PRODUCTS

POLYHEXAMETHYLENE BIGUANIDE

CAS No. : 28757-47-3 / 32289-58-0
EC No. : 608-723-9

Synonyms:
Polyhexanide; Polyhexamethylene biguanide; Polyhexamethylene guanide; Poly(iminoimidocarbonyl-iminoimidocarbonyl-iminohexamethylene) Hydrochloride; Poly(hexamethylenebiguanide); Polihexanide; PHMB; Polyhexanide; POLIHEXANIDE; 28757-47-3; 1-(diaminomethylidene)-2-hexylguanidine; Polyhexamethylene biguanide; n-hexylbiguanide; 1-Hexylbiguanide; POLYXEDININE; N-Hexylimidodicarbonimidic diamide; Poly (hexamethylene biguanide) hydrochloride; Poly(hexamethylenediguanide) Hydrochloride; Poly(iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl) hydrochloride; Poly(hexamethylene Biguanide)Hydrochloride; Polyhexanide; Polyhexamethylene biguanide; Polyhexamethylene guanide; Poly(iminoimidocarbonyl-iminoimidocarbonyl-iminohexamethylene) Hydrochloride; Poly(hexamethylenebiguanide); Polihexanide; PHMB; Poly(hexamethylenebiguanide) hydrochloride; Polyhexamethylene biguanide hydrochloride, PHMB; Poly(iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl)hydrochloride; Biguanide; 56-03-1; DIGUANIDE; Imidodicarbonimidic diamide; HBIG; 1-(diaminomethylidene)guanidine; UNII-FB4Q52I9K2; FB4Q52I9K2; 1,2,3-triimidodicarbonic diamide; H2N-C(=NH)-NH-C(=NH)-NH2; Guanylguanidine; Imidodicarbonimidicdiamide; N,N'''-1,6-hexanediylbis[N'-cyano-, polymer with1,6-hexanediamine, hydrochloride; 1,6-Hexanediamine, polymer with N,N'''-1,6-hexanediylbis{N'-cyanoguanidine}, hydrochloride; PHMB

Polyhexamethylene Biguanide

Polyhexanide (polyhexamethylene biguanide, PHMB) is a polymer used as a disinfectant and antiseptic. In dermatological use,[2] it is spelled polihexanide (INN) and sold under names such as Lavasept, Serasept, Prontosan and Omnicide.[3] Polyhexamethylene biguanide 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).[4]

Some products containing Polyhexamethylene biguanide 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.[5] Polyhexamethylene biguanide eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis.[6]

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.

Polyhexamethylene biguanide 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.

The Polyhexamethylene biguanide hydrochloride salt (solution) is used in the majority of formulations.

Safety
In 2011, Polyhexamethylenbiguanide (Polyhexamethylene biguanide, Polyhexanide) has been classified as carcinogenic category 2 by the European Chemical Agency (ECHA). Products containing concentrations of 1% Polyhexamethylene biguanide and more have to be declared as «suspected of causing cancer» and concentrations of 0.1% or above have to be noted in the safety datasheet. Polyhexamethylene biguanide is allowed as a part of cosmetic products (max. 0.1%) if exposure by inhalation is impossible.

On the 20th of April 2018, the european commission decided to ban preservative uses of Polyhexamethylene biguanide PT9 (Fibre, leather, rubber and polymerised materials preservatives). It’s still allowed for uses as disinfectants PT2 (Disinfectants and algaecides not intended for direct application to humans or animals). Furthermore, Polyhexamethylene biguanide has been declared as a candidate for substitution by the ECHA.

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.25

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 Polyhexamethylene biguanide include Kerlix AMD™, Excilon AMD™, and Telfa AMD™ (all from Tyco HealthCare Group, Mansfield, Mass) and XCell® Cellulose Wound Dressing Antimicrobial (Xylos Corp, Langhorne, Pa).

A review of the literature demonstrates in-vivo and in-vitro safety and effectiveness of Polyhexamethylene biguanide for a number of applications. For wound dressings, Wright and colleagues26 compared the effectiveness of a silver dressing to a dry gauze dressing containing Polyhexamethylene biguanide (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 Polyhexamethylene biguanide, which was not released and therefore did not result in killing beyond the edge of the dressing.26 Alternatively, Motta and associates6 demonstrated a good response using Kerlix AMD compared to gauze without Polyhexamethylene biguanide in wounds where packing the dressing into the wound was required. Results suggested that the Polyhexamethylene biguanide in the gauze resulted in a decrease in the number of organisms present in the wound.

The majority of literature describes effectiveness of Polyhexamethylene biguanide on various microorganisms associated with contact lens disinfecting solutions. Antimicrobial effectiveness has been demonstrated on Acanthamoeba polyphaga, A castellanii, and A hatchetti.25,27,28 Additional effectiveness was demonstrated for Polyhexamethylene biguanide use in water treatment. Barker and colleagues29 tested the effect of Polyhexamethylene biguanide on Legionella pneumophila. This bacterium causes Legionnaire’s disease and can be found in water systems, air conditioning machinery, and cooling towers.

Gilbert and colleagues30,31 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 Polyhexamethylene biguanide, were also the most effective agents against sessile bacteria found within biofilms. They suggested that the differences in effects of concentration of Polyhexamethylene biguanide on planktonic versus sessile bacteria was due to either the mechanism of action or the number or disposition of cationic binding sites.30–32 Kramer et al33 have studied the effects of various antiseptics including Polyhexamethylene biguanide on fibroblast proliferation and cytotoxicity. They noted that while octenidine-based products retarded wound healing, Polyhexamethylene biguanide promoted contraction and aided wound closure significantly more than octenidine and placebo.

