Actolind® w Solution Actolind® w Gel

Against all resistant microorganisms Irrigation, healing, moistening and care product for skin, including mucosa and wound

“Your first choice” for decontamination of antibiotic resistant microorganisms (MRSA, MRE, VRE)

“Your first choice” for burn and wound care

www.actogmbh.com [email protected] ACTIVE INGREDIENT

PROPERTIES PHMB to acidic phospholipids, i.e. Phosphatidylglycerol INGREDIENTS and Diphosphatidylglycerol that are present on the cell POLYHEXAMETHYLENE (PHMB) membrane of pathogenic microorganisms(1). Thus, the Polyhexamethylene biguanide (PHMB) is a strong cationic derivate is an ideal active substance for infected, dried chemical that shows a high tissue compatibility and persistent wounds. with a broad mıcrobial spectrum. It is also known as Action mechanism of PHMB is examined in detail(3). Polyhexanide, Poly(iminoimidocarbonyliminoimidocarb Steps of its primal bactericidal effect are listed below: onyliminohexamethylene) hydrochloride. The molecular • Rapid penetration on bacterial surfaces formula of the substance is (C8H17N5)n HCl. • Selective bonding to specific areas • Elimination of bacterial defense mechanism Chemical structure is as shown below: • Penetration to the cytoplasmic membrane • Disruption of cytoplasmic membrane and exuding of intracellular fluid, electrolyte and macromolecules to extracellular area • Lysis and eventually bacterial cell death Significant similarities were found in terms of structure and effect between antimicrobial peptides and PHMB. This issue is explained by the similarities between chain structures of antimicrobial peptides and linear POLOXAMER chain structure of PHMB, which is formed by cationic Poloxamers are synthetic tri-block copolymers of biguanide groups and hydrophobic hexamethylene polyethylene oxide and polypropylene oxide. They are groups(2). PHMB has below listed properties that are amphiphilic, non-ionic surfactants that cover over 50 required for new generation : different types and commonly used in pharmaceutical • Safe, broad-spectrum antimicrobial effect, and cosmetic formulations as a dispersing agent, • Rapid effect, emulsifying agent, solubilizing agent, tablet lubricant, • Continuous effect even under biological stress, wetting agent, gelling agent and thickener. Non-ionic • Accelerating effect of wound healing, surfactants show more surface and emulsification activity • High tissue and cell compliance, in comparison to anionic and amphoteric surfactants at • Less likely to cause allergic reactions, sensitization or same concentrations. Poloxamers are usually accepted resistance, as non-toxic and non-irritant ingredients used in oral, • Low rate of absorption into systemic circulation. parenteral and topical formulations and possess less toxicity compared to other surfactants i.e. betaines. The Pharmacokinetic Properties surface-active nature of poloxamer reduces the surface It is applied on skin, mucosa and wound topically. No tension on the skin, thus the adhesion of microorganisms evidence has been found on the systemic absorption to the wound is minimized. This effect improves the PHMB. efficiency of PHMB and reduces tissue damage arising The fact that, its polymeric chain structure and relatively from irrigation or debridement. high molecular weight, which is about 3000 g/mol reduce the risk getting in the circulatory system.

Chemical structure is as shown below: Antimicrobial Effects After lots of studies about antimicrobial effects of Polyhexamethylene biguanide, it is stated that PHMB has strong microbicide effects on gram positive and negative bacteria, fungi(6), HIV(7), some other viruses and amoebas(8,9). According to in vitro studies of gram PHARMACOLOGICAL PROPERTIES positive and negative bacteria, it is stated that PHMB Pharmacodynamic Properties kills E. coli, S. aureus, P. aeruginosa, E. hirae, C. albicans, Polyhexamethylene biguanide (PHMB) is a polymeric Klebsiella sp. and Enterobacter sp. in 5-10 seconds biguanide derivative (ATC-Code: D08AC05). It shows completely(4,5,10,11). a strong microbicide effect on gram +/- bacteria, According to studies, the antimicrobial effect continues fungi, some viruses and amoeba. Together with this in the presence of blood and albumin. The effect, strong microbicide effect it also possesses high tissue however, is reduced in the presence of mucin and compatibility. The effect is due to the selective binding of chondroitin sulfate.

