Benzalkonium Chloride Solution Research Articles

Call for worldwide withdrawal of benzalkonium chloride from nebulizer solutions

Call for worldwide withdrawal of benzalkonium chloride from nebulizer solutions

Effects of intrinsic denervation on intestinal morphology in rats with short-bowel syndrome.

When benzalkonium chloride solution (BACs) is locally applied, to the serosal surface of the intestine, it causes intrinsic denervation (ID) of the myenteric plexus (MP), changes intestinal morphology, and slows intestinal passage by prolonging small-bowel transit time. These effects of ID suggest that chemically-induced bowel denervation may be useful in the treatment of short-bowel syndrome (SBS). How ID affects intestinal morphology in rats with SBS has not previously been investigated. A 75%-80% mid-small-bowel resection was performed in 20 rats with mean body weight 247 +/- 30 g. The proximal and distal 2 cm of the resected bowel were examined histologically. After intestinal continuity was maintained by end-to-end anastomosis, a 2-cm jejunal segment was marked with silk sutures to form the test segment. BACs 0.1% was applied to 10 of the 20 test segments according to the modified Fox method, resulting in MP destruction (G1). Saline solution was applied to the other 10 test segments to form the control group (G2). Three months later, the rats were killed and the jejunal, ileal, and test segments were evaluated morphologically. Results were expressed as mean +/- standard deviation. The Wilcoxon parametric test was performed to compare the groups during the operation and after death, while the Mann Whitney U-test was used to compare the data in G1 and G2. No intestinal obstruction was observed in either group. In G1, the body weight increased by 19.1% and the total small-intestinal lengthening was 62.2% (P < 0.05). In the test segment of G1, 75% of the ganglia in the MP were destroyed and villus height, crypt depth, intestinal muscle thickness, number of enterocytes, and villus density increased compared to G2. In the ileal segments of G1, there was an increase of 28.8% in intestinal diameter, 14% in muscle thickness, and 15% in villus density (P < 0.05). No change was observed in the untreated jejunal segments of G1 and G2. Thus, ID of the MP after segmental BACs application of the jejunal level: (1) does not cause intestinal obstruction after 3 months; (2) the increase in bowel diameter in the test and ileal segments increases the absorptive surface of the mucosa; (3) the morphologic changes in the test and ileal segments verify an increase in intestinal adaptation; and (4) BACs application in rats with SBS is an easy procedure with no morbidity or mortality, and can be used to increase intestinal adaptation in rats with SBS.

Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group.

OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial....

Design of an intravaginal ring for the controlled delivery of 17β-estradiol as its 3-acetate ester

Suitable ester prodrugs of 17β-estradiol are identified, thus permitting effective sustained and controlled estrogen replacement therapy (ERT) from an elastomeric, silicone intravaginal ring (IVR). IVR devices of reservoir design were prepared by blending silicone elastomer base with n-propylorthosilicate (cross-linker) and 10% w/w of 17β-estradiol or an ester prodrug, the mix being activated with 0.5% w/w stannous octoate and cured at 80°C for 2 min. A rate-controlling membrane was similarly prepared, without the active agent. IVR devices were of cross-sectional diameter 9 mm, outer diameter 54 mm, with core cross-sectional diameter of 2 mm and core length varied as required. Sink conditions were evident for the 17β-estradiol esters in 1.0% aqueous benzalkonium chloride solution. The low release rates into 0.9% w/v saline of the lipophilic valerate and benzoate esters were due to their intrinsically low aqueous solubilities. In vivo, these esters failed to raise plasma estradiol above baseline levels in postmenopausal human volunteers, despite good in vitro release characteristics under sink conditions. The best release rates under sink conditions, in combination with substantial aqueous solubilities as indicated by the release rates into saline, were observed for the acetate and propionate esters. A combination of drug release characteristics, short plasma half-life and a toxicologically acceptable hydrolysis product indicated that 17β-estradiol-3-acetate was the prodrug of choice for IVR delivery of ERT. In vivo, an IVR device releasing 100 μg/day of estradiol as its 3-acetate ester maintained over 84 days a circulating plasma concentration in the region of 300 pmol l −1, within the clinically desirable range for ERT.

Efficacy of a surfactant, allantoin, and benzalkonium chloride solution for onychomycosis. Preliminary results of treatment with periodic debridement.

