CH620207A5 - - Google Patents
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- CH620207A5 CH620207A5 CH1325075A CH1325075A CH620207A5 CH 620207 A5 CH620207 A5 CH 620207A5 CH 1325075 A CH1325075 A CH 1325075A CH 1325075 A CH1325075 A CH 1325075A CH 620207 A5 CH620207 A5 CH 620207A5
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- liters
- diethylcarbamoyl
- embonic acid
- methylpiperazine
- embonate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0086—Inhalation chambers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von Embonsäuresalzen von 1-Diäthylcarba-moyl-4-methylpiperazin (Diäthylcarbamazin). The present invention relates to a process for the preparation of embonic acid salts of 1-diethylcarbamoyl-4-methylpiperazine (diethylcarbamazine).
l-Diäthylcarbamoyl-4-methylpiperazin (endgültig festgelegter internationaler Freiname: Diethylcarbamazin) ist aus den US-PS Nr. 2 467 893 und 2 467 895 bekannt. Seine Herstellung wurde von Kushner et al in J. Org. Chem. 13,151 (1948) beschrieben. Angaben über die pharmakologischen und toxikologischen Eigenschaften wurden von Harned et al in Ann. N.Y. Acad. Sei. 50,141 (1948) veröffentlicht. Auch das Hydrochlorid, Dihydrogencitrat, Maleat und Phosphat sowie die Äthyljodidverbindung wurden hergestellt. Diäthyl-carbamazin wird in der Humanmedizin als Anthelminthicum verwendet. l-diethylcarbamoyl-4-methylpiperazine (final international name: diethylcarbamazine) is known from US Pat. Nos. 2,467,893 and 2,467,895. Its manufacture was described by Kushner et al in J. Org. Chem. 13, 151 (1948). Information on the pharmacological and toxicological properties was provided by Harned et al in Ann. N.Y. Acad. Be. 50, 141 (1948). The hydrochloride, dihydrogen citrate, maleate and phosphate as well as the ethyl iodide compound were also produced. Diethyl carbamazine is used in human medicine as an anthelmintic.
Embonsäure [4,4'-Methylen-bis-(3-hydroxy-2-naphthoe-säure)] wird in der amerikanischen Literatur häufig als Pamo-säure («pamoic acid») bezeichnet. Embonic acid [4,4'-methylene-bis- (3-hydroxy-2-naphthoic acid)] is often referred to in the American literature as pamoic acid.
l-Diäthylcarbamoyl-4-methylpiperazin-embonat(Diäthyl-carbamazin-embonat) dient zur Behandlung von Asthma und wird zweckmässig in kleinen bekannten gleichmässigen genauen Dosen zugeführt, die nicht in Nase und Rachen, sondern hauptsächlich im Lungensystem absorbiert werden. Die physiologische Wirksamkeit wird verbessert, wenn die der gewünschten Stelle zugeführte Medikamentkonzentration, verglichen mit der Konzentration, die man erhält, wenn die Medikamente systemisch verabreicht werden, erhöht werden kann. l-diethylcarbamoyl-4-methylpiperazine embonate (diethyl carbamazine embonate) is used to treat asthma and is expediently administered in small, known, uniform, precise doses which are not absorbed in the nose and throat, but mainly in the lung system. Physiological effectiveness is improved if the drug concentration delivered to the desired site can be increased compared to the concentration obtained when the drugs are administered systemically.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man Embonsäure oder ein Salz davon mit Diäthyl-carbamazin oder dessen Salzen umsetzt. The process according to the invention is characterized in that embonic acid or a salt thereof is reacted with diethyl carbamazine or its salts.
Wenn man etwa äquimolare Mengen Diäthylcarbamazin (oder eines Salzes davon) und Embonsäure (oder eines Salzes davon) verwendet, so erhält man äquimolares 1-Diäthylcarba-moyl-4-methylpiperazin-embonat. Verwendet man dagegen etwa zwei Mol Diäthylcarbamazin (oder eines Salzes davon) pro Mol Embonsäure (oder eines Salzes davon), so erhält manBis-(l-diäthylcarbamoyl-4-methyl-piperazin)-embonat. If approximately equimolar amounts of diethylcarbamazine (or a salt thereof) and embonic acid (or a salt thereof) are used, equimolar 1-diethylcarbamoyl-4-methylpiperazine embonate is obtained. On the other hand, if about two moles of diethylcarbamazine (or a salt thereof) are used per mole of embonic acid (or a salt thereof), bis (l-diethylcarbamoyl-4-methyl-piperazine) embonate is obtained.