The mechanism of action of Polyhexamethylene biguanide has been described in a number of articles. Broxton et al34,35 demonstrated that maximal activity of the Polyhexamethylene biguanide 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 colleagues36 showed that the cationic Polyhexamethylene biguanide 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.37

Clinically, Polyhexamethylene biguanide has been used as a perioperative cleansing agent,38 in mouth wash,39 in ophthalmology,38,40 and as a topical wash.18 Hohaus et al19 reported on the oral use of Polyhexamethylene biguanide (Lavasept 1%, Fresenius-Kabi, Bad Homburg, Germany). A combination of oral terbinafine and topical ciclopirox and Polyhexamethylene biguanide were used to successfully treat a deep fungal infection (Trichophyton mentagrophytes) of the throat. Petrou-Binder40 describes the germicidal effects of Polyhexamethylene biguanide (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 Polyhexamethylene biguanide 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.41 The studies suggested that AMD gauze did not elicit any skin reactions.42

Biosynthesized Cellulose Wound Dressing—
Antimicrobial (BWD-Polyhexamethylene biguanide)

Biosynthesized cellulose wound dressings (XCell Cellulose Wound Dressing and XCell Cellulose Wound Dressing Antimicrobial) were developed to maintain a moist wound environment without causing maceration, reduce pain, and enable autolytic debridement. This is possible because the dressings effectively absorb exudate and hydrate dry areas of a wound different from other dressings that have only a single function.43

A 49-patient, multicenter, controlled, randomized clinical study was conducted to demonstrate effectiveness of BWD compared to standard of care on venous leg ulcers. Significantly more autolytic debridement, significantly reduced pain, and cleaner wound margins were demonstrated after the 12-week study period.44,45 Improved rate of wound closure, as demonstrated by increased epithelialization and granulation tissue, was also noted.43
The antimicrobial version of BWD (BWD-Polyhexamethylene biguanide) contains cellulose, water, and 0.3% polyhexamethylene biguanide (PHMB). BWD-Polyhexamethylene biguanide is indicated for use on partial- and full-thickness wounds. It is designed to cover a wound or burn, absorb areas of wound exudate, and provide a moist wound environment that supports autolytic debridement of nonviable tissue. The dressing may be used on moderately exuding, nonexuding, and dry wounds. It also protects against abrasion, desiccation, and external contamination. The moist environment has a cooling effect that has demonstrated a significant reduction of pain.45

Preclinical efficacy testing. BWD-Polyhexamethylene biguanide demonstrates it effectiveness against a variety of organisms. Following a modified American Association of Textile Chemists and Colorists (AATCC) Method 100, samples were incubated with approximately 106 CFU/mL of the various challenge organisms. After 24 hours, a second count was made to determine the reduction in the number of organisms present. Results indicated 99.9% reduction of MRSA, Escherichia coli, Enterococcus faecalis, Bacillus subtilis, and Candida albicans within the 24-hour period.

Release of Polyhexamethylene biguanide from BWD-Polyhexamethylene biguanide. A study was performed to demonstrate the release of Polyhexamethylene biguanide from BWD-Polyhexamethylene biguanide. Five sterile 3.5-in x 3.5-in samples were used. One quarter of the dressing was used to determine the initial Polyhexamethylene biguanide concentration in each dressing using UV-Vis (Ultraviolet-Visible) Spectroscopy (Genesys™ 10 UV, Thermo Spectronic, Rochester, NY) at a wavelength of 234 nm. The remainder of the sample was weighed and placed into 20 times its weight in filtered water. At various times, including 0.5, 1, 2, 3, 4, 5, 6, and 24 h, the solution was assayed for Polyhexamethylene biguanide concentration. At the 24-h time the dressing was removed from the tray, weighed, and an extract was taken and assayed for Polyhexamethylene biguanide concentration.

Figure 1 illustrates the concentration of Polyhexamethylene biguanide over time. Equilibrium was reached after about 3 hours with the concentration (in ppm) in the dressing equaling the concentration in the solution. This demonstrates that the Polyhexamethylene biguanide is not bound to the cellulose and therefore can be released into surrounding fluid along a concentration gradient.

Clinical case series. BWD-Polyhexamethylene biguanide was evaluated in an open enrollment, noncontrolled clinical trial. Standard procedures for wound care were followed and samples of wound fluid were tested for type and level of microbial colonization at initial administration and 1–7 days after BWD-Polyhexamethylene biguanide placement.

Materials and Methods

BWD-Polyhexamethylene biguanide pads (XCell Cellulose Wound Dressing–Antimicrobial) measuring 3.5-in x 3.5-in were provided to 2 clinical sites and used as the primary dressing. Secondary dressings, including compression wraps (where indicated), were the standard of care for the facilities. Patients were chosen on an “as needed” basis and neither randomized nor controlled.

The 2 sites evaluated a total of 12 patients with 26 wounds of various etiologies including venous stasis ulcers (12), diabetic (4), traumatic (8), vasculitic (1), and necrobiosis diabetica lipoidica (1). Eleven of the 12 patients were unresponsive to a silver impregnated or an iodine containing dressing in the 3–4 weeks prior to use of the BWD-Polyhexamethylene biguanide dressing. In these cases the wound had either increased in size or failed to progress. One patient was treated directly with BWD-Polyhexamethylene biguanide.