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Microbiologic Activity; Tissue Compatibility • Fast action PHMB shows high tissue compatibility. The tissue • Broad spectrum compatibility of PHMB based on its activity against the • Effective against whole gram positive and negative acid lipids contained within the bacterial cell membranes bacteria and minor effect on the neutral lipids of human cell • Effective against antibiotic resistant microorganisms membranes. This helps to prevent damage to the (MRE, i.e. MRSA and VRE) surrounding healthy tissue.Due to its low toxicity, it can • Effective against enveloped and some non-enveloped be applied over a long period of time. viruses In order to estimate the compatibility of an antiseptic, its cytotoxic effect is needed to be evaluated together with its microbicide effect(13).

Biocompatibility Index (BI)

Antiseptic concentration destroying 50% of mouse fibroblast cells BI: ------Antiseptic concentration decreasing 3 log10 (99.9%) of bacteria colony number

PHMB also helps and accelerates wound healing at microbicide concentrations. Antiseptics primarily need to provide reproduction of cells that are responsible for wound healing. A study with keratinocytes states that PHMB increases keratinocyte production about 0.2 PHMB is also effective on bacteria that form biofilms. µg/ml(14). Another study with pigs states that PHMB Biofilms are polymeric structures consist of bacteria and accelerates wound healing(15). polysaccharides secreted by bacteria and formed mainly on solid surfaces. The effect of antibiotics and antiseptics on bacteria in biofilms is generally is reduced. The effect of PHMB on S. epidermidis and E. coli is slightly reduced in existence of biofilm formation, even though it is stated as the most effective antiseptic(12).

-3- APPLICATION AREAS

APPLICATION AREAS Actolind® w Solution/Gel is used for cleaning, decontamination, irrigation and moistening of infected, dried and disintegrated (chronic and acute) skin and mucosa; it is also used before application of bandages, gauzes, compresses, wound fillers and other absorbent materials.

1. Decolonization of Antibiotic-Resistant Pathogens → MRSA Decolonization -resistant S. aureus is a gram positive bacterial strain, which causes pneumonia, wound and hospital for Acinetobacter infections are: use of mechanical infections. They are resistant to several antibiotics. ventilation, invasive processes i.e. central urinary catheter, Unsuitable antibiotic usage and insufficient protective and resistance against a broad spectrum of antibiotics. infection control cause these bacteria to spread. MRSA Mortality rates in A. baumannii infections vary depending can simply be passed by hand contact. on diverse factors; in fact it is known to be between 50-60 %. MRSA does not always cause an infection. Some people are The studies showed that polyhexanide is effectively used only carrier of MRSA and do not show any infection sign. on animate and inanimate surfaces that is colonized with Detection of MRSA carriers is very important for hospitals multi drug-resistant Acinetobacter for antisepsis and and nursing houses. Sterilization of MRSA carriers from disinfection. MRSA is called “decolonization”. Transmission of MRSA can only be prevented by continuous and systematic → Whole Body Decolonization infection control method. Depending on the location, Whole body, including hair, should be wiped with Actolind® colonization and infectivity of resistant pathogen, w Solution according to aseptic methods, for 15 minutes antisepsis and chemotherapy should be applied(29). for 3 days and the patient must subsequently be bathed. Actolind® w Solution is a perfect decolonization product Application with strong bactericidal effect on MRSA. It is easy to After showering for 1-2 minutes with warm water, handle and softly applicable to the infected area. Actolind®w Gel should abundantly be rubbed – just as → VRE Decolonization liquid soap and shampoo – on the moist and warm skin, -resistant Enterococci is a gram positive including the hair. After making sure that Actolind®w Gel bacterial strain, which cause severe hospitals infections contacted the skin for 10 – 15 minutes, the patient should mainly in chronic hemodialysis patients. VRE can be carried take a shower with warm water. by healthy people who have come into contact with the → Nasal Decolonization bacteria without any infection signs. The most likely place For cleaning and decontamination, apply Actolind® w Gel where such contact can occur is in a hospital. Actolind® to front side of the nostril with a cotton swab. Wait for 2-5 w Solution is a perfect VRE decolonization product with minutes until all sloughed and solidified secretion residuals strong bactericidal effect on VRE. It is easy to handle and are raveled out. After this, wipe with a clean cloth and softly applicable to the infected area. leave a moisturizing layer. Incrustation formation within → Acinetobacter baumannii Decolonization the nose should be prevented by scrupulously applying Acinetobacter baumannii is a pleomorphic gram negative this process a few times in a day, at least in the morning, bacterial species, which can remain alive for a long time in noon and evening. The intranasal gap should constantly be extreme environmental conditions and as an opportunistic cleaned with Actolind® w Gel to avoid new microorganism pathogen in humans, easily colonize and affecting formations. Frequent usage does not cause formation of people with compromised immune systems in hospital any resistance. environment. In last decades it is frequently observed that A. baumannii causes severe nosocomial infections in Intensive Care Units (ICU) such as pneumonia, urinary tract infection and surgical wound infection by colonizing in respiratory tract, oropharynx, skin, urinary, and gastro- intestinal system. Therefore it is rated as an increasingly serious hospital-derived infection. Principal risk factors