Beispiel 1 Diäthylcarbamazin-embonat 2,0 g (0,005 Mol) Diäthylcarbamazin-dihydrogencitrat (l-Diäthylcarbamoyl-4-methylpiperazin-dihydrogencitrat) werden bei Raumtemperatur in 20 ml Wasser gelöst. Die erhaltene Lösung versetzt man mit 2,16 g (0,005 Mol) des Di-natriumsalzes der Embonsäure. Es bildet sich sofort ein kristalliner Niederschlag, der jedoch nach etwa 5stündigem Stehen bei Raumtemperatur verschwindet und durch einen amorphen Niederschlag ersetzt wird. Nach weiterem 2tägigem Stehen geht der amorphe Niederschlag allmählich in eine kristalline Example 1 Diethylcarbamazine Embonate 2.0 g (0.005 mol) of diethylcarbamazine dihydrogen citrate (l-diethylcarbamoyl-4-methylpiperazine dihydrogen citrate) are dissolved in 20 ml of water at room temperature. The solution obtained is mixed with 2.16 g (0.005 mol) of the disodium salt of embonic acid. A crystalline precipitate forms immediately, but it disappears after standing for about 5 hours at room temperature and is replaced by an amorphous precipitate. After standing for a further 2 days, the amorphous precipitate gradually turns into a crystalline one
Form über, die man isoliert und trocknet, wodurch man 2,5 g Produkt erhält. Form over, which is isolated and dried, whereby 2.5 g of product are obtained.
Wenn man die obige Arbeitsweise wiederholt, aber das Natriumembonat in Form einer wässrigen Lösung zusetzt statt als trockenes Pulver, fällt sofort ein amorpher Feststoff aus, der im Verlauf von 2 Tagen allmählich kristallisiert. Der Feststoff wird isoliert und an der Luft getrocknet, wodurch man 2,7 g eines Produktes erhält, das bei 215 bis 220 °C unter Zersetzung schmilzt. If the above procedure is repeated, but the sodium embonate is added in the form of an aqueous solution instead of a dry powder, an amorphous solid precipitates immediately, which gradually crystallizes over the course of 2 days. The solid is isolated and air-dried to give 2.7 g of a product which melts at 215 to 220 ° C with decomposition.
Analyse: Analysis:
C C.
H H
N N
Berechnet: Calculated:
67,44 67.44
6,35 6.35
7,15 7.15
Gefunden: Found:
66,90 66.90
6,26 6.26
7,05 7.05
Beispiel 2 Example 2
Diäthylcarbamazin-embonat aus Embonsäure Diethylcarbamazine embonate from embonic acid
Bei Raumtemperatur werden 15,4 kg (32,4 Mol) technisch reines Dinatriumembonat-monohydrat zu 175 Liter Methanol in einem 378-Liter-Kessel aus rostfreiem Stahl gegeben, worauf man das Gemisch rührt bis zur maximalen, jedoch nicht vollständigen Auflösung. Sodann werden 1,5 kg Aktivkohle und 1,5 kg Diatomeenerde zugesetzt, worauf man das Gemisch 1 Stunde lang rührt. Das so erhaltene Gemisch wird dann durch Diatomeenerde filtriert. Den erhaltenen Filterkuchen wäscht man dreimal mit je 2 Liter Methanol. Filtrat und Waschflüssigkeiten werden in einen mit Glas ausgekleideten 378-Liter-Kessel gegeben, worauf man 21 Liter Wasser zusetzt und 10,9 Liter (130 Mol) konzentrierte Salzsäure ziemlich rasch zugibt. Es bildet sich sofort ein leuchtend gelber fester Niederschlag. Man rührt weitere 1,5 Stunden lang bei Raumtemperatur. Durch Abfiltrieren gewinnt man freie Embonsäure, die man dreimal mit je 20 Liter Wasser wäscht. Der erhaltene Filterkuchen wird 1 Stunde lang mit etwa 80 Liter Wasser aufgeschlämmt, worauf man die Feststoffe abfiltriert und den Filterrückstand zuerst dreimal mit je 2 