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

Abstract

The cerebrospinal fluid and intracranial pressure are two major reasons why central nervous system is so vulnerable to injuries. A composition and method for treating injured central nervous tissue, or preventing injury to central nervous system tissue is provided. The composition is comprised of a combination of colloidal osmotic agents and crystal osmotic agents. 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 which is dissolved by patient's own cerebrospinal fluid into subarachnoid spaces. The treatment can be augmented with agents that suppress production of cerebrospinal fluid, or with other known neuroprotective agents.

1 . A method for protecting Central Nervous System tissue in need of such protection in mammal, comprising the steps of: 
 a) Withdrawing a volume of cerebrospinal fluid from the subarachnoid space,    b) Injecting a neuroprotective composition which is dissolved by certain amount of said cerebrospinal fluid into said subarachnoid space.    
     
     
         2 . A method for protecting Central Nervous System tissue in need of such protection in mammal, comprising the steps of: 
 a). Withdrawing a volume of cerebrospinal fluid from the subarachnoid space,    b). Injecting a neuroprotective composition which is dissolved by certain amount of said cerebrospinal fluid into said subarachnoid space,    c). Administering an effective amount of agent selected from the group consisting of: calcium channel blockers, calcium chelators, potassium channel blockers, free radical scavengers, antioxidants, GABA agonists, GABA receptor antagonists, glutamate antagonists, NMDA antagonists, NMDA channel blockers, glycine site antagonists, polyamine site antagonists, adenosine receptor antagonists, growth factors, Glial cell line derived neurotrophic factor (GDNF), brain derived neurotrophic factor, insulin like growth factor, leukocyte adhesion inhibitors, nitric oxide inhibitors, opiod antagonists, Serotonin agonists, sodium channel blockers, potassium channel openers, anti-inflamatory agents, and protein kinase inhibitors to said mammal.    
     
     
         3 . A method for protecting Central Nervous System tissue in need of such protection in mammal, comprising the steps of: 
 a). Withdrawing a volume of cerebrospinal fluid from the subarachnoid space,    b). Injecting a neuroprotective composition which is dissolved by certain amount of said cerebrospinal fluid into said subarachnoid space,    c). Administering a CSF production-suppressing agent.    
     
     
         4 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition comprises a combination of one crystal osmotic agent and one colloidal osmotic agent.  
     
     
         5 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition comprises essentially a combination of at least one crystal osmotic agent and at least one colloidal osmotic agent.  
     
     
         6 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition comprises essentially consisting at least one crystal osmotic agent.  
     
     
         7 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition comprises at least one colloidal osmotic agent.  
     
     
         8 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition comprises at least one colloidal osmotic agent.  
     
     
         9 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5  and  6  wherein said neuroprotective composition comprises the crystal osmotic agent is selected from the clinical known agents, such as glucose, glycerin, mannitol, sorbitol, sodium chloride etc.  
     
     
         10 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5  and  6  wherein said neuroprotective composition comprises the crystal osmotic agent is glucose.  
     
     
         11 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in the neuroprotective composition is a vegetable protein.  
     
     
         12 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is selected from the group consisting of microbial proteins.  
     
     
         13 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is modified soybean protein.  
     
     
         14 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is chicken egg white.  
     
     
         15 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is the extract from chicken egg white.  
     
     
         16 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is chicken egg white without ovomucoid.  
     
     
         17 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7 ,  8 ,  14 ,  15  and  16  wherein the colloidal osmotic agent in said neuroprotective composition is dry chicken egg white  
     
     
         18 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is selected from the group consisting of animal proteins albumin, lipoprotein, globulin, fibrinogen and collagen.  
     
     
         19 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is selected from the group consisting of human proteins albumin, lipoprotein, globulin, fibrinogen and collagen.  
     
     
         20 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7 ,  8 ,  18  and  19  wherein the colloidal osmotic agent in said neuroprotective composition is dry powder albumin.  
     
     
         21 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is selected from the group of known colloidins consisting of daxtran, gelatin, polysaccharide, starch (amylose, amylopectin), gelatin, agarose, amphipathic lipids, such as phosphoglycerides, sphingomyelins, glycolipids, cholesterol, cholesterol hemisuccinate, sphingolipids, cerebrosides.  
     
     
         22 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is selected a blood plasma extender.  
     
