Trans sodium crocetinate/cyclodextrin to increase diffusion of oxygen

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Diffusion Pharmaceuticals Inc., a cutting-edge biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to bring oxygen to the areas where it is needed most, has been recently granted Patent Number EP2540696 B1 from the European Patent Office [1]This patent relates to pharmaceutical compositions of trans sodium crocetinate (“TSC”) and a cyclodextrin for use in therapy.  Specifically claimed are TSC compositions for use in conjunction with radiation or chemotherapy.  Secondary claims relate to various compositions of TSC. This patent has claims to TSC compositions for use in therapy generally and has claims to compositions for use in treating brain cancer.

Trans-sodium crocetinate (TSC) has been found to alleviate the symptoms of hemorrhagic shock in that, after the drug is given to hemorrhaged rats, blood pressure rises, elevated lactate levels are reduced, cellular damage in the liver and kidney is less, and survival is increased [2]. The mechanism of action proposed for TSC is that it increases the diffusion of oxygen through blood plasma and into the tissue. The drug acts via a mechanism that has not been previously exploited in a pharmaceutical. TSC increases the rate of oxygen diffusion between the erythrocytes and the tissues by altering the ‘structure’ of water in blood plasma. It does this by causing additional hydrogen bonds to form among the water molecules [3].

Animal toxicology studies have demonstrated that high levels of TSC are well-tolerated, and a Phase I clinical study has shown that TSC is also safe in humans [3].

Molecular mechanics geometry optimizations were used for modeling the interactions between crocetin and CDs. The energies of obtained geometry’s suggest that the alpha-CD has the strongest interaction to crocetin among the studied CDs. These results correspond to the experimentally observed enhanced photoresistance of crocetin/ alpha-CD solutions [4].

The featured image above shows the molecular model of crocetin/methyl alpha-cycloextrin complex.

Recently crocetin was found to have a potential in the treatment of Alzheimer disease and to be delivered through the blood brain barrier when complexed by gamma-CD. Read more: https://cyclodextrinnews.com/2020/06/29/delivering-crocetin-across-the-blood-brain-barrier-by-using-%ce%b3-cyclodextrin-to-treat-alzheimers-disease/

 

References

[1]  Diffusion Pharmaceuticals Receives European Patent Related Compositions of TSC. https://www.globenewswire.com/news-release/2020/02/07/1981770/0/en/Diffusion-Pharmaceuticals-Receives-European-Patent-Related-Compositions-of-TSC.html

[2]  Stennett, A. K., Murray, R. J., Roy, J. W., & Gainer, J. L. (2007) Trans-sodium crocetinate and hemorrhagic shock. Shock, 28(3), 339–344. doi: 10.1097/shk.0b013e3180487b2d 

[3] Gainer, J.L. (2008) Trans-sodium crocetinate for treating hypoxia/ischemia.Expert Opin Investig Drugs. 2008 Jun;17(6):917-24. doi: 10.1517/13543784.17.6.917 .

[4] Jicsinszky, L.; Hashimoto, H.; Mikuni, K.; Bako, I.; Szente, L. Molecular mechanics studies on cyclodextrin complexes: interaction of crocetin with cyclodextrins. Proc. Int. Symp. Cyclodextrins, 8th (1996), 263-266. Editor(s): Szejtli, J.; Szente, L. Publisher: Kluwer, Dordrecht, Neth.

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