Compositions and methods for treatment of neurological disorders

Abstract

Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.

1 . A method of providing reversible inhibition of one or more peripheral nerves to a subject in need thereof, said method comprising providing a biocompatible ice slurry to the peripheral nerves for a duration sufficient to inhibit the peripheral nerves in the subject, wherein said inhibition is reversible. 
     
     
         2 . The method of  claim 1 , wherein the biocompatible ice slurry comprises ice particles and a lactated Ringer's solution, electrolyte solution or a lactated electrolyte solution. 
     
     
         3 . The method of  claim 2 , wherein the biocompatible ice slurry further comprises hetastarch or dextrose. 
     
     
         4 . The method of  claim 2 , wherein the biocompatible ice slurry further comprises about 0.1% to about 20% glucose. 
     
     
         5 . The method of  claim 2 , wherein the biocompatible ice slurry further comprises about 0.1% to about 20% glycerol. 
     
     
         6 . The method of  claim 2 , wherein the biocompatible ice slurry further comprises about 0.1% to about 6% hetastarch. 
     
     
         7 . The method of  claim 1 , wherein the biocompatible ice slurry comprises ice particles and saline. 
     
     
         8 . The method of  claim 7 , wherein the biocompatible ice slurry further comprises about 0.1% to about 20% glycerol. 
     
     
         9 . The method of  claim 7 , wherein the biocompatible ice slurry further comprises about 0.1% to about 20% dextrose. 
     
     
         10 . The method of  claim 7 , wherein the biocompatible ice slurry further comprises about 0.1% to about 5% ethanol. 
     
     
         11 . The method of  claim 7 , wherein the biocompatible ice slurry further comprises about 0.1% to about 10% poly vinyl alcohol. 
     
     
         12 . The method of  claim 7 , wherein the biocompatible ice slurry further comprises at least one sugar, ion, polysaccharide, lipid, oil, lysolecithin, amino acid, caffeine, surfactant, anti-metabolite, detergent or a combination thereof. 
     
     
         13 . The method of  claim 12 , wherein the at least one sugar is glucose, mannitol, hetastarch, sucrose, sorbitol or a combination thereof. 
     
     
         14 . The method of  claim 12 , wherein the at least one ion is calcium, potassium, hydrogen, chloride, magnesium, sodium, lactate, phosphate, zinc, sulfur, nitrate, ammonium, carbonate, hydroxide, iron, barium, salts thereof or a combination thereof. 
     
     
         15 . The method of  claim 12 , wherein the at least one oil is canola oil, coconut oil, corn oil, cottonseed oil, flaxseed oil, olive oil, palm oil, peanut oil, safflower oil, soybean oil, sunflower oil or a combination thereof. 
     
     
         16 . The method of  claim 12 , wherein the surfactant is a detergent. 
     
     
         17 . The method of  claim 12 , wherein the detergent is at least one of deoxycholate, sodium tetradecyl sulphate, polidocanol, deoxycholate, sodium tetradecyl sulphate, polidocanol, polysorbate 20 (polyoxyethylen (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), sorbitan ester, poloxamater or a combination thereof. 
     
     
         18 . The method of  claim 1 , wherein the biocompatible ice slurry comprises a peritoneal dialysis solution. 
     
     
         19 . The method of  claim 1 , wherein the biocompatible ice slurry is provided along the perineural sheath of a peripheral nerve. 
     
     
         20 . The method of  claim 1 , where in the peripheral nerves are subcutaneous nerves. 
     
     
         21 . The method of  claim 1 , where in the peripheral nerves are autonomic nerves. 
     
     
         22 . The method of  claim 21 , where in the autonomic nerves are sympathetic nerves, parasympathetic nerves or enteric nerves. 
     
     
         23 . The method of  claim 21 , where in the peripheral nerves are somatic nerves. 
     
     
         24 . The method of  claim 1 , wherein the somatic nerves are sensory nerves, motor nerves, cranial nerves, or spinal nerves. 
     
