1-9 A-D E-G H-M N-P Q-S T-Z

POLYHEXAMETHYLENE BIGUANIDE (POLİHEGZAMETİLEN BİGUANİD)

POLYHEXAMETHYLENE BIGUANIDE

1-(diaminomethylidene)-2-hexylguanidine; C8H19N5; Polyhexanide; Baquacil; cosmocil; Lavasept; PHMB Polymer; polihexanide; polihexanide hydrochloride; poly (hexamethylene biguanide); poly(hexamethylenebiguanide) hydrochloride; poly (iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl); hydrochloride polyhexamethylen-biguanide; polyhexamethylenbiguanid; polyhexamethylenbiguanide; polyhexamethylene biguanide; polyhexamethylene biguanide hydrochloride; polyhexanide; Vantocil; Vantocil IB of Vantocil; Polyhexanide; PHMB; POLIHEXANIDE; 28757-47-3; Polyhexamethylene biguanide; n-hexylbiguanide; 1-Hexylbiguanide; POLYXEDININE; SCHEMBL45011; N-Hexylimidodicarbonimidic diamide; Poly(iminoimidocarbonyl)iminohexamethylene hydrochloride; N,N```-1,6-Hexanediylbis(N`-cyanoguanidine) hexamethylenediamine polymer hydrochloride; PHMB; Polihexanide;

 

 


Fiziksel formu:

20 ° C ve 101.3 kPa güçlü amonyak kokusu ile off-beyaz ila soluk sarı toz
Soluk sarı, lumpy katı için çok soluk sarı; belirgin bir koku yok.
Soluk sarı cam benzeri katı (teknik sınıf PHMB).
Çözünürlük:Su içinde çözünür.
Istikrar:Istikrarlı.
Risk:Tahriş, cilt tahrişi, göz.
Ekoloji:Çevre için tehlikeli olabilir. Su vücut özel dikkat verilmelidir.
Biodegradability:Biyobozunur.
Fonksiyonu ve kullanır
PHMB, dezenfektan olarak kullanılmak üzere 98/8/EC sayılı direktif kapsamında desteklenmektedir
PHMB koruyucu olarak ve antimikrobiyal bir ajan olarak kullanılır. Koruyucu olarak PHMB
Kozmetik kullanılan, kişisel bakım ürünleri, kumaş yumuşatıcılar, kontakt lens çözümleri, el
Yıkar ve daha fazlası.

KozmetikPHMB, geniş spektrumlu koruyucu olarak kullanılır. Serbestçe suda çözünür ve bu nedenle en hassas tomikroorganizma büyümesi olan su bazlı ürünlerde yaygın olarak kullanılmaktadır. Çok çeşitli Gram pozitif ve Gram negatif bakterilere, mantarlara ve mayalara karşı mükemmel bir aktiviteye sahiptir ve özellikle kontrol edilmesi zor Pseudomanas türleri gibi mikroorganizmalara karşı etkilidir.

