AR017973A1

AR017973A1 - PHARMACEUTICAL ISOTONIC FORMULATION, USE OF SUCH FORMULATION IN THE PREPARATION OF A MEDICINAL PRODUCT FOR USE IN THE THERAPY OF AN AUTOIMMUNE DISEASE, AND METHOD FOR IMPROVING THE STORAGE OF AN ANTIBODY

Info

Publication number: AR017973A1
Application number: ARP990100239A
Authority: AR
Original assignee: Astrazeneca Ab
Priority date: 1998-01-22
Filing date: 1999-01-21
Publication date: 2001-10-24
Also published as: WO1999037329A1; AU2444899A

Abstract

Formulacion farmacéutica isotonica que comprende un anticuerpo de IgG y un buffer, donde el anticuerpo está presente en, de 0,5 mg/ml a 10 mg/ml, elbuffer es un buffer de citrato presente en, de 5 mmol/l a 20 mmol/l y el pH de la formulacion es de 5,3 a 7,2. Las proteínas purificadas, particularmenteaquellas producidas usando tecnología de ADN recombinante, están ahora bien establecidas como agentes farmacéuticos. Dichas proteínas presentansin embargo, un rango de problemas asociados con su formulacion estable. Muchas preparaciones de proteínas son particularmente inestables en solucionesdiluidas y deben formularse de tal manera de prevenir niveles significativos de desnaturalizacion, aglomeracion o degradacion. Estos problemas sonparticularmente graves en la formulacion de proteínas grandes, tales como inmunoglobulinas. Las inmunoglobulinas o anticuerpos son propensos a formaragregados y particulados en solucion y desde hace bastante tiempo, esto ha llevado a problemas especiales paragenerar formulaciones adecuadaspara el almacenamiento y la administracion de anticuerpos terapéuticos. Las formulaciones de anticuerpos existentes requieren con frecuencia filtrarseantes de la inyeccion para extraer agregados o material particuladoque sea inconveniente y tienda a reducir la precision de la dosis inyectada.La presente formulacion de anticuerpos es más simple que aquella actualmente conocida, es adecuada para la administracion y mejora las propiedadesde almacenamiento. Las formulaciones de anticuerpos, requieren tanto el uso de un estabilizador como de un buffer. Sin embargo, los anticuerpos en laspresentes formulaciones se estabilizan solamente por el buffer de citrato en una solucion salina en un pH fisiologicamente preferible. Uso de dichaformulacion en la preparacion de un medicamento para uso en la terapia de una enfermedad autoinmune, y método para mejorar el almacenamiento de un anticuerpo.Isotonic pharmaceutical formulation comprising an IgG antibody and a buffer, where the antibody is present in, from 0.5 mg / ml to 10 mg / ml, elbuffer is a citrate buffer present in, from 5 mmol / la 20 mmol / The pH of the formulation is 5.3 to 7.2. Purified proteins, particularly those produced using recombinant DNA technology, are now well established as pharmaceutical agents. Such proteins, however, have a range of problems associated with their stable formulation. Many protein preparations are particularly unstable in dilute solutions and should be formulated in such a way to prevent significant levels of denaturation, agglomeration or degradation. These problems are particularly serious in the formulation of large proteins, such as immunoglobulins. Immunoglobulins or antibodies are prone to spreading and particulate in solution and for quite some time, this has led to special problems to generate appropriate formulations for the storage and administration of therapeutic antibodies. Existing antibody formulations often require filtering before injection to extract aggregates or particulate matter that is inconvenient and tends to reduce the accuracy of the injected dose. The present antibody formulation is simpler than that currently known, is suitable for administration and Improves storage properties. Antibody formulations require both the use of a stabilizer and a buffer. However, the antibodies in the present formulations are stabilized only by the citrate buffer in a saline solution at a physiologically preferable pH. Use of said formulation in the preparation of a medicament for use in the therapy of an autoimmune disease, and method for improving the storage of an antibody.