[go: up one dir, main page]

WO2000067770A1 - Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance - Google Patents

Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance Download PDF

Info

Publication number
WO2000067770A1
WO2000067770A1 PCT/SE2000/000844 SE0000844W WO0067770A1 WO 2000067770 A1 WO2000067770 A1 WO 2000067770A1 SE 0000844 W SE0000844 W SE 0000844W WO 0067770 A1 WO0067770 A1 WO 0067770A1
Authority
WO
WIPO (PCT)
Prior art keywords
growth hormone
substance
treatment
ischemic event
functionally equivalent
Prior art date
Application number
PCT/SE2000/000844
Other languages
English (en)
Inventor
Jörgen ISGAARD
Elmir Omerovic
Entela Bollano
Bengt-Åke BENGTSSON
Finn Waagstein
Original Assignee
Sahltech I Göteborg AB
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 Sahltech I Göteborg AB filed Critical Sahltech I Göteborg AB
Priority to EP00930008A priority Critical patent/EP1173190A1/fr
Priority to AU47908/00A priority patent/AU4790800A/en
Publication of WO2000067770A1 publication Critical patent/WO2000067770A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/30—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/27—Growth hormone [GH], i.e. somatotropin
    • 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

Definitions

  • Ischemic heart disease is the most common cause of death in both men and women in the Western world. Some of the clinical manifestations are angina pectoris, myocardial infarction, congestive heart failure (CHF) and sudden death. Despite marked improvements in the treatment including beta-blockers, trombolysis and PTCA, mortality of patients with acute myocardial infarction (MI) is still very high and almost 50% of patients surviving MI eventually develop CHF. Cardiac changes developing after MI include left ventricular dilatation and hypertrophy of the residual non-infarcted myocardium also known as remodeling. Moreover, contractile impairment often occurs after MI, clinically manifested as CHF.
  • MI myocardial infarction
  • a lowering of arterial blood pressure peripheral resistance by GH may also be beneficial for hemodynamics (see Caidahl K. et al . , Cardiovascular and renal effects of growth hormone, Clin. Endocrinol . (Oxf) 1994; 40:393-400; Jin H., et al . , Beneficial effects of growth hormone and insulin-like factor-1 in experimental heart failure in rats treated with chronic ACE inhibition, J. Cardiovasc . Pharmacol. 1995; 26:420-425). It may be speculated that this effect is more rapid and could be an important factor in studies demonstrating acute cardiovascular effects of GH (see Volterrani M., et al . Hemodynamic effects of intravenous growth hormone in congestive heart failure, Lancet 1997; 349:1067-1068).
  • Insulin-like growth factor I stimulates myofibril development and decreases smooth muscle I -actin of adult cardiomyocytes, Proc. Natl. Acad. Sci . USA 1994; 91:1686-1690) and increases isometric force and free cytosolic Ca 2+ (see Freestone N. S., et al . , The effect of insulin-like growth factor- 1 on adult rat cardiac contractility, Molecular and Cellular Biochemistry 1996; 163/164:223-229).
  • Apoptosis or programmed cell death, has been reported to occur in the myocardium of patients both after ischemic injury (see Saraste A., et al . , Apoptosis in human acute myocardial infarction, Circulation 1997; 95:320-323) and in conditions with dilated cardiomyopathy (see Narula J. , et al . , Apoptosis in myocytes in end- stage heart failure, N. Engl. J. Med. 1996; 335-1182- 1189) .
  • Some of the genes involved in the apoptotic process have been identified including the Fas-receptor which has been shown to mediate signals for apoptosis (see Itoh N.
  • Fas-receptor Upregulation of the Fas-receptor has been shown to be associated with apoptosis after myocardial infarction in rats (see Kajstura J., et al . , Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats, Lab. Invest. 1996; 74:86-107).
  • a possible mechanism contributing to the deterioration of heart function post MI may be altered energy metabolism and a reduction of energy reserve which have been observed in rats with experimental MI (see Neubauer S., et al . , Impairment of energy metabolism in intact residual myocardium of rat heart with chronic myocardial infarction, J. Clinical Invest. 1995; 95:1092-1100). However, until now the potential effects of GH on myocardial energy stores have not been evaluated.
  • the invention thus relates to the use of a substance related to the growth hormone axis, or of a combination of two or more such substances, for the production of a pharmaceutical preparation for treatment of an acute ischemic event.
