CH654840A5 - Compound having an antibiotic activity - Google Patents
Compound having an antibiotic activity Download PDFInfo
- Publication number
- CH654840A5 CH654840A5 CH546683A CH546683A CH654840A5 CH 654840 A5 CH654840 A5 CH 654840A5 CH 546683 A CH546683 A CH 546683A CH 546683 A CH546683 A CH 546683A CH 654840 A5 CH654840 A5 CH 654840A5
- Authority
- CH
- Switzerland
- Prior art keywords
- compound
- josamicin
- administration
- day
- salt
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 8
- 230000003115 biocidal effect Effects 0.000 title 1
- XJSFLOJWULLJQS-NGVXBBESSA-N josamycin Chemical compound CO[C@H]1[C@H](OC(C)=O)CC(=O)O[C@H](C)C\C=C\C=C\[C@H](O)[C@H](C)C[C@H](CC=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](N(C)C)[C@H](O[C@@H]2O[C@@H](C)[C@H](OC(=O)CC(C)C)[C@](C)(O)C2)[C@@H](C)O1 XJSFLOJWULLJQS-NGVXBBESSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- 229960004144 josamycin Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 10
- YMDXZJFXQJVXBF-STHAYSLISA-N fosfomycin Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O YMDXZJFXQJVXBF-STHAYSLISA-N 0.000 abstract description 8
- 239000003120 macrolide antibiotic agent Substances 0.000 abstract description 2
- 230000002906 microbiologic effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 7
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 241000220304 Prunus dulcis Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000020224 almond Nutrition 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 235000000434 Melocanna baccifera Nutrition 0.000 description 1
- 241001497770 Melocanna baccifera Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000187438 Streptomyces fradiae Species 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000132 chronic toxicity testing Toxicity 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960000308 fosfomycin Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000003192 teratological effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65502—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a three-membered ring
- C07F9/65505—Phosphonic acids containing oxirane groups; esters thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
La presente invenzione si riferisce a un sale dell'antibiotico macrolidico Josamicina con acido (—)-cis-l,4-epossipropioniI-fosfonico, altresì noto come fosfomicina. The present invention relates to a salt of the macrolide antibiotic Josamicin with (-) - cis-1, 4-epoxypropionI-phosphonic acid, also known as fosfomycin.
La Josamicina, da tempo nota e impiegata largamente in terapia, è stata descritta nella domanda di brevetto tedesca pubblicata n. 1 492 035. Le sue proprietà farmacologiche sono state riassunte su Drugs of Today Voi. 13, 8, (1977). Anche la fosfomicina è da tempo impiegata come agente antibatterico: essa viene prodotta per sintesi (Brevetti belgi n. 723 072 e 723 073) o per fermentazione da un ceppo di Streptomyces fradiae (Brevetto belga n. 718 507). Josamicin, long known and widely used in therapy, has been described in the published German patent application no. 1 492 035. Its pharmacological properties have been summarized in Drugs of Today Vol. 13, 8, (1977). Phosphomycin has also been used for some time as an antibacterial agent: it is produced by synthesis (Belgian patents No. 723 072 and 723 073) or by fermentation from a strain of Streptomyces fradiae (Belgian patent No. 718 507).
Si è ora trovato che il sale della Josamicina con la fosfomicina, avente la formula (I) seguente: Josamicin salt with phosphomycin has now been found to have the following formula (I):
CH3—CH CH--P03H: Jos® (I) CH3 — CH CH - P03H: Jos® (I)
in cui, per brevità, la formula di struttura della Josamicina non è riportata per esteso ma è abbreviata con la sigla Jos, è dotato di sorprendenti e favorevoli caratteristiche farmacocinetiche. in which, for brevity, the structural formula of Josamicin is not reported in full but is abbreviated with the abbreviation Jos, it has surprising and favorable pharmacokinetic characteristics.
In particolare, il sale I è dotato di elevato assorbimento per via orale e consente il raggiungimento di livelli ematici e tessutali di Josamicina prolungati nel tempo e pressoché doppi rispetto a quelli ottenibili dalla somministrazione di equivalenti quantità di Josamicina base o propionato. Inoltre il prodotto presenta un'elevata solubilità in acqua, tale da consentire la somministrazione anche per via parenterale. In particular, the salt I has high oral absorption and allows the achievement of blood and tissue levels of Josamicina prolonged over time and almost double compared to those obtainable by the administration of equivalent quantities of Josamicina base or propionate. Furthermore, the product has a high solubility in water, such as to allow administration also by parenteral route.
