Background: Hydrogen sulfide (H2S) is a colorless gas with a characteristic smell of rotten
eggs. Once only thought of as a toxic gas, evidence now shows that H2S plays major roles in pathological
and physiological activities. These roles are being utilized to treat diseases and disorders ranging
from hypertension, inflammation, edema, cardiovascular issues, chronic pain, cancer, and many more.
Challenges facing the use of H2S currently involve achieving the optimum therapeutic concentrations,
synthesizing chemically and physiologically stable donors, and developing clinically appropriate delivery
Methods: We did an extensive literature search on therapeutic potentials and related issues of H2S
which were presented in a systematic flow pattern in introduction. Patents accepted/filed on various
aspects of hydrogen sulfide were searched using the United States Patent and Trademark Office database
at http://patft.uspto.gov/ and google patents at https://patents.google.com/. The important search
terms combined with H2S were therapeutic effect, pharmacological action, biochemistry, measurement,
and delivery. We also incorporated our own experiences and publications while discussing the delivery
approaches and associated challenges.
Results: In the process, researchers have discovered novel techniques in preparing the noxious gas by
discovering and synthesizing H2S donors and developing controlled and predictable delivery systems.
Donors utilized thus far include derivatives of anti-inflammatory drugs like H2S -aspirin, Allium sativum
extracts, inorganic salts, phosphorodithioate derivatives, and thioaminoacid derivatives. Use of
controlled delivery systems for H2S is critical to maintain its physiological stability, optimum therapeutic
window, increase patient compliance, and make it easier to manufacture and administer. Numerous
patents overcoming the challenges of using H2S therapeutically with various donors and delivery
mechanisms have been reviewed.
Conclusion: The scientific knowledge gained from the last decade researches has moved H2S from a
foul smelling pungent gas to the status of a gasotransmitter with many potential therapeutic applications.
However, developing a suitable donor and a delivery system using that donor for providing precise
and sustained release of H2S for an extended period, is critically needed for any further development
towards its translation into clinical practices.