PHMB da kullanılırKorumak ıslak mendiller; Tekstildeki kokuyu kontrol etmek; mikroorganizmayı önlemek içinYara sulamada kontaminasyon ve steril pansumanlar; tıbbi/dental gereçler dezenfekte etmekVe tepsiler, çiftlik ekipmanları, hayvan içme suyu ve gıda işleme için sert yüzeylerKurumlar ve hastaneler; ve vakumlar ve tuvaletler deodorize etmek. PHMB kullanılırOzona alternatif olarak antimikrobiyal el yıkama ve ovalama ve hava filtresi tedavileri.
polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)PHMB ayrıca, çok çeşitli mikroorganizmalara karşı etkili olan klorsuz bir polimerik dezenfektan olarak, eğlence suyu arıtımı için aktif bir bileşen olarak kullanılır.
Phmb`nin daha fazla bildirilen kullanımları yüzme havuzu suyunun arıtılmasıdır, bira bardağıSterilize etme, bira fabrikalarında katı yüzey dezenfeksiyonu ve gizler kısa süreli korunması veDerileri. Poliheksanid (poliheksametilen biguanid, PHMB), dezenfektan ve antiseptik olarak kullanılan bir polimerdir. Dermatolojik kullanımda [1] poliheksanid (INN) olarak yazılır ve Lavasept, Serasept, (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Prontosan ve Omnicide gibi isimler altında satılır. [2] PHMB`nin Pseudomonas aeruginosa, Staphylococcus aureus (ayrıca metisiline dirençli tip, MRSA), Escherichia coli, Candida albicans (maya), Aspergillus brasiliensis (küf), vankomisine dirençli enterokok ve Klebsiella pneumoniae`ye karşı etkili olduğu gösterilmiştir. dirençli enterobacteriaceae). [Poliheksanid (poliheksametilen biguanid, PHMB), dezenfektan ve antiseptik olarak kullanılan bir polimerdir. Dermatolojik kullanımda [1] poliheksanid (INN) olarak yazılır ve Lavasept, Serasept, Prontosan ve Omnicide gibi isimler altında satılır. [2] PHMB`nin Pseudomonas aeruginosa, Staphylococcus aureus (ayrıca metisiline dirençli tip, MRSA), Escherichia coli, Candida albicans (maya), Aspergillus brasiliensis (küf), vankomisine dirençli enterokok ve Klebsiella pneumoniae`ye karşı etkili olduğu gösterilmiştir. dirençli enterobacteriaceae). (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)PHMB içeren bazı ürünler, inter-operatif irrigasyon, ameliyat öncesi ve sonrası cilt ve mukoz membran dezenfeksiyonu, ameliyat sonrası pansumanlar, cerrahi ve cerrahi olmayan yara pansumanları, cerrahi banyo / hidroterapi, diyabetik ayak ülseri ve yanık gibi kronik yaralar için kullanılır. yara yönetimi, küçük kesiler sırasında rutin antisepsi, kateterizasyon, skopi, ilk yardım, yüzey dezenfeksiyonu ve keten dezenfeksiyonu. [Acanthamoeba keratitinden etkilenen gözlerin tedavisi için PHMB göz damlaları kullanılmıştır.(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Baquacil markalı, klor veya brom bazlı ürünler yerine yüzme havuzu ve spa suyu dezenfektanı olarak da bir uygulamaya sahiptir. Baqua-Spa 3 sanitize olarak, Revacil Spa 3 dezenfektanı olarak ve Leisure Time Free sisteminde mevcuttur.(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)PHMB ayrıca bazı kontakt lens temizleme ürünlerinde, kozmetiklerde, kişisel deodorantlarda ve bazı veterinerlik ürünlerinde bir bileşen olarak kullanılır. Ayrıca, istenmeyen kokuların gelişmesini önlemek için olduğu iddia edilen kıyafetleri tedavi etmek için de kullanılır (Purista). (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)PHMB hidroklorür tuzu (çözelti), formülasyonların çoğunda kullanılır.Poliheksametilen biguanid hidroklorür -% 20 sulu çözeltiPHMB, poliheksanid veya poliheksanid olarak da bilinen poliheksametilen biguanidin, suda oldukça çözünür ve hidrolitik olarak stabil bir polimerik malzemedir. PHMB içinde çoklu hidrojen bağı ve şelasyon yerlerinin varlığı, onu supramoleküler kimya alanında potansiyel ilgi alanı haline getirir. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) PHMB, hem Gram-pozitif hem de Gram-negatif bakterilere karşı aktivite gösterir ve çeşitli dezenfektan solüsyonları ve antiseptiklerde, tipik olarak hidroklorür tuzu olarak çeşitli sektörlerde yaygın olarak kullanılmaktadır. PHMB, katı olarak da mevcuttur. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Aktif bileşen (ai) Poly Hexa Metilen Biguanide (PHMB), iki monomerin (1,6-heksanmetilendiamin ve N, N `` `- 1,6-heksandiilbis [N`-siyanoguanidin] polikondensasyonuyla elde edilen küçük boyutlu bir polimerdir. (yani. HMBDA)). PHMB küçük boyutlu bir polimer olduğundan, imalat işlemi sırasında meydana gelen bazı yan reaksiyonlar, polimerin yapısını önemli ölçüde değiştirebilir. Birim guanidin elde etmek için yan reaksiyon, işlemde% 10`a kadar meydana geldi. Bu nedenle PHMB`nin yapısının sadece tekrarlayan guanidin biriminden oluşmadığı, aynı zamanda tekrarlayan guanidin ve biguanid biriminden oluştuğu düşünülebilir. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Üretildiği haliyle aktif madde (TK3),% 20 a / a sulu PHMB çözeltisidir. "Saflık", polimerler ve ilgili maddelerin bir karışımı olan PHMB`ye uygulanması zor bir kavramdır. Bunun yerine, başvuru sahibi, "toplam katıların yüzdesi" veya "kurutulmuş malzeme" olarak tanımlanan polimerin "gücüne" atıfta bulunmaktadır. Tipik PHMB gücü% 20`dir. Ancak, eCA, "güç" yerine "aktif madde yüzdesi (% a.s.)" veya "aktif madde içeriği" terimlerinin kullanılmasının daha uygun olduğunu düşünmektedir. PHMB ve safsızlık içeriklerinin toplamı olarak tanımlanan etken madde içeriği, toplam katıların yüzdesi ve dolayısıyla mukavemetiyle aynı kabul edilebilir. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) Bununla birlikte, kuvvet veya kurutulmuş PHMB terimleri aynı zamanda özdeşlik ve fiziko kimyasal bölümlerde de kullanılır ve aynı şeyi ifade eder. Teknik malzeme, doğrudan üretim sürecinden elde edilen% 20 PHMB çözeltisi olduğundan (üretildiği haliyle aktif madde veya TK), karakterizasyon verileri, dondurarak kurutma tekniği kullanılarak kurutulmuş teknik malzemeden (TC4) oluşturulmuştur. PHMB içeriği, kurutulmuş teknik materyaldeki (artık su olmadan) safsızlıkların toplam içeriğinin 100`e çıkarılmasıyla hesaplanabilir. Bu değer gerçek bir saflık olarak kabul edilemez ancak mevcut en yakın veridir. PHMB TC`nin minimum içeriği>% 95.6 gösterildi. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) Aktif madde bir kopolimer olduğundan, kimlik karakterizasyon kriterleri (% katı, kurutulmuş materyaldeki PHMB içeriği, Mw, Mn ve biguanid / guanid oranına dayalı olarak) ve her kriter için limitler veya aralıklar, gizli olarak eCA tarafından önerilmektedir. Aktif maddenin onaylanması ve gelecekteki teknik eşdeğerlik kontrolleri durumunda referans spesifikasyonları belirlemek için PHMB kaynağını karakterize eden IIA belgesi. eCA, bu dosyada onaylanması düşünülen PHMB`yi "ortalama sayısal ortalama molekül ağırlığı (Mn) 1600 ve ortalama polidispersite (PDI) 1.8", yani "PHMB (1600; 1.8)" olarak yeniden adlandırmayı önermektedir. Kolaylık sağlamak için, PHMB (1600; 1.8) bundan sonra "PHMB" veya "a.s." olarak anılacaktır. % 0,4`lük bir maksimum içeriğe sahip bir ilgili safsızlık, Heksametilendiamin vardır. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Tüm potansiyel safsızlıklar aranmamış ve / veya ölçülmemiştir. Aktif madde ve safsızlıklar için safsızlıklar ve spesifikasyonlar hakkında ek veriler, onaydan önce sunulmalıdır. Yapısal özellikler (2003-2011) ile ilgili kalite kontrol verileri, bu gizli belgede, TK (sıvı form) üretiminin yapısal açıdan bu süre boyunca sabit kaldığını göstermek için rapor edilmiştir. Sunulan karakterizasyon verilerinin (2011) mevcut üretimi temsil ettiği sonucuna varılabilir, aynı zamanda eski üretimi ve risk değerlendirmesini gerçekleştirmek için kullanılan toksikolojik ve ekotoksikolojik çalışmaları gerçekleştirmek için kullanılan aktif madde materyalini de temsil ettiği sonucuna varılabilir (Gizli doküman IIA`ya bakınız). (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) Bu ifade sadece yapısal veriler için geçerlidir ve PHMB`deki safsızlık içeriğinin evrimi için geçerli değildir çünkü bu noktayı kapsayacak veri sunulmamıştır. Başvuru sahibi aynı zamanda katı bir malzeme olarak PHMB`yi de üretmektedir ("Katı PHMB"). Başlangıçta başvuran dosyadaki her iki kaynağı da sunmuştur. Sıvı ve Katı PHMB arasındaki karşılaştırma gizli belge IIA-02 "Sıvı ve katı PHMB karşılaştırması" nda tartışılmıştır. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) eCA, sıvı PHMB (VANTOCIL TG) ve Solid PHMB`nin yapısal hususlara bağlı olarak 2 farklı madde olduğunu düşünmektedir. Başvuru Sahibinin yeni bir kaynak olarak sağlam PHMB iddiasında bulunması halinde, ürün yetkilendirme aşamasında teknik denkliği gösterecek ek bilgiler gerekecektir. Bu dosyada onay için düşünülen aktif madde, üretildiği haliyle aktif maddedir (TK):% 20 w / w sulu PHMB (VANTOCIL TG) çözeltisi sıvı PHMB olarak da adlandırılır. TC (kurutulmuş PHMB), güçlü bir amonyak kokusu ile kirli beyaz, tozlu bir katı / tozdur. 90-91 ° C (kristal olmayan polimer) cam geçiş sıcaklığına sahiptir ve kaynamadan önce 205-210 ° C`de ayrışır. TK (üretildiği haliyle PHMB, suda% 20) 100,2 ° C`lik bir kaynama noktasına sahiptir. TC`nin bağıl yoğunluğu 20 ° C`de 1,20`dir ve TK`nin bağıl yoğunluğu 20 ° C`de 1,04`tür. Bir polimer olarak PHMB`nin uçucu olduğu düşünülmemektedir. PHMB uçucu olarak değerlendirilmediğinden ve nötr pH`da iyonik formda bulunduğundan Henry Yasası Sabiti uygulanamaz. PHMB`nin sudan havaya geçme olasılığının çok az olduğu varsayılmaktadır. Suda çok çözünür (426 g / L).