II composto oggetto dell'invenzione è inoltre dotato di bassa tossicità mentre lo spettro antibatterico è sovrapponibile a quello della Josamicina. The compound object of the invention is also endowed with low toxicity while the antibacterial spectrum is superimposable to that of Josamycin.
Ne consegue una notevole efficacia terapeutica nelle infezioni sostenute da germi sensibili alla Josamicina. The result is a remarkable therapeutic efficacy in infections sustained by germs sensitive to Josamicin.
Costituiscono pertanto oggetto dell'invenzione anche composizioni farmaceutiche contenenti come principio attivo il sale di formula I oltre ad eventuali eccipienti di impiego convenzionale in tecnica farmaceutica. Therefore, pharmaceutical compositions containing the salt of formula I as well as any excipients of conventional use in the pharmaceutical technique are also the object of the invention.
Il composto dell'invenzione può essere formulato sotto forma di compresse, di capsule o di granulato per somministrazione orale, di supposte per la somministrazione rettale, sotto forma di pomata par uso topico o di soluzione estemporanea per uso parenterale. Il nuovo sale può variare nelle precedenti formulazioni in quantità comprese fra 10 mg e 1500 mg. The compound of the invention can be formulated in the form of tablets, capsules or granules for oral administration, suppositories for rectal administration, in the form of ointment for topical use or of extemporaneous solution for parenteral use. The new salt can vary in the previous formulations in quantities ranging from 10 mg to 1500 mg.
Esempi non limitativi delle formulazioni secondo l'invenzione sono costituiti da: Non-limiting examples of the formulations according to the invention consist of:
capsule, compresse, confetti contenenti 125-500-1000 mg di prodotto attivo; supposte contenenti 0,25-0,5-1-2 g di prodotto attivo; pomata, crema, lozione contenente 10-25% di prodotto attivo; fiale per uso parenterale contenenti 500-2000 mg di prodotto attivo. capsules, tablets, sugared almonds containing 125-500-1000 mg of active product; suppositories containing 0.25-0.5-1-2 g of active product; ointment, cream, lotion containing 10-25% of active product; vials for parenteral use containing 500-2000 mg of active product.
Le dosi di prodotto somministrabile giornalmente variano secondo le necessità terapeutiche da 1-2 capsule, confetti, compresse 3-4 volte al giorno; 1-3 supposte al giorno; 3-6 cucchiaini di granulato al giorno; 1-2 o più fiale al giorno da 2-5-10 cc per via intramuscolare, endovenosa o per perfusione lenta due o più volte al giorno. The doses of product that can be administered daily vary according to the therapeutic needs from 1-2 capsules, sugared almonds, tablets 3-4 times a day; 1-3 suppositories per day; 3-6 teaspoons of granules per day; 1-2 or more 2-5-10 cc ampoules per day intramuscularly, intravenously or by slow perfusion two or more times a day.
II composto dell'invenzione è preparato convenientemente da Josamicina base e fosfomicina acido (ottenibile dalla fosfomicina sodica per trattamento con resine a scambio ionico) in acetone. The compound of the invention is conveniently prepared from Josamicin base and phosphomycin acid (obtainable from sodium phosphomycin by treatment with ion exchange resins) in acetone.
L'esempio seguente illustra il metodo di preparazione secondo l'invenzione, senza peraltro limitarla in alcun modo. The following example illustrates the preparation method according to the invention, without however limiting it in any way.
Esempio a) Grammi 1,1 (mol. 0,006) di fosfomicina disodica, vengono sciolti in 50 mi di metanolo; si aggiungono 10 g di Amberlite 200 e si lascia sotto agitazione per circa 10 minuti. Example a) 1.1 grams (0.006 mol) of disodium phosphomycin are dissolved in 50 ml of methanol; 10 g of Amberlite 200 are added and it is left under stirring for about 10 minutes.
