SE190891C1 - - Google Patents
Info
- Publication number
- SE190891C1 SE190891C1 SE190891DA SE190891C1 SE 190891 C1 SE190891 C1 SE 190891C1 SE 190891D A SE190891D A SE 190891DA SE 190891 C1 SE190891 C1 SE 190891C1
- Authority
- SE
- Sweden
- Prior art keywords
- salt
- penicillin
- diphenylpiperazine
- water
- solution
- Prior art date
Links
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- BZSJSZVGLGMMBK-UHFFFAOYSA-N 2,5-diphenylpiperazine Chemical compound C1NC(C=2C=CC=CC=2)CNC1C1=CC=CC=C1 BZSJSZVGLGMMBK-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 10
- 229940056360 penicillin g Drugs 0.000 claims description 8
- 230000003115 biocidal effect Effects 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 230000002035 prolonged effect Effects 0.000 claims description 2
- 229930182555 Penicillin Natural products 0.000 description 8
- 229940049954 penicillin Drugs 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 150000002960 penicillins Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229960004919 procaine Drugs 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- OMGKVOFOJBAAER-UHFFFAOYSA-N 2,5-diphenyl-1,2-dihydropyrazine Chemical compound C1(=CC=CC=C1)C1NC=C(N=C1)C1=CC=CC=C1 OMGKVOFOJBAAER-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- LLZRSOPHIGKISM-UHFFFAOYSA-N 1,4-diphenylpiperazine Chemical compound C1CN(C=2C=CC=CC=2)CCN1C1=CC=CC=C1 LLZRSOPHIGKISM-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000013008 thixotropic agent Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Uppfinnare: J Mathieu och G Nomine Prioritet begiird fran den 29 september 1955 (Frankrike) Foreliggande uppfinning avser ett satt att framstalla ett salt av penicillin G med snabb, stark och forldngd antiobiotisk verkan. Detta antibiotiska medel kan anvandas mom veterindrmedicinen, humanterapeutiken, inom jordbruket och boskapsskOtseln, pa samma sat som sjalva 2,5-difenylpiperazinen. Inventors: J Mathieu and G Nomine Priority Begired from September 29, 1955 (France) The present invention relates to a process for producing a salt of penicillin G with rapid, strong and prolonged antibiotic action. This antibiotic can be used in veterinary medicine, human therapy, in agriculture and animal husbandry, in the same way as the 2,5-diphenylpiperazine itself.
De salter, som penicillinet bildar med organiska baser, ha MU en allt storre betydelse, sasom exempelvis salterna av benshydralamin, prokain, kinin eller N,N'-dibensyletylendiamin. The salts formed by the penicillin with organic bases are of increasing importance to MU, such as the salts of benzhydralamine, procaine, quinine or N, N'-dibenzylethylenediamine.
Det har nu visat sig, att penicillinet med 2,5- difenylpiperazin bildar ett nytt salt, som är svarlosligt i vatten, Genom detta nya salt blir det mojligt att i blodet uppratthalla en effektiv koncentration av penicillin under ldngre tid. Penicillinsaltets mycket laga giftighet mOjliggor dess anvandning rationellt utan risk for komplikationer. Genom sin loslighet i vatten är penicillinsaltet av 2,5-difenylpiperazin mycket fordelaktigt i forhallande till andra former av detta antibiotikum, vilka ha fordrojd verkan. Sasom framgar av foljande tabell, erhaller ldkaren harigenom ett nytt hj dlpmedel, som joke utgor nagon overfloclig dubblering av de existerande formerna. Genom en mycket exakt dosering av penicillinet blir det i vissa fall mojligt att undvika upptradandet av re,sistenta mikrobstammar och att halla viss individuell kanslighet under kontroll, exempelvis pa grund av allergiska foreteelser. It has now been found that the penicillin with 2,5-diphenylpiperazine forms a new salt which is unresponsive in water. Through this new salt it becomes possible to maintain in the blood an effective concentration of penicillin for a longer time. The very low toxicity of penicillin salt allows its use rationally without the risk of complications. Due to its solubility in water, the penicillin salt of 2,5-diphenylpiperazine is very advantageous in relation to other forms of this antibiotic, which have a delayed action. As can be seen from the following table, the physician thereby obtains a new aid, which, as a joke, constitutes a superfluous duplication of the existing forms. Through a very precise dosage of the penicillin, it becomes possible in some cases to avoid the occurrence of pure microbial strains and to keep some individual probability under control, for example due to allergic phenomena.
