Novahealth Biosystems, LLC

Crinos Industria Farmacobiologica S.p.a.

Baxter International Inc.

Chemi S.p.a.

Other

Sanofi

Nicox S.a.

Sanofi Sa

Inalco S.p.a.

Sclavo, Inc.

Istituto Di Ricerche Chimiche E Biochimiche G Ronzoni

Sigma-tau Research Switzerland S.a.

Annamaria Naggi

Sergio Penco

Giangiacomo Torri

Benito Casu

Lorenzo De Ferra

Maurizio Zenoni

Ennio Lanzarotti

Armando Cedro

Barbara Pinto

Piero Del Soldato

Claudio Pisano

Enrico Petrella

Francesca Benedini

Giuseppe Giannini

Giorgio Zoppetti

Pasqua Anna Oreste

Roberto Porta

Giancarlo Sportoletti

Giuseppe Prino

Elena Vismara

Marisa Mantovani

Israel Vlodavsky

Rodolfo Pescador

Francesco De Santis

Paolo Gresele

Simona Venturini

A glycosaminoglycan derivative endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2-N-desulfated by two steps of oxidation. By the first oxidation, adjacent dials and optionally adjacent OH/NHof the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C2-C3 linkage of the ring of oxidable residues. The invention relates to a process for the preparation of said glycosaminoglycan derivatives and to their use as active ingredients of medicaments.

Carboxylated derivatives of glycosaminoglycans and use as drugs

A glycosaminoglycan derivative which is obtainable by a process that includes the steps of N-desulfation of from 25% to 100% of the N-sulfated residues of a glycosaminoglycan, and oxidation, by periodate at a pH of from 5.5 to 10.0, of from 25% to 100% of the 2-N-, 3-O-non-sulfated glucosamine residues, and of the 2-O-non-sulfated uronic acid residues of said glycosaminoglycan, under conditions effective to convert adjacent diols and adjacent OH/NHto aldehydes. The process further includes reduction, by sodium borohydride, of said oxidized glycosaminoglycan, under conditions effective to convert said aldehydes to alcohols, where the glycosaminoglycan is heparin, low molecular weight heparin, heparan sulfate or fractions thereof.

Derivatives of N-desulfated glycosaminoglycans and use as drugs

A method for the qualification and selection of manufacturing processes, raw materials, intermediates and batch production of pentosan polysulfate based on the identification of acetylated monosaccharide units, including units of xylose substituted with 4-O-methyl-glucuronic which also lead the acetyl group, as structural characterizing units, is disclosed.

Method for the qualification of preparations of pentosan polysulfate, raw materials and production processes thereof

The invention relates to N-desulfated and optionally 2-O-desulfated glycosaminoglycan derivatives, wherein at least part of the adjacent diols and OH/NHhave been converted into the corresponding aldehyde, which aldehydes have been then reduced to the corresponding alcohol. These products are endowed with heparanase inhibitory activity and anti-tumor activity. Said glycosaminoglycan derivatives are obtained from natural or synthetic glycosaminoglycan, preferably from unfractionated heparin, low molecular weight heparins (LMWHs), heparan sulfate or derivatives thereof. The invention further relates to the process for preparation of the same and further to their use as active ingredients of medicaments, also in combination with known established drugs or treatments. The present invention further relates to a process for breaking the C-Clinkage of glucosamine residues of a glycosaminoglycan by oxidation of said glycosaminoglycan.

The invention relates to glycosaminoglycan derivatives, endowed with heparanase inhibitory activity and antitumor activity, bearing carboxylate groups in positions 2 and 3 of at least part of the glycosaminoglycan residues, and to the process for preparing the same. The glycosaminoglycan derivatives of the present invention are generated starting from natural or synthetic glycosaminoglycans, preferably heparin or low molecular weight heparin, optionally 2-O- and 2N-desulfated by two steps of oxidation. By the first oxidation, adjacent diols and optionally adjacent OH/NHof the glycosaminoglycan residues are converted to aldehydes and by the second oxidation said dialdehydes are converted to carboxylate groups. The first oxidation preferably leads to the cleavage of C-Clinkage of the ring of oxidable residues. The invention further relates to a process for the preparation of said glycosaminoglycan derivatives and further to their use as active ingredients of medicaments. Furthermore, the invention relates to pharmaceutical compositions comprising di/tricarboxylated heparin derivatives, as active agent.