Liter Wasser und dann dreimal mit je 4 Liter Methanol wäscht. Der so erhaltene Feststoff wird dann 2 Tage lang bei 50 bis 55 °C getrocknet. Die rohe Embonsäure (11,8 kg) löst man bei 85 bis 90°C in 61 Liter Dimethylformamid. Die Lösung versetzt man mit etwa 900 g Diatomeenerde, worauf man das erhaltene Gemisch 0,5 Stunden lang rührt und dann durch vorerhitzte Trichter filtriert. Der Filterkuchen wird dreimal mit je 3 Liter Dimethylformamid gewaschen. Das erhaltene Filtrat gibt man in einen mit Glas ausgekleideten 189-Liter-Kessel zu 70 Liter Wasser. Sodann werden weitere 20 Liter Wasser zugesetzt, worauf man das erhaltene Gemisch unter Kühlen auf unter 25 °C 1,5 Stunden lang rührt. Die gereinigte Embonsäure wird abfiltriert, trockengepresst und dann dreimal mit je 6 Liter Wasser und anschliessend dreimal mit je 4 Liter Methanol gewaschen. Die so erhaltene Embonsäure trocknet man auf ein konstantes Gewicht von 10,8 kg (86 %, bezogen auf 95 %iges Dinatriumsalz als Ausgangsmaterial). At room temperature, 15.4 kg (32.4 mol) of technically pure disodium embonate monohydrate are added to 175 liters of methanol in a 378-liter stainless steel kettle, whereupon the mixture is stirred until the maximum but not complete dissolution. 1.5 kg of activated carbon and 1.5 kg of diatomaceous earth are then added, and the mixture is stirred for 1 hour. The mixture thus obtained is then filtered through diatomaceous earth. The filter cake obtained is washed three times with 2 liters of methanol. The filtrate and washing liquids are placed in a 378 liter glass-lined kettle, after which 21 liters of water are added and 10.9 liters (130 moles) of concentrated hydrochloric acid are added quite quickly. A bright yellow solid precipitate forms immediately. The mixture is stirred for a further 1.5 hours at room temperature. By filtering off, free embonic acid is obtained, which is washed three times with 20 liters of water. The filter cake obtained is slurried for 1 hour with about 80 liters of water, whereupon the solids are filtered off and the filter residue is washed first three times with 2 liters of water and then three times with 4 liters of methanol. The solid obtained in this way is then dried at 50 to 55 ° C. for 2 days. The crude embonic acid (11.8 kg) is dissolved in 61 liters of dimethylformamide at 85 to 90 ° C. About 900 g of diatomaceous earth is added to the solution, the mixture obtained is stirred for 0.5 hours and then filtered through a preheated funnel. The filter cake is washed three times with 3 liters of dimethylformamide. The filtrate obtained is placed in a 189 liter kettle lined with glass for 70 liters of water. A further 20 liters of water are then added, and the mixture obtained is stirred under cooling to below 25 ° C. for 1.5 hours. The cleaned embonic acid is filtered off, pressed dry and then washed three times with 6 liters of water and then three times with 4 liters of methanol. The embonic acid thus obtained is dried to a constant weight of 10.8 kg (86%, based on 95% disodium salt as the starting material).
10,1 kg (25,8 Mol) Diäthylcarbamazin-dihydrogencitrat werden in 80 Liter Wasser gelöst, worauf die erhaltene Lösung filtriert wird. 10.1 kg (25.8 mol) of diethyl carbamazine dihydrogen citrate are dissolved in 80 liters of water and the solution obtained is filtered.
