• Journal of Pharmaceutical Investigation
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• 제25권4호
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• pp.353-363
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• 1995

The purpose of this study was to investigate the intestinal and nasal absorption enhancement of cefotaxime (CTX) by ion-pairing with counterions and to design an effective oral and intranasal drug delivery system for antibiotics. Counterions for absorption promotion were cationic surfactants [cetylpyridinium chloride (CP), cetrimide (CT) and benzalkonium chloride (BA)]. In the presence of counterions, the apparent partition coefficient of cefotaxime was increased depending on the molar concentration of the counterions. Anion interference was observed for ion-pairing of cefotaxime with counterions because of the counterbalance between an anion and counterions. The present study employed the in situ simultaneous nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of cefotaxime were $1.43{\pm}0.04{\times}10^{-5}\;cm/sec(mean{\pm}S.E)$ in the nasal cavity and 0 in the jejunum, respectively, which indicated that the intrinsic absorptivity of cefotaxime was greater in the nasal cavity than in the jejunum. When ionupairing formers were used, the decreasing order of apparent cefotaxime permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was as followings: $BA\;(7.50{\pm}0.36)\;>\;CT\;(4.92{\pm}0.24)\;>\;CP\;(3.01{\pm}0.17)$ in the jejunum and $BA\;(22.31{\pm}1.36)\;>\;CP\;(18.24{\pm}0.81)\;>\;CT \;(16.22{\pm}1.87)$ in the nasal cavity. The increase in permeability of cefotaxime was about 13-fold in the rat nasal cavity and was marked in the rat jejunum for ion-pairing with counterions as compared to those without ion-pairing. The damages of jejunal and nasal mucosal membrane by counterions were observed within approximately 2hrs after removal of ion-pair of cefotaxime with counterions from the nasal cavity and jejunum. These results suggest that CP can be used as an ion-pairing former in the jejunum and CP and CT can be used as ion-pairing formers in the nasal cavity for cefotaxime, as well as for poorly absorbed drugs with a negative charge due to ionization.

• 한국환경보건학회지
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• 제48권3호
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• pp.183-194
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• 2022

Background: No study has examined the regulatory factors associated with fatal health problems due to the use of humidified disinfectants (HD) in South Korea. Objectives: This study aimed to identify and discuss the deficiencies and limitations found in the Toxic Chemical Control Acts (TCCA) that failed to prevent the health risk of chemicals in HD products. Methods: The South Korean TCCA was reviewed focusing on acts in operation from 1994 through the end of 2011, the period when HD was allowed in manufacturing and marketing. Results: The TCCA was the act intended to regulate the toxicity of chemicals in HD products. We found the TCCA to lack three key legal clauses which would have been essential to controlling the health risk of HD. First, there was the exemption of toxic and hazard testing for existing chemicals, including chloromethylisothiazolinone (CMIT), methylisothiazolinone (MIT), and benzalkonium chloride (BKC). Secondly, there were no articles requiring industry to provide animal inhalation test result for polymers such as polyhexamethylene guanidine (PHMG) and Oligo(2-)ethoxyethoxyethyl guanidine chloride (PGH). Finally, there was a lack of articles on examining the risk of products as well as on addressing changes in the usage of products. These articles were found to be generally provided in the US Toxic Substance Chemical Act (TSCA) and the EU Registration, Evaluation and Authorization of Chemicals (REACH). Conclusions: In conclusion, the Ministry of Environment of South Korea had not updated key articles for regulating hazardous chemicals, causing large-scale health problems due to HD which had been fundamentally addressed in chemical-related acts in other countries.

• 한국환경보건학회지
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• 제46권4호
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• pp.470-479
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• 2020