Salter av penicillin och: laslighet i vatten I g/1 -Benshydrylamin 6,4 -Prokain 4, -Kinin 2,7 -2,5-difenylpiperazin 0, En stor fordel med det antibiotiska medlet enligt uppfinningen bestir i att det i sin molekyl saknar flagon kanslig grupp. Det Or kant att prokainpenicillinet, exempelvis, bland annat kan Dupl. kl. 30 h: 2/03 framkalla allvarliga olyckor pa grund av att den manskliga organismen Ur kanslig for den paraaminerade gruppen i prokainmolekylen. Della forhallande har sarskilt studerats av Tzanck, Sidi och Dobkovitch (C. Albahny »Maladies Medicamenteuses, Masson-Paris 1953, sid. 121). Salts of penicillin and: lasiness in water I g / 1 -Benzhydrylamine 6,4 -Procaine 4, -Kinin 2,7 -2,5-diphenylpiperazine 0, A great advantage of the antibiotic agent according to the invention is that in its molecule lacks flagon chancery group. It Or edge that the procaine penicillin, for example, among other things can Dupl. at 30 h: 2/03 cause serious accidents due to the fact that the human organism is susceptible to the paraaminated group in the procaine molecule. This relationship has been studied in particular by Tzanck, Sidi, and Dobkovitch (C. Albahny »Maladies Medicamenteuses, Masson-Paris 1953, p. 121).
Enligt uppfinningen framstdlles det antibiotiska medlet genom att en losning av ett salt av 2,5-difenylpiperazin i vatten eller nagot med vatten blandbart losningsmedel bringas att reagem med en losning av ett salt av penicillin G i vatten eller i ett losningsmedel och att det utfallda saltet isoleras genom filtrering eller centrifugering samt tvattas och torkas. Det enligt uppfinningen framstallda penicillinsaltet tinker att man rnera exakt kan dosera antibiotika och att man kan undvika all resistenta mikrobstammar upptrdda. Saltets loslighet medfOr formanliga egenskaper, jamfOrt med andra »fordrOjande» former av penicillin. Saltets giftighet Or mycket ringa och det Or dven skonsamt ifraga om kanslighet av allergiskt ursprung. Det framstallda antibiotiska medlet har en Overldgsen terapeutisk aktivitet och andra betydelsefulla egenskaper, varfor det kan anvandas for manga skilda andamal. Betraffande Ovriga Overraskande egenskaper ma ndmnas att 2,5-difenylpiperazin Or ett utmarkt stimuleringsmedel for andningsverksamheten. Om klorhydratet av 2,5-difenylpiperazin i losning i destillerat vatten injiceras intravenost i kaniner, som anestesierats med uretan, och om karotistrycket och anclningen registreras, kan man iakttaga dels en stimulerad andningsverksamhet genom att andningsrorelsernas frekvens och amplitud Ras redan vid en dos av 4 mg/kg, och dels en overgaende och icke konstant trycksankning, atfOljd av en Mt och likaledes joke konstant tryckdkning for samma dos. According to the invention, the antibiotic agent is prepared by reacting a solution of a salt of 2,5-diphenylpiperazine in water or some water-miscible solvent with a solution of a salt of penicillin G in water or in a solvent, and the precipitated salt isolated by filtration or centrifugation and washed and dried. The penicillin salt produced according to the invention thinks that it is possible to dose antibiotics precisely and that all resistant microbial strains can be avoided. The solubility of the salt results in formative properties, compared with other "demanding" forms of penicillin. The toxicity of the salt is very low and it should be gently questioned about the possibility of allergic origin. The antibiotic produced has an over-the-counter therapeutic activity and other significant properties, for which it can be used for many different purposes. Regarding Other Surprising properties it is mentioned that 2,5-diphenylpiperazine Or is an excellent stimulant for the respiratory activity. If the chlorohydrate of 2,5-diphenylpiperazine in solution in distilled water is injected intravenously into rabbits anesthetized with urethane, and if carotid pressure and inflammation are recorded, a stimulated respiratory activity can be observed by increasing the frequency and amplitude of respiratory movements at a dose of 4 mg / kg, and partly a transient and non-constant pressure drop, followed by an Mt and also joke constant pressure drop for the same dose.
Giftigheten for 2,5-difenylpiperazin kan ligga vid DL = 60 + 4 mg/kg. 2— — Samma effekt iakttages for penicillin-G saltet av 2,5-difenylpiperazin. The toxicity of 2,5-diphenylpiperazine may be at DL = 60 + 4 mg / kg. The same effect is observed for the penicillin-G salt of 2,5-diphenylpiperazine.
