ATE269066T1 - Kombinationstherapie zur prophylaxe und/oder behandlung von gutartiger prostatischer hyperplasie - Google Patents

Kombinationstherapie zur prophylaxe und/oder behandlung von gutartiger prostatischer hyperplasie

Info

Publication number
ATE269066T1
ATE269066T1 AT99106510T AT99106510T ATE269066T1 AT E269066 T1 ATE269066 T1 AT E269066T1 AT 99106510 T AT99106510 T AT 99106510T AT 99106510 T AT99106510 T AT 99106510T AT E269066 T1 ATE269066 T1 AT E269066T1
Authority
AT
Austria
Prior art keywords
treatment
benign prostatic
prostatic hyperplasia
prophylaxis
combination therapy
Prior art date
Application number
AT99106510T
Other languages
English (en)
Inventor
Fernand Labrie
Original Assignee
Endorech Inc
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 Endorech Inc filed Critical Endorech Inc
Application granted granted Critical
Publication of ATE269066T1 publication Critical patent/ATE269066T1/de

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32Antioestrogens

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Fertilizers (AREA)
  • Medicinal Preparation (AREA)
AT99106510T 1989-07-07 1990-07-05 Kombinationstherapie zur prophylaxe und/oder behandlung von gutartiger prostatischer hyperplasie ATE269066T1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US37670089A 1989-07-07 1989-07-07
EP90909598A EP0480950B1 (de) 1989-07-07 1990-07-05 Kombinationstherapie zur prophylaxe und/oder behandlung benigner prostatahyperplasie
EP98104849A EP0857487A3 (de) 1989-07-07 1990-07-05 Kombinationspräparate zur Prophylaxe und/oder Behandlung benigner Prostatahyperplasie welche ein beta-hydroxysteroid-dehydrogenaseinhibitor und zumindest ein weiteres aktives Bestandteil enthalten

Publications (1)

Publication Number Publication Date
ATE269066T1 true ATE269066T1 (de) 2004-07-15

Family

ID=23486098

Family Applications (2)

Application Number Title Priority Date Filing Date
AT90909598T ATE177949T1 (de) 1989-07-07 1990-07-05 Kombinationstherapie zur prophylaxe und/oder behandlung benigner prostatahyperplasie
AT99106510T ATE269066T1 (de) 1989-07-07 1990-07-05 Kombinationstherapie zur prophylaxe und/oder behandlung von gutartiger prostatischer hyperplasie

Family Applications Before (1)

Application Number Title Priority Date Filing Date
AT90909598T ATE177949T1 (de) 1989-07-07 1990-07-05 Kombinationstherapie zur prophylaxe und/oder behandlung benigner prostatahyperplasie

Country Status (17)

