Preservative antimicrobial activity

Other Nitrogen Compounds. The basis of the sophisticated nitrogen compounds Hsted in Table 10 is the reaction of formaldehyde with amino compounds. A significant amount of Hterature details investigation of the mechanism of action, particularly whether or not the antimicrobial activity depends on decomposition to formaldehyde (40—42). These compounds tend to have substantial water solubiUty and are more effective against bacteria than fungi and yeasts. Key markets for these compounds are metalworking fluids, cosmetics, and in-can preservation of paints (see Alkanolamines Amines, fatty amines). 

Inorganic Acids. Strong inorganic acids have little antimicrobial activity in themselves but inhibit microorganism growth by lowering the pH. Disinfectant toilet bowl cleaners that contain 9.5% HCl or more are antimicrobial. Carbonic acid [463-79-6] in soft drinks provides some antibacterial preservation. Sulfurous acid [7782-99-2] is an effective preservative used to preserve wines (see Wine), fmit juices (qv), and dried fmits. 

Whereas tests (186) indicated that ampholytes were effective in skin cleansing for preoperative use, for wound cleansing, and as an antiseptic in the oral cavity (187), as well as other medical appHcations, the food and beverage industries have proved to be the principal employers of these compounds. Ampholytes are used as sanitizers and disinfectants, not as food preservatives. Low toxicity, absence of skin irritation, and noncorrosiveness, along with antimicrobial activity, has given ampholytes acceptance in dairies, meat plants, and the brewing and soft drink industries. These disinfectants have been manufactured and distributed in Europe and Japan, but not in the United States. 

Phenoxyethanol (2-phenoxyethanol). Typical in-use concentration 1%. It is more active against Ps. aeruginosa than against other bacteria and is usually combined with other preservatives such as the hydroxybenzoates to broaden the spectrum of antimicrobial activity. 

Many derivatives of phenol are now made by a synthetic process. Homologous series of substituted derivatives have been prepared and tested for antimicrobial activity. A combination of alkyl substitution and halogenation has produced useful derivatives including clorinated phenols which are constituents of a number of proprietary disinfectants. Two ofthe most widely used derivatives are/ -chloro-m-cresol (4-chloro-3-methylphenol, chlorocresol, Fig. 10.7C) which is mostly employed as a preservative at a concentration of 0.1%, and / -chloro-m-xylenol (4-chloro-3,5-dimethylphenol, chloroxylenol. Fig. 10.7C) which is used for skin disinfection, although less than formerly. Chloroxylenol is sparingly soluble in water and must be solubihzed, for example in a suitable soap solution in conjunction with terpineol or pine oil. Its antimicrobial capacity is weak and is reduced by the presence of organic matter. 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Cowen R. A. Steiger B. (1976) Antimicrobial activity—a critical review of test methods of preservative efficiency. J Soc Cosmet Chem, 27, 467-481. 

Reybrouck G. (1992) The evaluation of the antimicrobial activity of disinfectants. In Principles and Practice of Disinfection, Preservation and Sterilization (eds A.D. Russell, W.B. Hugo G.A.J. Ayliffe), 2nd edn, pp. 114-133. Oxford Blackwell Scientific Publications. 

The pH of the finished product may have a strong influence on the type of preservative used. A good example of this can be seen with the use of organic acids which may exist in a predominantly dissociated or an undissociated form as a consequence of the product pH. The undissociated form is considered to confer the antimicrobial activity and the effect of pH on benzoic, sorbic and dehydroacetic acid is described in the graph below. It can be seen that, at the normal pH of most personal care products ie. 5.5 to 7.0, there is little activity remaining. Hence organic acids would be suitable preservatives for predominantly acidic products, such as astringent washes made with lemons. 

