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SE7712891L - Nya spirolaktoner och sett att framstella densammma - Google Patents

Nya spirolaktoner och sett att framstella densammma

Info

Publication number
SE7712891L
SE7712891L SE7712891A SE7712891A SE7712891L SE 7712891 L SE7712891 L SE 7712891L SE 7712891 A SE7712891 A SE 7712891A SE 7712891 A SE7712891 A SE 7712891A SE 7712891 L SE7712891 L SE 7712891L
Authority
SE
Sweden
Prior art keywords
new
actons
spirol
produce
way
Prior art date
Application number
SE7712891A
Other languages
English (en)
Other versions
SE436425B (sv
Inventor
R Wiechert
D Bittler
U Kerb
J Casals-Stenzel
W Losert
Original Assignee
Schering Ag
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=5993550&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SE7712891(L) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Schering Ag filed Critical Schering Ag
Publication of SE7712891L publication Critical patent/SE7712891L/sv
Publication of SE436425B publication Critical patent/SE436425B/sv

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
    • C07J53/002—Carbocyclic rings fused
    • C07J53/004—3 membered carbocyclic rings
    • C07J53/007—3 membered carbocyclic rings in position 6-7
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
    • C07J1/0003—Androstane derivatives
    • C07J1/0033—Androstane derivatives substituted in position 17 alfa and 17 beta
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/001—Lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/003—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring the S atom directly linked to a ring carbon atom of the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
    • C07J53/002—Carbocyclic rings fused
    • C07J53/004—3 membered carbocyclic rings
    • C07J53/008—3 membered carbocyclic rings in position 15/16

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Non-Silver Salt Photosensitive Materials And Non-Silver Salt Photography (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
SE7712891A 1976-11-16 1977-11-15 Sett att framstella nya spirolaktoner SE436425B (sv)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE2652761A DE2652761C2 (de) 1976-11-16 1976-11-16 15,16-Methylen-Spirolactone, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel

Publications (2)

Publication Number Publication Date
SE7712891L true SE7712891L (sv) 1978-05-17
SE436425B SE436425B (sv) 1984-12-10

Family

ID=5993550

Family Applications (1)

Application Number Title Priority Date Filing Date
SE7712891A SE436425B (sv) 1976-11-16 1977-11-15 Sett att framstella nya spirolaktoner

Country Status (23)

Country Link
US (1) US4129564A (sv)
JP (2) JPS5363373A (sv)
AT (1) AT356827B (sv)
AU (1) AU512611B2 (sv)
BE (1) BE860877A (sv)
CA (1) CA1092094A (sv)
CH (2) CH631463A5 (sv)
CS (1) CS194823B2 (sv)
DD (1) DD132968B3 (sv)
DE (1) DE2652761C2 (sv)
DK (1) DK141967C (sv)
ES (1) ES464193A1 (sv)
FR (1) FR2370755A1 (sv)
GB (1) GB1550568A (sv)
GR (1) GR65227B (sv)
HU (1) HU174983B (sv)
IE (1) IE46076B1 (sv)
IL (1) IL53353A (sv)
IT (1) IT1092262B (sv)
LU (1) LU78514A1 (sv)
NL (1) NL7711946A (sv)
SE (1) SE436425B (sv)
SU (2) SU695560A3 (sv)

