POLYHEXAMETHYLENE BIGUANIDE
Polyhexamethylene biguanide, or PHMB or Polyhexamethylene biguanide hydrochloride, is a cationic biguanide polymer biocide used in various antimicrobial applications.
Polyhexamethylene biguanide is a substance that controls, prevents, or destroys harmful microorganisms (i.e., bacteria, viruses, or fungi) on inanimate objects and surfaces.
Polyhexamethylene biguanide is a disinfectant with a broad spectrum of activity against bacteria, viruses, and fungi.
Polyhexamethylene biguanide is a cationic biocide marketed worldwide due to its excellent antimicrobial activity, chemical stability, low toxicity, and reasonable cost.
Polyhexamethylene biguanide destroys or irreversibly inactivates most pathogenic microorganisms.
Polyhexamethylene biguanide (PHMB) is a broad-spectrum antiseptic that avoids many efficacy and toxicity problems associated with antimicrobials; in particular, it has a low risk of loss of susceptibility due to acquired antimicrobial resistance.
Polyhexamethylene biguanide is used as a sanitizer, bactericide ( antibacterial ), antiseptic, and disinfectant, widely effective against positive and negative gram bacteria with applications in surface cleaners, hand cleaners/sanitizing, close to neutral powder detergent, latex polymers, antimicrobial and dishwashing liquids, and other personal care applications with microbial activity.
20% Aqueous solution of Polyhexamethylene Biguanide is used as a biocide, antibacterial, Disinfectant, and Virucidal.
At a 1% to 2% dosage, this can be an adequate replacement for alcohol in your products as a water-based disinfectant.
This is very effective compared to Benzalkonium Chloride.
Polyhexamethylene biguanide is an excellent biocide that is an environmentally friendly product and is expected to be used widely in the future to provide valuable disinfection, cleaning, and hygiene functions in a broad type of products such as cosmetics, deodorant, contact lens solutions, fabric softeners, water treatments, wound care products, and antimicrobial foam dressings.
It is expected to be a component of pool cleaners, skin disinfectants, urinary catheter flush solutions, sanitizers in different applications, hospital disinfectants, and food and equipment in contact with food.
Other names: Polihexanide; Polyhexamethylene biguanide; Polyhexamethylene guanide; Poly(iminoimidocarbonyl-iminoimidocarbonyl-iminohexamethylene) Hydrochloride; Poly(hexamethylenebiguanide); Polihexanide
IUPAC Name CoPoly( bisiminoimidocarbonyl,hexamethylene hydrochloride),(iminoimidocarbonyl, hexamethylène hydrochloride)
Common name, synonym - PHMB (1415; 4.7), i.e., Polyhexamethylene biguanide hydrochloride with a mean number-average molecular weight (Mn) of 1415 and a mean polydispersity (PDI) of 4.7;
- Polyhexamethylene biguanide;
- PHMB
- Poly(hexamethylene biguanide) hydrochloride
Molecular formula (C8H18N5Cl)n(C7H16N3Cl)m with three possible end-chain groups.
Synonyms: PHMB; Polyhexamethylene biguanide; Poly(hexamethylene) biguanide hydrochloride; Polyhexamethylene biguanide hydrochloride; Poly(iminoimidocarbonyl)iminohexamethylene hydrochloride; N,N'''-1,6-Hexanediylbis(N'-cyanoguanidine) hexamethylenediamine polymer hydrochloride
Identifiers
CAS Number
28757-47-3
32289-58-0 (HCl)
CAS: 32289-58-0 / 27083-27-8 / 28757-47-3 / 133029-32-0
EC / List no.: 608-723-9
CAS no.: 32289-58-0
Polyaminopropyl biguanide hydrochloride
polyhexamethylene biguanide hydrochloride PHMB
polyhexamethylene biguanide hydrochloride; PHMB
EC / List no.: 608-042-7
CAS no.: 27083-27-8
1,6-Hexanediamine, polymer with N,N'''-1,6-hexanediylbis(N'-cyanoguanidine), hydrochloride
Guanidine, N,N'''-1,6-hexanediylbis(N'-cyano-, polymer with 1,6-hexanediamine, hydrochloride
N,N'''-1,6-Hexanediylbis(N'-cyanoguanidine), hexamethylenediamine polymer, hydrochloride
PHMB
Poly(hexamethylenebicyanoguanide-hexamethylenediamine) Hydrochloride
polyhexamethylene biguanide hydrochloride with a mean number-average molecular weight (Mn) of 1600 and a mean polydispersity (PDI) of 1.8 (PHMB(1600;1.8))
polyhexamethylene biguanide hydrochloride; PHMB
1,6-Hexanediamine, polymer with N,N′′′-1,6-hexanediylbis[N′-cyanoguanidine], hydrochloride
CoPoly(bisiminoimidocarbonyl, hexamethylene hydrochloride)
CoPoly(bisiminoimidocarbonyl, hexamethylene hydrochloride), (iminoimidocarbonyl, hexamethylene hydrochloride)
