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US 20170020885A1 (19) United States (2) Patent Application Publication (10) Pub. No.: US 2017/0020885 A1 Hsu (43) Pub. Date: Jan. 26, 2017 (54) COMPOSITION COMPRISING A (52) U.S. CI. THERAPEUTIC AGENT AND A CPC ......... A61K 31/5377 (2013.01); A61K 9/0053 RESPIRATORY STIMULANT AND (2013.01); A61K 31/485 (2013.01); A61 K METHODS FOR THE USE THEREOF 9/5073 (2013.01); A61K 9/5047 (2013.01): A61K 45/06 (2013.01); A61K 9/0019 (71) Applicant: John Hsu, Rowland Heights, CA (US) (2013.01); A61K 9/209 (2013.01) (72) Inventor: John Hsu, Rowland Heights, CA (US) (57) ABSTRACT (21) Appl. No.: 15/214,421 (22) Filed: Jul. 19, 2016 The present disclosure provides a safe method for anesthesia or the treatment of pain by safely administering an amount Related U.S. Application Data of active agent to a patient while reducing the incidence or severity of suppressed respiration. The present disclosure (60) Provisional application No. 62/195,769, filed on Jul. provides a pharmaceutical composition comprising a thera 22, 2015. peutic agent and a chemoreceptor respiratory stimulant. In one aspect, the compositions oppose effects of respiratory Publication Classification suppressants by combining a chemoreceptor respiratory (51) Int. Cl. stimulant with an opioid receptor agonist or other respira A6 IK 31/5377 (2006.01) tory-depressing drug. The combination of the two chemical A6 IK 9/24 (2006.01) agents, that is, the therapeutic agent and the respiratory A6 IK 9/50 (2006.01) stimulant, may be herein described as the “drugs.” The A6 IK 45/06 (2006.01) present compositions may be used to treat acute and chronic A6 IK 9/00 (2006.01) pain, sleep apnea, and other conditions, leaving only non A6 IK 31/485 (2006.01) lethal side effects. US 2017/0020885 A1 Jan. 26, 2017 COMPOSITION COMPRISING A [0006] Because the availability of opioids has increased, THERAPEUTIC AGENT AND A there are now more deaths and overdoses from prescription RESPIRATORY STIMULANT AND opioids than deaths from heroin overdoses. A study pub METHODS FOR THE USE THEREOF lished in the November 2014 issue of the journal Pain found an increased risk of death associated in patients with chronic BACKGROUND OF THE INVENTION pain prescribed opioids for long-term use while a somewhat lower risk was associated with short-term use. [0001] Certain pharmaceutical drugs are known to sup press respiration. Of those pharmaceutical drugs, opioid [0007] The increased availability of opioids was partially brought about by The Joint Commission On Accreditation of receptor agonists (also described herein as either “opioids” Healthcare Organizations (JCAHO) standards from 2000 or “narcotics”) are the most well-known. that demands pain be addressed by healthcare providers as [0002] Most often, opioids are currently used to treat pain. the fifth vital sign. The evaluation of pain was thus made Opioids are potent analgesics and they are prescribed for equivalent to the evaluation of a patient’s vital signs includ patients in pain who need powerful painkillers. Acute pain, ing the heartbeat, blood pressure, respiratory rate, and tem (for example, pain in duration of less than three months), is perature. A 2012 study showed that physicians played an treated most often with short acting immediate release important role in prescription drug overdoses as they opioid medications, while chronic pain, (for example, pain attempted to comply with Federal mandates, avoid malprac in duration of greater than three months), is treated often tice claims, avoid decreased patient satisfaction scores (as with long acting or extended release formulations of opioid patients began demanding more prescriptions for opioid pain medications. medications), and avoid decreased reimbursement. The [0003] Chronic nonmalignant pain is a silent epidemic in same study found that of 3,733 fatalities associated with the U.S. that affects approximately 116 million Americans. prescription opioid drugs, the drugs that caused or contrib Patients who take opioids for an extended period, can uted to nearly half of the deaths were prescribed to patients develop a tolerance and require higher and higher doses of by physicians. This public health issue confounds the clini the drugs, increasing the risk of overdose and other prob cal utility of opioids. The extent of their efficacy in the lems. It is also the most common reason patients seek treatment of pain when utilized on a chronic basis has not medical care, resulting in $635 billion annually in both been definitively proven and has made long-term treatment medical costs and decreased work productivity. Although of non-cancer pain with opioids controversial. Coupled with the physiology of chronic pain continues to be poorly the abuse and addiction potential, clinical safety concerns