whISOBAX-SH

https://www.doctorinspiredformulations.com

Our products were scientifically developed and their efficacy well documented

whISOBAX-SH (WH-SH) is a ready-to-use skin health product containing 2.5% whISOBAX

whISOBAX (WH) is a witch hazel extract containing a high concentration of Hamamelitannin, a molecule that prevents bacteria (e.g. Staphylococcus) from causing disease.

WH-SH prevents the growth of many microbes like:

– Gram positive bacteria (Enterococci, group B strep, corynbacteria, Staphylococcus aureus (including MRSA), Staphylococcus epidermidis (including MARCoNS).

– Gram negative bacteria (Pseudomonas fluorescens, Sphingomonas paucimobilis, Klebsiella oxytoca, Proteus mirabilis, Citrobacter koseri).

– Yeast (Candida albicans, Candida glabrata, Rhodotorula mucilaginosa, Hortaea werneckii, Candida parapsilosis).

– Mold (Cladosporium, Penicillium, Aspergillus flavus, Aspergillus niger).

Regulatory approvals of witch hazel:

FDA-Approved Uses:

 Skin Protectant Drug Products for over-the-counter human use.

 Anorectal Products for over-the-counter human use.

EMEA-Approved Uses:

 Relief of minor skin inflammation and dryness of the skin.

 Symptomatic relief of itching and burning associated with hemorrhoids.

 Mouthwash and gargles for relief of minor inflammation of mucous membranes.

WH-SH has already been used successfully:

• As a skin cleanser

• For maintenance of skin health

• To resolve skin infections

• To relieve sinus pain

• To relieve mouth sores

CLINICAL Ad hoc data: WH was used on over 4000 patients that have exhausted all other treatment options. Results demonstrate that

 up to 91% of the wounds were healed. These wounds were deemed ‘unhealable’ and would have resulted in a major limb amputation.

 The use of the WH technology significantly reduced healing time.

 WH is additive or synergistic to commonly used antibiotics.

With WH technology Time to heal a complex wound is reduced

With WH Device stayed in and limb remained on!

A 50-year-old man was kicked by a steer, shattering the tibia and fibula. He underwent open reduction and internal fixation of the fracture, resulting in a large nonhealing surgical wound over the metal plate. The surgeons suggested removal of the metal plate, and if it was, they would have to amputate his leg above the knee. Instead, the patient was treated with a topical preparation containing WH and triclosan and orally with Doxycycline for 8 weeks, resulting in closure of the wound over the implanted medical device, thus saving the limb and the device.

Scientific rationale and discovery

other living organisms, bacteria have to protect themselves in order to survive

Bacteria

Like humans who live in communities, bacteria form biofilms for protection

Biofilm: clusters of bacteria that are attached to a surface and/or to each other and embedded in a self-produced matrix. A biofilm is up to 1000 times more resistant to antibiotic treatment. Such infections are hard to treat.

Bacteria protect themselves by producing toxins

Phase variation:

NO DISEASE DISEASE

Bacteria communicate with one another through the release of molecules, a process known as quorum sensing. As a result, e.g. toxins are made.

TOXINS

Molecules that inhibit toxin production by S. aureus

RNAIII Inhibitory Peptide (RIP)

Hamamelitannin

Witch Hazel (Hamamelis)

WH inhibits disease by blocking bacterial cell to cell communication (quorum sensing), thus inhibiting toxin production and biofilm formation

whISOBAX-SH is superior to other available witch hazel products because:

 It contains a defined higher concentration of active ingredients.

 It is organic and is produced in the USA in a GMP-compliant, FDAregistered facility.

 Its potency and efficacy have been well demonstrated.

 Its mechanism of action is well documented in scientific journals.

Sample Bibliography

• Kiran MD, Vijayarangan N, Cirioni O, Giacometti A, Silvestri C, Scalise G, Ghiselli R, Saba V, Orlando F, Shoham M, Balaban N. Discovery of a quorum sensing inhibitor of staphylococcal infections by structure-based virtual screening. Mol Pharmacol. 73:1578-86. (2008).

• Balaban, N., Goldkorn, T., Nhan, R.T., Dang, L.B., Scott, S., Ridgley, R.M., Rasooly, A., Wright, S.C. Larrick, J.W., Rasooly, R. and Carlson, J. R. Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. Science 280:438-440 (1998).

• Balaban, N., Goldkorn, T., Gov, Y., Hirshberg, M., Koyfman, N., Matthews, H.R., Nhan, R.T. and Uziel, O. Regulation of Staphylococcus aureus pathogenesis via Target of RNAIIIActivating Protein (TRAP). J. Biol. Chem. 276, 2658-2667 (2001).

• Brackman, G., Breyne, K., De Rycke, R. et al. The Quorum Sensing Inhibitor Hamamelitannin Increases Antibiotic Susceptibility of Staphylococcus aureus Biofilms by Affecting Peptidoglycan Biosynthesis and eDNA Release. Sci Rep 6, 20321 (2016).

• Leitner G, Krifucks O, Kiran MD, Balaban N. Vaccine development for the prevention of staphylococcal mastitis in dairy cows. Vet Immunol Immunopathol. 142:25-35 (2011).

• Borges, A.; Ferreira, C.; Saavedra, M.J.; Simoes, M. Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb. Drug Resist. 2013, 19, 256–265.

• Rasooly R, Choi HY, Do P, Morroni G, Brescini L, Cirioni O, Giacometti A, Apostolidis E. whISOBAX TM Inhibits Bacterial Pathogenesis and Enhances the Effect of Antibiotics. Antibiotics (Basel). 2020 May 19;9(5):264.

• Rasooly R, Molnar A, Do P, Morroni G, Brescini L, Cirioni O, Giacometti A, Apostolidis E. Witch Hazel Significantly Improves the Efficacy of Commercially Available Teat Dips. Pathogens. 2020 Feb 1;9(2):92.

• Rasooly R, Molnar A, Choi HY, Do P, Racicot K, Apostolidis E. In-Vitro Inhibition of Staphylococcal Pathogenesis by Witch-Hazel and Green Tea Extracts. Antibiotics (Basel). 2019 Nov 29;8(4):244.

• Rasooly R, Howard AC, Balaban N, Hernlem B, Apostolidis E. The Effect of Tannin-Rich Witch Hazel on Growth of Probiotic Lactobacillus plantarum. Antibiotics (Basel). 2022 Mar 16;11(3):395.

• Balaban N, et al. Wound healing by biofilm eradication. Biofilm Perspectives. Springer Series on Biofilms Hans-Curt Flemming, Ed. Springer-Verlag Berlin Heidelberg (2011).

• Balaban N, et al. The control of Biofilm Infections by Signal Manipulation. Balaban N, Ed. Springer Springer-Verlag Berlin Heidelberg. (2008).

• Kiran MD, Giacometti A, Cirioni O, Balaban N. Suppression of biofilm related, device-associated infections by staphylococcal quorum- sensing inhibitors. International Journal of Artificial Organs. 31:761-770 (2008).

• Lopez-Leban F, Kiran MD, Wolcott R, Balaban N. Molecular mechanisms of RIP, an effective inhibitor of chronic infections. Int J Artificial Organs. 33:582-9 (2010).