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Actolind® w Solution Actolind® w Gel Irrigation, healing, moistening and care product for skin, Against all resistant microorganisms 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 INGREDIENTS POLYHEXAMETHYLENE BIGUANIDE (PHMB) Polyhexamethylene biguanide (PHMB) is a strong cationic chemical antiseptic that shows a high tissue compatibility with a broad mıcrobial spectrum. It is also known as Polyhexanide, Poly(iminoimidocarbonyliminoimidocarb onyliminohexamethylene) hydrochloride. The molecular formula of the substance is (C8H17N5)n HCl. PHMB to acidic phospholipids, i.e. Phosphatidylglycerol and Diphosphatidylglycerol that are present on the cell membrane of pathogenic microorganisms(1). Thus, the derivate is an ideal active substance for infected, dried and persistent wounds. Action mechanism of PHMB is examined in detail(3). Steps of its primal bactericidal effect are listed below: • Rapid penetration on bacterial surfaces • Selective bonding to specific areas • Elimination of bacterial defense mechanism • 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 chain structure of PHMB, which is formed by cationic biguanide groups and hydrophobic hexamethylene groups(2). PHMB has below listed properties that are required for new generation antiseptics: • Safe, broad-spectrum antimicrobial effect, • Rapid effect, • Continuous effect even under biological stress, • Accelerating effect of wound healing, • High tissue and cell compliance, • Less likely to cause allergic reactions, sensitization or resistance, • Low rate of absorption into systemic circulation. Chemical structure is as shown below: POLOXAMER Poloxamers are synthetic tri-block copolymers of polyethylene oxide and polypropylene oxide. They are amphiphilic, non-ionic surfactants that cover over 50 different types and commonly used in pharmaceutical and cosmetic formulations as a dispersing agent, emulsifying agent, solubilizing agent, tablet lubricant, wetting agent, gelling agent and thickener. Non-ionic surfactants show more surface and emulsification activity in comparison to anionic and amphoteric surfactants at same concentrations. Poloxamers are usually accepted as non-toxic and non-irritant ingredients used in oral, parenteral and topical formulations and possess less toxicity compared to other surfactants i.e. betaines. The surface-active nature of poloxamer reduces the surface tension on the skin, thus the adhesion of microorganisms to the wound is minimized. This effect improves the efficiency of PHMB and reduces tissue damage arising from irrigation or debridement. Pharmacokinetic Properties It is applied on skin, mucosa and wound topically. No evidence has been found on the systemic absorption PHMB. The fact that, its polymeric chain structure and relatively 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 positive and negative bacteria, it is stated that PHMB kills E. coli, S. aureus, P. aeruginosa, E. hirae, C. albicans, Klebsiella sp. and Enterobacter sp. in 5-10 seconds completely(4,5,10,11). According to studies, the antimicrobial effect continues in the presence of blood and albumin. The effect, however, is reduced in the presence of mucin and chondroitin sulfate. PHARMACOLOGICAL PROPERTIES Pharmacodynamic Properties Polyhexamethylene biguanide (PHMB) is a polymeric biguanide derivative (ATC-Code: D08AC05). It shows a strong microbicide effect on gram +/- bacteria, fungi, some viruses and amoeba. Together with this strong microbicide effect it also possesses high tissue compatibility. The effect is due to the selective binding of -2- ACTIVE INGREDIENT Microbiologic Activity; • Fast action • Broad spectrum • Effective against whole gram positive and negative bacteria • Effective against antibiotic resistant microorganisms (MRE, i.e. MRSA and VRE) • Effective against enveloped and some non-enveloped viruses Tissue Compatibility PHMB shows high tissue compatibility. The tissue compatibility of PHMB based on its activity against the acid lipids contained within the bacterial cell membranes and minor effect on the neutral lipids of human cell membranes. This helps to prevent damage to the surrounding healthy tissue.Due to its low toxicity, it can be applied over a long period of time. 