Hydroxyalkyl starch derivatives and process for their preparation

A hydroxyalkyl starch (HAS) derivative of formula (III)

• wherein A is an acetal or ketal group;
• L is a spacer bridging X and A;
• wherein X is the functional group resulting from the reaction of an amino group M of a crosslinking compound of formula (II)
• M-L-A (II)
• with hydroxyalkyl Stara (HAS) of formula (I)
• via carbon atom C* of the HAS, wherein C* is optionally oxidised prior to the reaction of HAS with M.
• wherein HAS′ is the remainder of the hydroxyalkyl starch molecule and R1, R2 and R3 are independently hydrogen or a linear or branched hydroxyalkyl group.

A hydroxyalkyl starch derivative of formula (IV)

• wherein X is a functional group resulting from the reaction of an amino group M of a crosslinking compound of formula (II)
• M-L-A (II)
• wherein X is not an amide group —C(═O)—NH—,
• with hydroxyalkyl starch (HAS) of formula (I)
• via carbon atom C* of the HAS, wherein C* is optionally oxidised, most preferably not oxidised prior to the reaction of HAS with M,
• wherein HAS′ is the remainder of the hydroxyalkyl starch molecule and R1, R2 and R3 are independently hydrogen or a linear or branched hydroxyalkyl group, wherein A is a residue according to formula (IIa)
• wherein
• Z1 and Z2 are each independently O or S or NRx, preferably O, wherein Rx is H or lower alkyl such as methyl, ethyl, or propyl such as n-propyl or i-propyl, or C(O)—Ry wherein Ry is preferably selected from the group consisting of C1-C6 alkyl and C6-C14 aryl, even more preferably selected from the group consisting of optionally substituted, preferably non-substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and tert-butyl;
• Rx preferably being H;
• A1 and A2 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, benzyl, 1,1,1-trichloroethyl, nitrobenzyl, methoxybenzyl, ethoxy benzyl, or are forming a ring according to formula (IIb)
• wherein A1 and A2, taken together, are —(CH2)2— or —(CH2)3— or —(CH2CH(CH3))—,
• and
• wherein A3 is H or methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, benzyl, or is forming a ring with the N atom of the amino group M or with a suitable atom comprised in L, A3 preferably being and wherein L is a spacer bridging M and A,
• wherein BA′ is the remainder of a biologically active agent BA′-NH2 remaining after the reaction of the amino group of BA′-NH2 via reductive amination with A or with the aldehyde group or keto group corresponding to A.