Starburst conjugates

Claim 2

A solvent soluble, radially symmetrical dense star polymer conjugate which comprises at least one solvent soluble, radially symmetrical dense star polymer wherein the dense star polymer has at least one core branch emanating from a core, said branch having at least one terminal group provided that (1) the ratio of terminal groups to the core branches is two or greater, (2) the density of terminal groups per unit volume in the polymer is at least 1.5 times that of an extended conventional star polymer having similar core and monomeric moieties and a comparable molecular weight and number of core branches, each of such branches of the extended conventional star polymer bearing only one terminal group, and (3) the dense star polymer has a molecular volume that is no more than about 80 percent of the molecular volume of said extended conventional star polymer as determined by dimensional studies using scaled Corey-Pauling molecular models, and has regular dendritic branching; attached to or linked to the surface of the dense star polymer or encapsulated within the interior of the dense star polymer by means of covalent bonding, hydrogen bonding, adsorption, absorption, metallic bonding, van der Waals forces, ionic bonding, coulombic forces, hydrophobic or hydrophilic forces, or any combination thereof, at least one carried material wherein the carried material is a contrast agent, a fluorescing entity, a paramagnetic entity, a radionuclide, or an aromatic ultraviolet absorber, with the proviso that the carried material maintains its effectiveness in the conjugate.

Claim 3

The conjugate of claim 1 wherein the dense star polymer is a dendrimer.

Claim 4

The conjugate of claim 1 wherein the carried material causes a detectable and measurable perturbation of a system.

Claim 5

The conjugate of claim 1 for use as a reagent in positron emission tomography, computer aided tomography, or magnetic resonance imaging.

Claim 6

The conjugate of claim 2 wherein the carried material is a contrast agent.

Claim 7

The conjugate of claim 5 wherein the contrast agent is prepared by reaction of an α,β-unsaturated ester, an α,β-unsaturated ketone, an α,β-unsaturated nitrile, an α,β-unsaturated carboxyl, isothiocyanato or epoxide moiety.

Claim 8

The conjugate of claim 6 wherein the contrast agent is hydrophobic.

Claim 9

The conjugate of claim 6 wherein the contrast agent is hydrophilic.

Claim 10

The conjugate of claim 5 wherein the contrast agent comprises a metal ion selected from Gd, Mn and Fe.

Claim 11

The conjugate of claim 5 wherein the contrast agent is a chelated metal ion selected from Gd, Mn and Fe.

Claim 12

The conjugate of claim 9 wherein the contrast agent is derived from 1,4,7,10-tetraazacyclododecane-N,N',N"-triacetic acid.

Claim 13

The conjugate of claim 11 wherein the dendrimer portion of the conjugate is polyamidoamine.

Claim 14

The conjugate of claim 11 wherein the dendrimer portion of the conjugate is polyethyleneimine.

Claim 15

The conjugate of claim 9 wherein the contrast agent is derived from diethylenetriaminepentaacetic acid.

Claim 16

The conjugate of claim 9 wherein the dendrimer portion of the conjugate is polyamidoamine.

Claim 17

The conjugate of claim 9 wherein the contrast agent is derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid.

Claim 18

The conjugate of claim 15 for use as a diagnostic agent.

Claim 19

The conjugate of claim 17 wherein the diagnostic agent is hydroxyethyl-1,4,7-tris(carbomethoxymethyl)-1,4,7,10-tetraazacyclododecane PAMAM conjugated with a metal ion selected from Gd, Mn and Fe.

Claim 20

The conjugate of claim 17 wherein the diagnostic agent is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid PAMAM conjugated with a metal ion selected from Gd, Mn and Fe.

Claim 21

The conjugate of claim 1 wherein the carried material is a fluorescing entity.

Claim 22

The conjugate of claim 20 wherein the dense star polymer is a polyethyleneimine.

Claim 23

The conjugate of claim 21 wherein the fluorescing entity is fluorescein and the dense star polymer is a polyethyleneimine.