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 µg/ml(14). Another study with pigs states that PHMB accelerates wound healing(15). PHMB is also effective on bacteria that form biofilms. Biofilms are polymeric structures consist of bacteria and 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 Methicillin-resistant S. aureus is a gram positive bacterial strain, which causes pneumonia, wound and hospital infections. They are resistant to several antibiotics. Unsuitable antibiotic usage and insufficient protective infection control cause these bacteria to spread. MRSA can simply be passed by hand contact. MRSA does not always cause an infection. Some people are only carrier of MRSA and do not show any infection sign. Detection of MRSA carriers is very important for hospitals and nursing houses. Sterilization of MRSA carriers from MRSA is called “decolonization”. Transmission of MRSA can only be prevented by continuous and systematic infection control method. Depending on the location, colonization and infectivity of resistant pathogen, antisepsis and chemotherapy should be applied(29). Actolind® w Solution is a perfect decolonization product with strong bactericidal effect on MRSA. It is easy to handle and softly applicable to the infected area. for Acinetobacter infections are: use of mechanical ventilation, invasive processes i.e. central urinary catheter, and resistance against a broad spectrum of antibiotics. Mortality rates in A. baumannii infections vary depending on diverse factors; in fact it is known to be between 50-60%. The studies showed that polyhexanide is effectively used on animate and inanimate surfaces that is colonized with multi drug-resistant Acinetobacter for antisepsis and disinfection. → Whole Body Decolonization Whole body, including hair, should be wiped with Actolind® w Solution according to aseptic methods, for 15 minutes for 3 days and the patient must subsequently be bathed. Application After showering for 1-2 minutes with warm water, Actolind®w Gel should abundantly be rubbed – just as liquid soap and shampoo – on the moist and warm skin, including the hair. After making sure that Actolind®w Gel contacted the skin for 10 – 15 minutes, the patient should take a shower with warm water. → VRE Decolonization Vancomycin-resistant Enterococci is a gram positive bacterial strain, which cause severe hospitals infections mainly in chronic hemodialysis patients. VRE can be carried by healthy people who have come into contact with the bacteria without any infection signs. The most likely place where such contact can occur is in a hospital. Actolind® w Solution is a perfect VRE decolonization product with strong bactericidal effect on VRE. It is easy to handle and softly applicable to the infected area. → Nasal Decolonization For cleaning and decontamination, apply Actolind® w Gel to front side of the nostril with a cotton swab. Wait for 2-5 minutes until all sloughed and solidified secretion residuals are raveled out. After this, wipe with a clean cloth and leave a moisturizing layer. Incrustation formation within the nose should be prevented by scrupulously applying this process a few times in a day, at least in the morning, noon and evening. The intranasal gap should constantly be cleaned with Actolind® w Gel to avoid new microorganism formations. Frequent usage does not cause formation of any resistance. → Acinetobacter baumannii Decolonization Acinetobacter baumannii is a pleomorphic gram negative bacterial species, which can remain alive for a long time in extreme environmental conditions and as an opportunistic pathogen in humans, easily colonize and affecting people with compromised immune systems in hospital 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 gastrointestinal system. Therefore it is rated as an increasingly serious hospital-derived infection. Principal risk factors -4- APPLICATION AREAS Application Actolind® w Gel should be applied within the wings of nose 3 times in a day during 5 days. For control, following the end of 5-day application period, 3 separate negative result should be obtained in the control examples which are to be taken beginning from 3rd day at the earliest. 