CH501004A - Theophylline 7-(beta-ethane sulphonic acid) Salts of (I) with mineral and organic bases. (I) and its salts have anti-fungal and anti-bacterial activ - Google Patents
Theophylline 7-(beta-ethane sulphonic acid) Salts of (I) with mineral and organic bases. (I) and its salts have anti-fungal and anti-bacterial activInfo
- Publication number
- CH501004A CH501004A CH2870A CH2870A CH501004A CH 501004 A CH501004 A CH 501004A CH 2870 A CH2870 A CH 2870A CH 2870 A CH2870 A CH 2870A CH 501004 A CH501004 A CH 501004A
- Authority
- CH
- Switzerland
- Prior art keywords
- salts
- sep
- theophylline
- fungal
- beta
- Prior art date
Links
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 229960000278 theophylline Drugs 0.000 title claims abstract description 22
- 150000003839 salts Chemical class 0.000 title claims abstract description 18
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 title abstract description 3
- 239000011707 mineral Substances 0.000 title abstract description 3
- 230000000843 anti-fungal effect Effects 0.000 title abstract 2
- 150000007530 organic bases Chemical class 0.000 title abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 9
- 229940088710 antibiotic agent Drugs 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 6
- 229930101283 tetracycline Natural products 0.000 claims description 6
- 239000004098 Tetracycline Substances 0.000 claims description 5
- 229960002180 tetracycline Drugs 0.000 claims description 5
- 235000019364 tetracycline Nutrition 0.000 claims description 5
- PGBHMTALBVVCIT-VZXHOKRSSA-N neomycin C Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VZXHOKRSSA-N 0.000 claims description 4
- 150000003522 tetracyclines Chemical class 0.000 claims description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 3
- 230000003115 biocidal effect Effects 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 3
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 claims description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- -1 theomycin B Natural products 0.000 claims description 2
- 229960003276 erythromycin Drugs 0.000 claims 1
- 229960000318 kanamycin Drugs 0.000 claims 1
- 229930027917 kanamycin Natural products 0.000 claims 1
- 229930182823 kanamycin A Natural products 0.000 claims 1
- 229960005322 streptomycin Drugs 0.000 claims 1
- 229920003043 Cellulose fiber Polymers 0.000 abstract description 2
- 239000000443 aerosol Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000007935 neutral effect Effects 0.000 abstract description 2
- 229920002994 synthetic fiber Polymers 0.000 abstract description 2
- 241000894006 Bacteria Species 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000000855 fermentation Methods 0.000 abstract 1
- 230000004151 fermentation Effects 0.000 abstract 1
- 239000004753 textile Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003221 ear drop Substances 0.000 description 2
- 229940047652 ear drops Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 229940051866 mouthwash Drugs 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 229940100662 nasal drops Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- RPABDKTXMKOGKI-OYTUFZPASA-N 6-methyl-n-[2-[(2s,5s,8s,11s,14s,17s,20s,23s)-8,11,14,20-tetrakis(2-aminoethyl)-5-[(1r)-1-hydroxyethyl]-17,23-bis(2-methylpropyl)-3,6,9,12,15,18,21,24-octaoxo-1,4,7,10,13,16,19,22-octazacyclotetracos-2-yl]ethyl]octanamide Chemical class CCC(C)CCCCC(=O)NCC[C@@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H]([C@@H](C)O)NC1=O RPABDKTXMKOGKI-OYTUFZPASA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960003704 framycetin Drugs 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical class N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- UOZODPSAJZTQNH-LSWIJEOBSA-N paromomycin Chemical class N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO UOZODPSAJZTQNH-LSWIJEOBSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940098956 topical powder Drugs 0.000 description 1
- 229940041677 topical spray Drugs 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Theophylline 7-(beta-ethane sulphonic acid) - Salts of (I) with mineral and organic bases. - (I) and its salts have anti-fungal and anti-bacterial activity. The salts are used in the paper- and textile industry against (fungi-, bacteria and unpleasant odours stemming from fermentation. They may be used in pharmaceuticals because of their high solubility in water, esp. for neutral aqueous injectable solutions or preparations for aerosols. The salts with basic antibiotics give improved activity. They may also be used for medical dressings of cellulose- or synthetic fibres for external application.