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Application 3. Wound Care with Actolind® Actolind® w Gel should be applied within the wings of Infection Control on Wound nose 3 times in a day during 5 days. For control, following Chronic Wound Infections the end of 5-day application period, 3 separate negative Chronic wounds are generally complicated and have a result should be obtained in the control examples which long healing process. It may not be healed for months or are to be taken beginning from 3rd day at the earliest. years because of underlying diseases and complications occurred during the recovery. For chronic wound 2. Body Care with Actolind® treatment, a multifactorial approach is needed while → Oral Care taking care of underlying pathophysiology. Before wound Carious clinic studies demonstrated that the oral care closure, an environment suitable for tissue repair is performed with PHMB removes the biofilm, which needed. ceases the damaged tissue recovery, more effectively Therefore the steps below are needed: and prevents the reformation of plaques and reduces the • Removal of dead tissue, oral bacteria level(28). • Ensuring moisture balance, • Removal of bacterial imbalance, Application • Removal of barriers to start healing at epidermal Actolind® w Solution is used with oral care sticks. For borders. oral care: clean inside the mouth two times in a day with If the number of bacteria on the surface tissue of the sticks that are moisturized with Actolind® w Solution. wound exceeds 105-106 per gram/tissue, it may slow → Facial Care down the recovery due to released toxins. In this case The face is thoroughly washed with a single-use shower antiseptic usage is necessary. Antiseptic should be chosen sponge, soaked with Actolind® w Solution. Special after a risk - benefit assessment. Otherwise, even though attention should be given that the whole face is covered the chosen antiseptic eradicates the bacteria, it may slow with Actolind® w Solution. Eyes should be closed during down the wound recovery. this step. Eyelids and edges are also carefully cleaned with With its strong broad spectrum microbicide effect, high the same sponge. Areas cleaned and decontaminated on tissue compatibility and accelerating effect on the wound the skin are wiped to dry after 1 – 2 minutes. Sponge recovery, PHMB is the first antiseptic choice for chronic should be thrown away afterwards. non-healing persistent wounds(16). This activity is stated on a number of pre-clinical and clinical studies. → Hair Washing Before taking bath, the hair should completely be → Decubitus, Diabetic Foot and Venous Ulcer Care wetted by means of a bath sponge completely soaked Related areas should primarily be cleaned and washed with Actolind® w Solution and covered with a clean with Actolind® w Solution. In order to provide the best towel. It should be wetted for 3 – 5 minutes to take effect, Actolind® w Gel should be applied as well, after effect. Afterwards, the hair is to be completely dried. cleaning of the related areas with Actolind® w Solution. Alternatively, the hair can be washed with any shampoo In this way, Actolind® w Gel takes the place of damaged and dried afterwards. skin and avoids heat loss and dehydration by forming a barrier between the outer environment and the skin, and → Body Care thus prevents the living tissues from drying by keeping Actolind® w Solution can also be used for washing, to them humid. It also prevents malodor and recolonization. remove unwanted scent and avoiding the deterioration With respect to the dressing change plan, Actolind® w of the skin integrity due to immobility, malnutrition, Gel should be applied as a thicker layer for long-interval circulatory disorder, skin dryness, long exposure of dressing changes, and as a thinner layer for frequent the skin to wetness and moistness, and so forth. Body dressing changes. Thus, the dressing is prevented from secretion, residuals and temporary microorganisms are sticking on the tissue. removed from the body with this application. Skin health is maintained and increased, while personal comfort of patients is ensured.