     
         25 . The method of  claim 1 , wherein the biocompatible ice slurry cools the nerves to between about 5° C. and about −40° C. 
     
     
         26 . The method of  claim 1 , wherein the biocompatible ice slurry has a first equilibration temperature of between about 4° C. and about −30° C. 
     
     
         27 . The method of  claim 1 , wherein the biocompatible ice slurry has a second equilibration temperature of between about 2° C. and about −30° C. 
     
     
         28 . The method of  claim 2 , wherein the ice particles are spherical or round with a diameter of about 1 mm to about 0.01 mm. 
     
     
         29 . The method of  claim 1 , wherein the biocompatible ice slurry further comprises an agent selected from the group consisting of a vasoconstricting agent, corticosteroid, a nonsteroidal anti-inflammatory drug (NSAID), anesthetic, glucocorticoid, a lipoxygenase inhibitor, and combinations thereof. 
     
     
         30 . The method of  claim 29 , wherein the vasoconstricting agent is epinephrine or norepinephrine. 
     
     
         31 . The method of  claim 29 , wherein the anesthetic is selected from the group consisting of lidocaine, bupivacaine, prilocaine, tetracaine, procaine, mepivicaine, etidocaine, QX-314 and combinations thereof. 
     
     
         32 . The method of  claim 1 , wherein the biocompatible ice slurry is injected. 
     
     
         33 . The method of  claim 32 , wherein the biocompatible ice slurry is provided to the peripheral nerves of the subject by injection into or around the nerve or nerves selected from the group consisting of the cutaneous nerve, trigeminal nerve, ilioinguinal nerve, intercostal nerve, interscalene nerve, intercostal nerve, supraclavicular nerve, infraclavicular nerve, axillary nerve, paravertebral nerve, transverse abdominis nerve, genitofemoral nerve, lumbar plexus nerve, femoral nerve, pudental nerve, celiac plexus nerve, and sciatic nerve. 
     
     
         34 . The method of  claim 1 , wherein the biocompatible ice slurry is provided to the peripheral nerves of the subject by tumescent pumping of the slurry. 
     
     
         35 . The method of  claim 1 , further comprising administering pressure to reduce blood flow at the site of injection. 
     
     
         36 . The method of  claim 1 , further comprising monitoring the biocompatible ice slurry by ultrasound or imaging. 
     
     
         37 . The method of  claim 1 , wherein the inhibition is reversed after about 5 months or less. 
     
     
         38 . The method of  claim 1 , wherein the subject in need thereof suffers from a disorder selected from the group consisting of neuropathic pain, diabetic neuropathy pain, trigeminal neuralgia, post-herpetic neuralgia, phantom limb pain, cancer related itch or pain, burn itch or pain, lichen sclerosus, scalp itch, nostalgia parastethica, atopic dermatitis, eczema, psoriasis, lichen planus, vulvar itch, vulvodynia, lichen simplex chornicus, prurigo nodularis, itch mediated by sensory nerves, peripheral neuropathy, peripheral nerve damage, post-thoracotomy pain, incisional pain, chest pain, coccydynia, lower back pain, superficial scars, neuromas, acute post-operation pain, lumbar facet joint syndrome, cutaneous pain disorder, and urinary incontinence. 
     
     
         39 . The method of  claim 38 , wherein the cutaneous pain disorder is selected from the group consisting of reflex sympathetic dystrophy (RSD), phantom limb pain, neuroma, post herpetic neuralgia, tension headache, occipital neuralgia and vulvodynia. 
     
     
         40 . The method of  claim 1 , wherein the subject in need thereof suffers from a motor disorder selected from the group consisting of hemifacial spasm, bladder spasm and laryngospasm. 
     
     
         41 . The method of  claim 1 , wherein the subject in need thereof suffers from hyperhidrosis disorder. 
     
     
         42 . The method of  claim 1 , wherein the tissue comprising the peripheral nerves is externally cooled prior to providing, during or after providing, the biocompatible ice slurry.