understood, it has been identified as a disorder associated and side effect profile, proper physician prescribing of with many psychosocial conditions, including lack of appe opioids may be prevented, and result in inadequate pain tite, depression, and sleep disturbances. management. [0004] Opioids have well-known pharmacodynamic pro [0008] Though the bulk of the current research is focused files associated with a significant number of side effects and on abuse deterrence, addiction avoidance and patient safety, complications. Common side effects of opioid administra prescription drug are still abused, overdoses occur and death tion include sedation, dizziness, nausea, vomiting, and con rates continue to rise. It is apparent that this approach is not stipation. Less common side effects may include delayed successful in preventing patient deaths. The abuse deterrent gastric emptying, hyperalgesia, immunologic and hormonal developments have either been too difficult to manufacture dysfunction, infertility, muscle rigidity, myoclonus, physical or fail in clinical use. “Mu receptor Modulation” has not dependence, tolerance, respiratory depression, respiratory worked. A different approach must to be tried to save patient arrest and death. Painkiller deaths quadrupled between 1999 lives. Presently, as abuse deterrence technologies are devel and 2011, mirroring a sharp rise in the number of prescrip oped, narcotic abusers and addicts quickly discover innova tions for such drugs. In 2009, overdoses involving painkill tive methods to achieve their goal of reaching a euphoric ers pushed drug fatalities past traffic accidents as a cause of “high”. They crush drugs, intravenously inject drugs, snort death. In 2011 the U.S. Centers for Disease Control and drugs, extract drugs with alcohol or combine multiple drugs Prevention declared prescription opioid abuse an epidemic. to defeat pharmaceutical abuse deterrence technology as [0005] Well-known complications of opioids include the they are developed. It is a cycle that has led to many deaths. phenomenon of both physical and psychological depen The CDC determined that abuse of prescription opioid drugs dence and addiction, which can in turn lead to opioid misuse, is an epidemic because it has led to a quadrupling of death abuse and diversion. More than 70% of the illegal users rates in recent years. Rethinking of the method in which pain obtain opioids by stealing them during pharmacy robberies, is treated with opioids must be done. The current trend to use purchasing them illegally on the black market, or receiving multimodal pain therapy, which utilizes non-narcotics in them from family or friends. These individuals seek to synergy to treat pain is a step in the right direction. Unfor achieve a “high” from prescription medications by taking an tunately, in clinical practice this has been implemented by excess number of pills orally or by crushing the pills, only about 30 percent of physicians in the country. Rethink followed by snorting, smoking, or injecting the new altered ing of the method in which opioids are used to treat pain formulation. The misuse or abuse of prescription opioid must also be done. There is an epidemic of prescription drug medications is a growing problem, with abuse rates having abuse and it is getting worse despite efforts to solve it. More quadrupled in the decade from 1990 to 2000. The deaths opioid pain medications are prescribed today than ever associated with abuse and misuse of prescription pain drugs before because of Federal JCAHO regulations mandating have also quadrupled between 1999 and 2011. Frequently the treatment of pain. The pharmaceutical industry’s death associated with the overdose of opioids occurs within attempts to develop effective abuse deterrent solutions have an hour of the administration of the opioid due to respiratory largely been unsuccessful. And even though the Federal suppression. government regulations including REMS (Risk Evaluation US 2017/0020885 A1 Jan. 26, 2017 and Mitigation Strategies), CURES (Controlled Substance an antihistamine, or pharmaceutically acceptable salts Review Evaluation System), and ETASU (Elements to thereof, and any combination thereof. An analgesic dis Assure Safe Use) regulations to restrict prescribing practices closed herein may be an opioid receptor agonist (an opioid) for opioid use have been implemented, deaths from over or a non-steroidal anti-inflammatory agent or NSAID. Opi dose still occurs. oid receptor agonists include mu and kappa receptor ago [0009] Progressive and ultimately life-threatening respi nists. A respiratory stimulant disclosed herein may be dox ratory events may go unrecognized until significant morbid apram, modafinil, almitrine, AMPAkines, GAL-021, ity or mortality
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