EPIEN Medical Technical Bulletin.
The Global Opportunity For HYBENX® Technology to
Reduce Pathogenic Biofilm
J.W. Bracke, PhD and Michael L. Basara, MD
Background
Everything on Earth is covered with a living microscopic lawn of microorganisms called
biofilm. Biofilm consists of a matrix of microbes interspersed with various biological
molecules and debris that form a tenacious glue-like, living film on all surfaces. Biofilms
are extremely resistant to disinfectants, detergents, and antimicrobial agents. The extent
of biofilm was largely unappreciated until the 1990’s and the advent of recent microbial
DNA analysis techniques. Now it is understood to be part of a dynamic genetic matrix
that intimately interacts with the human genetic system as part of the human microbiome
or “normal flora”.
A “normal” healthy biofilm microbial flora is essential to good health. Fortunately, it is
difficult to dislodge and eradicate from its host. The biofilm is composed of a balance of
beneficial and potentially harmful microbes. The normal healthy balance can be
disrupted by a decline in the overall health or hygiene of the host and lead to the
development of an unhealthy pathogenic biofilm. Medical research has clearly
demonstrated that this decline can lead to a variety of unhealthy medical conditions
including pathogenic infections, ulcers, cardiovascular diseases, diabetes, prostatitis,
obesity, surgical implant failures, etc. Death can result from the overgrowth of an
unhealthy biofilm. Therefore, this complex phenomenon must be carefully managed
during medical therapy.
Antibiotic therapy, once thought to be the answer to managing these issues, is now
contributing to worse outcomes due to overuse. We now know that antibiotic therapy can
unbalance a healthy biofilm and cannot inactivate and remove all of the unhealthy biofilm
components. As a result, surviving biofilm microbes (“persisters”) can acquire new
resistance to each subsequent antibiotic usage that makes them even stronger and
more deadly as they rebound from treatment. This phenomenon has led to an expensive
spiral of new antibiotic drug development that is increasingly less effective against
modern resistant infections. In addition, it is not focused and disrupts other non-target
healthy biofilm elsewhere on the body. Conventional commercial antimicrobial
development approaches have become a bankrupt strategy. A new simpler, less
expensive, and more focused approach to pathogenic biofilm therapy is needed.
EPIEN Medical’s novel HYBENX® Technology
To address the increasing problem of resistant biofilms, EPIEN Medical has developed a
novel, patented, safe, and effective topical chemical solution that is easily applied to any
tissue surface to eradiate infectious biofilm in seconds. Because of the simple universal
physical mechanism of the action of this product, development of biological resistance to
this treatment is not possible. The topically applied product is a medical device. It is not
a drug and has no residual or internal absorption effects. Because of this, biofilm outside
of the treatment area is not affected.
The scientific key to the beneficial action of EPIEN’s HYBENX® Solution comes from its
carefully blended mixture of sulfonated component chemistry. These components cause
the devitalization and denaturation of biofilm. The HYBENX sulfate components strongly
absorb molecularly bound water. This is because water and sulfate have a unique
complementary polarity and geometry of electrostatic charges on their respective
surfaces. These surface charges strongly favor the mutual attraction of water and
sulfates to form an intense thermodynamic hydrogen bond linkage. Water molecules
form hydrogen bonds with many types of molecules, but the characteristics of this
particular sulfate hydrogen bonding process are exceptional in strength, quality, and
quantity. This makes the product’s desiccation power extremely fast, strong, and
predictable. All of the bound water is instantly removed from vital organic biofilm
components such as DNA, proteins, bacterial endotoxin, etc. Removal of water in this
desiccation process results in instantaneous irreversible inactivation and denaturation of
their biological function. The result is a coagulation of the entire biofilm matrix that
destroys its attachment mechanisms to the underlying tissues and allows the biofilm to
be easily removed by rinsing.
Use of HYBENX® Solution
HYBENX ® Solution (Liquid or Gel) is simple to use and accomplishes its cleansing
action in seconds. It is applied to the biofilm surface for 5-20 seconds, at the clinician’s
discretion, and removed by rinsing with aspiration. Depending upon the clinical situation,
an application of HYBENX solution can further provide clinically significant secondary
benefits. For example, biofilms can damage underlying tissues. After attacking the
biofilm, the HYBENX Solution desiccating activity coagulates and seals underlying minor
tissue lesions and reduces associated inflammatory edema. These actions often make
patients more comfortable during and after medical treatment. Reduction of edema and
swelling is often associated with reduced pain. The HYBENX desiccation mechanism
has a minor transient effect on the underlying host tissue due to the natural resistance of
intact protective human cell membranes to desiccation. A slight harmless surface
blanching of the adjacent tissue may occur. This light surface desiccation will naturally
reverse itself after a brief period, depending on the extent of the treated lesion.
