US5658892A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Compound delivery using high-pressure impulse transients
Assignee: General Hospital Corp
•
Filing: 1995-02-07
•
Granted: 1997-08-19
•
Expires: 2015-02-07
Abstract
Abstract A method of increasing delivery of a compound from an exterior region to an interior region of a cell without causing substantial lethality to the cell. The method includes the steps of first providing the compound in the exterior region proximal to a membrane of the cell, and then exposing the membrane to a time-dependent impulse transient characterized by a rise time and a magnitude. In this manner, the exposing step temporarily increases the permeability of the membrane, resulting in an increase in the diffusion of the compound from the exterior region to the interior region thereby enhancing the delivery of the compound without causing substantial lethality to the cell.
Inventors
- 👤 Thomas J. Flotte
- 👤 Apostolos G. Doukas
- 👤 Daniel J. McAuliffe
- 👤 Therese M. Anderson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 12:30
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/13; A61K31/135; A61K31/21; A61K31/215; A61K31/235; A61K31/24; A61K31/33; A61K31/395; A61K31/40; A61K31/409; A61N; A61N1/00; A61N1/40; A61N7/00; C; C12; C12M; C12M35/00; C12M35/02; C12N; C12N13/00; C12N15/00; C12N15/09; C12N15/87; A61B; A61B18/00; A61B18/18; A61B18/20; A61B18/22; A61B18/26; A61K48/00; A61M; A61M37/00; A61M37/0092
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
103 words
A method of increasing delivery of a compound from an exterior region to an interior region of a cell, said method comprising: providing the compound in the exterior region proximal to a membrane of the cell, and exposing the membrane to a time-dependent impulse transient characterized by a rise time with a time constant of between 1 and 150 nanoseconds, and a magnitude of between 1 and 500 bars, wherein said exposing temporarily increases the permeability of the membrane to increase diffusion of the compound from the exterior region to the interior region, thereby enhancing the delivery of the compound to the cell.
Claim 2
Independent Claim
103 words
A method of increasing delivery of a compound from an exterior region to an interior region of a cell, said method comprising: providing the compound in the exterior region proximal to a membrane of the cell, and exposing the membrane to a time-dependent impulse transient characterized by a rise time with a time constant of between 1 and 150 nanoseconds, and a magnitude of between 1 and 500 bars, wherein said exposing temporarily increases the permeability of the membrane to increase diffusion of the compound from the exterior region to the interior region, thereby enhancing the delivery of the compound to the cell.
Claim 3
Dependent Claim
35 words
The method of claim 1, wherein said exposing further includes generating the impulse transient in the exterior region of the cell, and then allowing the impulse transient to propagate until incident on the cell membrane.
Claim 4
Dependent Claim
19 words
The method of claim 2, wherein said generating comprises impulsively exciting the exterior region using a rapid, time-dependent force.
Claim 5
Dependent Claim
17 words
The method of claim 3, wherein the time-dependent force results from thermoelastic expansion of the exterior region.
Claim 6
Dependent Claim
34 words
The method of claim 4, wherein said generating comprises depositing over a short time period an amount of heat in the exterior region, said heat resulting in thermal expansion to cause the time-dependent force.
Claim 7
Dependent Claim
28 words
The method of claim 5, wherein the heat is generated using a pulsed optical source emitting a wavelength which is absorbed by a portion of the exterior region.
Claim 8
Dependent Claim
13 words
The method of claim 6, wherein the pulsed optical source is a laser.
Claim 9
Dependent Claim
15 words
The method of claim 3, wherein the rapid, time-dependent force is generated using a transducer.
Claim 10
Dependent Claim
34 words
The method of claim 8, wherein the transducer is in direct contact with the exterior region, and undergoes rapid displacement following application of an optical, thermal, or electric field to generate the impulse transient.
Claim 11
Dependent Claim
20 words
The method of claim 9, wherein the transducer is ablated using the applied optical field to cause the rapid displacement.
Claim 12
Dependent Claim
22 words
The method of claim 9, wherein the transducer undergoes piezoelectric expansion following application of the electrical field to cause the rapid displacement.
Claim 13
Dependent Claim
23 words
The method of claim 9, wherein the transducer undergoes thermal expansion following application of heat or a plasma to cause the rapid displacement.
Claim 14
Dependent Claim
13 words
The method of claim 1, wherein the time constant is below 35 nanoseconds.
Claim 15
Dependent Claim
14 words
The method of claim 1, wherein the pressure is between 250 and 350 bars.
Claim 16
Dependent Claim
15 words
The method of claim 1, wherein multiple impulse transients are used during said exposing step.
Claim 17
Dependent Claim
21 words
The method of claim 1, wherein said providing comprises directly applying the compound to the exterior region proximal to the cell.
Claim 18
Dependent Claim
28 words
The method of claim 16, wherein the compound is applied to a solution in the exterior region, and the cell is exposed to the impulse transient in vitro.
Claim 19
Dependent Claim
30 words
The method of claim 1, wherein said providing comprises administering the compound to a patient prior to said exposing, and the cells are exposed to the impulse transient in vivo.
Claim 20
Dependent Claim
12 words
The method of claim 18, wherein the patient is a human patient.
Claim 21
Dependent Claim
12 words
The method of claim 19, wherein the patient has a genetic disease.
Claim 22
Dependent Claim
10 words
The method of claim 1, wherein said exposing is extracorporeal.
Claim 23
Dependent Claim
12 words
The method of claim 1, wherein said exposing is during invasive surgery.
Claim 24
Dependent Claim
19 words
The method of claim 1, wherein the cell is a diseased cell comprised in a region of diseased tissue.
Claim 25
Dependent Claim
50 words
The method of claim 22, wherein the compound has a delivery index of at least 50, and the impulse transient is administered when a level of the compound in a region of healthy tissue is less than 50 percent of the level of said compound present in the diseased tissue.
Claim 26
Dependent Claim
11 words
The method of claim 1, wherein the compound comprises nucleic acid.
Claim 27
Dependent Claim
11 words
The method of claim 25, wherein said nucleic acid is DNA.
Claim 28
Dependent Claim
11 words
The method of claim 25, wherein the nucleic acid is RNA.
Claim 29
Dependent Claim
11 words
The method of claim 26, wherein the DNA comprises a gene.
Claim 30
Dependent Claim
22 words
The method of claim 1, wherein the cell is a member of a population of cells exposed to said time-dependent impulse transient.
Claim 31
Dependent Claim
24 words
The method of claim 28, wherein the compound is a non-cytotoxic compound, and a substantial fraction of the population remains viable following said exposing.
Claim 32
Dependent Claim
15 words
The method of claim 1, wherein more that one compound is delivered to the cell.
References Cited (Backward Citations)
US4649151A
Cited
US4658023A
Cited
US4675338A
Cited
US4651739A
Cited
US4656186A
Cited
US4971991A
Cited
US5380411A
Cited
US5403590A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-08-18 | 2001-02-17 | 2001-08-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-08-18 | 2005-02-17 | 2005-08-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-08-18 | 2009-02-17 | 2009-08-19 | $7700.00 | Window Closed / Lapsed |