1,96 kg (49,0 Mol) Natriumhydroxid werden hierauf in 100 Liter Wasser gelöst; diese Lösung versetzt man mit 10,0 kg (25,8 Mol) der wie oben beschriebenen gereinigten Embonsäure. Das Gemisch aus Embonsäure und Natriumhydroxid wird 0,5 Stunden lang gerührt, worauf man etwa 900 g Diatomeenerde zugibt, eine weitere Stunde lang rührt und das Gemisch dann durch Filtrieren klärt. 1.96 kg (49.0 mol) of sodium hydroxide are then dissolved in 100 liters of water; this solution is mixed with 10.0 kg (25.8 mol) of the purified embonic acid as described above. The mixture of embonic acid and sodium hydroxide is stirred for 0.5 hours, after which about 900 g of diatomaceous earth is added, the mixture is stirred for a further hour and the mixture is then clarified by filtration.
Das dabei erhaltene Filtrat gibt man in einen mit Glas ausgekleideten 378-Liter-Kessel, worauf man unter Rühren mög5 The filtrate obtained is placed in a 378 liter kettle lined with glass, after which it is possible to stir it5
10 10th
IS IS
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620 207 620 207
liehst rasch mit der Diäthylcarbamizincitratlösung versetzt. Es bildet sich sofort ein sehr dicker cremefarbener Niederschlag. Hierauf werden 40 Liter Wasser zugegeben. Nach lstün-digem Rühren wird das Gemisch wesentlich flüssiger. Es wird 1 Stunde lang weitergerührt. Das erhaltene Produkt wird ab- s filtriert und dreimal mit je 15 Liter Wasser gewaschen. Das dabei erhaltene Material trocknet man bei 50 bis 55 ° C und mahlt es dann zweimal in einer Strahlmühle, wodurch man 13,5 kg eines mikrofeinen Produkts erhält. 10,8 kg dieses Diäthylcarbamazin-embonats werden in einem Gemisch aus io 25 Liter Dimethylsulfoxid und 50 Liter Methanol von 650 C gelöst. Die trübe Lösung wird durch Diatomeenerde filtriert und der Filterkuchen dreimal mit je 4 Liter Methanol gewaschen. Filtrat und Waschflüssigkeit werden in einen mit Glas ausgekleideten 189-Liter-Kessel gegeben und darin erwärmt, is um alles etwa abgeschiedene Material zu lösen. Sodann setzt man 40 Liter Methanol zu, worauf man die Lösung auf 0 ± 4° c abschreckt und über Nacht auf dieser Temperatur hält. Das Produkt wird abfiltriert und dreimal mit 1,5 Liter Methanol gewaschen. Nach Trocknen bei 45 bis 50° C mahlt man das 20 erhaltene Material in einer Mikromühle, wodurch man 8,0 kg Diäthylcarbamazin-embonat (l-Diäthylcarbamoyl-4-methyl-piperazinembonat) (äquimolar) erhält, von dem 90% oder mehr eine Teilchengrösse von 10 Mikron oder darunter besitzen. 25 quickly added the diethylcarbamizin citrate solution. A very thick, cream-colored precipitate forms immediately. 40 liters of water are then added. After stirring for an hour, the mixture becomes much more fluid. Continue stirring for 1 hour. The product obtained is filtered off and washed three times with 15 liters of water each. The material obtained is dried at 50 to 55 ° C and then ground twice in a jet mill, whereby 13.5 kg of a microfine product are obtained. 10.8 kg of this diethylcarbamazine embonate are dissolved in a mixture of 25 liters of dimethyl sulfoxide and 50 liters of methanol at 650.degree. The cloudy solution is filtered through diatomaceous earth and the filter cake washed three times with 4 liters of methanol. The filtrate and washing liquid are placed in a glass-lined 189 liter kettle and heated in it to dissolve any material that has separated out. Then 40 liters of methanol are added, whereupon the solution is quenched to 0 ± 4 ° C. and kept at this temperature overnight. The product is filtered off and washed three times with 1.5 liters of methanol. After drying at 45 to 50 ° C, the material obtained is ground in a micromill, whereby 8.0 kg of diethylcarbamazine embonate (l-diethylcarbamoyl-4-methylpiperazinembonate) (equimolar) are obtained, of which 90% or more is one Have particle sizes of 10 microns or less. 25th
Beispiel 3 Example 3
Eine auf 50°C erwärmte Suspension von 50,5 g (0,13 Mol) gereinigter Embonsäure in 400 ml Aceton wird unter Rühren mit 53,0 g (0,27 Mol) Diäthylcarbamazindihydrogencitrat versetzt. Die erhaltene klare gelbe Lösung lässt man auf Raumtemperatur abkühlen und filtriert sie dann. Das Filtrat wird im Vakuum bei 50°C zur Trockne eingeengt und das erhaltene Produkt dann 16 Stunden lang im Vakuum bei 75 bis 80 ° C getrocknet, wordurch man 102,0 g Bis-(l-diäthylcarbamoyl-4-methylpiperazin)-embonat in Form eines gelben amorphen Pulvers erhält, das bei 101 bis 105 °C schmilzt. A suspension of 50.5 g (0.13 mol) of purified embonic acid in 400 ml of acetone heated to 50 ° C. is mixed with 53.0 g (0.27 mol) of diethyl carbamazine dihydrogen citrate while stirring. The clear yellow solution obtained is allowed to cool to room temperature and then filtered. The filtrate is evaporated to dryness in vacuo at 50 ° C. and the product obtained is then dried in vacuo at 75 to 80 ° C. for 16 hours, whereby 102.0 g of bis- (l-diethylcarbamoyl-4-methylpiperazine) -embonate in Form of a yellow amorphous powder that melts at 101 to 105 ° C.