Guanidine, N,N'''-1,6-hexanediylbis(N'-cyano-, polymer with 1,6-hexanediamine, hydrochloride
Poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride
poly(iminoimidocarbonyl)iminohexamethylene hydrochloride
polyhexamethylene biguanide hydrochloride
Poly(hexamethylenebiguanide) hydrochloride
EC / List no.: 923-111-4
CAS no.: 28757-47-3
Poly(iminoimidocarbonyliminoimidocarbonyliminohexamethylene)
Poly(iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl)
Poly(iminoimidocarbonyliminoimidocarbonyliminohexamethylene)
Polyhexamethylene biguanide
Poly(iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl)
EC / List no.: 640-037-5
CAS no.: 133029-32-0
Polihexanide
Polyaminopropyl biguanide
IUPAC names
Poly(methylene), .alpha.,.omega.-bis[[[(aminoiminomethyl)amino]iminomethyl]amino]-, dihydrochloride
Trade names and abbreviations:
Baquacil
Caswell No. 676
Cosmocil CQ
EPA Pesticide Chemical Code 111801
PHMB
Polihexanide
Polihexanido
Polihexanidum
Polyhexanide
PP 073
UNII-322U039GMF
Vantocil IB
Vantocil TG
Polyhexamethylene biguanide hydrochloride is the chemical name with INCI Name: Polyaminopropyl Biguanide and IUPAC Name: Homopolymer of N-(3-Aminopropyl)-Imidodicarbonimidic Diamide.
Polyhexamethylene biguanide hydrochloride is a polymer that, in its neat form, represents a solid/powder of > 94.2 % purity, colorless, odorless, non-corrosive, and non-irritating
antimicrobial biocide.
It has a good water solubility of around 40 %.
It is also soluble in alcohol and used as a common solvent for paints and lacquers (ECA, 2010).
Average molecular weights range between 2670 and 4216 Da (SCCS, 2015).
Polyhexamethylene biguanide is a positively charged polymer having polymeric biguanide units in the backbone of its structure [−(CH2)6.NH.C(=NH). NH.C(=NH).NH-]n, where n ranges from 2 to 40, having an average value of 11.
These properties make it an exciting molecule for technological applications:
It is as good a metal chelator as its parent molecule, biguanide (de Paula, 2011); the five conjugated amines, when binding to neighboring molecules with multiple hydrogen bonds, will be attractive for supra molecular chemistry (Lebel et al.,2006).
Films of Polyhexamethylene biguanide are transparent and very adhesive to metal, plastics, and glass.
It is a proton conductor, potentially applicable to proton exchange membrane fuel cells (Britz et al., 2010).
The infrared absorption spectrum of Polyhexamethylene biguanide showed that the most important are those located at the 2,000–2,400 nm range, corresponding to nitrogen-related vibrations, including combination bands due to nitrogen-carbon bonds in the biguanide pseudo-aromatic ring.
other bonds are due to methylene groups and residual hydration water (SCCS, 2015).
Polyhexamethylene biguanide is a disinfectant with a broad spectrum of inducing cell death by disrupting cell membrane integrity.
Polyhexamethylene biguanide is an environmentally friendly, noncorrosive, and nontoxic to humans and animals.
Polyhexamethylene biguanide is a preservative in cosmetics, personal care products, fabric softeners, contact lens solutions, hand washes, and more.
In cosmetics, Polyhexamethylene biguanide enables the preservation of fruit and vegetables.
Polyhexamethylene biguanide is also used to preserve wet wipes, control odor in textiles, prevent microbial contamination in wound irrigation and sterile dressings; disinfect medical/dental utensils and trays, farm equipment, animal drinking water, and hard surfaces for food handling institutions and hospitals; and to deodorize vacuums and toilets.
Polyhexamethylene biguanide hydrochloride (PHMB) can work at low concentrations with swift action, a broad spectrum of action, and its wide acceptance and exploitation for potential multi-purpose functional use.
Polyhexamethylene biguanide hydrochloride (PHMB) will be promising for advanced environmental treatments, including food disinfection, water disinfection, and surface disinfection, and meet the criteria for an ideal antimicrobial agent.
Polyhexamethylene biguanide hydrochloride (Polyhexanide, PHMB) is a chemical biocide and a member of the polymeric guanidine family.
Polyhexamethylene biguanide is used as a disinfectant, antiseptic, and general disinfecting agent in the food industry and, very successfully, for the disinfection of swimming pools.
