RESUMO
BACKGROUND: Cosmetic care products contain a high proportion of water and nutrients. Therefore, preventing bacterial growth is an important issue to ensure product quality and safety. The application of antibacterial natural ingredients derived from plants is considered to have the potential to maintain product quality and reduce the use of chemicals in formulations. Additionally, chemically synthesized antiseptic and antibacterial agents are widely used in the industry at present. However, some preservative ingredients have been reported that may cause skin irritation, redness, allergies, and even dermatitis. AIMS: This study aimed to prepare extract from Camellia oleifera tea seed dregs (CTSD), investigate the antibacterial effects on two pathogenic bacteria and evaluate the product preservative ability. METHODS: Ethanol extraction was prepared and subjected to characterize their triterpenoid contents. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) were determined for Pseudomonas aeruginosa and Staphylococcus aureus. The product's stability and preservative qualities, along with its ability to scavenge free radicals through antioxidant activity, were also assessed. RESULTS: The gram-positive S. aureus showed greater susceptibility to the treatment. In additional, CTSD possessed significant free radical scavenging activity in vitro and cultured normal human skin fibroblast CCD-966SK cells under nontoxic concentration. The challenge test and accelerated storage test confirmed the CTSD containing formulated emulsion is eligible for commercialization. CONCLUSIONS: CTSD has the potential to be developed as an alternative agent to control microbial biofilm formation, or can be used as an adjuvant compound for infectious disease control.
Assuntos
Camellia , Cosméticos , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Sementes/química , Conservantes Farmacêuticos/farmacologia , Cosméticos/farmacologia , Biofilmes , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Testes de Sensibilidade MicrobianaRESUMO
AIMS: The cosmetic industry needs new preservatives that are effective, natural, safe, cost effective, sustainable and compliant with regulatory standards. This necessity has posed challenges requiring obligations, bioinformatics and bioinspiration as driving forces. METHODS AND RESULTS: Twenty natural extracts were selected from the Greenpharma Database with parameter filters corresponding to development constraints and antimicrobial properties. We confirmed using minimum inhibition concentration (MIC) assays that eight of the extracts have good bactericidal properties and that one has a high antifungal activity. The latter was purified hinokitiol, a bioproduct from Aomori Hiba wood. This substance provides high resistance against putrefaction; for instance, old Japanese temples were made of Aomori Hiba wood. The combination of hinokitiol with levulinic acid, another bioproduct, demonstrated complementary antimicrobial activities and synergistic effects in MIC studies and measurements according to Kull synergy index. Further, the mixture Hinoline® was tested at 2% in challenge tests and fulfilled criteria A of different standards. It also exerted complementary preservative effects with potassium sorbate and beneficial effects in unbalanced skin microbiota. CONCLUSION: Hinoline, a new effective preservative from renewable bioresources, was developed. SIGNIFICANCE AND IMPACT OF THE STUDY: This study accelerates the development of a preservative solution for cosmetics selected from Greenpharma Database, through bioinspiration and the identification of cost-effective investments and resources.
Assuntos
Anti-Infecciosos , Cosméticos , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Conservantes Farmacêuticos/farmacologia , Ácido SórbicoRESUMO
Marine resources exist in vast numbers and show enormous diversity. As a result, there are likely many possible applications for marine molecules of interest in the cosmetic industry, whether as excipients or additives, but especially as active substances. It is possible to obtain extracts from active substances; for example, quite a few algae species can be used in moisturizing or anti-ageing products. In the field of topical photoprotection, mycosporine-like amino acids and gadusol are important lines of enquiry that should not be overlooked. In the field of additives, the demonstration that certain seaweed (algae) extracts have antimicrobial properties suggests that they could provide alternatives to currently authorized preservatives. These promising leads must be explored, but it should be kept in mind that it is a long process to bring ingredients to market that are both effective and safe to use.
