Injectable liquid formulation for prolonged release of interleukin, e.g. for immunomodulation, based on aqueous colloidal suspension of water-soluble, biodegradable polymer forming gelled depot on injection

摘要

A liquid pharmaceutical formulation (I) for prolonged release of interleukin(s) (IL) comprises a low viscosity aqueous colloidal suspension of submicron particles of water-soluble, biodegradable polymers (II) carrying hydrophobic groups, non-covalently associated with IL(s) and optionally other active agent(s), where on parenteral injection (I) forms a gelled depot for prolonging the duration of active agent release to more than 24 hours. A liquid pharmaceutical formulation (I) for prolonged release of interleukin(s) (IL) comprises a low viscosity aqueous colloidal suspension (with water as dispersion medium) based on submicron particles (SMP's) of water-soluble, biodegradable polymers (II) carrying hydrophobic groups (HG's), non-covalently associated with IL(s) and optionally other active agent(s). On parenteral injection, (I) forms a gelled depot in vivo (at least partially due to physiological proteins), controlling and prolonging the duration of active agent release to more than 24 hours. (I) is liquid under the injection conditions; at physiological temperature and/or pH; and/or in presence of physiological electrolytes at physiological concentrations and/or surfactant(s). Independent claims are included for: (1) a variant of (I) as described above, where the duration of release of active agents is not restricted but the concentration of (II) is sufficiently high to form a gelled depot in vivo in presence of protein(s) after parenteral injection; (2) novel derived products (preferably in powder or gel form), consisting of SMP's formed by non-covalent association of (II) and active agents as above and obtained from (I); and (3) methods of preparation of (I). ACTIVITY : Antiinflammatory; immunomodulator. MECHANISM OF ACTION : T-Lymphocyte activator; T-lymphocyte proliferation profieration inducer.