Country Link
US (1) US5817649A (de)
EP (3) EP0943328B1 (de)
JP (2) JP3332377B2 (de)
KR (1) KR920703063A (de)
AT (2) ATE177949T1 (de)
AU (2) AU643445B2 (de)
CA (1) CA2062973C (de)
DE (2) DE69033020T2 (de)
DK (2) DK0480950T3 (de)
ES (2) ES2133270T3 (de)
HU (1) HU223662B1 (de)
IE (2) IE990530A1 (de)
IL (1) IL94990A (de)
MY (1) MY106484A (de)
NZ (1) NZ234414A (de)
WO (1) WO1991000731A1 (de)
ZA (1) ZA905312B (de)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204337A (en) * 1988-10-31 1993-04-20 Endorecherche Inc. Estrogen nucleus derivatives for use in inhibition of sex steroid activity
ES2189784T3 (es) * 1989-07-07 2003-07-16 Endorech Inc Procedimiento para el tratamiento de enfermedades relacionadas con adrogenos.
IL101245A0 (en) * 1991-03-20 1992-11-15 Merck & Co Inc Pharmaceutical compositions for the treatment of prostatic cancer
AU1893492A (en) * 1991-04-17 1992-11-17 Merck & Co., Inc. Pharmaceutical combination for the treatment of benign prostatic hyperplasia comtaining a 5 alpha-reductase inhibitor
US5175155A (en) * 1991-10-07 1992-12-29 Sterling Winthrop Inc. Win 49596-finasteride method of use and compositions
GB9506678D0 (en) * 1995-03-31 1995-05-24 Glaxo Inc Substituted 6-azacholesten-3-ones
US5780435A (en) 1995-12-15 1998-07-14 Praecis Pharmaceuticals Incorporated Methods for treating prostate cancer with LHRH-R antagonists
RU2000125533A (ru) 1998-03-11 2002-10-20 Эндорешерш, Инк. (Ca) Ингибиторы 17-бета-гидроксистероиддегидрогеназ 5 и 3 типа и способы их применения
EP1321146A3 (de) * 1998-03-11 2004-06-02 Endorecherche Inc. Typ 5 und Typ 3 17 Beta-Hydroxisteroid-Dehydrogenasehemmer und Verfahren zu ihrer Anwendung
DE19825591A1 (de) * 1998-06-09 1999-12-23 Jenapharm Gmbh Pharmazeutische Kombinationen zum Ausgleich eines Testosteron-Defizits beim Mann mit gleichzeitigem Schutz der Prostata
US6268377B1 (en) * 1998-09-28 2001-07-31 Merck & Co., Inc. Method for treating androgen-related conditions
EP1253966B1 (de) * 1999-08-13 2011-04-27 Curadis GmbH Substanzen und mittel zur positiven beeinflussung von kollagen
US6200573B1 (en) 1999-12-03 2001-03-13 Starcor Pharmaceuticals, Inc. Method of medical management for lower urinary tract symptoms and benign prostatic hyperplasia
US7001911B2 (en) * 2000-06-28 2006-02-21 Bristol-Myers Squibb Company Fused cyclic modulators of nuclear hormone receptor function
US20040077605A1 (en) 2001-06-20 2004-04-22 Salvati Mark E. Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function
JP2004509072A (ja) * 2000-06-28 2004-03-25 ブリストル−マイヤーズ スクイブ カンパニー 選択的アンドロゲン受容体モジュレーター並びにその同定、設計及び使用方法
AU2001267904A1 (en) * 2000-06-30 2002-01-14 Chugai Seiyaku Kabushiki Kaisha Novel antiandrogenic agent
EP1854798A3 (de) 2000-09-19 2007-11-28 Bristol-Myers Squibb Company Kondensierte heterozyklische Succinimid-Verbindungen und Analoga daraus, Modulatoren der nuklearen Hormonrezeptorfunktion
US6953679B2 (en) 2000-09-19 2005-10-11 Bristol-Myers Squibb Company Method for the preparation of fused heterocyclic succinimide compounds and analogs thereof
US20040087548A1 (en) 2001-02-27 2004-05-06 Salvati Mark E. Fused cyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function
AU2002259147A1 (en) 2001-05-08 2002-11-18 Schering Corporation Use of neurokinin receptor antagonists to treat androgen-dependent diseases
WO2003005889A2 (en) * 2001-07-10 2003-01-23 Ams Research Corporation Surgical kit for treating prostate tissue
US6903102B2 (en) 2001-09-06 2005-06-07 Schering Corporation 17β-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases
PE20030705A1 (es) 2001-10-17 2003-08-21 Schering Corp Inhibidores de la 17beta-hidroxiesteroide deshidrogenasa tipo 3 para el tratamiento de enfermedades androgeno-dependientes
AU2002364082A1 (en) 2001-12-19 2003-07-09 Bristol-Myers Squibb Company Fused heterocyclic compounds and analogs thereof: modulators of nuclear hormone receptor function
CA2506290C (en) 2002-11-18 2012-04-24 Schering Corporation 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases
AU2003293555A1 (en) 2002-12-17 2004-07-29 Schering Corporation 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases
US20060258628A1 (en) * 2004-07-20 2006-11-16 Steiner Mitchell S Compositions comprising 5-alpha reductase inhibitors, and SARMs and methods of use thereof
CN102357248A (zh) 2004-10-20 2012-02-22 恩多研究公司 单独的性甾体前体或与选择性雌激素受体调节剂联合用于防治绝经后女性的阴道疾病和病症
GB0513702D0 (en) 2005-07-04 2005-08-10 Sterix Ltd Compound
EP2099375B1 (de) 2007-01-02 2014-09-24 AquaBeam LLC Minimal invasive vorrichtungen zur behandlung von prostataerkrankungen
US9232959B2 (en) 2007-01-02 2016-01-12 Aquabeam, Llc Multi fluid tissue resection methods and devices
US12290277B2 (en) 2007-01-02 2025-05-06 Aquabeam, Llc Tissue resection with pressure sensing
US9284345B2 (en) * 2007-04-12 2016-03-15 Endorecherche, Inc. 17alpha-substituted steroids as systemic antiandrogens and selective androgen receptor modulators
GB0708376D0 (en) 2007-05-01 2007-06-06 Alligator Bioscience Ab Novel polypeptides and uses thereof
US8268806B2 (en) 2007-08-10 2012-09-18 Endorecherche, Inc. Pharmaceutical compositions
GB0722779D0 (en) 2007-11-20 2008-01-02 Sterix Ltd Compound
JP5506702B2 (ja) 2008-03-06 2014-05-28 アクアビーム エルエルシー 流体流れ内を伝達される光学エネルギーによる組織切除および焼灼
US9848904B2 (en) 2009-03-06 2017-12-26 Procept Biorobotics Corporation Tissue resection and treatment with shedding pulses
US10524822B2 (en) 2009-03-06 2020-01-07 Procept Biorobotics Corporation Image-guided eye surgery apparatus
WO2015035249A2 (en) 2013-09-06 2015-03-12 Procept Biorobotics Corporation Automated image-guided tissue resection and treatment
US20150031656A1 (en) * 2012-02-29 2015-01-29 Repros Therapeutics Inc. Combination therapy for treating androgen deficiency
CN104203078B (zh) 2012-02-29 2018-04-20 普罗赛普特生物机器人公司 自动化图像引导的组织切除和处理
BR112016031037B1 (pt) 2014-06-30 2023-02-07 Procept Biorobotics Corporation Aparelho para ablação de tecido vascular
CN107072591B (zh) 2014-09-05 2021-10-26 普罗赛普特生物机器人公司 与靶器官图像的治疗映射结合的医师控制的组织切除