Assuntos
Organismos Aquáticos/química , Cosméticos/farmacologia , Extratos Vegetais/farmacologia , Alga Marinha/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Cosméticos/química , Cosméticos/isolamento & purificação , Humanos , Excipientes Farmacêuticos/química , Excipientes Farmacêuticos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Conservantes Farmacêuticos/química , Conservantes Farmacêuticos/isolamento & purificação , Conservantes Farmacêuticos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
This study aimed at investigating the antimicrobial activity of different solvent extracts of Chinese cabbage Brassica rapa subsp. pekinensis (BRARP) and their antioxidant and cytotoxicity properties. Of the different solvents extracts, the chloroform extracts (CE) were significantly inhibited the bacterial pathogens at minimum inhibitory concentration (MIC) of 16.5 mg.mL-1. Biochemical analysis revealed that total phenol (62.6 ± 0.05 mg GAE.g-1) and flavonoids (27.6 ± 0.04 mg QE.g-1) were higher in the extracts of BRARP, which resulted in enhanced antioxidant activity in CE. A total of eight dominant compounds were detected in the potent antimicrobial extract from BRARP based on GC-MS analysis. The molecular interactions study revealed that, among the screened compounds the 1,2-benzenedicarboxylic acid and 2,3-dicyanopropionamide interacted with the active site of pathogenicity and survival related protein with lipopolysaccharide (LpxC) with higer binding energy. This work concluded that the 1, 2-Benzenedicarboxylic acid and 2, 3-Dicyanopropionamide from BRARP was reported to be good non-cytotoxic and antioxidant antimicrobials against bacterial pathogens.
Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Brassica rapa/química , Extratos Vegetais/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Flavonoides/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Fenóis/química , Extratos Vegetais/química , Conservantes Farmacêuticos/química , Conservantes Farmacêuticos/farmacologiaRESUMO
AIMS: The aim of this work was to evaluate the efficacy and safety of Lippia origanoides essential oil as a preservative in industrial products. METHODS AND RESULTS: The composition, antimicrobial activity, mutagenic and toxic potential of L. origanoides were determined. Then, the effect of essential oil as a preservative in food, cosmetics and pharmaceutical products was evaluated. The essential oil of L. origanoides consisted mainly of oxygenated monoterpenes (38·13%); 26·28% corresponded to the compound carvacrol. At concentrations ranging from 0·312 to 1·25 µl ml-1 and in association with polysorbate 80, the essential oil of L. origanoides inhibited the growth of all the tested micro-organisms. The medium lethal dose in mice was 3·5 g kg-1 , which categorizes it as nontoxic according to the European Union criteria, and negative results in the Ames test indicated that this oil was not mutagenic. In combination with polysorbate 80, the essential oil exerted preservative action on orange juice, cosmetic and pharmaceutical compositions, especially in the case of aqueous-based products. CONCLUSIONS: Lippia origanoides essential oil is an effective and safe preservative for orange juice, pharmaceutical and cosmetic products. SIGNIFICANCE AND IMPACT OF THE STUDY: This study allowed for the complete understanding of the antimicrobial action and toxicological potential of L. origanoides essential oil. These results facilitate the development of a preservative system based on L. origanoides essential oil.
Assuntos
Cosméticos , Conservantes de Alimentos/farmacologia , Lippia/química , Óleos Voláteis/farmacologia , Conservantes Farmacêuticos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Cimenos , Conservantes de Alimentos/química , Conservantes de Alimentos/toxicidade , Camundongos , Monoterpenos/química , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Excipientes Farmacêuticos/química , Excipientes Farmacêuticos/farmacologia , Excipientes Farmacêuticos/toxicidade , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Óleos de Plantas/toxicidade , Conservantes Farmacêuticos/química , Conservantes Farmacêuticos/toxicidadeRESUMO
For high-throughput screening of novel cosmetic preservatives, a rapid and simple assay to evaluate the antimicrobial activities should be developed because the conventional agar dilution method is time-consuming and labor-intensive. To address this issue, we evaluated a microbial sensor as a tool for rapid antimicrobial activity testing. The sensor consists of an oxygen electrode and a filter membrane that holds the test microorganisms, Staphylococcus aureus and Candida albicans. The antimicrobial activity of the tested cosmetic preservative was evaluated by measuring the current increases corresponding to the decreases in oxygen consumption in the microbial respiration. The current increases detected by the sensor showed positive correlation to the concentrations of two commercially used preservatives, chlorphenesin and 2-phenoxyethanol. The same tendency was also observed when a model cosmetic product was used as a preservative solvent, indicating the feasibility in practical use. Furthermore, the microbial sensor and microfluidic flow-cell was assembled to achieve sequential measurements. The sensor system presented in this study could be useful in large-scale screening experiments.