Description
Procédé de préparation de sels de l'acide théophylline 7-[ss-éthane sulfoniquel avec les antibiotiques basiques La présente invention a pour objet un procédé de préparation de nouveaux sels de l'acide théophylline 7- [(3-éthane sulfonique] avec les antibiotiques basiques.
L'acide théophylline 7-[ss-éthane sulfonique] répond à la formule
EMI0001.0002
Ledit acide est un acide fort qui, par salification, fournit des sels bien définis et stables, les sels ainsi formés sont solubles dans l'eau.
L'invention a donc pour objet un procédé d'obten tion des sels hydrosolubles de l'acide théophylline 7-[P éthane sulfonique] avec les antibiotiques basiques et notamment les sels d'antibiotiques basiques comme par exemple les sels de néomycine B ou de néomycine C, le sel de tétracycline, le sel de streptomycine, le sel d'érythromycine, le :sel de kanamycine, le sel de coli- mycine, le sel d'hygromycine ou le sel d'hydroxy- mycine.
Les sels de l'acide théophylline 7-[ss-éthane sulfo- nique] avec les antibiotiques basiques peuvent être uti lisés dans l'industrie pharmoceutique grâce à leur solu bilité dans l'eau. Ils permettent la préparation de solutés injectables aqueux neutres ou de préparations pour aérosols. Les formes injectables tirent de cette hydrosolubilité une activité, une diffusibilité ou une vitesse d'action nettement améliorées.
Ils peuvent enfin servir à la préparation de panse ments médicamenteux en fibres cellulosiques ou en fibres artificielles lorsqu'une action thérapeutique externe est préconisée.
Parmi les sels susceptibles d'être préparés par le procédé selon l'invention, le théophylline 7-[ss-éthane sul- fonate] de tétracycline présente un intérêt particulier. Il est doté, en effet, de propriétés pharmacologiques inté ressantes, notamment une action antibiotique et anti bactérienne importante.
Il peut être utilisé pour le traitement des staphylo coccies, des streptococcies et des infections provoquées par des germes à Gram négatif, comme par exemple, les bacilles typhiques.
Le théophylline 7-(ss-éthane sulfonate) de tétracycline est utilisé par voie buccale, transcutanée ou par voie locale en application topique sur la peau et les muqueu ses ou par voie rectale.
Il peut se présenter sous forme de solutions injec tables, conditionnées en ampoules, en flacons à prises multiples ou de poudre stérile pour préparation extem poranée de solutions injectables, de comprimés, de com primés enrobés, de poudre aromatisée, de granulés, d'émulsions, de sirops, de suppositoires, d'ovules, de comprimés intravaginaux, de pommades, de crèmes, de gouttes nasales et auriculaires, de collyre, de collutoire et de poudres topiques en pulvérisations.
La posologie utile s'échelonne entre 200 mg et 800 mg par prise et 1 à 4 g par jour chez l'adulte en fonction de la voie d'administration.
Les formes pharmaceutiques telles que solutions in jectables, poudre stérile pour préparation extemporanée de solutions injectables, comprimés, comprimés enrobés, poudre aromatisée, granulés, émulsions, sirops, suppo sitoires, ovules, comprimés intravaginaux, pommades, crèmes, gouttes nasales et auriculaires, collyre, collutoire et poudres topiques en pulvérisations, sont préparées se lon les procédés usuels.
Les sels de l'acide théophylline 7-[ss-éthane sulfoni- que] avec les antibiotiques basiques sont préparés par réaction dudit acide avec un antibiotique basique, dans un solvant inerte, après quoi l'on isole le sel formé.
La salification est effectuée de préférence dans l'eau. Elle peut également être effectuée dans un solvant orga nique en présence ou en l'absence d'eau.
L'acide théophylline 7-[ss-éthane sulfurique] est ob tenu en soumettant le théophylline 7-[ss-chloroéthyle] à l'action d'un sulfite métallique, puis en acidifiant au moyen d'un acide minéral fort la solution de théophyl line 7-[ss-éthane sulfonate] métallique ainsi obtenue.
