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(12) Patent Application Publication (10) Pub. No.: US 2006/0177381 A1 Brooks-Korn (43) Pub

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(12) Patent Application Publication (10) Pub. No.: US 2006/0177381 A1 Brooks-Korn (43) Pub US 2006O177381A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0177381 A1 Brooks-KOrn (43) Pub. Date: Aug. 10, 2006 (54) OPIOPATHIES (52) U.S. Cl. ........................................... 424/10.1; 514/282 (76) Inventor: Heard Brooks-Korn, Pacifica, CA (57) ABSTRACT The present invention provides novel methods for classify Correspondence Address: ing, diagnosing and/or treating a group of human and David A. Lowin veterinary ailments involving endogenous opioid concentra Windenweg 9 tions. Also provided is a novel use for an existing class of Neuheim CH6345 (CH) compounds, the opioids, to treat opiopathic ailments, par ticularly paresis/paralysis, pseudo-atrophy and/or opiopathic (21) Appl. No.: 11/395,200 pain, and in the manufacture of pharmaceutical and Veteri nary formulations therefor. The invention also relates to (22) Filed: Apr. 3, 2006 neuropathic, polyneuropathic, neurologic and neurogenic ailments typically characterized by paresis/paralysis. These Related U.S. Application Data ailments can involve an abnormal concentration of one or (63) Continuation-in-part of application No. 10/367.386, O endogenous opioids, or the blockade, underexpression filed on Feb. 14, 2003. or overexpression of one or more opioid receptors. In that regard, the invention encompasses therapeutic uses, meth (60) Provisional application No. 60/357,389, filed on Feb. ods and compositions employing opiates and/or their recep 15, 2002. tors. In particular, the invention relates to certain laboratory testing methods, clinical testing methods, research and Publication Classification development methods, business methods, methods of treat ment, novel therapeutic uses, and human and veterinary (51) Int. Cl. pharmaceutical dosage forms, dosing regimens and formu A6 IK 3/485 (2006.01) lations, especially those pertaining to opiopathy (particularly A6 IK 49/00 (2006.01) hypo-opiopathy). US 2006/0177381 A1 Aug. 10, 2006 OPOPATHIES of hydrocodone, oxycodone and morphine Sulfate, and teaches the similar use of other opiates. The present appli CROSS-REFERENCE TO RELATED cation further elucidates these teachings, particularly in view APPLICATIONS of the premise that abnormal concentrations of one or more 0001. This application is a continuation-in-part of co endogenous opioids, or the blockade, underexpression or pending U.S. application Ser. No. 10/367,386, filed Feb. 14, overexpression of one or more opioid receptors, can repre 2003 and published on Sep. 24, 2003 as US03/0166670-A1, sent an underlying etiology of an ailment requiring treat which in turn claims priority to U.S. Provisional Application ment, but for which only palliative care has previously been 60/357,389, filed Feb. 15, 2002, each incorporated herein by available. reference. Overview and Ailments of the Mammalian Nervous FIELD OF THE INVENTION System 0002 This invention relates to neuropathic, polyneuro 0006 The mammalian nervous system is comprised of pathic, neurologic and neurogenic ailments typically char the Central and Peripheral Nervous Systems. The Central acterized by paresis/paralysis. These ailments can involve an Nervous System (“CNS) is comprised of the brain and its abnormal concentration of one or more endogenous opioids, functional components. The Peripheral Nervous System or the blockade, underexpression or overexpression of one (“PNS) is comprised of all the cranial and spinal nerves and or more opioid receptors. In that regard, the invention their functional components. Paired cranial and spinal encompasses therapeutic uses, methods and compositions nerves provide the means of communication between the employing opiates and/or their receptors. In particular, the brain, the spinal cord and the rest of the body, acting through invention relates to certain laboratory testing methods, clini a complex series of dynamically balanced intracellular cal testing methods, research and development methods, chemical reactions. business methods, methods of treatment, novel therapeutic 0007 Terminology. In ailments of the nervous system, uses, and human and Veterinary pharmaceutical dosage when the cause originates from outside the nervous system forms, dosing regimens and formulations, especially those the disorder is termed “neurologic, and when the cause pertaining to opiopathy (particularly hypo-opiopathy). originates from within the nervous system it is termed “neurogenic.” When a group of neurologic or neurogenic BACKGROUND OF THE INVENTION signs or Symptoms are recognized together as a single 0003 Interest in the opioids and their receptors has ailment, it is referred to as a “disorder. When two or more largely focused on their analgesic use for the treatment of disorders (with their attendant signs and symptoms) are pain. A secondary medicinal focus has centered on uses Such recognized as part of a larger neurologic or neurogenic as cough Suppression, treatment of diarrhea and sedation disease state, it is referred to as a “syndrome'. When the without loss of consciousness. The identification and under clinical signs associated with a disorder or syndrome are the standing of opioid side effects (such as constipation, emesis, result of the dysfunction of a single nerve it is referred to as cardiac and respiratory depression, inducement of euphoria a “neuropathy.’ When the clinical signs associated with an and addictiveness) has also been the Subject of much ailment are the result of the dysfunction of two or more research. individual nerves it is referred to as a “polyneuropathy.' The dysfunctioning nerves in a polyneuropathy can be located in 0004 While some reports have noted the role of endog either the CNS, the PNS, or in both systems simultaneously. enous opioids as neuromuscular transmitters, these com pounds potential for abuse and their status as controlled 0008 Ailments involving the CNS, PNS or both systems Substances are believed to have given rise to significant bias together impact the area(s) of the body normally innervated against the opioid drug class as a whole, dissuading the by that system or systems. In certain ailments treated accord further elucidation of their properties and the development ing to the present invention, the area impacted by the of active pharmaceutical agents within the drug class. In nervous system dysfunction is muscle tissue, resulting in a particular, the role played by endogenous opioids in main partial or total loss of muscular function, and the ailment is taining normal body functions and the impact of abnormal called a “neuromyopathy.” These ailments are observed endogenous opioid concentration has remained unassociated individually or as part of a larger neurologic and/or neuro with the etiology and/or pathophysiology of human or genic syndrome, and can be inherited or acquired. When animal ailments. This and the therapeutic potential of opiates partial function remains in the innervated muscle tissue, it is for treating such ailments has for all practical purposes been termed “paresis.” When no function remains in the inner overlooked until the present and my below-referenced prior vated muscle tissue, it is termed “paralysis.”“Paresis/paraly patent applications. sis” or “P” is defined for purposes of the present invention as partial or total loss of function in innervated muscle 0005) My prior application (US03/0166670-A1: Ser. No. tissue. 10/367.386) discloses the use of opiates for treatment of centrally and peripherally mediated neuropathies, poly 0009 Lingual paresis/paralysis (“LiP) affects the ability neuropathies, disorders and syndromes including but not of an individual to prehend food, pass a food bolus to the limited to lingual, pharyngeal, laryngeal, esophageal, uri back of the pharynx and interferes with the individuals nary bladder sphincter, lumbar and lumbo-sacral spine, ability to swallow food, saliva or water; the resulting dis pelvis and pelvic-limb paresis/paralysis. This earlier appli order is known as “Oral or Lingual Dysphagia.” If the cation reports the Successful reversal of paresis/paralysis in individual’s nutritional needs are not effectively addressed, Such disorders and syndromes, particularly by administering death can occur as the result of the body's physical dete immediate or Sustained release pharmaceutical formulations rioration and eventual organ shutdown from the prolonged US 2006/0177381 A1 Aug. 10, 2006 effects of dehydration, malnutrition and eventual starvation. prevent the passive backward movement of foodstuffs into LiP can also obstruct the upper airway, potentially leading to the oral/nasal pharynx, and treating the effects of aspiration aspiration pneumonia and/or Suffocation. To date there is no pneumonia if they occur. known cure for LiP. The focus of therapy remains on strategies to insure an adequate dietary intake of food and 0013 Neurogenic urinary bladder sphincter paresis/pa water, maintaining an open airway, management of effective ralysis (“NUBSP) can result in intermittent or continual oral hygiene and treating the consequences of aspiration leaking of urine out of the bladder; the resulting disorder is pneumonia. known as “Neurogenic Urinary Bladder Sphincter Inconti nence.” The leaking urine's pathway or site of accumulation 0010) Pharyngeal paresis/paralysis (“PhP) can disrupt determines the symptoms associated with this incontinence. normal gag and/or Swallow reflexes resulting in the ineffec Urethritis, Cystitis, Nephritis, Vaginitis, Perivulvar and Vul tive Swallowing of food and water, can lead to aspiration var Vaginitis
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