Negligible Irritation Research Articles

THE RISK OF SKIN IRRITATION OF CLARTÉ IN EXPERIMENTAL RABBITS

CLARTÉ is an external genital hygiene product, thus assessing skin irritation is an important test before commercializing the product for the community. Objectives: The study evaluated the local irritation on healthy rabbit skin of CLARTÉ manufactured and supplied by VIHECO PHARMA., JSC. Methods: The study was conducted according to the guidelines of the Vietnam Ministry of Health, ISO 10993-10, and OECD on skin irritation assessment for topical products. Three healthy white New Zealand rabbits were shaved off the fur on the back. Animals were applied directly 0.5 mL of CLARTÉ solution on the back skin and covered the application sites with a 2,5 cm × 2,5 cm non-occlusive dressing for 4 hours. We evaluated the irritation index including erythema and edema on the skin at 1, 24, 48, and 72 hours after removing the patches. Results: Three rabbits were still healthy, and living normally. There was very slight or well-defined erythema and very slight edema on the rabbit's skin applied by CLARTÉ after the first 24-hour treatment. The irritation index of CLARTE’ was 0.44, corresponding to negligible skin irritation during 72 hours of continuous monitoring. Conclusions: CLARTÉ product applied topically caused negligible irritation on healthy rabbit skin.

Investigating the potential of Quercetin enthused nano lipoidal system for the management of dermatitis

Objective: The present research work was undertaken to develop quercetin enthused nanolipoidal systems and its characterization. The objective was to investigate potential of prepared system in the management of DNCB induced dermatitis. Method: Nanolipoidal system was prepared in different combinations with quercetin, L-α phosphatidylcholine (SPC) and ethanol and characterized for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, percentage drug release, skin retention and skin permeation. Selected batches were further incorporated into Carbopol 934 base gel. The vesicles were in size range 324.19-359 nm while polydispersity index (PDI) ranges from 0.241-0.554 and for zeta potential, it was from -26.33 to -39.3 nm. Entrapment efficiency was from 23.77-94.68 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin up to 45.23 µm which was significantly higher than the rhodamine solution (10 µm). In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed a marked decrease in amount of inflammatory cell nucleus in mice treated with quercetin loaded ethosomal gel followed by 76.13% decrease in-ear swelling and ear mass respectively in morphology study. The conventional marketed formulation showed a nominal decrease in epidermal thickness. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Results: The optimized formulation F6 with SPC and ethanol in the ratio of 20:80 displayed the highest drug content and entrapment efficiency of 94.68±1.14%. PDI was 0.241±0.11 and skin retention 7.7%. Batch F6 with vesicle size and zeta potential of 324.9±19 nm and -26.33 mV, respectively, was incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spreadability, in vitro, ex vivo release study, and kinetics study and in vivo studies. Conclusion: The present study revealed that the developed ethosomal gel can be used for enhanced delivery of Quercetin via skin. The in vitro studies indicated that the gel serves as an efficient carrier for Quercetin. It showed its effectiveness in the management of dermatitis. Further, Quercetin loaded nanoethosomal gel formulation can be viewed as a promising drug delivery system for the management of dermatitis.

Methanol extract from the seeds of Persea americana displays antibacterial and wound healing activities in rat model

