Apparatus and method for protecting neurons and reducing inflammation and scarring

Abstract

A device for protecting neurons and reducing inflammation and adhesion formation following surgery is provided. Also provided is a method for protecting neurons and reducing inflammation and adhesion formation following surgery. The device includes a bioabsorbable substrate and a layer of an oxidation inhibitor mimicking the effects of superoxide dismutase and catalase enzymes located on a surface of the substrate. Oxidation inhibitors that may be used include EUK-8, EUK-134, EUK-189, and EUK-207 (a mimetic of superoxide dismutase/catalase), monosodium luminol or phenyl N-t-butylnitrone or an analog with similar anti-oxidant properties. The oxidation inhibitors reduce oxidative stress and trigger the subject's natural anti-oxidant and anti-inflammatory defenses, thereby reducing neuron death, loss of neuron connectivity, inflammation and scarring and restoring excitatory function of neurons.

What is claimed is: 
     
         1 . A device for protecting neurons, reducing inflammation and scarring, and accelerating tissue recovery, the device comprising:
 a substrate having a top surface and a bottom surface, the substrate capable of being absorbed when inserted into a site of disease within a subject where it is in contact with the subject's tissue; and   a first layer of an oxidation inhibitor located on the top surface or the bottom surface of the substrate, wherein the layer is configured to trigger the subject's natural anti-oxidant defenses.   
     
     
         2 . The device of  claim 1 , wherein the oxidation inhibitor is selected from the group consisting of EUK-8, EUK-134, EUK-189, and EUK-207. 
     
     
         3 . The device of  claim 2 , wherein the oxidation inhibitor is EUK-207. 
     
     
         4 . The device of  claim 1 , wherein the oxidation inhibitor is monosodium luminol or phenyl N-t-butylnitrone. 
     
     
         5 . The device of  claim 1 , wherein the substrate is configured to be customizable by a physician prior to insertion into the site of disease. 
     
     
         6 . The device of  claim 1 , wherein the first layer is located on the bottom surface of the substrate, the layer being configured to contact the subject's tissue upon insertion of the device into the site of disease. 
     
     
         7 . The device of  claim 1 , wherein the first layer is located on the top surface of the substrate, the bottom surface of the substrate configured to contact the subject's tissue upon insertion of the device into the incision site. 
     
     
         8 . The device of  claim 3 , further comprising a second layer of EUK-207, the first layer being located on the top surface of the substrate, and the second layer being located on the bottom surface of the substrate and configured to contact the subject's tissue upon insertion of the device into the incision site. 
     
     
         9 . The device of  claim 4 , further comprising a second layer of monosodium luminol or phenyl N-t-butylnitrone, the first layer being located on the top surface of the substrate, and the second layer being located on the bottom surface of the substrate and configured to contact the subject's tissue upon insertion of the device into the site of disease. 
     
     
         10 . The device of  claim 1 , wherein the site of disease is degenerated or herniated disc, epidural cavity, weakened or structurally compromised lamina, space on top of dura matter or nucleus pulposus or a spinal surgery incision. 
     
     
         11 . The device according to  claim 1 , wherein the substrate is configured to be inserted into and enclosed within the site of disease upon suturing of the incision site. 
     
     
         12 . The device according to  claim 1 , wherein the substrate is a surgical film. 
     
     
         13 . The device according to  claim 1 , wherein the substrate is a bioabsorbable polymer or a gel or a foam. 
     
     
         14 . A method for protecting neurons and reducing inflammation and scarring in a subject, the method comprising,
 providing a device, the device comprising a substrate having a top surface and a bottom surface, wherein a first layer of an oxidation inhibitor is located on the top surface or the bottom surface of the substrate;   inserting the device into a site of disease such that the substrate covers at least a portion of the tissue at the site of disease; and   closing an incision site at the site of the disease if the substrate is applied as part of a surgery, thereby securing the device within the site of disease;   wherein the substrate is capable of being absorbed when inserted into the site of disease within the subject where it is in contact with the subject's tissue, and the layer of oxidation inhibitor is configured to trigger the subject's anti-oxidant defenses, thereby protecting neurons and reducing inflammation and scarring.   
     
     
         15 . The method of  claim 14 , wherein the oxidation inhibitor is selected from the group consisting of EUK-8, EUK-134, EUK-189, and EUK-207. 
     
     
         16 . The method of  claim 15 , wherein the oxidation inhibitor agent is EUK-207. 
     
     
         17 . The method of  claim 14 , wherein the oxidation inhibitor agent is monosodium luminol or phenyl N-t-butylnitrone. 
     