<I>Préparation de l'acide théophylline</I> 7-[ss-éthane sulfonique] On porte au reflux, pendant sept heures, une solu tion de 72,6 g de théophylline 7(ss-chloro éthyle) (obtenu selon le procédé décrit par G. di Paco, Ann. chim. Ro- ma, 47, 698-704, 1957) dans 1000 cm3 d'eau et une solu tion de 41,6 g de sulfite de sodium dans 200 cm d'eau ; on filtre et la solution est évaporée à sec sous pression réduite.
Le résidu est repris par 200 cm3 d'acide chlor hydrique ; on filtre le précipité minéral et évapore à sec le filtrat. On lave le résidu à l'alcool et sèche; on obtient 68 g d'acide théophylline 7 (ss-éthane.sulfonique) que l'on purifie par dissolution dans l'eau et précipita tion par l'acétone (Rendement: 65 %).
L'acide théophylline 7 (ss-éthane sulfonique) se pré sente sous forme de cristaux incolores, très solubles dans l'eau, insolubles dans l'alcool, l'acétone, l'éther et le benzène, fondant à 3200 C.
EMI0002.0006
Analyse: <SEP> C9H12N405S <SEP> = <SEP> 288,29
<tb> Calculé <SEP> : <SEP> C <SEP> % <SEP> 37,50 <SEP> H <SEP> % <SEP> 4,19 <SEP> N <SEP> % <SEP> 19,44
<tb> Trouvé <SEP> : <SEP> C <SEP> % <SEP> 37,3 <SEP> H <SEP> % <SEP> 4,3 <SEP> N <SEP> % <SEP> 19,1 Spectre I.R. (Nujol) Absence de NH vers 3300-3500 cm-Ú Présence de C=O à 1675 cm-' Présence de R-S03(-) à 1150 et l060 cm-1 Pour autant que l'on sache, ce composé n'est pas décrit dans la littérature.
Exemple Théophylline 7-(ss-éthane sulfonate) de tétracycline On dissout<B>26,31</B> g de tétracycline base dans 1050 cm de méthanol et ajoute 16,72 g d'acide théophyl line 7-(ss-éthane sulfonique) ; on évapore à sec sous pres sion réduite, lave le résidu à l'éther et sèche, on obtient 43 g de théophylline 7-(ss-éthane sulfonate) de tétra cycline sous forme d'une poudre microcristalline jaune clair, soluble dans l'eau et le méthanol, peu soluble dans l'éthanol, insoluble dans l'éther, fondant vers 2500 C avec décomposition, son pouvoir rotatoire est
EMI0002.0008
[a]20D= <SEP> -168 <SEP> <SEP> 1 <SEP> (c <SEP> = <SEP> 1%, <SEP> eau).
<tb> Analyse <SEP> : <SEP> C31H36N6013S <SEP> = <SEP> 732,71
<tb> Calculé <SEP> : <SEP> N% <SEP> 11,47
<tb> Trouvé <SEP> :
<SEP> N <SEP> % <SEP> 11,49 Pour autant que l'on sache, ce composé n'est pas décrit dans la littérature.
Process for the preparation of salts of theophylline 7- [ss-ethane sulfonic acid with basic antibiotics The present invention relates to a process for the preparation of new salts of theophylline 7- [(3-ethanesulfonic acid] with the basic antibiotics. basic antibiotics.
Theophylline 7- [ss-ethanesulfonic acid] has the formula
EMI0001.0002
Said acid is a strong acid which, on salification, provides well-defined and stable salts, the salts thus formed are soluble in water.
The subject of the invention is therefore a process for obtaining the water-soluble salts of theophylline 7- [P ethanesulfonic acid] with basic antibiotics and in particular the salts of basic antibiotics such as for example the salts of neomycin B or of neomycin C, tetracycline salt, streptomycin salt, erythromycin salt, kanamycin salt, colimycin salt, hygromycin salt or hydroxymycin salt.
The salts of theophylline 7- [ss-ethanesulfonic acid] with basic antibiotics can be used in the pharmaceutical industry due to their water solubility. They allow the preparation of neutral aqueous injectable solutions or aerosol preparations. The injectable forms derive from this water solubility a markedly improved activity, diffusibility or speed of action.
Finally, they can be used for the preparation of medicated dressings made from cellulose fibers or artificial fibers when an external therapeutic action is recommended.