Objectives: The Coronavirus Disease 2019 (COVID-19) pandemic has caused the death of 740,000 people around the world as of August 12, 2020. Foot-and-Mouth Disease, Avian Influenza, and African Swine Fever are serious livestock diseases. Government agencies in Korea have provided ingredient information and usage instructions for disinfectants used to counter those infectious diseases. The purpose of this study was to provide information on the chemical ingredients in disinfectant products used against COVID-19 and certain livestock diseases. Methods: We collected information from the Korean government. The Central Disaster Management Headquarters and Central Disease Control Headquarters provided information on disinfectant products used against COVID-19. The Animal and Plant Quarantine Agency of Korea provided information on efficacy-certified disinfectant products for use against selected livestock diseases. Health hazard and environmental hazard information on the ingredients in the disinfectants was collected from the Korea Occupational Safety & Health Agency's Material Safety Data Sheets, and toxicity value information was collected from United States Environmental Protection Agency's CompTox Chemicals Dashboard. Results: There were 76 COVID-19 disinfectant products in use, and the most common ingredients were benzalkonium chloride (51%), alkylbenzyl dimethyl ammonium (30%), and ethanol (3%). There were 216 livestock disease disinfectant products comprised of 89 acidic, 88 oxidic, 30 aldehydic, three alkaline, and six other products. Among the 49 active ingredients used in the disinfectants that were investigated, health and environmental hazard information was provided for many of them, but only 20 chemicals had official toxicological information. Conclusion: Since the disinfectants included numerous chemicals, an understanding of their chemical characteristics could be critical to prevent unintended human or environmental exposure.

• 한국환경보건학회지
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• 제46권5호
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• pp.481-494
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• 2020

Objectives: No study has been conducted to review characteristics of humidifier disinfectants (HD) products, such as real numbers, levels and types of HD substances contained, or the volume marketed. We aimed to review the characteristics of HD through a literature review. Methods: We collected literature reporting the names, numbers, and ingredients of HD and discussed them with a focus on the number of HD products and the chemicals used as a disinfectant. Results: A total of eight publications has reported the names of HD brands or types of disinfectants from 2011 to 2020. To date, a total of 40 HD products have been used, excluding four products. Eight HD products used polyhexamethylene guanidine phosphate (PHMG) and 14 used a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) as disinfectants. Benzalkonium chloride (BKC) and sodium dichloroisocyanurate (NaDCC) were also used as a disinfectant in several HD products. A total of 19 HD products were associated with the development of HD associated lung injury (HDLI). The Oxy Saksak HD product containing PHMG showed the highest number of HD associated health effects. The type of disinfectant from a total of 14 HD products has not been identified. Conclusions: A total of 40 HD products have been marketed in South Korea since 1994. Further studies should be conducted to identify the association of product characteristics, including type of HD ingredients, with health effects.

• 한국식품과학회지
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• 제39권1호
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• pp.104-107
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• 2007

유통식품에서 분리한 E. coli 및 S. aureus의 차아염소산나트륨과 염화벤잘코늄에 대한 감수성을 현탁액시험법으로 청정조건과 오염조건에서 각각 조사한 결과 차아염소산나트륨의 오염조건에서 S. aureus가 5 log 감소의 살균소독력이 나타나지 않았을 뿐, 모든 균주가 사용범위 내에서 살균소독력을 나타내었으며, 항생제 내성균과 감수성균에 대한 살균소독제 감수성의 차이는 발견되지 않았다(p>0.05).

• 대한치과의사협회지
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• 제22권9호통권184호
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• pp.793-801
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• 1984

Though oral microgranisms were among the first to be observed by humans, the interest in oral microbiology lagged. When it became apparent that the oral microflora did influence systemic disease of the body, interest was aroused in the nature and kinds of the microgranisms. The risk of infection in dental procedures is due to the abundant flora of the mouth. This hazard can be reduced to some extent by the use of a local disinfectant. The present studies were undertaken to evaluate and compare the various disinfectants which are commonly used in clinics and hospitals. The results were as follows. 1. The bactericidal activity of the disinfectants mainly depends upon the kinds of the agents, not upon the kinds of the microorganisms. 2. In H₂O₂(3%), the bactericidal activity was greatly related to the contact time. So, at least 4 minitues of contract time was required to use it as an oral antiseptic. 3. In ethyl alcohol (70%), Pseudomonas aeruginosa and Streptococcus salivarius surived a little after 15 seconds of contact time, but, no other colony was discovered after more than 15 seconds of contact time in any kins of microorganisms. 4. Merthiolate (0.1%) showed low antibacterial activity, more in Gram-positive organisms and less in Gram-negative organisms. 5. Benzalkonium chloride (0.1%) and povidone-iodine (10%) showed the most excellent results, revealing no surviving organisms only after 14 seconds of contact time.