Swabs of the wound were taken to determine if bacterial colonization was the reason for the lack of response to previous dressings. Organisms were identified in the wounds of 8 patients prior to and after BWD-Polyhexamethylene biguanide application. Systemic antibiotics were not given in conjunction with the use of BWD-Polyhexamethylene biguanide to ensure bacterial reductions were solely due to the Polyhexamethylene biguanide.
The organisms identified included methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Diphtheroid gram-positive rods, beta hemolytic Streptococcus B, Enterobacter aerogenes, mixed skin flora, and Enterococcus sp. The most common was Staphylococcus (including MRSA) and Pseudomonas. Semiquantitative scores ranged from 0 to 4+ (0 represents no bacterial growth and 4+ represents the largest amount of bacterial growth on the culture). The various bacteria found in the wounds of all 8 patients and the relative abundance prior to and after application of the BWD-Polyhexamethylene biguanide dressing are shown in Table 1.

Results

Four patients (5 wounds) from 1 site were used strictly for the economic analysis below. Of the remaining 8, 1 patient (3 wounds) was lost to follow-up after 1 week of BWD-Polyhexamethylene biguanide treatment. The remaining patients had BWD-Polyhexamethylene biguanide applied over periods of 1 to 7 weeks. Results of the 8 patients demonstrated a decrease in wound size on average from 6.79 cm2 to 4.57 cm2 (42% reduction) in an average of 25 days (Table 2). Two of the wounds completely healed during the study, 13 improved, and 2 showed a slight increase in size.

Case Reports

Case 1. A 58-year old woman presented with a full-thickness draining wound over the dorsal foot secondary to an incision (Figure 2). The patient's wound extended to the level of tendon and was recalcitrant to topical gels, ointments, foam dressings, silver dressings, and moist saline gauze. Past medical history was significant for Hodgkin’s disease, heart valve replacement, pacemaker, hemolytic anemia, and chemo and radiation therapy for breast cancer, which was on-going at the time of presentation. After 3 weeks of treatment with a papain-urea ointment (Panafil®, Healthpoint, Fort Worth, Tex), the majority of fibrotic tissue was removed although the wound did not decrease in size. The patient was then placed exclusively on BWD-Polyhexamethylene biguanide for approximately 4 weeks with the dressing being changed once a week. The wound rapidly improved and progressed to complete closure during this time period.

Case 2. A 78-year-old woman presented with a large wound secondary to a hematoma occurring after trauma (Figure 3). The patient was not on anticoagulants and had a medical history significant for hypertension. The wound had been present for 1 week prior to presentation. Following extensive debridement, the patient was started exclusively on BWD-Polyhexamethylene biguanide dressing changes every 4 days. The wound closed completely in approximately 2 months. The patient had a history of similar lesions that required up to 6 months of treatment.

Case 3. An 89-year-old woman with diabetes presented with venous disease and psoriasis (Figure 4). She had 2 wounds, one each on her right and left lower extremities (RLE and LLE) that were treated separately over a period of 209 days.

Upon presentation, the RLE wound was 17.5 cm x 7.0 cm x 0.3 cm. It was treated for 167 days using various products including Acticoat™ (46 applications, [Smith & Nephew, Largo, Fla]), Santyl® (7 applications, [Healthpoint, Fort Worth, Tex]), Apligraf® (6 applications, [Organogenesis, Canton, Mass]), and Xeroform™ (7 applications, [Tyco-Kendall HealthCare Group, Mansfield, Mass]). After these treatments the wound measured 9.0 cm x 4.4 cm x 0.1 cm. Following an initial decrease in size, the wound became unresponsive to these treatments. At that time, BWD-Polyhexamethylene biguanide was substituted as the exclusive primary dressing. Over the next 42 days, a total of 10 BWD-Polyhexamethylene biguanide dressings were applied. The patient subsequently went on to heal 1 week after her final treatment (49 days total) using this protocol.

Upon presentation, the LLE wound was 1.0 cm x 0.9 cm x 0.3 cm. It was treated for 156 days using various products including Acticoat (2 applications), XCell (2 applications), Santyl/Panafil (70 applications), Apligraf (4 applications), Sulfamylon (26 applications), Aquacel® (3 applications, [ConvaTec, Skillman, NJ]), OpSite™ (8 applications, [Smith & Nephew, Largo, Fla]), and Xeroform (7 applications). The wound remained unhealed after these treatments. The wound was recalcitrant to care; therefore, BWD-Polyhexamethylene biguanide was substituted as the exclusive primary dressing. Over the next 53 days, a total of 12 BWD-Polyhexamethylene biguanide dressings were applied as the exclusive treatment. The wound healed at approximately 60 days.

Case 4. A 79-year-old woman presented with venous leg ulcer on her lower extremity (Figure 5). She was treated over a period of 104 days. The wound was 15.0 cm x 9.0 cm x 0.1 cm. The wound was initially treated for 34 days using Panafil (13 applications) and Iodosorb (22 applications). After these treatments the wound measured 10.0 cm x 9.0 cm x 0.3 cm. The wound was determined to be recalcitrant after an initial decrease in size (15.0 cm x 9.0 cm to 10.0 cm x 9.0 cm, [≈ 35%]) and BWD-Polyhexamethylene biguanide was substituted as the exclusive primary dressing. Over the next 70 days, a total of 10 BWD-Polyhexamethylene biguanide dressings were applied.

Effect on wound bioburden and pain. By evaluating the bacterial load pre- and post-BWD-Polyhexamethylene biguanide, it was demonstrated that the dressing resulted in elimination of Pseudomonas aeruginosa, Diptheroid gram-positive rods, beta hemolytic streptococcus, and Enterobacter aerogenes in some patients. In other patients, decreased levels of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were observed.
A reduction in pain has been noted with BWD44 as was observed in the present study.

