Abstract: High molecular weight derivatives of activated poly(ethylene glycol) and the like polymers are prepared in high purity by conjugating a large PEG molecule to a small PEG molecule. Most of the reaction steps can be accomplished on the more readily purified small molecule to avoid laborious purification of the high molecular weight derivatives.

Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).

Abstract: A substantially hydrophilic conjugate is provided having a peptide that is capable of passing the blood-brain barrier covalently linked to a water-soluble nonpeptidic polymer such as polyethylene glycol. The conjugate exhibits improved solubility and in vivo stability and is capable of passing the blood-brain barrier of an animal.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble prodrugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the drug at a controllable rate as the gel degrades.

Abstract: The present invention provides water-soluble polymer conjugates of retinoic acid. The conjugates of the invention are prepared by covalent attachment of a water-soluble and non-peptidic polymer such as polyethylene glycol to a retinoid such as retinoic acid. The polymer portion of the conjugate may be linear (i.e., prepared using an end-capped or methoxy PEG or a linear bifunctional PEG), branched or forked. The conjugates of the invention are water soluble, and are, in particular, useful for inhalation therapy of conditions of the respiratory tract responsive to retinoid therapy.

Abstract: The invention provides a polymeric structure comprising a multifunctional poly(alkylene oxide), such as a poly(ethylene glycol) derivative, covalently cross-linked to a polymer selected from the group consisting of chitosan and conjugates of chitosan and a monofunctional poly(alkylene oxide), such as methoxy poly(ethylene glycol). In aqueous media, the polymeric structure forms a hydrogel that is useful as a drug delivery device, a surgical sealant, or as a delivery system for a medical imaging agent.

Abstract: The invention provides polymer conjugates of protein kinase C (PKC) inhibitors comprising a polymer, such as poly(ethylene glycol), covalently attached to a PKC inhibitor, such as a bisindolylmaleimide molecule. The linkage between the polymer and the PKC inhibitor is preferably hydrolytically degradable. The invention also includes a pharmaceutical composition comprising a polymer conjugate of a PKC inhibitor and a method of treating any condition responsive to a PKC inhibitor by administering a polymer conjugate of the invention.

Abstract: The present invention is directed to branched reactive water-soluble polymers comprising at least two polymer arms, such as poly(ethylene glycol), attached to a central aliphatic hydrocarbon core molecule through heteroatom linkages. The branched polymers bear at least one functional group for reacting with a biologically active agent to form a biologically active conjugate. The functional group of the branched polymer can be directly attached to the aliphatic hydrocarbon core or via an intervening linkage, such as a heteroatom, -alkylene-, —O-alkylene-O—, -alkylene-O-alkylene-, -aryl-O—, —O— aryl-, (—O-alkylene-)m, or (-alkylene-O—)m linkage, wherein m is 1-10.

Abstract: A substantially hydrophilic conjugate is provided having a peptide that is capable of passing the blood-brain barrier covalently linked to a water-soluble nonpeptidic polymer such as polyethylene glycol. The conjugate exhibits improved solubility and in vivo stability and is capable of passing the blood-brain barrier of an animal.

Abstract: A substantially hydrophilic conjugate is provided having a peptide that is capable of passing the blood-brain barrier covalently linked to a water-soluble nonpeptidic polymer such as polyethylene glycol. The conjugate exhibits improved solubility and in vivo stability and is capable of passing the blood-brain barrier of an animal.

Abstract: The invention provides polymer conjugates of opioid antagonists comprising a polymer, such as poly(ethylene glycol), covalently attached to an opioid antagonist. The linkage between the polymer and the opioid antagonist is preferably hydrolytically stable. The invention also includes a method of treating one or more side effects associated with the use of opioid analgesics, such as constipation, nausea, or pruritus, by administering a polymer conjugate of the invention.

Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: A water soluble polymer is provided having two or more oligomers linked to each other by hydrolytically degradable carbonate linkages. The polymer can be hydrolytically degraded into oligomers (e.g., oligomers of ethylene oxide) under physiological conditions. The polymer can be conjugated to biologically active agents such as proteins or peptides to impart improved water solubility, reduced immunogenicity, reduced rate of renal clearance, and increased stability. The polymer is useful in making hydrolytically degradable hydrogels which can be used in drug delivery and related biomedical applications. On example of the polymer is a poly(ether carbonate) of the formula X—O—[(—CH2CH2—O—)n—CO2—]n(CH2CH2))n-y where X and Y are independently H, alkyl, alkenyl, aryl, or a reactive moiety, and at least one of X and Y is a reactive moiety.

Abstract: The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).

Abstract: The present invention provides water-soluble polymer conjugates of triazine derivatives using water soluble and non-peptidic polymer backbones, such as poly(ethylene glycol). The invention includes conjugates made using mPEG, bifunctional PEG, branched or multi-arm PEG, and forked PEG. The invention further includes a method of forming such conjugates and a method of treating conditions responsive to triazine derivatives using the conjugates.

Abstract: The present invention provides water-soluble polymer conjugates of the anti-malarial drug, artelinic acid, using water soluble and non-peptidic polymer backbones, such as poly(ethylene glycol). The invention includes conjugates made using mPEG, bifunctional PEG and multi-arm PEG. The invention further includes a method of forming such conjugates and a method of treating malaria using the conjugates.

Abstract: Poly(ethylene glycol) carbamate derivatives useful as water-soluble pro-drugs are disclosed. These degradable poly(ethylene glycol) carbamate derivatives also have potential applications in controlled hydrolytic degradation of hydrogels. In such degradable hydrogels, drugs may be either trapped in the gel and released by diffusion as the gel degrades, or they may be covalently bound through hydrolyzable carbamate linkages. Hydrolysis of these carbamate linkages releases the amine drug at a controllable rate as the gel degrades.

Abstract: This invention provides a method for preparing, in high purity and high yield, heterobifunctional derivatives of poly(ethylene glycol) or related polymers. A chromatographic purification step is not necessary in the method. In accordance with the method of the invention, an intermediate polymer having a formula of W-Poly-OH is provided bearing a removable group W at one terminus. The intermediate polymer W-Poly-OH is first altered by modifying the OH group to a first functional group X, followed by the removal of W to generate a second hydroxyl group. The latter hydroxyl group may then be further converted to a second functional group Y, thus providing the desired heterobifunctional derivative.