发明公开
- 专利标题: Process for preparing a pharmaceutical formulation of contrast agents
- 专利标题(中): 制备造影剂药物制剂的方法
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申请号: EP14165008.5申请日: 2009-02-18
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公开(公告)号: EP2799090A3公开(公告)日: 2015-01-14
- 发明人: Meyer, Dominique , Corot, Claire , Port, Marc , Barbotin, Vincent , Bonnemain, Bruno
- 申请人: GUERBET
- 申请人地址: 15, Rue des Vanesses 93420 Villepinte FR
- 专利权人: GUERBET
- 当前专利权人: GUERBET
- 当前专利权人地址: 15, Rue des Vanesses 93420 Villepinte FR
- 代理机构: Regimbeau
- 优先权: FR0851055 20080219; EP08154745 20080417; US155997 20080612
- 主分类号: A61K49/10
- IPC分类号: A61K49/10 ; A61K51/04
摘要:
The invention relates to a process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and a mol/mol amount of free macrocyclic chelate of between 0.002% and 0.4%, said process comprising the following successive steps:
b) preparation of a liquid pharmaceutical composition containing the complex of macrocyclic chelate with a lanthanide, free macrocyclic chelate that is not under the form of an excipient X[X',L] in which L is the macrocyclic chelate and X and X' are a metal ion, in particular chosen independently from calcium, sodium, zinc and magnesium, and/or free lanthanide,
said step b) consisting in the preparation of a solid complex [chelate-lanthanide] and in the dissolution of the said complex in water ;
c) measurement in the pharmaceutical formulation obtained in step b) of the concentration of free macrocyclic chelate C ch 1 or of free lanthanide C lan 1 ;
d) adjustment of C ch 1 and/or of C lan 1 by adding to the formulation obtained in step b) :
- if C lan 1 > 0 and/or C ch 1 ch 1 , free macrocyclic chelate,
- if C lan 1 = 0 and C ch 1 > C t ch 1 , free lanthanide,
so as to obtain C ch 1 = C t ch 1 and C lan 1 = 0 wherein Ct ch 1 is the target concentration of the free macrocyclic chelate in the final liquid pharmaceutical formulation and is selected in the range of between 0.002 % and 0.4 % mol/mol,
wherein the amount of free macrocyclic chelate in the final liquid pharmaceutical formulation corresponds to the proportion of free macrocyclic chelate relative to the amount of complexed macrocyclic chelate in the final liquid pharmaceutical formulation.
b) preparation of a liquid pharmaceutical composition containing the complex of macrocyclic chelate with a lanthanide, free macrocyclic chelate that is not under the form of an excipient X[X',L] in which L is the macrocyclic chelate and X and X' are a metal ion, in particular chosen independently from calcium, sodium, zinc and magnesium, and/or free lanthanide,
said step b) consisting in the preparation of a solid complex [chelate-lanthanide] and in the dissolution of the said complex in water ;
c) measurement in the pharmaceutical formulation obtained in step b) of the concentration of free macrocyclic chelate C ch 1 or of free lanthanide C lan 1 ;
d) adjustment of C ch 1 and/or of C lan 1 by adding to the formulation obtained in step b) :
- if C lan 1 > 0 and/or C ch 1 ch 1 , free macrocyclic chelate,
- if C lan 1 = 0 and C ch 1 > C t ch 1 , free lanthanide,
so as to obtain C ch 1 = C t ch 1 and C lan 1 = 0 wherein Ct ch 1 is the target concentration of the free macrocyclic chelate in the final liquid pharmaceutical formulation and is selected in the range of between 0.002 % and 0.4 % mol/mol,
wherein the amount of free macrocyclic chelate in the final liquid pharmaceutical formulation corresponds to the proportion of free macrocyclic chelate relative to the amount of complexed macrocyclic chelate in the final liquid pharmaceutical formulation.
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