Economics of BWD-Polyhexamethylene biguanide. The estimated cost for the treatment of chronic wounds including services and associated products is close to $40,000 or in some cases even more.45 Any delay to heal a wound can increase that cost. Mulder46 described an economic model for determining the cost of 2 different treatments for removing necrotic tissue. The analysis demonstrated that a hydrogel/polyurethane combination was slightly more expensive than wet-to-dry gauze but was more cost effective when time to reach ≥ 50% debridement was included.

The cost of BWD-Polyhexamethylene biguanide is similar to other advanced wound dressings. An economic analysis was performed in this study to determine the cost of BWD-Polyhexamethylene biguanide use over time. An economic analysis of the use of BWD-Polyhexamethylene biguanide dressings demonstrates the low cost of using BWD-Polyhexamethylene biguanide on recalcitrant wounds. The average cost of material was calculated to be $5.99 to $9.01 per day with the wounds demonstrating improvement or healing. No attempt was made to quantify the remaining cost of treatment (clinic visit, staff time, etc.).

Data were gathered retrospectively for 2 patients that presented at the UCSD Healthcare System in San Diego, Calif. These patients had a total of 3 wounds that were initially treated with an array of advanced wound care products prior to exclusive use of a BWD-Polyhexamethylene biguanide dressing. The costs associated with the products used in Cases 3 and 4 appear in Tables 3 and 4, respectively. Table 5 illustrates the cost of the use of BWD-Polyhexamethylene biguanide including the use of saline and gauze to clean the wound.

Conclusion

A greater understanding of the role bacteria plays in the wound matrix repair process is resulting in an increasingly important role for antimicrobial dressings and products used in chronic wound care. The differences between various antimicrobial components and dressings require that clinicians have a basic understanding of different antimicrobial agents and their role in tissue repair before selecting the most appropriate dressing for a wound. The introduction of noncytotoxic levels of antimicrobial agents, including silver and Polyhexamethylene biguanide, provides a means to potentially decrease levels of bacterial colonization that may impede closure while providing dressings that may assist with the development of a wound environment conducive to tissue repair, and ultimately, successful wound closure. Currently, Polyhexamethylene biguanide does not have a history of resistance or cytotoxicity, has demonstrated promotion of healing,33 and may play a new and important role as an antimicrobial agent in dressings. The need for decreased frequency of dressing changes, dressing tolerance, and ease-of-use are factors, which are equally important when selecting an appropriate antimicrobial dressing.

The limited amount of information on the ability of antimicrobial dressings to significantly affect the healing process and wound closure supports the need for well designed and adequately powered clinical trials to determine the true role of these devices in the treatment of chronic wounds. Current information and publications indicate a potential benefit regarding the use of these products in wounds where bacterial burden may be delaying or impeding wound closure.

Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in a variety of products including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. There are regulatory concerns with regard to its safety in humans for water treatment. We decided to assess the safety of this chemical in Sprague-Dawley rats. Polyhexamethylene biguanide was administered in a single dose by gavage via a stomach tube as per the manufacturer's instruction within a dose range of 2 mg/kg to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg, 8 mg/kg and 32 mg/kg body weight and hematological, biochemical and histopathological findings of the major organs were assessed. Administration of a dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% Polyhexamethylene biguanide solution (equivalent to 6.4x103 mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in the acute toxicity studies showed that no histopathological lesions were observed in the heart and kidney samples but 30% of the animals had mild hydropic changes in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with or without lymphocyte infiltration and feathery degeneration. Lymphocyte infiltration was, for the first time, observed in one heart sample, whereas one kidney sample showed mild tubular damage. The acute studies showed that the median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% Polyhexamethylene biguanide. Subchronic toxicological studies also revealed few deleterious effects on the internal organs examined, as seen from the results of the biochemical parameters evaluated. These results have implications for the use of Polyhexamethylene biguanide to make water potable.

Keywords: polyhexamethylene biguanide, toxicity, biochemical hematology, histopathology, LD50, therapeutic index

Introduction
Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and antibacterial properties used in several ways including wound care dressings, contact lens cleaning solutions, perioperative cleansing products, and swimming pool cleaners. It is also known as polyhexanide and polyaminopropyl biguanide, polymeric biguanide hydrochloride; polyhexanide biguanide. It is a commonly applied antiseptic, often used as a preservative in cosmetics and personal care products (Schnuch et al., 2007).

The antimicrobial efficacy has been demonstrated on Acanthamoeba polyphaga, A castellanii, and A hatchetti (Hughes et al., 2003; Wright et al., 2003; Burgers et al., 1994; Hiti et al., 2002). In vivo studies have also demonstrated that a miltefosine–polyhexamethylene biguanide combination is highly effective for the treatment of Acanthamoeba keratitis (Polat et al., 2013).

As a biocide, additional pharmacological effects have been demonstrated against Legionella pneumophila, against gram positive and gram negative bacteria. It is a broad spectrum virucide and has amebicidal activities (Gilbert et al., 1990; Kramer et al., 2004; Broxton et al., 1984; Lee et al., 2007). Polyhexamethylene biguanide retains its activity in hard water and does not cause surface streaks or tackiness (Broxton et al., 1984b; Ikeda et al., 1984). Consistent with previous studies, a Polyhexamethylene biguanide mouthrinse was shown to inhibit plaque re-growth and reduced oral bacterial counts, indicating that Polyhexamethylene biguanide could be an alternative to established mouth rinses in preventive applications (Welk et al., 2005). Recreational water maintained and sanitized with Polyhexamethylene biguanide is however assumed to serve as a medium for transmission of ocular adenovirus infections, mainly because at a concentration of 50 ppm, Polyhexamethylene biguanide was not virucidal against adenovirus at temperatures consistent with swimming pools or hot tubs (Romanowski et al., 2013).