• Journal of Microbiology and Biotechnology
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• 제33권6호
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• pp.771-779
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• 2023

Biofilms are a significant concern in the food industry. The utilization of plant-derived compounds to inactivate biofilms on food contact surfaces has not been widely reported. Also, the increasing negative perception of consumers against synthetic sanitizers has encouraged the hunt for natural compounds as alternatives. Therefore, in this study we evaluated the antimicrobial activities of ethanol extracts, acetone extracts, and essential oils (EOs) of seven culinary herbs against Salmonella enterica serotype Typhimurium and Listeria innocua using the broth microdilution assay. Among all tested extracts and EOs, the ethanol extract of Piper betle L. exhibited the most efficient antimicrobial activities. To evaluate the biofilm inactivation effect, S. Typhimurium and L. innocua biofilms on pitted and smooth stainless steel (SS) coupons were exposed to P. betle ethanol extract (12.5 mg/ml), sodium hypochlorite (NaClO; 200 ppm), hydrogen peroxide (HP; 1100 ppm), and benzalkonium chloride (BKC; 400 ppm) for 15 min. Results showed that, for the untreated controls, higher sessile cell counts were observed on pitted SS versus smooth SS coupons. Overall, biofilm inactivation efficacies of the tested sanitizers followed the trend of P. betle extract ≥ BKC > NaClO > HP. The surface condition of SS did not affect the biofilm inactivation effect of each tested sanitizer. The contact angle results revealed P. betle ethanol extract could increase the surface wettability of SS coupons. This research suggests P. betle extract might be utilized as an alternative sanitizer in food processing facilities.

• 한국식품위생안전성학회지
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• 제28권3호
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• pp.227-233
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• 2013

신선편의 샐러드와 유기농 채소에 오염되어 있는 식중독균인 B. cereus, S. aureus 그리고 E. coli를 대상으로 살균소독제와 유기산에 대한 감수성을 평가하여 신선편의 식품의 미생물학적 안전성의 확보를 위한 올바른 세척제와 사용량을 제시하고자 하였다. S. aureus는 2% acetic acid, malic acid, tartaric acid와 1% CaO에 대하여 고농도의 염소계, 과산화수소계 보다 높은 살균 효과를 보였고 E. coli의 경우에는 1% acetic acid와 CaO처리에 의해 80%의 분리주가 감소하여 50% 에탄올과 400 ppm 차아염소산나트륨과 대등한 감소율을 보였다. B. cereus 분리주에 대한 1% CaO, 0.5% acetic acid, 2% malic acid와 tartaric acid 처리는 200 ppm의 차아염소산나트륨보다 높은 감소율을 나타내었고, 1%의 과산화수소와 대등한 감소율을 나타내었다. 본 연구에 따라 천연 물질 유래 살균 소독제인 CaO와 유기산은 기존의 화학적 살균제를 대체할 수 있는 천연 살균 소독제로 활용될 수 있을 것이고 특히 환경 친화적이고 안전한 유기산은 고품질의 신선편의 채소를 안전성으로 공급하는데 효과적인 것으로 판단되었다.

• Biomolecules & Therapeutics
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• 제10권2호
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• pp.104-113
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• 2002

