A new generation of topical chronic wound treatments containing specific MMP inhibitors

Abstract

Incidence of chronic wounds is constantly rising worldwide, but all currently available treatments are intended either to provide symptomatic relief or to assist cicatrization to some extent, but not to directly stimulate cellular growth. Physiologically, chronic wound healing simply requires cell growth to fill the injured cavity. To grow, our cells need to attach onto a cushion, called extracellular matrix (ECM), secreted by the mother cells and composed of multiple proteins. Recent scientific works prove that the concentration of certain matrix metalloproteinases (MMPs) is extremely high in all chronic wounds and, because of their proteolytic nature, some MMPs completely degrade the ECM, hindering cell attachment and cell growth. The aim of this study was to identify, neutralize, and eliminate these MMPs from the wound surface so as to design an effective treatment for chronic wounds. Methods: Acute and chronic models of human epithelial and fibroblast cells were prepared on a defined ECM cushion in vitro and MMPs were added in the culture medium to identify the MMPs causing ECM disintegration for each cell type. ECM-degrading MMPs were then incubated with selected procyanidin-rich plant extracts (PCDs) and cell growth was reanalyzed. Results: It was observed that: 1) multiple MMPs are involved in cellular matrix destruction; 2) ECM-destroying MMPs are specific with respect to cell type; and 3) specific PCDs may bind and neutralize selected MMPs. Conclusion: Topical application of specific plant PCDs to selectively neutralize ECMdestroying MMPs in acute and chronic wounds represents a novel approach for the treatment of superficial and deep skin wounds.

Aktisor® Wound Suspension in the Treatment of Ulcers with Multiple Etiologies

“…MMPs in the chronic wound are products of both the host and bacteria. Shrivastava et al have shown that the MMPs in pressure ulcers, diabetic ulcers and venous leg ulcers are more or less identical, which might explain why the chronic wounds with diverse etiologies that were treated with Aktisor® suspension healed [8].…”

“…Glycerol is also known as an anti-microbial substance, often used in medicine for preserving tissues and cells, and is therefore an excellent choice as a cleansing and moisturizing ingredient, being totally safe for topical application on wounds and having also demonstrated wound healing properties [1997 patent N˚PCT/FR99/01340; 2013 patent N˚PCT/EP2013/061835] [7]. The tannin-rich plant extract component stops and prevents the destructive action of MMPs in the wound bed, thus preserving the cell matrix integrity crucial to cellular attachment and cellular growth [8] [9]. Additionally, medical honey products have proved to be effective because they cleanse the wound and accelerate wound healing, even in immune-compromised patients with colonization of multi-resistant bacteria [10] [11].…”

Clinical Efficacy of Novel Filmogen, Antimicrobial, Cleaning, Fluidizing Cough Treatment

“…Almost all systemic drugs induce side effects and cause more harm than good, whereas topically applying any chemical on the LRT would block the healing of damaged URT mucosa [28]. Taking into consideration the future research on mono-target anticough drugs, multiple side effects [29,30], development of bacterial resistance and inefficacy of antibiotics for the treatment of dry cough [31,32], F-VB-Gy opens a totally new horizon not only for the treatment of dry or wet cough, but potentially also for the treatment of other topical diseases having a multifactorial origin [33][34][35]. Further research is required to use this non-invasive technology for the treatment of other topical diseases for which there is still no effective treatment available.…”

Clinical Efficacy of a New Filmogen Polymeric Glycerol Solution for the Treatment of Rhinosinusitis

“…A few patients of this study complained about moderate nasal irritation right after each TP application, lasting for about [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] seconds. This may be attributable to the fact that FPG solution is osmotic and draws intracellular hypotonic liquid as soon as it is sprayed as a film over the nasal mucosa.…”

“…To prevent instant dilution of the film a small quantity of VB-Gy binding plant extracts rich in polymeric tannins was added to it as experiments and studies conducted by our laboratory have shown that certain specific tannins bind to the VB-Gy molecules and create a flexible film with increased resistance to dilution resulting in improved duration of action [29]. Tannins are large, inert and highly branched molecules which do not interact with the cellular structures are noncytotoxic even at higher concentrations and they are easily expelled with hypotonic liquid flow once the FPG film is disintegrated.…”