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Use of xenon as neuroprotectant in a neonatal subject

a technology of neuroprotectant and xenon, which is applied in the direction of antinoxious agents, drug compositions, biocides, etc., can solve the problems of significant cost involved in the production of xenon through fractional distillation of liquid air, failure to materialize every day use of xenon anesthesia, and relatively small percentage of the total refined quantity of xenon available for anesthesia

Inactive Publication Date: 2009-12-17
IP2IPO INNOVATIONS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about using xenon to treat, prevent, or alleviate neurological deficits in neonates caused by anesthesia. The technical effect is the use of a specific gas to treat these issues in newborns.

Problems solved by technology

However, despite some impressive displays of clinical efficacy in patients (Luttropp et al., 1994; Lynch et al., 2000), everyday use of xenon anesthesia has failed to materialize.
This is largely associated with the significant cost involved in production of xenon through fractional distillation of liquid air, and hence the relatively small percentage of the total refined quantity of xenon available for anesthesia (Hanne Marx et al., 2001).
Consequently, use of xenon is likely to be restricted to special areas where there is an appreciable cost-benefit advantage.
Later work done by Jevtovic-Todorovic et al. showed that neonatal rats are vulnerable to harmful side effects of anesthesia during the synaptogenic period.
They demonstrated up to a 68-fold increase in the number of degenerating neurones above baseline in areas such as the laterodorsal and anteroventral thalamic nuclei (and to some extent layer II of the parietal cortex) after exposure to anesthetic agents (Jevtovic-Todorovic et al., 2003), which resulted in a functional neurological deficit in behaviour tests later in life.

Method used

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  • Use of xenon as neuroprotectant in a neonatal subject
  • Use of xenon as neuroprotectant in a neonatal subject
  • Use of xenon as neuroprotectant in a neonatal subject

Examples

Experimental program
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Effect test

example 1

Exposure to Anesthetic Gases

Animals

[0200]7 day old Sprague-Dawley rat pups were placed in individual wells of a custom-built anesthetic chamber, and randomised to groups A-F to receive one of 6 gas combinations for 6 hours. Previous work has established that NMDA receptor antagonists have their maximal neurodegenerative affect 7 days after birth (Ikonomidou et al., 1999).

Gas Delivery

[0201]Group B received 75% nitrous oxide and 25% oxygen as delivered by a calibrated anesthetic machine, whereas group C received 75% xenon along with 25% oxygen through a customised anesthetic machine modified for xenon delivery (Ohmeda, modified by Air Products, Surrey, UK). Group D were exposed to 25% oxygen along with 0.75%; isoflurane. The remaining 2 groups were exposed to combinations of gases—namely 25% oxygen+75% A nitrous oxide+0.75% isoflurane (group E) and 25% oxygen+60% xenon+15% nitrogen+0.75% isoflurane (group F). The high cost of xenon precludes its use in an open-circuit, consequently gr...

example 2

Methods

Neuronal Glial Co-Culture

[0217]Whole cerebral neocortices (devoid of the hippocampus, basal ganglia and meninges) were obtained from early post natal (1-2 day old) pups of BALB / c mice. The pups were anaesthetised with isoflurane and then decapitated with the heads placed immediately into 4° C. HSG solution, an isotonic, high sucrose glucose solution made primarily from Hank's balanced salt solution (HBSS, GibroBRL) enhanced with NaHCO3 (0.04 M), sucrose (0.2 M) and D-Glucose (0.3 M) also containing antibiotic-anti-mycotic solution (AAS, GibroBRL). Throughout the micro dissection process, brain tissues were kept in 4° C. HSG solution.

[0218]The brain tissue was then immersed in 0.25% trypsin and a placed in a shaking air chamber for 50 minutes at 37° C. filled with 5% CO2 and 95% room air. DNase was then added to the mixture and placed back into the shaking air chamber for a further 15 minutes. The mixture was then centrifuged at 1600 rpm for 10 minutes at 4° C. and the superna...

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Abstract

The present invention relates to the use of xenon in the preparation of a medicament for preventing and / or alleviating one or more anesthetic-induced neurological deficits in a neonatal subject. The present invention further relates to combinations of xenon and sevoflurane, and use thereof as preconditioning agents for administration prior to hypoxic-ischaemic injury.

Description

[0001]The present invention relates to the field of anesthetics. More specifically, the invention relates to anesthetic agents suitable for use in newborn and / or fetal subjects.BACKGROUND TO THE INVENTION[0002]Xenon's anesthetic properties have been known to the medical profession for over 50 years (Cullen and Gross, 1951). However, despite some impressive displays of clinical efficacy in patients (Luttropp et al., 1994; Lynch et al., 2000), everyday use of xenon anesthesia has failed to materialize. This is largely associated with the significant cost involved in production of xenon through fractional distillation of liquid air, and hence the relatively small percentage of the total refined quantity of xenon available for anesthesia (Hanne Marx et al., 2001). Consequently, use of xenon is likely to be restricted to special areas where there is an appreciable cost-benefit advantage. One such area may be neonatal anesthesia, where xenon may lack harmful side effects seen with other c...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/00A61P25/00A61K31/08A61K45/06
CPCA61K31/08A61K33/00A61K45/06A61K2300/00A61P23/00A61P25/00A61P25/04A61P25/28A61P39/00A61P43/00
Inventor FRANKS, NICHOLAS PETERMAZE, MERVYN
Owner IP2IPO INNOVATIONS LTD
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