Previous studies have shown increased frequency of sensitization to 0.5% and 0.4% Polyhexamethylene biguanide in unselected dermatitis patients (Schnuch et al., 2007). Polyhexamethylene biguanide proved also toxic to keratocytes (Lee et al., 2007) and was shown to have acute toxic effects in human cells where it caused severe inflammation, atherogenesis, and aging. Moreover, Polyhexamethylene biguanide produced embryo toxicity and heart failure in zebrafish (Kim et al., 2013).

Though, officially not used in the treatment of drinking water, there have been instances where toxic effects were experienced in certain individuals. For example in the period from August 2006 to May 2007, more than 12,500 patients were admitted to hospital with a history of drinking illegal cheap “vodka” in 44 different regions in Russia, of whom 9.4% died. In reality, the “vodka” was an antiseptic liquid composed of ethanol (≈93%), diethyl phthalate, and 0.1-0.14% polyhexamethylene guanidine (PHMG) (“Extrasept-1”) (Ostapenko et al., 2011). Previous studies have also shown that another biocide – polyhexamethylene guanidine hydrochloride – has an LD50 of 600 mg/kg in rats (Asiedu-Gyekye et al., 2014). There have been various regulatory concerns with regard to the use of these biocides in water treatment. We therefore evaluated the safety of Polyhexamethylene biguanide when used in treating water to make it potable and also in the case of survivors of drowning events, concentrating especially on its effect on the major organs.

Materials and methods
Polyhexamethylene biguanide concentrate was purchased from AGRIMAT-Ghana as an aqueous solution. A stock solution of 0.1% concentration of Polyhexamethylene biguanide was prepared using deionized water. This was equivalent to 1.0 mg/mL of Polyhexamethylene biguanide. Further dilutions were made using deionized water.

Animal husbandry and groupings
Eight-week-old Sprague-Dawley rats (250 g body weight) of both sexes were acquired from Noguchi Memorial Institute for Medical Research, University of Ghana, Legon and housed in rooms with regulated room temperature of 26°C and humidity of 40 to 60%. The animals were exposed to 12 h light and 12 h darkness. The females were nulliparous and non-pregnant. The animals were randomly assigned to 4 groups of 10 animals each for the acute toxicity test. A similar provision was made for the subchronic study. Animal feed (Kosher Feed Mills Ltd, Osu, Accra) and water were given ad libitum. To ensure effective absorption from the gastrointestinal tract after oral administration, feed was withdrawn 8 h prior to treatment and further withheld for an extra 30 min after administration of Polyhexamethylene biguanide before being reintroduced. Equal numbers of rats were randomized and each marked in their individual cages for 7 days prior to Polyhexamethylene biguanide administration. Equal numbers of animals of both sexes were used at each dose level of Polyhexamethylene biguanide.

Acute toxicity
Polyhexamethylene biguanide was administered as a single dose by gavage in view of the potential mode of ingestion. The animals received doses of 2 mg/kg (500 mg/L), 4 mg/kg (2000 mg/L), 32 mg/kg (8000 mg/L) and 40 mg/kg (10000 mg/L of 0.1% Polyhexamethylene biguanide solution). Since the maximum volume of liquid that could be administered was 1 mL/100 g of body weight, an appropriate adjustment was made in preparing the concentrations so as to avoid exceeding the recommended volume of not more than 2 mL for oral administration (Lee, 1985). Thus 5 different concentrations were prepared. Control animals received only deionized water. The animals were observed every 30 min for the first 4 h, and every 8 h for the next 24 h. The number of animals that died within the 24 h period was recorded for each treatment. The rest of the animals were observed daily for 14 days and any clinical signs were recorded. Clinical signs monitored included respiratory distress, frequency of urination, swellings, abnormal gait, etc.

Discussion
This study aimed to assess the safety level of Polyhexamethylene biguanide when used to sanitize water to make it potable. The LD50 calculated from the study was found to be 25.6 mg/kg (equivalent to 6.4x103 mg/L of 0.1% Polyhexamethylene biguanide solution). Blood chemistry studies also indicated little or no adverse reaction on cellular components of the blood. All the indices examined were comparable to those of controls, suggesting that the chemical may not have any adverse effects on cellular components of the blood at doses below 25.6 mg/kg, the dose which elicited LD50.

Potassium concentrations detected were very high compared to controls, p<0.0057, suggesting that at LD50 level most of the rats might have experienced abnormal heart beats, but this was not confirmed by the histopathological study on the heart as there were no cellular lesions detected. This finding may suggest that in spite of the high dose tested, which possibly might have caused abnormal heart beat in some animals, the integrity of the architecture of the vital organs was not compromised. This observation is similar to that made for PHMGH (Asiedu-Gyekye et al., 2014). Sodium concentrations, on the other hand, did not show any change in either

Polyhexamethylene biguanide-treated or control groups (p<0.08), thus most of the clinical manifestations such as lethargy, weakness, etc, usually associated with sodium imbalance were not observed in the study. It is worth noting that most of the animals that died exhibited various nervous manifestations such as abnormal gait and tonic-clonic convulsions. These observations were not supported by the electrolyte profile obtained from blood chemistry analysis. A chronic toxicity study, which is beyond the goal of this study, is recommended to be carried out to further investigate this nervous phenomenon. It should be emphasized that mortality only occurred at very high doses.