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2922500A1 (de) * 1979-05-31 1980-12-04 Schering Ag 6 beta .7 beta
DE3051166C2 (en) * 1980-06-11 1990-10-18 Schering Ag, 1000 Berlin Und 4709 Bergkamen, De Compsns. for contraception or treatment of gynaecological disorders
DE3022337A1 (de) * 1980-06-11 1982-01-07 Schering Ag Berlin Und Bergkamen, 1000 Berlin Praeparate zur kontrazeption und zur behandlung gynaekologischer stoerungen
DE3111951A1 (de) * 1981-03-23 1982-09-30 Schering Ag, 1000 Berlin Und 4619 Bergkamen 7(alpha)-alkoxycarbonyl-15ss-methylen-4-androstene, verfahren zu ihrer herstellung und verwendung als arzneimittel
ATE15206T1 (de) * 1981-09-21 1985-09-15 Schering Ag 3-beta,7-beta,15-alpha-trihydroxy-5-androsten-1 - one, ihre 3,15-trimethylessigsaeure-ester und ihre herstellung.
DE3213962A1 (de) * 1982-04-13 1983-10-13 Schering AG, 1000 Berlin und 4709 Bergkamen 1(alpha).2(alpha);6(beta).7(beta).15(beta).16(beta)-trimethylen-3-oxo-17(alpha)-pregn-4-en-21.17-carbolacton, dessen herstellung und verwendung als arzneimittel
DE3227598A1 (de) * 1982-07-22 1984-01-26 Schering AG, 1000 Berlin und 4709 Bergkamen 7(alpha)-acylthio-15.16-methylen-3-oxo-17(alpha)-pregna-1.4-dien-21,17-carbolactone, verfahren zu ihrer herstellung und verwendung als arzneimittel
DE3234972A1 (de) * 1982-09-17 1984-03-22 Schering AG, 1000 Berlin und 4709 Bergkamen 7(alpha)-alkyl-17(alpha)-pregn-4-en-21.17-carbolactone und -21-carbonsaeuresalze sowie verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate
DE3240510A1 (de) * 1982-10-29 1984-05-03 Schering AG, 1000 Berlin und 4709 Bergkamen Neue 7(alpha)-acylthio-1(alpha),2(alpha)-methylen-3-oxo-17(alpha)-pregn-4-en-21,17-carbolactone, deren herstellung und diese enthaltende arzneimittel
JPS59139400A (ja) * 1983-01-31 1984-08-10 Shionogi & Co Ltd 抗アルドステロン活性ステロイド誘導体
DE3306554A1 (de) * 1983-02-22 1984-08-23 Schering AG, 1000 Berlin und 4709 Bergkamen Verfahren zur herstellung von 3-((delta)(pfeil hoch)4(pfeil hoch)-3-ketosteroid-17(alpha)-yl)-propionsaeurelactonen
US4559332A (en) * 1983-04-13 1985-12-17 Ciba Geigy Corporation 20-Spiroxanes and analogues having an open ring E, processes for their manufacture, and pharmaceutical preparations thereof
DE3481707D1 (de) * 1983-08-17 1990-04-26 Schering Ag 7-alpha-substituierte 3-oxo-17alpha-pregn-4-en-21.17-carbolactone, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate.
DE3347510A1 (de) * 1983-12-27 1985-08-01 Schering AG, 1000 Berlin und 4709 Bergkamen Verfahren zur herstellung von 3-oxo-17(alpha)-pregna-4,6-dien-21,17-carbolactonen
DE3402329A1 (de) * 1984-01-20 1985-08-01 Schering AG, 1000 Berlin und 4709 Bergkamen 6,6-ethylen-15,16-methylen-3-oxo-17(alpha)-pregn-4-en-21,17-carbolactone, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate
US4670551A (en) * 1984-06-21 1987-06-02 Ciba-Geigy Corporation Epoxy steroids
JPS6248694A (ja) * 1985-08-28 1987-03-03 Shionogi & Co Ltd 抗アルドステロン活性ステロイド誘導体
DE3544661A1 (de) * 1985-12-13 1987-06-19 Schering Ag Verfahren zur herstellung von 7(alpha)-acetylthiosteroiden
JPS62132932U (sv) * 1986-02-14 1987-08-21
US4837211A (en) * 1987-04-06 1989-06-06 Carolina Medical Products, Inc. Spironolactone composition
JPS6453026U (sv) * 1987-09-29 1989-03-31
DE3916112A1 (de) * 1989-05-16 1990-11-22 Schering Ag Dihydrospirorenon als antiandrogen
DE4344462C2 (de) 1993-12-22 1996-02-01 Schering Ag Zusammensetzung für die Empfängnisverhütung
PT831911E (pt) * 1995-06-07 2002-09-30 Searle & Co Terapeutica de combinacao de espironolactona e antagonista da angiotensina ii para o tratamento de insuficiencia cardiaca congestiva