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

This aromatic alcohol has been an effective preservative and still is used in several ophthalmic products. Over the years it has proved to be a relatively safe preservative for ophthalmic products [138] and has produced minimal effects in various tests [99,136,139]. In addition to its relatively slower rate of activity, it imposes a number of limitations on the formulation and packaging. It possesses adequate stability when stored at room temperature in an acidic solution, usually about pH 5 or below. If autoclaved for 20-30 minutes at a pH of 5, it will decompose about 30%. The hydrolytic decomposition of chlorobutanol produces hydrochloric acid (HC1), resulting in a decreasing pH as a function of time. As a result, the hydrolysis rate also decreases. Chlorobutanol is generally used at a concentration of 0.5%. Its maximum water solubility is only about 0.7% at room temperature, which may be lowered by active or excipients, and is slow to dissolve. Heat can be used to increase dissolution rate but will also cause some decomposition and loss from sublimation. Concentrations as low as 0.125% have shown antimicrobial activity under the proper conditions. 

Potential therapeutic applications of host defense peptides also include the lantibiotic nisin. Indeed, nisin has had an impressive history as a food preservative with FDA approval in 1988 for use in pasteurized, processed cheese spreads. The attractiveness of nisin as a potential therapeutic is also enhanced due to its relative resistance to proteases and broad spectrum Gram-positive antimicrobial activity including multidrug-resistant strains. Biosynexus Inc. has licensed the use of nisin for human clinical applications and Immucell Corp. has licensed the use of Mast Out, an antimastitic nisin-containing product, to Pfizer Animal Health." Indeed, nisin formulations have been used as an active agent in the topical therapies Mast Out and Wipe-Out for bovine mastitis, an inflammatory disorder of the udder that is the most persistent disease in dairy cows." ... 

In addition, the solubility of many preservatives in a mostly aqueous system may not be high enough for effective antimicrobial activity. For example, the para-bens often require heating in order to be solubilized. Additionally, it is essential to understand that bacteriostatic agents can partition between organic and aqueous phases in such a way that their activity is significantly reduced. Methyl paraben... 

Parabens are approved for use in oral solution and suspensions at a concentration of 0.015% to 0.2% w/v. Due to their low solubility, the sodium salts of parabens are often used in aqueous formulations. The parabens are most effective in the pH range of 2 to 6, and their antimicrobial activity decreases with increasing pH. Additionally, they are very unstable at pH 8 or above in solution. Methyl paraben has also demonstrated incompatibility with sorbitol and may show some discoloration in the presence of iron. The absorption of methylparaben by plastics has been reported with the amount absorbed being dependent upon the type of plastic and vehicle. However, no absorption has been reported for low density polyethylene (LDPE) or high density polyethylene (HDPE) containers. Certain coloring agents such as yellow iron oxide, ultramarine blue, and aluminum silicate can extensively absorb ethyl paraben in simple aqueous systems, thus reducing its preservative efficacy. 

EDTA Chelates alkaline earth and heavy metals 0.005-0.01% w/v antimicrobial activity synergy Often used in combination with other antimicrobial preservatives, and other antioxidants based on their synergy... 

Little or no loss of antimicrobial activity was further observed after fermentation of raw sausages containing streptomycin (6). However, smoking/scalding processes could cause a 32-45% reduction of the streptomycin activity (7). When semi- or fully preserved sausages were heated at 90-95 C for 1 h, the microbiological activity of the contained streptomycin exhibited a 50% reduction of the initial dose (8) however, some of the initial activity could be demonstrated in the juices exuded from the heated sausages even when the temperature was raised to 120-125 C. 

The stability of oxytetracycline in sausages can also depend on the particular procedure applied for their preparation. Thus, no loss of antimicrobial activity was observed during raw fermented sausage preparation (6), but oxytetracycline was completely inactivated in semi- and fully preserved sausages (7, 8). 

Shelf stability of a product is of critical importance because it is affected by longterm antimicrobial and antioxidizing activity enhanced by preservative agents compared to only antimicrobial agents that are added to dressings for thwarting infection in a wound. Preferably, a preservative can be added to a product that possesses broad-spectrum antimicrobial activity that will allow the product to maintain activity before reaching a planned expiration date, and prevent infection when applied to wounds. 

The follow information (italics) is from Russell, A. D., Chapter 3. Principles of Antimicrobial Activity and Resistance, Disinfection, Sterilization, and Preservation, Block, S. S., editor., 5th ed., Lippincott, Williams and Wilkins, New York, 2001 ... 

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