Blood biochemistry included analysis of AST, ALT, GGT and lipid profile. ALT and AST are found usually in the liver, but small quantities are found in kidneys, muscles and pancreas (Friedman & Keefe, 2012). The ALT and AST levels in Polyhexamethylene biguanide-treated rats were comparable to those of controls, suggesting that the integrity of the liver cell membrane was not compromised by Polyhexamethylene biguanide treatment. The histopathological study, however, revealed mild hepatic injuries in 50% of animals at a high dose of treatment, suggesting that the integrity of the liver, and perhaps of all the other organs, may have been compromised. Biochemical analysis, carried out for all the animals, indicated that there was no significant difference between the control and the treated groups, lending further support to the assertion that the chemical may not be toxic to rats at the manufacturer's recommended dose of 8 mg/kg. Acute liver injury has however been associated with the use of another biocide, polyhexamethylene guanidine hydrochloride (PHMGH 0.1–0.14%) or PHMG ingested with either ethanol or diethyl phthalate. The injury caused following such ingestion produced lesions similar to cholestatic hepatitis with a severe inflammatory component causing high mortality (Ostapenko et al., 2011).

In the acute toxicity study, high levels of urea were recorded in the rats treated with Polyhexamethylene biguanide compared with the controls (p<0.2). However, histopathological examination revealed no lesions, suggesting that kidney function may not have been significantly compromised, even at the dose that caused 50% mortality (Greaves, 2007). A similar observation was made with PHMGH, a structurally-related compound (Asiedu-Gyekye et al., 2014).

In the subchronic toxicity study, three dose levels were tested and the results were devoid of clinical signs suggesting adverse events related to Polyhexamethylene biguanide ingestion. Analysis of blood chemistry for red blood cells, mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin levels did not show any differences between the Polyhexamethylene biguanide doses tested and the controls. This shows that, at least for the period and at the dose levels tested, Polyhexamethylene biguanide does not appear to exert adverse effects on the hematopoietic system. The surge in white blood cell count and neutrophils at the dose level of 8 mg/kg cannot be explained as the other dose levels tested yielded data comparable with the controls.

Biochemical analysis included AST, ALT, GGT and ALP as a reflection of liver function. The results suggest that the liver was in no serious toxic danger from the insult of the chemical. This was confirmed by the low level of degenerative lesions observed in the specimens at histopathological examination. In this study, the lipid profile in the Polyhexamethylene biguanide-treated rats were similar to that of controls, suggesting that at the levels investigated, Polyhexamethylene biguanide did not alter the metabolism of lipids. Other studies involving zebrafish have reported a rise in serum triacylglycerol level and fatty liver induction, which resulted in the death of the fish within 70 min when exposed to the working concentration of 0.3% PHMG (Kim et al., 2013).

Electrolyte imbalance mediates various pathological events (Hala et al., 2014: Jusmita et al., 2015). In this study, Polyhexamethylene biguanide had no significant effect on electrolyte levels of the rats. This suggests that Polyhexamethylene biguanide may not influence the electrolyte composition of the blood even when used subchronically. Mean urea values rather indicated that Polyhexamethylene biguanide appeared to have a positive effect on renal function in the long run, as the urea levels appeared to be significantly lower than those of the controls. This observation was not entirely supported by the histopathological evaluation of kidney tissue, as some mild to severe degeneration lesions were observed in a few specimens. Although the level obtained for the group that produced the LD50 was high compared to the control, the difference was not statistically significant. It is rather interesting to note that creatinine levels were comparable between the treated and control groups (p<0.0009), which is in contrast to what was observed with PHMGH in rats (Asiedu-Gyekye et al., 2014). Urea levels, though, may be influenced by diet (Kang et al., 2015). This study has revealed that Polyhexamethylene biguanide (LD50 25.6 mg/kg bwt) may have a narrow margin of safety compared to PHMGH (LD50 600 mg/kg bwt), which are both biocides and investigated for their possible use in treating water to make it potable.

In spite of these observations, the manufacturers recommend to use Polyhexamethylene biguanide for water treatment at a dose of 8 mg/kg. Judging from the LD50 of both Polyhexamethylene biguanide (25.6 mg/kg) and PHMGH (600 mg/kg) with their respective recommended doses from the manufacturer (Asiedu-Gyekye et al., 2014), the therapeutic indices of the two chemicals may stand at 3.2 and 50,000 respectively. On comparing the therapeutic indices, PHMGH appears to have a wider margin of safety than does Polyhexamethylene biguanide. Yet it is likely that organ toxicity or cumulative toxicity may result after prolonged use more especially with Polyhexamethylene biguanide and it might be safer to use PHMGH rather than Polyhexamethylene biguanide in water treatment. A comparison of both the biochemical and the histopathological effects may give a reasonable idea about the possible adverse effects during long-term use of these biocides in humans.

Conclusion
The median lethal concentration (LC50) of Polyhexamethylene biguanide is 1.6 mL of 0.4%, which is equivalent to 6.4x103 mg/L of 0.1% solution. Thus the LD50 is equivalent to 25.6 mg/kg. Subchronic toxicological studies showed few deleterious effects on the major organs examined, as seen from the results of the biochemical parameters evaluated. Gross pathology and histopathology also revealed that the integrity of the major organs was compromised especially at high doses compared with controls. This has implications for the use of Polyhexamethylene biguanide in treating water to make it potable.

It is recommended that chronic toxicity studies be done to ascertain the long-term effect of Polyhexamethylene biguanide.