Assuntos
Anti-Infecciosos/farmacologia , Técnicas Biossensoriais/métodos , Cosméticos , Avaliação Pré-Clínica de Medicamentos/métodos , Conservantes Farmacêuticos/farmacologia , Candida albicans/efeitos dos fármacos , Clorfenesina/farmacologia , Eletricidade , Eletrodos/microbiologia , Etilenoglicóis/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided.
Assuntos
Antibacterianos/farmacologia , Cinnamomum zeylanicum , Cosméticos , Contaminação de Medicamentos/prevenção & controle , Conservantes de Alimentos/farmacologia , Doenças Transmitidas por Alimentos/prevenção & controle , Extratos Vegetais/farmacologia , Conservantes Farmacêuticos/farmacologia , Animais , Antibacterianos/efeitos adversos , Antibacterianos/isolamento & purificação , Cinnamomum zeylanicum/química , Qualidade de Produtos para o Consumidor , Microbiologia de Alimentos , Conservantes de Alimentos/efeitos adversos , Conservantes de Alimentos/isolamento & purificação , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Conservantes Farmacêuticos/efeitos adversos , Conservantes Farmacêuticos/isolamento & purificação , Medição de RiscoRESUMO
Aqueous hypromellose gels are not microbiologically stable - they show signs of microorganism growth during storage. To extend the shelf-life of the gels, antimicrobial preservatives are needed. Some substances of plant origin are known for their antimicrobial properties, and thus they may be used as an alternative to synthetic preservatives. Therefore, the aim of this study was to evaluate the microbiological stability of aqueous hypromellose gel and the effectiveness of natural substances - grapefruit seed extract (GSE), concentrated cranberry juice, and a combination thereof - on the antimicrobial protection of the gel. The evaluation of the antimicrobial activity of GSE and cranberry juice showed that their antimicrobial effects differed. Both cranberry juice and GSE inhibited the growth of the standard gram-positive and gram-negative bacteria, but the effect of GSE was significantly stronger. Candida albicans was sensitive only to GSE. For this reason, in order to affect all the microorganisms studied, either a combination of 0.7% GSE and 10% cranberry juice, or 5% GSE alone may be used. The combination of GSE and cranberry juice was effective only in acidic medium (pH being 2.5-5), while the antimicrobial effect of GSE was not dependent on the pH value.
Assuntos
Anti-Infecciosos/farmacologia , Citrus paradisi/química , Conservantes Farmacêuticos/farmacologia , Vaccinium macrocarpon/química , Candida albicans/efeitos dos fármacos , Géis , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Derivados da Hipromelose/química , Extratos Vegetais/farmacologia , SementesRESUMO
Cosmetic multidose preparations, as well as pharmaceutical ones, are at risk of contamination by microorganisms, due to their high water content. Besides the risk of contamination during manufacturing, multidose cosmetic preparations may be contaminated by consumers during their use. In this paper, the results of the utilization of nanoparticles as reservoir systems of parabens, the most used class of preservatives, were reported. Two different systems, solid lipid nanoparticles (SLN) made of pure precirol and nanostructured lipid carriers (NLC) made of precirol and almond oil, containing three parabens as single molecules or as a mixture, were prepared and tested. All the systems were characterized for size, polydispersion index, zeta potential and encapsulation efficiency. Release experiments, carried out in steady state and sink conditions, allowed to evidence that both SLN and NLC were able to act as reservoir systems. The antimicrobial activity of the systems was tested against Candida albicans ATCC 10231 with repeat insult tests. The results of the release experiments and the antimicrobial tests showed very low water concentration of parabens still maintaining their antimicrobial activity.