Among the salts capable of being prepared by the process according to the invention, tetracycline theophylline 7- [ss-ethane sulphonate] is of particular interest. It is endowed, in fact, with interesting pharmacological properties, in particular an important antibiotic and anti-bacterial action.
It can be used for the treatment of staphylococcal disease, streptococcal disease and infections caused by gram-negative germs, such as, for example, typhoid bacilli.
Tetracycline theophylline 7- (ss-ethanesulphonate) is used orally, transcutaneously or locally as topical application to the skin and mucous membranes or rectally.
It can be in the form of injectable solutions, packaged in ampoules, in multi-dose vials or as sterile powder for external preparation of injectable solutions, tablets, coated tablets, flavored powder, granules, emulsions. , syrups, suppositories, ova, intravaginal tablets, ointments, creams, nasal and ear drops, eye drops, mouthwash and topical powder sprays.
The useful dosage ranges between 200 mg and 800 mg per dose and 1 to 4 g per day in adults depending on the route of administration.
Pharmaceutical forms such as injectable solutions, sterile powder for extemporaneous preparation of injectable solutions, tablets, coated tablets, flavored powder, granules, emulsions, syrups, suppositories, ova, intravaginal tablets, ointments, creams, nasal and ear drops, eye drops , mouthwash and topical spray powders are prepared according to the usual methods.
The salts of theophylline 7- [ss-ethanesulfonic acid] with basic antibiotics are prepared by reacting said acid with a basic antibiotic, in an inert solvent, after which the salt formed is isolated.
The salification is preferably carried out in water. It can also be carried out in an organic solvent in the presence or absence of water.
The theophylline 7- [ss-ethane sulfuric acid] is obtained by subjecting the theophylline 7- [ss-chloroethyl] to the action of a metal sulphite, then by acidifying the solution with a strong mineral acid. theophyl line 7- [ss-ethane sulfonate] metal thus obtained.
<I> Preparation of theophylline acid </I> 7- [ss-ethane sulfonic] A solution of 72.6 g of theophylline 7 (ss-chloroethyl) (obtained according to the process described by G. di Paco, Ann. chim. Ro- ma, 47, 698-704, 1957) in 1000 cm3 of water and a solution of 41.6 g of sodium sulphite in 200 cm3 of water ; it is filtered and the solution is evaporated to dryness under reduced pressure.
The residue is taken up in 200 cm3 of hydrochloric acid; the inorganic precipitate is filtered off and the filtrate evaporated to dryness. The residue is washed with alcohol and dried; 68 g of theophylline 7 (ss-ethane.sulfonic acid) are obtained, which is purified by dissolving in water and precipitating with acetone (yield: 65%).
Theophylline 7 (ss-ethanesulphonic acid) occurs as colorless crystals, very soluble in water, insoluble in alcohol, acetone, ether and benzene, melting at 3200 C.
EMI0002.0006
Analysis: <SEP> C9H12N405S <SEP> = <SEP> 288.29
<tb> Calculated <SEP>: <SEP> C <SEP>% <SEP> 37.50 <SEP> H <SEP>% <SEP> 4.19 <SEP> N <SEP>% <SEP> 19.44
<tb> Found <SEP>: <SEP> C <SEP>% <SEP> 37.3 <SEP> H <SEP>% <SEP> 4.3 <SEP> N <SEP>% <SEP> 19.1 IR spectrum (Nujol) Absence of NH around 3300-3500 cm-Ú Presence of C = O at 1675 cm- 'Presence of R-S03 (-) at 1150 and l060 cm-1 As far as we know, this compound is not described in the literature.
Example Theophylline 7- (ss-ethane sulfonate) of tetracycline <B> 26.31 </B> g of tetracycline base is dissolved in 1050 cm 3 of methanol and 16.72 g of theophyl line 7- (ss-ethane sulfonic); evaporated to dryness under reduced pressure, the residue washed with ether and dried, 43 g of tetra cyclin theophylline 7- (ss-ethane sulfonate) are obtained in the form of a light yellow microcrystalline powder, soluble in water and methanol, sparingly soluble in ethanol, insoluble in ether, melting at around 2500 C with decomposition, its optical rotation is
EMI0002.0008
[a] 20D = <SEP> -168 <SEP> <SEP> 1 <SEP> (c <SEP> = <SEP> 1%, <SEP> water).
