page]

WO2016133069A1 - Médicament pour la prévention ou le traitement de l'insuffisance cardiaque - Google Patents

Médicament pour la prévention ou le traitement de l'insuffisance cardiaque Download PDF

Info

Publication number
WO2016133069A1
WO2016133069A1 PCT/JP2016/054392 JP2016054392W WO2016133069A1 WO 2016133069 A1 WO2016133069 A1 WO 2016133069A1 JP 2016054392 W JP2016054392 W JP 2016054392W WO 2016133069 A1 WO2016133069 A1 WO 2016133069A1
Authority
WO
WIPO (PCT)
Prior art keywords
heart failure
administration
patients
drug
bnp
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/JP2016/054392
Other languages
English (en)
Japanese (ja)
Inventor
新太郎 九鬼
千尋 日比
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanwa Kagaku Kenkyusho Co Ltd
Fuji Yakuhin Co Ltd
Original Assignee
Sanwa Kagaku Kenkyusho Co Ltd
Fuji Yakuhin Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sanwa Kagaku Kenkyusho Co Ltd, Fuji Yakuhin Co Ltd filed Critical Sanwa Kagaku Kenkyusho Co Ltd
Priority to JP2017500675A priority Critical patent/JP6684264B2/ja
Publication of WO2016133069A1 publication Critical patent/WO2016133069A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

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
    • A61K31/33—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
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone

Definitions

  • the present invention comprises 4- [5- (pyridin-4-yl) -1H-1,2,4-triazol-3-yl] pyridine-2-carbonitrile (generic name: topyroxostat) as an active ingredient. , Relates to a medicament for the prevention or treatment of heart failure.
  • the cause of death among Japanese people is due to heart disease (January 1, 2014, published by the Ministry of Health, Labor and Welfare, annual estimates of 2013 demographic statistics), and death from heart disease is increasing worldwide.
  • the trend is particularly prominent in regions such as Asia and the Middle East, where Western lifestyles and industrial modernization are rapidly advancing.
  • the aging rate is higher than in developed countries, and there is concern about a further increase in heart failure patients.
  • Heart failure is caused by basic heart diseases such as ischemic heart disease and hypertensive heart disease, and the heart cannot pump enough blood to meet the oxygen demand of the major peripheral organs as a pump function. It indicates a pathological condition in which persistent dyspnea appears, resulting in decreased exercise tolerance and impairment of daily living functions. Heart failure has been exacerbated and the readmission rate is high, resulting in increased medical costs. The prognosis for heart failure is poor, and improvement of QOL and reduction of readmission rate for patients with heart failure are the issues.
  • angiotensin converting enzyme inhibitors As therapeutic agents for heart failure, angiotensin converting enzyme inhibitors, calcium antagonists, adrenergic receptor antagonists, vasodilators such as cardiotonic drugs, and diuretics, etc. are generally known. Although it is effective in alleviating the symptoms associated with it, it has various side effects and is not always satisfactory in the treatment of heart failure.
  • treatment of heart failure is mainly to reduce subjective symptoms for the purpose of improving cardiac function, improving QOL and improving life prognosis by treating basic heart disease.
  • it is important to improve the diet, avoid excessive exercise, and make a habit of continuing moderate exercise.
  • Blood BNP brain natriuretic peptide
  • NYHA New York York Heart Association
  • Allopurinol is widely used worldwide for patients with hyperuricemia, but the drug is seriously fatal, such as mucocutaneous ocular syndrome (Stevens-Johnson syndrome) and toxic epidermal necrosis (Rayer syndrome). It is also known as a drug that causes side effects. Especially in patients with impaired renal function, it is reported that oxypurinol, an active metabolite, accumulates excessively in the body, increasing the frequency of the above-mentioned serious side effects, and dose adjustment according to renal function is required. Yes. As described above, heart failure patients often have a decrease in renal function, and there is a problem that allopurinol is difficult to use.
  • An object of the present invention is to provide a drug that exhibits clinically meaningful reduction in blood BNP value, which is considered to reflect improvement of cardiac function, and is highly safe for a long time, as a preventive or therapeutic agent for heart failure It is to be.
  • the present invention is as follows.
  • the present invention it is possible to provide a medicament that is excellent in the prevention or treatment of heart failure and highly safe to the human body.
  • the medicament of the present invention exhibits a clinically meaningful lowering effect, particularly in blood BNP levels.
  • Topiroxostat used in the present invention is disclosed in, for example, WO03 / 064410A1 and WO2014 / 017514A1.
  • the dosage form of the medicament of the present invention is not particularly limited, and examples thereof include oral preparations, injection preparations, transdermal absorption preparations, etc. Among them, oral preparations are preferable.
  • Such dosage form drugs are administered in dosage forms suitable for the dosage form.
  • the medicament of the present invention can be administered not only alone but also in combination with other drugs.
  • an oral preparation it can be made into tablets, granules, fine granules, powders, capsules, etc. by conventional methods, and can be appropriately coated with sugar coating, gelatin coating, and other components usable for pharmaceutical products. You can also In the formulation, additives such as pharmaceutically acceptable excipients, binders, disintegrants, lubricants, colorants, and corrigents can be used in appropriate combinations as necessary.
  • an injection it can be made into a dosage form suitable for administration to sites that can be administered intravenously, subcutaneously, intramuscularly, intradermally, or other injections.
  • the storage shape may be either solid or liquid.
  • pharmaceutically acceptable solubilizers, pH adjusters, buffers, suspending agents, stabilizers, tonicity agents, preservatives, etc. may be used in appropriate combination. Can do.
  • the dosage of the pharmaceutical composition of the present invention is such that the degree of symptoms, patient age, sex, body weight, sensitivity difference, administration route, administration method, administration timing, administration interval, pharmaceutical formulation Depending on the nature, type of concomitant medication, dosage and form of concomitant use, it can be adjusted in a timely manner within the discretion of the doctor, but usually 1 to 1000 mg / day, preferably 5 to 600 mg / day, more preferably 10 to 300 mg / day.
  • the adaptive disease according to the present invention is heart failure, specifically, chronic heart failure, hate of chronic heart failure, congestive heart failure, acute heart failure, acute decompensated heart failure, systolic heart failure, diastolic heart failure, right heart failure, left heart failure , Cardiac dysfunction, cardiac decompensation, high-output heart failure, low-output heart failure, etc., particularly effective are chronic heart failure, ashamed of chronic heart failure, and acute heart failure. Among them, the effect is particularly excellent for chronic heart failure.
  • topiroxostat During the administration of topiroxostat, no new additions such as diuretics or other changes in dosage or administration, which are particularly likely to affect blood BNP levels, were performed. There were 15 patients, 13 males and 2 females, and the age was 67-94 years. Among them, the breakdown of 13 cases by similar drugs before administration of topiroxostat was allopurinol 2 cases and febuxostat 11 cases. There were 2 non-similar patients. In addition, the BNP level in blood during the allopurinol or febuxostat administration period (for 3 months) prior to topiroxostat administration did not show any significant fluctuation.
  • the change in blood BNP value when switching to topiroxstat in 13 patients with heart failure who are receiving the similar drugs allopurinol or febuxostat is 431 ⁇ 272 pg / ml before administration (mean ⁇ SD) From 3 to 3 months after administration, the dose decreased significantly to 293 ⁇ 243 pg / ml, and 6 months after administration (final evaluation), it further decreased to 248 ⁇ 136 pg / ml. In addition, the changes in blood BNP levels from before administration to 6 months after administration (at the time of the final evaluation) of 2 patients who did not receive similar drugs showed a marked decrease in -184 pg / ml and -660 pg / ml, respectively. It was.
  • FIG. 1 shows the changes in the blood BNP values of the 15 subjects after administration of topiroxstat.
  • the change in blood BNP which is a cardiac function marker, decreased by 45% on average at -173 pg / ml as early as 3 months after administration.
  • Non-patent Document 2 that the cardiovascular mortality rate increases by 3% every 6 years with an increase in BNP of 10 pg / ml in moderate or higher heart failure, the amount of decrease in blood BNP level due to the administration of topiroxostat is surprising It is to be done.
  • the mean pre-dose value of 469 pg / ml is the severity of heart failure equivalent to approximately III degrees in the NYHA classification, and the mean blood BNP values after 3 and 6 months are 296 pg / ml and 254 pg / ml, respectively. Corresponds to approximately II degrees.
  • This decrease in blood BNP level (average -215 pg / ml) improved the heart failure severity (NYHA severity) by 1 degree, especially for medical benefits such as the possibility of reduced cardiovascular mortality It was also suggested that there are significant medical economic benefits such as the possibility of a reduction in the readmission rate.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'objectif de la présente invention est un médicament pour la prévention ou le traitement de l'insuffisance cardiaque. Ce médicament comprend 4- [5- (pyridin-4-yl) -1 H -1,2,4-triazol-3-yl] pyridine-2-carbonitrile (nom générique : Topiroxostat) en tant que principe actif.
PCT/JP2016/054392 2015-02-17 2016-02-16 Médicament pour la prévention ou le traitement de l'insuffisance cardiaque Ceased WO2016133069A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2017500675A JP6684264B2 (ja) 2015-02-17 2016-02-16 心不全の予防又は治療のための医薬

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015028707 2015-02-17
JP2015-028707 2015-02-17

Publications (1)

Publication Number Publication Date
WO2016133069A1 true WO2016133069A1 (fr) 2016-08-25

Family

ID=56689011

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/054392 Ceased WO2016133069A1 (fr) 2015-02-17 2016-02-16 Médicament pour la prévention ou le traitement de l'insuffisance cardiaque

Country Status (2)

Country Link
JP (1) JP6684264B2 (fr)
WO (1) WO2016133069A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018135278A (ja) * 2017-02-20 2018-08-30 株式会社スタージェン 循環器疾患及び／又はミトコンドリア病の改善用医薬