     
         23 . A method for protecting Central Nervous System tissue according to the claims  1 ,  2  and  3  wherein said neuroprotective composition is directly selected from any of the plasma extenders used clinically, such as 10% dextra (MW 40,000), 6% dextra (MW 70,000) and 6% hydroxyethyl starch, 4% modified fluid gelatin (Gelofusine®).  
     
     
         24 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is milk.  
     
     
         25 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is dry milk powder.  
     
     
         26 . A method for protecting Central Nervous System tissue according to  claim 1 ,  2 ,  3 ,  4 ,  5 ,  7  and  8  wherein the colloidal osmotic agent in said neuroprotective composition is plasma.  
     
     
         27 . A method for protecting Central Nervous System tissue according to  claim 4 ,  5 ,  6 ,  7  and  8  wherein said neuroprotective composition further comprises a CSF production-suppressing agents.  
     
     
         28 . A method for protecting Central Nervous System tissue according to  claim 3  and  27  wherein said neuroprotective composition can be selected from any of the known diuretic such as furosemide, acetazolamide, mersalyl, thiaxides, spironolactone, triamterene.  
     
     
         29 . A method for screening agents for neuroprotective effect comprising the steps of: 
 a). Withdrawing a volume of cerebrospinal fluid from the subarachnoid space of a living test subject,    b). Injecting a said neuroprotective composition which is dissolved by certain amount of said cerebrospinal fluid into said subarachnoid spaces, and    c). administering a proposed neuroprotective agent to said living test subject and determining the effectiveness of said neuroprotective agent.    
     
     
         30 . A method for treating stroke in a mammal requiring such treatment comprising: 
 a). Withdrawing a volume of cerebrospinal fluid from the subarachnoid space,    b). Injecting a said neuroprotective composition which is dissolved by certain amount of said cerebrospinal fluid into said subarachnoid spaces, and    c). Administering a thrombolytic agent to said mammal in an amount effective to restore blood flow to central nervous system tissue.    
     
     
         31 . A method according to  claim 30  wherein said thrombolytic agent is recombinant tissue plasminogen activator (rt-PA).  
     
     
         32 . A modified method for protecting Central Nervous System tissue according to  claim 1 ,  2  and  3  wherein said neuroprotective composition is dissolved in 0.9% sodium chloride, in water and injected into said subarachnoid spaces.  
     
     
         33 . A modified method for protecting Central Nervous System tissue according to  claim 1 ,  2  and  3  wherein said neuroprotective composition is dissolved in 5% Glucose, in water and injected into said subarachnoid spaces.  
     
     
         34 . A neuroprotective composition consisting a combination of one crystal osmotic agent and one colloidal osmotic agent.  
     
     
         35 . A neuroprotective composition consisting essentially a combination of at least one crystal osmotic agent and at least one colloidal osmotic agent.  
     
     
         36 . A neuroprotective composition according to  claim 34 ,  35  wherein the crystal osmotic agent is selected from the clinical known agents, such as glucose, glycerin, mannitol, sorbitol, sodium chloride etc.  
     
     
         37 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is selected from any vegetable proteins, such as soybean protein.  
     
     
         38 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is selected from any microbial proteins.  
     
     
         39 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is modified soybean protein.  
     
     
         40 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is chicken egg white.  
     
     
         41 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is the extract from chicken egg white.  
     
     
         42 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is chicken egg white without ovomucoid.  
     
     
         43 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is dry chicken egg white.  
     
     
         44 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is selected from any animal proteins. Such as albumin, lipoprotein, globulin, fibrinogen, collagen.  
     
     
         45 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is selected from any human proteins, such as albumin, lipoprotein, globulin, fibrinogen, collagen.  
     
     
         46 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is dry powder albumin.  
     
     
         47 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is selected from any of the known colloidins, such as daxtran, gelatin, polysaccharide, starch (amylose, amylopectin), gelatin, agarose, amphipathic lipids, such as phosphoglycerides, sphingomyelins, glycolipids, cholesterol, cholesterol hemisuccinate, sphingolipids, cerebrosides.  
     
     
         48 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is directly selected from any of the plasma extenders used clinically, such as 10% dextra (MW 40,000), 6% dextra (MW 70,000) and 6% hydroxyethyl starch, 4% modified fluid gelatin (Gelofusine®).  
     
     
         49 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is milk.  
     
     
         50 . A neuroprotective composition according to  claim 34 ,  35  wherein the colloidal osmotic agent is plasma.  
     
     
         51 . A neuroprotective composition according to  claim 34 ,  35  further comprising a CSF production suppressing agent.