Rhone-poulenc Industries

Rhone-poulenc Specialites Chimiques

Flamel Technologies

Adocia

Orogil

Rhone-poulenc Chimie

Rhone-poulenc Chimie De Base

Rhone-poulenc Specialties Chimiques

Flamel Ireland Limited

Rhone-progil

Flamel Technologies (societe Anonyme)

Societe Orogil

Gerard Soula

Olivier Soula

Remi Soula

Remi Meyrueix

Catherine Castan

Louis Linguenheld

Jean-Luc Lepage

Jean-Claude Morawski

Jean Machurat

Gerard Mignani

Florence Guimberteau

Richard Charvet

Jean-Michel Grosselin

Jean-Louis Locatelli

Alain Lemercier

Rafael Jorda

Joel Le Ludec

Sylvain Huille

Philippe Duteurtre

Jacques Cavezzan

Michel Desbois

Alexandre Geissler

Claude Millet

Pierre Autant

Alain Constancis

Christian Gagnieu

Daniel Michelet

David Duracher

Florence Nicolas

Frederic Dargelas

Jean-Philippe Selles

Emmanuel Dauty

Christian Simonnet

Valérie Legrand

Guy Dubreucq

Jacques Metzger

Martin Gaudier

Latifa Dahri-Correia

Jean-Paul Lefevre

R Ramanadin

Jose Correia

Alain Roustan

Maurice Balme

Jeff Tonnar

Louis Lena

A composition in aqueous solution includes insulin and at least one substituted anionic compound chosen from substituted anionic compounds consisting of a backbone formed from a discrete number u of between 1 and 8 (1&#x2264;u&#x2264;8) of identical or different saccharide units, linked via identical or different glycoside bonds, the saccharide units being chosen from the group consisting of hexoses, in cyclic form or in open reduced form, said compound comprising partially substituted carboxyl functional groups, the unsubstituted carboxyl functional groups being salifiable. A pharmaceutical formulation including the composition is also set forth.

Rapid-acting insulin formulation comprising a substituted anionic compound

The field of the invention is that of oral pharmaceutical medicinal products or compositions, more particularly of the type of those comprising one or more active principles. The aim of the invention is to provide an improved oral medicinal product that can be administered in one or more daily doses, with modified release of active principle (in particular an active principle), for improving the prophylactic and therapeutic efficacy of such a medicinal product. This aim is achieved by means of the multimicrocapsular oral pharmaceutical form according to the invention in which the release of the AP is controlled by means of a double mechanism of triggering the release: 'time triggering' and 'pH triggering'. This medicinal product comprises microcapsules with modified release of active principle, each containing a core comprising the active principle and one or more swelling agents, and at least one coating making possible the modified release of the active principle.

Oral medicinal product with modified release of at least one active principle in multimicrocapsular form

A composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, includes at least a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and a dextran substituted by radicals carrying carboxylate charges and hydrophobic radicals. Single-dose formulations at a pH of between 7 and 7.8 includes a basal insulin whose isoelectric point is between 5.8 and 8.5 and a prandial insulin.

Injectable solution at pH 7 comprising at least one basal insulin whose PI is between 5.8 and 8.5

The invention relates to a complex between an insulin and a polysaccharide comprising carboxyl functional groups, said polysaccharide being chosen from polysaccharides functionalized with at least one phenylalanine derivative, noted Phe, said phenylalanine derivative being chosen from the group consisting of phenylalanine and its alkali metal cation salts, phenylalaninol, phenylalaninamide and ethylbenzylamine or from phenylalanine esters, and said insulin being either a human insulin or an insulin analog. The invention also relates to a pharmaceutical composition comprising at least one complex according to the invention, especially in the form of an injectable solution.

Fast-acting insulin formulation

The invention relates to a dextran functionalized by at least one hydrophobic alpha-amino acid radical, said alpha-amino acid being grafted or bonded to the dextran by a bonding arm and a functional group. A hydrophobic amino acid radical is understood as being the product of coupling between the amine of the amino acid and an acid carried by the bonding arm, said dextran being amphiphilic at neutral pH. In an embodiment, the hydrophobic amino acid is selected from tryptophan derivatives, such as tryptophan, tryptophanol, tryptophanamide, 2-indole ethyl-amine and their alkaline cation salts. The present invention relates also to a pharmaceutical composition comprising one of the dextrans according to the invention.

Dextran functionalized by hydrophobic amino acids

Osteogenic compositions composed of a coprecipitate that contains at least one insoluble calcium salt and at least one complex between an osteogenic protein and a polysaccharide, the coprecipitate being in divided form, are described. Kits are also described, as are a process for preparing the coprecipitate in divided form, containing at least one insoluble calcium salt and at least one complex between an osteogenic protein and a polysaccharide.

