Flamel Technologies

Flamel Technologies (societe Anonyme)

Florence Nicolas

Olivier Soula

Rémi Meyrueix

Gerard Soula

Remi Meyrueix

Alain Constancis

Christian Gagnieu

Gauthier Pouliquen

Nathan J Bryson

Sylvain Huille

G&eacute;rard Soula

Nathan Brison

The present invention relates to novel pharmaceutical formulations based on stable, fluid aqueous colloidal suspensions for the prolonged release of active principle(s), particularly protein active principle(s), and to the applications, especially therapeutic applications, of these formulations. The object of the invention is to propose a fluid pharmaceutical formulation for the prolonged release of active principle(s) that makes it possible, after parenteral injection, to increase significantly the in vivo release time of a therapeutic protein while at the same time reducing the plasma concentration peak of the active protein, said formulation furthermore being stable on storage and also being biocompatible, biodegradable, non-toxic and non-immunogenic and having a good local tolerance. The formulation according to the invention is an aqueous colloidal suspension of low viscosity based on submicronic particles of water-soluble biodegradable polymer PO carrying hydrophobic groups (HG), said particles being non-covalently associated with at least one active principle (AP) and forming a gelled deposit at the injection site, this gelling being caused by a protein present in the physiological medium.

Pharmaceutical formulations for the prolonged release of active principle(s) and their applications

The invention relates to injectable long-acting insulin formulations for the treatment of types I and II diabetes in humans and animals. The essential object of the invention is to provide an injectable long-acting insulin formulation in the form of a colloidal suspension which is stable, which has a good local tolerance and toxicity compatible with the chronic treatment of diabetics, and which maintains a substantial hypoglycemic effect extending over at least 24 hours after a single administration, e.g. by the subcutaneous route. To achieve this object, the invention relates to a stable aqueous colloidal formulation of insulin-laden nanoparticles of at least one poly(Leu-block-Glu) in which the pH is between 5.8 and 7.0, the osmolarity O (in mOsmol) . . . : 270&#x2266;O&#x2266;800, and the viscosity v (in mPa&#xb7;s) is low, namely v&#x2266;40. The nanoparticles of poly(Leu-block-Glu) have a mean hydrodynamic diameter Dh such that: 15&#x2266;Dh&#x2266;40. The invention relates to an antidiabetic drug based on this long-acting insulin formulation and injectable using needles of gauge 29 G, 30 G or 31 G.

Long-acting colloidal insulin formulation and its preparation

The invention relates to novel collagen peptides that are modified by grafting free or substitued thiol functions carried by mercaptoamine radicals. The aim of the invention is to provide thiol collagens that can be cross-linked in a sufficient and controlled manner by forming S&#x2014;S bridges and which are biocompatible. This is achieved by means of the inventive thiol collagens which are characterized in that the mercaptoamine radicals are identical to or different from each other and are exclusively grafted on the aspartic and glutamic acids of the collagen chain by amide bonds. The invention also relates to a method for the production of said thiol and cross-linkable collagens. The novel modified cross-linkable and/or cross-linked collagens can be used as biomaterials.

Collagen peptides modified by grafting mercapto functions, method for the production thereof and uses thereof as biomaterials

The invention concerns delivery particles (DP's) for active principles (AP's) based on linear amphiphilic polyamino-acids (PAA's), with &agr;-peptide chains, capable of being spontaneously formed by contacting PAA's with a liquid medium, preferably with water, wherein the hydrophile part of the PAA's is solubilized more than the hydrophobic parts of said PAA's, such that the latter precipitate while being organised in discrete supra-molecular arrangements, of average size ranging between 0.01 and 20 &mgr;m, capable of combining with at least an AP and releasing the latter in vivo, in prolonged and controlled manner. The inventive suspension is characterised in that the recurrent amino acids (rAA's) constituting the main chain of PAA's are identical to or different from one another and are glutamic acid and/or aspartic acid and/or their salts; and some of said rAA's bear at least one hydrophobic group, said hydrophobic group, being identical to or different from one another. The invention is useful as carriers for active principles, in particular pharmaceutical, insulin or for therapeutic uses.

Particles based on polyamino-acid(s) and methods for preparing same

Collagen derivatives, process for producing them and their application

Growing community of inventors

Manissieux, France

Florence Nicolas