  • the pharmaceutical preparation according to the invention should thus be administered to a patient shortly after the ischemic event first has occurred, and the sooner the better.
  • the invention also relates to a method for treatment of an acute ischemic event, wherein a therapeutically active amount of a substance related to the growth hormone axis is administered to a patient, preferably within a short period of time from the first manifestation of the ischemic event.
  • the invention relates to the use of substances related to the growth hormone axis.
  • substance related to the growth hormone axis relates to all substances related to, linked to or involved in the sequence of successive activation reactions wherein GH is involved, comprising GH it self, hormones from the hypothalamus affecting GH and hormones or growth factors affected by GH.
  • Preferred examples of such substances are growth hormone (GH) , growth hormone secreta- gogues (GHSs) , or insulin like growth factor I (IGF-I) .
  • GH growth hormone
  • GHSs growth hormone secreta- gogues
  • IGF-I insulin like growth factor I
  • GH or an analogue thereof is especially preferred.
  • the growth hormone (GH) used according to the invention is preferably human growth hormone. It is possible to use both naturally derived GH and synthetically produced GH.
  • a growth hormone secretagogue is a substance that stimulates secretion of GH. According to the invention it is possible to use both naturally derived GHSs and synthetically produced GH. Furthermore, the GHS used may be either a peptidic or a non-peptidic substance.
  • a peptidic GHS suitable for use according to the present invention is growth hormone release peptide (GHRP) , which is a substance that leads to increased secretion of GH.
  • the insulin like growth factor I (IGF-I) used according to the invention is preferably human IGF-I. It is possible to use both naturally derived IGF-I and synthetically produced IGF-I.
  • the pharmaceutical preparation produced according to the invention and the method according to the invention are suitable for treatment of ischemic events.
  • Ischemic event is a term describing a condition with a relative shortage of oxygen supply to the myocardium manifested e.g. as angina pectoris, myocardial infarction, contractile dysfunction, arrythmia, fatigue, decreased exercise performance and breathlessness.
  • the pharmaceutical preparation and the method according to invention are intended for treatment of acute ischemic events such as acute myocardial infarctions, angina pectoris and sudden cardiac decompensation.
  • patient relates to any human or non-human mammal in need of treatment according to the invention.
  • treatment used herein relates to measures taken in order to cure or alleviate a disease or a condition.
  • a "therapeutically active amount" of the substance is used. This expression relates to a dose of the substance that will lead to the desired pharmacological effect.
  • the desired pharmacological effect is, as stated above, to improve the systolic function by improving the myocardial energy handling.
  • the pharmaceutical preparation according to the invention may also comprise other substances, such as an inert vehicle, or pharmaceutical acceptable adjuvants, carriers, preservatives etc., which are well known to persons skilled in the art.
  • Fig. 1 is a diagram illustrating the creatine phosphate to ATP ratio measured with 31 P-MRS in MI rats treated with rhGH; the values are mean ⁇ SEM, **p ⁇ 0.01 compared to effect of saline treatment;
  • Fig. 2 is a diagram illustrating the fractional shortening measured with echocardiography in MI rats treated with rhGH; the values are mean ⁇ SEM, **p ⁇ 0.01 compared to effect of saline treatment.
  • MI myocardial infarction
  • the rats were anesthetized with ketamine hydrochloride 100 mg/kg (Parke-Davis, Morris Plains, NJ, USA) and xylazine hydrochloride (Bayer AG, Leverkusen, Germany) 10 mg/kg i.p., intubated and connected to a respirator for artificial ventilation with room air and oxygen using a Carlsson ventilator (Astra-Hassle, Goteborg, Sweden) . A 2.5 cm long parasternal incision was made in the left thoracic area to the skeletal muscle. The muscle layers were separated with minimal damage using blunt dissection. Left thoracotomy was than performed between the fourth and fifth ribs, exposing the left ventricular wall .
  • ECHO Transthoracal echocardiography