 

 

Polyhexanide (polyhexamethylene biguanide, PHMB) is a polymer used as a disinfectant and antiseptic. In dermatological use,[1] it is spelled polihexanide (INN) and sold under names such as Lavasept, Serasept, Prontosan and Omnicide.[2] PHMB has been shown to be effective against Pseudomonas aeruginosa, Staphylococcus aureus (also the methicillin-resistant type, MRSA), Escherichia coli, Candida albicans (yeast), Aspergillus brasiliensis (mold), vancomycin-resistant enterococci, and Klebsiella pneumoniae (carbapenem-resistant enterobacteriaceae) (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Some products containing PHMB are used for inter-operative irrigation, pre- and post-surgery skin and mucous membrane disinfection, post-operative dressings, surgical and non-surgical wound dressings, surgical bath/hydrotherapy, chronic wounds like diabetic foot ulcer and burn wound management, routine antisepsis during minor incisions, catheterization, scopy, first aid, surface disinfection, and linen disinfection.[4] PHMB eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Branded as Baquacil, it also has an application as a swimming-pool and spa water sanitizer in place of chlorine- or bromine-based products. It is available as Baqua-Spa 3 sanitize, as Revacil Spa 3 sanitizer, and in the Leisure Time Free system. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)PHMB is also used as an ingredient in some contact lens cleaning products, cosmetics, personal deodorants and some veterinary products. It is also used to treat clothing (Purista), purportedly to prevent the development of unpleasant odors. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)The PHMB hydrochloride salt (solution) is used in the majority of formulations. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Polyhexamethylene biguanide hydrochloride - 20% aqueous solutionPolyhexamethylene biguanidine, also known as PHMB, polyhexanide or polihexanide, is a highly water soluble and hydrolytically stable polymeric material. The presence of multiple hydrogen bond and chelation sites within PHMB renders it of potential interest in the field of supramolecular chemistry. PHMB shows activity against both Gram-positive and Gram-negative bacteria and is widely used across several sectors, typically as the hydrochloride salt, in a variety of disinfectant solutions and antiseptics. PHMB is available also as a solid. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)The active ingredient (a.i.) Poly Hexa Methylene Biguanide (PHMB) is a small size polymer obtained by the polycondensation of two monomers (1,6- hexanemethylenediamine and N,N```-1,6-hexanediylbis[N`-cyanoguanidine] (ie. HMBDA)). As PHMB is a small size polymer, some side reactions that occurred during the manufacturing process could modify significatively the structure of the polymer. The side reaction to obtain the unit guanidine occurred up to 10% in the process. Therefore, it can be considered that the structure of PHMB is not only composed by repetitive unit of guanidine but it is composed by repetitive unit of guanidine and biguanide. The active substance as manufactured (TK3 ) is a 20% w/w aqueous solution of PHMB. "Purity" is a difficult concept to apply to PHMB which is a mixture of polymers and related substances. Instead the applicant refers to the "strength" of the polymer which is defined as "% total solids" or "dried material". The typical PHMB strength is 20 %. However, eCA considers more appropriate to use the term "% of active substance (% a.s.)" or (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) "active substance content" instead of "strength". The active substance content being defined as the sum of PHMB and its impurities contents, it can be considered identical to the % total solids and thus to the strength. However, the terms strength or dried PHMB are also used in identity and physico chemical sections and refer to the same thing. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) As the technical material is the 20 % PHMB solution obtained directly from the manufacturing process (active substance as manufactured or TK), characterisation data were generated from the dried technical material (TC4 ) using the technique of freeze drying. The content of PHMB can be calculated by subtracting the total content of impurities in the dried technical material (without residual water) to 100. This value cannot be considered as a real purity but is the closest available data. The minimum content of PHMB TC was demonstrated > 95.6%. Since the active substance is a copolymer, identity characterisation criteria (based on % solid, content of PHMB in dried material, Mw, (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Mn and the biguanide/guanide ratio) as well as limits or range for each criterion are proposed by eCA in the confidential document IIA to characterise the source of PHMB in order to set reference specifications in case of approval of the active substance and future technical equivalence checks. eCA proposes to rename PHMB considered for approval in this dossier as "PHMB with a mean number-average molecular weight (Mn) of 1600 and a mean polydispersity (PDI) of 1.8" i.e. "PHMB (1600; 1.8)". For convenience, PHMB (1600; 1.8) is referred to hereafter as "PHMB" or "a.s.". There is one relevant impurity, Hexamethylenediamine with a maximal content of 0.4%. All potential impurities have not been looked for and/or quantified. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Additional data about impurities and specifications for the active substance and the impurities should be submitted prior to approval. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Quality control data on structural characteristics (2003-2011) are reported in this confidential document to demonstrate that production of TK (liquid form) remained stable during this period of time from a structural point of view. It can be concluded that submitted characterisation data (2011) are representative of current production but also of older production and of active substance material used to perform the toxicological and ecotoxicological studies used to perform the risk assessment (See confidential doc IIA). This statement is only valid for structural data and not for evolution of impurity content in PHMB as no data was submitted to cover this point. The applicant also manufactures PHMB as a solid material ("Solid PHMB"). Initially the applicant submitted both sources in the dossier. Comparison between liquid and Solid PHMB is discussed in confidential document IIA-02 "Comparison of liquid and solid PHMB". (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) eCA considers that liquid PHMB (VANTOCIL TG) and Solid PHMB are 2 different substances, based on structural considerations. Additional information to demonstrate technical equivalence will be required at product authorisation stage if Applicant claims solid PHMB as a new source. The active substance considered for approval in this dossier is the active substance as manufactured (TK): 20 % w/w aqueous solution of PHMB (VANTOCIL TG) also called liquid PHMB. TC (dried PHMB) is a dusty solid/powder, off white with a strong ammonia smell. It has a glass transition temperature of 90-91°C (non crystalline polymer) and decomposes at 205-210°C before boiling. The TK (PHMB as manufactured, 20% in water) has a boiling point of 100.2°C. The relative density of TC is 1.20 at 20°C and the relative density of the TK is 1.04 at 20°C. As a polymer, PHMB is not considered to be volatile. Henry`s Law Constant is not applicable as PHMB is not considered to be volatile and is present in ionic form at neutral pH. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) It is assumed that PHMB has only slight possibility to go from water to air. It is very soluble in water (426 g/L). It is also soluble in methanol (41%), in ethanol (0.5%) and sparingly soluble in organic solvents (10-3 g/L). The pKa is calculated as approximately 4.4 at 25°C. Log Pow is - 2.3 at pH=7.4 and 25°C. TC is not highly flammable, and does not have oxidizing and explosive properties. A surface tension study should be performed but PHMB is not expected to be surface active based on structural considerations. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) The lethal action of PHMB is an irreversible loss of essential cellular components as a direct consequence of cytoplasmic membrane damage. It is concluded that cytoplasmic precipitation is a secondary event to the death of the bacterial cell. It has been shown that the lethal sequence consists of a series of cytological and physiological changes - some of which are reversible - which culminate in the death of the cell. The important steps are: (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)