DE19633685C1 (de) * 1996-08-12 1997-10-09 Schering Ag Verfahren zur Herstellung von Drospirenon (6beta,7beta;15 beta,16beta-Dimethyl-en-3-oxo-17alpha-pregn-4-en-21,17-carbolacton, DRSP) sowie 7alpha-(3-Hydroxy-1-propyl)-6beta,7beta;15beta, 16beta-dimethylen-5beta-androstan-3beta,5,17beta-triol (ZK 92836) und 6beta,7beta;15beta,16beta-dimethylen-5beta-hydroxy-3-oxo-17alpha-androstan-21,17-carbolacton (90965) als Zwischenprodukte des Verfahrens
DE19651000A1 (de) * 1996-12-01 1998-06-04 Schering Ag Oxyiminopregnancarbolactone
KR20010100986A (ko) * 1998-11-06 2001-11-14 로저 에이. 윌리암스 심장혈관 질병으로 인한 이병률 및 사망률 감소용안지오텐신 전환 효소 억제제 및 알도스테론 길항제의결합 치료방법
EP2305267A3 (en) 1999-08-31 2011-08-17 Bayer Schering Pharma Aktiengesellschaft Pharmaceutical combination of ethinylestradiol and drospirenone for use as a contraceptive
RU2269342C2 (ru) * 1999-08-31 2006-02-10 Шеринг Акциенгезелльшафт Фармацевтическая комбинация этинилэстрадиола и дроспиренона для использования в качестве контрацептива
DE122009000007I2 (de) 1999-08-31 2011-07-21 Bayer Schering Pharma Pharmazeutische kombination von ethinylestradiol und drospirenone als empfangnisverhutendes mittel.
US6787531B1 (en) * 1999-08-31 2004-09-07 Schering Ag Pharmaceutical composition for use as a contraceptive
US20020132801A1 (en) * 2001-01-11 2002-09-19 Schering Aktiengesellschaft Drospirenone for hormone replacement therapy
AU2001225413B2 (en) * 2000-01-18 2005-06-23 Bayer Schering Pharma Aktiengesellschaft Drospirenone for hormone replacement therapy
US6716829B2 (en) 2000-07-27 2004-04-06 Pharmacia Corporation Aldosterone antagonist and cyclooxygenase-2 inhibitor combination therapy to prevent or treat inflammation-related cardiovascular disorders
JP2004518611A (ja) * 2000-07-27 2004-06-24 ファルマシア・コーポレーション 炎症関連障害を予防するか又は治療するためのアルドステロン遮断薬療法
EP1216712A1 (en) 2000-12-20 2002-06-26 Schering Aktiengesellschaft Cyclodextrin-drospirenone inclusion complexes
EP1216713A1 (en) 2000-12-20 2002-06-26 Schering Aktiengesellschaft Compositions of estrogen-cyclodextrin complexes
JP2004521951A (ja) * 2001-07-13 2004-07-22 シエーリング アクチエンゲゼルシャフト Ｈｒｔのためのドロスピレノン及びエストロゲンスルファメートの組み合わせ
MXPA04009033A (es) * 2002-03-18 2005-01-25 Pharmacia Corp Combinacion de un antagonista de receptor de aldosterona y acido nicotinico o un derivado de acido nicotinico.
KR20040107481A (ko) * 2002-03-18 2004-12-20 파마시아 코포레이션 알도스테론 수용체 길항물질 및 담즙산 격리제의 혼합물
ITMI20040367A1 (it) * 2004-03-01 2004-06-01 Ind Chimica Srl Processo per la preparazione di drospirenone
US20050220825A1 (en) * 2004-03-10 2005-10-06 Adrian Funke Molecular dispersions of drospirenone
HUP0402466A2 (en) * 2004-11-30 2006-07-28 Richter Gedeon Vegyeszet Industrial process for preparing 17-hydroxy-6-betha, 7-betha, 15-betha, 16-betha-bis-methylene-3-oxo-17-alpha-pregn-4-ene-21-carboxylic acid gamma lacton and the main, intermediates of the process
HUP0402465A2 (en) * 2004-11-30 2006-07-28 Richter Gedeon Vegyeszet Industrial process for preparing 17-hydroxy-6-betha, 7-betha, 15-betha, 16-betha-bis-methylene-3-oxo-17-alpha-pregn-4-ene-21-carboxylic acid gamma lacton and the main intermediates of the process
US8617597B2 (en) 2006-07-06 2013-12-31 Bayer Intellectual Property Gmbh Pharmaceutical composition containing a tetrahydrofolic acid
MX2008016571A (es) * 2007-05-01 2009-03-09 Sicor Inc Proceso para preparar drospirenona y su intermediarios.
FR2917975B1 (fr) 2007-06-26 2009-10-16 Ceva Sante Animale Sa Compositions et traitement de l'insuffisance cardiaque chez les animaux mammiferes non humains
US20090035374A1 (en) * 2007-07-31 2009-02-05 Katrin Mittmann Method of making a single-stage pharmaceutical preparation for oral therapy to regulate blood pressure and kit containing same
