Cytoprotective therapeutic agents for the prevention of...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C514S021910

Reexamination Certificate

active

07956037

ABSTRACT:
The present invention relates generally to the use of γ-glutamyl antioxidants, particularly γ-glutamyl-cysteine, as cytoprotective agents to prevent reperfusion injury (i.e., hemorrhagic transformation) of the blood-brain barrier during reperfusion following an ischemic stroke. The γ-glutamyl antioxidants can be used alone or used in combination with an agent which inhibits the reverse movement of Na/Ca exchange in the blood-brain barrier such as 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate (KB-R7943).

REFERENCES:
http://www.nlm.nih.gov/medlineplus/antioxidants.html.
Gilgum-Sherki et al. “Antioxidant Therapy in Acute Central Nervous System Injury: Current State” Pharm. Rev., 2002, 54, 271-84.
Drake et al. “Elevation of brain glutathione by-glutamylcysteine ethyl ester protects against peroxynitrite-induced oxidative stress” J. Neurosci., 2002, 68, 776-84.
Yamamoto et al. “Protective actions of YM737, a new glutathione analog, against cerebral ischemia in rats.” Res Commun Chem Pathol Pharmacol., 1993, 81, :221-32.
Pilitsis et al. “Inhibition of Na(+)/Ca(2+) exchange by KB-R7943, a novel selective antagonist, attenuates phosphoethanolamine and free fatty acid efflux in rat cerebral cortex during ischemia-reperfusion injury.” Brain Res., 2001, 916, 192-8.
Lipton “Ischemic cell death in brain neurons,” Physiol. Rev., 1999, 79, 1431-1568).
Clark et al., “Efficacy of antioxidant therapies in transient focal ischemia in mice,” Stroke, 2001, 32, 1000-1004.
Carroll et al. “Nuclear factor-nB activation during cerebral reperfusion: effect of attenuation with N-acetylcysteine treatment,” Mol. Brain Res., 1998, 56, 186-191.
Khan et al. (“Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke,” J. Neurosci. Res., 2004, 76, 519-527).
Anderson et al. (“Glutathione monoethyl ester provides neuroprotection in a rat model of stroke,” Neurosci. Lett., 2004, 354, 163-165).
Park et al., (“Dose-response analysis of the effect of 21-aminosteroid tirilazad mesylate (U-74006F) upon neurological outcome and ischemic brain damage in permanent focal cerebral ischemia,” Brain Res., 1994, 645, 157-163).
Xue et al. (“Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats,” Stroke, 1992, 23, 894-899).
Yu et al. (“Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo,” J. Neurosci. Res., 1998, 53, 613-625).
Kilic et al. (Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia, J. Cereb. Blood Flow Metab., 1999, 19, 511-516).
Pei et al. (“Pre-treatment with melatonin reduces volume of cerebral infarction in a permanent middle cerebral artery occlusion stroke model in the rat,” Neurosci. Lett., 2002, 318, 141-144).
Kilic et al. (“Prophylactic use of melatonin protects against focal cerebral ischemia in mice: role of endothelin converting enzyme-1,” J. Pineal. Res., 2004, 37, 247-251).
Cao et al. (“a-Phenyl-tert-butyl-nitrone reduces cortical infarct and edema in rats subjected to focal ischemia,” Brain Res. 1994, 644, 267-272).
Zhao et al. (“Delayed treatment with the spin trap a-phenyl-n-tert-butyl nitrone (PBN) reduces infarct size following transient middle cerebral artery occlusion in rats,” Acta Physiol. Scand., 1994, 152, 349-350).
Schulz et al. (“Facilitation of postischemic reperfusion with a-PBN: assessment using NMR and doppler flow techniques,” Am. J. Physiol., 1997, 272, H1986-H1995).
Zausinger et al. (“Neurological impairment in rats after transient middle cerebral artery occlusion: A comparative study under various treatment paradigms,” Brain Res., 2000, 863, 94-105).
Yang et al. (“Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tertbutyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (SPBN), in rats subjected to focal embolic cerebral ischemia,” Exp. Neurol., 2000, 163, 39-45).
Kuroda et al. (“Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat,” J. Cereb. Blood Flow Metab., 1999, 19, 778-787).
Sydserff et al. (“Effect of NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window,” Br. J. Pharmacol., 2002, 135, 103-112).
Ginsberg et al. (“Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia,” Ann. Neurol., 2003, 54, 330-342).
van der Worp et al. (“Dietary vitamin E levels affect outcome of permanent focal cerebral ischemia in rats,” Stroke, 1998, 29, 1002-1006).
Mishima et al. (“Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral infarction in mice,” Neurosci. Lett., 2003, 337, 56-60).
Garcia-Estrada et al. (An alpha-lipoic acid-vitamin E mixture reduces postembolism lipid peroxidation, cerebral infarction, and neurological deficit in rats. Neurosci. Res., 2003, 47, 219-224).
Huang et al. (“Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke,” Proc. Natl. Acad. Sci. USA, 2001, 98, 11720-11724).
Takamatsu et al. (“Hydroxyl radical generation after the third hour following ischemia contributes to brain damage,” Eur. J. Pharmacol., 1998, 352, 165-169).
Sinha et al. (“Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats,” Life Sci., 2002, 71, 655-665).
Andrabi et al. (“Oxyresveratrol (trans-2,3V,4,5V-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia,” Brain Res., 2004, 1017, 98-107).
Mizuno et al. (“Inhibitory effect of MCI-186, a free radical scavenger, on cerebral ischemia following rat middle cerebral artery occlusion,” Gen. Pharm., 1998, 30, 575-578).
Shichinohe et al. (“Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia,” Brain Res., 2004, 1029, 200-206).
The Edaravone Acute Brain Infarction Study Group, “Effect of a novel free radical scavenger, Edaravone (MCI-186), on acute brain infarction, placebo-controlled, double-blind study at multicenters,” Cerebrovasc. Dis., 2003,15, 222-229).
Toyoda et al. “Free radical scavenger, Edaravone, in stroke with internal carotid artery occlusion,” J. Neurol. Sci., 2004, 221, 11-17).
Lee et al. “Sequential Combination of Intravenous Recombinant Tissue Plasminogen Activator and Intra-Arterial Urokinase in Acute Ischemic Stroke,” Am. J. Neuroradiology, 2004, 25, 1470-5).
Pilitsis et al. (“Inhibition of Na(+)/Ca(2+) exchange by KB-R7943, a novel selective antagonist, attenuates phosphoethanolamine and free fatty acid efflux in rat cerebral cortex during ischemia-reperfusion injury.” Brain Res., 2001, 916, 192-8).
Agarwal, R. and Shukla. Potential role of cerebral glutathione in the maintenance of blood-brain barrier integrity in rat. Neurochem. Res. 24:1507-1514, 1999.
Betz, A.L. Transport of ions across the blood-brain barrier. Fed Proc. 45:2050-2054, 1986.
Betz, A.L., Firth, J.A. And Goldstein, G.W. Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res. 192, 17-28, 1980.
Betz, A.L. and Goldstein, G.W. Specialized properties and solute transport in brain capillaries. Ann. Rev. Physiol. 48:241-250, 1986.
Homma, M., Suzuki, H., Kusuhara, H., Naito, M., Tsuruo, T. and Su

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Cytoprotective therapeutic agents for the prevention of... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Cytoprotective therapeutic agents for the prevention of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cytoprotective therapeutic agents for the prevention of... will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2708885

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.