Claim 24

The conjugate of claim 1 wherein the carried material is a paramagnetic entity.

Claim 25

The conjugate of claim 23 wherein the paramagnetic entity is a metal ion selected from Gd, Mn, and Fe.

Claim 26

The conjugate of claim 23 wherein the paramagnetic entity is a chelated metal ion selected from Gd, Mn, and Fe.

Claim 27

The conjugate of claim 1 wherein the carried material is a radionuclide.

Claim 28

The conjugate of claim 26 wherein the radionuclide is selected from 90 Y and 111 In.

Claim 29

The conjugate of claim 1 wherein the carried material is an aromatic ultraviolet absorber.

Claim 30

The conjugate of claim 28 wherein the aromatic ultraviolet absorber is salicyclic acid.

Claim 31

A solvent soluble, radially symmetrical dense star polymer conjugate of the formula: (P).sub.x *(M).sub.y (I) wherein each P represents a dendrimer of a dense star polymer wherein the dense star polymer has at least one core branch emanating from a core, said branch having at least one terminal group provided that (1) the ratio of terminal groups to the core branches is two or greater, (2) the density of terminal groups per unit volume in the polymer is at least 1.5 times that of an extended conventional star polymer having similar core and monomeric moieties and a comparable molecular weight and number of core branches, each of such branches of the extended conventional star polymer bearing only one terminal group, and (3) the dense star polymer has a molecular volume that is no more than about 80 percent of the molecular volume of said extended conventional star polymer as determined by dimensional studies using scaled Corey-Pauling molecular models, and has regular dendritic branching; x represents an integer of 1 or greater; each M represents a carried material, or a different carried material and is a contrast agent, fluorescing entity, paramagnetic entity, radionuclide, or aromatic ultraviolet absorber; y represents an integer of 1 or greater; and * indicates that the carried material is attached to or linked to the surface of the dense star polymer or encapsulated within the interior of the dense star polymer by means of covalent bonding, hydrogen bonding, adsorption, absorption, metallic bonding, van der Waals forces, ionic bonding, coulombic forces, hydrophobic or hydrophilic forces, or any combination thereof; with the proviso that the carried material maintains its effectiveness in the conjugate.

Claim 32

A solvent soluble, radially symmetrical dense star polymer conjugate of the formula: (P).sub.x *(M).sub.y (I) wherein each P represents a dendrimer of a dense star polymer wherein the dense star polymer has at least one core branch emanating from a core, said branch having at least one terminal group provided that (1) the ratio of terminal groups to the core branches is two or greater, (2) the density of terminal groups per unit volume in the polymer is at least 1.5 times that of an extended conventional star polymer having similar core and monomeric moieties and a comparable molecular weight and number of core branches, each of such branches of the extended conventional star polymer bearing only one terminal group, and (3) the dense star polymer has a molecular volume that is no more than about 80 percent of the molecular volume of said extended conventional star polymer as determined by dimensional studies using scaled Corey-Pauling molecular models, and has regular dendritic branching; x represents an integer of 1 or greater; each M represents a carried material, or a different carried material and is a contrast agent, fluorescing entity, paramagnetic entity, radionuclide, or aromatic ultraviolet absorber; y represents an integer of 1 or greater; and * indicates that the carried material is attached to or linked to the surface of the dense star polymer or encapsulated within the interior of the dense star polymer by means of covalent bonding, hydrogen bonding, adsorption, absorption, metallic bonding, van der Waals forces, ionic bonding, coulombic forces, hydrophobic or hydrophilic forces, or any combination thereof; with the proviso that the carried material maintains its effectiveness in the conjugate.

Claim 33

The conjugate of claim 30 wherein the contrast agent is hydrophobic.

Claim 34

The conjugate of claim 30 wherein the contrast gent is hydrophilic.

Claim 35

The conjugate of claim 30 wherein the M is encapsulated and the weight ratio of M to P is 10:1.

Claim 36

The conjugate of claim 30 wherein the M is encapsulated and the weight ratio of M to P is 8:1.

