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Methods of treating vascular disease

A technique of angioplasty and angioplasty, which is applied in the direction of cardiovascular system diseases, blood diseases, extracellular fluid diseases, etc., and can solve problems such as limitations

Inactive Publication Date: 2005-07-27
BETH ISRAEL DEACONESS MEDICAL CENT INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Intimal hyperplasia continues to limit the success of these therapeutic interventions

Method used

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  • Methods of treating vascular disease
  • Methods of treating vascular disease
  • Methods of treating vascular disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0143] Example 1 CO Inhibition of arteriosclerosis, formation of intimal hyperplasia and proliferation of SMC

[0144] Animals Male (250-350g) Brown Norway rats (Brown Norway rats) (RT1 n ) for aortic graft donors, male (250-350g) Lewis rats (RT1 1 ) are used as receptors. Dawley (400-450 g) rats were used in the balloon injury model. Mature male C57BL / 6, C57 / S 129, p21 - / - and p53 - / - Nude mice were purchased from Jackson Laboratory (Bar Harbor, ME). mkk3 (- / -) Nude mice were generated as described by Lu et al. (EMBO. 18:1845-1857 (1999)). inos - / - and enos - / - Mice were housed at the University of Pittsburgh.

[0145] Aortic Graft Model Aortic grafting was performed as described by Shimizu et al. (Nat Med. 7:738-741 (2001)). Briefly, a 3-4 cm descending aorta was harvested from the donor and implanted between the recipient's renal artery and the aortic bifurcation. Both ends of the native abdominal aorta were sutured.

[0146] Balloon Injury Model Balloon ang...

Embodiment 2

[0203] Example 2. Protocol for handling patients during angioplasty and transplant procedures

[0204] The following examples show protocols for patient management during angioplasty and for the use of carbon monoxide therapy to treat donors, organs and / or recipients during transplant surgery. Any one or several of the following methods may be used in transplant surgery.

[0205] Angioplasty

[0206] CO may be administered systemically or locally to the patient prior to, during and / or after the angioplasty procedure on the patient. The dose administered can be from 10 ppm to 1000 ppm (eg, about 100 ppm to about 800 ppm, about 150 ppm to about 600 ppm (eg, about 150 ppm), or about 200 ppm to about 500 ppm (eg, about 250 ppm to about 500 ppm)). For example, CO can be administered to the patient intermittently or continuously, starting 0-20 days before the procedure, for example, starting at least about 30 minutes before the procedure, for example, about 1, 2, 3, 5, 7, or 10 ...

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Abstract

The present invention relates to a method of treating patients suffering from, or at risk for, intimal hyperplasia and / or arteriosclerosis. The treatment includes administering a pharmaceutical composition that includes carbon monoxide to the patient.

Description

[0001] References to related applications [0002] This application claims priority to US Provisional Application No. 60 / 356,718, filed February 13, 2002, the entire contents of which are incorporated herein by reference. [0003] Statement of Federally Funded Research [0004] This invention was made with government support under National Institutes of Health (NIH) grant numbers HL55330, HL60234, HL67040, HL58688, HL53458, HL60234, HL5785405, and AI42365. The government has certain rights in this invention. technical field [0005] The present invention generally relates to the treatment of vascular disease. Background technique [0006] Heme oxygenase-1 (Hemeoxygenase-1 (HO-1)) catalyzes the first step in the degradation of heme. HO-1 cleaves the α-meso carbon bridge of the b-type heme molecule by oxidation to produce equimolar amounts of biliverdin IXa, carbon monoxide (CO), and free iron. Biliverdin is then converted to bilirubin by biliverdin reductase, and free iro...

Claims

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Application Information

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IPC IPC(8): A61B18/20A61F2/82A61F2/958A61K33/00A61M25/00A61M25/10A61P7/02A61P9/10A61P9/14A61P41/00
CPCA61K33/00A61P41/00A61P7/02A61P9/00A61P9/10A61P9/14A61K33/44
Inventor 利奥·E·奥特贝因奥古斯丁·M·K·乔伊弗里茨·H·巴赫布赖恩·朱克布朗
Owner BETH ISRAEL DEACONESS MEDICAL CENT INC