     
         18 . The method of  claim 14 , wherein closing the incision site comprises suturing the incision site if the substrate is used during a surgery. 
     
     
         19 . The method of  claim 18 , wherein the sutures are coated with one of EUK-8, EUK-134, EUK-189, EUK-207, monosodium luminol, and phenyl N-t-butylnitrone to further prevent neuron death and reduce scarring and inflammation. 
     
     
         20 . The method of  claim 19 , wherein the sutures are infused with EUK-207 or monosodium luminol or phenyl N-t-butylnitrone to further prevent neuron death, scarring and reduce inflammation. 
     
     
         21 . The method of  claim 14 , further comprising cutting the substrate to a physician determined sized based upon a shape and size of the incision made during the surgery. 
     
     
         22 . The method of  claim 16 , wherein the device is inserted such that the first layer of EUK-207 contacts the subject's tissue. 
     
     
         23 . The method of  claim 17 , wherein the device is inserted such that the first layer of monosodium luminol or phenyl N-t-butylnitrone contacts the subject's tissue. 
     
     
         24 . The method of  claim 16 , wherein the device further includes a second layer of EUK-207, the first layer being located on the top surface of the substrate, and the second layer being located on the bottom surface of the substrate. 
     
     
         25 . The method of  claim 17 , wherein the device further includes a second layer of monosodium luminol or phenyl N-t-butylnitrone, the first layer being located on the top surface of the substrate, and the second layer being located on the bottom surface of the substrate. 
     
     
         26 . The method according to  claim 14 , wherein the site of disease is degenerated or herniated disc, weakened or structurally compromised lamina, space on top of dura matter or nucleus pulposus or a spinal surgery incision site. 
     
     
         27 . A device for reducing inflammation and scarring comprising,
 a vehicle having at least one substrate, the substrate capable of being absorbed when in contact with the subject's tissue; and   a first layer of an oxidation inhibitor located on the at least one substrate of the vehicle, the first layer being configured to trigger the subject's anti-oxidant defenses, thereby reducing inflammation and scarring.   
     
     
         28 . The device of  claim 27 , wherein the oxidation inhibitor is selected from the group consisting of EUK-8, EUK-134, EUK-189, and EUK-207. 
     
     
         29 . The device of  claim 27 , wherein the oxidation inhibitor agent is EUK-207. 
     
     
         30 . The device of  claim 27 , wherein the oxidation inhibitor agent is monosodium luminol or phenyl N-t-butylnitrone. 
     
     
         31 . The device of  claim 27 , wherein the vehicle is at least one selected from the group consisting of a film, a suture, a mesh, and a scaffold. 
     
     
         32 . A method for treating pain associated with a disease of the spine in a subject in need thereof, the method comprising,
 injecting a pharmaceutical composition into a spinal space of the subject, the pharmaceutical composition comprising a bioabsorbable substrate and an oxidation inhibitor,   wherein the substrate is capable of being absorbed when injected into the spinal space and the oxidation inhibitor is capable of triggering the subject's anti-oxidant defenses, whereby the pain is reduced or eliminated.   
     
     
         33 . The method of  claim 32 , wherein the spinal space is one or more spaces selected from the group consisting of: epidural space, disc space, subarachnoid space, nucleus pulposus, and intervertebral space. 
     
     
         34 . The method of  claim 32 , wherein the oxidation inhibitor is selected from the group consisting of EUK-8, EUK-134, EUK-189, and EUK-207. 
     
     
         35 . The method of  claim 34 , wherein the oxidation inhibitor is EUK-207. 
     
     
         36 . The method of  claim 32 , wherein the oxidation inhibitor is monosodium luminol or phenyl N-t-butylnitrone. 
     
     
         37 . The method of any of  claims 32 - 36 , wherein the bioabsorbable substrate is a gel or a foam. 
     
     
         38 . The method of  claim 37 , wherein the gel is a hydrogel. 
     
     
         39 . The method of  claim 32 , wherein the reduction or the elimination of the pain is accompanied with reduction of elimination of inflammation associated with the disease. 
     
     
         40 . The method of  claim 32 , wherein the reduction or the elimination of the pain is accompanied with reduction or elimination of neuronal injury associated with the disease. 
     
     
         41 . The method of  claim 32 , wherein the disc space is nucleus pulposus. 
     
     
         42 . The method of  claim 32 , wherein the disease is selected from the group consisting of degenerative disc disease, spondylolisthesis, spondylolysis, osteomyelitis, stenosis, disc herniation, and scoliosis.