Application The whole body, especially armpits and inguinal should be wiped with Actolind® w Solution on a daily basis according to aseptic methods followed by a bath.

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→ Burn Treatment 4. Surgical Site Care with Actolind® The most important complication on burns is infections → Actolind® Usage before Surgical Operation since the necrotic tissue creates a favorable medium In accordance with the aseptic methods, the area which for the formation of microorganisms. Infection control is to be operated should be wiped with Actolind® w on wound requires debridement of the dead tissue, Solution. strengthening of the immune response, adequate nutrition and usage of topical and systemic antimicrobial → Catheter Care with Actolind® agents. Plenty of topical antimicrobial agents kill In accordance with the aseptic methods, the area on fibroblasts and keratinocytes that are proliferated during which the catheter is to be applied should be wiped with tissue recovery while they kill pathogens on burn surface. Actolind® w Solution. This situation causes a delay in burn recovery and increases the infection risk. Therefore most of the antimicrobial → Stoma Care agents are not suitable for long term burn treatment due It can be used for colostomy, tracheostomy and urostomy to their high cytotoxic effects. PHMB is one of the most care. suitable antiseptics for chronic wound and long term burn treatment thanks to its strong microbicide effect Application and high tissue compatibility. According to a comparative In accordance with the aseptic methods, stoma area study with Povidone- and nitrate, which should be wiped with Actolind® w Solution. are commonly used antiseptics for burn treatment, it is stated that PHMB predominates on long term burn treatment compared to other agents(17).

Application For the burn treatment, removal and decontamination of organic dirt, which are stuck on the tissue surface, preventing the damaged tissue surface from drying and secondary infection are the primary objectives. For this reason, related areas should be washed with Actolind® w • First stage Solution or wiped with a dressing cloth wetted with the solution. In order to avoid bleeding and pain that might occur during burn dressing, bandages should be wetted with Actolind® w Solution and hence they can easily be loosened.

• Second stage

• Third stage

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5. Actolind® Usage in Clinics THE RULES FOR THE PERSONNEL WHO APPLIES THE → Usage in Urology Service (Urologic Catheter) CARE TO COMPLY WITH In order to avoid urinary infections, perianal area care • Ornaments should be removed before the operation. should be applied with Actolind® w Solution before • Hands should be washed with Actoman® and disinfected mounting urinary catheter and during the period that the with Actoderm® according to EN 1500. patient caries it. • Gloves should be worn. Aseptic technique should be followed in all applications. → Usage in Gynecology Clinics • If different applications on one patient have to be (Abortion and Spiral Mounting) performed (e.g. perianal, wound care), hands should It is used for cleaning, care and removal of malodors of be washed and the gloves should be changed during perineum area before the operations such as abortion intervals. and spiral mounting in gynecology clinics. Perineum and • Gloves should absolutely be changed when passing perianal area should be wiped with Actolind® w Solution from one patient to another. from top to bottom. • Hands should be disinfected with Actoderm® after removing the gloves. → Usage in Otorhinolaryngology • All dressing materials should be deemed as medical Wetting the pads placed inside the nose after nose waste. operations with Actolind® w Solution, provides easy and painless removal of the pads.

