Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2011-06-07
2011-06-07
Bradley, Christina (Department: 1654)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
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
Bradley Christina
Fuchs Joseph A.
Macaluso Avani C.
Rockey Depke & Lyons, LLC
Rosalind Franklin University of Medicine and Science
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