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003064410A1 (fr) * 2002-01-28 2003-08-07 Fuji Yakuhin Co., Ltd. Nouveau compose 1,2,4-triazole
JP2006514051A (ja) * 2002-12-20 2006-04-27 タツプ・フアーマシユーテイカル・プロダクツ・インコーポレイテツド 慢性心不全の治療
JP2008088107A (ja) * 2006-10-02 2008-04-17 Fujiyakuhin Co Ltd 新規ピリダジン誘導体

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003064410A1 (fr) * 2002-01-28 2003-08-07 Fuji Yakuhin Co., Ltd. Nouveau compose 1,2,4-triazole
JP2006514051A (ja) * 2002-12-20 2006-04-27 タツプ・フアーマシユーテイカル・プロダクツ・インコーポレイテツド 慢性心不全の治療
JP2008088107A (ja) * 2006-10-02 2008-04-17 Fujiyakuhin Co Ltd 新規ピリダジン誘導体

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
GAVIN, A.D. ET AL.: "Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure", HEART, vol. 91, no. 6, 2005, pages 749 - 753 *
IWAO ONO: "Role of tiyperuricemia in cardiorenal syndrome", JAPANESE SOCIETY OF GOUT AND NUCLEIC ACID METABOLISM SOKAI PROGRAM., vol. 47th, 2014, pages 85 *
SHINTARO KUKI ET AL.: "The Clinical Experience of Topiroxostat in Patients at High Risk of Cardiovascular Disease", THERAPEUTIC RESEARCH, vol. 37, no. 1, 20 January 2016 (2016-01-20), pages 49 - 57 *
SHINTARO KUKI: "Topiroxostat no Yukosei no Kento", THE JOURNAL OF THE JAPANESE SOCIETY OF INTERNAL MEDICINE, vol. 104, no. Suppl., 20 February 2015 (2015-02-20), pages 148 *
ZENTA TSUTSUMI: "Ko Nyosan Kessho Chiryoyaku no pleiotropic effect", TSUFU TO KAKUSAN TAISHA, vol. 38, no. 2, 2014, pages 157 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2018135278A (ja) * 2017-02-20 2018-08-30 株式会社スタージェン 循環器疾患及び／又はミトコンドリア病の改善用医薬

Also Published As

Publication number Publication date
JPWO2016133069A1 (ja) 2018-01-25
JP6684264B2 (ja) 2020-04-22

Similar Documents

Publication Publication Date Title
JP5924699B2 (ja) 糖尿病の治療薬
WO2023006923A1 (fr) Schéma posologique pour agonistes du récepteur glp1/glucagon à action prolongée
JP6509729B2 (ja) 慢性腎臓病の進行抑制又は改善剤
JPWO2019106851A1 (ja) 非アルコール性脂肪性肝疾患（ｎａｆｌｄ）および／または非アルコール性脂肪性肝炎（ｎａｓｈ）、および／または肝脂肪性変性の治療と予防に適した、配合剤
Madsbad Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists: no
JP2025509278A (ja) 小細胞肺癌を治療する方法
JP6684264B2 (ja) 心不全の予防又は治療のための医薬
KR102512518B1 (ko) 페마피브레이트를 함유하는 의약
AU2020393489A1 (en) Pharmaceutical composition for the treatment of pulmonary vascular disease and/or cardiac dysfunction in Fontan-palliated patients
KR20230143978A (ko) 시클로-히스프로를 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약제학적 제제
WO2020080451A1 (fr) Inhibiteur de fibrose rénale dans une néphropathie diabétique
JPWO2017022787A1 (ja) 収縮力低下随伴性排尿筋過活動改善剤
US20030105108A1 (en) Method of treating peripheral vascular diseases, peripheral neuropathies, and autonomic neuropathies
JP6563375B2 (ja) 腎症治療剤
KR20220004643A (ko) 신규 의약 조성물
Safdar et al. Longitudinal Use of Midodrine to Optimize Pulmonary Hypertension Therapies
Meyer et al. Sex differences in early dyspnea relief between men and women hospitalized for
TWI674094B (zh) 治療或緩解慢性骨髓性白血病用之醫藥組合物
JP2024520755A (ja) 変力剤として使用するためのピペリジン尿素誘導体
JP2007008845A (ja) 慢性心不全治療および／または予防薬
Takahashi et al. Effects of Switching from Allopurinol to Febuxostat in Chronic Kidney Disease Patients
CN1972715A (zh) 含有胰岛素抵抗改善剂的糖尿病治疗剂
Paterno et al. [PP. 13.11] BENEFIT IN CENTRAL HAEMODYNAMIC PARAMETERS BY ASSOCIATION ANGIOTENSIN II RECEPTOR BLOCKERS AND CANRENONE THERAPY IN HYPERTENSIVE PATIENTS WITH NORMAL KIDNEY FUNCTION
Mohammed et al. Comparison between the Effect of Sildenafil versus Nifedipine in the Treatment of Pulmonary Hypertention in Children
JP2006193516A (ja) ＦＢＰａｓｅ阻害剤を含有する医薬組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16752455

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2017500675

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16752455

Country of ref document: EP

Kind code of ref document: A1