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包含glp-1激动剂、n-(8-(2-羟基苯甲酰基)氨基)辛酸盐和润滑剂的固体组合物

专利摘要

本发明涉及包含肽例如GLP-1肽和N-(8-(2-羟基苯甲酰基)氨基)辛酸盐的药物组合物。本发明还涉及此类组合物的制备方法及其在医学中的用途。 ......

基本信息

专利类型:
发明专利
申请/专利号:
EP2023182039
申请日期:
2019-02-01
专利申请人:
分类号:
A61P3/10
发明/设计人:
PEDERSEN, BETTY LOMSTEIN ， NISSEN, BIRGITTE
权利要求: 1. A pharmaceutical composition comprising a) a GLP-1 agonist and b) a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid wherein said salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid constitutes at least 90 w/w %, such as at least 95 w/w %, of the excipients of the composition.2. The pharmaceutical composition according to any of the previous claims, wherein the composition comprises at least one lubricant, such as magnesium stearate or glyceryl dibehenate.3. The pharmaceutical composition according to any of the previous claims, wherein the compositions comprises 1-8 mg, such as 2-5 mg or such as 2-3 mg magnesium stearate per 100 mg of said salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid.4. The pharmaceutical composition according to any of the previous claims, wherein the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC).5. The pharmaceutical composition according to any of the previous claims, wherein the GLP-1 agonist is a GLP-1 analogue, such as a GLP-1 peptide comprising at least one substituent.6. The pharmaceutical composition according to claims 5, wherein the GLP-1 analogue has at least 80 % sequence identity to GLP-1(7-37) (SEQ ID NO.:1).7. The pharmaceutical composition according to any of the previous claims wherein the GLP-1 agonist is a GLP-1 peptide substituted with a fatty acid or a fatty diacid, such as a GLP-1 agonist selected from the group consisting of: i. semaglutide, ii. Nε26{2-[2-(2-{2-[2-(2-{(S)-4-Carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}-ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl}, Nε37-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}-ethoxy)ethoxy]-acetyl}-[Aib8,Arg34,Lys37]GLP-1(7-37)-peptide (GLP-1 agonist B) and iii. Nε27-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]-amino] ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]-acetyl], Nε36-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]-amino]ethoxy]ethoxy]acetyl]-[Aib8,Glu22,Arg26,Lys27, Glu30,Arg34,Lys36]-GLP-1-(7-37)-peptidyl-Glu-Gly (GLP-1 agonist C).8. The pharmaceutical composition according to any of the previous claims wherein the dose corrected exposure (AUC) for t=0-30 min is increased relative to a reference composition of type F/H of WO2013/139694.9. The pharmaceutical composition according to claim 8, wherein the dose corrected exposure (AUC) for T=0-30 min is increased at least 1.5 fold, such as at least 2 fold.10. The pharmaceutical composition according to any of the previous claims, wherein a dose unit comprises 0.5-50 mg of the GLP-1 agonist.11. The pharmaceutical composition according to any of the previous claims, wherein a dose unit comprises a) 1-10 mg of semaglutide, b) 50-300 mg of SNAC and c) 1-10 mg magnesium stearate.12. The pharmaceutical composition according to any of the previous claims, wherein the composition comprises at least one granulate.13. The pharmaceutical composition according to claim 12, wherein the at least one granulate comprises, a. the salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid, b. the GLP-1 agonist and/or c. a lubricant, such as magnesium stearate.14. The pharmaceutical composition according to any of the previous claims 13-14, wherein the at least one granulate is prepared by dry granulation, such as by roller compaction.15. The pharmaceutical composition according to any of the previous claims, wherein the composition is a solid composition, such as a tablet for oral administration for use in medicine, such as for use in a method of treatment of diabetes and/or obesity.