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MMP Inhibition


1st Topical MMP Inhibitor for the Treatment of Chronic Wounds

Oral mucositis

20mL Class I Medical Device for the treatment of Radiotherapy & Chemotherapy-induced Oral Mucositis (Official Indication)

Oral ulcers

10mL Class I Medical Device for the treatment of Canker sores & Dental brace injuries (Official Indication)

A priori, the repair of chronic wounds (bedsores, diabetic foot ulcers, venous leg ulcers, oral mucositis, skin fissures, canker sores) should be extremely simple as it merely requires the growth of epithelial and fibroblast cells to fill up the wound cavity. In order for this cellular growth to take place, the presence of a matrix for new cells to attach onto is an absolute prerequisite. This matrix, which is specific to each cell type, is made up of components such as Elastin, Collagen, Laminin, Fibronectin, Hyaluronic acid, etc… which are proteins secreted by the mother cells to form a cushion for the new daughter cells.

In the last 10 years, the scientific community has unanimously recognized that all chronic wounds contain very high concentrations (20 to 40-fold superior to normal) of proteolytic enzymes: the MMPs (Matrix Metalloproteinases), secreted by the cells to break down the waste proteins into smaller molecules to facilitate cleaning of the wound.

Unfortunately, these MMPs cannot differentiate between beneficial (“good”) and harmful (“bad”) proteins, and therefore equally destroy the proteins composing the extracellular matrix (ECM). In absence of ECM, there is no support for cell adhesion; as a result, the daughter cells cannot grow and the wound never heals.

The only possible and efficient treatment should consist in neutralizing selectively only those MMPs which destroy the ECM.

Furthermore, the same treatment not only must not interfere with the functions of the other, innocuous MMPs, but should also replace the “cleaning” functions of the MMPs it neutralizes, and, if possible, act as a safe antiseptic, antimicrobial and lastingly hydrating agent.

None of the currently available treatments takes into account every single ECM-degrading MMP, for the simple reason that these MMPs have not all been identified yet.

Moreover, it is practically impossible to block selectively the total activity of multiple MMPs using a unique chemical entity.

Therefore, only symptomatic treatments, at the cost of 4 billion US $, are presently used.

VB-Gy :

Anyone who has ever entered the sea with a skin injury will have observed that upon getting out of the water, the injury comes out cleaned, whitish, and appears to heal faster. This is attributable to the osmotic action of sea water.

Although normal saline or sea water constitute a cleaning agent of choice, they are not often used because they prove too irritating, lack filmogen properties, have a short-lived or low efficacy, and cannot be patented.

Therefore, VITRO-BIO identified, and patented in 1997, a glycerol-type, non-irritant, cell-friendly solution, 18 times more osmotically active than sea water. An improved version of this solution with enhanced film retention capabilities has been invented and patented by VITRO-BIO in 2013.

Through its strong osmotic activity, VB-Gy induces instant exudation of hypotonic fluids across the injured surface, thus cleaning the lesion of free-floating protein conjugates, as well as all contaminants present, including bacteria, thus acting as an instant, natural antiseptic, antimicrobial, non-irritant and hydrating device.

Selective MMP Neutralization: The Role of Tannins or Vegetal Polymers :

In vitro cell culture models were used to identify the ECM-destroying MMPs for each type of wounds.

Skin is a proteinous structure. Notably in human history, the skin proteins have been blocked using specific tannins to transform skin into leather. Tannins are polymers. This proves that tannins have long been known to have a strong affinity for proteins and other macromolecules.

Since MMPs are proteins, VITRO-BIO’s objective was to identify, among the thousands of synthetic and natural polymers, the specific polymers or fractions thereof capable of neutralizing those selected MMPs.

Being large and inert molecules, these polymers do not interact with the cellular structures, thus presenting the tremendous advantage of acting only on the surface of the injury without any cellular interaction.

VITRO-BIO incorporated those selected polymers into VB-Gy as an antiseptic, antibacterial, hydrating, specific MMP inhibitor solution to promote the healing of chronic wounds.

 Honey :

It was observed that the addition of a small quantity of honey, which at a pH between 6 & 6.5 becomes activated, generating H2O2 bubbles which remove the smaller and snuggly lodged contaminants from the cellular tissues, thus acting as substitutes for MMPs’ residue removal role.

  • Shrivastava R, Cucuat N, Rousse M, et al. A New Generation of Topical Chronic Wound Treatments Containing Specific MMP Inhibitors. Chronic Wound Care Management and Research (Dove Press). 2014; 1, 31-40. ISSN: 2324-481X.
  • Shrivastava R. Clinical evidence to demonstrate that simultaneous growth of epithelial and fibroblast cells is essential for deep wound healing. Diabetes Research and Clinical Practice, 92-99, 2011.
  • Shrivastava R, Cucuat N, John GW. Effects of Alchemilla vulgaris and Glycerine on Epithelial and Myofibroblast Cell Growth and Cutaneous Lesion Healing in Rats. Phytotherapy Research 21, 369-373, 2007.
  • Shrivastava R, John GW. Treatment of common mouth ulcers with topical Alchemilla vulgaris in glycerine (Aphtarine®). Clin Drug Investig, 26(10): 567-573, 2006.

The following Medical Devices implement this completely new therapeutic approach conceived by VITRO-BIO Pharma, France:

ANTISCAR is a specific cellular matrix-degrading MMP inhibitor in the form of a topical antimicrobial, lastingly hydrating, filmogen solution for the treatment of superficial bedsores, diabetic ulcers and venous leg ulcers. (50ml tube)

OROSOL is an oral MMP-inhibiting spray for the treatment of chemo- and radiotherapy-induced oral mucositis ulcers. (20ml spray)

APHTARINE is the first specific topical MMP inhibitor and healing gel for the treatment of traumatic oral sores. (10ml tube)