Claim 37

The conjugate of claim 30 wherein the M is encapsulated and the weight ratio of M to P is 5:1.

Claim 38

The conjugate of claim 30 wherein the M is encapsulated and the weight ratio of M to P is 3:1.

Claim 39

The conjugate of claim 30 wherein the M is encapsulated and the weight ratio of M to P is from 0.5:1 to 0.1:1.

Claim 40

The conjugate of claim 30 wherein the M is on the surface and the molar ratio of an ionic M to P is 0.1-1,000:1.

Claim 41

The conjugate of claim 30 wherein the M is on the surface and the molar ratio of an ionic M to P is 1-50:1.

Claim 42

The conjugate of claim 30 wherein the M is on the surface and the molar ratio of an ionic M to P is 2-6:1.

Claim 43

A conjugate of claim 30 wherein the carried material is a contrast agent.

Claim 44

The conjugate of claim 41 wherein the contrast agent comprises a metal ion selected from Gd, Mn and Fe.

Claim 45

The conjugate of claim 42 wherein the contrast agent is a chelated metal ion selected from Gd, Mn and Fe.

Claim 46

The conjugate of claim 41 wherein the contrast agent is prepared by reaction of an α,β-unsaturated ester, an α,β-unsaturated ketone, an α,β-unsaturated nitrile, an α,β-unsaturated carboxyl, isothiocyanato or epoxide moiety.

Claim 47

The conjugate of claim 44 wherein the contrast agent is derived from 1,4,7,10-tetraazacyclododecane-N,N',N"-triacetic acid.

Claim 48

The conjugate of claim 45 wherein the dendrimer portion of the conjugate is polyamidoamine.

Claim 49

The conjugate of claim 45 wherein the dendrimer portion of the conjugate is polyethyleneimine.

Claim 50

The conjugate of claim 44 wherein the contrast agent is derived from diethylenetriaminepentaacetic acid.

Claim 51

The conjugate of claim 44 wherein the contrast agent is derived from 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid.

Claim 52

The conjugate of claim 41 for use as a diagnostic agent.

Claim 53

The conjugate of claim 50 wherein the diagnostic agent is hydroxyethyl-1,4,7-tris(carbomethoxymethyl)-1,4,7,10-tetraazacyclododecane PAMAM conjugated with a metal ion selected from Gd, Mn and Fe.

Claim 54

The conjugate of claim 50 wherein the diagnostic agent is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid PAMAM conjugated with a metal ion selected from Gd, Mn and Fe.

Claim 55

The conjugate of claim 30 wherein the carried material is a fluorescing entity.

Claim 56

The conjugate of claim 53 wherein the fluorescing entity is fluorescein and the dendrimer portion is a polyethyleneimine.

Claim 57

The conjugate of claim 53 wherein the fluorescing entity is fluorescein and the dendrimer portion is a polyamidoamine.

Claim 58

The conjugate of claim 30 wherein the carried material is paramagnetic entity.

Claim 59

The conjugate of claim 56 wherein the paramagnetic entity is a metal ion selected from Gd, Mn, and Fe.

Claim 60

The conjugate of claim 56 wherein the paramagnetic entity is a chelated metal ion selected from Gd, Mn and Fe.

Claim 61

The conjugate of claim 30 wherein the carried material is a radionuclide.

Claim 62

The conjugate of claim 59 wherein the radionuclide is selected from 90 Y and 111 In.

Claim 63

The conjugate of claim 59 wherein the dendrimer is polyethyleneimine and the radionuclide is 90 Y.

Claim 64

The conjugate of claim 30 wherein the carried material is an aromatic ultraviolet absorber.

Claim 65

The conjugate of claim 62 wherein the aromatic ultraviolet absorber is salicyclic acid.

Claim 66

The conjugate of claim 30 wherein the carried material causes a detectable and measurable perturbation of a system.

Claim 67

The conjugate of claim 30 for use as a reagent in positron emission tomography, computer aided tomography, or magnetic resonance imaging.