  • Pulsed wave Doppler spectra of mitral inflow from the apical four- chamber view were used to asses LV diastolic flow characteristics. Stroke volume (SV) was calculated using Doppler recording from the pulmonary artery (as described by Baily R. G. , et al . in Non- invasive assessment of ventricular damage in rats with myocardial infarction, Car- diovasc . Res. 1993; 27: 851-855). All investigations were stored as cine- loop pictures, M-mode tracings and Doppler spectra on optical disc for off-line analysis. All measurements were averaged at least on 3 consecutive cardiac cycle using EchoPac 5.4 off-line analysis system (GE Ving Med, USA) .
  • EchoPac 5.4 off-line analysis system GE Ving Med, USA
  • WS Left ventricular meridional wall-stress
  • P is the systolic blood pressure
  • Am is the myocardial area determined by subtraction of the LV cavity area (Ac) from the total LV area and 1.33 is conversion constant from millimeters of mercury to dynes/cm 2 . Echocardiographic estimation of infarct size
  • the size of MI was estimated according to the score system as described by Baily R. G. (supra) .
  • the left ventricle was arbitrary divided into 4 regions in LAX and SAX.
  • Each of the segments in parasternal LAX and SAX views was assigned a point for the presence of akinesis and/or dyskinesis. Additional point was assigned for the presence of LV dilatation on the M-mode tracing. Dilatation was defined as 15% more than the average of the left ventricular internal diameter (LVDd) in end diastole of the control group.
  • a myocardial infarction was considered to be small if the total score was 1-2 points, moderate if 3 or 4 and large if > 5 points.
  • MI > 1/3 of LV is associated with progressive LV remodeling and hemodynamic abnormalities characteristic for heart failure while MI ⁇ 1/3 of LV or nontransmural infarcts do not consistently cause this changes (see Pfeffer M. A., et al . , Myocardial infarct size and ventricular function in rats, Circ. Res. 1979; 44:503-512).
  • the inclusion criteria for rats with MI were that > 1/3 of the LV circumference was showing signs of irreversible ischemia.
  • MR imaging and volume-selective cardiac 31 P-MRS were performed on a 2.35 Tesla (T) horizontal magnet with a 20 cm bore (Bruker Biospec 24/30) according to the method previously described by our laboratory.
  • the magnetic field homogeneity was optimized until line width of the water 1 H-signal at half height was ⁇ 0.5 ppm.
  • a surface coil of 5 cm diameter dual tuned ( 1 H and 31 P) was used for radio frequency transmission and reception.
  • Rats were given induction anesthesia with fenta- nyl/fluanizon (Hypnorm, Janssen) 0.5 mg/kg and diazepam (Stesolid) 2.5 mg/kg. Constant body temperature (36.5 ⁇ 0.5C°) was maintained by specially adapted homeothermic blanket system (Harvard Apparatus) . The animals were placed with heart region lying on the surface coil in prone position to minimize respiratory movements of the chest wall. The paws were wrapped in thin copper foil and connected via carbon electrodes to the Physiogard SM 785 MR monitoring system (Bruker, Düsseldorf, Germany) . Continuous ECG signal was then acquired and used for synchronization of RF pulses and monitoring of HR. The animals were maintained anaesthetized by continuous gas anesthesia with isoflurane delivered in the mixture of oxygen and nitrous oxide (1:1) in the concentration 0.4-1 % and at flow rate 0.4 1/min.
  • a gradient echo imaging method was used for visualization of the heart and selection of VOI for 31 P-MRS. All images as well as spectroscopic data acquisition were obtained with synchronized RF pulses to the cardiac rhythm with triggering delay of 1 ms after the R wave. Five images (2.5 mm slice thickness and field of view of 8 cm) were acquired in the sagittal plane in order to visualize the thoraco-abdominal region and the heart. Starting from the scout image in the sagittal plane 5 additional (2.5 mm) images were taken perpendicular on the LV long axis. Image selected in vivo spectroscopy (ISIS) (see Ordridge R. J., et al .
  • ISIS Image-Selected In vivo Spectroscopy
  • Accumulation parameters were 512 scans, 4k data points and 2500 Hz sweep width with a 4.5 s repetition time giving the total scan time 38 min.
  • Spectroscopic processing consisted of Fourier transformation followed by first order phase correction, Lorenzian curve fitting and integration of PCr, ⁇ -ATP, 2,3-DPG + and Pi peaks.
  • Phosphocreatine, ATP, and 2,3-DPG were calculated by computer integration of the areas under the respective peaks.
  • Myocardial PCr/ATP ratio was corrected for partial saturation for each animal separately by use of the correction factor calculated from PCr/ATP measured from unlocalized spectra of the chest region acquired at 4.5 s and 15 s repetition time (see Bottomley P.
  • FS fractional shortening

