The Immune Health Benefit Of Sleep Becomes More Important Than Ever Before, As Primary Care Sleep Specialists Broaden Their Endorsement Of Remfresh®, A Pharmaceutical Science Advance In Sleep Management, As Their #1 Recommended Nonprescription Sleep Brand

BOCA RATON, Fla., April 21, 2020 /PRNewswire/ --

• Drug-free, nonprescription REMfresh®, the first continuous release and absorption melatonin (CRA-melatonin®), ranks for the third year as the #1 recommended modified-release melatonin brand, for the second year as the #1 recommended melatonin brand and for the first year as the #1 recommended nonprescription sleep aid brand by primary care physicians with certification in sleep disorders¹
• In a pivotal trial, approved after peer review and then published, the REM Absorption Kinetics Trial (REMAKT), demonstrated REMfresh mimics the body's own 7-hour Mesa Wave® a natural pattern of melatonin blood levels during a normal night's sleep cycle
• A second study, the 1,116 patient-reported outcomes (PRO) study, REMfresh  Duration Validation (REMVAL), peer-reviewed and then presented at a major sleep medicine conference, SLEEP 2019, provided confirmatory real-world evidence of the 7-hour action of REMfresh, a 99% ultrapure melatonin

Physician's Seal, LLC®, innovators of REMfresh® (CRA-melatonin®), a clinically studied, drug-free, nonprescription sleep brand, revealed positive results of a nationwide survey conducted among a representative sample of U.S. primary care physicians with certification in sleep disorders. These primary sleep specialists broadened their endorsement for REMfresh as the:

• #1 recommended modified-release melatonin brand for the third consecutive year;
• #1 recommended melatonin brand for the second consecutive year; and
• #1 recommended nonprescription sleep aid brand for the first year.¹

Melatonin: The Body's Natural Sleep Ingredient
Melatonin is produced by the pineal gland in the brain and is the body's natural sleep ingredient. Melatonin levels normally begin to rise in the mid-to-late evening and remain high for the majority of the night. Levels begin to decline towards early morning as the body's wake cycle is triggered.

Recent research demonstrates that sleep is a strong regulator of immune function, essentially contributing to the regulation of adaptive immunity.² The study also shows that chronic sleep loss poses an enhanced risk for various diseases as a consequence of persistent low-grade systemic inflammation and immunodeficiency, characterized by an enhanced susceptibility to infections, which have detrimental effects on health.²

"Now more than ever, the role of sleep has become paramount in immune health," said David C. Brodner, M.D., a leading sleep specialist who is Double Board-Certified in Otolaryngology – Head and Neck Surgery as well as Sleep Medicine, Founder and Principle Physician at the Center for Sinus, Allergy, and Sleep Wellness, in Palm Beach County, Florida and Senior Medical Advisor for Physician's Seal, LLC. "During this particularly challenging time in our nation, any way to improve the nation's sleep deficit will greatly improve public health." Dr. Brodner continued, "There is growing, widespread adoption of REMfresh among primary care physicians with certification in sleep disorders and an increased willingness to recommend this brand based on their real-world experience in receiving positive feedback from their patients who suffer from sleep disturbances."   

Over 5,000 physicians are recommending REMfresh and the number of REMfresh endorsers among nurse practitioners, physicians assistants and pharmacists is growing rapidly.

About IQVIA ProVoice Survey
ProVoice has the largest sample size of any professional healthcare survey in the U.S., with nearly 60,000 respondents across physicians, nurse practitioners, physician assistants, optometrists, dentists and hygienists, measuring recommendations across more than 120 over-the-counter categories. Manufacturers use ProVoice for claim substantiation, promotion measurement and HCP targeting.

IQVIA fielded a U.S. survey among a representative sample of primary care physicians with certification in sleep disorders between February 26, 2020, through March 16, 2020, for Physician's Seal. The ProVoice survey methodology validated the claim at a 95 percent confidence level that "REMfresh® is the #1 recommended modified-release melatonin brand for the third year, #1 recommended melatonin brand for the second year and  #1 recommended nonprescription sleep aid brand for the first year by primary care physicians with certification in sleep disorders.¹

IQVIA is a leading global provider of advanced analytics, technology solutions and contract research services to the life sciences industry formed through the merger of IMS Health and Quintiles.

