发明名称 RAPID-ACTING INSULIN FORMULATION COMPRISING A SUBSTITUTED ANIONIC COMPOUND
摘要 The invention relates to a composition in aqueous solution, including insulin and at least one substituted anionic compound chosen from substituted anionic compounds consisting of a backbone formed from a discrete number u of between 1 and 8 (1≦u≦8) of identical or different saccharide units, linked via identical or different glycoside bonds, said saccharide units being chosen from the group consisting of hexoses, in cyclic form or in open reduced form, said compound comprising partially substituted carboxyl functional groups, the unsubstituted carboxyl functional groups being saliflable. The invention also relates to a pharmaceutical formulation comprising a composition as claimed in any one of the preceding claims.
申请公布号 US2014378373(A2) 申请公布日期 2014.12.25
申请号 US201314079516 申请日期 2013.11.13
申请人 ADOCIA 发明人 SOULA Olivier;SOULA Gerard;DAUTY Emmanuel;CHARVET Richard
分类号 A61K38/28 主分类号 A61K38/28
代理机构 代理人
主权项 1. A composition in aqueous solution, comprising insulin in hexameric form, at least one substituted anionic compound and a polyanionic compound: said substituted anionic compound being chosen from substituted anionic compounds, in isolated form or as a mixture, consisting of a backbone formed from a discrete number u of between 1 and 8 (1≦u≦8) of identical or different saccharide units, linked via identical or different glycoside bonds, said saccharide units being chosen from the group consisting of hexoses, in cyclic form or in open reduced form, wherein they are substituted with: a) at least one substituent of general formula I: —[R1]a-[AA]m  Formula I the substituents being identical or different when there are at least two substituents, in which: the radical -[AA]- denotes an amino acid residue, the radical —R1— being: either a bond and then a=0 and the amino acid residue -[AA] is directly linked to the backbone via a function G, or a C2 to C15 carbon-based chain, and then a=1, optionally substituted and/or comprising at least one heteroatom chosen from O, N and S and at least one acid function before the reaction with the amino acid, said chain forming with the amino acid residue -[AA] an amide function, and is attached to the backbone by means of a function F resulting from a reaction between a hydroxyl function borne by the backbone and a function or substituent borne by the precursor of the radical —R1—, F is a function chosen from ether, ester and carbamate functions, G is a carbamate function, m is equal to 1 or 2, the degree of substitution of the saccharide units, j, in —[R1]a-[AA]m being strictly greater than 0 and less than or equal to 6, 0<j≦6 b) and, optionally, one or more substituents —R′1, the substituent —R′1 being a C2 to C15 carbon-based chain, which is optionally substituted and/or comprising at least one heteroatom chosen from O, N and S and at least one acid function in the form of an alkali metal cation salt, said chain being linked to the backbone via a function F′ resulting from a reaction between a hydroxyl function or a carboxylic acid function borne by the backbone and a function or substituent borne by the precursor of the substituent —R′1, F′ is an ether, ester or carbamate function, the degree of substitution of the saccharide units, i, in —R′1, being between 0 and 6−j, 0≦i≦6−j, and F and F′ are identical or different, F and G are identical or different, i+j≦6, —R′1 is identical to or different from —R1—, the free saliflable acid functions borne by the substituent —R′1 are in the form of alkali metal cation salts, said glycoside bonds, which may be identical or different, being chosen from the group consisting of glycoside bonds of (1,1), (1,2), (1,3), (1,4) or (1,6) type, in an alpha or beta geometry, and said polyanionic compound being a non-polymeric polyanionic (NPP) compound whose affinity for zinc is less than the affinity of insulin for zinc and whose dissociation constant Kdca=[NPP compound]r[Ca2+]s/[(NPP compound)r-(Ca2+)s] is less than or equal to 10−1.5.
地址 Lyon FR