A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/718 (2006.01) A61K 31/335 (2006.01) A61K 31/35 (2006.01) A61K 31/7048 (2006.01) A61K 31/715 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01) C08B 31/00 (2006.01) C08B 31/04 (2006.01) C08B 31/08 (2006.01) C08B 31/12 (2006.01) C08B 31/16 (2006.01) C08B 33/00 (2006.01) C08B 33/02 (2006.01) C08B 33/04 (2006.01) C08B 33/06 (2006.01) C08B 35/00 (2006.01) C08B 35/02 (2006.01) C08B 35/04 (2006.01) C08B 35/06 (2006.01)
Patent
CA 2446205
The invention relates to novel pharmaceutical forms for antibiotics containing amino sugar, amphotericin B, daunorubicin and doxorubicin, in which the known side effects are reduced and which can be used in a simple manner. The antimycotic agent B is nephrotoxic. The cytostatic agents daunorubicin and doxorubicin are highly cardiotoxic. The novel pharmaceutical forms are antibiotic-starch conjugates, wherein the antibiotic is combined with the polysaccharide at the reducing end thereof by means of a peptide bond. According to the invention, said bond is carried out by means of J~2-oxidation of the starch derivative at the reducing end thereof in an aqueous alkaline solution, and by coupling the starch derivative oxidised thereby to the antibiotic in an organic solution. The conjugates obtained are less toxic. The polysaccharide part can be decomposed by serum-.alpha.-amylase and the peptide bond can be accessed by an enzymatic attack.
L'invention concerne de nouvelles formes gal~niques pour les antibiotiques ~ base de sucre amin~, Amphot~ricine B, Daunorubicine et Doxorubicine, dans lesquelles les effets secondaires connus sont r~duits et qui s'utilisent de manire simple. L'antibiotique Amphot~ricine B est n~phrotoxique. Les cytostatiques que sont la Daunorubicine et la Doxorubicine sont fortement cardiotoxiques. Les nouvelles formes gal~niques sont des conjugu~s antibiotiques-amidon, l'antibiotique ~tant combin~ au polysaccharide ~ son extr~mit~ r~ductrice par l'interm~diaire d'une liaison peptidique. Selon l'invention, cette liaison s'effectue par oxydation J´2? du d~riv~ amidon ~ son extr~mit~ r~ductrice en solution alcaline aqueuse, puis par couplage du d~riv~ amidon ainsi oxyd~ avec l'antibiotique en solution organique. Les conjugu~s obtenus sont moins toxiques. La part de polysaccharide peut Útre d~compos~e par s~rum-.alpha.-amylase et la liaison peptidique est accessible ~ un agent enzymatique.
Fetherstonhaugh & Co.
Fresenius Kabi Deutschland Gmbh
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