US20090035373A1 (en) * 2007-07-31 2009-02-05 Katrin Mittmann Pharmaceutical composition for contraception and blood pressure regulation, kit for contraception containing same and method of production of same
HUP0700826A3 (en) 2007-12-20 2010-03-29 Richter Gedeon Nyrt Coated tablet containing drospirenone and process for producing the same
WO2009111574A2 (en) * 2008-03-05 2009-09-11 Evestra, Inc. BISMETHYLENE-17α CARBOLACTONES AND RELATED USES
WO2010068500A2 (en) * 2008-11-25 2010-06-17 Evestra, Inc. PROGESTATIONAL 3-(6,6-ETHYLENE-17b-HYDROXY-3-OXO-17a-PREGNA-4-ENE-17a -YL) PROPIONIC ACID g-LACTONES
EP2398467A1 (en) 2009-02-18 2011-12-28 Bayer Pharma Aktiengesellschaft Particles comprising drospirenone encapsulated in a polymer
US20120064166A1 (en) 2009-02-18 2012-03-15 Bayer Pharma Aktienesellschaft Formulation comprising drospirenone for subcutaneous or intramuscular administration
US8334375B2 (en) * 2009-04-10 2012-12-18 Evestra, Inc. Methods for the preparation of drospirenone
ES2432063T3 (es) 2009-06-16 2013-11-29 Crystal Pharma, S.A.U. Procedimiento para la obtención de 17-espirolactonas en esteroides
US8957052B2 (en) 2010-05-10 2015-02-17 Universite Paris Descartes Methods and compositions for the treatment of fluid accumulation in and/or under the retina
WO2011157798A1 (en) 2010-06-16 2011-12-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for stimulating reepithelialisation during wound healing
US10849857B2 (en) 2010-07-28 2020-12-01 Laboratorios Leon Farma Sa Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same
AR081670A1 (es) 2010-06-29 2012-10-10 Leon Farma Sa Lab Composicion farmaceutica que comprende drospirenona y kit anticonceptivo
US11351122B1 (en) 2010-07-28 2022-06-07 Laboratorios Leon Farma Sa Synthetic progestogens and pharmaceutical compositions comprising the same
US9603860B2 (en) 2010-07-28 2017-03-28 Laboratorios Leon Farma Sa Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same
CN102887934B (zh) * 2012-09-20 2015-05-27 杭州福斯特药业有限公司 一种屈螺酮的制备方法
WO2016063269A1 (en) 2014-10-20 2016-04-28 Prendergast Patrick T Use of antagonists to the nuclear steroid receptor alone or in combination as direct antiviral agents to inhibit alphavirus, togaviridae, arenaviridae, filoviridae, bunyaviridae, flaviviridae and rhabdoviridae
EP3313408B1 (en) 2015-06-23 2023-12-06 Laboratorios Leon Farma SA Drospirenone-based contraceptive for a female patient affected with excess weight
EP3108889A1 (en) 2015-06-23 2016-12-28 Philippe Perrin Drospirenone-based contraceptive for a female patient affected with excess weight
WO2017055248A1 (en) 2015-09-28 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of heart failure
US20180280414A1 (en) 2015-10-13 2018-10-04 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and pharmaceutical compositions for the treatment of choroidal neovascularisation
US20190262363A1 (en) 2016-07-26 2019-08-29 INSERM (Institut National de la Santé et de la Recherche Médicale Antagonist of mineralocorticoid receptor for the treatment of osteoarthritis
EP4134082A1 (en) 2021-08-12 2023-02-15 Chemo Research, S.L. Method for treating endometriosis and providing effective contraception
EP4395785A1 (en) 2021-08-31 2024-07-10 Inserm (Institut National de la Santé et de la Recherche Scientifique) Methods for the treatment of ocular rosacea
WO2023152658A1 (en) 2022-02-10 2023-08-17 Lupin Limited Slow release drospirenone tablet composition
EP4486311A1 (en) 2022-03-01 2025-01-08 Chemo Research, S.L. Chewable oral contraceptive