Administration form of osteogenic protein complexes

The invention relates to a polysaccharide comprising carboxyl functional groups, one at least of which is substituted by a derivative of a hydrophobic alcohol. The invention also relates to a pharmaceutical composition comprising one of the polysaccharides according to the invention and at least one active principle. It also relates to a pharmaceutical composition, wherein the active principle is chosen from the group consisting of proteins, glycoproteins, peptides and nonpeptide therapeutic molecules. The invention also relates to the use of the functionalized polysaccharides according to the invention in the preparation of pharmaceutical compositions as described above.

Polysaccharides comprising carboxyl functional groups substituted by a hydrophobic alcohol derivative

The invention relates to an amphiphilic-BMP polymer complex which is physically and chemically stable and soluble in water, characterized in that: The invention also relates to the process for preparing the amphiphilic-BMP polymer complex in an aqueous medium and in the absence of organic solvents likely to denature the protein. The invention also relates to therapeutic compositions of an amphiphilic-BMP polymer complex according to the invention.

Complexes between an amphiphilic polymer and an osteogenic protein belonging to the family of BMPs

The invention relates to a complex consisted of a polysaccharide and an HBP, said polysaccharide being consisted from glycoside bonds of (1,6) and/or (1,4) and/or (1,3) and/or (1,2) type and functionalized with at least one salifiable or salified tryptophan derivative. The invention also relates to a pharmaceutical composition comprising a complex according to the invention and to the use of a polysaccharide consisted of glycoside bonds of (1,6) and/or (1,4) and/or (1,3) and/or (1,2) type and functionalized with at least one salifiable or salified tryptophan derivative, for the preparation of a pharmaceutical formulation of stable HBPs.

Complex consisted of a polysaccharide and an HBP

Physically and chemically stable, water-soluble, amphiphilic polymer-PDGF complex, characterized in that the amphiphilic polymers include a hydrophilic polymeric backbone functionalized with hydrophobic substituents and hydrophilic groups.

Complex polymere amphiphile-PDGF

The invention concerns an oral galenic form for prolonged release of anti-hyperglycaemic (metformin) active principles. Said medicine enables to obtain an efficient therapeutic protection over 24 hours by overcoming the problems of bypass of the absorption window and the massive localised release of active principles. Therefor, said medicine comprises several thousand anti-hyperglycaemic (metformin) microcapsules each consisting of a core comprising at least an anti-hyperglycaemic agent and of a coating film applied on the core and enabling the prolonged release in vivo of the anti-hyperglycaemic agent. Said microcapsules have a grain size distribution ranging between 50 and 100 microns. The reproducibility of the transit kinetics and hence of bioavailability are very high. There results for the patient a lesser risk of hyperglycaemic or hypoglycaemic. The invention also concerns the preparation of said medicine and the use of a plurality of said microcapsules for making an anti-hyperglycaemic medicine. The invention is applicable to the treatment of type II diabetes.

Medicine based on anti-hyperglycaemic microcapsules with prolonged release and method for preparing same

The invention relates to vectors for delivering medicinal, nutritional, plant-protection or cosmetic active principles, these delivery particles being of small, controllable and adjustable particle size, which protect the active principle, and being biocompatible, biodegradable, non-immunogenic, stable and free of solvent. The particles do not denature the active principle and allow the active principle to be released. The microparticles of the invention are of a cohesive structure made of a physicochemically stable and integral composite gel which includes an oil such as coconut oil, an aqueous phase and a linear, non-crosslinked copolyamino acid of Leu/Glu type (random or diblock). The microparticles have a controllable and adjustable size of between 0.05 and 500 &mgr;m.

Composite gel microparticles as active principle carriers

The present invention relates to microcapsules for the oral administration of medicinal and/or nutritional active principles (AP), which are smaller than or equal to 1000 .mu.m in size. These microcapsules consist of particles which are coated with a coating material consisting of a mixture of a film-forming polymer derivative, a hydrophobic plasticizer, a functional agent and a nitrogen-containing polymer. These microcapsules are also characterized by their ability to remain in the small intestine for a long time (at least 5 hours) and to allow, during the residence, release and absorption of the AP. The invention also relates to a process for the production of the said microcapsules.

Medicinal and/or nutritional microcapsules for oral administration

Aerosol composition for forming a hydrated membrane, and applications

Growing community of inventors

Meyzieu, France

Gerard Soula