3. Wound Care with Actolind® Infection Control on Wound Chronic Wound Infections Chronic wounds are generally complicated and have a long healing process. It may not be healed for months or years because of underlying diseases and complications occurred during the recovery. For chronic wound treatment, a multifactorial approach is needed while taking care of underlying pathophysiology. Before wound closure, an environment suitable for tissue repair is needed. Therefore the steps below are needed: • Removal of dead tissue, • Ensuring moisture balance, • Removal of bacterial imbalance, • Removal of barriers to start healing at epidermal borders. If the number of bacteria on the surface tissue of the wound exceeds 105-106 per gram/tissue, it may slow down the recovery due to released toxins. In this case antiseptic usage is necessary. Antiseptic should be chosen after a risk - benefit assessment. Otherwise, even though the chosen antiseptic eradicates the bacteria, it may slow down the wound recovery. With its strong broad spectrum microbicide effect, high tissue compatibility and accelerating effect on the wound recovery, PHMB is the first antiseptic choice for chronic non-healing persistent wounds(16). This activity is stated on a number of pre-clinical and clinical studies. 2. Body Care with Actolind® → Oral Care Carious clinic studies demonstrated that the oral care performed with PHMB removes the biofilm, which ceases the damaged tissue recovery, more effectively and prevents the reformation of plaques and reduces the oral bacteria level(28). Application Actolind® w Solution is used with oral care sticks. For oral care: clean inside the mouth two times in a day with sticks that are moisturized with Actolind® w Solution. → Facial Care The face is thoroughly washed with a single-use shower sponge, soaked with Actolind® w Solution. Special attention should be given that the whole face is covered with Actolind® w Solution. Eyes should be closed during this step. Eyelids and edges are also carefully cleaned with the same sponge. Areas cleaned and decontaminated on the skin are wiped to dry after 1 – 2 minutes. Sponge should be thrown away afterwards. → Hair Washing Before taking bath, the hair should completely be wetted by means of a bath sponge completely soaked with Actolind® w Solution and covered with a clean towel. It should be wetted for 3 – 5 minutes to take effect. Afterwards, the hair is to be completely dried. Alternatively, the hair can be washed with any shampoo and dried afterwards. → Decubitus, Diabetic Foot and Venous Ulcer Care Related areas should primarily be cleaned and washed with Actolind® w Solution. In order to provide the best effect, Actolind® w Gel should be applied as well, after cleaning of the related areas with Actolind® w Solution. In this way, Actolind® w Gel takes the place of damaged skin and avoids heat loss and dehydration by forming a barrier between the outer environment and the skin, and thus prevents the living tissues from drying by keeping them humid. It also prevents malodor and recolonization. With respect to the dressing change plan, Actolind® w Gel should be applied as a thicker layer for long-interval dressing changes, and as a thinner layer for frequent dressing changes. Thus, the dressing is prevented from sticking on the tissue. → Body Care Actolind® w Solution can also be used for washing, to remove unwanted scent and avoiding the deterioration of the skin integrity due to immobility, malnutrition, circulatory disorder, skin dryness, long exposure of the skin to wetness and moistness, and so forth. Body secretion, residuals and temporary microorganisms are 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. -5- APPLICATION AREAS 4. Surgical Site Care with Actolind® → Actolind® Usage before Surgical Operation In accordance with the aseptic methods, the area which is to be operated should be wiped with Actolind® w Solution. → Burn Treatment The most important complication on burns is infections since the necrotic tissue creates a favorable medium for the formation of microorganisms. Infection control on wound requires debridement of the dead tissue, strengthening of the immune response, adequate nutrition and usage of topical and systemic