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4329364A (en) * 1974-09-11 1982-05-11 Schering Corporation Antiandrogenic agents and methods for the treatment of androgen dependent disease states
US4039669A (en) * 1975-08-01 1977-08-02 Sterling Drug Inc. Composition for topical application and use thereof
US4087461A (en) * 1976-02-26 1978-05-02 The Johns Hopkins University Anti-androgenic steroids
DE2817157A1 (de) * 1978-04-17 1979-10-25 Schering Ag Verwendung von antioestrogenen und antigonadotrop wirkenden antiandrogenen zur prophylaxe und therapie der prostatahyperplasie
US4235893A (en) * 1978-05-08 1980-11-25 Brodie Angela M Ester derivatives of 4-hydroxy-4-androstene-3,17-dione and a method for inhibiting estrogen biosynthesis
FR2465486A1 (fr) * 1979-09-21 1981-03-27 Roussel Uclaf Nouvelle application utilisant la lh-rh ou des agonistes
US4474813A (en) * 1980-10-24 1984-10-02 Schering Corporation Pharmaceutical preparations comprising flutamide
DE3121152A1 (de) * 1981-05-22 1982-12-09 Schering Ag, 1000 Berlin Und 4619 Bergkamen "verwendung der kombination eines aromatase-hemmers mit einem antiandrogen zur prophylaxe und therapie der prostatahyperplasie"
DE3121153A1 (de) * 1981-05-22 1982-12-09 Schering Ag, 1000 Berlin Und 4619 Bergkamen "verwendung von aromatase-hemmern zur prophylaxe und therapie der prostatahyperplasie"
US4347363A (en) * 1981-09-17 1982-08-31 Sterling Drug Inc. Process for preparing 1,2-dihydro-6-methyl-2-oxo-5-(pyridinyl)nicotinonitriles
DE3339295A1 (de) * 1982-11-15 1984-05-17 Schering AG, 1000 Berlin und 4709 Bergkamen 4-hydroxy- und 4-acyloxy-4-androsten-3,17-dione zur verwendung bei der prophylaxe und therapie der prostatahyperplasie und diese enthaltende mittel fuer derartige verwendung
GR79447B (de) * 1982-12-31 1984-10-30 Mortimer Christopher H Dr
DE3323321A1 (de) * 1983-06-24 1985-01-03 Schering AG, 1000 Berlin und 4709 Bergkamen Prophylaxe und therapie von koronaren herzkrankheiten durch senkung des oestrogenspiegels
AU584070B2 (en) * 1983-12-12 1989-05-18 Edwin G. Kaszynski Hair growth modification
US5053403A (en) * 1984-05-11 1991-10-01 Norman Orentreich Methods for treatment of male-pattern baldness
US4684635A (en) * 1984-05-11 1987-08-04 Norman Orentreich Compositions and methods for inhibiting the action of androgens
DE3586053D1 (de) * 1984-08-02 1992-06-17 Labrie Pharmazeutische zusammensetzung fuer die kombinationstherapie von hormonabhaengigem krebs.
US4659695A (en) * 1985-02-08 1987-04-21 Fernand Labrie Method of treatment of prostate cancer
ATE43499T1 (de) * 1984-10-10 1989-06-15 Ile De France Synergistische empfaengnisverhuetende mischung.
GB8503940D0 (en) * 1985-02-15 1985-03-20 Erba Farmitalia 4-substituted androstendione derivatives
GB8505862D0 (en) * 1985-03-07 1985-04-11 Erba Farmitalia Steroidic 5alpha-reductase inhibitors
DE3607651A1 (de) * 1986-03-06 1987-09-10 Schering Ag Kombination von aromatasehemmer und testosteron-5(alpha)-reduktase-hemmer
IE60964B1 (en) * 1986-12-11 1994-09-07 Roussel Uclaf Zootechnical compositions containing a beta-adrenergic
US4888336A (en) * 1987-01-28 1989-12-19 Smithkline Beckman Corporation Steroid 5-alpha-reductase inhibitors
DE3888378T2 (de) * 1987-04-03 1994-09-29 Merck & Co Inc Behandlung von Prostatacarcinoma mit 17-beta-n-monosubstituierten-Carbamoyl-4-aza-5-alpha-Androst-1-en-3-onen.
US4895715A (en) * 1988-04-14 1990-01-23 Schering Corporation Method of treating gynecomastia

