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Bedsores

Launched or under launch (2012-2016): Australia, Colombia, Djibouti, Dubai, Egypt, Finland, France, Israel, Malaysia, Middle east, New Zealand,, South Africa, South Korea, Tunisia…

CHRONIC WOUNDS

(Bedsores, Diabetic & Venous Leg Ulcers, Post-Op Wounds…)

Chronic Wounds

A chronic wound develops when an acute wound fails to heal in the expected time frame for that type of wound, which might be a couple of weeks or up to six weeks in some cases.

Wounds can fail to heal due to a lack of one or more of the key requirements of healing, including a good supply of blood, oxygen and nutrients, and a clean and infection-free environment.

Cells are like babies ! If even 1 of these 6 conditions is not met, a baby will not survive…. Cells will not grow!!

Baby

Cells

Ground to stand on ECM to attach onto & grow
Food for nourishment Proper circulation to provide nourishment
Water for hydration Continuous hydration
Air to breathe Oxygen
Absence of infection Absence of bacterial contamination
No chemicals in contact No contact with cytotoxic chemicals

 

 

Ulcers are the most common type of chronic wounds:

Bedsore / Pressure ulcer: The constant pressure and friction resulting from body weight over a localized area for prolonged duration can lead to breakage of skin and ulceration (also known as bed sores); especially on the back and on the ankles and feet.

Arterial ulcers: These can occur from hypertension, atherosclerosis (plugging) and thrombosis (clotting), where the reduced blood supply leads to an ischemic state.

Venous ulcers: These ulcers account for more than half of ulcer cases, especially in the lower limbs (mainly the legs) as associated with deep vein thrombosis, varicose veins and venous hypertension. Venous ulcers can lead to stasis, where the blood fails to circulate normally.

Diabetic ulcers: These are a common complication in uncontrolled diabetes mellitus, resulting in impaired immune function, ischemia (due to poor blood circulation) and neuropathy (nerve damage), which eventually lead to breakage of skin and ulceration.

Physiopathology: Situated on the surface of the body, all chronic wounds are highly prone to contamination, particularly with bacteria & cell debris. To clean the wounds, our body produces >27 proteolytic enzymes (MMPs) to break “proteins” into smaller molecules, but these MMPs equally destroy Extra-Cellular matrix (ECM) essential for daughter cell attachment & growth. In the absence of ECM, new cells cannot attach nor grow, and the wound cannot heal.

Additionally, 60-90% chronic wounds contain bacterial biofilms that not only impede healing but also lead to prolonged inflammation (to fight and eliminate microbial contamination), which causes further damage and pain.

An ideal treatment should neutralize ECM-destroying MMPs, remove surface contaminants (bacteria, microbes and debris) & keep the wound surface hydrated and oxygenated in order to provide the conditions necessary for healthy cellular growth and tissue repair. The treatment should also block pro-inflammatory proteins to stop pain & irritation.

Finally, such a treatment must be totally safe and cell-friendly (non-chemical) and should produce results rapidly.

 

Conception of VITROBIO Wound Healing Filmogen Dressing

1. Highly osmotic film to clean the injury:

The film was conceived using polymeric VB-Gy: a highly osmotic filmogen solution as described in the patent PCT/FR99/01340. Applying such a film on an injured &/or infected biological surface creates an instant & strong exudation of hypotonic liquid from the inner parts of the surface, thereby detaching and draining away all the contaminants, and breaking the bacterial biofilms. Cleaning the wound bed surface favors symptomatic relief by reducing pain and dryness, and, importantly, progressively clears the microbial load while lastingly hydrating the wound microenvironment so as promote cell growth and allow the wound healing process to take place.

What can be claimed: Instant and long-lasting mechanical biofilm disruption & wound cleaning + pain relief.

 2. Anti-MMP polymers to stop degradation of ECM and restore environment conducive to healthy cellular growth and healing:

The concentration of undesired MMP proteinases varies according to the location, chronicity, and the type of insult to the body. MMP-2, -3, -8, -9 & -13 are the main proteinases responsible for destroying the Extra Cellular Matrix onto which new cells need to attach to repair the tissue and continue filling the wound cavity. A completely novel approach consisting in blocking free proteins using polymers was deployed to neutralize these undesirable MMPs & thus restart the healing process.

To evaluate MMP – polymer binding, each MMP was incubated with specific polymers for 5 min. The concentration of free MMP was then quantified by ELISA (Enzolife sciences) or AlphaLISA (PerkinElmer). Polymers showing statistically significant binding with selected MMPs were then tested in association to obtain maximum inhibitory response. These polymers were then incorporated in the final product composition.

Results indicate that only a few polymers bind to proteins, this binding is specific and varies considerably according to the structure, length & concentration of polymer(s) used, as well as the pH & the filmogenicity of the medium in which polymers are suspended.

A. Formulation 1

 

B. Formulation 2

 

As shown in the example of polymer–MMP binding figures above, the best polymers or their associations (“MMP-cyanidin” polymeric associations) incorporated in the final wound treatment formulations are capable of binding and neutralizing between 40-73% each individually, and up to 98.8% as a final formulation, of the ECM-degrading MMPs (MMP-2, -3, -8, -9 & -13) within 5 min of contact. Longer contact time further improves their binding.

What can be claimed: Neutralization of ECM-destroying, wound healing-impeding MMPs within 5 minutes.

3. Pro-inflammatory cytokine-inhibiting polymers to stop pain-generating chronic inflammation

Both MMP overexpression and bacterial biofilm colonization of chronic wounds lead the body to secrete inflammatory proteins (as part of the defense process). Chronic wounds thus show increased levels and prolonged presence of inflammatory cytokines. However, this chronic inflammation ends up causing further tissue damage and more pain. To stop the inflammatory cycle in chronic wounds, MMP-cyanidin polymers showed to inhibit > 40%IL-6, > 80% IL1-β, >90% TGF-β, and >70% TNF-a.

