Water-soluble polymeric carriers for drug delivery
AssigneeVivorx, Inc.
InventorsNeil P. Desai, P. Soon-Shiong, Paul A. Sandford
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Abstract
In accordance with the present invention, there are provided polymeric drug delivery systems in which the drug is bound to a water-soluble polymer to provide a form of soluble drug delivery especially for those cases in which the drug by itself is water-insoluble. In particular, the drug taxol is covalently bound to water-soluble polyethylene glycols such as linear polyethylene glycols, branched polyethylene glycols, star polyethylene glycols, and branched copolymers of polyethylene glycols with other functional monomers to comprise a form of polymeric drug delivery. Also, crosslinked insoluble gels of these materials are prepared to serve as a form of implantable drug delivery.
Claims15
A taxol derivative having the general formula R.sub.1 --T--R.sub.2 :
- wherein R.sub.1 =--X--P or --OH, and R.sub.1 is located on the 2'-carbon of the taxol side chain;
- wherein R.sub.1 =--X--P or --OH, and R.sub.2 is located on the 7-carbon atom of the ring structure;
- but R.sub.1 and R.sub.2 are not simultaneously --OH;
- and the drug taxol T, is covalently linked to a water-soluble polymer P, based on polyethylene glycol, through a covalent linking group X,
- wherein P is selected from a branched chain polyethylene glycol, a star polyethylene glycol or a branched copolymer of a linear polyethylene glycol and a functional monomer, and
- wherein X is selected from ester, diester, urethane, amide, secondary or tertiary amine or ether linking groups.
A water-soluble drug-polymer conjugate having the general formula P--X--D:
- wherein P is a water-soluble polymer based on polyethylene glycol, wherein P is selected from a branched chain polyethylene glycol, a star polyethylene glycol or a branched copolymer of a linear polyethylene glycol and a functional monomer;
- wherein the drug D is taxol;
- and the drug and polymer are linked by the covalent linkage X, wherein X is selected from ester, diester, urethane, amide, secondary or tertiary amine or ether linking groups.
A method of solubilizing taxol by attaching taxol to a water-soluble polymeric carrier by a covalent linkage;
- wherein said polymer carrier is based on polyethylene glycol, and wherein said polymeric carrier is selected from a branched chain polyethylene glycol, a star polyethylene glycol, or a branched copolymer of a linear polyethylene glycol and a functional monomer;
- and
- wherein said covalent linkage is selected from ester, diester, urethane, amide, secondary or tertiary amine or ether linking groups.
A water-soluble drug delivery system comprising water-soluble polymers of polyethylene glycol conjugated to a drug D by a covalent linking group, X or W,
- wherein D is taxol;
- wherein said polymers of polyethylene glycol are selected from branched polyethylene glycols, star polyethylene glycols, or branched copolymers of linear polyethylene glycol and a functional monomer, and
- wherein said drug-polymer conjugates have the general formulas:
- ##STR6## wherein A=R.sub.5 (CH.sub.2 CH.sub.2 O).sub.n CH.sub.2 CH.sub.2 --Y-- and R.sub.5 =HO--, or alkoxy, or aryloxy, or D--X--;
- wherein B=D--X--(CH.sub.2 CH.sub.2 O).sub.p CH.sub.2 CH.sub.2 --Y--;
- wherein R.sub.6 =--H or --CH.sub.3 ;
- wherein X is a covalent linking group selected from ester, diester, urethane, amide, secondary or tertiary amine or ether linking groups;
- wherein Y is independently selected from the same groups as X;
- wherein m, n, and p are numbers between, and including, 5 and 2500;
- or ##STR7## wherein A and R.sub.6 are defined as above;
- wherein R.sub.7 is selected from --H, --CH.sub.3, alkyl, or aryl;
- wherein E is selected from alkyl or aryl;
- and G=--W--D, wherein W is a covalent linking group independently selected from the same groups as X, and D is linked to E through W;
- wherein r is a number between, and including, 5 and 2500;
- or
- (D--X--(CH.sub.2 CH.sub.2 O).sub.n CH.sub.2 CH.sub.2).sub.q -(central core)
- wherein q is the number of arms of a linear polyethylene glycol attached to a central core and q is a number between, and including, 2 and 100;
- and n is defined as above.
Dependencies are inferred from the claim text.