Polyhexamethylene biguanide is best known for its broad-spectrum antimicrobial and antifungal activity. It is the standard of care for treatment of Acanthamoeba keratitis6 and an ingredient in multipurpose contact lens solutions, such as Renu (Bauch & Lomb, Rochester, NY). Polyhexamethylene biguanide is a cationic disinfectant that is effective against Gram-negative and Gram-positive bacteria through its electrostatic interaction with negative sites on the lipopolysaccharide component of bacterial cell membranes. This interaction results in the disturbance of the cell membrane structure and leakage of the intracellular contents, leading to cell lysis.26 Polyhexamethylene biguanide works in a similar fashion at a minimal concentration of 0.02% to be an effective treatment for Acanthamoeba keratitis by targeting the cystic form of the protozoa. It is also known to be minimally toxic to the corneal epithelium.27

Environmentally friendly high molecular polymer sterilization and disinfectant-polyhexamethylene biguanide, with a broad spectrum of sterilization; low effective concentration; fast action speed; stable properties; excellent performance of being easily soluble in water; can be used at room temperature; long-term inhibition Bacteria, no side effects; non-corrosive; colorless, odorless; non-toxic; non-flammable, non-explosive, safe to use; moderate price; convenient transportation, it can be said to be the best fungicide. In fact, the product is an environmentally-friendly, multi-purpose new polymer, which has extremely wide applications in industry, agriculture, medicine and daily life.

Chemical name: Polyhexamethylene Biguanide / PHMB

Molecular formula: C10H23N5
Appearance: colorless to light yellow liquid & white powder
Purity: 20% & 99%
Molecular weight: 213.32312
EINECS NO.: 1308068-626-2

Molecular formula & molecular weight:（C8H18N5Cl）n n=12-16

Characters: An almost colorless or pale-yellow transparent liquid; viscosity, 5cP；pH 4.5-6.5; specific gravity, 1.04g/ml, boiling point 102℃, soluble random proportion with water.

Quality Standard: Enterprise standard.

Usage: It is an antiseptic and bactericide. This is broad-spectrum antibacterial fugicide, take effective for kill gram-positive bacteria, gram-negative bacteria, fungus and yeast; usually used for swimming pool bactericide, universal detergent and disinfector as a fugicide.Compare with PHMG, it has a better bacteriostasis effect for Aspartate bacillis, beer yeast and Aspergillus niger than PHMG.

Storage: It should be kept in cool and dry place, and away from light; stored in sealed containers.

Packing: Plastic drum, 25kg/plastic drum，200kg/plastic drum.

Use of PHMB：

It can be used as a disinfectant, antibacterial, bactericide, mildew-proof, algae-inhibitor, flocculant, etc.
Widely used in health care, chemicals, textiles, paper, wipes, livestock, aquaculture, fisheries, plastics, agriculture, water treatment and other fields.
It can be used directly after dilution with purified water or with other additive agent compounds. Reference amount 1:125~1:1000 (w/w).

Package of PHMB：

25kg/drum 200kg/drum

Storage of PHMB:

Stored in a dry, ventilated environment and flammable area.

Polyhexamethylene biguanide is best known for its broad-spectrum antimicrobial and antifungal activity. It is the standard of care for treatment of Acanthamoeba keratitis6 and an ingredient in multipurpose contact lens solutions, such as Renu (Bauch & Lomb, Rochester, NY). PHMB is a cationic disinfectant that is effective against Gram-negative and Gram-positive bacteria through its electrostatic interaction with negative sites on the lipopolysaccharide component of bacterial cell membranes. This interaction results in the disturbance of the cell membrane structure and leakage of the intracellular contents, leading to cell lysis.26 PHMB works in a similar fashion at a minimal concentration of 0.02% to be an effective treatment for Acanthamoeba keratitis by targeting the cystic form of the protozoa.
It is also known to be minimally toxic to the corneal epithelium.27

PHMB Biocide is widely recognized as the safest and most effective broad-spectrum antibacterial agent in the 21st century. 2. PHMB Biocide is colorless and odorless, has low bacteriostatic concentration, can be widely used in baby product. 3. Polyhexanide is low foam volume, and can form a layer of cations on the surface It lasts for a long time and does not cause the generation of antibacterial bacteria. 4. PHMB preservatives is currently widely used in medical devices, public environments, households, fabrics, food, milk, and care products. 5. polyhexamethylene biguanide is broad-spectrum bactericidal effect, especially for Gram-negative bacteria that are difficult to handle with general bactericides. High activity against food pathogens and contaminants.

This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively “bind” to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways.

Polyhexamethylene biguanide (PHMB) is a cationic polymer with antimicrobial and antiviral properties. It has been commonly accepted that the antimicrobial activity is due to the ability of PHMB to perforate the bacterial phospholipid membrane leading ultimately to its death. In this study, we show by the means of atomistic molecular dynamics (MD) simulations that, while the PHMB molecules attach to the surface of the phospholipid bilayer and partially penetrate it, they do not cause any pore formation at least within the microsecond simulation times. The polymers initially adsorb onto the membrane surface via the favorable electrostatic interactions between the phospholipid headgroups and the biguanide groups and then partially penetrate the membrane slightly disrupting its structure. This, however, does not lead to the formation of any pores. The microsecond-scale simulations reveal that it is unlikely for PHMB to spontaneously pass through the phospholipid membrane. Our findings suggest that PHMB translocation across the bilayer may take place through binding to the phospholipids. Once inside the cell, the polymer can effectively “bind” to DNA through extensive interactions with DNA phosphate backbone, which can potentially block the DNA replication process or activate DNA repair pathways.

Unlike the related polymer polyhexanide (PHMB), PHMG has been described as a relatively new compound with properties, potency, and effects being not yet fully recognized. Preliminary findings indicate that PHMG and its derivatives primarily rely on damaging the cell membrane by inhibiting the activity of cellular dehydrogenases.