A 10-month, hospital-based, open-label clinical study was undertaken of a unique antimicrobial nail solution containing surfactant, allantoin, and benzaikonium chloride to determine its effectiveness, in conjunction with periodic debridement, against pedal onychomycosis. Forty patients with microbial infection of the nails were enrolled in this study, in which a new, objective nail-scoring system was used. At the start of the study, the mean nail score was 8.3, and 79.8% of the nails scored had severe disease (on a scale of 0 to 10, with 10 defined as total nail involvement, accompanied by pain and thickening). By the conclusion of the study, the mean score had decreased to 2.5, 32.6% of the patients' nails were scored 0 or 1, and 90% of the patients subjectively judged their improvement as excellent or good.

第４級アンモニウムイオンをインターカレートした層状リン酸ジルコニウムおよびリン酸アルミニウム化合物の合成と評価

The layered phosphates, mainly represented as MIV(HPO4)2·nH2O (M：metal ion), are the compounds which have the layered crystal structures. The layered phosphates have a lot of advantages such as high selectivity, and high stability against the strong acid solutions, radioactive rays and temperature owing to their steric structure as inorganic ion exchangers. Lately, the layered phosphates are remarked increasingly as a host material for intercalation compounds. If the quaternary ammonium ions can be intercalated into the layered phosphates, the disadvantages of heat resistance for organic medicaments might be improved and antibacterial properties might be provided to the phosphates. Zr(HPO4)2·H2O and AlH2P3O10·2H2O were selected for the present investigation as hosts of intercalation of the quaternary ammonium ions. It is clarified that benzalkonium ion intercalates easily in Zr(HPO4)2·H2O by the reaction between benzalkonium chloride solution and Zr(HPO4)2·H2O, and almost pure intercalation compounds can be obtained at the concentration of the benzalkonium chloride less than 5.7 mmol dm-3. On the contrary, butyl amine treatment is necessary for the intercalation of the quaternary ammonium ions to AlH2P3O10·2H2O. The intercalation compounds obtained here show the sterilizing effect for several bacteria and improvement of the thermal stability of quaternary ammonium ions by holding in Zr(HPO4)2 and AlH2P3O10·2H2O.

Benzalkonium Chloride

The efficacy of benzalkonium chloride was evaluated as an irrigating solution for the eradication of Staphylococcus aureus from a contaminated orthopaedic wound. Thirty Sprague Dawley rats were randomized into two groups. A stainless steel wire was placed in a lumbar spinous process, and the wound was inoculated with 10(7) or 10(6) colony forming units of Staphylococcus aureus. The wound was irrigated with 1 L of normal saline or 0.1% benzalkonium chloride solution. The animals were sacrificed, and cultures were obtained. Rats inoculated with 10(7) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. Rats inoculated with 10(6) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride also had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. In a parallel noninoculation study, histologic evaluation of tissues did not show toxicity in the rats irrigated with benzalkonium chloride. This study shows that benzalkonium chloride is more effective than normal saline as an irrigating agent for eradicating Staphylococcus aureus from a contaminated orthopaedic wound.

Changes in lactate dehydrogenase activity in bovine corneal stroma and epithelium in response to in vitro toxic challenges in the enucleated eye test.

To assess whether changes in lactate dehydrogenase (LDH) activity, as a marker of cell damage, could be detected in corneal stroma and corneal epithelium after toxicity measurements using the enucleated eye test (EET). The corneal surface of isolated bovine eyes was continuously wetted with commercial balanced salt solution (BSS) over 4 h at 37 degrees C and central corneal thickness (CCT) was measured. Initial 5-min challenges were made with dilute solutions of benzalkonium chloride (up to 0.032%) or NaOH (up to 0.4 M). The residual LDH activity in the corneal epithelium and corneal stroma were then assessed. Dose-dependent increases in CCT of up to 70% were measured. A strong correlation (r = -0.961) was found between increases in CCT and decreases in stromal LDH activity, but the correlation was much less (r = -0.512) for epithelial LDH activity. LDH activity can be used as one marker for cell integrity in the corneal stroma and epithelium, although dose-dependent correlations may not be high.

Microbial contamination of antiseptic-soaked cotton balls.