Det enligt foreliggande uppfinning framstallda penicillinsaltets egenskaper framtrada sarskilt vid akommor i luftvagarna, t. ex. lunginflamma- tion, pa grund av aft detta salt kombinerar en stimulering av andningen med en anmarknings- yard antibiotisk effekt. Kombinationen av dessa tva effekter är helt ovantad och medfor utomordentligt goda terapeutiska resultat. The properties of the penicillin salt produced according to the present invention were particularly evident in airway murmurs, e.g. pneumonia, due to the fact that this salt combines a stimulation of respiration with a marking yard antibiotic effect. The combination of these two effects is completely unexpected and leads to exceptionally good therapeutic results.
Man anvander lampligen acetatet av 2,5-difenylpiperazin och trietylaminpenicillin-G varvid den dubbla omsattningen genomfores i vatten och saltet isoleras genom sugfiltrering eller centrifugering, varefter det tvattas med vatten och torkas. Dessa reaktioner bora naturligtvis genom- Was under sterila forhallanden, om man onskar erhalla en produkt, som kan anvandas terapeu- tiskt. 2,5-difenylpiperazin binder tvá molekyler penicillin. Det nya saltet har, raknat pa vikten, mycket hog aktivitet, sa att man kan undvika den alltid besvarande tillfOrseln av stora mangder av lakemedlet. The acetate of 2,5-diphenylpiperazine and triethylamine penicillin-G are suitably used, the double reaction being carried out in water and the salt being isolated by suction filtration or centrifugation, after which it is washed with water and dried. These reactions must, of course, be carried out under sterile conditions, if one wishes to obtain a product which can be used therapeutically. 2,5-Diphenylpiperazine binds two molecules of penicillin. The new salt has, due to its weight, very high activity, so that the always satisfying supply of large quantities of the drug can be avoided.
Det nya saltet av 2,5-difenylpiperazin och penicillin-G tillfores inom veterinar- och humanmedicinen vanligen parenteralt sasom en suspension i form av ett lampligt medel, sasom destillerat vatten, en normal saltlosning, 20 % propylenglykol eller nagot annat av de vanligen anva.nda vattenhaltiga utspadningsmedlen. Man kan aven anvanda en olja, sasom jordnotolja, sesamolja, bomullsfroolja eller andra assimilerbara triglycerider. Det dr alltid lampligt att pa i och for sig kant satt till preparatet satta eft stabiliseringsmedel, ett tixotropiskt medel, ett modiferingsmedel for viskositeten och ett vatmedel, sã att preparatet far lampliga egenskaper for injektion med hjalp av en injektionsspruta. Kristallerna kunna finfordelas i forvag. Det nya saltet kan Oven anvandas i andra farmaceutiska eller industriella, kanda former, sasom pastiller, drageer, granuler eller pa flytande eller fasta barare, sh. att det kan sattas till fader fOr kreatur eller utspridas pa vaxter. 2,5-difenylpiperazinen, som icke har beskrivits tidigare, framstalles genom reduktion av 2,5-difenyl-dihydro-pyrazin, som framstalles enligt Gabriel (Ber. 1908, 41, 1127). 2,5-difenylpiperazinen enligt foreliggande uppfinning med smaltplaten 195-196° far icke forvaxlas med N,N'- difenylpiperazinen, som har beskrivits for lange sedan och smalter vid 164-165° C. The new salt of 2,5-diphenylpiperazine and penicillin-G is usually administered parenterally in veterinary and human medicine as a suspension in the form of a suitable agent, such as distilled water, a normal saline solution, 20% propylene glycol or any other commonly used form. aqueous diluents. You can also use an oil, such as peanut oil, sesame oil, cottonseed oil or other assimilable triglycerides. It is always advisable to add the stabilizer, a thixotropic agent, a viscosity modifier and a wetting agent per se to the edge of the preparation, so that the preparation has suitable properties for injection by means of a syringe. The crystals can be finely divided in advance. The new salt can also be used in other pharmaceutical or industrial, known forms, such as lozenges, dragees, granules or on liquid or solid carriers, sh. that it can be put to father for cattle or spread on plants. The 2,5-diphenylpiperazine, which has not been previously described, is prepared by reduction of 2,5-diphenyl-dihydropyrazine, which is prepared according to Gabriel (Ber. 1908, 41, 1127). The 2,5-diphenylpiperazine of the present invention having a melting plate of 195-196 ° should not be confused with the N, N'-diphenylpiperazine described long ago and melting at 164-165 ° C.