→ Cutaneous Disorders (Dermatology) Actolind® w Solution is used as skin decontamination and supportive skin treatment for patients susceptible to infections, due to underlying diseases that deteriorate Apply each figure for 5 sec. the skin integrity, such as neurodermatitis or atopic eczema.

→ Usage in Dentistry Before and after surgical operation, it removes efficaciously the “bacterial dental plaque” that causes diphtheria illness and avoids foul breath. Several clinical researches demonstrated that the reformation of plaques is prevented and the amount of oral bacteria is decreased by mouth washing with Polihexanide(28).

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Actolind® w Solution • People who have hypersensitivity against any Actolind® w Gel ingredients should not use it. Irrigation, healing, moistening and care products used • Should not be applied on hyaline cartilage, central for skin, mucosa and wound. nervous system, middle and inner ear. • Should not be used in the first four months of pregnancy. DESCRIPTION • Should not be used with anionic soaps, enzymes, oils Actolind® w Solution and Gel are medical products and ointments. containing PHMB, auxiliary substances, and distilled water. GENERAL SAFETY INSTRUCTIONS For external use only. Do not use it as an infusion or for ANTIMICROBIAL EFFECTS injection purposes. Do not drink! If swallowed, drink plenty Microbiological studies of Actolind® w Solution/Gel of water and consult a physician immediately. Since there were performed on test organisms shown below by is no sufficient information and experience available for Hygiene Nord GmbH Greifswald, Prof. Dr. A. Kramer and usage on inner ear canal, it is recommended to prevent found effective in 30 seconds(23-24). direct contact of the product with the eardrums. Do not MRSA strain H-5-24 expose product bottles to direct sun light and store at Staphylococcus aureus MRSA strain “E. Nord” room temperature. It is a medical product. Keep out of Staphylococcus aureus MRSA strain, DSM 2569 reach of children and store in original packaging. Staphylococcus aureus ATCC 6538 ATCC 15442 Composition NCTC 10538 100 g of Actolind® w Solution contain; Polyhexanide, auxiliary substances, distilled water. Enterococcus hirae ATCC 10541 Candida albicans ATCC 10231

Regarding these studies, it is stated that the antimicrobial effect continues in the presence of blood and albumin in the medium, but is decreased in the presence of mucin and chondroitin sulfate.

PHYSICAL PROPERTIES • Clear, colorless and odorless. • Non-toxic • Actolind® does not contain iodine compounds, alcohol, and octenidine Composition dihydrochloride. 100 g of Actolind® w Gel contain; • Actolind® can be applied directly and undiluted onto Polyhexanide, auxiliary substances, carrier substances (un)damaged skin and transition zones of mucosa (glycerin, hydroxyethyl cellulose), distilled water. membrane. Rinsing is not required. • Actolind® is compatible with the pH of the skin. • Actolind® does not cause any irritation and can be applied in an easy and painless manner. • Actolind® can be used in the needed frequency, as required for an effective treatment. • Actolind® effects actively in a quick manner. • Actolind® eliminates undesirable odors caused by the colonization of bacteria or fungi. • Actolind® clinically and dermatologically tested, rated as “very good”.

CONTRAINDICATIONS Actolind® w Solution and Gel are Class III Medical Actolind® is contraindicated for situations as shown Products within the scope of 93/42/EEC Medical Devices below: Directive with amendment 2007/47/EC.

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Actolind® Genital Actolind® Swab Cleaning, care, deodorizer and anti-itch gel for genital CATHETER INLET CLEANING WIPE area. It prevents the entry of microorganisms into the body • Dermatologically tested during mounting the catheter. • Non-allergic. AREA OF USE • Non-toxic. • It is used to clean the inlet before mounting the catheter • Colorless, odorless. (such as intravenous, urinary catheters). • Compatible with vaginal pH. • Cleaning of dialysis fistula and graft site. • Supports treatment. • Instalment and maintenance of Central Venous Catheter • For itching and irritation in external genitalia after (CVC). menstruation, pregnancy and during menopause. • Cleaning of the area before cardiac catheterization. • For postpartum antisepsis of genitalia. • Cleaning of the peritoneal dialysis area. • For eliminating odors generated in the genital area caused by bacterial infection. METHOD OF USE • As an external genital wash for removal of Clean the direct catheter inlet by wiping with a single microorganisms and prevention of infection before and gesture from far to near and from clean areas to dirty after sexual intercourse. areas. After using Actolind® w Swab, dispose it as a • Relief of itching and irritation caused by microorganisms. medical waste. • For hygiene in genital area after diseases or surgical operations. SIDE EFFECTS • Before and after fitting a urinary catheter. It should not be used on patients allergic to any of the ingredients.