Also Published As

Publication number Publication date
IE902459A1 (en) 1991-02-13
CA2062973A1 (en) 1991-01-08
ATE177949T1 (de) 1999-04-15
DK0480950T3 (da) 1999-10-11
US5817649A (en) 1998-10-06
IL94990A0 (en) 1991-06-10
HUT60138A (en) 1992-08-28
IE990530A1 (en) 2000-11-15
AU5217493A (en) 1994-02-10
AU643445B2 (en) 1993-11-18
AU668434B2 (en) 1996-05-02
ES2222633T3 (es) 2005-02-01
DE69034148D1 (de) 2004-07-22
JPH04506798A (ja) 1992-11-26
JP3332377B2 (ja) 2002-10-07
WO1991000731A1 (en) 1991-01-24
KR920703063A (ko) 1992-12-17
AU5854590A (en) 1991-02-06
DE69034148T2 (de) 2005-06-30
EP0943328A3 (de) 1999-12-08
DE69033020T2 (de) 1999-08-05
DK0943328T3 (da) 2004-10-18
IL94990A (en) 1997-01-10
JP2001354590A (ja) 2001-12-25
DE69033020D1 (de) 1999-04-29
HU223662B1 (hu) 2004-11-29
CA2062973C (en) 2003-09-23
EP0943328A2 (de) 1999-09-22
EP0480950A1 (de) 1992-04-22
EP0857487A3 (de) 1999-12-08
ZA905312B (en) 1992-02-26
NZ234414A (en) 1999-05-28
ES2133270T3 (es) 1999-09-16
EP0943328B1 (de) 2004-06-16
MY106484A (en) 1995-05-30
HU9200047D0 (en) 1992-06-29
EP0480950B1 (de) 1999-03-24
IE990531A1 (en) 2000-11-15
EP0857487A2 (de) 1998-08-12