About Nonprescription REMfresh®
REMfresh® (CRA-melatonin®) is the first and only, continuous release and absorption formulation of 0.5mg (Lite), 2 mg and 5mg (Extra Strength) UltraMelÒ melatonin. UltraMel melatonin is a high-quality, 99 percent ultra-pure melatonin sourced, from an FDA DMF-approved facility in Western Europe, exclusively for Physician's Seal.

REMfresh caplets, 99% ultrapure melatonin, continuously released and absorbed, over 7 hours, is designed to help a person fall asleep faster, stay asleep longer and experience quality sleep, such as deep sleep and REM sleep.

REM Absorption Kinetics Trial (REMAKT), a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults compared REMfresh (CRA-melatonin) with a market-leading, immediate-release melatonin (IR-melatonin).

The study results, which were approved after peer review and then published in Primary Care Companion for CNS Disorders in August 2019, showed that melatonin levels with REMfresh exceeded the targeted sleep maintenance threshold for a median of 6.7 hours, compared with 3.7 hours with the leading IR-melatonin. Conversely, the levels of the market-leading IR-melatonin formulation dramatically increased 23 times greater than the targeted levels of exogenous melatonin for sleep maintenance and had a rapid decline in serum levels that did not allow melatonin levels to be maintained above target beyond 4 hours. Additionally, the published paper noted the advance beyond a prolonged release prescription melatonin available in Europe. The author's concluded that "CRA-melatonin shows an enhancement over the release profile of prolonged release melatonin(PR-melatonin) by extending in vivo exposure to 7 hours, making it an important advancement in the use of melatonin as a chronobiotic, potentially with drug-free hypnotic effects to initiate and maintain sleep."³

Another study, the post marketing REMfresh Duration Validation (REMVAL) study was peer reviewed and then presented at SLEEP 2019, the 33^rd Annual Meeting of the Associated Professional Sleep Societies (APSS), LLC, a joint partnership of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS). This 1,116-patient REMVAL study was designed to obtain clinically relevant information about patients' past usage of melatonin and non-melatonin sleep aids, sleep patterns prior to taking CRA-melatonin, sleep duration before and after taking CRA-melatonin, frequency of CRA-melatonin usage, improvement in sleep latency, sleep maintenance and sleep quality after taking CRA-melatonin, and overall satisfaction with CRA-melatonin.

In the study, patients with sleep disturbances in the general population received a sample of REMfresh from their physicians and were invited to complete a 13-question online survey. After taking REMfresh, the majority (78.8 percent) of patients achieved a sleep duration of ³ 6 hours (p<.0001). More than 91 percent of patients reported a major/moderate improvement in sleep onset, maintenance and sleep quality (p<.0001). Of the 30.7 percent of patients (342 in total), who reported never having taken other brands of melatonin, 99.4 percent indicated they were likely or very likely to continue taking REMfresh for their sleep issues.⁴

REMfresh was designed as a hydrogel matrix tablet with its patented, scientifically advanced Ion-Powered Pump® (IPPÒ) technology, pioneered by Physician's Seal. Initially, there is a rapid release of the melatonin from the surface of the tablet in the acidic environment of the stomach. As the tablet moves into the higher pH of the small intestine, where melatonin is unlikely to dissolve, food grade organic acid built inside the tablet, helps maintain a lower pH within the tablet over 7 hours, to allow for continuous release and absorption of active melatonin throughout the GI tract.

REMfresh is a dietary supplement and is regulated under the Federal Dietary Supplement Health and Education Act, which does not require pre-approval. Melatonin has been in common use for over two decades and has a well-established profile of safe use by millions of people around the world. Physicians note that melatonin has an advantage when it comes to morning dysfunction, drowsiness or unusual night occurrences such as sleepwalking. Additionally, the REM Safety Update at 24 months (REMSU24), a 24-month post-marketing safety study of more than 320,000 users showed no pattern of side effects.⁵ As with all supplements, individual results may vary.

REMfresh is non-habit forming and does not contain narcotics, hypnotics, barbiturates, sedatives, antihistamines, alcohol or other harsh additive chemicals. The usual adult recommended dose is 1-2 tablets 30-90 minutes before bedtime. Specific dosing instructions found on the back of the box should be followed for proper use of supplements. REMfresh is available in 0.5mg (Lite), 2mg and 5mg (Extra Strength) versions.