Ethnopharmacological relevancePersea americana Miller (Lauraceae) known as “pear” in Cameroon is comestible by the fruit. The leaves of the plant are traditionally used in the treatment of microbial infections, malaria, diabetes, high blood pressure, to stimulate uterine contractions and relief painful menstruations. The leaves and stem bark are also used to cure malaria and typhoid fever. Fresh pulps are used to lower cholesterol, prevents mental strain and cardiovascular diseases whilst the seeds are used against intestinal worms and skin infections. Aim of the studyThis study aimed to investigate the antibacterial activity and wound healing efficacy of methanol extract of Persea americana seed on an excision wound infected with Staphylococcus aureus using a rat model and characterise the mode of action of this extract. Materials and methodsThe antibacterial activities of the methanol extract were done against a panel of bacteria using broth microdilution method. The phytochemical analysis as well as the antioxidant activities were evaluated using colorimetric methods. The mode of action of P. americana was studied by targeting bacterial membranes, cytoplasmic contents, and the formation of biofilms. The therapeutic effect of the methanol extract was evaluated on an excision wound infected with Staphylococcus aureus. ResultsThe methanol extract of P. americana seed displayed antibacterial properties MIC varying from 64 to 128 μg/mL which can be linked to its total phenolic, flavonoid and tannin contents. The antibacterial activity of the extract is due to the bacterial biofilm inhibition and the perturbation of the bacterial membrane through the leakage of intracellular materials, the inhibition of H+-ATPases pumps. The gel based on P. americana extract showed a significant increase in the percentage of wound closure and had a significant reduction of the number of Colony Forming Units (CFU) of S. aureus at the infection site. The plant has antioxidant activity for wound healing which is lower than vitamin C. The toxicological report showed that the gel-based extract had negligible irritation on the skin and non-irritating to the eye, and therefore can be consider safe for use. ConclusionThe present study revealed the antibacterial and wound healing properties of the MEPa and could possibly be used to tackle bacterial infections.

Formulation and Optimization of Butenafine-Loaded Topical Nano Lipid Carrier-Based Gel: Characterization, Irritation Study, and Anti-Fungal Activity.

The present study aims to prepare and optimize butenafine hydrochloride NLCs formulation using solid and liquid lipid. The optimized selected BF-NLCopt was further converted into Carbopol-based gel for topical application for the treatment of fungal infection. Box Behnken design was employed to optimize the nanostructure lipids carriers (NLCs) using the lipid content (A), Tween 80 (B), and homogenization cycle (C) as formulation factors at three levels. Their effects were observed on the particle size (Y1) and entrapment efficiency (Y2). The selected formulation was converted into gel and further assessed for gel characterization, drug release, anti-fungal study, irritation study, and stability study. The solid lipid (Compritol 888 ATO), liquid lipid (Labrasol), and surfactant (tween 80) were selected based on maximum solubility. The optimization result showed a particle size of 111 nm with high entrapment efficiency of 86.35% for BF-NLCopt. The optimized BF-NLCopt converted to gel (1% w/v, Carbopol 934) and showed ideal gel evaluation results (drug content 99.45 ± 2.11, pH 6.5 ± 0.2, viscosity 519 ± 1.43 CPs). The drug release study result depicted a prolonged drug release (65.09 ± 4.37%) with high drug permeation 641.37 ± 46.59 µg (32.07 ± 2.32%) than BF conventional gel. The low value of irritation score (0.17) exhibited negligible irritation on the skin after application. The anti-fungal result showed greater efficacy than the BF gel at both time points. The overall conclusion of the results revealed NLCs-based gel of BF as an ideal delivery system to treat the fungal infection.

Ionic Network Based on Dynamic Ionic Liquids for Electronic Tattoo Application

Electronic tattoos as an emerging epidermal electronic are alluring in the field of wearable electronics for their lightweight and noninvasive properties. However, the combination of flexibility, skin biocompatibility, adhesion, repairability, and erasability remains a challenge for fabricating electronic tattoos. Hence, a dynamic ionic liquid is prepared which is ideally suited for making an electronic tattoo with these challenging features at the same time. Such an intrinsically flexible electronic tattoo can be firmly attached to human skin with negligible irritation. More importantly, the existence of dynamic covalent chemistry provides the electronic tattoo with healing and erasable abilities under mild redox conditions. Owing to the high ionic conductivity of ionic liquids, the electronic tattoo exhibits excellent sensing performance in response to the temperature variation and tensile strain, which can intelligently monitor body temperature, pulse, and movement. As an extension of the application, a specially designed quadrilateral electronic tattoo can sense and distinguish multiple signals simultaneously. This concept of electronic tattoo based on the dynamic ionic liquid shows great potentials in the applications of intelligent wearable electronics.