Si filtra ed il filtrato è evaporato a pressione ridotta. Si ottiene così la fosfomicina acido come residuo oleoso. It is filtered and the filtrate is evaporated under reduced pressure. The acid phosphomycin is thus obtained as an oily residue.
b) Il residuo oleoso ottenuto in a) è sciolto in 10 mi di acetone; a tale soluzione si aggiunge una soluzione in 50 mi di acetone di Josamicina base (5,0 g; mol. 0,006). Si lascia sotto agitazione per circa 10 minuti e quindi si evapora il solvente a pressione ridotta. b) The oily residue obtained in a) is dissolved in 10 ml of acetone; to this solution is added a solution in 50 ml of Josamicin acetone base (5.0 g; 0.006 mol). The mixture is left under stirring for about 10 minutes and then the solvent is evaporated under reduced pressure.
Si ottiene un residuo cristallino che viene lavato con etere etilico anidro. A crystalline residue is obtained which is washed with anhydrous ethyl ether.
Si filtra e si ottiene un prodotto cristallino bianco (6 g). P.f. = 149-158°C; IR (nujol muli): 3450, 1730, 1600, 1510, 1460 cm-1; NMR (DMSO-d6; 60 MHz, standard interno TMS): 0,99 (m), 2,01 (s), 2,4 (s), 3,4 (s), 4,15 (s), 5 (s), 9,6 (s) 8. It is filtered and a white crystalline product (6 g) is obtained. M.P. = 149-158 ° C; IR (nujol muli): 3450, 1730, 1600, 1510, 1460 cm-1; NMR (DMSO-d6; 60 MHz, internal TMS standard): 0.99 (m), 2.01 (s), 2.4 (s), 3.4 (s), 4.15 (s), 5 (s), 9,6 (s) 8.
Sul prodotto così ottenuto sono state condotte prove di tossicità acuta, cronica, teratogenesi, farmacocinetica e di attività antibatterica. Acute, chronic toxicity, teratogenesis, pharmacokinetics and antibacterial activity tests were carried out on the product thus obtained.
PROVE TOSSICOLOGICHE Prove di tossicità acuta TOXICOLOGICAL TESTS Acute toxicity tests
È stata determinata la DL50 del prodotto sia nel topo che nel ratto (topi di ambedue i sessi, ceppo Swiss e ratti di ambedue i sessi, ceppo Wistar) dopo sua somministrazione per via orale oppure per via endovenosa. The LD50 of the product was determined both in the mouse and in the rat (mice of both sexes, Swiss strain and rats of both sexes, Wistar strain) after its administration orally or intravenously.
Per somministrazione endovenosa la DL50 calcolata secondo il metodo di Litchfield e Wilcoxon è risultata essere pari a 418 mg/kg nel ratto e pari a 386 mg/kg nel topo. For intravenous administration the LD50 calculated according to the Litchfield and Wilcoxon method was found to be equal to 418 mg / kg in the rat and equal to 386 mg / kg in the mouse.
Per via orale non si è potuto invece determinare la DL50 sopportando gli animali senza venire a morte fino ad oltre 5000 mg/kg. Orally, it was not possible to determine the LD50 bearing the animals without coming to death up to over 5000 mg / kg.
PROVE DI TOSSICITÀ CRONICA CHRONIC TOXICITY TESTS
È stato somministrato il prodotto sia per via orale che per via sottocutanea ogni giorno per tre mesi consecutivi in tre gruppi di ratti maschi del ceppo Wistar e del peso medio di 155 g di cui un gruppo serviva come controllo e gli altri due ricevevano 250 mg/kg del prodotto per via orale oppure 50 mg/kg per via sottocutanea. The product was administered both orally and subcutaneously every day for three consecutive months in three groups of male rats of the Wistar strain and the average weight of 155 g of which one group served as a control and the other two received 250 mg / kg of the product orally or 50 mg / kg subcutaneously.
Sia prima che durante e dopo questo trattamento tutti i ratti venivano sottoposti ad una serie di esami riguardanti l'accresci5 Both before and during and after this treatment all rats underwent a series of tests concerning growth 5
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654 840 654 840
mento ponderale, la crasi ematica, l'eliminazione urinaria ed i diversi parametri biochimici. Alla fine del trattamento poi tutti gli animali venivano uccisi e sottoposti ad esame anatomopato-logico. weight chin, blood crasis, urinary elimination and various biochemical parameters. At the end of the treatment then all the animals were killed and subjected to an anatomopathological-logical examination.
I risultati di tutti questi esami non hanno rivelato alcuna alterazione di carattere tossico riferibile alla somministrazione del prodotto esaminato. The results of all these tests did not reveal any toxic alterations related to the administration of the product examined.