antimicrobial agents. Plenty of topical antimicrobial agents kill fibroblasts and keratinocytes that are proliferated during tissue recovery while they kill pathogens on burn surface. This situation causes a delay in burn recovery and increases the infection risk. Therefore most of the antimicrobial agents are not suitable for long term burn treatment due to their high cytotoxic effects. PHMB is one of the most suitable antiseptics for chronic wound and long term burn treatment thanks to its strong microbicide effect and high tissue compatibility. According to a comparative study with Povidone-iodine and silver nitrate, which are commonly used antiseptics for burn treatment, it is stated that PHMB predominates on long term burn treatment compared to other agents(17). → Catheter Care with Actolind® In accordance with the aseptic methods, the area on which the catheter is to be applied should be wiped with Actolind® w Solution. → Stoma Care It can be used for colostomy, tracheostomy and urostomy care. Application In accordance with the aseptic methods, stoma area should be wiped with Actolind® w Solution. 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 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. • First stage • Second stage • Third stage -6- APPLICATION AREAS 5. Actolind® Usage in Clinics → Usage in Urology Service (Urologic Catheter) In order to avoid urinary infections, perianal area care should be applied with Actolind® w Solution before mounting urinary catheter and during the period that the patient caries it. THE RULES FOR THE PERSONNEL WHO APPLIES THE CARE TO COMPLY WITH • Ornaments should be removed before the operation. • Hands should be washed with Actoman® and disinfected with Actoderm® according to EN 1500. • Gloves should be worn. Aseptic technique should be followed in all applications. • If different applications on one patient have to be performed (e.g. perianal, wound care), hands should be washed and the gloves should be changed during intervals. • Gloves should absolutely be changed when passing from one patient to another. • Hands should be disinfected with Actoderm® after removing the gloves. • All dressing materials should be deemed as medical waste. → Usage in Gynecology Clinics (Abortion and Spiral Mounting) It is used for cleaning, care and removal of malodors of perineum area before the operations such as abortion and spiral mounting in gynecology clinics. Perineum and perianal area should be wiped with Actolind® w Solution from top to bottom. → Usage in Otorhinolaryngology Wetting the pads placed inside the nose after nose 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 the skin integrity, such as neurodermatitis or atopic eczema. Apply each figure for 5 sec. → 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). -7- PROSPECTUS Actolind® w Solution Actolind® w Gel Irrigation, healing, moistening and care products used for skin, mucosa and wound. • People who have hypersensitivity against any ingredients should not use it. • Should not be applied on hyaline cartilage, central nervous system, middle and inner ear. • Should not be used in the first four months of pregnancy. • Should not be used with anionic soaps, enzymes, oils and ointments. DESCRIPTION Actolind® w Solution and Gel are medical products containing PHMB, auxiliary substances, and distilled water. GENERAL SAFETY INSTRUCTIONS For external use only. Do not use it as an infusion or for injection purposes. Do not drink! If swallowed, drink plenty of water and consult a physician immediately. Since there is no sufficient information and experience available for usage on inner ear canal, it is recommended to prevent direct contact of the product with the eardrums. Do not expose product bottles to direct sun light and store at room temperature. It is a medical product. Keep out of reach of children and store in original packaging. ANTIMICROBIAL EFFECTS Microbiological studies of Actolind® w Solution/Gel were performed on test organisms shown below by Hygiene Nord GmbH Greifswald, Prof. Dr. A. Kramer and found effective in 30 seconds(23-24). Staphylococcus aureus MRSA strain H-5-24 Staphylococcus aureus MRSA strain “E. Nord” Staphylococcus aureus MRSA strain, DSM 2569 Staphylococcus aureus ATCC 6538 Pseudomonas aeruginosa ATCC 15442 Escherichia coli NCTC 10538 Enterococcus hirae ATCC 10541 Candida albicans ATCC 10231 Composition 100 g of Actolind® w Solution contain; Polyhexanide, auxiliary substances, distilled water. 