Gas-filled microspheres with fluorine-containing shells

Claim 2

A composition for use as an ultrasonic imaging agent comprising an aqueous suspension of microspheres, said microspheres comprising a shell of fluorine-containing amphiphilic, biocompatible material surrounding a microbubble of at least one biocompatible gas.

Claim 3

The composition of claim 1, wherein the gas has a solubility of less than 0.01 mL per mL of water at 25° C. and 1 atm.

Claim 4

The composition of claim 2, wherein the gas is a perfluorocarbon.

Claim 5

The composition of claim 3, wherein the perfluorocarbon gas is selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane and perfluoropentane.

Claim 6

The composition of claim 1, wherein the gas is a hydrocarbon.

Claim 7

The composition of claim 5, wherein the hydrocarbon gas is selected from the group consisting of methane, ethane, propane, n-butane, isobutane and pentane.

Claim 8

The composition of claim 1, wherein the shell comprises a fluorine-containing amphiphilic, biocompatible material selected from the group consisting of lipids, proteins, and synthetic organic polymers.

Claim 9

The composition of claim 1, wherein the fluorine-containing amphiphilic biocompatible material is a lipid.

Claim 10

The composition of claim 8, wherein the lipid is a phospholipid.

Claim 11

The composition of claim 1, wherein the fluorine-containing amphiphilic biocompatible material is a protein.

Claim 12

The composition of claim 10 wherein the protein is human serum albumin.

Claim 13

The composition of claim 1, wherein the fluorine-containing amphiphilic biocompatible material is a synthetic organic polymer.

Claim 14

The composition of claim 1 wherein the microsphere shells contain 0.5 to 20 percent by weight fluorine.

Claim 15

A process for making pressure resistant microspheres, said microspheres comprising a shell of fluorine-containing amphiphilic, biocompatible material surrounding a microbubble of at least one biocompatible gas, said process comprising the steps of: (a) introducing fluorine into an amphiphilic, biocompatible material by reacting a fluorine-containing reactive compound with said amphiphilic, biocompatible material to form a fluorine-containing amphiphilic, biocompatible shell material; and (b) simultaneously or subsequently forming said microspheres from said fluorine-containing amphiphilic, biocompatible shell material and said biocompatible gas.

Claim 16

A process for making pressure resistant microspheres, said microspheres comprising a shell of fluorine-containing amphiphilic, biocompatible material surrounding a microbubble of at least one biocompatible gas, said process comprising the steps of: (a) introducing fluorine into an amphiphilic, biocompatible material by reacting a fluorine-containing reactive compound with said amphiphilic, biocompatible material to form a fluorine-containing amphiphilic, biocompatible shell material; and (b) simultaneously or subsequently forming said microspheres from said fluorine-containing amphiphilic, biocompatible shell material and said biocompatible gas.

Claim 17

The process of claim 14 wherein the reactive compound is selected from the group consisting of aldehydes, isocyanates, isothiocyanates, epoxides, alkyl esters, acyl halides, sulfonyl halides, anhydrides, acid halides, and alkyl sulfonates.

Claim 18

The process of claim 14 wherein the reactive compound contains at least one perfluorocarbon moiety selected from the group consisting of --CF 3 , --C 2 F 5 , --C 3 F 7 and --C(CF 3 ) 3 .

Claim 19

The process of claim 14, further comprising forming the microspheres in the presence of at least one gas having a solubility of less than 0.01 mL per mL of water at 25° C. and 1 atm.

Claim 20

The process of claim 17 wherein the gas is a perfluorocarbon gas.

Claim 21

A method to enhance the contrast of tissues and organs of a patient in an ultrasonic image comprising: (a) injecting the composition of claim 1 into the patient; and (b) ultrasonically imaging the tissues and organs while the composition is present therein.