We investigated microbial contamination of in-use antiseptics at a hospital. No microbial contamination was observed in 70 samples of 0.02% benzalkonium chloride solution (500-ml volume), 70 samples of 1% titratable I2 povidone-iodine solution (250-ml volume), or 15 samples of 0.1% ethacridine lactate solution (500-ml volume) during use in reduced amounts. Nor was any microbial contamination observed in 70 samples of cotton balls soaked in 1% titratable I2 povidone-iodine solution in canisters or cotton gauze soaked in 70% (w/v) ethanol solution in canisters. However, among 70 samples of cotton balls soaked in 0.02% benzalkonium chloride solution in canisters, 6 (8.6%) were contaminated with 10(4) to 10(6) viable cells/ml. The microbial species detected were glucose non-fermentative bacilli such as Alcaligenes xylosoxidans and Pseudomonas putida. The contaminants obtained from cotton balls soaked in 0.02% benzalkonium chloride solution did not proliferate in that solution or in distilled water but showed rapid growth in the cotton balls soaked in either of these liquids. These findings suggested that benzalkonium chloride solution tends to become contaminated when cotton balls are immersed. Therefore, cotton balls soaked in benzalkonium chloride solution are not recommended as an antiseptic. When no other choice is available, the cotton balls should be soaked in benzalkonium chloride solution at the time of usage.

市販滅菌蒸留水を利用した塩化ベンザルコニウム希釈液の無菌的調製法

We developed a new method for preparing a diluted aseptic solutipn of benzalkonium chloride (BAC) using a commercially available plastic bottle of sterile distilled water for injection. A rubber patch was attached to the shoulder of the plastic bottle immediately after the sterilization had been done using 70% ethanol. A solution containing 10% BAC filtered through a membrane with a mean pore size of 0.22μm was injected into the plastic bottle through the rubber patch: In order to assess the aseptic lezel of the solution prepared according to this method, we aseptically filled the bottle with two culture media consisting of soybean casein digest broth (n=20) or glucose peptone broth (n=20). Tap water was also injected into the bottle according to the procedure. Each of these resulted in a negative bacterial contamination. No change was observed in the BAC contents, pH values and bactericidal activities against five strains (S. aureus, E. coli, P. aeruginosa, S. marcescens, and F. meningosepticum) of the BAC solutions (0.02% and 0.1%) tested during the storage period of six months at room temperature. The time required for preparing a solution by this method was about one-fifth of that according by the preestablished method where a grass bottle containing a diluted disinfectant solution was sterilized using an autoclave.

Disinfecting Agents for Removing Adherent Bacteria From Orthopaedic Hardware

This investigation seeks to determine whether surfactants or detergents can be used to clean and disinfect orthopaedic wounds with implanted hardware. Thus, a stepwise investigation of biocompatible surfactants and detergents was performed to identify an irrigation agent for disinfecting orthopaedic wounds. Bacterial adhesions assays, irrigation studies, and bactericidal assays determined that benzalkonium chloride showed the greatest efficacy. Testing involved stainless steel screws colonized with a preformed biofilm of Staphylococcus epidermidis, Staphylococcus aureus, or Pseudomonas aeruginosa, which were immersed in benzalkonium chloride solutions for various time intervals under static conditions. After 10 minutes, benzalkonium chloride achieved a minimum 4 log kill (10,000-fold) for all 3 strains of bacteria. Additional studies demonstrated that the high mechanical energy of jet irrigation improved the disinfecting properties of this agent. With jet lavage, both 1:1000 and 1:5000 concentrations of benzalkonium chloride achieved a minimum 2 log kill (100-fold) for all 3 bacteria. The results or this study suggest that at tissue compatible concentrations, benzalkonium chloride has significant disinfection properties for in vitro colonized orthopaedic devices, and these properties may be enhanced via jet lavage.

希釈調製したグルコン酸クロルヘキシジンと塩化ベンザルコニウムの高圧蒸気滅菌後の安定性

We investigated the stability of 0.05% chlorhexidine gluconate solution (CHG) and 0.05 % benzalkonium chloride solution (BAC) sterilized by high-pressure steam. When CHG was stored at 70°C and 90°C for 21 days, the residual rate decreased to 64.6% and 21.0%, respectively. When CHG was stored at room temperature (R. T.) for 12 months, the residual rate decreased to 84.7%. CHG stored at R. T. for 6 months was completely effective against Escherichia coli and Candida albicans, but not Staphylococcus aureus by the bacteriological test. On the other hand, BAC was stable at high temperature and under the light, and the initial concentration of BAC was kept unchanged for 12 months at R. T.