• binding to a receptive site on the surface; 
• leakage of low molecular weight cytoplasmic components; 
• precipitation of cell contents. 
The molecular interaction between PHMB and bacterial membranes has been deduced by over laying this lethal sequence with the findings of experiments modelling the possible interactions of polymeric biguanides and membrane components - particularly phospholipids.
The intended uses of BAQUACIL PHMB and VANTOCIL TG initially claimed by the applicant are the following (please refer also to Appendix II): 
- Disinfection of medical equipment (small scale disinfection): 
o By dipping; 
o By wiping; 
- Disinfection of accommodation for man and industrial areas (small scale disinfection): o By mopping; 
o By wiping; 
o By spraying; 
- Disinfection of industrial areas (large scale disinfection) by fogging; 
- Disinfection of chemical toilets; 
- Swimming pool treatment. 
The table below present the efficacy data which support the efficacy of the PHMB in the frame of the active substance dossier. The data are generated from laboratory studies and have to be consolidated at the product authorisation stage related to the claims with data generated with real products. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)
The evaluation of the literature studies provided by the applicant does not show particular resistance to PHMB with bacteria. Nevertheless it is not appropriate to conclude that PHMB resistance is not an issue and that a resistance management strategy is not required. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)
In particular, the description in the literature of: 
• cross resistances; 
• modifications of the expression of genes as a mechanism of tolerance to subletal concentrations of PHMB; (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)
should be taken into account in the strategy of resistance management. In particular, the concentration of 7,5 ppm of PHMB, which is in the order of magnitude of concentration found for swimming pool water desinfection, is shown subletal and thus susceptible to generate tolerance to E. Coli.Standard methods of measuring resistance brought about by biocide use are not available and should be developed for all type of biocides. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) Oral absorption of PHMB ranges approximately from 0.3 to 8% but the value of 4% is retained based on the oral absorption of PHMB from diet at the lower dose tested. This value was selected as it corresponds to the closest conditions to the experimental conditions of the study in which the relevant oral NOAEL was determined. A dermal absorption of PHMB was determined to be 4% by default based on EFSA guidance on dermal absorption (2012), corresponding to the oral absorption value. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Since no information is available on absorption of PHMB by inhalation, an absorption of 100% is retained. A classification for acute oral or dermal toxicity is not justified for the active substance as manufactured, PHMB 20% in water. For respiratory route, a classification Xn; R20 or Acute Tox 4 - H332 is proposed based on the RAC opinion for PHMB. PHMB is not irritant by dermal contact. For eye irritation, classification is not justified based on the data of the PHMB 20% w/w. PHMB is considered as a moderate to strong potency skin sensitizer based on animal data. Human studies indicate that PHMB is a skin sensitizer in humans, although with a rare frequency of sensitisation in the current conditions of consumer uses. Classification Xi; R43 (may cause sensitisation by skin contact) or (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Skin sens 1 - H317 for CLP, is therefore warranted. Relatively low incidences from human data support classification as CLP Skin Sens 1B - H317 according to the 2nd ATP to CLP Regulation. On the basis of the severity of the effects caused by inhalation of PHMB (mortality and to a lesser extent histopathological changes in the respiratory tract and in the thymus), the absence of reversibility of inflammation in the respiratory tract and the very low doses causing these effects, classification T; R48/23 is warranted (CLP STOT RE 1 - H 372). By inhalation the primary target organ is the respiratory tract and no effect warranting classification are identified by oral and dermal route. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)The target organs are kidneys and liver via oral route. By dermal contact, local effects are expected. PHMB is not considered to be mutagenic or genotoxic, according to the results of the in vitro (Ames test and chromosomal aberration test) and in vivo studies (mouse bone marrow micronucleus test and UDS assay). PHMB increases the incidence of benign and malign vascular tumours in female rats by oral route and in male and female mice by oral and dermal route. The tumours are induced mainly in the liver, which is one of the target organ of PHMB and the increase is clearly seen at doses above the MTD. However, it is also observed more equivocally at doses below MTD (mouse oral study at mid-dose and rat oral study at high dose). These increases are not considered incidental when considering the clear induction of vascular tumours at higher doses and they are considered biologically significant and attributed to treatment. A classification as carcinogenic category 3; R40 or Carc 2 - H351 for CLP, is warranted. In absence of carcinogenicity data by inhalation, it is proposed to allocate the general hazard statement H351 without indication of the route of exposure. PHMB has no teratogenic effect and has no effect on fertility or reproductive performance at dose levels up to 2000 ppm. For non-professionals, PHMB concentration in BAQUACIL PHMB product is above classification limit for sensitisation properties. As a common practice, it is considered that non-professional users do not wear any personal protective equipment. However, according to the document "Authorisation of biocidal products classified as skin sensitizers requiring PPE for non-professional users" exposure assessment for nonprofessionals could be performed without and with the wearing of PPE as a Tier II assessment and the local risk characterisation should be performed considering potential exposure both with and without gloves. In this case, as explain above gloves will only reduce the quantity of product in contact with skin, not the concentration. So contact with the product could still occur. Only the combination of PPE, training to handle PPE and chemicals allow a safe use. As consumers are not trained to use PPE and chemicals, they can be exposed to the product when removing the gloves or they can use the gloves provided with the product for other uses. So providing PPE with the product is not sufficient to lead to a safe use for consumers against local effects. However, as BAQUACIL PHMB (PHMB 20%) is classified STOT RE 1, it shall not be authorised for making available on the market for use by the general public according to the BPR article 19.4.b). Polyhexanide (polyhexamethylene biguanide, PHMB) is a polymer used as a disinfectant and antiseptic. In dermatological use, it is spelled polihexanide (INN) and sold under names such as Lavasept, Serasept, and Omnicide. PHMB has been shown to be effective against Pseudomonas aeruginosa, Staphylococcus aureus (also the methicillin-resistant type, MRSA), Escherichia coli, Candida albicans (yeast), Aspergillus brasiliensis (mold), vancomycin-resistant enterococci, and Klebsiella pneumoniae (carbapenem-resistant enterobacteriaceae).