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, benzalkonium chloride and octenidine dihydrochloride. • Actolind® can be applied directly and undiluted onto (un)damaged skin and transition zones of mucosa 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”. Composition 100 g of Actolind® w Gel contain; Polyhexanide, auxiliary substances, carrier substances (glycerin, hydroxyethyl cellulose), distilled water. CONTRAINDICATIONS Actolind® is contraindicated for situations as shown below: Actolind® w Solution and Gel are Class III Medical Products within the scope of 93/42/EEC Medical Devices Directive with amendment 2007/47/EC. -8- PROSPECTUS Actolind® Swab CATHETER INLET CLEANING WIPE Actolind® Genital Cleaning, care, deodorizer and anti-itch gel for genital area. • Dermatologically tested • Non-allergic. • Non-toxic. • Colorless, odorless. • Compatible with vaginal pH. • Supports treatment. • For itching and irritation in external genitalia after menstruation, pregnancy and during menopause. • For postpartum antisepsis of genitalia. • For eliminating odors generated in the genital area caused by bacterial infection. • As an external genital wash for removal of microorganisms and prevention of infection before and after sexual intercourse. • Relief of itching and irritation caused by microorganisms. • For hygiene in genital area after diseases or surgical operations. • Before and after fitting a urinary catheter. It prevents the entry of microorganisms into the body during mounting the catheter. AREA OF USE • It is used to clean the inlet before mounting the catheter (such as intravenous, urinary catheters). • Cleaning of dialysis fistula and graft site. • Instalment and maintenance of Central Venous Catheter (CVC). • Cleaning of the area before cardiac catheterization. • Cleaning of the peritoneal dialysis area. METHOD OF USE Clean the direct catheter inlet by wiping with a single gesture from far to near and from clean areas to dirty areas. After using Actolind® w Swab, dispose it as a medical waste. SIDE EFFECTS 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) Isopropyl Alcohol 62,8% Ethanol 3% Clorhexidine Gluconate 2% PHMB 0,05% Actolind® w Mouth For the treatment of mucosal infections of the mouth and mouth ulcers. For oral hygiene before, during and after dental and oral surgery. • Actolind® w Mouth has a fresh mint flavor and is sugar free. Freshens instantly and deodorizes. • Alcohol free formula kills germs that cause foul breath, 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. WARNINGS • Only for topical application. Store it under 25°C and out of the reach of children. • Do not use it if the seal under the cap is torn or broken. • Shelf life is three (3) years at room temperature. -9- REFERENCES REFERENCES 15. Kramer A, Roth B, Müller G et al. Influence of the antiseptic agents polihexanide and octenidine on FL-cells and on healing of experimental superficial aseptic wounds in piglets. A doubleblind, randomised, stratified controlled, parallel-group study. Skin Pharmacol Physiol; 17:141–6, 2004. 16. Kramer A, Hübner N. O., Weltmann K. D., Lademann J., Ekkernkamp A., Hin P. and Ojan Assadian. Polypragmasia in the therapy of infected wounds conclusions drawn from the perspectives of low temperature plasma technology for plasma wound therapy. GMS Krankenhaushygiene Interdisziplinär, Vol. 3(1), 2008. 17. Daeschlein G., Assadian O., Bruck J.C., Meinl C., Kramer A. and S. Koch. Feasibility and Clinical Applicability of Polihexanide for Treatment of Second-Degree Burn Wounds. Skin Pharmacol Physiol;20:292–296 2007. 18. Müller G, Kramer A. Effect of selected wound antiseptics on adult articular cartilage (bovine sesamoid bone) in the presence of Escherichia coli and Staphylococcus aureus. J Orthopaed Res.;23:127-33 2005. 19. Müller G, Kramer A. In vitro action of combinations of selected antimicrobial agents and adult bovine cartilage (bovine sesamoid bone). Chem Biol Interact;145:331-6, 2003. 