US1120233A - Cocain isovalerianate. - Google Patents
Cocain isovalerianate. Download PDFInfo
- Publication number
- US1120233A US1120233A US71903112A US1912719031A US1120233A US 1120233 A US1120233 A US 1120233A US 71903112 A US71903112 A US 71903112A US 1912719031 A US1912719031 A US 1912719031A US 1120233 A US1120233 A US 1120233A
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- US
- United States
- Prior art keywords
- acid
- isovalerianate
- cocain
- ether
- isovalerianic
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- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
Definitions
- mmIN-ovEnLncn DECEASED, LATE or CHARLOTTENBURG, BY META OVERLACH, or cmnmrrnnnum, Immnss, AND MORITZ xoRNEn, or BERLIN, GERMANY,
- e hitherto unknown :cQcain isovalerialiate has a number of important advantages over freeisoyalerianieacid and other isovalerianates for, medical purposes.
- Isovalerianic hcid itself as welldas its salts cannot be ior subcutaneous-in- 'ecti on,; as .”when they are ingected, yiolent urning. painis producedfand moreover there is a mechanical-caustidaction exercised on (the subcutaneous tissue producing necrosis at the point of lIlJGCtlOD.
- cocain isovalerianate as regards the removal of burning pain and necrosis being'sufiicient to render isovalerianic acid bound to the" other bases innocuous alsoin that respect. ,It therefore becomes possible in that way to. introduce into the body by subcutaneous 1n ection su'chbases together'with isovalerianic acid, the influence of which on the organism is to be modified by the presence of isovalerianic acid.
- Isovalerianic salts of various alkaloids couLd be used, which sup-- plement the action ofeach other, the unpleasant by-efiects otone being counteracted by the other, and their. favorableact'ion being combined with the favorable action of isovaleria-nic acid.
- roniorphid and apomorphin is prevented by hydrochlorid of inorphin.
- Sulfate Q of barium is precipitated, whilethe isovaleizianat'e of cocam remains in solution, and after the filtering off, canbe obtained by carefulevaporat-ion, preferably in a high vacuum.-
- the syrup thus obtained, is converted into crystalline salt in the manner above referred to.
Description
STATES TENT OFFICE.
mmIN-ovEnLncn, DECEASED, LATE or CHARLOTTENBURG, BY META OVERLACH, or cmnmrrnnnum, Immnss, AND MORITZ xoRNEn, or BERLIN, GERMANY,
mm oss T THEODOR 'rnrcnsmn'nn, or warm, GERMANY, A'FIRM, AND;
shccnmmranmx ax'rmnsnsnnnscnan'r, Y VORM. FAHLBERG, LIST & 00., or ssnnxn-wnsmmtnnsnn, GERMANY, A' rum.
cocam ISOVALERIANATE.
15 120, 33 30 Drawin To all it may concern;
Be it known thatMm'rrNOvERnAcH, late a subject of the German Emperor, and resident of. Ch ar-lottenburg, near Berlin, in the Kingdom ofPruss'ia, German Empire, do
ceased, and Monrrz KbRNElg'a subject of the German Emperor, and resident of Berlin, in the, Kingdomof Prussia, German Empire, have invented new and useful Improvements in Oocain Isovalerianate, of which the following is a full, clear, and exinventionjrelates to a new alkaloid salt viz., isovalerianate. 4
e hitherto unknown :cQcain isovalerialiate has a number of important advantages over freeisoyalerianieacid and other isovalerianates for, medical purposes.
Isovalerianic hcid itself as welldas its salts, cannot be ior subcutaneous-in- 'ecti on,; as ."when they are ingected, yiolent urning. painis producedfand moreover there is a mechanical-caustidaction exercised on (the subcutaneous tissue producing necrosis at the point of lIlJGCtlOD. Thl's disadvantage' .which hitherto preventedisovalerianic jaci: being introduced directly into the of the body, -1s completely avoided-by binding the acid to cocain, as burning pain is thereby avoided,
and mechanical combustion o1; necrosis prevented. "jCocain isovalerianate has however a further advantage that the dose of isoualerianic acid can be increased. The preparationshither'to known in which sovalerianic acid was bound; to alkaloids,
could notbe. used for injection, for (apart from the disadvantage already mentioned,; the dose of isovaleriani-c acid that could be usedwas too small, in order to insurecompletely thetonic eflectof "isova'lerianic acid onthe neri es', .asotherwise the dose of the base combined with it, became too large. Iii-that respect also cdcain"isova'lerianate removes the existing disadvantages as t makesit possible tocombme it with 15mmlerianic salts of other bases, the action of Specification Letters Patent.
