Acute or chronic cutaneous lesions of various origin are managed by application of medical devices to aid wound healing, promote revascularization, absorb exudate and, where necessary, exert an antibacterial/antimicrobial action.
Normally, exudate is the consequence of the increased permeability of capillaries in the inflammatory tissue. Exudate has the task to confine the pathological process, preventing the diffusion of microorganisms and blocking the action of possible dangerous antigens through an immune mechanism.
On the contrary, in chronic lesions exudate is produced in an abnormal way and it determines a blockage of the process of tissue repair by destruction of the proteins of the extracellular matrix and growth factors, and by inhibition of cell proliferation. Clinically, hyperexudation can determine maceration of perilesional skin and promote infection, in particular by the bacterial species Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecium, Staphilococcus aureus and by fungi such as Candida albicans. 
Additionally, hyperproduction of exudate results in the need for continuous replacement of the wound dressings. In these situations, neither the discomfort felt by the patient who sees his/her quality of life worsened by the constant need of healthcare nor the consequent increase of health costs should be underestimated.
Today, numerous devices containing antibacterial agents are commercially available and have different characteristics depending on the application they are intended for. Among the others, foams, adhesive or not, based on polyurethane and hydrocolloid (Contreet®) or based on hydrofiber (Aquacel Ag); multilayer polyethylene nets (Acticoat®). Gauzes containing absorbent powders should be mentioned. These products are characterized by an absorbent polymeric support and a metal, in particular silver. The antibacterial properties of silver are well known (Fraser, J. F. et al. ANZ J. Surg. 2004, 74, 139-212) and are generally related to the oxidized form of ionic silver. Silver inhibits the synthesis of structural proteins composing the bacterial wall preventing its formation, and binds to enzymatic proteins of bacterial DNA, disrupting its functionality. However, such bindings occur in an aspecific way, that is silver acts both on bacterial cells present in the wound and on surrounding cutaneous/dermic cells, which results in toxicity of silver for the wounded patient. In fact, silver inhibits proliferation of keratinocytes and fibroblasts (fundamental components of dermis and epidermis), slowing down the regeneration of the wound bed on which it is applied, and this is detrimental to complete healing of the lesion, insomuch that from the results of some in vitro tests on keratinocyte cultures, some go as far as recommending to avoid the application of silver based devices (Lam, P. K. et al. Br. J. Biomed. Sci., 2004, 61, 125-127). Additionally, silver is a sensitizing agent, mainly when applied for long periods, exactly as it occurs in the case of decubitus ulcers, burns, or slow healing wounds in general (“Chronic exposure to Silver or Silver salts, Patty's Industrial Hygiene and Toxicology”, Vol. 2, G. D. Clayton, F. E. Clayton, Eds. Wiley-Interscience, New York, 3rd Ed., 1981, p. 1881-1894).
Hyaluronic acid (HA) is a heteropolysaccharide, i.e. a polymer, that can have a wide range of molecular weights, generally correlated to different biological effects.
The multiplicity of biological effects of the HA is well known, and is essentially bound to its chemical nature.
High MW fractions (of the order of millions of Daltons) have very high viscosity and find specific application in ocular surgery and also in particular cases of soft tissue filling, for both surgical and dermocosmetic purposes; the effect on wound healing, instead, is strongly controversial insomuch that some authors have demonstrated very positive effects on cell proliferation by high mean MW HA, while others have highlighted exactly the opposite effect.
Intermediate molecular weight fractions (500-750 kDa) (Brun et al. Osteoarthritis Cartilage, 2003, 11, 208-16) are normally used as viscosupplements in osteoarthrosis and joint diseases in general. Because they may generate solutions with viscosity which is very similar to that of the synovial fluid, in fact, these fractions exert a mechanical lubrication action. Last, low molecular weight HA (oligomeric HA, generally meant as having mean MW comprised between 1 and 10 kDa) has remarkable angiogenic action; thus it particularly promotes revascularization of the tissues on which it is applied, promoting wound healing. Additionally, low molecular weight HA has the known ability of stimulating cell mobility and activating fibroblast migration, which is obviously of great importance for repairing processes (West et al., Science, 1985, 228, 1324-6; Deed et al., Int. J. Cancer, 1997, 71, 251-6). For these reasons, low molecular weight HA is employed as a component of numerous products and devices with wound healing action. One of the objects of the invention is to provide a composition for wound dressing and healing that is more efficient and less toxic than those presently available for the treatment of skin lesions
Another object of the invention is to meet the clinical need of dressings with a strong antimicrobial/antifungal active agent while minimizing inhibitory effects on tissue regeneration and toxicity on the tissues to be treated.
USPTO Backgrounds
USPTO Backgrounds