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Endocrinology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne l'utilisation d'une substance liée à l'axe de l'hormone de croissance, notamment l'hormone de croissance, de sécrétagogues de l'hormone de croissance, par exemple le peptide de libération de l'hormone de croissance, et du facteur de croissance insulinoïde I (IGF-I), ou d'une combinaison de deux de ces substances au moins, pour la production d'une préparation pharmaceutique destinée au traitement d'un événement ischémique aigu, tel que l'infarctus myocardique aigu. L'invention concerne également une méthode de traitement d'un événement ischémique aigu, tel que l'infarctus myocardique aigu, traitement qui consiste à administrer à un patient une substance liée à l'axe de l'hormone de croissance.
PCT/SE2000/000844 1999-05-05 2000-05-03 Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance WO2000067770A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP00930008A EP1173190A1 (fr) 1999-05-05 2000-05-03 Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance
AU47908/00A AU4790800A (en) 1999-05-05 2000-05-03 Treatment of acute myocardial infarction with a substance related to the growth hormone axis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9901634-7 1999-05-05
SE9901634A SE9901634D0 (sv) 1999-05-05 1999-05-05 Treatment of myocardial infarction with a substance related to the growth hormone axis

Publications (1)

Publication Number Publication Date
WO2000067770A1 true WO2000067770A1 (fr) 2000-11-16

Family

ID=20415485

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2000/000844 WO2000067770A1 (fr) 1999-05-05 2000-05-03 Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance

Country Status (4)

Country Link
EP (1) EP1173190A1 (fr)
AU (1) AU4790800A (fr)
SE (1) SE9901634D0 (fr)
WO (1) WO2000067770A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004017986A1 (fr) * 2002-08-23 2004-03-04 Valorisation-Recherche, Societe En Commandite Peptides liberant l'hormone de croissance pour le traitement ou la prevention de l'atherosclerose et de l'hypercholesterolemie
EP1529533A1 (fr) * 2003-11-06 2005-05-11 Sahltech I Göteborg AB Utilisation de sécrétagogues de l'hormone de croissance dans le traitement des lésions cérébrales ischémiques et hypoxiques

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992011865A1 (fr) * 1991-01-11 1992-07-23 Kabi Pharmacia Ab Utilisation du facteur humain de croissance de type i proche de l'insuline (igf-i)
WO1995028174A1 (fr) * 1994-04-15 1995-10-26 Genentech, Inc. Combinaison d'hormone de croissance et de facteur de croissance de type insuline dans le traitement de l'insuffisance cardiaque
WO1999001151A1 (fr) * 1997-07-04 1999-01-14 Pharmacia & Upjohn Ab Utilisation d'hormone de croissance dans des compositions traitant la resistance du coeur a l'insuline, et renforçant l'action de la proteine kinase b (pkb)

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992011865A1 (fr) * 1991-01-11 1992-07-23 Kabi Pharmacia Ab Utilisation du facteur humain de croissance de type i proche de l'insuline (igf-i)
WO1995028174A1 (fr) * 1994-04-15 1995-10-26 Genentech, Inc. Combinaison d'hormone de croissance et de facteur de croissance de type insuline dans le traitement de l'insuffisance cardiaque
WO1999001151A1 (fr) * 1997-07-04 1999-01-14 Pharmacia & Upjohn Ab Utilisation d'hormone de croissance dans des compositions traitant la resistance du coeur a l'insuline, et renforçant l'action de la proteine kinase b (pkb)