Assuntos
Diglicerídeos/química , Portadores de Fármacos , Contaminação de Medicamentos/prevenção & controle , Nanopartículas , Parabenos/química , Óleos de Plantas/química , Conservantes Farmacêuticos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Química Farmacêutica , Preparações de Ação Retardada , Cinética , Testes de Sensibilidade Microbiana , Parabenos/farmacologia , Tamanho da Partícula , Polietilenoglicóis/química , Conservantes Farmacêuticos/farmacologia , Colato de Sódio/química , Solubilidade , Tecnologia Farmacêutica/métodos , Água/químicaRESUMO
The chemical composition, antimicrobial activity, total phenol content, total antioxidant activity, and total oxidant status of the essential oil from Micromeria congesta Boiss. & Hausskn. ex Boiss. were investigated. Steam distillation was used to obtain the essential oil, and the chemical analyses were performed by gas chromatography-mass spectrometry. The antimicrobial activity was tested by an agar disc diffusion method against the tested microorganisms: Bacillus subtilis NRRL B-744, Bacillus cereus NRRL B-3711, Staphylococcus aureus ATCC 12598, S. aureus ATCC 25923, S. aureus ATCC 25933, Escherichia coli 0157H7, E. coli ATCC25922, Micrococcus luteus NRLL B-4375, Enterococcus faecalis ATCC 19433, Proteus vulgaris RSKK 96026, and Yersinia enterecolitica RSKK 1501. The major compounds found in volatiles of M. congesta were piperitone oxide, linalool oxide, veratrole, pulegone, dihydro carvone, naphthalene, iso-menthone, para-menthone, and cyclohexanone. Compared to that of reference antibiotics, the antibacterial activity of the essential oil is considered as significant. Results showed that M. congesta has the potential for being used in food and medicine depending on its antioxidant and antibacterial activity.
Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Lamiaceae/química , Óleos Voláteis/farmacologia , Componentes Aéreos da Planta/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bacillales/efeitos dos fármacos , Bacillales/crescimento & desenvolvimento , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Etnofarmacologia , Conservantes de Alimentos/química , Conservantes de Alimentos/isolamento & purificação , Conservantes de Alimentos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Hidrocarbonetos Cíclicos/análise , Lamiaceae/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Fenóis/análise , Componentes Aéreos da Planta/crescimento & desenvolvimento , Conservantes Farmacêuticos/química , Conservantes Farmacêuticos/isolamento & purificação , Conservantes Farmacêuticos/farmacologia , Terpenos/análise , TurquiaRESUMO
BACKGROUND: Although in vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Despite the conflicting evidence, BAK is the most commonly used preservative in ophthalmic products largely due to its proven antimicrobial efficacy. This study was designed to characterize the antimicrobial performance of two commonly used topical ocular hypotensive agents that employ different preservative systems: latanoprost 0.005% with 0.02% BAK and travoprost 0.004% with sofZia, a proprietary ionic buffer system. METHODS: Each product was tested for antimicrobial effectiveness by European Pharmacopoeia A (EP-A) standards, the most stringent standards of the three major compendia, which specify two early sampling time points (6 and 24 hours) not required by the United States Pharmacopeia or Japanese Pharmacopoeia. Aliquots were inoculated with between 10(5) and 10(6) colony-forming units of the test organisms: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis. Sampling and enumeration were conducted at protocol-defined time points through 28 days. RESULTS: BAK-containing latanoprost met EP-A criteria by immediately reducing all bacterial challenge organisms to the test sensitivity and fungal challenges within the first six hours while the preservative activity of travoprost with sofZia did not. Complete bacterial reduction by travoprost with sofZia was not shown until seven days into the test, and fungal reduction never exceeded the requisite 2 logs during the 28-day test. Travoprost with sofZia also did not meet EP-B criteria due to its limited effectiveness against Staphylococcus aureus. Both products satisfied United States and Japanese pharmacopoeial criteria. CONCLUSIONS: Latanoprost with 0.02% BAK exhibited more effective microbial protection than travoprost with sofZia using rates of microbial reduction, time to no recovery for all challenges and evaluation against EP-A criteria as measures. The rapid and complete reduction of all microbial challenges demonstrates that antimicrobial activity of latanoprost with 0.02% BAK exceeds that of travoprost with sofZia preservative system in these products and provides a more protective environment in the event of contamination and subsequent exposure to microorganisms during use.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Benzalcônio/farmacologia , Cloprostenol/análogos & derivados , Fungos/efeitos dos fármacos , Soluções Oftálmicas/farmacologia , Conservantes Farmacêuticos/farmacologia , Prostaglandinas F Sintéticas/farmacologia , Anti-Hipertensivos/farmacologia , Cloprostenol/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Latanoprosta , Células-Tronco/efeitos dos fármacos , TravoprostRESUMO
This work aimed to test if milk preserved with bronopol can be reliably used for fatty acid determination. Dairy production and milk quality are often monitored regularly to assess performance and contribute to selection indices. With evidence that fat composition can be influenced by selective breeding, there might be an interest in using samples collected in routine testing to evaluate individual cow fatty acid profiles, contributing to breeding indices. However, most recording services use a preservative such as bronopol and there is no published record if this influences subsequent fatty acid analysis. This study used milk from an oil seed supplementation trial, generating a wide range of milk fatty acid profiles, to test if the concentration of 31 individual fatty acids determined by GC were influenced by bronopol. Provided preserved samples are subsequently frozen, milk treated with bronopol can reliably be used to evaluate fatty acid composition in most cases; however bronopol might influence a few long-chain fatty acids present in relatively low concentrations. This is one small step towards simplifying milk compositional analysis but it could ultimately streamline the inclusion of milk fat quality into breeding indices, either with a view to 'healthier' milk or potentially reducing methane output and the environmental impact of dairy production.
