Compositions and treatment method for brain and spinal cord injuries

Abstract

Cerebral edema is the final common pathway for all CNS tissue injuries. The CSF is the major player for cerebral edema and the resultant blood perfusion deficit. A composition and method for treating injured central nervous tissue, or preventing injury to central nervous system tissue is provided. The composition includes two washing solutions, a first solution comprising an emulsion of oil, water, at least one osmotic agent and at least one emulsifier; the second solution comprising a pre-emulsion comprising water, oil, at least one osmotic agent, and at least one emulsifier. The method provides for withdrawing a volume of cerebrospinal fluid from the subarachnoid space and flushing the subarachnoid space with one or both washing solutions. Other materials may be added to the solutions to treat or prevent injury to nerve tissue resulting from injury or interruption of circulation.

Description

[0001] This application is a continuation in part of application Ser. No. 09 / 962,009, filed Sep. 24, 2001, the disclosure of which is hereby incorporated by reference.FIELD OF THE INVENTION[0002] This invention is related to medical formulations used to treat and protect the brain and spinal cord and methods of using those formulations. In particular, the invention relates to neuroprotective formulations and methods using those formulations to protect the brain and spinal cord or minimize lasting damage.BACKGROUND INFORMATION[0003] Central Nervous System (CNS) tissue including brain and spinal cord is very vulnerable to injuries. For example, the brain is believed to tolerate complete interruption of blood flow (such as cardiac arrest) for a maximum of about 5 to 10 minutes.[0004] Most CNS injuries, including stroke, trauma, hypoxia-ischemia, multiple sclerosis, seizure, infection, and poisoning directly or indirectly involve a disruption of blood supply to the CNS, and share the sa...

AI Technical Summary

Benefits of technology

[0016] One advantage is it provides an effective treatment and prevention for CNS tissue injuries.

[0034] The first washing solution is an emulsion. It should contain oil, an osmotic agent, water and at least one emulsifier. Typically, the emulsion contains up to about 31-80% oil. Generally a water in oil emulsion is preferred. However, oil in water emulsions have also been effective. Intralipid solutions (10%, 20% and 30%), used clinically for parental nutrition, such as those manufactured and distributed by Baxter, Fresenius Kabi, Pharmacia & Upjohn etc may also be effective. The first washing solution acts as a hook to pull out edematous CSF fluids away from the CNS tissue into the oil. The oil can be any non-toxic, organic liquid. Hydrocarbon oils and silicone oils are effective. Any hydrocarbon oils from plant, animal sources and mineral oil such as soybean oil, cod liver oil, vitamin E oil, olive oil, canola oil, corn oil, and mixtures of these oils in any concentration ratio may be used.

Problems solved by technology

Central Nervous System (CNS) tissue including brain and spinal cord is very vulnerable to injuries.

He found that a large amount of the brain suffered from perfusion deficits.

Clinical treatment for CNS injury induced edema including intravenous administration of osmotic agent, diurtic, removal of cerebrospinal fluid, coticosterroids, however, the efficacy is temporary and limited.

Current search for a neuroprotective treatment has yielded a disappointing result including oxygen free radical scavengers, calcium channel blockers and glutamate receptor antagonists to monoclonal antibodies that attempt to curtail inflammatory cascades occurring in cerebral injuries.

Acetazolamide can inhibit cerebrospinal fluid production, but administering of acetazolamide alone does not have a neuroprotective effect.

Clinical treatment for CNS injury induced edema including intravenous administration of osmotic agent, diurtic, removal of cerebrospinal fluid, coticosterroids, however, the efficacy is temporary and limited.

Current search for a neuroprotective treatment has yielded a disappointing result.

In ischemic injury, CSF has a toxic effect of facilitating cerebral edema.

While intracellularly excessive water content is directly toxic to the CNS cells, the cerebral edema can also block cerebral blood flow and collateral circulation to damaged nerve tissue, causing the "no-reflow" phenomenon or "hypoperfusion".

This failure of circulation results in continuing damage to CNS tissue after the interruption of blood flow is reversed leading to irreversible damage.

Swelling of the tissue makes the Virchow-Robin space (also known as the perivascular space or extracellular space) smaller and may even cause it to collapse, thereby compressing the small blood vessels and resulting in a obstruction of the blood flow, such as a "hypoperfusion" or even "no-reflow" phenomenon, which prolongs the original ischemic duration, blocks collateral circulation and induces a feedback loop.

As the duration of blood flow interruption increases, the edema spreads throughout the CNS tissue causing additional damage in an ischemic cascade.

However, during ischemic episodes, CFS has a toxic effect by facilitating cerebral edema and the resulting in no-reflow phenomenon after disruption of blood flow to CNS tissue.

When injury occurs, CSF readily available to penetrate CNS tissues through water channels, while intracellular water unbalance exert direct toxicity to cells, swelling of the tissue around the Virchow-Robin space results in "hypoperfusion" or even "no-reflow" phenomenon, which prolongs the original ischemic duration, blocks collateral circulation and induces a feedback loop.

However, it is very difficult, almost impossible, mechanically to remove CSF completely from the subarachnoid spaces because the CNS (i.e. brain and spinal cord) contour is very complex with many sulci, gyri and pools.

Mechanically withdrawing CSF alone is not sufficient enough to achieve the neuroprotective effect.

This residual aqueous CSF after manual withdrawal can still cause edema and resultant "hypoperfusion" or "no-reflow" phenomenon, significantly decreasing the protective effect because it is a continued source of edematous fluid that can cause delayed or recurring injury.

However, such pressure control does not achieve the neuroprotective effect in the case of more general ischemia.

However, simple withdrawal of CSF even under controlled conditions in thoracoaortic surgery, is not predictably effective protecting CNS tissue.