Patent ES-2614161-T3 (ES)
Title: Preparados acuosos de insulina que comprenden metionina
Inventor: SCHOETTLE ISABELL
IPC: A61K47/00
Filed: 2010-07-02
Granted: 2017-05-29
Abstract: Una formulación farmacéutica acuosa que contiene un compuesto análogo de insulina o un derivado de insulina, o una sal farmacológicamente tolerable del mismo, y metionina, siendo el valor del pH de la formulación de 4,5 o más pequeño y (I) siendo escogido el compuesto análogo de insulina entre un conjunto que se compone de Gly(A21), Arg(B31), Arg(B32)-Insulina humana, Lys(B3), Glu(B29)-Insulina humana, Asp(B28)-Insulina humana, Lys(B28) Pro(B29)-Insulina humana, Des(B30)-Insulina humana y un compuesto análogo de insulina de la Fórmula I, **Fórmula** correspondiendo A0 a Lys o Arg; A5 a Asp, Gln o Glu; A15 a Asp, Glu o Gln; A18 a Asp, Glu o Asn; B-1 a Asp, Glu o a un grupo amino; B0 a Asp, Glu o a un enlace químico B1 a Asp, Glu o Phe; B2 a Asp, Glu o Val; B3 a Asp, Glu o Asn; B4 a Asp, Glu o Gln; B29 a Lys o a un enlace químico B30 a Thr o a un enlace químico B31 a Arg, Lys o a un enlace químico B32 a Arg-Amida, Lys-Amida o a un grupo amino correspondiendo dos radicales de aminoácidos del conjunto que se compone de A5, A15, A18, B-1, B0, B1, B2, B3 y B4, simultánea e independientemente uno de otro, a Asp o Glu, y estando escogido el compuesto análogo de insulina en particular a partir de un conjunto que se compone de: Arg (A0), His (A8), Glu (A5), Asp (A18), Gly (A21), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Asp (A18), Gly (A21), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Asp (A18), Gly (A21), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Asp (A18), Gly (A21), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu(A5), Glu (A15), Gly (A21), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Glu (A15), Gly (A21), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His(A8), Glu (A5), Gly (A21), Asp (B3), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His(A8), Glu (A5), Gly (A21), Asp (B3), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B3), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B3), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His(A8), Gly (A21), Asp (B3), Glu (B4), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Gly (A21), Asp (B3), Glu (B4), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B4), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B4), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B4), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B4), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B4), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B4), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B0), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Glu (B0), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B0), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Glu (B0), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B0), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Glu (B0), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Asp (B1), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A5), Gly (A21), Asp (B1), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B1), Arg (B31), Arg(B32)-NH2 Insulina humana, Arg (A0), His (A8), Glu (A15), Gly (A21), Asp (B1), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B1), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B1), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B0), Asp (B1), Arg (B31), Arg (B32)-NH2 Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B0), Asp (B1), Arg (B31), Lys (B32)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B30), Arg (B31)-NH2 Insulina humana, Arg (A0), His (A8), Asp (A18), Gly (A21), Asp (B3), Arg (B30), Lys (B31)-NH2 Insulina humana, (II) siendo escogido el compuesto análogo de insulina entre un conjunto que se compone de un compuesto análogo de insulina de la fórmula (II): **Fórmula** correspondiendo A-1 a Lys, Arg o a un grupo amino; A0 a Lys, Arg o a un enlace químico A1 a Arg o Gly; A5 a Asp, Glu o Gln; A15 a Asp, Glu o Gln; A18 a Asp, Glu o Asn; A21 a Ala, Ser, Thr o Gly; B-1 a Asp, Glu o a un grupo amino; B0 a Asp, Glu o a un enlace químico B1 a Asp, Glu, Phe o a un enlace químico B3 a Asp, Glu o Asn; B4 a Asp, Glu o Gln; B29 a Arg, Lys o a un aminoácido que se escoge entre un conjunto que se compone de los aminoácidos Phe, Ala, Thr, Ser, Val, Leu, Glu o Asp, o a un enlace químico; B30 a Thr o a un enlace químico; B31 a Arg, Lys o a un enlace químico; B32 a Arg-Amida o Lys-Amida; no correspondiendo más de un radical de aminoácido del conjunto que se compone de A5, A15, A18, B-1, B0, B1, B2, B3 y B4, simultánea e independientemente uno de otro, a Asp o Glu, y siendo escogido el derivado de insulina en particular entre un conjunto que se compone de Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), Glu (A5), His (A8), Gly (A21), Lys (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), Glu (A15), His (A8), Gly (A21), Lys (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B0), Lys (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B30)-NH2Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Asp (B3), Lys (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B30)-NH2 Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Glu (B4), Lys (B30)-NH2 Insulina humana, Arg (A0), His (A8), Gly (A21), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), Glu (A5), His (A8), Gly (A21), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), Asp (A18), His (A8), Gly (A21), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), Glu (A15), His (A8), Gly (A21), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Asp (B3), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B4), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B31), Arg (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Glu (B0), Arg (B31), Lys (B32)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Arg (B30)-NH2-Insulina humana, Arg (A0), His (A8), Gly (A21), Lys (B30)-NH2-Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Arg (B30)-NH-Insulina humana, Arg (A-1), Arg (A0), His (A8), Gly (A21), Lys (B30)-NH2-Insulina humana, Arg (A0), Arg (A1), His (A8), Gly (A21), Arg (B30)-NH2-Insulina humana, Arg (A0), Arg (A1), His (A8), Gly (A21), Lys (B30)-NH2-Insulina humana, His (A8), Gly (A21), Arg (B31), Arg (B32)-NH2-Insulina humana, o (III) siendo escogido el derivado de insulina entre un conjunto que se compone de B29-N-miristoíl-des(B30) Insulina humana, B29-N-palmitoíl-des(B30) Insulina humana, B29-N-miristoíl Insulina humana, B29-N-palmitoíl Insulina humana, B28-N-miristoíl LysB28ProB29 Insulina humana, B28-N-palmitoíl-LysB28ProB29 Insulina humana, B30-N-miristoíl-ThrB29LysB30 Insulina humana, B30-N-palmitoíl-ThrB29LysB30 Insulina humana, B29-N-(N-palmitoíl-γ-glutamil)-des(B39) Insulina humana, B29-N-(N-litocolil-γ-glutamil)-des(B30) Insulina humana, B29-N-(ω-65 carboxiheptadecanoíl)-des(B30) Insulina humana y B29-N-(ω-carboxiheptadecanoíl) Insulina humana.