申请人:Rhone-Poulenc Rorer S.A.
公开号:US06107286A1
公开(公告)日:2000-08-22
Cationic lipids of general formula (I), wherein m is an integer from 2 to 6 inclusive; n is an integer from 1 to 9 inclusive, preferably 1-5, where, when n is 2-9, a single R grouping other than hydrogen is present in the general formula, and m has variable or identical values within the groupings (a) or --(CH.sub.2).sub.m ; R is a hydrogen atom or a radical of general formula (II), wherein X or X.sup.1, which are the same or different, are an oxygen atom, a methylene grouping --(CH.sub.2).sub.q -- where q is 0, 1, 2 or 3, or an amino grouping --NH-- or NR.sup.1 --, where R is a C.sub.1-4 alkyl grouping; Y and Y.sup.1, which are the same or different, are a hydrogen atom or an optionally substituted C.sub.1-4 alkyl radical, and p is 0-5; and R.sub.6 is a cholesterol derivative or an alkylamino grouping --NR.sub.1 R.sub.2, where R.sub.1 and R.sub.2 are, independently of each other, a straight or branched, saturated or unsaturated C.sub.12-22 aliphatic radical. Pharmaceutical compositions containing said lipids, and their uses for transfecting nucleic acids whether in vitro or in vivo in cells, are also disclosed.
通式(I)中的阳离子脂质,其中m是一个从2到6的整数,包括2和6;n是一个从1到9的整数,最好是1-5,其中当n为2-9时,在通式中存在除氢之外的单个R基团,并且m在(a)或--(CH.sub.2).sub.m的基团内具有可变或相同的值;R是一个氢原子或通式(II)的基团,其中X或X.sup.1,它们相同或不同,是一个氧原子,一个亚甲基基团--(CH.sub.2).sub.q--其中q为0、1、2或3,或一个氨基基团--NH--或NR.sup.1--,其中R是一个C.sub.1-4烷基基团;Y和Y.sup.1,它们相同或不同,是一个氢原子或一个可选择取代的C.sub.1-4烷基基团,p为0-5;R.sub.6是一个胆固醇衍生物或一个烷基氨基基团--NR.sub.1 R.sub.2,其中R.sub.1和R.sub.2是,彼此独立地,直链或支链的,饱和或不饱和的C.sub.12-22脂肪基团。还披露了含有这些脂质的药物组合物,以及它们在体内或体外细胞内转染核酸的用途。