WO2005074928A1 - Remede pour l'hypertension - Google Patents

Remede pour l'hypertension Download PDF

Info

Publication number
WO2005074928A1
WO2005074928A1 PCT/JP2005/001467 JP2005001467W WO2005074928A1 WO 2005074928 A1 WO2005074928 A1 WO 2005074928A1 JP 2005001467 W JP2005001467 W JP 2005001467W WO 2005074928 A1 WO2005074928 A1 WO 2005074928A1
Authority
WO
WIPO (PCT)
Prior art keywords
intracranial pressure
therapeutic agent
hypertension
eucardipine
pharmaceutically acceptable
Prior art date
Application number
PCT/JP2005/001467
Other languages
English (en)
Japanese (ja)
Inventor
Yoichi Katayama
Masanori Suzuki
Asuka Hayashi
Original Assignee
Yamanouchi Pharmaceutical Co., Ltd.
Nihon University
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 Yamanouchi Pharmaceutical Co., Ltd., Nihon University filed Critical Yamanouchi Pharmaceutical Co., Ltd.
Priority to KR1020067015131A priority Critical patent/KR101147308B1/ko
Priority to JP2005517685A priority patent/JPWO2005074928A1/ja
Publication of WO2005074928A1 publication Critical patent/WO2005074928A1/fr