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3257390A (en) * 1963-06-12 1966-06-21 Merck & Co Inc Ring a unsaturated 21-hydroxy-3-oxo-17alpha-pregnane-17-carboxylic acid lactone diuretic agents
NL166267C (nl) * 1968-03-22 1981-07-15 Merck & Co Inc Werkwijze ter bereiding van farmaceutische preparaten, de onder toepassing daarvan verkregen gevormde voort- brengselen, alsmede werkwijze ter bereiding van 6,7-methyleen-20-spirox-4-en-3-onderivaten met aldoste- ron remmende werking.
DE2237143A1 (de) * 1972-07-28 1974-02-14 Hoechst Ag Verfahren zur herstellung von beta(3-keto-7alpha-acetylthio-17beta-hydroxy4-androsten-17alpha-yl)-propionsaeuregamma-lacton und dessen 1-dehydro-derivat
CH601352A5 (sv) * 1973-09-26 1978-07-14 Hoffmann La Roche

Also Published As

Publication number Publication date
CH631463A5 (de) 1982-08-13
FR2370755B1 (sv) 1980-06-06
DD132968A5 (de) 1978-11-22
ATA815577A (de) 1979-10-15
JPS61218595A (ja) 1986-09-29
AU3050977A (en) 1979-05-17
JPS5363373A (en) 1978-06-06
BE860877A (fr) 1978-05-16
FR2370755A1 (fr) 1978-06-09
NL7711946A (nl) 1978-05-18
ES464193A1 (es) 1978-09-01
IL53353A (en) 1982-04-30
DE2652761C2 (de) 1985-11-21
GR65227B (en) 1980-07-30
CH632774A5 (de) 1982-10-29
DK508077A (da) 1978-05-17
SU695560A3 (ru) 1979-10-30
SE436425B (sv) 1984-12-10
IE46076B1 (en) 1983-02-09
HU174983B (hu) 1980-04-28
DK141967B (da) 1980-07-28
AU512611B2 (en) 1980-10-16
SU743582A3 (ru) 1980-06-25
CA1092094A (en) 1980-12-23
DD132968B3 (de) 1991-03-28
AT356827B (de) 1980-05-27
IL53353A0 (en) 1978-01-31
LU78514A1 (sv) 1978-03-20
JPH0242840B2 (sv) 1990-09-26
JPS6156240B2 (sv) 1986-12-01
GB1550568A (en) 1979-08-15
DE2652761A1 (de) 1978-05-18
IT1092262B (it) 1985-07-06
CS194823B2 (en) 1979-12-31
IE46076L (en) 1978-05-16
DK141967C (da) 1980-12-08
US4129564A (en) 1978-12-12

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