US5123414A — Liposomes as contrast agents for ultrasonic imagi…

Claim 1

Independent Claim 123 words

A method of synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a cooled gas, thereby dissolving a first portion of said gas into said liquid media, so that a portion of said dissolved gas enters said liposomes, (c) rapidly depressurizing said vessel by releasing a second portion of said gas from said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes, (d) administering said liposomes to a patient, and (e) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 2

Independent Claim 123 words

A method of synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a cooled gas, thereby dissolving a first portion of said gas into said liquid media, so that a portion of said dissolved gas enters said liposomes, (c) rapidly depressurizing said vessel by releasing a second portion of said gas from said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes, (d) administering said liposomes to a patient, and (e) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 3

Independent Claim 117 words

A method of synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a gas, (c) bubbling said gas through said liquid media, thereby dissolving a portion of said gas in said liquid media, so that a portion of said dissolved gas enters said liposomes, (d) depressurizing said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes, (e) administering said liposomes to a patient, and (f) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 4

Independent Claim 117 words

A method of synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a gas, (c) bubbling said gas through said liquid media, thereby dissolving a portion of said gas in said liquid media, so that a portion of said dissolved gas enters said liposomes, (d) depressurizing said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes, (e) administering said liposomes to a patient, and (f) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 5

Independent Claim 93 words

A method for synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a gas, (c) cavitating said liquid media, (d) cooling said liquid media during said cavitation, (e) depressurizing said vessel, thereby resulting in a liposome having encapsulated therein a gas, (f) administering said liposomes to a patient, and (g) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 6

Independent Claim 93 words

A method for synthesizing a liposome having encapsulated therein a gas and employing said liposome in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a gas, (c) cavitating said liquid media, (d) cooling said liquid media during said cavitation, (e) depressurizing said vessel, thereby resulting in a liposome having encapsulated therein a gas, (f) administering said liposomes to a patient, and (g) scanning said patient with a medical imaging device to obtain enhanced visible images of an internal region of said patient.

Claim 7

Independent Claim 94 words

A method of synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a cooled gas, thereby dissolving a first portion of said gas into said liquid media, so that a portion of said dissolved gas enters said liposomes, and (c) rapidly depressurizing said vessel by releasing a second portion of said gas from said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes.

Claim 8

Independent Claim 94 words

A method of synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a cooled gas, thereby dissolving a first portion of said gas into said liquid media, so that a portion of said dissolved gas enters said liposomes, and (c) rapidly depressurizing said vessel by releasing a second portion of said gas from said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes.

Claim 9

Dependent Claim 25 words

The method according to claim 4 wherein said gas is selected from the group consisting of nitrogen, oxygen, carbon dioxide, xenon, argon, neon and helium.

Claim 10

Dependent Claim 16 words

The method according to claim 4 wherein said liquid media is a phosphate buffered saline solution.

Claim 11

Dependent Claim 14 words

The method according to claim 4 wherein said liposomes are comprised of egg phosphatidylcholine.

Claim 12

Dependent Claim 30 words

The method according to claim 4 wherein the step of pressurizing said vessel comprises the step of pressurizing said vessel to a pressure between about 50 and about 120 psi.

Claim 13

Dependent Claim 28 words

The method according to claim 4 wherein the temperature of said cooled gas prior to said pressurization of said vessel is between about 1° to about 4° C.

Claim 14

Independent Claim 90 words

A method of synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a gas, (c) bubbling said gas through said liquid media, thereby dissolving a portion of said gas in said liquid media, so that a portion of said dissolved gas enters said liposomes, and (d) depressurizing said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes.

Claim 15

Independent Claim 90 words

A method of synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in a vessel, (b) pressurizing said vessel with a gas, (c) bubbling said gas through said liquid media, thereby dissolving a portion of said gas in said liquid media, so that a portion of said dissolved gas enters said liposomes, and (d) depressurizing said vessel, thereby causing said dissolved gas having entered said liposomes to form bubbles within said liposomes.

Claim 16

Dependent Claim 29 words

The method according to claim 10 wherein the step of depressurizing said vessel further comprises the step of rapidly releasing a portion of said liquid media from said vessel.

