Therapeutic Solutions International Leverages Filed and Issued Intellectual Property to Develop COVID-19 Nutraceutical Candidate: QuadraMune™

OCEANSIDE, California, May 5, 2020 /PRNewswire/ -- Therapeutics Solutions International, Inc., (OTC Markets: TSOI) announced the filing of a patent application covering QuadraMune™, a nutraceutical developed to address issues of susceptibility, inflammation, and viral immunity, for COVID-19 patients. 

Initial work on QuadraMune™ was based on patent application 62/735867, filed Sept 25, 2018, which disclosed uses of pterostilbene to treat cytokine release syndrome in a variety of conditions including severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS).  Furthermore, issued patent #9,682,047 described the use of pterostilbene to decrease neutrophil activation in cancer patients. 

"Given the fundamental role of unrestrained inflammation [1], as well as pulmonary and systemic neutrophil activation in COVID19 patients [2], we sought to leverage the potential of this molecule to address the current pandemic," said Thomas Ichim, Ph.D., Board Member of TSOI and co-inventor of the patent. "We decided to expand our work by applying a multi-angled nutraceutical solution that addressed various aspects of COVID-19. For example, at the beginning of the disease process, the body's susceptibility to infection with the SARS-CoV-2 virus is a major determining factor as to progression of the disease.  Belonging to the coronavirus family of viruses, it is well recognized that natural killer cells and interferon responses play a role in host susceptibility [3]."

The role of inflammatory cytokines in the progression of ARDS and its pathology may be seen in several situations. For example, tumor necrosis factor (TNF) –alpha, has been demonstrated to correlate with the severity of ARDS in several studies [4]. Ingredients in QuadraMune such as pterostilbene [5], sulforaphane [6], and thymoquinone [7] have been shown to inhibit TNF-alpha by independent investigators.

Another cytokine that has been studied extensively in ARDS is interleukin-6. This cytokine is known to possess pro-inflammatory properties, as well as to suppress the generation of T regulatory cells and promote Th17 cells.  It is accepted that in ARDS there is a reduction in T regulatory cells, whose role is tissue protection, and Th17 cells, which are commonly associated with inflammation [8].

"We have demonstrated the pterostilbene administered in the form of NanoStilbene in cancer patients results in increased NK cell activity, as well as interferon-gamma production. Additionally, pterostilbene has shown to inhibit inflammatory cytokines associated with ARDS," said Dr. James Veltmeyer, Chief Medical Officer of TSOI. "For example, studies have demonstrated inhibition of interleukin-1, interleukin-6, interleukin-8, and TNF-alpha, by pterostilbene."

"QuadraMune, as the name applies, consists of four unique ingredients that in tandem provide synergism in reducing inflammation," said Tim Dixon, President, and CEO of TSOI and co-inventor of the patent. "We have of course included pterostilbene, a very potent inhibitor of inflammatory molecules, along with sulforaphane, a phase II detox promoter which also protects lungs from damage by activating the Nrf2 gene [9], EGCg (epigallocatechin gallate), extracted from green tea that can stimulate T cells [10], inhibit pathological immunity [11], and also protect the lungs, and thymoquinone which comes from the plant nigella sativa that suppresses autophagy, potential antiviral mechanistic effects on cells [12], and has been demonstrated to stimulate NK cells [13] which are antiviral."

About Therapeutic Solutions International, Inc.

Therapeutic Solutions International is focused on immune modulation for the treatment of several specific diseases. Immune modulation refers to the ability to upregulate (make more active) or downregulate (make less active) one's immune system. The Company's corporate website is at www.therapeuticsolutionsint.com and our e-commerce is at www.youcanordernow.com and for additional info on QuadraMune™ visit www.areyoucovidmune.com/covidmune/.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

[1] Liu et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020 Apr 18;55:102763.

[2] Zuo et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020 Apr 24. pii: 138999

[3] Yaqinuddin et al. Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents. Med Hypotheses. 2020 Apr 22;140:109777.

[4] Li et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 2020 Apr 12. pii: S0091-6749(20)30495-4.

[5] Hsu et al. The inhibitory effect of pterostilbene on inflammatory responses during the interaction of 3T3-L1 adipocytes and RAW 264.7 macrophages. J Agric Food Chem. 2013 Jan 23;61(3):602-10.

[6] Liu et al. Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder. Sci Rep. 2020 Apr 2;10(1):5822

[7] Akter et al. Targeting inflammatory mediators: An anticancer mechanism of thymoquinone action. Curr Med Chem. 2019 Oct 11.

[8] Toyama et al. Attenuated accumulation of regulatory T cells and reduced production of interleukin 10 lead to the exacerbation of tissue injury in a mouse model of acute respiratory distress syndrome. Microbiol Immunol. 2018 Feb;62(2):111-123

[9] Qi et al. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway. Int J Mol Med. 2016 Jan;37(1):182-8.

[10] Rawangkan et al. Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth. Molecules. 2018 Aug 18;23(8). pii: E2071

[11] Wheeler et al. The green tea polyphenol epigallocatechin-3-gallate improves systemic hemodynamics and survival in rodent models of polymicrobial sepsis. Shock. 2007 Sep;28(3):353-9.

[12] https://chemrxiv.org/articles/Identification_of_Compounds_from_Nigella_Sativa_as_New_Potential_Inhibitors_of_2019_Novel_Coronasvirus_Covid-19_Molecular_Docking_Study_/12055716

[13] Majdalawieh et al. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol. 2015 Sep;28(1):295-304.

Safe Harbor Statement

This release contains forward-looking statements that are based upon current expectations or beliefs, as well as a number of assumptions about future events. Although we believe that the expectations reflected in the forward-looking statements and the assumptions upon which they are based are reasonable, we can give no assurance that such expectations and assumptions will prove to have been correct. Forward-looking statements are generally identifiable by the use of words like "may," "will," "should," "could," "expect," "anticipate," "estimate," "believe," "intend," or "project" or the negative of these words or other variations on these words or comparable terminology. The reader is cautioned not to put undue reliance on these forward-looking statements, as these statements are subject to numerous risk factors as set forth in our SEC filings. To the extent that statements in this press release are not strictly historical, including statements as to product launch timing, revenue projections, business strategy, outlook, objectives, future milestones, plans, intentions, goals, future collaboration agreements, or otherwise as to future events, such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The forward-looking statements contained in this release are subject to certain risks and uncertainties that could cause actual results to differ materially from the statements made.

Contact Information:

• Therapeutic Solutions International, Inc.
  [email protected], +1(760) 295-7208, Timothy Dixon
• New Patent Filing Based on Stimulation of Immunity While Suppressing Inflammation

SOURCE Therapeutic Solutions International, Inc.