20. Müller G, Kramer A. In vitro action of a combination of selected antimicrobial agents and chondroitin sulfate. Chem Biol Interact;124:77-85 2000. 21. Effect of polyhexanide and gentamicin on human osteoblasts and endothelial cells. Akif Incea, Norbert Schützea, Christian Hendricha, Franz Jakoba, Jochen Eulerta, Jochen F. Löhrb SWISS MED WKLY 2007;137:139–145. 22. Chemico-Biological Interactions 124 (2000) 77–85 23. Alhede M., Geisler C. S., and Bjarnsholt T. Improving Antibiofilm Efficacy of PHMB with a Low-intensity Ultrasound Wound Debridement Device. The 24th Conference of the European Wound Management Association. OP 138 24. Lacqueire J., Climent L. Use of a New Product for the Treatment of Chronic Leg Ulcers. The 24th Conference of the European Wound Management Association. OP 333 25. Gimenez-Tebar J. L., Lillo-Rodenas I., et all. How to Reduce Infection and Bacterial Burden by Using 0.1% Polyhexanide gel. The 24th Conference of the European Wound Management Association. EP 400 26. Hygiene Nord GmbH Greifswald. Dipl. Biol. T. Koburger, Dr. med. P. Rudolph 27. Monika Feltgen Hygcen GmbH 28. Welk A, Splieth CH, Schmidt-Martens G, Schwahn Ch, Kocher T, Kramer A, Rosin M; The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan inse and a chlorhexidine rinse on bacterial counts and 4-day plaque regrowth.; J Clin Periodontol. 2005 May;32(5):499-505. 29. Rudolph, H., 2005, AWMF Working Group for Hygiene in Hospital and Practice, “Krankenhaushygiene, Hygiene in hospital and practice”, 3rd ed. ISBN: 3-88681-070-4, p. 135-148) 1. Broxton P. Woodcock F., Heatle Y. and Gilbert P. Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli. Journal qf Applied Bacteriology, 57, 115-124, 1984. 2. Werthe M., Davoudi M., Sonesson A., Nitsche D. P. Mörgelin M., Blom1 K. and A. Schmidtchen. Pseudomonas aeruginosainduced infection and degradation of human wound fluid and skin proteins ex vivo are eradicated by a synthetic cationic polymer. Journal of Antimicrobial Chemotherapy 54, 772–779, 2004. 3. P. Gilbert and L.E. Moore. Cationic antiseptics: diversity of action under a common epithet. Journal of Applied Microbiology, 99, 703–715 2005. 4. Koburger T., Müller G., Eisenbeiß W., Assadian O. and A. Kramer. Mikrobiozide Wirksamkeit von Polihexanid. GMS Krankenhaushyg Interdiszip, 2(2):Doc44 2007. 5. Chawner, J.A. and Gilbert, P. A comparative study of the bactericidal and growth inhibitory activities of the bisbiguanides alexidine and chlorhexidine. J Appl Bacteriol 66, 243–252 1989. 6. Panda A., Ahuja R., Biswas N. R., Satpathy G. and S. Khokhar. Role of 0.02% Polyhexamethylene Biguanide and 1% Povidone Iodine in Experimental Aspergillus Keratitis. Cornea 22(2): 138– 141, 2003. 7. Krebs F. C., Miller S. R., Ferguson M. L., Labib M., Rando R. F. and B. Wigdahl. Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomedicine and Pharmacotherapy, 59 438–445, 2005. 8. Larkin DF, Kilvington S, Dart JK. Treatment of Acanthamoeba keratitis with polyhexamethylene biguanide. Ophthalmol; 99:185–191, 1992. 9. Seal DV, Hayt J, Kirkness CM, et al. Successful medical therapy of Acanthamoeba keratitis with topical chlorhexidine and propamidine. Eye; 10:413–421, 1996. 10. Werner, H.P. Microbicidal effectiveness of selected antiseptics. Hyg. Med. 17, 51–59, 1992. 11. Pittena F.-A., Wernerb H.-P. and A. Kramer. A standardized test to assess the impact of different organic challenges on the antimicrobial activity of antiseptics. Journal of Hospital Infection 55, 108–115, 2003. 12. Gilbert P., Das J.R., Jones M.V. and D.G. Allison. Assessment of resistance towards biocides following the attachment of microorganisms to, and growth on, surfaces. Journal of Applied Microbiology, 91, 248-254, 2001. 13. Müller G, Kramer A. Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. J Antimicr Chemother 61(5): 1281–1287, 2008 14. The protektive effect of Polyhexanide on keratinocytes in co-culture with Staphylococcus aureus. C. Wiegand, M. Abel, P. Ruth, U.C. Hipler Poster für EWMA 2008. -10- ISO 9001 ISO 14001 ISO 13485 K_12_EN_Rev.2_31.10.2014 ACTO GmbH Büchnerstrasse 11 38118 Braunschweig / Germany Tel : + 49 531 / 239 50 80 Fax : + 49 531 / 239 50 81 1 www.actogmbh.com • [email protected] GMP 1984 www.actogmbh.com [email protected]