This widely used biocide has been reviewed by the US Environmental Protection Agency (EPA) and noted, except for occupational users, as having a shallow aggregate risk of adverse health effects on the public or environment(EPA, 2005).
Polyhexamethylene biguanide binds to the negatively charged phosphate head groups of phospholipids at the bacteria cell wall, causing increased rigidity, sinking nonpolar segments into hydrophobic domains, and disrupting the membrane with subsequent cytoplasmic shedding culminating in cell death.
There have been no reported instances of bacteria acquiring resistance to Polyhexamethylene biguanide. Polyhexamethylene biguanide is well tolerated when used topically on skin, eyes, the ciliated epithelium of the nose, and wounds.
The market for Polyhexamethylene biguanide-containing products, which now include liquids, gels, and antimicrobial dressings, is expanding rapidly.
Polyhexanide (polyhexamethylene biguanide, PHMB) is a polymer used as a disinfectant and antiseptic.
Polyhexamethylene biguanide is best known for its broad-spectrum antimicrobial and antifungal activity.
Polyhexamethylene biguanide is part of the same pharmaceutical family as chlorhexidine and is active against many bacteria.
In dermatological use, it is spelled polihexanide (INN) and sold under Lavasept, Serasept, Prontosan, and Omnicide.
Polyhexamethylene biguanide is effective against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans, Aspergillus brasiliensis, enterococci, and Klebsiella pneumoniae.
Applications
PHMG is a new generation of disinfectant with a wide scope of applications in agriculture and food processing plants, logistics, kitchens, transport vehicles.
Polyhexamethylene biguanide is a disinfectant with a broad spectrum of activity against bacteria, viruses and fungi, inducing cell death by disrupting cell membrane integrity (Ikeda et al, 1983; Ikeda et al, 1984; Moore and Gray, 2007;) and it is used as a preservative in cosmetics, personal care products, fabric softeners, contact lens solutions, hand washes, and more.
In cosmetics, the preservation of fruit and vegetables (KoffiNevry et al., 2011; Kabara, 1984; Dugard and Mawdsley, 1982).
Polyhexamethylene biguanide is also used to preserve wet wipes; to control odor in textiles; to prevent microbial contamination in wound irrigation, sterile dressings; to deodorize vacuums and toilets (SCCS, 2005); to disinfect medical/dental utensil and trays, farm equipment, animal drinking water and hard surfaces for food handling institutions and hospitals.
Polyhexamethylene biguanide is used in antimicrobial hand washes, rubs, and air filter treatments as an alternative to ozone.
Polyhexamethylene biguanide is also used as an active ingredient for recreational water treatment and as a chlorine-free polymeric sanitizer, which is effective against a wide variety of microorganisms.
It has been used in many applications, from swimming pool sanitizers to preservatives in cosmetics and contact lens solutions (Bucher,2012).
Clinical studies indicate it has a broad spectrum of activity, including against human immunodeficiency virus (HIV) (Wérthen et al, 2004; Krebs et al, 2005).
Polyhexamethylene biguanide appears to be available in presentations that provide clinicians with effective wound care modalities for most clinical scenarios and has also been used as a perioperative cleansing agent (Kramer, 1997), in mouthwash, (Rosin, 2002) in ophthalmology (Kramer, 1997; Petrou-Binder, 2003).
Petrou-Binder describes the germicidal effects of PHMB (Lavasept 0.02%) as eye drops before cataract
surgery.
Polyhexamethylene biguanide can be found in swimming pool sanitizers, cosmetics, leather preservatives, contact lens disinfectants, cleansers in agriculture and food handling, in the treatment of hatching eggs, fibers and textiles, and technical fluids like cutting oils and glues (Kaehn, 2010).
It is the standard of care for treating Acanthamoeba keratitis and an ingredient in multipurpose contact lens solutions, such as Renu (Bauch & Lomb, Rochester, NY).
Polyhexamethylene biguanide is a cationic disinfectant effective against Gram-negative and Gram-positive bacteria through its electrostatic interaction with harmful sites on the lipopolysaccharide component of bacterial cell membranes.
This interaction results in the disturbance of the cell membrane structure and leakage of intracellular contents, leading to cell lysis.
Polyhexamethylene biguanide works similarly 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.
Most Multipurpose Solutions contain polyhexanide (polyhexamethylene biguanide, PHMB), initially developed as a presurgery antimicrobial scrub and then marketed for the sanitization of swimming pools and spas.
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, first aid, surface disinfection, and linen disinfection.
Polyhexamethylene biguanide eye drops have been used to treat eyes affected by Acanthamoeba keratitis.
It is sold as a swimming pool and spa disinfectant instead of chlorine or bromine-based products under Baquacil.
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 PHMB hydrochloride salt (solution) is used in most formulations.
