Composition and method to prevent and treat brain and spinal cord injuries

Abstract

A composition and method for treating and preventing injury to central nervous system tissue are provided. The composition is comprised of agents that can increase colloidal osmotic pressure and osmolality. The method comprise of: a). Withdrawing cerebrospinal fluid from the subarachnoid spaces around the tissue to be treated or protected and b). Injecting the composition into subarachnoid spaces.

Description

[0001] This application is a continuation in part of application Ser. No. 09 / 962,009, filed Sep. 24, 2001, and a continuation in part of two continuation Application filed Nov. 7, 2003, the disclosure of which is incorporated by reference.[0002] 1. Field of the Invention[0003] This invention is related to prevention and treatment for brain and spinal cord injuries. In particular, the invention relates to osmotic agents and the methods of using osmotic agents to prevent and protect the brain and spinal cord injuries in patients.[0004] 2. Background Information[0005] Central nervous system (CNS) consisting of the brain and spinal cord is very vulnerable to injuries, such as hypoxia-ischemia, trauma, poisoning etc. Cerebral edema is a common pathway to all CNS injuries. Clinical prevention and treatment for CNS injuries induced edema includes intravenous administration of osmotic agent, diuretic, removal of cerebrospinal fluid, coticosterroids etc, however, the efficacy is temporary an...

AI Technical Summary

Problems solved by technology

Central nervous system (CNS) consisting of the brain and spinal cord is very vulnerable to injuries, such as hypoxia-ischemia, trauma, poisoning etc.

Clinical prevention and treatment for CNS injuries induced edema includes intravenous administration of osmotic agent, diuretic, removal of cerebrospinal fluid, coticosterroids etc, however, the efficacy is temporary and limited.

Current search for a neuroprotective treatment based on other molecular mechanisms 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 etc.

Second, the interstitial fluid and lymphatic fluid pressure at capillary level is believed to be very low or even negative.

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

While excessive water inside the cell body is toxic, swelling of the tissue makes the Virchow-Robin 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.

These events result in irreversible cell death, tissue necrosis and liquefaction, finally neurological deficits and even brain death become clinical outcomes.

Although the inventor increase the colloidal osmotic pressure in an artificial CSF fluid, it will be difficult to reduce the ICP with the method invented.

In addition, there are many disadvantages regarding to this artificial CSF regarding its use, store, safety, high cost for patient etc.

All current clinical measures for prevention and treatment of CNS injuries induced edema only provide temporary and limited effect.

Current search for a neuroprotective agent based on other molecular mechanisms has yielded a disappointing result.

The ICP promotes cerebral edema While excessive water inside the cell body is toxic, swelling of the tissue makes the Virchow-Robin space smaller, thereby compressing the small blood vessels and resulting in blood perfusion deficit, such as "hypoperfusion" or even "no-reflow" phenomenon, which prolongs the original ischemic duration, blocks collateral circulation and induces a feedback loop.

These cascade events result in irreversible cell death, tissue necrosis and liquefaction, finally neurological deficits and even brain death become clinical outcomes.

This failure of circulation results in continuing damage to CNS tissue after the interruption of blood flow is reversed leading to irreversible damage and eventually cell death, tissue necrosis and liquefaction, finally neurological deficits and even brain death become clinical outcomes.

U.S. Pat. No. 6,500,809 to Frazer Glenn discloses a hyperoncotic artificial cerebrospinal fluid and method of treating neural tissue edema Although the inventor increase the COP in an artificial CSF fluid, it will be difficult to reduce the ICP with the method invented.

There are many disadvantages for this artificial CSF.

First of all, putting albumin in an artificial CSF is not more advantageous than just dissolving the albumin in patient's own CSF.

Although albumin is good for maintain colloidal osmotic pressure, it is expensive and may be risky for being infected by HIV, Hepatitis virus B etc if the albumin is from human.

In addition, it is not convenient to store and transfer this hyperoncotic artificial cerebrospinal fluid because it requires large volume of it to circulate in the cranium; Manufacturing a hyperoncotic artificial cerebrospinal fluid and circulating it are complicated and will have to add additional cost to a patient without enhancing drug effects.

Although as the inventor stated in claim 31, the hyperoncotic artificial cerebrospinal fluid can be ultrafiltered and recirculated, the procedure is complicated and it seems wasting albumin is inevitable.

Although mechanically withdrawing CSF alone is not sufficient enough to achieve the neuroprotective effect, it reduces the ICP and cut off the major water supply to the cerebral tissue.

It is very difficult to completely remove all the CSF, the 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.

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.