Analyse für C43H5sN60s(787): Analysis for C43H5sN60s (787):
C H N C H N
Berechnet: 65,62 7,44 10,68 Gefunden: 65,22 7,79 10,80 Calculated: 65.62 7.44 10.68 Found: 65.22 7.79 10.80
Das vorliegende l-Diäthylcarbamoyl-4-methylpiperazin-embonat ergibt bei einer Verabreichung in Dosen von etwa 0,5 bis 30 mg Diäthylcarbamazin, und zwar dreimal täglich verabfolgt, wobei die jeweilige Dosierung dem Patienten und der Stärke der erforderlichen Therapie angepasst ist, bei einer Reihe asthmatischer Zustände eine gute Langzeitsteuerung. The present 1-diethylcarbamoyl-4-methylpiperazine embonate, when administered in doses of approximately 0.5 to 30 mg of diethylcarbamazine, administered three times a day, the respective dosage being adapted to the patient and the strength of the therapy required, in one A number of asthmatic conditions provide good long-term control.
B B
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US00374176A US3809294A (en) | 1973-06-27 | 1973-06-27 | Dispensing lung contacting powdered medicaments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH620207A5 true CH620207A5 (en) | 1980-11-14 |
Family
ID=23475640
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH555174A CH577832A5 (en) | 1973-06-27 | 1974-04-23 | |
| CH1325075A CH620207A5 (en) | 1973-06-27 | 1975-10-13 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH555174A CH577832A5 (en) | 1973-06-27 | 1974-04-23 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US3809294A (en) |
| JP (1) | JPS6010737B2 (en) |
| AR (1) | AR198562A1 (en) |
| AT (1) | AT342211B (en) |
| BE (1) | BE813512A (en) |
| CA (1) | CA1043208A (en) |
| CH (2) | CH577832A5 (en) |
| CS (1) | CS182257B2 (en) |
| DD (1) | DD125188A5 (en) |
| DE (1) | DE2415360C2 (en) |
| DK (1) | DK152967C (en) |
| ES (1) | ES427755A1 (en) |
| FR (1) | FR2234905B1 (en) |
| GB (1) | GB1471917A (en) |
| IE (1) | IE40616B1 (en) |
| IL (1) | IL44401A (en) |
| IT (1) | IT1003994B (en) |
| NL (1) | NL178655C (en) |
| PH (1) | PH11643A (en) |
| PL (1) | PL89980B1 (en) |
| SE (1) | SE405448B (en) |
| SU (1) | SU537614A3 (en) |
| YU (1) | YU36435B (en) |
| ZA (1) | ZA741633B (en) |
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| WO2006031775A2 (en) * | 2004-09-13 | 2006-03-23 | Oriel Therapeutics, Inc. | Dry powder inhalers that inhibit agglomeration, related devices and methods |
| NL1027255C2 (en) * | 2004-10-15 | 2006-04-19 | Lab Tickner Ag | Device for removing a tick. |
| US8148377B2 (en) | 2007-02-11 | 2012-04-03 | Map Pharmaceuticals, Inc. | Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile |
| US20110171141A1 (en) * | 2009-06-26 | 2011-07-14 | Kellerman Donald J | Administration of dihydroergotamine mesylate particles using a metered dose inhaler |
| CA151549S (en) | 2013-02-14 | 2014-06-04 | Clement Clarke Int Ltd | Spacer for an asthma inhaler |
| US10207065B2 (en) | 2013-07-12 | 2019-02-19 | John H. Silva | Mouthpiece for inhalers |