Some products containing PHMB are used for inter-operative irrigation, pre- and post-surgery skin and mucous membrane disinfection, post-operative dressings, surgical and non-surgical wound dressings, surgical bath/hydrotherapy, chronic wounds like diabetic foot ulcer and burn wound management, routine antisepsis during minor incisions, catheterization, scopy, first aid, surface disinfection, and linen disinfection. PHMB eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis.
Branded as Baquacil, it also has an application as a swimming-pool and spa water sanitizer in place of chlorine- or bromine-based products. It is available as Baqua-Spa 3 sanitize, as Revacil Spa 3 sanitizer, and in the Leisure Time Free system.
PHMB is also used as an ingredient in some contact lens cleaning products, cosmetics, personal deodorants and some veterinary products.
The PHMB hydrochloride salt (solution) is used in the majority of formulations.
The broad-spectrum antimicrobial biocide polyhexamethylene biguanide (PHMB; polyhexanide) kills bacteria, fungi, parasites and certain viruses with a high therapeutic index; it is widely used in clinics, homes and industryIt is most commonly used as a biocide, but is also an important drug used in several topical applications. PHMB is composed of repeating basic biguanidine units connected by hexamethylene hydrocarbon chains, providing a cationic and amphipathic structure. Despite extensive use over several decades, and efforts to identify acquired resistant mutants, resistance to PHMB has not been reported. The evidence for a lack of acquired resistance is necessarily negative, and the possibility of mutation to resistance remains; nevertheless, it is striking that bacteria with acquired resistance have not been identified following extensive and varied usage.
The bactericidal properties of PHMB have been demonstrated against a range of species , follow first order kinetics and have been observed within one hour at concentrations below 10 μg/mL. Also, its high therapeutic index has long been attributed to the polymer having comparatively less activity against mammalian membranes. The prevailing model for PHMB`s microbe-selective toxicity holds that PHMB disrupts microbial membranes preferentially. However, this model relies on data from artificial membrane studies and it does not explain how PHMB is able to kill diverse microbes, which differ in cell barrier composition , nor does it explain observations that PHMB can induce DNA repair pathways. Therefore, the literature contains conflicting evidence and interpretations regarding the antibacterial mechanism of action of PHMB. When considering the membrane disruption model and possible alternatives, it may be important to recognize that PHMB has a capacity for both electrostatic and H-bonding interactions which could occur at many possible targets in cells. For example, PHMB binding to nucleic acid has been demonstrated in vitro, raising at least one possible alternative mechanism of action.To re-examine its mechanism(s) of action, we subjected PHMB to cellular, molecular and biophysical analysis, using both bacterial and mammalian cell systems. We examined its membrane activities and cellular effects using a PHMB-fluorophore conjugate together with cell growth, microscopy and physiological assays. Also, we examined PHMB/nucleic acid interactions using biophysical methods. Surprisingly, the results reveal that PHMB enters both bacterial and mammalian cells, condenses bacterial chromosomes and is excluded from mammalian nuclei. The outcome suggests a new model to explain its selective antimicrobial activities. If the antibacterial activity of PHMB is due to membrane disruption, as widely reported, it would be expected to permeabilise bacterial cell barriers at growth inhibitory and sub growth inhibitory concentrations. To test this model, we first established the minimal inhibitory concentrations (MIC) and time kill properties for PHMB against (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Escherichia coli (strains K-12 and MG1655) and Salmonella enterica serovar Typhimurium (strain LT2). As reported previously, PHMB displayed potent growth inhibitory and cidal properties Also, following treatment, we examined cells using light microscopy. Unexpectedly, growth inhibitory concentrations of PHMB did not lyse cells, as monitored by bright-field microscopy. To assess cell barrier damage that could be invisible to microscopy, E. coli K-12 cultures were grown to mid-log phase, treated with PHMB in the presence of the fluorescent membrane integrity probe and then monitored using fluorimetry. This probe is useful as an indicator of membrane damage; because it is normally excluded from intact bacteria and its fluorescence quantum yield increases upon DNA binding. Therefore, intact bacteria are expected to display low fluorescence, and fluorescence is expected to increase following cell barrier damage As anticipated, freshly grown E. coli cultures displayed large increases in fluorescence following treatment with the known cell wall disruptor polymyxin B or heat treatment .Unexpectedly, PHMB treatment resulted in comparatively lower levels of fluorescence. Most strikingly, higher concentrations of PHMB resulted in fluorescence at background levels. These observations are not compatible with membrane disruption as the main antibacterial mechanism, and therefore raised further doubt about the established model. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) PHMB condenses bacterial chromosomes inside cells, this could occur via direct or indirect effects on DNA. We suspected direct effects, because PHMB has been shown to bind to DNA fragments in vitro. We decided to examine the DNA binding properties of PHMB using isolated E. coli chromosomal DNA. PHMB-DNA interactions were first examined using an electrophoretic mobility shift assay (EMSA) and a dye exclusion assay. PHMB was mixed with chromosomal DNA isolated from E. coli K-12, and the mixtures were fractionated in agarose/TBE gels, followed by DNA staining with ethidium bromide. PHMB:DNA mixtures having wt:wt ratios of ≥0.5 displayed clearly retarded electrophoretic mobility, as indicated by retention of DNA in the well . Similar results were obtained for PHMB-FITC. Retarded mobility and retention in wells is consistent with stable interactions between PHMB and DNA. Also, the EMSA assays indicated reduced ethidium bromide fluorescence in the presence of PHMB or PHMB-FITC, (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) suggesting that ethidium bromide was prevented from binding to DNA due to formation of PHMB:DNA complexes. This observation was further investigated using the DNA binding dye SYTOX®Green in a dye exclusion assay. In the absence of PHMB, SYTOX®Green bound isolated E. coli DNA, as indicated by a large increase in fluorescence, relative to the addition of dye alone. However, prior addition of PHMB reduced fluorescence >80% . Therefore PHMB forms complexes with bacterial DNA in a way that retards electrophoretic mobility and masks DNA access to DNA ligands. The results of each of these experiments indicate that PHMB binds directly to DNA. Chronic wounds are often complex, difficult to heal, and may persist for months or years due to underlying disease processes or complications within the healing process. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Treating chronic wounds requires a multifaceted approach in order to address the underlying pathophysiology while promoting healing of the wound.1-4 Before a wound can close, the wound bed status needs to be addressed to assist in creating an environment conducive to tissue repair. This may require 1) removal of nonviable tissue, 2) maintenance of a moisture balance, 3) resolution of any bacterial imbalance, and 4) removal of impediments to healing at the epidermal margins.4 While each of these require attention, concern with bacterial imbalance in the wound bed has lead to the development and commercialization of a variety of antimicrobial (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) products and therapies.
Bacterial imbalance. When wounds fail to heal or are classified as recalcitrant, one of the factors delaying healing that merits consideration is bacterial load in the wound bed and its effect on the tissue repair process.5,6 All chronic wounds are believed to have some level of bacterial bioburden. Depending on the number of organisms, the level of bacteria in the wound bed may be classified as contaminated, colonized, critically colonized, or infected.4,7 Contamination (the presence of organisms in a wound) and colonization (the proliferation of those organisms) are not routinely treated with oral or systemic antibiotics. Once a wound becomes critically colonized (a level of colonization affecting skin cell proliferation and tissue repair), it may progress to a "classic" infection, which may include erythema, cellulitis, edema, and increases in odor, pain, exudate, white blood cell count, and increased body temperature.(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Delayed closure may suggest the formation of an extracellular polysaccharide matrix film or layer (sometimes called a glycocalyx) that shields the bacteria from attack while maintaining the moist environment in which they thrive. These colonies of bacteria are called biofilms and are produced by Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and E coli, among others. The biofilm makes it difficult to eliminate pathogens by requiring as much as 50-1000 times the minimal inhibitory concentration (MIC) of an antibiotic or antiseptic.
(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Clinicians may attempt to address the bacterial imbalance by combining treatment modalities. To address infection in the wound bed systemic or oral antibiotics should be considered the first line of therapy, especially in complicated skin infections with clinical signs of cellulitis, leukocytosis, or fever. In conjunction with systemic therapy, there are a number of antimicrobial dressings currently on the market indicated for use on infected wounds. Antimicrobial dressings are comprised of a variety of different base materials to which antimicrobial agents are added. The major purported benefits of these dressings are that they may reduce the presence of pathogens and decrease the risk of infection while creating a wound bed that will readily support the normal sequence of wound repair. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide) The use of topical antimicrobial agents for wound care gained a wide acceptance in the 1960s once it was discovered that treating burns with silver nitrate decreased the number of deaths that were a result of sepsis from 60% to 28%. Antiseptic silver sulfadiazine (SSD) was associated with additional decreases in infection, eventually making a place for itself in general wound care. Silver sulfadiazine demonstrated improved outcomes and decreased infection rates. Antiseptics differ from antibiotics in that they have broad-spectrum activity and can be effective against many types of organisms including aerobic and anaerobic bacteria, yeasts, fungi, and molds. While there is concern that certain antiseptics may delay healing as a result of cytotoxicity to viable cells,14 current wound treatment products must demonstrate biocompatibility and effectiveness to reduce bioburden prior to approval for an antimicrobial indication. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Antiseptics used in current wound dressings include silver, iodine, and polyhexamethylene biguanide (PHMB).
Bacterial resistance to antibiotics is extensively documented in medical literature. Resistance to antiseptics, however, has only been studied more recently. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Tambe and associates compared the ability of Staphylococcus epidermidis to develop resistance to various antibiotics and antiseptics after 20 S epidermidis cell culture passages. Results suggested that the bacteria developed resistance to the antibiotics minocycline and rifampicin, however no evidence of resistance was observed with chlorhexidine, silver sulfadiazine, and PHMB. Minor resistance was seen with Triclosan.
Silver. Silver has been used as an antimicrobial agent for thousands of years. Silver ions exert varying antimicrobial effects depending on their binding site. When binding occurs at the bacterial cell wall, ruptures can occur. When bound to proteins involved in respiration and nutrition of the organism, silver blocks these processes and the bacterium dies. When binding to DNA, silver can affect the replication and division of the organism.
The activity of silver lies in its ionic form.Elemental silver and silver salts demonstrate substantially less effectiveness against microbes. Previously, silver salt solutions, such as silver nitrate, were used to bathe the wound. These required large amounts of silver to achieve the desired effect. Silver sulfadiazine (SSD) creams enable much lower amounts of silver to be effective and act by discharging silver ions when in contact with wound exudate. Fox and Modak18 describe the mechanism by which sulfadiazine binds the silver and releases it into the wound over time at concentrations that are bactericidal. The silver ions, however, may be rapidly neutralized and require daily or more frequent application of SSD. The amount of silver released into the wound is not always clearly defined and can be a concern for toxicity in healthy tissue. More recent technological advancements have lead to methods of delivering silver to wounds over longer periods of time and at more predictable levels. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)There are a variety of silver containing wound dressings available. Delivery systems vary and include polyethylene mesh (Acticoat®, Smith and Nephew, Largo, Fla), polyurethane foam (Contreet Ag®, Coloplast, Holtedam, Denmark), activated carbon (Actisorb 220®, Johnson and Johnson, Somerville, NJ), hydrocolloid (Contreet-H®, Coloplast), alginate with polymers (Arglaes®, Medline, Mundelein, Ill), alginate with carboxymethylcellulose (CMC) (SilverCel®, Johnson and Johnson), sodium carboxymethylcellulose (Aquacel Ag®, ConvaTec, Skillman, NJ), nylon (Silverlon®, Argentum Medical, Asheville, NC), and polyacrylate (Silvasorb®, Medline). (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Thomas and McCubbin20,21 compared the in-vitro effectiveness of various silver containing products using 3 methods-zone of inhibition, challenge testing, and microbial transmission testing to demonstrate differences in the various dressings. Results against Staphylococcus aureus, Escherichia coli, and Candida albicans suggested that polyethylene mesh had the most rapid antimicrobial effect due to its rapid release of silver. Hydrocolloid was similar but had a slower onset. Activated carbon had little activity on the surface, but organisms that were absorbed into the dressing were inactivated by the silver.