The effects of enzyme inhibitors and penetration enhancers on the permeation of leucine enkephalin (Leu-Enk) and its synthetic analog, [${D-ala}^2$]-leucine enkephalinamide (YAGFL) across the nasal, rectal and vaginal mucosae were evaluated. Enzyme inhibitors and penetration enhancers employed for Leu-Enk permeation study were amastatin(AM), thimerosal(TM) and ethylenediaminetetraacetic acid disodium salt(EDTA), and sodium taurodihydrofusidate (STDHF). Those for YAGFL permeation study were TM, benzalkonium chloride(BC) and EDTA, and STDHF, sodium deoxycholate(SDC), sodium glycholate(SGC), glycyrrhizic acid ammonium salt (GAA), L-$\alpha$-Iysophosphatidylcholine(LPC) and mixed micelle (MM, STDHF: linoleic acid = 15 mM : 5 mM). The addition of TM alone on the donor and receptor solutions for Leu-Enk permeation study across all the three kinds of mucosae failed to inhibit the degradation; it completely degraded in 6 hrs, and no permeation occurred. However, with addition of three kinds of inhibitors together, the fluxes across nasal, rectal and vaginal mucosae were $\20.7{pm}2.5$>/TEX>,$\0.3{pm}0.05$>/TEX> and $\1.4{pm}0.5$ $\mu$\mid$textrm{m}$/$\textrm{cm}^2$/hr, respectively. Moreover, the addition of STDHF in the presence of the above three inhibitors enhanced permeation across nasal, rectal and vaginal mucosae 1.3, 15 and 1.3 times, respectively. YhGFL also degraded in the donor and receptor solutions rapidly as time went. With mixed inhibitors of TM and EDTA, the percents of YAGFL remaining in the donor solutions facing nasal, rectal and vaginal mucosae were 69.7, 69.8 and 79.8%, respectively; the percent permeated increased to 10, 2.1 and 5.7%, respectively. The addition of STDHF in the presence of either BC/EDTA or TW/EDTA increased the permeation 2.2, 11.0 and 2.9 times, and 2.21, 14.0 and 2.7 times for nasal, rectal and vaginal mucosae, respectively. With SDC, SGC, GAA, LPC ud MM in the presence of TM/EDTA increased permeation; especially, they increased permeation across vaginal mucosae effectively, and the enhancement factors were 12.5, 7.6, 8.7, 5.7 and 5.5, respectively. The degradation extent of YAGFL was correlated with protein concentrations in the epidermal and serosal extracts. The flux of YAGFL across nasal mucosa increased dose-dependently.

• Journal of Pharmaceutical Investigation
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• 제26권3호
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• pp.175-185
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• 1996

To inhibit the enzymatic degradation of leucine enkephalin (Leu-Enk) and its synthetic analog. $[D-ala^2]$-leucine enkephalinamide (YAGFL), in the nasal, rectal and vaginal mucosal and serosal extracts of rabbits, effects of enzyme inhibitors such as amastatin (AM), puromycin (PM), thiorphan (TP), thimerosal (TM), EDTA, N-carboxymethyl-Phe-Leu (CPL), phenylethyl alcohol (PEA), phenylmercuric acetate (PMA), benzalkonium chloride (BC) and modified cyclodextrins, alone or in combination, were observed by assaying the pentapeptides staying intact during incubation. Mucosa extracts were prepared by exposing freshly-excised mucosal specimens mounted on Valia-Chien cells to isotonic phosphate buffer while stirring. The degradation of Leu-Enk and YAGFL followed the apparent first-order kinetics. The half-lives (mean) in the nasal, rectal and vaginal mucosal extracts were found to be 1.07, 0.33 and 1.14 hr for Leu-Enk, and 16.9, 6.2 and 6.8 hr for YAGFL, respectively. AM or PM, which is an aminopeptidase inhibitor, did not show a sufficient inhibition of Leu-Enk $(50\;{\mu}g/ml)$ degradation in all kinds of extracts. $Dimethyl-{\beta}-cyclodextrin\;(DM-{\beta}-CyD)$ decreased the degradation rate constants of Leu-Enk about 2 or 3 times, comparing with no additive. However, the use of mixed inhibitors of AM $(50\;{\mu}M)$/TM (0.25 mM)/EDTA (5 mM) resulted in a full stabilization of Leu-Enk by decreasing the degradation rate constants 67.3, 161.3 and 113.8 times far the nasal, rectal and vaginal mucosal extracts, respectively, comparing with no inhibitor. With mixed inhibitors, Leu-Enk remained intact more than 90% after 6 hr-incubation. In the stabilization of YAGFL, hM, TP or CPL alone showed little efffct, and some additives demonstrated a considerable inhibition of YAGFL degradation in the rank order of TM > BC > EDTA. However, the addition of mixed inhibitors such as TM (0.5 mM) and EDTA (5 mM) into the extracts protected YAGFL from the degradation by more than 85% even after 24 hr-incubation, suggesting almost complete inhibition of YAGFL degradation in the extract. On the other hand, $DM-{\beta}-CyD\;or\;hydroxypropyl-{\beta}-cyclodextrin$ (10%) were also found to retard enzymatic degradation rates of YAGFL markedly, and resulted in staying intact more than 80% of YAGFL in the nasal and vaginal mucosal extracts, and more than 60% in the rectal mucosal extract after 16 hr-incubation.