| USD748242S1 (en) * | 2014-07-11 | 2016-01-26 | H. Stuart Campbell | Inhaler mouthpiece |
| US20220168297A1 (en) * | 2020-12-01 | 2022-06-02 | Reverspah Llc | Methods and compositions for treating chronic obstructive pulmonary disease, asthma, pneumonia, bronchitis, cystic fibrosis, pulmonary edema, interstitial lung disease, sarcoidosis, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary arterial hypertension |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE555972A (en) * | 1956-03-21 | |||
| US2890697A (en) * | 1957-03-15 | 1959-06-16 | Wilton E Van Sickle | Enclosed medicament container and atomizer |
| US3012555A (en) * | 1959-05-18 | 1961-12-12 | Meshberg Philip | Dispensing package for material under pressure |
| US3183907A (en) * | 1962-06-25 | 1965-05-18 | Merck & Co Inc | Device for inhalation aerosol |
| JPS4214552Y1 (en) * | 1964-12-30 | 1967-08-18 | ||
| JPS4514212Y1 (en) * | 1966-11-02 | 1970-06-16 | ||
| US3559851A (en) * | 1969-05-27 | 1971-02-02 | Valve Corp Of America | Fully-emptying valve assemblage |
| JPS566680Y2 (en) * | 1972-04-19 | 1981-02-13 |
-
1973
- 1973-06-27 US US00374176A patent/US3809294A/en not_active Expired - Lifetime
-
1974
- 1974-03-08 CA CA194,459A patent/CA1043208A/en not_active Expired
- 1974-03-12 ZA ZA00741633A patent/ZA741633B/en unknown
- 1974-03-12 IL IL44401A patent/IL44401A/en unknown
- 1974-03-19 IE IE574/74A patent/IE40616B1/en unknown
- 1974-03-21 PH PH15648A patent/PH11643A/en unknown
- 1974-03-21 GB GB1270674A patent/GB1471917A/en not_active Expired
- 1974-03-28 AR AR253017A patent/AR198562A1/en active
- 1974-03-29 DE DE2415360A patent/DE2415360C2/en not_active Expired
- 1974-04-02 IT IT49957/74A patent/IT1003994B/en active
- 1974-04-04 NL NLAANVRAGE7404626,A patent/NL178655C/en not_active IP Right Cessation
- 1974-04-08 DD DD177768A patent/DD125188A5/xx unknown
- 1974-04-09 SU SU2017264A patent/SU537614A3/en active
- 1974-04-09 YU YU00989/74A patent/YU36435B/en unknown
- 1974-04-09 BE BE143026A patent/BE813512A/en not_active IP Right Cessation
- 1974-04-10 AT AT299974A patent/AT342211B/en not_active IP Right Cessation
- 1974-04-10 JP JP49041581A patent/JPS6010737B2/en not_active Expired
- 1974-04-10 FR FR7412670A patent/FR2234905B1/fr not_active Expired
- 1974-04-11 SE SE7405022A patent/SE405448B/en unknown
- 1974-04-23 CH CH555174A patent/CH577832A5/xx not_active IP Right Cessation
- 1974-06-25 PL PL1974172163A patent/PL89980B1/pl unknown
- 1974-06-26 DK DK343874A patent/DK152967C/en not_active IP Right Cessation
- 1974-06-27 CS CS7400004539A patent/CS182257B2/en unknown
- 1974-06-27 ES ES427755A patent/ES427755A1/en not_active Expired
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1975
- 1975-10-13 CH CH1325075A patent/CH620207A5/de not_active IP Right Cessation
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| PL | Patent ceased |