Patented Dec. 8,1914.
Application filed September 6, 1912. Serial No. 719,031,
cocain isovalerianate. as regards the removal of burning pain and necrosis being'sufiicient to render isovalerianic acid bound to the" other bases innocuous alsoin that respect. ,It therefore becomes possible in that way to. introduce into the body by subcutaneous 1n ection su'chbases together'with isovalerianic acid, the influence of which on the organism is to be modified by the presence of isovalerianic acid. Isovalerianic salts of various alkaloids couLd be used, which sup-- plement the action ofeach other, the unpleasant by-efiects otone being counteracted by the other, and their. favorableact'ion being combined with the favorable action of isovaleria-nic acid. All these results canbe obtained only owing to the above mentioned .yaluable properties of cocain isovalerianate. It'is especially .possible'to preparein this way acomposition which combines the painrelieving actionof morphin v 'wlth-the appeaslng action of isovalerlanic acid, by mixing lsovalerianates of imorp'hin, cafi'ein and cocain in suitable prov p0rtions'. By theco'mbination of these three salts, it becomes for the first time possible to manufacture a preparation vsuitable for subcutaneous injection, in which the complete pain-relieving act on of morphln 1s combined to the fuliextent with the tonic action of isovalerianic acid 'on the nerves,-
without the appearance of injurious actions of morphin on the heart, breathing centerand the digestive organs, and the injurious actions which hitherto made impossible sub of isoyalerianic acid cutaneous injection preparations.
Injurious actions of which hitherto was generally used as .hydro-chloridof morphin' are of various kinds. 7 First ant consequences, but also the dangerous action of morphiu on the heart, breathing center and digestive organs, and on the other hand, owing to .the presence ofhydnoof all, it is noton'lythe generally unpleas' the original The possibility'of-the formation of clilo-.
, roniorphid and apomorphin is prevented by hydrochlorid of inorphin.
the present preparation making it unnecessary to use morphin in the form ofhydrochlorid and enabling it to be usedas isovalerianate. Isovalerianic acid in' its turn counteracts the injurious effects of morphin.
Its use in a preparation for subcutaneousinjection 18 however rendered possible only by the simultaneous use of cocain 1sovaler1-.
anate. The latter doesaway with the very strong burning pain which otherwise always appears in case of subcutaneous injection of isovalerianic acid preparations, and with the caustic action on the subcutaneous tissue leading to necrosis, to such an extent that injurious effects inthat direction of isovaler-ianic acid combined with the other bases, are also counteracted at. the same time In that way, it is possible to introducea suflicient quantity of isovalerianicacid into the body by subcutaneous injection, without causing' any injury by the introduction of such large quantity of base as would be required for bindingsuch a great'quantity of isovaleri-anic acid, as would be the case if iosvalerianic acid were used'bound only to one base, the quantity of which would then become toogreat'for subcutaneous injection. The combination described theretore makes it'possible first of all to utilize completely.
the desired tonic action of "isovalerianic acid by subcutaneous injection, and on the other hand to obviate injurious by-efi'ectsof morphi'n while fully keeping'its desired properties, by the counter effect of cafi'ein, c0- cain'and isovalerianicucid, and by the impossibility of formation of poisonous derivaties such as chloromorphid and apomorphin which areeasilyproduceddnczise of In preparing cocain isova-lerianate we proceed as follows.
