US5527532A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Extraluminal regulation of the growth and repair of tubular structures in vivo
Assignee: Harvard University
•
Filing: 1993-09-02
•
Granted: 1996-06-18
•
Expires: 2013-09-02
Abstract
Abstract A method of regulating repair in a physiological system following injury to the lumen of a tubular structure in that system, and of testing the effectiveness of regulatory agent, is presented. The method includes administering a modulator of cell or tissue growth to an extraluminal site adjacent the injured tissue. Administration of substances such as heparin over sustained, prolonged periods controls intimal hyperplasia and smooth muscle cell proliferation, even at doses that are insufficient to have such a beneficial effect if administered systemically. Bolus administration of such compounds at higher doses typically used to achieve systemic effects may have no effect or may even produce adverse effects.
Inventors
- 👤 Elazer R. Edelman
- 👤 David H. Adams
- 👤 Morris J. Karnovsky
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 17:31
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
124 words
A method of regulating repair of a wall of luminal tissue following injury at a location on said wall, said method comprising, administering outside said luminal tissue wall at said location, a biocompatible compound-releasing system, said biocompatible compound-releasing system releasing a smooth muscle cell antiproliferative agent into said wall at said location, said releasing taking place over a period of at least 24 hours and being characterized by a rate and a dosage that is selected to be: a) high enough to control proliferation of smooth muscle cells in said wall at said location; and b) low enough to substantially avoid systemic levels of said agent that are high enough to control proliferation of smooth muscle cells at a location remote from said location.
Claim 2
Independent Claim
124 words
A method of regulating repair of a wall of luminal tissue following injury at a location on said wall, said method comprising, administering outside said luminal tissue wall at said location, a biocompatible compound-releasing system, said biocompatible compound-releasing system releasing a smooth muscle cell antiproliferative agent into said wall at said location, said releasing taking place over a period of at least 24 hours and being characterized by a rate and a dosage that is selected to be: a) high enough to control proliferation of smooth muscle cells in said wall at said location; and b) low enough to substantially avoid systemic levels of said agent that are high enough to control proliferation of smooth muscle cells at a location remote from said location.
Claim 3
Dependent Claim
62 words
The method of claim 1 in which the smooth muscle cell antiproliferative agent is heparin and the release rate is low enough to avoid transport of said heparin through said wall to establish a heparin level in the blood system equivalent to an anticoagulant heparin level that would have a discernable effect on clotting function as measured by activated prothrombin time (aPTT).
Claim 4
Independent Claim
26 words
The method of claims 1 or 2 in which the agent is heparin and said heparin is administered at a rate of less than 110 mg/day.
Claim 5
Dependent Claim
20 words
The method of claim 3 in which the heparin is administered at a rate less than 20.0 μmg/hr (0.48 mg/day).
Claim 6
Dependent Claim
20 words
The method of claim 4 in which the heparin is administered at a rate less than 5.0 μg/hr (0.12 mg/day).
Claim 7
Dependent Claim
20 words
The method of claim 5 in which the heparin is administered at a rate less than 0.5 μg/hr (0.012 mg/day).
Claim 8
Dependent Claim
28 words
The method of claim 1 in which the agent is delivered locally to a site of vascular injury from the perivascular space at the site of the injury.
Claim 9
Dependent Claim
21 words
The method of claim 1 in which the agent is administered substantially continuously over a period of at least 5 days.
Claim 10
Dependent Claim
21 words
The method of claim 8 in which the agent is administered substantially continuously over a period of at least 10 days.
Claim 11
Dependent Claim
17 words
The method of claim 3 in which the biocompatible compound-releasing system is a polymeric based releasing system.
Claim 12
Dependent Claim
15 words
The method of claim 1 in which the biocompatible compound-releasing system is an infusion pump.
Claim 13
Dependent Claim
16 words
The method of claim 1 in which the tissue comprises a portion of the vascular system.
Claim 14
Dependent Claim
12 words
The method of claim 12 in which the tissue comprises an artery.
Claim 15
Dependent Claim
16 words
The method of claim 1 in which the tissue comprises a portion of the reproductive system.
Claim 16
Dependent Claim
13 words
The method of claim 14 in which the tissue comprises a fallopian tube.
Claim 17
Dependent Claim
13 words
The method of claim 14 in which the tissue comprises the vas deferens.
Claim 18
Dependent Claim
16 words
The method of claim 1 in which the tissue comprises a portion of the genitourinary system.
Claim 19
Dependent Claim
16 words
The method of claim 17 in which the tissue comprises the ureter or the prostate gland.
Claim 20
Dependent Claim
16 words
The method of claim 1 in which the tissue comprises a portion of the gastrointestinal tract.
Claim 21
Dependent Claim
12 words
The method of claim 19 in which the tissue comprises the bowel.
Claim 22
Dependent Claim
16 words
The method of claim 1 in which the tissue comprises a portion of the pulmonary system.
Claim 23
Dependent Claim
16 words
The method of claim 21 in which the tissue comprises the trachea or the bronchial tree.
Claim 24
Dependent Claim
10 words
The method of claim 2 the heparin is anticoagulant heparin.
Claim 25
Dependent Claim
12 words
The method of claim 2 in which the heparin is non-anticoagulant heparin.
References Cited (Backward Citations)
US3797485A
Cited
US3993071A
Cited
US4391797A
Cited
US4495174A
Cited
US4808402A
Cited
US4898732A
Cited
US5120322A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-06-18 | 1999-12-18 | 2000-06-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-06-18 | 2003-12-18 | 2004-06-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-06-18 | 2007-12-18 | 2008-06-18 | $7700.00 | Window Closed / Lapsed |