US 20100311704A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0311704 A1 G00 berman (43) Pub. Date: Dec. 9, 2010 (54) PHARMACEUTICAL DELIVERY SYSTEMS Publication Classification FORTREATMENT OF SUBSTANCE ABUSE (51) Int. Cl. AND OTHER ADDICTIONS A 6LX 3/573 (2006.01) A63L/439 (2006.01) A63/4985 (2006.01) (76) Inventor: Lance L. Gooberman, A63L/454 (2006.01) Haddonfield, NJ (US) A6II 3/478 (2006.01) A6II 3L/27 (2006.01) Correspondence Address: A6IP 25/32 (2006.01) LERNER, DAVID, LITTENBERG, A6IP 25/34 (2006.01) KRUMHOLZ. & MENTLIK A6IP 25/36 (2006.01) 6OO SOUTHAVENUE WEST A6IP 25/30 (2006.01) (52) U.S. Cl. ......... 514/171; 514/282; 514/279:514/250; WESTFIELD, NJ 07090 (US) 514/326; 514/397: 514/491 (21) Appl. No.: 12/788,770 (57) ABSTRACT Disclosed are injectable pharmaceutical compositions that contain a therapeutically effective amount of an anti-addic (22) Filed: May 27, 2010 tive agent, an anti-inflammatory agent, and a pharmaceuti cally acceptable liquid carrier, methods of making the com Related U.S. Application Data positions, and uses thereof for treating addictions including Substance abuse (or addiction to an abused substance) and (60) Provisional application No. 61/217,337, filed on May addictive or compulsive behavior, by administering the com 29, 2009. position to a subject in need thereof. US 2010/031 1704 A1 Dec. 9, 2010 PHARMACEUTICAL DELVERY SYSTEMS tial therapeutic effect on alcohol abuse. Naltrexone, acamp FORTREATMENT OF SUBSTANCE ABUSE rosate, and disulfiram have been proven to be of a certain AND OTHER ADDICTIONS utility and approved for the treatment of alcoholism. Among these medications, the non-selective opioid antagonist naltr CROSS-REFERENCE TO RELATED exone is currently considered the pharmacological gold stan APPLICATIONS dard. 0001. This application claims the benefit of the filing date 0007. The National Institute on Drug Abuse estimates that of U.S. Provisional Patent Application No. 61/217,337 filed 72 million Americans, about one-third of the population, have May 29, 2009, the disclosure of which is hereby incorporated tried marijuana. Acute effects of marijuana use include herein by reference. memory and learning problems, distorted perception, diffi culty problem solving, loss of coordination, and increased BACKGROUND OF THE INVENTION heart rate. Long term abuse can cause the same respiratory problems observed in tobacco smokers, such as daily cough, 0002. Substance addiction is a chronic, relapsing disease phlegm production, increased risk of lung infections, and an characterized by a loss of control over drug use, compulsive increased chance of developing cancer of the head, neck and drug seeking and craving for a substance, use that persists lungs. Depression, anxiety, and job-related problems have despite negative consequences, and physical and/or psycho been associated with marijuana use. Longterm marijuanause logical dependence on the Substance. Substance addiction can result in addiction with compulsive use that interferes typically follows a course of tolerance, withdrawal, compul with daily activities. Cravings and withdrawal symptoms, sive drug taking behavior, drug seeking behavior, and relapse. Such as irritability, increased aggression, sleeplessness, and Addictive Substances include alcohol, caffeine, nicotine, can anxiety make it difficult for addicts to stop using marijuana. nabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine 0008 Psychostimulants, such as cocaine and amphet and phencyclidine-like compounds, sedative ipnotics such as amines, cause euphoria, increased alertness, and increased benzodiazepines and barbiturates and psychoStimulants such physical capacity in humans. These Substances first increase as cocaine, amphetamines and amphetamine-related drugs dopamine transmission, but long term drug usage results in a Such as dextroamphetamine and methylamphetamine. Sub reduction of dopamine activity, leading to dysregulation of stance abuse and addiction are public health issues. They have the brain reward system and dysporia. The WHO estimates 33 significant social and economic impact on both the addict and million people around the world abuse amphetamines. Society by playing a major role in violent crime and the spread 0009 Chronic cocaine abuse can result in hyperstimula of infectious diseases. tion, tachycardia, hypertension, mydriasis, muscle twitching, 0003. According to the World Health Organization, an sleeplessness, extreme nervousness, hallucinations, paranoia, estimated 13 million people abuse opiates worldwide, includ aggressive behavior, and depression. Cocaine overdose may ing 9 million heroin addicts. More than 25% of opiate abusers lead to tremors, convulsions, delirium, and death