Links

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
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a drug for treating hypertension. More specifically, the present invention relates to a novel use of a drug for treating hypertension containing ecardipine or a salt thereof as an active ingredient.
  • Ucardipine or a salt thereof is a useful compound having an effect of increasing cerebral blood flow, an effect of increasing coronary blood flow, and an antihypertensive effect, and has already been marketed as a therapeutic agent for hypertension (Pervidin registered injection) Liquid: Yamanouchi Pharmaceutical Co., Ltd.). Its effects include emergency treatment of abnormal hypertension during surgery, hypertensive emergency, and acute heart failure. As contraindications, patients who are presumed to have not completed hemostasis due to intracranial hemorrhage, patients with increased intracranial pressure during acute stroke, and others are specified (Non-Patent Document 1). . The reason is stated that each of them may promote bleeding and may increase intracranial pressure.
  • Non-Patent Document 3 it has been reported that Ca antagonists-fludipine and diltiazem significantly increased the cranial pressure in anesthetized dogs.
  • the Ca antagonist may affect the cranial pressure, and cardiopine or a salt thereof, which is the main component of the therapeutic agent for hypertension of the present invention, is conventionally used. It is probable that the above contraindications were specified.
  • Non-patent document 1 Pervidin registered trademark Injection package: Yamanouchi Pharmaceutical Co., Ltd.
  • Non-patent document 2 Hypertension treatment guideline 2000 edition: Japanese Society of Hypertension Hypertension Treatment Guideline Development Committee
  • Non-Patent Document 3 Life Sciences, Vol.62, No.19 p283_288 1998
  • Non-patent document 4 The 21st Annual Meeting of the Japan Stroke Society Abstract number 219 (1996)
  • Non-Patent Document 5 Stroke Volume 20 No. 1 page 110 (1998)
  • Non-Patent Document 6 General Meeting of the Japanese Society of Resuscitation Volume 13 page 107 (1994)
  • the present invention examined whether ecardipine or a salt thereof exhibits side effects that are specifically contraindicated in patients with increased intracranial pressure during the acute phase of stroke, for which indications have been contraindicated. It is an object of the present invention to eliminate indication restrictions that have been conventionally contraindicated. Means for solving the problem
  • ecardipine or a salt thereof is in a group in which intracranial pressure is increased in the acute phase of onset
  • the present invention provides:
  • a drug for treating hypertension in a patient with increased intracranial pressure during acute stroke comprising eucardipine or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the therapeutic agent according to the above item 1 or 2 which is used in combination with a therapeutic agent for cerebral edema.
  • the pharmaceutical composition according to the above item 4 which is an injection. 6.
  • a method for treating hypertension in a patient with increased intracranial pressure during acute stroke comprising administering to the patient a therapeutically effective amount of eucardipine or a pharmaceutically acceptable salt thereof.
  • the present invention has achieved the elimination of contraindications in clinical indications of eucardipine or a salt thereof.
  • the main component of the present invention is a dihydropyridine calcium antagonist-cardipine or a salt thereof. Particularly preferred is hydrochloride-cardipine.
  • a method for synthesizing eucardipine or a salt thereof is known in Japanese Patent Publication No. 56-6417 (US Pat. No. 3,985,758) (applicant, Yamanouchi Pharmaceutical Co., Ltd.), and the method is used.
  • the dosage form can be widely applied to oral preparations, sustained-release preparations, injections, etc., and these are usually prepared using organic or inorganic carriers, excipients and other additives suitable for oral or parenteral use. It can be manufactured according to the law.
  • oral preparations and sustained-release preparations Perdipine (registered trademark) (trade name, LA, tablets, powders) are marketed, and they can be applied to these and their equivalents.
  • Perdipine registered trademark
  • LA tablets, powders
  • sustained-release preparation amorphous eucardipine or a salt thereof is suitably used, and the specific preparation method thereof is described in JP-B-59-48810 (US 4,343,789) and JP-B 64-7047 (US 4,758,437). All of which are incorporated by reference.
  • Injectables are commercially available under the trade name of Perdipine®, and these and their equivalents are also applicable.
  • a formulation containing 2-7 w / v% polyhydric alcohol, preferably D-sorbitol is preferably exemplified, and the specific preparation method is described in Japanese Patent Publication No. 2-47964 (RE 34,618). All are referred to.
  • the most suitable formulation for the indication of the present invention is an injectable formulation because it is intended for acute stroke patients.
  • the administration method of the therapeutic agent for hypertension of the present invention is generally oral administration, transdermal administration, and intravenous administration, and is not limited to any conventionally known administration form.
  • a preferable administration method is an intravenous administration, because it is intended for stroke patients in the acute phase.
  • the dose can be determined according to the conventionally known dosage.
  • dilute a preparation containing dicardipine or its salt for example, 2-30 mL liquid preparation containing 1-30 mg of dicarpidine hydrochloride
  • physiological saline or 5% dextrose injection for example, 2-30 mL liquid preparation containing 1-30 mg of dicarpidine hydrochloride
  • the infusion rate should be 0.5 to 10 per kg of body weight per minute.
  • 10 to 30 ⁇ g of dicardipine hydrochloride per kg of body weight should be administered intravenously as it is without diluting a liquid formulation containing 1 to 30 mg of dicarpidine hydrochloride.
  • the treatment period is one to two weeks, the onset of acute stroke, and is generally administered sixteen times a day.
  • Dicardipine or a salt thereof is administered, and is generally administered 1 to 6 times a day.
  • the remedy for hypertension of the present invention is used in the acute phase of stroke, and can be used in combination with a drug.
  • a combination use of a therapeutic agent for cerebral edema and a cerebral metabolism improving agent is preferably exemplified.
  • combination use with a therapeutic agent for cerebral edema is suitable, and examples thereof include glycerol preparations (glyceol) and mannitol.
  • examples of the prescription are 1 (In the case of %% glycerol preparations, 200 ml at a time is infused intravenously over 1 to 2 hours, and it is common to administer 2 to 6 times a day.
  • Intravenous infusion over a period of time is usually 1 to 13 times.
  • Other concomitant drugs are diuretics, corticosteroids, barbituric acid derivatives, and anticonvulsants (aleviatin, fuetoin, etc.) It is exemplified in.
  • a patient with an increased intracranial pressure in the acute phase of stroke which is an indication for the present invention, means that ICP11 to 15 mmHg or more, which is determined to be abnormal in the ICP-enhanced classification, is persistent.
  • ICP11 to 15 mmHg or more which is determined to be abnormal in the ICP-enhanced classification, is persistent.
  • headache, vomiting and depressed blood nipples are the main signs.
  • liquid preparations of eucardipine hydrochloride were prepared [(nicardipine low-dose preparation) 2 ml preparation: eucardipine hydrochloride 2 mg, D-sorbitol 100 mg, pH adjuster, clear pale yellow, pH 3.0-4.5, osmotic pressure ratio Approx.1.0 (ratio to physiological saline)], [10 ml formulation: dicardipine hydrochloride 10 mg, D-sorbitol 500 mg, pH adjuster, clear pale yellow, pH 3.0-4.5, osmotic pressure ratio approx.
  • Intracranial pressure (ICP) was measured using a Camino brain parenchymal implantable ICP sensor, and regional cerebral blood flow at the center of ischemia was measured using laser Doppler flowmetry. Rectal temperature was maintained at 37 ⁇ 0.5 ° C. A catheter was placed in the femoral artery to measure body blood pressure and blood gas analysis was performed.
  • ICP during ischemia was 6.7 ⁇ 0.5 mmHg, and significantly increased to 13 ⁇ ImmHg 1 hour after reperfusion (p ⁇ 0.05).
  • the mean arterial pressure was reduced by about 19.05% in the nicardipine high-dose group and by about 11.6% in the nicardipine low-dose group.
  • ICP of the group administered with nicardipine high-dose preparation and low-dose preparation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention vis à éliminer l'indication limitée dans des cas de pression intracrânienne élevée au stade aigu de crise cérébrale pour lesquels on a proposé des contre-indications concernant la nicardipine ou son sel. On a découvert pour la première fois que, dans les rats modèles d'infarctus cérébral, la nicardipine ou son sel ne vont pas affecter la pression intracrânienne, contrairement à la perception commune, même chez un groupe avec une pression intracrânienne élevée au stade aigu d'attaque. Notamment, l'invention a trait à un remède pour l'hypertension pour des patients souffrant de pression intracrânienne élevée au stade aigu de crise cérébrale qui contient comme principe actif la nicardipine et son sel.
PCT/JP2005/001467 2004-02-03 2005-02-02 Remede pour l'hypertension WO2005074928A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
KR1020067015131A KR101147308B1 (ko) 2004-02-03 2005-02-02 고혈압증 치료약
JP2005517685A JPWO2005074928A1 (ja) 2004-02-03 2005-02-02 高血圧症治療薬