CHEMICAL COMPOSITION Content of the solution used in the Actolind® w Swab: Name Concentration (w/w) 62,8% 3% Clorhexidine Gluconate 2% Actolind® w Mouth PHMB 0,05% For the treatment of mucosal infections of the mouth and mouth ulcers. For oral hygiene before, during and after WARNINGS dental and oral surgery. • Only for topical application. Store it under 25°C and out • Actolind® w Mouth has a fresh mint flavor and is sugar of the reach of children. free. Freshens instantly and deodorizes. • Do not use it if the seal under the cap is torn or broken. • Alcohol free formula kills germs that cause foul breath, • Shelf life is three (3) years at room temperature. plaque and the gum disease gingivitis. • It prevents the formation of microorganisms and pathogenic microbes when the mouth is dry. • Actolind® w Mouth is antiseptic and keeps the oral area moisturized. It prevents and reduces the formation of bacteria and microorganisms. • Suitable for daily use. • Minty taste refreshes the mouth. It is not toxic and irritant. Does not cause any pain.

-9- REFERENCES

REFERENCES 15. Kramer A, Roth B, Müller G et al. Influence of the antiseptic 1. Broxton P. Woodcock F., Heatle Y. and Gilbert P. Interaction agents polihexanide and octenidine on FL-cells and on healing of some polyhexamethylene and membrane of experimental superficial aseptic wounds in piglets. A double- phospholipids in Escherichia coli. Journal qf Applied Bacteriology, blind, randomised, stratified controlled, parallel-group study. 57, 115-124, 1984. Skin Pharmacol Physiol; 17:141–6, 2004. 2. Werthe M., Davoudi M., Sonesson A., Nitsche D. P. Mörgelin 16. Kramer A, Hübner N. O., Weltmann K. D., Lademann J., M., Blom1 K. and A. Schmidtchen. Pseudomonas aeruginosa- Ekkernkamp A., Hin P. and Ojan Assadian. Polypragmasia in induced infection and degradation of human wound fluid and the therapy of infected wounds conclusions drawn from the skin proteins ex vivo are eradicated by a synthetic cationic perspectives of low temperature plasma technology for plasma polymer. Journal of Antimicrobial Chemotherapy 54, 772–779, wound therapy. GMS Krankenhaushygiene Interdisziplinär, Vol. 2004. 3(1), 2008. 3. P. Gilbert and L.E. Moore. Cationic antiseptics: diversity of 17. Daeschlein G., Assadian O., Bruck J.C., Meinl C., Kramer A. action under a common epithet. Journal of Applied Microbiology, and S. Koch. Feasibility and Clinical Applicability of Polihexanide 99, 703–715 2005. for Treatment of Second-Degree Burn Wounds. Skin Pharmacol 4. Koburger T., Müller G., Eisenbeiß W., Assadian O. and A. Physiol;20:292–296 2007. Kramer. Mikrobiozide Wirksamkeit von Polihexanid. GMS 18. Müller G, Kramer A. Effect of selected wound antiseptics on Krankenhaushyg Interdiszip, 2(2):Doc44 2007. adult articular cartilage (bovine sesamoid bone) in the presence 5. Chawner, J.A. and Gilbert, P. A comparative study of the of Escherichia coli and Staphylococcus aureus. J Orthopaed bactericidal and growth inhibitory activities of the bisbiguanides Res.;23:127-33 2005. alexidine and . J Appl Bacteriol 66, 243–252 1989. 