Home About us Contact
|
Home About us Contact | ||
|
|
||
Skin Irritation Potential (skin + irritation_potential)
Selected AbstractsIn vivo Skin Irritation Potential of a Castanea sativa (Chestnut) Leaf Extract, a Putative Natural Antioxidant for Topical ApplicationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2008Isabel F. Almeida However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40°. The IC50 found for the iron chelation and DPPH scavenging assays were 132.94 ± 9.72 and 12.58 ± 0.54 µg/ml (mean ± S.E.M.), respectively. The total phenolic content was found to be 283.8 ± 8.74 mg GAE/g extract (mean ± S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application. [source] Oak leaf extract as topical antioxidant: Free radical scavenging and iron chelating activities and in vivo skin irritation potentialBIOFACTORS, Issue 4 2008Isabel F. Almeida Abstract The topical application of antioxidants may be beneficial for the protection of the skin against UV damage. An extract of Quercus robur leaves was prepared and evaluated considering its putative application as topical antioxidant. The solvent and extractive method selection was monitored by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron chelating activity and the phenolic composition (HPLC/DAD) were assessed on the extract obtained under optimized conditions. Skin irritation potential was investigated by performing an in vivo patch test in 19 volunteers. The extraction solvent which resulted in the highest activity was ethanol:water (4:6) and thus it was selected for further preparation of this extract. The IC50a for the iron chelation and DPPH scavenging assays were 153.8 ± 26.3 ,g.mL,1 and 7.53 ± 0.71 ,g.mL,1 (mean ± SD), respectively. The total phenolic content was found to be 346.3 ± 6.7 mg gallic acid equivalents (GAE)/g extract (mean ± SD). Three phenolic compounds were identified in the extract namely: ellagic acid, rutin and hyperoside. The major identified component was ellagic acid. The patch test carried out showed that the extract can be regarded as safe for topical application. [source] Determination of skin irritation potential in the human 4-h patch testCONTACT DERMATITIS, Issue 1 2004David A. Basketter Recently adopted legislation in Europe has increased the focus that must be placed on the development of in vitro alternatives to the traditional toxicology tests employed to identify the human health hazards associated with chemicals. Included in these is the rabbit skin-irritation test which is used to discriminate those substances which possess significant acute skin irritation potential from those which are of more limited irritation potential. So far, the considerable efforts to replace this assay with in vitro alternatives have not been successful, which may in part be due to the relatively poor quality of the existing in vivo dataset. To help address this problem, we have elected to present our complete database of information on the skin irritation potential of some 65 substances, all of which have been tested in a standard human 4-h patch test. These provide a high quality dataset, generated in man (the goal of toxicologists' health protection-related activities). The data are presented in the context of results with a concurrent positive skin irritation control to ensure that results from individual experiments can be correlated. Consequently, in vitro or in silico alternatives which can identify the significant acute human skin irritants in this group may well represent suitable alternatives to the rabbit. [source] Validity and ethics of the human 4-h patch test as an alternative method to assess acute skin irritation potentialCONTACT DERMATITIS, Issue 1 2001Michael K. Robinson For more than 50 years, the Draize rabbit skin irritation test has reigned supreme as the regulatory method of choice for the identification of skin irritant chemicals. To date no in vitro alternative test has been validated as an adequate replacement. However, one potential option, to test the endpoint of concern (skin irritation) in the species of concern (man) has been overlooked. The advent of predictive in vitro tools for the identification of substances corrosive to the skin has opened up the practical possibility of carrying out safe and ethical studies on small panels of humans. The human 4-h patch test has been developed to meet the needs of identifying chemical skin irritation potential, providing data which is inherently superior to that given by a surrogate model, such as the rabbit. This paper reviews in detail the present state of the human 4-h patch test, highlighting its advantages and noting its utility as the ,gold standard' on which to build future in vitro models. [source] Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopeciaDRUG DEVELOPMENT RESEARCH, Issue 3 2003Allen L Seligson Abstract Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3-amino-2-hydroxy-2-methyl- N -(4-nitro-3-trifluoromethyl)phenyl) propanamide (BP-34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 ,M decreased expression of the AR in LNCaP human cells by 95%, its serum half-life was 6 h; it decomposes hydrolytically to BP-34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270,300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double-blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP-34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292,306, 2003. © 2003 Wiley-Liss, Inc. [source] Acrylate terpolymer in fabrication of medicated skin patchesPOLYMERS FOR ADVANCED TECHNOLOGIES, Issue 8 2001Vibha S. Mare Abstract An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug-in-adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2-Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by 1H-NMR, FT-IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick-up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP-1 (K,=,24.892 mcg/cm2/hr) followed zero-order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K,=,17.413 mcg/cm2/hr). TP-1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25,°C or below. Copyright © 2001 John Wiley & Sons, Ltd. [source] Oak leaf extract as topical antioxidant: Free radical scavenging and iron chelating activities and in vivo skin irritation potentialBIOFACTORS, Issue 4 2008Isabel F. Almeida Abstract The topical application of antioxidants may be beneficial for the protection of the skin against UV damage. An extract of Quercus robur leaves was prepared and evaluated considering its putative application as topical antioxidant. The solvent and extractive method selection was monitored by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron chelating activity and the phenolic composition (HPLC/DAD) were assessed on the extract obtained under optimized conditions. Skin irritation potential was investigated by performing an in vivo patch test in 19 volunteers. The extraction solvent which resulted in the highest activity was ethanol:water (4:6) and thus it was selected for further preparation of this extract. The IC50a for the iron chelation and DPPH scavenging assays were 153.8 ± 26.3 ,g.mL,1 and 7.53 ± 0.71 ,g.mL,1 (mean ± SD), respectively. The total phenolic content was found to be 346.3 ± 6.7 mg gallic acid equivalents (GAE)/g extract (mean ± SD). Three phenolic compounds were identified in the extract namely: ellagic acid, rutin and hyperoside. The major identified component was ellagic acid. The patch test carried out showed that the extract can be regarded as safe for topical application. [source] Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2004Sunil Thomas Kumar Narishetty Abstract The objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm,2 h,1, which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||