Benzalkonium compounds

Minimum Heparin in a Lacquer. Earlier work (3) using coagulation tests in cones showed that the anticoagulant effect of a lacquer containing heparin-benzalkonium compound (GBH) depended not only on the total amount of heparin in the lacquer, but also required a minimum concentration. Variation of heparin content at constant film thickness (5 microns) indicates a critical level between 0.3 and 0.5 fig./cm.2 variation of film thickness at 0.3 or 0.6% BH in the film indicates a similar critical level,... 

BENZALKONIUM COMPOUNDS fSED-15, 421 SEDA-32, 440 SEDA-33, 481 SEDA-34, 379J ... 

Disinfectants. Several disinfecting agents can be used in hatcheries and two are of particular interest. Because they are not considered dmg or food additive uses by FDA, povidone—iodine compounds can be used to disinfect the surface of eggs (9). Benzalkonium chloride [68424-85-1] and benzethonium chloride (quaternary ammonium compounds), are allowed at 2 mg/L by FDA to disinfect water containing fish. These compounds are also known to have therapeutic properties, especially against external bacteria (9). 

Fig. 10.8 Quaternary ammonium compounds (QACs) A, general structure ofQACs B, benzalkonium chloride (n - S - 18) C, cetrimide (n - 12 - 14 or 16) D, cetylpyridinium chloride.

Fig. 10.8 A where the R substituents are alkyl or heterocyclic radicals to give compounds such as cetyltrimethylammonium bromide (cetrimide), cetylpyridinium chloride and benzalkonium chloride. Inspection of the stmctures of these compounds (Fig. 10.8B) indicates the requirement for good antimicrobial activily of having a chain length in the range Cg to Cig in at least one of the R substituents. In the pyridinium compounds (Fig. 10.8C) three of the four covalent links may be satisfied by the nitrogen in a pyridine ring. Polymeric quaternary ammonium salts such as polyquatemium 1 are finding increasing use as preservatives.

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

Quaternary ammonium salts are organically substituted nitrogen compounds in which the nitrogen atom is pentavalent. Four of the substituents are alkyl, aryl or heterocyclic radicals and the fifth is an anion (a cationic charge). This anion is mostly chloride. Therefore we call them benzalkonium chlorides. 

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

The most widely used preservative remains benzalkonium chloride, which often is supplemented with disodium edetate. The benzalkonium chloride defined in the USP monograph is the quaternary ammonium compound alkylbenzyldimethylammonium chloride, in which the alkyl portion is composed of a mixture of chain lengths ranging from C8 to C16. This compound s popularity is based, despite its compatibility limitations, on its being the most effective and rapid-acting preservative with excellent chemical stability. It is stable over a wide pH range and does not... 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

This preservative is comparatively new to ophthalmic preparations and is a polymeric quaternary ammonium germicide. Its advantage over other quaternary ammonium seems to be its inability to penetrate ocular tissues, especially the cornea. It has been used at concentrations of 0.001-0.01% in contact lens solutions as well as dry eye products. At clinically effective levels of preservative, POLYQUAD is approximately 10 times less toxic than benzalkonium chloride [87,137], Various in vitro tests and in vivo evaluations substantiate the safety of this compound [137,141,142], This preservative has been extremely useful for soft contact lens solutions because it has the least propensity to adsorb onto or absorb into these lenses, and it has a practically nonexistent potential for sensitization. Its ad-sorption/absorption with high water and high ionic lenses can be resolved by carefully balancing formulation components [143],... 

Using regression analysis on a data set of about 50 different molecules, it was found that a. = —4.4,8 = —0.5, Df = 12 cm2/s, and =2.5x 10 5 cm2/s [192], A graphic representation of the effect of relative molecular mass (Mr) and distribution coefficient on corneal permeability is shown in Fig. 13. One observes a rapid reduction in permeability coefficient with decreasing P and increasing Mr. The addition of pores to the model, a mathematical construct, is necessary to account for permeability of polar molecules, such as mannitol and cromolyn. These would also be required for correlating effects of compounds, such as benzalkonium chloride, which may compromise the... 

Other disinfectants include quartemary ammonium compounds (QACs) such as benzalkonium chloride (BACl) and didecyldimethylammonium chloride (DDMAC). Disinfectants have been shown to denitrifying bacteria at concentrations as low as 1-2 ng L (Kiimmerer, 2004b). QACs are specifically not used for disinfecting clothing, but their use is central in other purposes. Triclocarban and triclosan have an aromatic structure that is rich in chlorides, which contribute to their persistence in the environment. QACs are also quite persistent in the environment (Al-Ahmad et al., 2000). Other disinfectants include chloramines and 1,3-dichlorosucyanuric acid as well as PVP-iodide-based disinfectants. 

Quaternary compounds are used for sanitation of noncritical surfaces (floors, bench tops, etc). Their low toxicity has led to their use as sanitizers in food production facilities. The CDC recommends that quaternary ammonium compounds such as benzalkonium chloride not be used as antiseptics because several outbreaks of infections have occurred that were due to growth of pseudomonas and other gram-negative bacteria in quaternary ammonium antiseptic solutions. 

CBH. The sparingly water soluble compound of heparin with an organic base (BH), such as benzalkonium—e.g., Zephiran (Winthrop) or cetyl trimethyl ammonium bromide or octadecyl amine can be dissolved in ethyl alcohol and mixed with an organic polymer matrix—e.g., collodion in ether and alcohol (4). Such lacquer mixtures are designated CBH. 

Pre-treatment of the filter membrane (regenerated cellulose, molecular cut off 10 KDa) with 5 % Tween 80 or benzalkonium chloride showed significantly less nonspecific binding for compounds that had a tendency toward high membrane binding (Lee et al. 2003). 

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