About Physician's Seal®  

Physician's Seal® is the Innovator of REMfresh®, the first and only continuous release and absorption, 99 percent ultrapure melatonin (CRA-melatonin™), that mimics the way the body naturally releases and takes up melatonin over a 7-hour period. Physician's Seal (PS), founded in 2015, is a privately held company based in Boca Raton, Florida. It is committed to bringing cutting-edge life science applications to doctors and their patients. For more information, visit www.REMfresh.com.

Physician's Seal's sister subsidiary, IM HealthScience® (IMH), is the innovator of the two medical foods IBgard® and FDgard® for the dietary management of Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD or recurring meal-triggered indigestion), respectively. IMH rounds out its line of digestive products with Fiber Choice®, a well-known, natural prebiotic chewable daily fiber that helps support regularity. IMH® is a privately held company based in Boca Raton, Florida. It was founded in 2010 by a team of highly experienced pharmaceutical executives. Both PS and IMH are dedicated to developing products to address overall health and wellness in digestive health and sleep. The Physician's Seal and IM HealthScience advantage comes from developing products based on patented, targeted-delivery technologies, including IPP® (Ion-Powered Pump®) and SST® (Site Specific Targeting®) technologies. For more information, visit www.imhealthscience.com to learn about the company, or www.IBgard.com, www.FDgard.com and www.FiberChoice.com.

Copyright © 2020 Remfresh^® This information is for educational purposes only and is not meant to be a substitute for the advice of a physician or other health care professional. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.  You should not use this information for diagnosing a health problem or disease. REMfresh is intended to relieve occasional sleeplessness.   Statements made in this release rely upon reviews of literature, input from PS's advisors and PS's own expertise. There may always be other opinions or emphasis points. Some of the statements from different sources may not mesh with each other. There may be inadvertent inaccuracies that PS is not aware of. Space limitations in this release only allow limited reference to some guidelines or practices which may, or may not, be fully agreed to by all scientific, medical or regulatory experts. For any of PS's products this release does not make or have any intent to make drug claims or any comparison or implied claims against FDA approved interventions for sleep disorders. Any comments on any products are based on literature reviews and input from PS's own advisors. There may be others who have other points of view. Pre-clinical findings do not always correlate with clinical or real-world findings. The reader is urged to check all current information, including the latest website disclosures and/or package inserts, of any of the medical products mentioned here, as information, including government regulations, changes all the time. The statements of individual opinions are those of the individuals quoted and do not necessarily reflect opinions of PS. Please fully read all disclaimers/clarifications/explanations. PS disclaims any injury or alleged injury resulting from any ideas, methods, instructions or products referred to here. Health care practitioners should use their independent, professional judgment in helping their patients best manage their sleep conditions. The company will strive to keep information current and consistent but may not be able to do so at any specific time. Generally, the most current information can be found on www.REMfresh.com. Individual results may vary.                

REMfresh is protected by U.S. Patents No.: 8,691,275; 9,186,351; 9,241,926;  9,549,900; 10,226,447. Keep out of reach of children. Store at room temperature. Individual results may vary.  Do not use if blister is torn or ripped or if there is any other evidence of tampering. Consult a physician if using any supplement for the first time. Please read package insert and the website for more information.

References:

1. IQVIA. ProVoice Survey REMfresh is the #1 recommended modified-release melatonin brand for the third consecutive year, #1 recommended melatonin brand for the second consecutive year and #1 recommended nonprescription sleep aid brand for the first year for sleep management; 2020 [Among primary care physicians with certification in sleep disorders].
   
   
2. Besedovsky, L., Lange, T. & Born, J. Sleep and immune function. Pflugers Arch - Eur J Physiol 463, 121–137 (2012). https://doi.org/10.1007/s00424-011-1044-0.
   
   
3. Seiden DJ, Shah SM. A Randomized, Crossover, Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin Formulation versus a Same Strength Immediate-Release Formulation. Primary Care Companion for CNS Disorders. 2019. 21(4):19m 02450.
   
   
4. Brodner DC, Seiden DJ, Shah SM (2019). Observed Hypnotic Effects with a Continuous-Release Ion Powered Pump Melatonin Delivery System: Self-Reported Patient Outcomes Study Results Demonstrating Improvement in Sleep Duration and Quality. (Abstract 0399). Poster Presented at SLEEP 2019, San Antonio, Texas.
   
   
5. Physician's Seal (2019). Real-world data from surveillance study confirms excellent safety and tolerability profile of REMfresh at 24 months (REMSU-24); Data on file; Press Release 9/27/19.

SOURCE Physician's Seal