Assuntos
Ácidos Graxos/química , Leite/química , Conservantes Farmacêuticos/farmacologia , Propilenoglicóis/farmacologia , Animais , Bovinos , Feminino , Manejo de EspécimesRESUMO
AIMS: The aim of the study was to verify the antimicrobial activity of commercial essential oils: lavender, tea tree and lemon as the components of a preservative system in oil in water body milks. METHODS AND RESULTS: The inhibition efficacy of essential oils alone (0.5%), in mixtures (1%) as well as combined with the synthetic preservative 1,3-dimethylol-5,5-dimethylhydantoin and a 3-iodo-2-propynyl butyl carbamate mixture (0.1% and 0.2%) was tested against Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Candida sp. LOCK 0008 and Aspergillus niger ATCC 16404 in compliance with the standards of the European Pharmacopoeia Commission. The in vitro activity of oils determined by an impedimetric method was also compared with their activity in cosmetic preparations. Criterion A for bacteria (reduction in the inoculum by 3 logarithmic units within 7 days with no increase up to the 28th day) and fungi (reduction in the inoculum by 2 logarithmic units within 14 days with no increase up to the 28th day) was fulfilled for cosmetic formulations containing the tested essential oils with 0.2% of the synthetic preservative. The preservative concentration could be decreased to 0.1% (with preserving the same efficacy) in combination with lavender and tea tree oils at a concentration of 0.5% each. CONCLUSIONS: In all combinations of essential oils with the synthetic preservative, a synergistic effect of the preservative system components was observed, which made it possible to reduce the usable level of the synthetic preservative up to 8.5 times. SIGNIFICANCE AND IMPACT OF THE STUDY: To develop an effective preservative system in cosmetics in which a synthetic chemical preservative is replaced by natural essential oils.
Assuntos
Anti-Infecciosos/farmacologia , Cosméticos/química , Lavandula/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Óleo de Melaleuca/farmacologia , Aspergillus niger/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Carbamatos/farmacologia , Hidantoínas/farmacologia , Conservantes Farmacêuticos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Nasal spray products containing desmopressin acetate (DDAVP) were tested in vitro to evaluate the effect of the contained preservatives on drug permeation across rabbit nasal mucosa. Experiments were performed using Franz-type diffusion cells with rabbit nasal mucosa as model barrier. Transport profiles obtained in comparison with a preservative-free solution evidenced that in the presence of preservatives DDAVP permeation in vitro always increased (p<0.05), although at different extents (chlorobutanolAssuntos
Desamino Arginina Vasopressina/administração & dosagem
, Desamino Arginina Vasopressina/farmacocinética
, Mucosa Nasal/efeitos dos fármacos
, Mucosa Nasal/metabolismo
, Conservantes Farmacêuticos/farmacologia
, Ácido Sórbico/farmacologia
, Adjuvantes Farmacêuticos/farmacologia
, Administração Intranasal
, Animais
, Compostos de Benzalcônio/química
, Clorobutanol/química
, Difusão/efeitos dos fármacos
, Técnicas In Vitro
, Permeabilidade/efeitos dos fármacos
, Coelhos
, Equivalência Terapêutica
RESUMO
BACKGROUND: Parabens are widely used preservatives in cosmetics and pharmaceutical products, and approved as food additives. Parabens have been considered safe for these uses for many years. Recently, adverse effects on male reproductive parameters in rats have been reported when parabens were given orally for 8 weeks starting at three weeks of age. Our studies used two representative parabens, methyl- and butylparaben, to try to replicate these studies and thereby evaluate potential reproductive effects in male Wistar rats. METHODS: Diets containing 0, 100, 1000 or 10,000 ppm of either butyl- or methylparaben were fed to male rats for eight weeks. Rats were 22 days of age at the start of exposure. Parameters evaluated included organ weights, histopathology of reproductive tissues, sperm production, motility, morphology and reproductive hormone levels (butylparaben