PROVE TERATOLOGICHE E NEONATALI TERATOLOGICAL AND NEWBORN TESTS
La somministrazione del prodotto nella ratta gravida (50 mg/kg se. oppure 300 mg/kg per os nella ratta del primo al quindicesimo giorno di gravidanza) oppure nella coniglia gravida (50 mg/kg se. oppure 300 mg/kg per os dal settimo al quindicesimo giorno di gravidanza) non ha portato nelle condizioni sperimentali adottate ad alcuna alterazione del normale sviluppo embrionale o fetale. The administration of the product in the pregnant rat (50 mg / kg if or 300 mg / kg per os in the rat of the first to the fifteenth day of pregnancy) or in the pregnant rabbit (50 mg / kg if or 300 mg / kg per os from seventh to fifteenth day of pregnancy) did not lead in the experimental conditions adopted to any alteration of normal embryonic or fetal development.
Anche la crescita e !a sopravvivenza dei neonati osservata dopo trenta giorni dalla nascita appare equiparabile a quella dei controlli. The growth and survival of newborns observed thirty days after birth also appears comparable to that of controls.
PROVE DI ASSORBIMENTO E LIVELLI EMATICI ABSORPTION TESTS AND BLOOD LEVELS
Una delle caratteristiche del nuovo sale di Josamicina è quella di provocare delle concentrazioni ematiche di Josamicina all'incirca doppie di quelle ottenibili con la somministrazione di dosi equivalenti di Josamicina base o di Josamicina propionato. One of the characteristics of the new Josamicina salt is that of causing blood concentrations of Josamicina approximately double those obtainable with the administration of equivalent doses of Josamicina base or Josamicina propionate.
In prove eseguite su conigli New Zealand è stato possibile osservare che la somministrazione per via orale del nuovo sale 5 di Josamicina (dosi equivalenti a 20 e a 75 mg/kg di Josamicina base) si ottengono picchi ematici più elevati di Josamicina (0,794 mcg/ml per il composto della invenzione rispetto a 0,407 mcg/ml per la Josamicina base, in identiche condizioni sperimentali). In tests carried out on New Zealand rabbits it was possible to observe that the oral administration of the new salt 5 of Josamicina (doses equivalent to 20 and 75 mg / kg of Josamicina base) higher blood peaks of Josamicina are obtained (0.794 mcg / ml for the compound of the invention compared to 0.407 mcg / ml for Josamicin base, under identical experimental conditions).
io II nuovo sale si presenta anche capace di indurre concentrazioni ematiche di Josamicina, oltre che più elevate, anche più prolungate nel tempo, rilevabili anche dopo sei ore dalla somministrazione (0,297 mcg/ml per il composto di formula I e 0,139 mcg/ml per la Josamicina base). Il dosaggio della Josa-15 micina è stato eseguito sia con metodo biologico (metodo di Grove D.C. e Randall W.A., 1955) che con metodo cromatografico (HPLC). io The new salt is also capable of inducing blood concentrations of Josamicin, as well as higher, even more prolonged over time, detectable even after six hours from administration (0.297 mcg / ml for the compound of formula I and 0.139 mcg / ml for Josamicina base). The dosage of Josa-15 mycin was performed both with biological method (Grove D.C. and Randall W.A. method, 1955) and with chromatographic method (HPLC).
PROVE MICROBIOLOGICHE MICROBIOLOGICAL TESTS
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Prove eseguite «in vitro» con il metodo della diluizione in agar ed «in vivo» nel topo infettato hanno dimostrato l'analogo spettro antibatterico del nuovo sale con quello riconosciuto per la Josamicina. Tests performed "in vitro" with the method of dilution in agar and "in vivo" in the infected mouse have demonstrated the analogous antibacterial spectrum of the new salt with that recognized for Josamicin.
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Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH546683A CH654840A5 (en) | 1983-10-07 | 1983-10-07 | Compound having an antibiotic activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH546683A CH654840A5 (en) | 1983-10-07 | 1983-10-07 | Compound having an antibiotic activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH654840A5 true CH654840A5 (en) | 1986-03-14 |
Family
ID=4294081
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH546683A CH654840A5 (en) | 1983-10-07 | 1983-10-07 | Compound having an antibiotic activity |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH654840A5 (en) |
-
1983
- 1983-10-07 CH CH546683A patent/CH654840A5/en not_active IP Right Cessation
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