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
CITTADINI A. ET AL.: "Growth hormone and the heart", MINER. ELECTROLYT. METAB., vol. 25, no. 1-2, 1999, pages 51 - 55, XP002931983 *
H.E. CASTAGNINO ET AL.: "Preservation of the myocardial collagen framework by human growth hormone in experimental infarctions and reduction in the incidence of ventricularaneurysms", INTERNATIONAL JOURNAL OF CARDIOLOGY, vol. 35, 1992, pages 101 - 114, XP002931985 *
HO K.K. ET AL.: "Metabolic actions of growth hormone in man", ENDOCR. J., vol. 43 (SUPPL), October 1996 (1996-10-01), pages S57 - S63, XP002931984 *
HUGO E. CASTAGNINO: "Great expectations from a different approach to the treatment of acute myocardial infarction: cytoprotection", INTERNATIONAL JOURNAL OF CARDIOLOGY, vol. 69, 1999, pages 15 - 18, XP002931986 *
ISGAARD J. ET AL.: "The role of the GH/IGF-I axis for cardiac function and structure", HORM. METAB. RES., vol. 31, no. 2-3, 1999, pages 50 - 54, XP002931982 *
M. SCHWEINOWITZ ET AL.: "The role of insulin-like and basic fibroblasts growth factors on ischemic and infarcted myocardium: a mini review", INTERNATIONAL JOURNAL OF CARDIOLOGY, vol. 59, 1997, pages 1 - 5, XP002931981 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004017986A1 (fr) * 2002-08-23 2004-03-04 Valorisation-Recherche, Societe En Commandite Peptides liberant l'hormone de croissance pour le traitement ou la prevention de l'atherosclerose et de l'hypercholesterolemie
US7785567B2 (en) 2002-08-23 2010-08-31 Valorisation-Recherche, Société en Commandite Growth hormone-releasing peptides in the treatment or prevention of atherosclerosis and hypercholesterolemia
EP1529533A1 (fr) * 2003-11-06 2005-05-11 Sahltech I Göteborg AB Utilisation de sécrétagogues de l'hormone de croissance dans le traitement des lésions cérébrales ischémiques et hypoxiques

Also Published As

Publication number Publication date
AU4790800A (en) 2000-11-21
EP1173190A1 (fr) 2002-01-23
SE9901634D0 (sv) 1999-05-05

Similar Documents

Publication Publication Date Title
US7026293B2 (en) Treatment or prophylaxis of ischemic heart disease
US20080032933A1 (en) Type V Phosphodiesterase Inhibitors and Natriuretic Polypeptides
EP4106744A1 (fr) Utilisation d'inhibiteurs de sglt-2 pour la prévention et/ou le traitement de maladies cardiaques chez les félins
JP4726797B2 (ja) 消耗症に罹患している患者の治療における成長ホルモン放出因子類似体の使用
Kyhl et al. Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction
Tivesten et al. Similar cardiovascular effects of growth hormone and insulin-like growth factor-I in rats after experimental myocardial infarction
WO2000067770A1 (fr) Traitement de l'infarctus myocardique aigu a l'aide d'une substance liee a l'axe de l'hormone de croissance
US20160101117A1 (en) Use of Megestrol Acetate for Improving Heart Function and the Treatment of Heart Insufficiency
WO2023205183A1 (fr) Formulation intraveineuse contenant de l'istaroxime pour le traitement d'un pré-choc cardiogénique et d'un choc cardiogénique
US6878689B2 (en) Preventives or remedies for heart failure
US20060205642A1 (en) Oral methods of treatment using proANF peptides
US20070032557A1 (en) Method for administering levosimendan
Zierhut et al. Time course of spirapril-induced structural and functional changes after myocardial infarction in rats followed with magnetic resonance imaging
SK19332001A3 (sk) Použitie antagonistov kortizolu v liečení srdcového zlyhania
KR20180102091A (ko) 당뇨병의 치료를 위한 약제학적 제제
Yang et al. Effects of growth hormone in rats with postinfarction left ventricular dysfunction
TW202021610A (zh) 短胜肽用於治療/預防高血壓及其相關疾病之用途
US20050009744A1 (en) Treatment of congestive heart failure
US10716798B2 (en) Compositions and methods for tranquilizing heart muscle
JP2003527420A (ja) 鬱血性心不全の治療方法
Shimakura et al. Improvement of cardiac function after treatment with octreotide followed by trans-sphenoidal surgery in an acromegalic patient who presented with congestive heart failure
WO2025128432A1 (fr) Istaroxime et dérivés métabolites associés pour réduire le risque d'arythmie myocardique aiguë
CN102085208B (zh) 一种治疗冠心病、心绞痛的药物组合物
HK40022791A (en) Methods of treating heart failure with preserved ejection fraction
CN104586872A (zh) 一种预防和治疗血管内皮功能紊乱的药物组合物及其应用

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ CZ DE DE DK DK DM DZ EE EE ES FI FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2000930008

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 09959308

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 2000930008

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Ref document number: 2000930008

Country of ref document: EP