only). RESULTS: None of the parameters evaluated for either paraben showed compound- or dosage-dependent adverse effects. Metabolism experiments of butylparaben indicate that it is rapidly metabolized by non-specific esterases to p-hydroxybenzoic acid and butanol, neither of which is estrogenic. CONCLUSIONS: Exposure to methyl- or butylparaben in the diet for eight weeks did not affect any male reproductive organs or parameters at exposures as high as 10,000 ppm, corresponding to a mean daily dose of 1,141.1+/-58.9 or 1,087.6+/-67.8 mg/kg/day for methyl- and butylparaben, respectively. The rapid metabolism of parabens by esterases probably explains why these weakly estrogenic substances elicit no in vivo effects when administered by relevant exposure routes (i.e., topical and oral).
Assuntos
Genitália Masculina/efeitos dos fármacos , Parabenos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Genitália Masculina/anatomia & histologia , Genitália Masculina/fisiologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Parabenos/farmacocinética , Conservantes Farmacêuticos/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Antimicrobial efficacy of methyl and propylparaben combination as potential preservatives for submicron emulsions, and the effect of oil and lecithin concentration on the microbial growth were investigated. Parabens were ineffective in standard or doubled concentrations as per pharmacopoeial criteria. Poor growth inhibition and multiplication of reference strains point to protective and growth properties of submicron emulsions. No correlation was observed between oil/lecithin ratio and efficacy of parabens; partitioning of the latter into the oily phase and lipophilic domains could be the reason for such effect. Further studies are necessary to establish a stable and safe composition of such formulations.
Assuntos
Parabenos/farmacologia , Conservantes Farmacêuticos/farmacologia , Anti-Infecciosos/farmacologia , Fenômenos Químicos , Físico-Química , Emulsões , Lecitinas/química , Óleo de Soja/químicaRESUMO
A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.
Assuntos
Anticonvulsivantes/farmacologia , Química Farmacêutica/estatística & dados numéricos , Bases de Dados Factuais , Parabenos/farmacologia , Conservantes Farmacêuticos/farmacologia , Animais , Anticonvulsivantes/química , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Eletrochoque , Conservantes de Alimentos/química , Conservantes de Alimentos/farmacologia , Camundongos , Estrutura Molecular , Parabenos/química , Conservantes Farmacêuticos/química , Relação Quantitativa Estrutura-Atividade , Convulsões/tratamento farmacológico , Convulsões/etiologiaRESUMO
Thimerosal, also known as thimersal, Merthrolate, or sodiumethyl-mercurithiosalicylate, is an organic mercurial compound that is used in a variety of commercial as well as biomedical applications. As a preservative, it is used in a number of vaccines and pharmaceutical products. Its active ingredient is ethylmercury. Both inorganic and organic mercurials are known to interfere with glutamate homeostasis. Brain glutamate is removed mainly by astrocytes from the extracellular fluid via high-affinity astroglial Na+-dependent excitatory amino acid transporters, glutamate/ aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1). The effects of thimerosal on glutamate homeostasis have yet to be determined. As a first step in this process, we examined the effects of thimerosal on the transport of [3H]-d-aspartate, a nonmetabolizable glutamate analog, in Chinese hamster ovary (CHO) cells transfected with two glutamate transporter subtypes, GLAST (EAAT1) and GLT-1 (EAAT2). Additionally, studies were undertaken to determine the effects of thimerosal on mRNA and protein levels of these transporters. The results indicate that thimerosal treatment caused significant but selective changes in both glutamate transporter mRNA and protein expression in CHO cells. Thimerosal-mediated inhibition of glutamate transport in the CHO-K1 cell line DdB7 was more pronounced in the GLT-1-transfected cells compared with the GLAST- transfected cells. These studies suggest that thimerosal accumulation in the central nervous system might contribute to dysregulation of glutamate homeostasis.