HIV Transmission in a Dialysis Center— Colombia, 1991-1993

Health personnel must adhere to strict infection control practices during dialysis to prevent the patient-to-patient transmission of HIV. The finding of HIV-seropositive blood samples in May 1993 from three patients of a dialysis center in Colombia prompted the subsequent testing of blood specimens from all dialysis center patients which had been stored during January 1988-December 1993 as part of an affiliated kidney transplant program. A retrospective cohort study among all patients dialyzed in the center from January 1992 through December 1993 was launched subsequent to HIV antibody testing of the specimens. Blood specimens were available for 59 of the 84 patients treated during January 1988 to December 1993. 22% of these individuals were HIV-seropositive including ten who were HIV seroconverters. All HIV seroconverters had undergone ten or more dialysis sessions. Of the nine who seroconverted during the epidemic period of January 1992 through December 1993 seven were male two had a history of paying for sex and five had received blood products within six months before seroconversion. None reported IV or illicit drug use or receiving unscreened blood products and none of the males reported having had sex with other men. The center had no written policies about reprocessing patient access needles dialyzers or blood lines. Interviews with staff nurses however revealed that all dialyzers and blood lines were labeled appropriately and individually reprocessed with 5% formaldehyde while still attached to the machine placed in separate labeled containers and stored for reuse only on the same patient. In contrast patient access needles were reprocessed through the use of a 0.16% solution of benzalkonium chloride with the pairs of access needles for two-four patients placed unlabeled in a common soaking pan for disinfection and the disinfectant changed only every seven days. As a result of the investigation patient care equipment is no longer reprocessed at the dialysis center and HIV counseling is provided to all infected patients. Furthermore national surveillance was initiated for HIV infection among patients undergoing dialysis and the Ministry of Health has banned the use of quaternary ammonium compounds for disinfecting intravascular devices.

Mesenteric neurons in the adult rat are responsive to ileal treatment with benzalkonium chloride

The application of a 2 mM solution of the cationic surfactant benzalkonium chloride (BAC) to an ileal segment produced a selective and extensive myenteric denervation. The aim of the present study was to investigate whether such a selective unbalance of the enteric nervous system in the adult rat elicited any plastic response within the mesenteric nervous structures contacting it. Acetylcholinesterase (AChE) staining, β-nicotinamide adenine dinucleotide (NADH) and β-nicotinamide adenine dinucleotidephosphate (NADPH) diaphorase histochemistry and glyoxilic acid-induced fluorescence were performed on whole-mount preparations of myenteric plexus and mesenteric nerves. In both control and BAC-treated animals nervous elements were detected along the mesenteric nerves. Although rather similar in position, shape and size, these neurons displayed striking differences with regard to their arrangement and density per nerve. In the controls, few small aggregates of neurons could be detected; more commonly, isolated nerve cell bodies were scattered along the nerve trunks. In the BAC-treated animals, numerous spherical or spindle-shaped clusters of neurons were located along the nerves; the mean neuronal density per nerve displayed a two-five-fold increase over the control values. The observed changes within the mesenteric nerves might be involved in an attempt at reinnervation of the BAC-treated intestinal segments from extraenteric sources.

Microencapsulation of benzalkonium chloride

A method based on the interfacial polycondensation of isocyanates has been used to prepare microcapsules containing an aqueous solution of benzalkonium chloride. Since the compound to be encapsulated is amphiphilic, particular attention was paid to the formulation of a starting system for encapsulation. To this end, we investigated the influence of the hydrophilic-lipophilic balance (HLB) of both the surfactants and the oil on the initial emulsion. Our results demonstrate that designing of the formulation in accordanc with the HLB concept of Griffin ( J. Soc. Cosm. Chem., 1 (1949) 311–326) constitutes a good approach to the choice of the components of the microencapsulation system. The phase diagram constructed for a pseudo-ternary system showed that the area of the domain of the lipophilic continuous phase emulsion decreased with increasing concentration of benzalkonium chloride. This observation can be explained as being due both to the amphiphilic nature of the benzalkonium chloride and to modification of the aqueous solubility of the surfactants in its presence. The encapsulation yield of benzalkonium chloride was high (60%). The remaining 40% may either be present in the lipophilic phase or become incorporated into the shell of the microcapsules.

The Opacifying Effects of Carteolol HCl and Benzalkonium Chloride on Porcine Isolated Corneas

Porcine isolated corneas (intact, with the epithelium or endothelium plus Descemet's membrane or both epithelium and endothelium plus Descemet's membrane removed) have been incubated with solutions of carteolol HCl (5 x 10-4 M-5 x 10 2M), or solutions of benzalkonium chloride (0.005%–0.05%), or solutions of carteolol (5 x 10 4M-5 x 10 2M) plus benzalkonium chloride (0.005%). Concentration-dependent opacities developed in corneas with both compounds, but whereas the effect of carteolol seems to involve mainly the endothelium, the effect of benzalkonium seems to involve mainly the epithelium. Possible modes of action of the two compounds are discussed.