First method: 'Equi-molecular quantities of cocain base and i'sovalerianie acid, or a small excess of the latter are brought together, dissolved either both in ether, a'ce tone or any other solvent, or only one of the two compounds is dissolved, and the other is introduced as it is, whereupon the solvent is removed by a slight heat, preferably in a vacuum. The two bodies could also be heat- =vneral injurious eii'ccts of inorphin I ed together in a pure state in equalmolccular quantities, until the liquefaction of the cocain indicated the end of the reaction. In an y case, after the cooling,a-syrup like liquid obtained from which after a certain time needles begin to separate. Af.ter standing for a long tim the product forms a thick mass of crystal needles. For the; purpose of further purification, these crystal needles are rubbed \Vltllfit' little ethyl-ether in" which the salt is soluble only to a sli ht extent.
, The amorphous )arts then. beeome crystalline. Petroleum ether is then added, in which the salt is practically insoluble, until the precipitation is completed. The salt is then removed and washed'fwith petroleum ether. v V
1st example: 30.3 gr. ofcocain' are heated with 11' gr. of isovalerianiclacid, in awater bath, until liquid. After the cooling, 50 cubic centimeters of ethyl-ether are added,
.and the whole is stirred "until the mass is of uniform solidity. Thcreupon 100 gr. of petroleum ether of the Specific gravity of .6 10 are added, the whole is left to stand for a short time, filtered, washed with a little petroleum ether-and dried in a vacuum over sulfuric acid. The salt is obtained practically in a theoretical ieliin the form of fine, white needles which begin to melt at 125 and have a distinctsmell of isovaleria'nic acid. They are soluble in water and alcohol, little "soluble in ether andpractic-ally insoluble in petroleum-ether.
Second 12wt7zo'(l.'-'Instead of causing the free base and {the free acid to act on each other, a eoc'ain' salt could be of course brought together with anisovalerianate in a solvent, inwvhich the acid of the-cocain suit gives an insolul compound with the based the isov'alcriunate and after filtering 03f the latter, the cocain isovalerianate could be separated in a suitablemahner.--For inj stance, isovalerianate of bariuincould be dis solved in water,- and an aqueous solution of sulfate of coealn added 1n equal molecular quantities. Sulfate Q of barium is precipitated, whilethe isovaleizianat'e of cocam remains in solution, and after the filtering off, canbe obtained by carefulevaporat-ion, preferably in a high vacuum.- The syrup thus obtained, is converted into crystalline salt in the manner above referred to.
ind-example: 10 gr. of isovalerianate of barium are dissolved'in v100. gr. of warm dis tilled water, and 11.8 gr. of sulfa-tecfrQO-HZO cain dissolved in 50 cubic eentimete rsarof water, are added with stirring; Afterzstanding for some time, the substance is-carefully filteredoff from the barium, sulfate, and the solvents evaporated at about 10 mm. pressure. The remaining syrup is dried for 24 hours in a vacuum over sulfuric acid and converted in the manner described into crystaulne salt which has the same compoinvention of MARTIN OVERLAGH, deceased, sition as that obtained in the Example 1, and Monrrz KiJRXER, we have signed our and is obtained in a good yield. names in presence of two subscribing wit- 15 lllilhaltl We cliaim nesses.
5 e erein escri e cocain isovalerianate, I a
crystallizing in the form of fine, white F t, th of needles which. begin to melt at 125 and f it 5 d are soluble in Water and alcohol, little solum4 m7 at? I 6066 ble in ether and practically insoluble in MORITZ KORNER.
l0 petroleum-ether. Vitnesses:
In testiniony, that We META OVERLAGH and *QLDEMAR HAUPT, MORITZ Koimnn' claim the foregoing as the ARTHUR SCHROEDER.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71903112A US1120233A (en) | 1912-09-06 | 1912-09-06 | Cocain isovalerianate. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71903112A US1120233A (en) | 1912-09-06 | 1912-09-06 | Cocain isovalerianate. |
Publications (1)
Publication Number | Publication Date |
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US1120233A true US1120233A (en) | 1914-12-08 |
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US71903112A Expired - Lifetime US1120233A (en) | 1912-09-06 | 1912-09-06 | Cocain isovalerianate. |
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1912
- 1912-09-06 US US71903112A patent/US1120233A/en not_active Expired - Lifetime
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