Negatol (Policresulen) is a topical hemostatic and antiseptic indicated for common anal disorders, such as hemorrhoids, and for gynecological infections. Policresulen has hemostatic activity by causing coagulation of blood proteins and promoting the contraction of the muscular fibers of the blood vessels of small caliber. Policresulen promotes selective chemical debridement: being an anion, it has the ability to interact only with the phospholipid molecules of the plasma membranes of to devitalized cells, which have lost its original electric charge. This contact provides the denaturation of cellular proteins, facilitating their removal. Its acidity, together with coagulating properties, give policresulen antimicrobial activity against staphylococcus spp., streptococcus spp. and Candida albicans. Policresulen is often used for gynecological infections. It is also used to treat canker sore in some countries.

Hyaluronic acid (HA) is a high molecular weight biopolysacharide, discovered in 1934, by Karl Meyer and his assistant, John Palmer in the vitreous of bovine eyes. Hyaluronic acid is a naturally occurring biopolymer, which has important biological functions in bacteria and higher animals including humans. It is found in most connective tissues and is particularly concentrated in synovial fluid, the vitreous fluid of the eye, umbilical cords and chicken combs. It is naturally synthesized by a class of integral membrane proteins called hyaluronan synthases, and degraded by a family of enzymes called hyaluronidases. Hyaluronan synthase enzymes synthesize large, linear polymers of the repeating disaccharide structure of hyaluronan by alternating addition of glucuronic acid and N-acetylglucosamine to the growing chain using their activated nucle¬otide sugars (UDP – glucuronic acid and UDP-N-acetlyglucosamine) as substrates. The number of repeat disaccharides in a completed hyaluronan molecule can reach 10 000 or more, a molecular mass of ~4 million daltons (each disaccharide is ~400 daltons). The average length of a disaccharide is ~1 nm. Thus, a hyaluronan molecule of 10 000 repeats could ex¬tend 10 μm if stretched from end to end, a length approximately equal to the diameter of a human erythrocyte. Although the predominant mechanism of HA is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. Hyaluronic acid possesses a number of protective physiochemical functions that may provide some additional chondroprotective effects in vivo and may explain its longer term effects on articular cartilage. Hyaluronic acid can reduce nerve impulses and nerve sensitivity associated with pain. In experimental osteoarthritis, this glycosaminoglycan has protective effects on cartilage. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. In addition to its function as a passive structural molecule, hyaluronan also acts as a signaling molecule by interacting with cell surface receptors and regulating cell proliferation, migration, and differentiation. Hyaluronan is essential for embryogenesis and is likely also important in tumorigenesis. HA plays several important organizational roles in the extracellular matrix (ECM) by binding with cells and other components through specific and nonspecific interactions. Hyaluronan-binding pro¬teins are constituents of the extracellular matrix, and stabilize its integrity. Hyaluronan receptors are involved in cellular signal transduction; one receptor family includes the binding proteins aggrecan, link protein, versican and neurocan and the receptors CD44, TSG6, GHAP and LYVE-1. The chondroprotective effects of hyaluronic acid, e.g., that it stimulates the production of tissue in¬hibitors of matrix metalloproteineses (TIMP-1) by chondrocytes, inhibits neutrophil-mediated cartilage degradation and attenuates IL-1 induced matrix de¬generation and chondrocyte cytotoxicity have been observed in vitro. Articular chondrocytes cultured in the presence of HA have a significantly greater rate of DNA proliferation and ex¬tracellular matrix production, compared with chon¬drocytes cultured without HA.

Polihexanide is a broad-spectrum antiseptic with excellent cell and tissue tolerability, ability to bind to the organic matrix, low risk of contact sensitization, and wound healing promoting effect. Polihexanide interacts with acidic, negatively charged phospholipids in the bacterial membrane, leading to increased fluidity, permeability and loss of integrity, followed by the death of the organism. Polihexanide is also transferred to the cytoplasm, where it leads to disruption of the bacterial metabolism. Neutral phospholipids on the other hand are little or not affected by Polihexanide. This is commonly seen as the main reason for the low toxicity of Polihexanide against human cells and its high therapeutic range. Due to its nonspecific, strong interaction with negatively charged phospholipids, Polihexanide has a broad antimicrobial spectrum, including Gram-positive and Gramnegative bacteria, plaque-forming and biofilm-building bacteria, spore-forming bacteria (but not bacterial spores), intracellular bacteria such as chlamydiae and mycoplasma, and fungi including Candida spp. as well as Aspergillus spp. Polihexanide is classified as ‘practically nontoxic’. The therapeutic index of Polihexanide is more than 200-fold that of chlorhexidine.

Dextranomer is a hydrophilic dextran polymer used as a biocompatible bulking agent, administered by submucosal injection. Dextranomer / hyaluronic acid treatment was associated with symptomatic improvement in adult fecal incontinence patients participating in a randomized, double-blind, study and non-comparative multinational study. Although there is limited discussion of the mechanism of action of dextranomer / hyaluronic acid in the literature, it is assumed that the dextranomer can expand the submucosal layer of the proximal anal canal, thereby increasing intestinal control. Dextranomer has been used as a 'cleansing agent' for various types of exudative wounds or ulcers, including stasis and pressure ulcers. Dextranomer appears to exert its effect due to capillary action, which absorbs wound exudate, as well as wound debris and microorganisms into the dextranomer beads or between the balls, thus removing such products from the surface of the wound. Dextranomer is an adjunct to the treatment of wounds or ulcers and does not have a direct effect on tissue repair in such ulcers, but, as in the case of other “cleansing” agents or methods, one can expect removal of residues (and possibly microorganisms) from the wound will promote natural healing.