 

What can be claimed: Neutralization of chronic inflammation cytokines within 5 minutes.

Conclusion: These results indicate that Vev6, Vnm5, Rsn6 and Crs3 (elements of VITROBIO’s “MMP-cyanidin” polymer family) have an excellent specific anti-MMPs and/or anti-cytokines potential providing a tremendous therapeutic tool to promote healing and closure of otherwise non-healing chronic wounds.

Filmogen Wound Treatment Gel Formulations: In addition to Filmogen VB-Gy anti-microbial (anti-bacterial), cleaning & hydrating + anti-MMP polymers + inflammatory cytokine-inhibiting polymers, the final formulations may also contain some honey as dilution of honey with the osmotically attracted hypotonic liquid generates H2O2 bubbles. These air bubbles attach to hidden bacteria & the contaminant is then removed along with the air bubble. Some preparations may also contain vegetal or essential oils to improve the smell &/or sensation of the product and to render it hydrophobic, thereby minimizing its dilution with the hypotonic liquid outflow.

CLINICAL EFFICACY: Pilot Clinical Study

Study Design: “A pilot clinical trial to evaluate the efficacy and the safety of a medical device AS-22 on the healing of bedsore wounds and ulcers of diabetic origin against a placebo.” conducted respecting GCP after Ethical Approval.

Place of study: Raj Hospital and Research center, Main Road Ranchi, 834001 Jharkand, India, under the supervision of Dr. Ravishankar DAS (MBBS, MS) Chief Surgeon.

Duration: 6 weeks (42 days)

Test product: VITROBIO Filmogen Wound Treatment Gel (Antiscar); Comparator/Control products: honey + saline (For ethical reasons, the placebo product contained a honey + saline solution and not only saline as honey is traditionally used for wound healing and is an ingredient of VB Filmogen Wound Treatment formula.)

Products were applied usually 2 times per day but some patients also used the product 3 times per day.

Number of patients: VITROBIO Wound Gel: 52 patients (43M + 9F) showing a total of 69 wounds (n=69); Control: 41 patients (34M + 7F) showing a total of 49 wounds (n=49).

The primary cause of wounds was diagnosed as diabetic origin (65%), pressure ulcers (17%) or venous insufficiency ulcers (18%).

Parameters evaluated: Primary: Wound Surface Area; Wound Volume; Wound Tissue Hydration; Pain.

Secondary: Local tolerance, side effects and any undesirable reaction were also assessed at the time of each product application.

Results:

Results: A statistically significant difference was observed between the control group and the group treated with VB Filmogen Wound Treatment Gel with respect to reduction in the wound surface area (33.37 vs 97.87%) and wound volume (29.45 vs 94.17%) after 6 weeks of treatment. Mean wound humidity was lastingly enhanced without application of any other humidifying product, whereas pain scores were drastically reduced as early as from week 1 and continued decreasing markedly throughout the treatment period.

Adverse effects: No treatment-related serious adverse effect was observed. No incidence of any unwanted local irritation or allergic reaction was recorded.

Conclusions:

This novel hypertonic, highly osmotic, antibacterial, MMP & inflammatory cytokine inhibitor filmogen liquid bandage is a safe and effective treatment to promote fast healing of chronic, otherwise non-healing, wounds.

Clinical Publication: R. Shrivastava : Clinical evidence to demonstrate that simultaneous growth of epithelial and fibroblast cells is essential for deep wound healing, in Diabetes Research and Clinical Practice 92 (2011) 92-99.

Advantages over competition:

Available treatments Þ

 

Required properties ▼

Hydrocolloid Dressings Absorbant Hydrogels Alginates Bio-membranes Anti-

biotics

Anti-

septics

Growth Factors Chemical agents Surgical mrthods VITROBIO WOUND /ULCER

TREATMENTS

Neutralize MMPs NO NO NO NO NO NO NO NO NO YES
Stop inflammation NO / YES NO NO NO NO NO NO NO NO YES
Wound hydration YES YES YES NO NO NO NO NO NO YES
Fibro cell growth NO NO NO NO NO NO YES NO NO YES
Epi cell growth NO NO NO NO NO NO YES NO NO YES
Non-irritant YES YES YES YES YES YES YES NO NO YES
Anti-bacterial NO NO NO NO YES YES NO NO / YES NO YES
No cell toxicity YES YES YES YES NO NO YES NO NO YES
Cell nutrition NO NO NO NO NO NO NO NO NO YES
Topical use YES YES YES YES YES / NO YES YES YES YES YES
Not painful YES YES YES YES YES YES YES NO / YES NO YES
Avoid dressing NO NO NO NO NO NO NO NO NO YES
Reduce pain YES YES YES YES NO NO NO YES / NO NO YES
Easy application YES YES YES YES YES / NO YES YES YES NO YES
Inexpensive NO NO YES NO YES YES NO YES NO YES
100% Natural NO / YES YES YES YES NO NO YES NO YES YES
Home Use YES NO / YES YES NO YES YES NO YES NO YES

NB: ANTISCAR Wound Healing Gels with cicatrization, antimicrobial, anti-inflammatory properties can be used for post-surgical wounds to promote fast healing with no infection and reduced scarring.

Patented worldwide: Glycerol PCT/FR99/01340; Filmogen Glycerol: PCT/EP2013/061835; Deep Wound Healing: WO2010/045969 A1. For further details please contact VITROBIO France.