The present invention is directed to sulfated oligosaccharides having 4, 5 or 6 saccharidic units and wherein a glycosidic bond between two saccharide units is substituted by a C&#x2014;C bond, and wherein the sulfation degree expressed as percentage of OH groups substituted by a OSOgroup is comprised between 50 and 100%. The sulfated oligosaccharides according to the invention are useful as a drug, in particular in the treatment of angiogenesis, metastasis, and inflammation.

Mimetics of sulfated oligosaccharides

The present invention provides a peritoneal dialysis solution that contains heat stable osmotic agents such as D-glucitols, gluconic acids and alkylglycosides produced the reduction, oxidation or glycosylation of icodextrins respectively. As a result, osmotic agents that are stable under autoclaving or heat sterilization conditions are provided which reduces the amount of bioincompatible materials in the sterilized peritoneal dialysis solutions. Methods of preparing the D-glucitols, gluconic acids and alkylglycosides are disclosed.

Peritoneal dialysis solution containing modified icodextrins

The present invention provides a new class of compounds presenting a high compatibility with tissues and organic fluids. Such new compounds are polysaccharides essentially formed of units of uronic acid and/or hexosamine, containing nitro groups &#x2014;ONOcovalently bonded to the saccharide structure. Preferably, the polysaccharides according to the invention are prevalently formed of disaccharide repeating units formed of uronic acid and hexosamine. These compounds, in psychological conditions, selectively release NO, allowing a reduction in the amount of NO needed to achieve a determined therapeutical effect. This result has been achieved by functionalizing polysaccharides essentially formed of units of uronic acid and/or hexosamine, with subsituents containing a ONO2 ? group.

Nitroderivatives of polysaccharides

Sulphaminoheparosansulphates obtainable from the,K5 polysaccharide by deacetilation and the subsequent sulfation with the sulphuric anhydride/trimethylamine adduct carried out at 0&deg; C., for times ranging from 0.25 to 2 hours and using a reactant/polysaccharide ratio (SO,equivalents/available OH groups equivalents) equal to 5 have been found having high anti-metastatic activity and low anticoagulant activity.

Semi-synthetic sulphaminoheparosansulphates having high anti-metastatic activity and reduced haemorrhagic risk

Glycosaminoglycans having high antithrombotic activity in vitro, obtained by various kinds of glycosaminoglycans supersulfated by the preparation of the salt of an organic base of the starting supersaturated glycosaminoglycan, by partial solvolytic desulfation of said salt and N-resulfation of said partially desulfated product.

Glycosaminoglycans having high antithrombotic activity

By ultrafiltration of an aqueous solution wherein there have been formerly dissolved alfa-cyclodextrin and a raw lipidic mixture, the latter characterized in that it contains monosialoganglioside (GMl) either as the sole ganglioside or otherwise in a prevailing quantity over the other associated gangliosides, and after the removal of cyclodextrin at the end of the process, it is obtained GMl with a titer of at least 95%. The present invention concerns also the intermediate complex that it is being formed between the hereabove said monosialoganglioside and alfa-cyclodextrin.

Process for the isolation and purification of monosialoganglioside from

Heparins, heparin fractions or fragments, optionally salified with pharmaceutically acceptable cations, having molecular weight ranging from 1.000 to 30.000 D, characterized by an EDTA content lower than 0.1%, by the absence, in the .sup.1 H--NMR spectra, of the signals due to EDTA between 2.50 and 4.00 p.p.m. and substantially free from bleeding effect and optionally free from signals, in the .sup.13 C--NMR spectrum, from 80 to 86 ppm.

Process for preparing EDTA-free heparins, heparin fractions and fragments

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Annamaria Naggi