One treatment used is polyhexamethylene biguanide, PHMB.
The PHMB hydrochloride salt (solution) is used in the majority of formulations.
PHMB is also used as an ingredient in some contact lens cleaning products, cosmetics, personal deodorants and some veterinary products.
Purista is a PHMB-based preparation that is added to socks to slow the development of body odor.
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).
In vitro studies on clinical isolates of E. coli and S. epidermidis have demonstrated the anti-biofilm efficacy of PHMB. The activity of five biocides at various concentrations was recorded following exposure to the isolates. The biocides found to be most active towards planktonic (free floating) cells were PHMB and peracetic acid. A corresponding level of activity towards biofilm phenotype bacteria was also found with the two agents.

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.
A recent Cochrane review found one study that compared the effectiveness of chlorhexidine eye drops against PHMB eye drops, for eyes with "Acanthamoeba" keratitis. While the differences between treatments were not statistically significant, the review found that 86% of eyes treated with chlorhexidine eye drops reported a resolution of infection, compared to 78% of eyes treated with PHMB eye drops. The study also found that 71% of eyes treated with chlorhexidine eye drops reported improved visual acuity after treatment, compared to 57% of eyes in the PMGB group; these results were also not significant.
Polyhexamethylene biguanide hydrochloride is a fast-acting, broad-spectrum synthetic compound that binds to the cell envelope of both Gram-positive and Gram-negative bacteria, disrupting the bacterial cell membrane and enabling seepage of ions. PHMB has a long history of use as a contact lens cleanser, mouthwash and more recently in wound care.

Prontosan® (B Braun) Wound Irrigation Solution and Prontosan® Wound Gel are proprietary preparations of PHMB with betaine, an alkaloid surfactant. Surfactants lower surface tension of the fluid medium making it easier to infiltrate wound coatings, debris and bacteria. Both the wound irrigation solution and the wound gel are colourless cleansing agents that are indicated for use in acute and chronic wounds. They also have the potential to be used in conjunction with a range of dressing materials which include occlusive dressings.
"Lecythophora hoffmannii" has proven to be resistant to multiple anti-fungal agents, including amphotericin B, flucytosine, ketoconazole, and fluconazole. Because of this, precautions have been taken, such as antifungal susceptibility testing, in order to circumvent such drawbacks. Through this method, polyhexamethylene biguanide (PHMB) has been identified and utilized in conjunction with invasive surgical procedures to successfully treat one of the only cases of infection at the hands of this fungus. This method of treatment is employed in order to safeguard against fungal infection even in an immunocompetent host.

Wound bed preparation is an accepted strategy that facilitates wound management interventions. Management of wound exudate, bioburden and debridement are all associated with effective wound cleansing and are thus integral components of effectual wound bed preparation. Choice of cleansing solution should consider not only the piecemeal wound requirements but also the patient and be reinforced by a sound knowledge/experience base. This knowledge should include insight into bacterial phenotype ‘behaviour’ and the most appropriate methods of management. Current findings indicate that PHMB in conjunction with a surfactant (betaine) is superior to Ringer’s solution and saline when used as wound cleansers and also appears to demonstrate efficacy when used in wounds where biofilms are suspected or present.

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.

Polyhexamethylene guanidine (PHMG) acts as cationic polymeric disinfectant whose active component is guanidine. It is colourless and odourless disinfectant that is non irritating and unharmful to most materials. It forms thin deposits on the objects and surfaces and helps to eliminate germs and bacteria by penetrating in their cell wall and choking off the channels necessary for their survival. In addition to this, it offers many advantages such as: • showing of stability at high temperature• has a long lasting effect• easily soluble in water,• completely eco friendly,• non corrosive to most of the metals, wood, plastics and rubber.
It can be applied as a hand disinfectant, used for instrument and surface disinfection. PHMG has a long lasting effect and is useful for pre-surgical procedures to avoid re-contamination. PHMG also finds its use in Poultry Disinfection, Aquaculture, etc. It is used in combination with QAC and Aldehydes.

Polyhexamethylenebiguanide (PHMB) serves to be an antiseptic or disinfectants, also known as polyaminopropylbiguanide and polyhexanide. It is effective against a broad spectrum of microorganisms such as Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus. It finds application in many wound care products and is compatible with a wide gamut of aqueous based personal care formulations as preservatives. It also manifests as disinfectant of industrial fluids such as drilling oils, polymer dispersions, mineral slurries, polymer resins, and protein glues etc.

Features and Benefits:
Serves to be a preservative in the cosmetics products such as shampoos, skin creams, skin lotions, baby products, and wet wipes.
Possess full potential of its broad antimicrobial actions
Acts Disinfectants for swimming pool and bathing water.
Forms antimicrobial coating for textiles

PHMB - Polyhexamethylene Biguanide is a broad spectrum, fast acting bactericide for the formulation of disinfectants and sanitisers, for use in industrial, institutional, agricultural, food, beverage and domestic applications.

APPLICATION :
PHMB is effective in a wide range of industrial disinfection applications, primarily as a solid surface disinfectant.

APPLICATION AREAS INCLUDE :

Hospitals
Institutions
Veterinary establishments
Dairies
Milking parlours
Poultry hatcheries
Food processing plant
Breweries
Pasteuriers in canned food & beverage bottling plants,Yoghurt fermentation,Air-conditioning units,Cheese moulds,Beer glass cleaners

AMOUNT TO USE :

PHMB can be used alone or in combination with other biocides to create products for a wide range of disinfection applications. Considerable data exists which provides a measure of the intrinsic anti-microbial activity of PHMB, generated via European suspension test protocols relevant to application in Food, Industrial, Domestic and Institutional Hygiene.

Its activity had been further demonstrated under conditions representative of practical use. However, it is recommended that fiels tests under practical conditions be undertaken to determine the most cost-effective dose for your application.