Method for controllably releasing a drug conjugate within subcutaneous tissue in response to the local concentration of an indicator
First Claim
1. A method for controllably releasing a conjugate within subcutaneous tissue in response to the local concentration of an indicator comprising subcutaneously administering, to a patient in need thereof, a material that comprises:
- a plurality of conjugates that each include a drug covalently linked to a polymer that is a polysaccharide that includes repeating chains of 1,4-linked alpha-D-glucose residues or the polymer is covalently linked to said drug via a spacer that includes a plurality of 1,4-linked alpha-D-glucose residues, wherein said conjugates are susceptible to digestion by an enzyme present in the extracellular space of subcutaneous tissue; and
a plurality of multivalent cross-linking agents each containing two or more cross-link receptors, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between the indicator analogs and the cross-link receptors, wherein said interactions are competitively disrupted if an amount of the indicator is present, and wherein competitive disruption of the interactions between the indicator analogs and the cross-link receptors causes the material to release the conjugate in a manner that is dependent on the local concentration of the indicator.
1 Assignment
0 Petitions
Accused Products
Abstract
A conjugate that includes a drug covalently linked to a polymer. Upon administration, the conjugate is digested by an enzyme that is present at the site of administration thereby releasing a therapeutic agent. The conjugate may demonstrate substantially the same pharmacokinetic and pharmacodynamic behavior as the drug itself. A material for controllably releasing a conjugate in response to the local concentration of a molecular indicator. The material includes a plurality of conjugates and a plurality of multivalent cross-linking agents. The polymers of the conjugates include an analog of the indicator within their covalent structure. The multivalent cross-linking agents include cross-link receptors that interact with the indicator analog and thereby cross-link the conjugates. These non-covalent interactions are competitively disrupted when an amount of the molecular indicator is present thereby causing the material to release the conjugate in a manner that is dependent on the local concentration of indicator.
-
Citations
17 Claims
-
1. A method for controllably releasing a conjugate within subcutaneous tissue in response to the local concentration of an indicator comprising subcutaneously administering, to a patient in need thereof, a material that comprises:
-
a plurality of conjugates that each include a drug covalently linked to a polymer that is a polysaccharide that includes repeating chains of 1,4-linked alpha-D-glucose residues or the polymer is covalently linked to said drug via a spacer that includes a plurality of 1,4-linked alpha-D-glucose residues, wherein said conjugates are susceptible to digestion by an enzyme present in the extracellular space of subcutaneous tissue; and a plurality of multivalent cross-linking agents each containing two or more cross-link receptors, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between the indicator analogs and the cross-link receptors, wherein said interactions are competitively disrupted if an amount of the indicator is present, and wherein competitive disruption of the interactions between the indicator analogs and the cross-link receptors causes the material to release the conjugate in a manner that is dependent on the local concentration of the indicator. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
-
-
13. A method for treating diabetes comprising subcutaneously administering to a patient in need thereof, a material that comprises:
-
a plurality of conjugates that each include an antidiabetic agent covalently linked to a polymer that is a polysaccharide that includes repeating chains of 1,4-linked alpha-D-glucose residues or the polymer is covalently linked to said drug via a spacer that includes a plurality of 1,4-linked alpha-D-glucose residues, wherein said conjugates are susceptible to digestion by an enzyme present in the extracellular space of subcutaneous tissue; a plurality of multivalent cross-linking agents each comprising containing two or more cross-link receptors, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between the glucose analogs and the cross-link receptors, wherein said interactions are competitively disrupted if an amount of glucose is present, and wherein competitive disruption of the interactions between the glucose analogs and the cross-link receptors causes the material to release the conjugate in a manner that is dependent on the local concentration of glucose. - View Dependent Claims (14, 15, 16, 17)
-
Specification