19. Müller G, Kramer A. In vitro action of combinations of 6. Panda A., Ahuja R., Biswas N. R., Satpathy G. and S. Khokhar. selected antimicrobial agents and adult bovine cartilage (bovine Role of 0.02% Polyhexamethylene Biguanide and 1% Povidone sesamoid bone). Chem Biol Interact;145:331-6, 2003. Iodine in Experimental Aspergillus Keratitis. Cornea 22(2): 138– 20. Müller G, Kramer A. In vitro action of a combination of 141, 2003. selected antimicrobial agents and chondroitin sulfate. Chem 7. Krebs F. C., Miller S. R., Ferguson M. L., Labib M., Biol Interact;124:77-85 2000. Rando R. F. and B. Wigdahl. Polybiguanides, particularly 21. Effect of polyhexanide and gentamicin on human osteoblasts polyethylene hexamethylene biguanide, have activity against and endothelial cells. Akif Incea, Norbert Schützea, Christian human immunodeficiency virus type 1. Biomedicine and Hendricha, Franz Jakoba, Jochen Eulerta, Jochen F. Löhrb SWISS Pharmacotherapy, 59 438–445, 2005. MED WKLY 2007;137:139–145. 8. Larkin DF, Kilvington S, Dart JK. Treatment of Acanthamoeba 22. Chemico-Biological Interactions 124 (2000) 77–85 keratitis with polyhexamethylene biguanide. Ophthalmol; 23. Alhede M., Geisler C. S., and Bjarnsholt T. Improving 99:185–191, 1992. Antibiofilm Efficacy of PHMB with a Low-intensity Ultrasound 9. Seal DV, Hayt J, Kirkness CM, et al. Successful medical therapy Wound Debridement Device. The 24th Conference of the of Acanthamoeba keratitis with topical chlorhexidine and European Wound Management Association. OP 138 . Eye; 10:413–421, 1996. 24. Lacqueire J., Climent L. Use of a New Product for the 10. Werner, H.P. Microbicidal effectiveness of selected Treatment of Chronic Leg Ulcers. The 24th Conference of the antiseptics. Hyg. Med. 17, 51–59, 1992. European Wound Management Association. OP 333 11. Pittena F.-A., Wernerb H.-P. and A. Kramer. A standardized 25. Gimenez-Tebar J. L., Lillo-Rodenas I., et all. How to Reduce test to assess the impact of different organic challenges on the Infection and Bacterial Burden by Using 0.1% Polyhexanide gel. antimicrobial activity of antiseptics. Journal of Hospital Infection The 24th Conference of the European Wound Management 55, 108–115, 2003. Association. EP 400 12. Gilbert P., Das J.R., Jones M.V. and D.G. Allison. Assessment 26. Hygiene Nord GmbH Greifswald. Dipl. Biol. T. Koburger, Dr. of resistance towards biocides following the attachment of med. P. Rudolph microorganisms to, and growth on, surfaces. Journal of Applied 27. Monika Feltgen Hygcen GmbH Microbiology, 91, 248-254, 2001. 28. Welk A, Splieth CH, Schmidt-Martens G, Schwahn Ch, 13. Müller G, Kramer A. Biocompatibility index of antiseptic Kocher T, Kramer A, Rosin M; The effect of a polyhexamethylene agents by parallel assessment of antimicrobial activity and biguanide mouthrinse compared with a inse and a cellular cytotoxicity. J Antimicr Chemother 61(5): 1281–1287, chlorhexidine rinse on bacterial counts and 4-day plaque re- 2008 growth.; J Clin Periodontol. 2005 May;32(5):499-505. 14. The protektive effect of Polyhexanide on keratinocytes in 29. Rudolph, H., 2005, AWMF Working Group for Hygiene co-culture with Staphylococcus aureus. C. Wiegand, M. Abel, P. in Hospital and Practice, “Krankenhaushygiene, Hygiene in Ruth, U.C. Hipler Poster für EWMA 2008. hospital and practice”, 3rd ed. ISBN: 3-88681-070-4, p. 135-148)

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