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004027053 2004-02-03
JP2004-027053 2004-02-03

Publications (1)

Publication Number Publication Date
WO2005074928A1 true WO2005074928A1 (fr) 2005-08-18

Family

ID=34835879

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2005/001467 WO2005074928A1 (fr) 2004-02-03 2005-02-02 Remede pour l'hypertension

Country Status (5)

Country Link
JP (1) JPWO2005074928A1 (fr)
KR (1) KR101147308B1 (fr)
CN (1) CN1913894A (fr)
TW (1) TW200526217A (fr)
WO (1) WO2005074928A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105921223B (zh) * 2016-06-18 2018-10-16 江苏新春兴再生资源有限责任公司 一种处理废铅酸蓄电池细铅栅分离机的分离筒

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
TAKENAKA T. ET AL: "Cerebrovascular effects of YC-93, a new vasodilator, in dogs, monkeys and human patients", INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY, vol. 17, no. 1, 1979, pages 1 - 11, XP002987945 *
WELTY T.E. ET AL: "Pathophysiology and treatment of subarachnoid hemorrhage", CLINICAL PHARMACY, vol. 9, no. 1, 1990, pages 35 - 39, XP002987946 *

Also Published As

Publication number Publication date
KR20070000445A (ko) 2007-01-02
TW200526217A (en) 2005-08-16
CN1913894A (zh) 2007-02-14
TWI339579B (fr) 2011-04-01
JPWO2005074928A1 (ja) 2007-09-13
KR101147308B1 (ko) 2012-05-18

Similar Documents

Publication Publication Date Title
KR101186029B1 (ko) 신경병증성 당뇨병성 족부 궤양을 치료하기 위한트레프로스티닐의 용도
JP6353577B2 (ja) 組み合わせ組成物
US20070197544A1 (en) Iloprost in combination therapies for the treatment of pulmonary arterial hypertension
TW200306799A (en) Combination of organic compounds
BG64540B1 (bg) Използване на дексмедетомидин за постигане на седативен ефект в отделение за интензивна терапия
Joppich et al. Analgesic efficacy and tolerability of intravenous morphine versus combined intravenous morphine and oxycodone in a 2-center, randomized, double-blind, pilot trial of patients with moderate to severe pain after total hip replacement
Minor et al. Prolonged methylene blue infusion in refractory septic shock: a case report
SK138095A3 (en) Transdermal therapeutic system for the administration of serotonin agonists
Park et al. Efficacy of D-CPPene, a competitive N-methyl-D-aspartate antagonist in focal cerebral ischemia in the rat
JP2002511875A (ja) 勃起機能障害治療用のヨヒンビンおよびアルギニン含有薬
JP2002534477A (ja) メラガトランの新規使用
KR100405161B1 (ko) 록소프로펜 함유 근육주사제 조성물
CN109833481B (zh) 一种阿利沙坦酯或其盐与利尿剂的药物组合物
WO2005074928A1 (fr) Remede pour l'hypertension
JP2004536076A (ja) Ｐ−ｇｐインヒビターおよび抗癲癇薬を含んでなる組合せ剤
JP2003201238A (ja) 脳梗塞治療用医薬組成物
KR20060136415A (ko) 고혈압증 치료약
BR112014015276B1 (pt) Combinação de (3s,3s) 4,4-dissulfanodiilbis(ácido 3-aminobutano 1-sulfônico) e um segundo agente anti-hipertensivo
RU2267335C1 (ru) Способ комбинированной анальгезии у пожилых пациентов после операций на тазобедренном суставе и бедре
CN117243947A (zh) 瑞香素及包含其的组合在制备糖尿病并发症药物中的应用
Dinakar Comparative study of variations in blood pressure and heart rate among normotensive patients and hypertensive patients receiving angiotensin receptor blockers during surgery under spinal anesthesia
Tarkase Spinal Anaesthesia With 0.5% Hyperbaric Ropivacaine and 0.5% Hyperbaric Bupivacaine: A Comparative Study
JP2004535457A (ja) ピリダジノン誘導体の新しい用途
WO2022089544A1 (fr) Application du bzp dans le traitement de maladies vasculaires cérébrales et cardiovasculaires ischémiques
CA3212160A1 (fr) Formulations de tasipimidine et leur utilisation

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

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

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1020067015131

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2005517685

Country of ref document: JP

Ref document number: 200580003924.6

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 12006501513

Country of ref document: PH

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

WWP Wipo information: published in national office

Ref document number: 1020067015131

Country of ref document: KR

122 Ep: pct application non-entry in european phase