The chronological relationship between the thickening of smooth muscle, epithelial cell proliferation and myenteric neural denervation in the rat jejunum

The jejunum of rats was treated by serosal application of a 0.2% solution of benzalkonium chloride (BAC) for 30 min. Control animals were treated with saline (0.9% NaC1). The animals were allocated to eight groups of 10 rats each and sacrificed 15, 30, 45, 60 days after BAC treatment. Segments were removed from the jejunum for neuronal counting, measurement of the smooth muscle area and morphokinetic study of the epithelium. There was a significant reduction in neuron number in the myenteric plexus 30 days after BAC treatment, thickening of smooth muscle 15-60 days after BAC treatment, but no change in epithelial cell proliferation in the jejunum at either time.

Enteric neuronal ablation: Structure-activity relationship in a series of alkyldimethylbenzylammonium chlorides

Serosal application of a commerical solution of benzalkonium chloride (BAC) has been shown to selectively ablate myenteric neurons in the rat jejunum. This experimental model has proven useful in the study of the role of the myenteric plexus in intestinal function. The commercial BAC is a mixture of at least three homologous N-alkyldimethylbenzylammonium chlorides (ADBAC). The purpose of this study was to determine neuronal ablative activity in a series of ADBAC homologs when applied on the serosa of rat jejunum. Homologs not commercially available were synthesized and purified. Seven ADBAC homologs with alkyl chain lengths ranging from C6 to C18 were tested. A solution of each homolog (2 m m in saline) was applied directly on the serosa of an exteriorized portion of jejunum from anesthetized rats. Fifteen days after treatment, animals were sacrificed and treated tissues were processed for neuronal cell counts and muscle thickness determinations. All ADBAC homologs, except C18, ablated neurons of the myenteric plexus and produced thickening of intestinal smooth muscle. The number of submucosal neurons was not affected by any of the homologs. The structure-activity relationship observed in this study paralleled that of the reported antimicrobial activity of the ADBAC homologs, and is related to the aqueous solubility and relative surface activities of the homologs. The C14 homolog was found to be the most effective ablative agent, and reduced the number of myenteric neurons in a concentration-dependent manner. Thus, the C14 homolog can be used to produce a selectively denervated jejunal model for use in acute or chronic in vitro or in vivo studies of intestinal function.

The Inhibition of Granulocyte Phagocytosis by Various Components of Nasal Drops

The effect of two decongestive substances and two preservatives used in nasal drops on phagocytosis by human granulocytes was studied. The vasoactive substances oxymetazoline chloride and zylometazoline chloride incubated with human granulocytes during 20 min. gave a reduction of phagocytosis to almost zero when using concentrations found in commercially used nasal drops (500 mg/l respectively 1000 mg/l). However, a dilution of 1:100 was consistent with an almost normal phagocytic function. The preservatives benzalkonium chloride and thiomersal gave a dose related reduction of phagocytosis down to zero. A dilution of 1:100 of the benzalkonium chloride solution used commercially (200 mg/l) and a dilution of 1:10 of the thiomersal solution used commercially (24 mg/l) were needed to get an almost normal phagocytic function. These results together with previous studies indicate that the addition of preservatives in nasal drops should be questioned, excluded or replaced with other less harmful substances.

Effect of subgingival plaque control by direct irrigation technique--2. Clinical and microbiological changes after irrigation with acrinol or benzalkonium chloride solution

The aim of the study was to evaluate the effect of the subgingival plaque control by direct irrigation. Twelve adult patients with periodontal pockets of 4 mm or more received an initial treatment. The patients were followed by irrigation using the device called Pocket Irrigator PT-01 with 0.05% acrinol solution or 0.025% benzalkonium chloride solution. The clinical and microbiological parameters were recorded prior to the irrigation and immediately after, at 1 hour, 1 day and 1 week after the irrigation. The Plaque Index, Gingival Index, gingival crevicular fluid and probing depth were used as clinical parameters. Samples of the subgingival plaque were collected with sterilized paper points from the periodontal pockets. The samples were examined by dark field microscopy with the Petroff-Hauser counting chamber with a magnification of 1,500x. The total number of bacteria and the proportion of the motile rods and spirochetes of the pockets were examined. All clinical parameters showed no significant changes after the irrigation. Intracrevicular irrigation by both acrinol and benzalkonium chloride solution significantly reduced the relative number of bacteria and the percentage of spirochetes/motile rods, when compared to those before the irrigation on day 1, though the differences did not persist on day 7. Thus, only by the single irrigation of the deep pockets with acrinol or benzalkonium chloride, the beneficial effects did not appear to continue clinically and microbiologically for a week.