Jones et al22 found that some of the differences observed between polyethylene mesh and sodium CMC may be related to the conformability of the dressing. A greater wound bed conformability and contact correlated with an increased antimicrobial effect.
As described in the literature, there are a wide variety of silver dressings available and various in-vitro responses from these dressings. Well-designed and adequately powered randomized trials to support the clinical benefits of silver are lacking, (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)are warranted, and requested by the medical community.
Iodine. Iodine is used as a disinfectant for cleaning surfaces and storage containers, in skin soaps, medicines, and for purifying water. It has been purported to have negative effects on wound healing, however some hypothesize that it may be due to the carrier. Carriers for iodine have demonstrated less toxicity by releasing iodine at a slower rate, yet show the same lethality as iodine in other forms. Cadexomer iodine (Iodoflex® and Iodosorb®, marketed in the United States by Smith & Nephew, Largo, Fla) is a 3-dimensional starch lattice formed into spherical microspheres that trap iodine in the lattice. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)As fluid is absorbed, the pore size of the lattice increases, releasing iodine. Mertz et al tested cadexomer iodine against MRSA in an in-vitro porcine model. They demonstrated significant reduction of the bacteria over a period of 72 hours.
Hansson and colleagues compared cadexomer iodine to hydrocolloid and paraffin gauze dressings in a randomized, open, controlled, multicenter clinical trial. In the 153-patient study they demonstrated 62% reduction in ulcer size with the cadexomer iodine as compared to 41% and 24% for the hydrocolloid and paraffin gauze, respectively. Patients were treated until the wound was dry or until 12 weeks, whichever came first. The investigators also compared the cost of the dressing over the 12-week period and demonstrated cost savings with the cadexomer iodine(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide).
Studies suggest that iodine`s mechanism of action is through destabilization of the bacterial cell wall and disruption of the membrane that results in leakage of the intracellular components
(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Polyhexamethylene biguanide (PHMB). Polyhexamethylene biguanide (PHMB), also known as polyhexanide and polyaminopropyl biguanide, is a commonly used antiseptic. It is used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners.
Wound care products containing PHMB include Kerlix AMDTM, Excilon AMDTM, and Telfa AMDTM (all from Tyco HealthCare Group, Mansfield, Mass) and XCell® Cellulose (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Wound Dressing Antimicrobial (Xylos Corp, Langhorne, Pa).
A review of the literature demonstrates in-vivo and in-vitro safety and effectiveness of PHMB for a number of applications. For wound dressings, Wright and colleagues compared the effectiveness of a silver dressing to a dry gauze dressing containing PHMB (Kerlix AMD). Results demonstrated reduction in bioburden with both dressings when tested in an in-vitro bactericidal assay. Using a Kirby-Bauer zone of inhibition study, the gauze was not as effective. This was believed to be due to a tight bond between the dressing and PHMB, which was not released and therefore did not result in killing beyond the edge of the dressing. Alternatively, Motta and associates demonstrated a good response using Kerlix AMD compared to gauze without PHMB in wounds where packing the dressing into the wound was required. Results suggested that the PHMB in the gauze resulted in a decrease in the number of organisms present in the wound.
The majority of literature describes effectiveness of PHMB on various microorganisms associated with contact lens disinfecting solutions. Antimicrobial effectiveness has been demonstrated on Acanthamoeba polyphaga, A castellanii, and A hatchetti. Additional effectiveness was demonstrated for PHMB use in water treatment. Barker and colleagues tested the effect of PHMB on Legionella pneumophila. This bacterium causes Legionnaire`s disease and can be found in water systems, air conditioning (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)machinery, and cooling towers.
Gilbert and colleagues have performed numerous studies on bacteria, especially those that form biofilms, such as Klebsiella pneumoniae. In studying biofilms produced from E coli and S epidermidis, they noted that those compounds with higher activity against planktonic bacteria, including PHMB, were also the most effective agents against sessile bacteria found within biofilms. They suggested that the differences in effects of concentration of PHMB on planktonic versus sessile bacteria was due to either the mechanism (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)of action or the number or disposition of cationic binding sites.Kramer et al have studied the effects of various antiseptics including PHMB on fibroblast proliferation and cytotoxicity. They noted that while octenidine-based products retarded wound healing, PHMB promoted contraction and aided wound closure significantly more than octenidine and placebo.
The mechanism of action of PHMB has been described in a number of articles. Broxton et al demonstrated that maximal activity of the PHMB occurs at between pH 5-6 and that initially the biocide interacts with the surface of the bacteria and then is transferred to the cytoplasm and cytoplasmic membrane. Ikeda and colleagues showed that the cationic PHMB had little effect on neutral phospholipids in the bacterial membrane-its effect was mainly on the acidic negatively charged species where it induced aggregation leading to increased fluidity and permeability. This results in the release of lipopolysaccharides from the outer membrane, potassium ion efflux, and eventual organism death.
(polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)Clinically, PHMB has been used as a perioperative cleansing agent, in mouth wash,in ophthalmology, and as a topical wash. Hohaus et al reported on the oral use of PHMB (Lavasept 1%, Fresenius-Kabi, Bad Homburg, Germany). A combination of oral terbinafine and topical ciclopirox and PHMB were used to successfully treat a deep fungal infection (Trichophyton mentagrophytes) of the throat. Petrou-Binder describes the germicidal effects of PHMB (Lavasept 0.02%) as eye drops prior to cataract surgery. It was well tolerated with low tissue response and minimal patient discomfort.
While there is no peer-reviewed clinical literature of PHMB used on wounds, industry literature describes the effectiveness of AMD Gauze (Kerlix) as a bacterial barrier against Staphylococcus epidermidis (penicillin resistant) on volunteers. Results suggest that clinically, this dressing was an effective barrier against bacterial colonization. The studies suggested that AMD gauze did not elicit any skin reactions. (polihekzametilen biguanid) (polihexametilenbiguanid) (polyhexamethylene biguanide) (polyhexamethylene bıguanıde) ( poly hexa methylene biguanide) (poli hegza metilen biguanid) ( polyhexa methylene biguanide) ( polyhexa methylenebiguanide) (polyhexamethylenebiguanide)

 

 

Ataman Kimya A.Ş. © 2015 Tüm Hakları Saklıdır.