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/genética , Compostos de Etilmercúrio/farmacologia , Transportador 2 de Aminoácido Excitatório/genética , Ácido Glutâmico/farmacocinética , Timerosal/farmacologia , Animais , Transporte Biológico , Northern Blotting , Western Blotting , Encéfalo/metabolismo , Células CHO , Linhagem Celular , Sistema Nervoso Central/efeitos dos fármacos , Cricetinae , DNA Complementar/metabolismo , Técnicas In Vitro , Conservantes Farmacêuticos/farmacologia , RNA Mensageiro/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
OBJECTIVE: To investigate the effects of latanoprost, timolol maleate, and benzalkonium chloride on cell damage and induction of the secretion of chemical mediators of stress and wound healing by human lens epithelial cells in culture. METHODS: Cells from a human lens epithelial cell line (SRA01/04) were cultured in Dulbecco minimum essential medium supplemented with 5% fetal bovine serum. The amounts of latanoprost (50 micro g/mL), timolol maleate (5 mg/mL), or benzalkonium chloride (200 micro g/mL) used in eyedrops, and x10 to x1000 dilutions thereof, were added to the medium. After 7 days' culture, cell morphological changes were assessed using phase-contrast microscopy, and cell-free culture supernatants were collected for prostaglandin E2 (PGE2), interleukin 1alpha (IL-1alpha), and interleukin 6 (IL-6) iodine I 125 radioimmunoassay, enzyme-linked immunosorbent assay, and chemiluminescent enzyme immunoassay, respectively. RESULTS: All cells that were cultured with the concentrations of latanoprost, timolol, or benzalkonium chloride used in eyedrops detached from the culture dish and died within 3 days. At a x10 dilution of latanoprost or timolol or a x100 dilution of benzalkonium chloride, no proliferation or elongation of the cells was observed. Secretions of PGE2, IL-1alpha, and IL-6 at x10 dilutions of latanoprost or timolol were 3 to 77 times higher than in controls, whereas they were 190 to 305 times higher at a x180 dilution of benzalkonium chloride. The amounts of these soluble mediators in culture supernatants depended on the dose of latanoprost, timolol, or benzalkonium chloride added. CONCLUSION: Our results indicate that benzalkonium chloride, used as the preservative in eyedrops containing latanoprost or timolol, is the agent most damaging to lens epithelial cells and most strongly stimulates the expression of soluble chemical mediators in these cells.
Assuntos
Anti-Hipertensivos/farmacologia , Dinoprostona/biossíntese , Células Epiteliais/efeitos dos fármacos , Interleucina-1/biossíntese , Interleucina-6/biossíntese , Cristalino/citologia , Conservantes Farmacêuticos/farmacologia , Compostos de Benzalcônio/farmacologia , Linhagem Celular Transformada , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Latanoprosta , Microscopia de Contraste de Fase , Prostaglandinas F Sintéticas/farmacologia , Radioimunoensaio , Timolol/farmacologiaRESUMO
AIMS: This study was focused on the preserving properties of Calamintha officinalis essential oil, a plant known for its diaphoretic, expectorant and aromatic properties. METHODS AND RESULTS: The commercial aerial parts of C. officinalis Moench were hydrodistilled and the essential oil analysed by Gas chromatography/Electron impact mass spectrometry (GC/EIMS). The inhibition efficacy of this essence, alone (0.5 and 1.0% v/v) and in combination with 2.0 mM EDTA, was assayed, in culture medium and in cetomacrogol cream, using preservative efficacy testing against standard microrganisms (E. coli ATCC 25922, Ps. aeruginosa ATCC 9027, Staph. aureus ATCC 6538P, C. albicans ATCC 10231 and A. niger ATCC 16404). C. officinalis essential oil in cetomacrogol cream with EDTA showed long-lasting antimicrobial activity, satisfying the European Pharmacopoeia Commission (E. P.) criteria. CONCLUSION: C. officinalis essential oil could have a potential for a future use as a cosmetic preservative. IMPACT OF THE STUDY: To find natural compounds with antimicrobial activity which could be alternatives to the synthetic chemical preservatives.