Similar Documents

Publication Publication Date Title
DE69034148D1 (de) Kombinationstherapie zur Prophylaxe und/oder Behandlung von gutartiger prostatischer Hyperplasie
ATE218854T1 (de) Behandlung von herzrythmusstörungen durch hemmung einer multifunktionalen calcium/calmodulin- abhängigen protein kinase
UA26213C2 (uk) Засіб для профілактики та лікуваhhя остеопорозу та фармацевтичhа композиція hа їх осhові
MX9702380A (es) Nuevas carboxamidas con actividad antifungica.
DK1039912T3 (da) Angiostatiske midler og præparater til behandling af GLC1A-glaukom
IL87885A (en) Pharmaceutical compositions having antiprogestational and anti-estrogenic activities for the treatment of hormone- dependent tumors
DE69725293D1 (de) N-(2 oxoacetyl oder sulphonyl)-pyrrolidine/piperidine-2-carbonsäurederivate mit verbesserter multi-drug resistenz aktivität
SE7903186L (sv) Cerebralverksamt medel
ATE211384T1 (de) Verwendung von adenosinantagonisten zur vorbeugung und behandlung von pankreatitis und ulcera
DE69424537D1 (de) Therapeutischer wirkstoff zur behandlung von melanomen
ATE128870T1 (de) Zusammensetzungen zur behandlung von fettablagerungen.
PT705100E (pt) Guanidinas substituidas terapeuticas
ATA11989A (de) Mittel zur vorbeugung gegen und behandlung von parodontopathien
UA35567C2 (uk) Фармацевтичний препарат для лікування хворих з порушеннями функції коагуляції, спосіб лікування таких хворих, спосіб одержання фармацевтичного препарату
ATE162073T1 (de) Pharmazeutische zusammensetzung zur behandlung von osteoporose enthaltend xanthohumol
BG100930A (bg) Фармацевтични състави и лекарствени средства за профилактика и лечение на ендотелиални нарушения
DE3854121D1 (de) Arzneimittelzusammensetzungen zur behandlung von psoriasis.
ES2091712A1 (es) Asociaciones sinergizantes que tienen un efecto antagonista de los receptores nk1 y nk2.
DE58904722D1 (de) Arzneimittelzubereitung aus esterderivaten des hecogenins und dessen verwendung zur behandlung von benigner prostatahyperplasie.
DE3582935D1 (de) Mittel zur behandlung von erkrankungen der venen und des analbereichs.
HUP0000110A2 (hu) Azaciklusos, azabiciklusos vagy tetrahidropiridinszármazékokat tartalmazó, fájdalom kezelésére alkalmas gyógyászati készítmények
DE69103773D1 (de) Derivate von hydroxaminsäure die lipoxygenase hemmen.
ATE193206T1 (de) Zusammensetzung zur behandlung oder vorbeugung von herpes
DE59101818D1 (de) Arzneimittelzubereitung, enthaltend Stigmasta-4-en-3-on sowie deren Verwendung.
DE69230644D1 (de) Verwendung von protease nexin-i als mittel gegen entzündungen

Legal Events

Date Code Title Description
UEP Publication of translation of european patent specification

Ref document number: 0943328

Country of ref document: EP

EELA Cancelled due to lapse of time