Product Development Activity
ORAL BIOFILMS. One of the primary sources of all biofilm pathology is considered to
be that found in the oral cavity. The development of an unhealthy oral biofilm primarily
results from the lack of adequate oral hygiene (careful flossing and brushing). This can
result in increasing pathology associated with tooth decay, periodontal disease, tooth
loss, tooth pain, peri-implantitis, and ulceration.
Current EPIEN research activity and a variety of published clinical reports
(www.hybenx.it) have demonstrated that a single 5- to 20-second treatment of affected
oral sites with HYBENX Solution is completely effective, as an adjunct agent with
mechanical cleaning, in eradicating sub-gingival and supra-gingival biofilm, without the
use of antibiotics. Clinicians evaluating the product routinely state that they have never
seen another oral cleansing product demonstrate the instantaneous thorough cleaning
and reversal of pathology and pain and suffering in their clinics that they experience with
HYBENX products. They indicate that the product is easier, safer, and more effective to
use than alternatives such as bleach, antibiotics, and laser therapies. In early controlled
clinical studies, the pathology in periodontal disease has been significantly reduced
when compared to conventional dental treatments. In further preliminary studies,
HYBENX treatment also eliminated the pathogenic biofilm associated with periimplantitis around dental implants and alleviated pain and swelling within 7-10 days.
In previous controlled research studies, HYBENX Technology also instantly eliminated
the symptoms of aphthous ulcers (canker sores) with a single treatment and promoted
rapid healing.
Current Global Oral Product Status:
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HYBENX has been granted EU and Canadian Clearance as a Class I
Medical Device for general adjunctive oral cleanser applications
throughout the oral cavity.
An older product version of the HYBENX Technology, called
Debacterol® Canker Sore Pain Relief, is accepted by FDA as a preamendment “drug” category for the treatment of aphthous ulcers
EPIEN has received FDA 510(k) clearance for HYBENX® Oral
Decontaminant as a Root Cleanser for use in endodontic therapy. The
Company is in the process of trying to obtain a broader FDA clearance
as a general cleanser throughout the mouth.
Over seven million units of the HYBENX® Technology have been used safely and
effectively.
EPIEN is in the process of evaluating the prioritization of further research in several
areas. These include:
Infection Control. Extensive published medical studies have now shown that many
internal medical problems are associated with the pathogenic microbes originating in
oral biofilm. The Company is currently pursuing broader research opportunities to
evaluate the technology’s ability to reduce the incidence of disseminated biofilm
infections. This could be accomplished by using simple oral biofilm control procedures
employing HYBENX Solution as a general oral biofilm control agent.
Wound Biofilms. The association of pathogenic biofilms with the surface of chronic
wounds is well established. This area is a major component of Infection Control efforts in
medicine. Current healthcare practices and available products are not effective in
controlling and resolving these chronic wounds. This has resulted in long-term care
patients with expensive treatment histories. A chronic wound treatment specialist,
Director of the CHRISTUS Hospital Centers Chronic Wound Treatment Clinics in Texas,
has begun using HYBENX as a chronic wound debridement rinse in a variety of wound
types. The treated wounds included pressure ulcers, diabetic ulcers, trauma, and nonhealing surgical wounds. Ten-second treatments with HYBENX were used to reverse
patient’s months- or years-long histories of chronic wounds. The treated wounds
reverted to a normal wound-healing timeline after one treatment. Two of the patients
were removed from scheduled amputation surgery. This clinician, reminiscent of the oral
clinicians experiences, stated that he has never before seen such a simple, easy-to-use,
fast-acting, effective, pain-relieving product. These preliminary results have resulted in
the signing of collaboration agreement with a major military research center.
The Company is currently pursing an IND application with FDA to further investigate
HYBENX as a wound debridement rinse.
Skin Disorders. Extensive anecdotal reports have been supplied to the Company
regarding the use of HYBENX Solution for the effective treatment of skin disorders such
as acne, as well as dermatophyte infections (e.g., athlete’s foot) and other skin disorders
and insect bites. The Company has completed initial studies in pig models that
demonstrate the eradication of challenging wound infections such as MRSA,
Pseudomonas, etc.
Veterinary Applications. For all of the same reasons listed above there is strong
interest by members of the veterinary clinical community in applications for HYBENX
solutions. The Company is currently in discussions with veterinary distributors about the
expansion of appropriate animal medical applications in the USA. Numerous
veterinarians have already supplied the Company with results from several challenging
animal applications where they have again received unique outcomes unprecedented
with their previous veterinary products experiences.
Current Product Status: Under US regulatory law, Veterinarians may currently purchase
the human product for use in animals where the clinician believes there is no other
current treatment available.
Rev. 12Oct15