Salvinorin compositions and uses thereof

A technology of carnosin and sage, applied in the field of carnosin compositions, can solve the problems of inapplicability for routine clinical use, inapplicability and the like

Active Publication Date: 2017-04-26
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these solvents are not suitable for routine clinical use, especially for intravenous (IV) delivery

Method used

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  • Salvinorin compositions and uses thereof
  • Salvinorin compositions and uses thereof
  • Salvinorin compositions and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0114] Carnosin A produces cerebral vasodilation via activation of nitric oxide synthase, kappa receptors, and adenosine triphosphate-sensitive potassium channels

[0115] In this example, we show that carnosin A acts via activation of nitric oxide synthase, adenosine triphosphate-sensitive potassium (K ATP ) channels and κ receptors dilate pial arteries.

[0116] Materials and methods

[0117] Carnosin A (purity ≥ 98%), sodium nitroprusside (SNP), N(G)-nitro-L-arginine (L-NNA), glibenclamide, iberidetoxin (iberiotoxin), cromakalim, calcitonin gene-related polypeptide (CGRP), NS 1619, naloxone, methionine enkephalin, norbinaltorphimine , 7-nitroindazole (7-NINA), sulpiride and isoproterenol were obtained from Sigma-Aldrich (St. Louis, MO, USA). All other chemicals were also obtained from Sigma and were of reagent grade.

[0118] Animals and Surgery

[0119] Neonatal pigs (1-6 days old, weighing 1.3-1.8 kg) of both sexes were used in this study. Protocols were approved by...

example 2

[0150] Administration of carnosin A following global cerebral hypoxia / ischemia preserves cerebrovascular autoregulation in piglets via the kappa opioid receptor

[0151] Neuronal death and behavioral dysfunction caused by hypoxia / ischemia (HI)-induced brain injury are not uncommon during the perinatal period. Worldwide, 23% of all newborn deaths are associated with asphyxia, and 30% of children born with moderate hypoxic-ischemic encephalopathy (HIE) may develop mental retardation, learning difficulties, and other disabilities. Unfortunately, there are no medications available to manage this devastating condition.

[0152] KOR agonists cause cerebral vasodilation, a key feature required to maintain brain autoregulation and reduce brain damage from ischemia. Following ischemia, brain autoregulation is impaired, causing decreased cerebral blood flow and neuronal death. We demonstrate in a piglet model that administration of carnosin A prior to global HI preserves cerebral arte...

example 3

[0186] Carnosin A pretreatment preserves cerebrovascular autoregulation via ERK / MAPK after cerebral hypoxic / ischemic injury in piglets

[0187] Cerebral hypoxia / ischemia due to interruption of cerebral blood flow during cardiopulmonary bypass and deep hypothermic circulatory arrest (DHCA) procedures for congenital heart surgery is an important clinical problem. Fifty percent of children with complex congenital heart disease who undergo cardiopulmonary bypass and DHCA have developmental deficits such as speech disability and attention deficit disorder by school age. The cerebral hypoxia / ischemia that occurs during DHCA is predictable and, therefore, it is possible to pharmacologically minimize ischemia-induced brain damage. Unfortunately, no drugs with proven clinical benefit have been identified.

[0188] Loss of cerebrovascular autoregulation is one of the key features of cerebral hypoxia / ischemia. Loss of autoregulation to hypotension can cause pressure-passive cerebral ci...

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Abstract

The invention relates to salvinorin compositions and uses thereof. Specifically, the invention relates to administering salvinorin compositions to treat diseases and disorders associated with vasoconstriction, vaso-occlusion, or disruption of blood flow and autoregulation. For example, salvinorin compositions may be administered to subjects with cardiac arrest, subarachnoid hemorrhage, stroke, cerebral vascular spasm, cerebral hypoxia / ischemia, cerebral artery occlusion, or any condition involved in autoregulation impairment.

Description

technical field [0001] The present invention relates to salvinorin compositions and uses thereof. In particular, the present invention relates to the administration of carnosin compositions to treat diseases and conditions associated with vasoconstriction, vascular occlusion, or disruption of blood flow and autoregulation. For example, a carnosin composition can be administered to an individual suffering from cardiac arrest, subarachnoid hemorrhage, stroke, cerebral vasospasm, cerebral hypoxia / ischemia, cerebral artery occlusion, or any condition involving impaired autoregulation. Background technique [0002] Carnosin A is the active component of Mexican sage (Salvia divinorum), a perennial herb native to Mexico in the Lamiaceae (Mentha) family. For religious purposes, Mexican sage has long been traditionally used to produce visionary states of consciousness during spiritual healing sessions. Carnosin A has been shown to be the most highly potent, naturally occurring non-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/537
CPCA61K9/0043A61K9/08A61K31/366A61K47/40A61P9/00A61P9/08A61P25/00
Inventor 刘仁玉
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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