Claim 17

Dependent Claim 112 words

The method according to claim 11 wherein: (a) said vessel is approximately cylindrically shaped, said vessel having an inlet port, and outlet port, and a bottom, a tube disposed in said vessel, said tube having first and second ends, said first end of said tube disposed in said bottom of said vessel, said second end of said tube in flow communication with said inlet port, and (b) the step of pressurizing said vessel and bubbling said gas comprises the steps of introducing said gas into said inlet port under pressure and allowing said gas to flow through said tube, said gas discharging from said tube at said first end of said tube.

Claim 18

Dependent Claim 21 words

The method according to claim 12 wherein the step of depressurizing said vessel is performed in less than about 5 seconds.

Claim 19

Dependent Claim 52 words

The method according to claim 12 wherein: (a) said second end of said tube is in flow communication with said outlet port, and (b) the step of depressurizing said vessel comprises the step of allowing said pressurizing gas to force said liquid to flow through said tube and out said outlet port.

Claim 20

Dependent Claim 32 words

The method according to claim 12 wherein said bottom of said vessel curves convexly inward, said first end of said tube being closest to the most inward point on said convex bottom.

Claim 21

Dependent Claim 25 words

The method according to claim 10 wherein said gas is selected from a group consisting of nitrogen, oxygen, carbon dioxide, xenon, argon, neon and helium.

Claim 22

Dependent Claim 29 words

The method according to claim 10 wherein the step of pressurizing said vessel comprises the step of pressurizing said vessel to a pressure in approximately the 50-120 psi range.

Claim 23

Dependent Claim 16 words

The method according to claim 10 wherein said liquid media is a phosphate buffered saline solution.

Claim 24

Dependent Claim 14 words

The method according to claim 10 wherein said liposomes are comprised of egg phosphatidylcholine.

Claim 25

Independent Claim 66 words

A method for synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a gas, (c) cavitating said liquid media, (d) cooling said liquid media during said cavitation, and (e) depressurizing said vessel, thereby resulting in a liposome having encapsulated therein a gas.

Claim 26

Independent Claim 66 words

A method for synthesizing a liposome having encapsulated therein a gas, said liposome being particularly useful in medical imaging, comprising the steps of: (a) placing a liquid media containing liposomes in (b) pressurizing said vessel with a gas, (c) cavitating said liquid media, (d) cooling said liquid media during said cavitation, and (e) depressurizing said vessel, thereby resulting in a liposome having encapsulated therein a gas.

Claim 27

Dependent Claim 27 words

The method according to claim 20 wherein the step of cavitating said liquid media comprises the step of generating high frequency sound waves in said liquid media.

Claim 28

Dependent Claim 39 words

The method according to claim 21 wherein the step of generating high frequency sound waves comprises the step of generating waves at a frequency of about 20 kHz and an amplitude about in the range of about 30-120 μm.

Claim 29

Dependent Claim 27 words

The method according to claim 21 wherein the step of generating high frequency sound waves in said liquid media comprises the step of sonicating said liquid media.

Claim 30

Dependent Claim 45 words

The method according to claim 22 wherein the step of pressurizing said vessel comprises the step of pressurizing said vessel to a pressure in the range of about 50 to about 120 psi using carbon dioxide cooled to about 1° to about 4° C. range.

Claim 31

Dependent Claim 28 words

The method according to claim 23 wherein the step of cooling said liquid media comprises the step of circulating a cooling fluid over the exterior of said vessel.

Claim 32

Dependent Claim 36 words

The method according to claim 24 wherein the step of cooling said liquid media comprises the step of maintaining the temperature of said liquid media in a range of about 1° C. to about 4° C.

Claim 33

Dependent Claim 15 words

The method according to claim 24 wherein said liposomes comprise cholesterol mixed with egg phosphatidylcholine.

Claim 34

Dependent Claim 15 words

The method according to claim 24 wherein said liposomes comprise cholesterol mixed with saturated phospholipids.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1995-06-23	1995-12-23	1996-06-23	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1999-06-23	1999-12-23	2000-06-23	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2003-06-23	2003-12-23	2004-06-23	$7700.00	Window Closed / Lapsed

Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same

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