Foljande exempel belysa uppfinningen utan att begransa densamma. Man kan salunda framstalla 2,5-difenylpiperazinen ur godtyckligt 2,5-difenyldihydropyrazin, anvanda andra losningsmedel, andra reduceringsmedel, tilldmpa andra temperaturer och andra reaktionstider utan att dad& overskrida uppfinningens ram. For att framstalla penicillinsaltet av 2,5-difenylpiperazin kan man aven anvanda andra losningsmedel, tillarnpa andra temperaturer och reaktionstider, ersatta acetatet av 2,5-difenylpiperazinen med nagot annat salt av denna has med onskad loslighet, eller i stallet for trietylaminpenicillinet anvanda ett penicillinsalt av nagon alkalimetall, j ordalkalimetall eller organisk bas, blott ifragavarande salt har sadan loslighet, aft den dubbla omsattningen kan genomforas. The following examples illustrate the invention without limiting it. Thus, the 2,5-diphenylpiperazine can be prepared from any 2,5-diphenyldihydropyrazine, using other solvents, other reducing agents, applying other temperatures and other reaction times without departing from the scope of the invention. To prepare the penicillin salt of 2,5-diphenylpiperazine, other solvents may be used, different temperatures and reaction times may be used, the acetate of the 2,5-diphenylpiperazine may be replaced with some other salt of this hash with the desired solubility, or a penicillin salt may be used instead of the triethylamine penicillin. of any alkali metal, alkaline earth metal or organic base, only the salt in question has such solubility, since the double reaction can be carried out.
Exempel. Framstallning av penicillin-G saltet av 2,5-difenylpiperazin. 1 g 2,5-difenylpiperazin, med en smaltpunkt 195-196° C pa block, infores i 100 ml destillerat vatten, 0,55 ml isattika tillsattes och produkten varmes pa vattenbad till 60-80° C, tills alit Or upplOst. Man filtrerar och later filtratet svalna till rumstemperatur. Den pa detta satt erhallna losningen sattes sedan under omroring till en losning av 4 g trietylaminpenicillin-G i 20 ml destillerat vatten. Man kyler till 10° C och sugfiltrerar den bildade, kristalliserade massan, som sedan tvdttas med destillerat vatten. Man erhailer harvid och efter torkning under vakuum i narvaro av fosforsyraanhydrid 3, 5 g bipenicillinat av 2,5-difenylpiperazin, Ogonblicklig smaltpunkt ph. block 219° C under sonderdelning [a] = + 212° + 2 (c = 1 % dimetylformamid). Utbytet uppgar till 94 %. Denna forening har icke beskrivits tidigare. Den har formen av ofargade, prismatiska nalar, Or loslig i formarnid, dimetylformamid, metoxietanol, loslig till 0,35 delar pa 1000 i vatten, samt oloslig i aceton, alkohol, kloroform, eter och de vanliga, organiska losningsmedian. Example. Preparation of the penicillin-G salt of 2,5-diphenylpiperazine. 1 g of 2,5-diphenylpiperazine, with a melting point of 195-196 ° C per block, is introduced into 100 ml of distilled water, 0.55 ml of glacial acetic acid was added and the product was heated on a water bath to 60-80 ° C, until the sol was dissolved. Filter and allow the filtrate to cool to room temperature. The resulting solution was then added with stirring to a solution of 4 g of triethylamine penicillin-G in 20 ml of distilled water. Cool to 10 ° C and suction filter the formed, crystallized mass, which is then washed with distilled water. 3.5 g of bipenicillinate of 2,5-diphenylpiperazine are obtained during and after drying under vacuum in the presence of phosphoric anhydride. Immediate melting point ph. block 219 ° C with probing [a] = + 212 ° + 2 (c = 1% dimethylformamide). The yield amounts to 94%. This association has not been described before. It is in the form of uncoloured, prismatic needles, or soluble in formaride, dimethylformamide, methoxyethanol, soluble to 0.35 parts per 1000 in water, and insoluble in acetone, alcohol, chloroform, ether and the usual organic solvents.
Analys: C48H5dOsN6S, = 907 Beraknat: C % 63,6 H % 8,0 N % 9,2 S % 7,0 Funnet:63,46,09,07,0 Analysis: C 48 H 50 O 5 N 6 S, = 907 Calculated: C% 63.6 H% 8.0 N% 9.2 S% 7.0 Found: 63.46.09.07.0
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE190891T |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SE190891C1 true SE190891C1 (en) | 1964-01-01 |
Family
ID=41977458
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE190891D SE190891C1 (en) |
Country Status (1)
| Country | Link |
|---|---|
| SE (1) | SE190891C1 (en) |
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0
- SE SE190891D patent/SE190891C1/sv unknown
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