Therapeutic Solutions International Reports Unexpected

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Therapeutic Solutions International Reports Unexpected Findings of Synergy between QuadraMune™ and Diabetes Drug Metformin in Animal Models of COVID-19 Lung Damage
New Data Suggests Nutraceutical Product May Amplify Known Beneficial Effects of AMPK Activation in Pulmonary Inflammation

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Therapeutic Solutions International, Inc.
Jul 22, 2020, 09:40 ET

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OCEANSIDE, Calif., July 22, 2020 /PRNewswire/ -- Therapeutics Solution International, Inc., (OTC Markets: TSOI), announced today filing of a patent showing potent synergy between QuadraMune™ and the antidiabetic drug metformin in treating COVID-19 associated lung damage models.

It was discovered that the ability of QuadraMune™ to protect the lungs from inflammation that resembles coronavirus-induced pathology is markedly amplified by concurrent administration of metformin.

At a mechanistic level, it was shown that metformin increased the ability of QuadraMune™ to:

a) increase the number of "healing macrophages" ("M2" macrophages);
b) augment production of anti-inflammatory and regenerative proteins; and
c) suppress production of pathological inflammatory proteins.

"We are currently preparing to conduct a 500-person study evaluating protection from COVID-19 in individuals at high risk of infection, which is listed on the NIH website1," said Dr. James Veltmeyer, Chief Medical Officer of the Company. "In light of the current findings, we are extremely interested in evaluating outcomes in patients already taking metformin, which is one of the commonly used drugs in elderly populations."

Metformin has previously been shown to possess numerous therapeutic benefits in addition to its activities on diabetes. Beneficial effects of metformin include stimulation of immune responses2, suppression of cancer3, reduction of nicotine withdrawal side effects4, and inhibition inflammation5.

"It is naïve to believe that therapeutics that we develop will be used in isolation," said Timothy Dixon, President and CEO of the Company. "We are grateful for our scientific advisors who have guided us to perform 'out of the box' experiments in terms of combining QuadraMune™ with clinically relevant companion medications. We are continuing our journey to develop QuadraMune™ as a science-based nutraceutical, as well as to understand mechanistically its modes of action in order to continually work to improve potential for efficacy."

About Therapeutic Solutions International, Inc.
Therapeutic Solutions International is focused on immune modulation for the treatment of several specific diseases. The Company's corporate website is www.therapeuticsolutionsint.com, our public forum is https://board.therapeuticsolutionsint.com/.

1 https://clinicaltrials.gov/ct2/show/NCT04421391
2 Eikawa et al. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1809-14. https://www.pnas.org/content/112/6/1809.long
3 Malinowski et al. Metformin's Modulatory Effects on miRNAs Function in Cancer Stem Cells-A Systematic Review. Cells . 2020 Jun 4;9(6):1401 https://www.mdpi.com/2073-4409/9/6/1401
4 Brynildsen et al. Activation of AMPK by metformin improves withdrawal signs precipitated by nic

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