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 diamino1,6-hexane, bis(dicyanoamide) salt]
As Polyhexamethylene biguanide is a small polymer, some side reactions that occurred during the manufacturing process could significantly modify the structure of the polymer.
The side reaction to obtain the unit guanidine occurred up to 10%.
Therefore, it can be considered that the structure of Polyhexamethylene biguanide is composed not only of repetitive units of guanidine but also of repetitive units of guanidine and biguanide.
The active substance as manufactured (TK3) is a 20% w/w aqueous solution of Polyhexamethylene biguanide.
“Purity,” a mixture of polymers and related substances, is challenging to apply to Polyhexamethylene biguanide.
Instead, the applicant refers to the “strength” of the polymer, which is defined as “% total solids” or “dried material.”
The typical Polyhexamethylene biguanide strength is 20 %.
Mode of action
The lethal action of Polyhexamethylene biguanide is an irreversible loss of essential cellular components as a direct consequence of cytoplasmic membrane damage.
Indeed, the lethal event is believed to be a Polyhexamethylene biguanide-acid phospholipid interaction leading to a phase separation in the outer leaflet of the membrane bilayer. Such phase separation will lead to instability in the membrane and also loss of membrane-bound enzyme function, resulting in destabilization, which is
followed rapidly by a total loss of membrane function owing to the phospholipids assuming a hexagonal rather than a bi-layered phase.
The contact time is 30 seconds for a bactericidal activity of Polyhexamethylene biguanide.
How does the widely used antimicrobial polyhexamethylene biguanide (PHMB) kill the bacteria selectively over host cells?
Contrary to the accepted model of microbial membrane disruption by Polyhexamethylene biguanide, cell entry into a range of bacterial species is observed.
The treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism.
A DNA-level mechanism was confirmed by observations that Polyhexamethylene biguanide formed nanoparticles when mixed with isolated bacterial chromosomal DNA.
Pairing with the DNA-binding ligand Hoechst 33258 suppressed its effects on growth.
Polyhexamethylene biguanide also entered mammalian cells but was trapped within endosomes and excluded from nuclei.
Therefore, Polyhexamethylene biguanide displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes.
Because acquired resistance to Polyhexamethylene biguanide has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.
The broad-spectrum antimicrobial biocide poly hexamethylene biguanide (PHMB; polyhexanide) kills bacteria, fungi, parasites, and certain viruses with a high therapeutic index; it is widely used in clinics, homes, and industry.
It is most commonly used as a biocide but is also an essential drug in several topical applications.
Polyhexamethylene biguanide comprises repeating basic biguanide 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 Polyhexamethylene biguanide has not been reported.
The evidence for a lack of acquired resistance is necessarily harmful, 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 Polyhexamethylene biguanide 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's comparatively less activity against mammalian membranes.
The prevailing model for PHMB’s microbe-selective toxicity holds that Polyhexamethylene biguanide disrupts microbial membranes preferentially.
However, this model relies on data from artificial membrane studies, and it does not explain how Polyhexamethylene biguanide can kill diverse microbes, which differ in cell barrier composition, nor does it explain observations that Polyhexamethylene biguanide can induce DNA repair pathways.
Therefore, the literature contains conflicting evidence and interpretations regarding the antibacterial mechanism of action of Polyhexamethylene biguanide.
When considering the membrane disruption model and possible alternatives, it may be essential to recognize that Polyhexamethylene biguanide has a capacity for electrostatic and H-bonding interactions, which could occur at many potential cell targets.
For example, Polyhexamethylene biguanide binding to nucleic acid has been demonstrated in vitro, raising at least one possible alternative mechanism of action.
PREPARATION OF Polyhexamethylene biguanide
Several methods have been devised to prepare Polyhexamethylene biguanide.
For instance, one of the current methods is to obtain Polyhexamethylene biguanide by polycondensation of sodium dicyanamide and hexamethylenediamine in two steps (de Paula et al., 2011).
Preparations of Polyhexamethylene biguanide are polydisperse mixtures of polymeric biguanides, with a weighted average number (n) of 12 repeating hexamethylene biguanide units. The heterogeneity of the molecule is increased further by the presence of either amine, cyanoguanidine, or guanidine end-groups in any combination at the terminal positions of each chain.
Equal amounts (in molar) of hexamethylenediamine and guanidine hydrochloride to be mixed in a round-bottomed three-necked flask, which is equipped with a
mechanical stirrer and vacuum system.
The mixture reacts at 100 °C for 60 min and then at 170 °C for a specific time.
During the reaction, by-product ammonia is neutralized by bubbling through aqueous HCl.
At the end of the reaction, the slightly yellow, viscous liquid solidifies upon cooling, giving PHMG samples (Wei et al., 2009).