resulting die from Suicide, homicide, or an infectious disease. Such as from heart arrhythmias and cardiovascular failure. HIV and hepatitis, within 10-20 years of becoming addicted. Desipramine, amantadine and bromocriptine have been Tolerance and physical dependence can develop within two to shown to decrease cocaine withdrawal symptoms. three days. 0010 Amphetamine withdrawal symptoms include EEG 0004. The goals for treatment of opiate addiction, as with changes, fatigue, and mental depression. Tolerance develops other types of substance addictions, are to discontinue the use over time and may be associated with tachycardia, auditory of the opiate while minimizing painful withdrawal symptoms and visual hallucinations, delusions, anxiety reactions, para and preventing relapse. Current treatments involve replacing noid psychosis, exhaustion, confusion, memory loss, and pro the addictive drug with a substitution of an opioid receptor longed depression with Suicidal tendencies. Current treat agonist or mixed agonist/antagonist. An alternative approach ments for amphetamine addiction include phenothiazines, consists of the use of an opioid receptor antagonist to block haloperidol, and chlorpromazine for hallucinations. the effect of the agonist. 0005 Alcohol is one of the most commonly abused sub BRIEF SUMMARY OF TEE INVENTION stances at a global level. Alcoholism leads to serious liver and cardiovascular disease and generates dependence resulting in 0011. The present invention provides an injectable phar severe mental disorders, Social problems and adverse conse maceutical delivery system for anti-addictive agents, quences including the division of families, tragic accidents examples of which include antagonists and aversive agents of and the reduction of work performance. According to the substances of abuse, which are useful in the treatment of WHO, alcohol consumption is responsible for 20-30% of Substance abuse and addictive or compulsive behaviors. oesophageal and liver cancer, liver cirrhosis, homicides, epi Thus, they can be administered non-surgically. In so doing, lepsy, and motor vehicle accidents world wide. Globally, they provide several advantages compared to Subcutaneous alcohol abuse leads to about 1.8 million deaths per year. implants, such as pellets, or oral dosage forms of anti-addic Compulsive behavior towards the consumption of alcohol is a tive agents which require patient compliance. For example, core symptom of the disorder. In recent years several the inventive delivery systems require less time for actual approaches have been investigated to help alcoholic patients administration and, over the course of time, fewer adminis to not only control alcohol drinking but also alcohol cravings trations. Since they are less invasive and do not require Sur and relapse. gical incision, there is no need for removal of Sutures and 0006. Several classes of medications such as naltrexone, there is no scarring. Further, there is less risk of infection. acamprosate, ondansetron, disulfiram, gamma hydroxybu Even further, the presence of the anti-inflammatory agent is tyrate (GHB), and topiramate have been tested for their poten believed to decrease any inflammatory response caused by US 2010/031 1704 A1 Dec. 9, 2010 the injection and the presence of a foreign Substance, and that ramide, propheptazine, promedol, properidine, propiram, attraction of phagocytic cells to the site of injection is propoxyphene Sufentanil, tramadol, tilidine, salts thereof, reduced. mixtures of any of the foregoing, mixed L-agonists/antago 0012. Accordingly, a first aspect of the present invention is nists, and the like. directed to an injectable pharmaceutical composition that 0016 Examples of addictive or compulsive behaviors that contains an anti-addictive agent, an anti-inflammatory agent, may be treated in accordance with embodiments of the and a pharmaceutically acceptable liquid carrier. Methods of present invention include pathological gambling, sex addic making the compositions are also provided. The anti-addic tion, addiction to pornography, compulsive overeating, com tive agent is present in a therapeutically effective amount, pulsive overexercising, compulsive overexercising, and com which broadly refers to that amount that can result in a reduc pulsive use of electronic gadgets and devices such as tion, decrease or even a cessation of addictive use or compul electronic video games and cellular telephones and commu sive behavior. nication devices such as BlackBerry(R) devices. 0013. A second aspect of the present invention is directed 0017 Anti-addictive agents that may be included in the to a method for treating Substance abuse (or addiction to an inventive pharmaceutical