Berberine Chloride Dihydrate Enthused Nanovesicles for the Management of Dermatitis Nanovesicles for Dermatitis

Background: Dermatitis is a common inflammatory skin disease that is affecting up to 25% of children and 1%-3% of adults worldwide. The paucity of the exact cure for dermatitis and untoward side effects of topical immunosuppressive steroids, has resulted in a great need for making use of complementary medicine to treat dermatitis. Objective: The present research work involved the development of Berberine chloride dihydrate (BCD) enthused nanovesicles i.e. ethosomes for the management of dermatitis. Method: Ethosomes were prepared by slight modification of cold method using varying concentrations of SPC (1-3%) and ethanol (10-40%) Optimized batch BCD 12 was further added to Carbopol 934P for gel formation. GEL BCD 12 was subjected to “anti-bacterial, dermatitis and skin irritation study. Result: The vesicles were in size range 142.42-398.31 nm while polydispersity index (PDI) ranges from 0.114-1.56 and for zeta potential it was from-18.8 to -39.4. Entrapment efficiency was from 46.05-88.79 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin upto 110 µm which was significantly higher than rhodamine solution (10 µm). In the anti-bacterial study, BCD loaded ethosomal gel (EG) showed maximum zone of inhibition of 18.5 mm against E. coli, 14.5 mm against P. aeruginosa and 23.0 mm against S. aureus. In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed marked decrease in amount of inflammatory cell nucleus in mice treated with BCD loaded ethosomal gel followed by 56% and 50 % increase in ear swelling and ear mass respectively in morphology study. Conventional marketed formulation showed nominal decrease in epidermal thickness, 66.67 % increase in ear thickness and 63.64 % increase in ear mass. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Conclusion: It can be concluded that ethosomal gel is not only an efficient carrier for BCD but also proves its potential for the management of dermatitis.

A sustained release cysteamine microsphere/thermoresponsive gel eyedrop for corneal cystinosis improves drug stability.

Cystinosis is a rare, metabolic, recessive genetic disease in which the intralysosomal accumulation of cystine leads to system wide organ and tissue damage. In the eye, cystine accumulates in the cornea as corneal cystine crystals and severely impacts vision. Corneal cystine crystals are treated with cysteamine eyedrops when administrated 6 to 12 times day and used within 1 week. The strict dosing regimen and poor stability are inconvenient and add to the burden of therapy. To reduce the dosing frequency and improve the stability, we present reformulation of cysteamine into a novel controlled release eyedrop. In this work, we characterize and evaluate a topical drug delivery system comprised of encapsulated cysteamine in polymer microspheres with a thermoresponsive gel carrier. Spray-dried encapsulation of cysteamine was performed. In vitro cysteamine release, stability, and ocular irritation and corneal permeation were evaluated. The data suggest that encapsulated cysteamine improves the stability to 7 weeks when compared with 1-week aqueous cysteamine eyedrops. Release studies from one drop of our system show that cysteamine release was present for 24h and above the minimum cysteamine eyedrop amount (6 drops). Cysteamine from our system also resulted in negligible irritation and enhanced permeation when compared with traditional cysteamine eyedrops. In vivo studies were implemented to support ease of administration, tolerability, and retention for 24h. These studies suggest that our controlled releasedelivery system may provide stable cysteamine from a safe, once daily gel eyedrop.

Formulation and evaluation of butenafine loaded PLGA-nanoparticulate laden chitosan nano gel

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BT-NPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection.

The effect of variation of tetrahydropentagamavunon-0 concentration in lotion and emulgel formula toward acute dermal irritation study.

ABSTRACTTetrahydropentagamavunon-0 (THPGV-0) is a curcumin metabolite analog which known has a higher antioxidant activity than Vitamin E. This compound has been formulated in lotion as antiaging cosmetics, but the irritation effect is unknown yet. This study aims to analyze the effect of variation of THPGV-0 concentration in lotion and emulgel formula toward acute dermal irritation. The concentrations of THPGV-0 varied to 0.1%, 0.2%, and 0.4% in lotion/emulgel and tested for their physical properties such as organoleptic, homogeneity, pH, spreadability, and adhesion. Acute dermal irritation test is done in accordance with the In vivo Nonclinical Toxicity Test Guidelines by the Indonesian Food and Drug Administration (BPOM). This study showed that Primary Irritation Index (PII) value concentrations of 0.1%, 0.2%, and 0.4% THPGV-0 in lotion formula are 0.014, 0.014, and 0.028 (close to 0) and in emulgel formula are 0.08 at concentration of 0.1%, 0.33 at concentration of 0.2%, and 0.25 at concentration of 0.4%. PII of 0.1%, 0.2%, and 0.4% THPGV-0 in lotion and emulgel is included in negligible irritation response. Hence, the both of THPGV-0 formula in lotion and emulgel are considered safe to use on skin according to this study.

Facile skin targeting of a thalidomide analog containing benzyl chloride moiety alleviates experimental psoriasis via the suppression of MAPK/NF-κB/AP-1 phosphorylation in keratinocytes

BackgroundThalidomide can be a TNF-α inhibitor for treating skin inflammation. This drug exhibits a strong toxicity that limits its application. ObjectiveWe synthesized a thalidomide analog containing the benzyl chloride group (2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione, CDI) to examine anti-inflammatory activity against psoriasis. MethodsThe evaluation was conducted by the experimental platforms of in vitro TNF-α- or imiquimod (IMQ)-stimulated HaCaT cells and in vivo IMQ-induced psoriasiform plaque. ResultsUsing the in vitro keratinocyte model, we demonstrated a greater inhibition of IL-1β, IL-6, and IL-24 by CDI than by thalidomide. No significant cytotoxicity was observed at 100 μM. CDI delivered facilely into the skin with a cutaneous targeting ability 228-fold greater than thalidomide. CDI caused a negligible irritation on healthy mouse skin. We showed that topically applied CDI reduced IMQ-induced red scaly lesions, hyperplasia, microabscesses, and cytokine expression in the mouse model. The skin-barrier function measured by transepidermal water loss (TEWL) could be partially recovered from 50.6–36.3 g/m2/h by CDI. The mechanistic study showed that CDI suppressed cytokine production by inhibiting the phosphorylation of NF-κB and AP-1 via MAPK pathways. ConclusionCDI would be beneficial for the development of a therapeutic agent against psoriasis.

In-Vivo Effectiveness of 5% Azadirachta indica Oil Cream as Anti-Scabies

Scabies is an infectious skin disease caused by mite Sarcoptes scabiei. Neem tree (Azadirachta indica) has the potential to be used as an anti-parasite due to the presence of azadirachtin compound that is commonly found in the seeds. The aim of this study was to evaluate in-vivo effectiveness of neem oil as an anti-scabies. This study used an experimental method. The effectiveness of the cream as an anti-scabies was tested on New Zealand white rabbits which were infected with scabies. Permethrin cream was used as a positive control and cream base was used as a negative control. Cream was applied once daily and left for 8 hours. The data were analyzed using Kruskal Wallis and Mann Whitney. Dermal acute irritation test was performed by applying 0.5 g cream on the rabbit dorsal. We found that 5% neem oil cream was effective as an anti-scabies with 20-21 days recovery time. The recovery time is longer than permethrin cream (7-8 days), but shorter compared to negative control with recovery time over 30 days. Primary irritation index for 5% neem oil creams was 0, indicating negligible irritation category. In conclusion, A. indica cream was effective for the treatment of scabies although its recovery time is shorter than permethrin cream. Keywords: effectiveness test, irritation test, neem oil cream, scabies

Ocular Drug Delivery System-An Update Review

Eye being a unique and complex organ the access of exogenous substances to the ocular tissues are restricted by its physiology and defense mechanism. Thus the delivery of therapeutic agents to the ocular tissues is not an easy assignment. Cornea an important component present in eye is protected by very effective protective mechanisms which provide the pharmaceutical scientists a challenge of designing a formulation and delivering it to the targeted sites in sufficient concentrations. Development of newer approaches and novel therapeutic agents continue to provide delivery system a high therapeutic efficacy. Due to the defects in the traditional treatment, and also the therapeutic drug levels in targeted site is not maintained for longer time, the search of new type of ophthalmic approaches and technologies has drawn more and more attentions. In past two decades research in ocular delivery system have been accelerated towards a novel, safe and patient compliance formulation and medical devices to surpass the barriers and maintain the therapeutic level in tissues. Recently various technologies with good efficacy and biocompatibility have also been developed to treat the ocular diseases at both the anterior and posterior portion of eye. Anterior segment approaches for ocular treatment, advances are witnessed through the modulation of conventional topical drops with permeation enhancers and it also includes the development as ointments, gels etc. Several nano-formulations are also introduced for treating the anterior portion of the eye. Furthermore for posterior delivery, research focused immensely towards the development of releasing devices and also nano-formulation. Therefore these novel approaches and devices are easy to formulate, possess negligible irritation, prolonged precorneal residence time, sustained drug release, and enhanced bioavailability. An update of research advancement in ocular drug delivery provides and helps the scientists to modulate and develop safe drug delivery strategies. This review article gives update information about various approaches for delivering the drug to ocular region.

Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte-derived chemokine expression and neutrophil infiltration.

Psoriasis is an inflammatory autoimmune skin disorder possessing a complex etiology related to genetic and environmental triggers. Keratinocytes show a potential role for the origin of psoriasis. In this study, we estimated the efficiency of 2 anthranilate derivatives-(E)-4-( N-{2-[1-(hydroxyimino)ethyl]phenyl}sulfamoyl)phenyl pivalate (HFP031) and butyl 2-[2-(2-fluorophenyl)acetamido]benzoate (HFP034)-on psoriasis amelioration in a mouse model. The results showed that topical treatment with both compounds could attenuate epidermal thickness and scaling in an imiquimod (IMQ)-induced psoriasis mouse model via decreased expression of cytokines and chemokines [C-X-C chemokine ligand (CXCL)1 and CXCL2], leading to the reduction of neutrophilic abscess in the skin. The in vivo cutaneous absorption of HFP034 was 7.6-fold greater than that of HFP031. Both compounds caused negligible irritation on healthy mouse skin. In addition, we examined the effect of the anthranilate derivatives on chemokine expression in IMQ-treated HaCaT keratinocytes. Our results elucidated a mechanism for anti-inflammatory activity of HFP034 that involved the elevation of intracellular cAMP concentration, suppression of NF-κB activity, and attenuation of neutrophil chemoattractant expression. These results suggest that HFP034 could increase the cutaneous concentration of cAMP to suppress neutrophil infiltration into the skin. Topically applied HFP034 may demonstrate a potential for future clinical application as a novel therapy for psoriasis treatment.-Lin, Z.-C., Hsieh, P.-W., Hwang, T.-L., Chen, C.-Y., Sung, C. T., Fang, J.-Y. Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte-derived chemokine expression and neutrophil infiltration.

The physicochemical, safety and antimicrobial properties of Phyllanthus amarus herbal cream and ointment

The ethanol extract of Phyllanthus amarus (Schum and Thonn), a plant of ethnomedicinal importance, was formulated into herbal cream and ointment and evaluated using physicochemical, safety and antimicrobial properties. The extract was obtained by maceration and the antimicrobial properties tested on clinically isolated pathogenic bacteria (Staphylococcus aureus and Pseudomonas aeruginosa) and dermatophytes (Trichophyton rubrum and Candidaalbicans) using established methods. Cream and ointment formulations containing 1–10 % w/w extract was prepared and 4 % w/w humectant (glycerin) was incorporated into the cream while 5 % w/w surfactant (cetomacrogol 1000) was incorporated to the ointment. The results showed that the pH of the formulations was acidic and the viscosity ranged from 1250 to 4950 cP for ointments and 570–1233 cP for creams. The presence of humectant and surfactant significantly (p < 0.05) reduced the viscosities of the formulations. The results of dermal irritation showed negligible irritation index while sub-chronic toxicity tests showed that the formulations did not cause any visible lesions in the skin of the animals after application for twenty-one days. The in vitro antimicrobial properties of formulations were concentration-dependent with the creams showing higher activity. Furthermore, the in vivo activity of the cream on S. aureus showed increased antibacterial activity with increase in extract concentration and humectant presence. The herbal cream and ointment of Phyllanthus amarus extract had acceptable physicochemical and safety profiles with significant (p < 0.05) in vitro and in vivo antimicrobial activity. Thus, the formulations could be useful in the treatment of skin infections instead of using the extract for bathing and rubbing.

Safety of daily ethanol locks for urinary catheters in critically ill children: A pilot study

Catheter-associated urinary tract infections represent a significant medical burden in critically ill children. Ethanol locks have been shown to be effective and safe for central line-associated bloodstream infection prevention and we propose utilizing this strategy for urinary catheters. Because this has never been done, we evaluated its safety with a pilot study hypothesizing that ethanol locks in urinary catheters would result in negligible alcohol absorption and negligible irritation of the bladder.

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.

Essential Oils from Sweet Basil (Ocimum basilicum) as Novel Enhancers to Accelerate Transdermal Drug Delivery

The purpose of this study was to evaluate the essential oils from sweet basil (Ocimum basilicum, OB) as skin permeation enhancers to promote the percutaneous absorption of drugs. The in vitro and in vivo irritancy of the essential oils was also examined. Terpenes with various carbon numbers (mono-, sesqui-, di-, and tri-) were identified in both the lower-polarity fraction (OB-1) and higher-polarity fraction (OB-2). In vitro skin permeation and deposition of indomethacin were significantly enhanced after treatment with OB essential oils. The enhancing effect of OB-1 was greater than that of OB-2 in the in vitro permeation and in vivo cutaneous microdialysis analyses as well as in the plasma concentration of indomethacin. On the other hand, the in vivo study showed that OB-2 had a greater ability to retain the drug within the skin than did OB-1. Enhancement of the skin permeation of drugs by OB essential oils might be mainly due to improvement in the partitioning of the drugs to the stratum corneum. Both in vitro cell cultures (keratinocytes and skin fibroblasts) and in vivo transepidermal water loss showed no or only negligible irritation to skin by OB essential oils.

Dextranase および Monofluorophosphate 配合歯磨剤のウサギおよびハムスターに対する局所刺激性について

Experiment was done as to irritation on rabbit skin, eye and cheek pouch of hamster by applying three different types of toothpaste;1. Toothpaste which was mixed Dextranase 10, 000u/g & Monofluorophosphate 1, 000p.p.m(F), 2. Toothpaste which was only contained Monofluorophosphate, 3. And which was contained none of each.1. Evaluation score by Draize Method was ranged between 0.5-0.67 of each toothpaste as to irritation on the rabbit skin.Same evaluation score was ranged between 0.83-1.00 as to pinching method to the rabbit skin by means of injection needle, inflammation by which was induced disappeared within 72 hours.2. No responce was observed as to either cornea or iris on the irritation to the eye due to Draize Method from each of three types of toothpaste.Only slight responce was, however, noticed on the conjunctiva, which disappeared within 72 hours.3. No abnormality was observed as to either optic or histological observation on mucous membrane, connective tissue beneath, and muscle layer of hamster cheek pouch by trree types of toothpastes.Conclusion was drawn that irritation induced on skin, eye and oral membrane was extremely slight by toothpaste either of which mixed Dextranase 10, 000u/g or Monofluorophosphate 1, 000p.p.m.It was not observed accebrated effect on irritation out of toothpaste which was even mixed both components up, which stayed within the range of irritation of ordinal toothpaste.It was also obrerved that ordinall toothpaste had negligible irritation in contrast to the standard level of Draize Method.

Treatment of condyloma acuminatum with peltatins.

PODOPHYLLOTOXIN 1 quercetin, 2 α-peltatin, 3 and β-peltatin 4 are crystalline compounds in podophyllin. We contended previously 5 that podophyllotoxin was the component responsible for involution of condyloma acuminatum. When α- and β-peltatin became available, 6 32 patients were treated (Table 1). Satisfactory results necessitate including these substances as effective agents against moist genital warts. The clinical response to the topically applied peltatins was identical with that described in detail for podophyllin and podophyllotoxin 7 except that the peltatins produced negligible irritation to circumjacent normal tissue. Microscopic examination of involuting warts at 24 and 48 hours showed changes 7 identical with those