Methods for preparing active carbonate esters of water-soluble polymers are provided. Also provided are other methods related to the active carbonate esters of water-soluble polymers, as well as corresponding compositions.

A method for producing a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end, a polymerization initiator for use in the method, and a precursor of the polymerization initiator are provided.

The present invention provides: a method for producing a polyalkylene glycol derivative having an amino group at an end, using, as a polymerization initiator, a compound represented by the general formula (I); a compound represented by the following general formula (I); and a precursor thereof:

##STR00001## wherein R.sub.A.sup.1a and R.sub.A.sup.1b each independently represent a protective group of the amino group, or one of R.sub.A.sup.1a and R.sub.A.sup.1b represents H and the other represents a protective group of the amino group, or R.sub.A.sup.1a and R.sub.A.sup.1b bind to each other to represent a cyclic protective group forming a ring; R.sub.A.sup.2 represents a linear, branched, or cyclic hydrocarbon group having 1 to 6 carbon atoms; R.sub.A.sup.3 represents a single bond, or a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms, and the hydrocarbon group may contain a heteroatom; the total number of carbon atoms (or the total number of carbon atoms and heteroatoms) of R.sub.A.sup.2 and R.sub.A.sup.3 is 4 or more; and M represents an alkali metal.

A method for producing a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end, a polymerization initiator for use in the method, and a precursor of the polymerization initiator are provided.

The present invention provides: a method for producing a polyalkylene glycol derivative having an amino group at an end, using, as a polymerization initiator, a compound represented by the general formula (I); a compound represented by the following general formula (I); and a precursor thereof:

##STR00001## wherein R.sub.A.sup.1a and R.sub.A.sup.1b each independently represent a protective group of the amino group, or one of R.sub.A.sup.1a and R.sub.A.sup.1b represents H and the other represents a protective group of the amino group, or R.sub.A.sup.1a and R.sub.A.sup.1b bind to each other to represent a cyclic protective group forming a ring; R.sub.A.sup.2 represents a linear, branched, or cyclic hydrocarbon group having 1 to 6 carbon atoms; R.sub.A.sup.3 represents a single bond, or a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms, and the hydrocarbon group may contain a heteroatom; the total number of carbon atoms (or the total number of carbon atoms and heteroatoms) of R.sub.A.sup.2 and R.sub.A.sup.3 is 4 or more; and M represents an alkali metal.

Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]: ##STR00001##
wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is H or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]: ##STR00001##
wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is H or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

This disclosure relates to new injectable hydrogel materials that consist of water gellants comprising linear hydrophilic polymers that comprise hydrogen bonding units in the backbone combined with cross-linkable end groups, resulting in dynamic yet firm hydrogel materials that are easily processable, are highly elastic, show adhesive properties and are self-healing and are especially suitable for biomedical applications.

A method for producing a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end, a polymerization initiator for use in the method, and a precursor of the polymerization initiator are provided. The present invention provides: a method for producing a polyalkylene glycol derivative having an amino group at an end, using, as a polymerization initiator, a compound represented by the general formula (I); a compound represented by the following general formula (I); and a precursor thereof: ##STR00001## wherein R.sub.A.sup.1a and R.sub.A.sup.1b each independently represent a protective group of the amino group, or one of R.sub.A.sup.1a and R.sub.A.sup.1b represents H and the other represents a protective group of the amino group, or R.sub.A.sup.1a and R.sub.A.sup.1b bind to each other to represent a cyclic protective group forming a ring; R.sub.A.sup.2 represents a linear, branched, or cyclic hydrocarbon group having 1 to 6 carbon atoms; R.sub.A.sup.3 represents a single bond, or a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms, and the hydrocarbon group may contain a heteroatom; the total number of carbon atoms (or the total number of carbon atoms and heteroatoms) of R.sub.A.sup.2 and R.sub.A.sup.3 is 4 or more; and M represents an alkali metal.

A method for producing a narrowly distributed and high-purity polyalkylene glycol derivative having an amino group at an end, a polymerization initiator for use in the method, and a precursor of the polymerization initiator are provided. The present invention provides: a method for producing a polyalkylene glycol derivative having an amino group at an end, using, as a polymerization initiator, a compound represented by the general formula (I); a compound represented by the following general formula (I); and a precursor thereof: ##STR00001## wherein R.sub.A.sup.1a and R.sub.A.sup.1b each independently represent a protective group of the amino group, or one of R.sub.A.sup.1a and R.sub.A.sup.1b represents H and the other represents a protective group of the amino group, or R.sub.A.sup.1a and R.sub.A.sup.1b bind to each other to represent a cyclic protective group forming a ring; R.sub.A.sup.2 represents a linear, branched, or cyclic hydrocarbon group having 1 to 6 carbon atoms; R.sub.A.sup.3 represents a single bond, or a linear, branched, or cyclic hydrocarbon group having 1 to 20 carbon atoms, and the hydrocarbon group may contain a heteroatom; the total number of carbon atoms (or the total number of carbon atoms and heteroatoms) of R.sub.A.sup.2 and R.sub.A.sup.3 is 4 or more; and M represents an alkali metal.

Water-soluble supramolecular complexes formed from a water soluble block copolymer and at least one associative gelling adjuvant. The copolymer includes at least two blocks of polyethylene oxide and at least one block of polypropylene oxide. The adjuvant has a water solubility less than 0.5 g/100 ml at 20 C. When combined with water, the complexes form a transparent reversely thermo-reversible hydrogel or solution that may be repeatedly hydrated and dehydrated. The hydrogel exhibits improved gelling efficiency and enhanced solubility and/or stability for sparely soluble and insoluble pharmaceutical agents. The complexes are useful in a variety of pharmaceutical and cosmetic products and applications and may be combined with an effective amount of a cosmetic, medicament, or diagnostic in a solid dosage form.

A hydrophilic polymer derivative having a cyclic benzylidene acetal linker represented by the following formula (1):

##STR00001##

wherein R.sup.1 and R.sup.6 are each independently a hydrogen atom or a hydrocarbon group; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; X.sup.1 is a chemically reactive functional group; P is a hydrophilic polymer, s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 8; and Z.sup.1 and Z.sup.2 are each independently a selected divalent spacer.