<tb> Analysis <SEP>: <SEP> C31H36N6013S <SEP> = <SEP> 732.71
<tb> Calculated <SEP>: <SEP> N% <SEP> 11.47
<tb> Found <SEP>:
<SEP> N <SEP>% <SEP> 11.49 As far as we know, this compound has not been described in the literature.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR107454 | 1967-05-23 | ||
| FR116130A FR6525M (en) | 1967-05-23 | 1967-07-28 | |
| CH746368A CH496015A (en) | 1967-05-23 | 1968-05-20 | Process for obtaining a novel acid derived from theophylline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH501004A true CH501004A (en) | 1970-12-31 |
Family
ID=27175798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH2870A CH501004A (en) | 1967-05-23 | 1968-05-20 | Theophylline 7-(beta-ethane sulphonic acid) Salts of (I) with mineral and organic bases. (I) and its salts have anti-fungal and anti-bacterial activ |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH501004A (en) |
-
1968
- 1968-05-20 CH CH2870A patent/CH501004A/en not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1234106A (en) | COMPOUNDS HAVING ANTIINFLAMMATORY ACTIVITY, OBTAINED BY COMPLEXATION WITH .beta.-CYCLODEXTRIN, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM | |
| EP0714386B1 (en) | Water-soluble nimesulide salt, and uses thereof for the treatment of inflammations | |
| EP0885234B1 (en) | Novel erythromycin derivatives, method for preparing same, and use thereof as drugs | |
| EP0716093A1 (en) | Erythromycin derivatives, their process of preparation and application as medicaments | |
| EP0051023A1 (en) | Derivatives of the benzoyl and alpha hydroxybenzyl-phenyl osides family, method for their preparation and their therapeutic application | |
| FR2601016A1 (en) | NOVEL 1H, 3H-PYRROLO (1,2-C) THIAZOLE DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM | |
| CH501004A (en) | Theophylline 7-(beta-ethane sulphonic acid) Salts of (I) with mineral and organic bases. (I) and its salts have anti-fungal and anti-bacterial activ | |
| DE3787437T2 (en) | SIALOSYL CHOLESTEROL, METHOD FOR THE PRODUCTION THEREOF, AND MEDICINAL PRODUCTS FOR TREATING DISEASES OF THE NERVOUS SYSTEM. | |
| US4782141A (en) | Process for preparing primycin salts | |
| CA1046058A (en) | Preparation of a novel aminoglycosidic derivative and its salts thereof | |
| EP0288898B1 (en) | Substituted chinoxalyl-imidazolidine-2,4-diones, process for their preparation, their use as medicaments and pharmacological preparations | |
| WO1997013776A2 (en) | Novel amine derivatives of epipodophyllotoxin 2', 3'-dideoxyglycosides, preparation method therefor and use thereof as a drug and for treating cancer | |
| CA2142560C (en) | Acronycin analogues; process for preparing the same and pharmaceutical compositions containing them | |
| CH637650A5 (en) | PROCESS FOR THE PREPARATION OF A CHROMONE CARBOXYLIC ACID. | |
| FR2701261A1 (en) | New glucuronide compounds of diosmetin, process for their preparation and the pharmaceutical compositions containing them | |
| IT9022047A1 (en) | 13-DESOSSO-4'-deoxy-4'-IODOANTRACICLINE | |
| FR2534588A2 (en) | New erythromycin-derived oximes, process for preparing them and their use as medicinal products | |
| EP0006784A2 (en) | Derivatives of L-cysteine, their use as medicaments and process for their preparation | |
| JPH0341459B2 (en) | ||
| CH469807A (en) | Process for preparing a new erythromycin salt | |
| JPH07116216B2 (en) | Method for producing sialosil cholesterol | |
| FR2491927A1 (en) | WATER-SOLUBLE CEPHALEXIN DERIVATIVES AND PROCESS FOR THEIR PREPARATION | |
| FR2718M (en) | ||
| CH404649A (en) | Process for preparing a new colchicium derivative | |
| CA1082697A (en) | Process for the preparation of a deoxystreptamine and of its salts thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |