Research & Studies

Ethnopharmacological relevance: Cedrus deodara (Roxb.) Loud. is used in Ayurvedic medicine to treat peptic ulcer. AIM OF THE STUDY: To evaluate the gastric antisecretory and antiulcer activity of Cedrus deodara. MATERIALS AND METHODS: The volatile oil extracted by steam distillation of Cedrus deodara wood was examined for its gastric antisecretory and antiulcer effect in the pylorus-ligated rat model and ethanol induced gastric lesions in rats. RESULTS: The volatile oil showed significant antisecretory activity as evidenced by decreased gastric fluid volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. Our studies also revealed that pretreatment with Cedrus deodara significantly reduced the number of ulcer, ulcer score and ulcer index in pylorus-ligated and ethanol treated rats. The antiulcer activity of Cedrus deodara is further supported by histopathological study which showed protection of mucosal layer from ulceration and inflammation. CONCLUSION: The present findings conclude that volatile oil of Cedrus deodara wood has potent antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Aidance does not test on animals and did not conduct this study. It is referenced as scientific evidence of the effectiveness of ingredients in our products. Studies on the anti-inflammatory and analgesic activity of Cedrus deodara (Roxb.) Loud. wood oil. Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ, Saraf MN. J Ethnopharmacol. 1999 Apr;65(1):21-7. The volatile oil extracted by steam distillation of the wood of Cedrus deodara was examined for its oral anti-inflammatory and analgesic activity at the doses of 50 and 100 mg/kg body weight. It produced significant inhibition of carrageenan-induced rat paw edema and of both exudative-proliferative and chronic phases of inflammation in adjuvant arthritic rats at doses of 50 and 100 mg/kg body weight. The oil at both tested doses was found to possess analgesic activity against acetic acid-induced writhing and hot plate reaction in mice.

A study of tinea versicolor organisms was conducted in one patient by scanning electron microscopy. Morphologic changes in the organisms during treatment with topical clotrimazole and miconazole nitrate consisted of initial wrinkling of the surface, followed by fragmentation. These changes may have reflected cell wall alterations resulting from inhibited ergosterol synthesis induced by both treatment agents. The two drugs were effective in eliminating the organisms.

Formulation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery. Hashem FM, Shaker DS, Ghorab MK, Nasr M, Ismail A. AAPS PharmSciTech. 2011 Sep;12(3):879-86. Epub 2011 Jul 2. The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.

Antimicrobial activity of topical skin pharmaceuticals - an in vitro study. Alsterholm M, Karami N, Faergemann J. Acta Derm Venereol. 2010 May;90(3):239-45. The aim of this study was to investigate the antimicrobial activity of currently available topical skin pharmaceuticals against Candida albicans, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The agar dilution assay was used to determine the minimal inhibitory concentration for cream formulations and their active substances. Corticosteroid formulations with the antiseptics clioquinol or halquinol were active against all microbes. The hydrogen peroxide formulation was primarily active against staphylococci. Clotrimazole, miconazole and econazole showed an effect against staphylococci in addition to their effect on C. albicans. In contrast, terbinafine had no antibacterial effect. Fusidic acid was active against staphylococci, with slightly weaker activity against S. pyogenes and no activity against C. albicans or E. coli. In summary, some topical skin pharmaceuticals have broad antimicrobial activity in vitro, clioquinol and halquinol being the most diverse. In limited superficial skin infection topical treatment can be an alternative to systemic antibiotics and should be considered. With the global threat of multi-resistant bacteria there is a need for new, topical, non-resistance-promoting, antimicrobial preparations for the treatment of skin infections.

Of the ingredients in this study, Aidance products contain clotrimazole only. Comparative evaluation of effectivity and safety of topical amorolfine and clotrimazole in the treatment of tinea corporis. Banerjee M, Ghosh AK, Basak S, Das KD, Gangopadhyay DN. Indian J Dermatol. 2011 Nov;56(6):657-62. BACKGROUND: Tinea corporis is a common superficial dermatophytosis seen in tropical countries. Newer molecules are constantly being introduced for its treatment. Topical clotrimazole is in vogue as the treatment for this condition for a long time. Amorolfine is a comparatively recently introduced drug for topical use in this condition. AIMS: To assess the effectivity and safety of amorolfine 0.25% cream in patients with tinea corporis, in comparison to clotrimazole 1% cream. MATERIALS AND METHODS: Patients presenting with symptoms of tinea corporis were mycologically confirmed for the presence of fungal hyphae. They were randomly divided into two groups: one group received amorolfine and the other received clotrimazole. Treatment duration was for 4 weeks and study duration was for 8 weeks. Evaluation was carried out using the standard clinical parameters on day 1, day 14, day 28 and a follow-up on day 56. Adverse effects were also recorded. Data entry was done in Excel datasheet and analyzed with Epiinfo 2002. Chi-square test and t-test were used according to the type of data. RESULTS: The patients of the two groups were matched at baseline in respect to their demographic profile. Analysis of collected data showed significant improvement in both the groups, suggesting that both the drugs were effective agents in tinea corporis infection. Between-groups comparison of mycological cure rate and clinical improvement showed no significant difference. CONCLUSION: Amorolfine 0.25% cream is found to be safe and effective, like clotrimazole, when used topically in tinea corporis.

The essential oil extracted from the dried flower buds of clove, Eugenia caryophyllata L. Merr. & Perry (Myrtaceae), is used as a topical application to relieve pain and to promote healing and also finds use in the fragrance and flavouring industries. The main constituents of the essential oil are phenylpropanoids such as carvacrol, thymol, eugenol and cinnamaldehyde. The biological activity of Eugenia caryophyllata has been investigated on several microorganisms and parasites, including pathogenic bacteria, Herpes simplex and hepatitis C viruses. In addition to its antimicrobial, antioxidant, antifungal and antiviral activity, clove essential oil possesses antiinflammatory, cytotoxic, insect repellent and anaesthetic properties. This short review addresses the chemical composition and biological effects of clove essential oil, and includes new results from GC/MS analysis and a study of its antimicrobial activity against a large number of multi-resistant Staphylococcus epidermidis isolated from dialysis biomaterials. (c) 2007 John Wiley & Sons, Ltd.

Jadhav BK, Khandelwal KR, Ketkar AR, Pisal SS. Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Dev Ind Pharm. 2004 Feb;30(2):195-203. PubMed PMID: 15089054. Eugenol is the principle chemical constituent of clove oil and has been used to cure dental problems for ages. Eugenol is an integral part of the dentist's kit due to its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects. It is used in the form of a paste or mixture as dental cement, filler, and restorative material. This study reports the development and evaluation of controlled-release mucoadhesive tablets for gingival application, containing eugenol, which are prepared by taking carbopol 934 P and Hydroxypropyl methylcellulose (HPMC) K4M in the ratio of 1:2, 1:1, and 2:1. Incorporation of eugenol (10 mg) in a mucoadhesive formulation provides controlled release for a period of 8 hours, which is advantageous over conventional use. In vitro mucoadhesion measured as detachment force in grams and the formulations show good correlation in vivo. The release study indicates that increase in carbopol increases the release rate of eugenol from the formulation whereas HPMC retards it. Increased in vitro bioadhesion is related to HPMC content of the formulation. The release kinetics of eugenol in vitro correlates with the in vivo results. This indicates the increased potential of eugenol as antibacterial, local analgesic, and anaesthetic treatment.

Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. Pinto E, Vale-Silva L, Cavaleiro C, Salgueiro L. J Med Microbiol. 2009 Nov;58(Pt 11):1454-62. Epub 2009 Jul 9. The composition and antifungal activity of clove essential oil (EO), obtained from Syzygium aromaticum, were studied. Clove oil was obtained commercially and analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3 %). MICs, determined according to Clinical and Laboratory Standards Institute protocols, and minimum fungicidal concentration were used to evaluate the antifungal activity of the clove oil and its main component, eugenol, against Candida, Aspergillus and dermatophyte clinical and American Type Culture Collection strains. The EO and eugenol showed inhibitory activity against all the tested strains. To clarify its mechanism of action on yeasts and filamentous fungi, flow cytometric and inhibition of ergosterol synthesis studies were performed. Propidium iodide rapidly penetrated the majority of the yeast cells when the cells were treated with concentrations just over the MICs, meaning that the fungicidal effect resulted from an extensive lesion of the cell membrane. Clove oil and eugenol also caused a considerable reduction in the quantity of ergosterol, a specific fungal cell membrane component. Germ tube formation by Candida albicans was completely or almost completely inhibited by oil and eugenol concentrations below the MIC values. The present study indicates that clove oil and eugenol have considerable antifungal activity against clinically relevant fungi, including fluconazole-resistant strains, deserving further investigation for clinical application in the treatment of fungal infections.

Clove oil cream: a new effective treatment for chronic anal fissure. Elwakeel HA, Moneim HA, Farid M, Gohar AA. Colorectal Dis. 2007 Jul;9(6):549-52. OBJECTIVE: Anal fissure is a common painful condition affecting the anal canal and causes considerable morbidity and reduction in quality of life. Surgical treatment has been associated with a degree of incontinence in up to 30% of patients. This study discussed the results of clove oil 1% cream in healing of chronic anal fissure. METHOD: A single-blind randomized comparative trial was setup to compare traditional treatment with stool softeners and lignocaine cream 5% against clove oil 1% cream for 6 weeks. RESULTS: 55 patients were included in this study, 30 patients in clove oil group and 25 patients in control group. Healing had occurred in 60% of patients in clove oil group and in 12% of patients in the control group after 3-month follow up (P < 0.001). Patients in clove oil group showed significant reduction in resting anal pressure and almost all other anorectal manometric pressures compared with patients in control group. CONCLUSION: Topical application of clove oil cream demonstrated a significant beneficial effect when applied to patients suffering from chronic anal fissure.

Aidance does not test on animals and did not conduct this study. It is referenced as scientific evidence of the effectiveness of ingredients in our products. Antimicrobial activity of clove oil and its potential in the treatment of vaginal candidiasis. Ahmad N, Alam MK, Shehbaz A, Khan A, Mannan A, Hakim SR, Bisht D, Owais M. J Drug Target. 2005 Dec;13(10):555-61. In the present study, we evaluated antimicrobial activity of clove oil against a range of fungal pathogens including that responsible for urogenital infection. Clove oil was found to possess strong antifungal activity against opportunistic fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, etc. The oil was found to be extremely successful in the treatment of experimental murine vaginitis in model animals. On evaluating various formulations, topical administration of the liposomized clove oil was found to be most effective against treatment of vaginal candidiasis.

Of the ingredients in this study, Aidance products contain clove flower oil only. Alqareer A, Alyahya A, Andersson L. The effect of clove and benzocaine versus placebo as topical anesthetics. J Dent 2006;34(10):747-50. OBJECTIVES: The purpose of this study was to examine whether the natural herb clove can replace benzocaine as a topical anesthetic. METHODS: Topical agents were applied to the maxillary canine buccal mucosa of 73 adult volunteers. Four substances were tested in the study: (1) homemade clove gel, (2) benzocaine 20% gel, (3) placebo that resembles clove and (4) a placebo that resembled benzocaine. After 5 min of material application in a randomized, subject-blinded manner, each participant received two needle sticks. Pain response was registered using a 100 mm visual analogue pain scale. RESULTS: Both clove and benzocaine gels had significantly lower mean pain scores than placebos (p=0.005). No significant difference was observed between clove and benzocaine regarding pain scores. CONCLUSION: Clove gel might possess a potential to replace benzocaine as a topical agent before needle insertion.

The leaf-essential oil from Eucalyptus robusta and E. saligna, the latter in two phenologic stages, were analysed by gas chromatography coupled to mass spectrometry (GC-MS). The major constituent in E. robusta oil was the monoterpene alpha-pinene (73.0% of the total amount). The oil composition of the E. saligna was dependent of the phenologic stage. In the vegetative phase, the major constituents were p-cymene (54.2%) and gamma-terpinene (43.8%), while during the blossoming alpha-pinene became the major constituent followed by p-cymene (22.5%). Additionally, the antimicrobial activity for all three oils was evaluated against Staphylococcus aureus, Escherichia coli and Candida albicans. The E. robusta oil presented the highest growth inhibition for all the microorganisms tested.

Mulyaningsih S, Sporer F, Reichling J, Wink M. Antibacterial activity of essential oils from Eucalyptus and of selected components against multidrug-resistant bacterial pathogens. Pharm Biol. 2011 Sep;49(9):893-9. Epub 2011 May 19. CONTEXT: Eucalyptus globulus Labill (Myrtaceae) is the principal source of eucalyptus oil in the world and has been used as an antiseptic and for relieving symptoms of cough, cold, sore throat, and other infections. The oil, well known as 'eucalyptus oil' commercially, has been produced from the leaves. Biological properties of the essential oil of fruits from E. globulus have not been investigated much. OBJECTIVE: The present study was performed to examine the antimicrobial activity of the fruit oil of E. globulus (EGF) and the leaf oils of E. globulus (EGL), E. radiata Sieber ex DC (ERL) and E. citriodora Hook (ECL) against multidrug-resistant (MDR) bacteria. Furthermore, this study was attempted to characterize the oils as well as to establish a relationship between the chemical composition and the corresponding antimicrobial properties. MATERIALS AND METHODS: The chemical composition of the oils was analyzed by GLC-MS. The oils and isolated major components of the oils were tested against MDR bacteria using the broth microdilution method. RESULTS: EGF exerted the most pronounced activity against methicillin-resistant Staphylococcus aureus (MIC ~ 250 µg/ml). EGF mainly consisted of aromadendrene (31.17%), whereas ECL had citronellal (90.07%) and citronellol (4.32%) as the major compounds. 1,8-cineole was most abundant in EGL (86.51%) and ERL (82.66%). DISCUSSION AND CONCLUSION: The activity of the oils can be ranked as EGF > ECL > ERL ~ EGL. However, all the oils and the components were hardly active against MDR Gram-negative bacteria. Aromadendrene was found to be the most active, followed by citronellol, citronellal and 1,8-cineole.

Of the ingredients in this study, Aidance products contain eucalyptus oil, tea tree oil, clove flower oil, peppermint oil and sage oil only. The battle against multi-resistant strains: Renaissance of antimicrobial essential oils as a promising force to fight hospital-acquired infections. Warnke PH, Becker ST, Podschun R, Sivananthan S, Springer IN, Russo PA, Wiltfang J, Fickenscher H, Sherry E. J Craniomaxillofac Surg. 2009 Oct;37(7):392-7. Epub 2009 May 26. Hospital-acquired infections and antibiotic-resistant bacteria continue to be major health concerns worldwide. Particularly problematic is methicillin-resistant Staphylococcus aureus (MRSA) and its ability to cause severe soft tissue, bone or implant infections. First used by the Australian Aborigines, Tea tree oil and Eucalyptus oil (and several other essential oils) have each demonstrated promising efficacy against several bacteria and have been used clinically against multi-resistant strains. Several common and hospital-acquired bacterial and yeast isolates (6 Staphylococcus strains including MRSA, 4 Streptococcus strains and 3 Candida strains including Candida krusei) were tested for their susceptibility for Eucalyptus, Tea tree, Thyme white, Lavender, Lemon, Lemongrass, Cinnamon, Grapefruit, Clove Bud, Sandalwood, Peppermint, Kunzea and Sage oil with the agar diffusion test. Olive oil, Paraffin oil, Ethanol (70%), Povidone iodine, Chlorhexidine and hydrogen peroxide (H(2)O(2)) served as controls. Large prevailing effective zones of inhibition were observed for Thyme white, Lemon, Lemongrass and Cinnamon oil. The other oils also showed considerable efficacy. Remarkably, almost all tested oils demonstrated efficacy against hospital-acquired isolates and reference strains, whereas Olive and Paraffin oil from the control group produced no inhibition. As proven in vitro, essential oils represent a cheap and effective antiseptic topical treatment option even for antibiotic-resistant strains as MRSA and antimycotic-resistant Candida species.

The aim of this study was to investigate the immunomodulatory effects of the volatile oil of ginger (Zingiber officinale Roscoe) in vitro and in vivo in mice. In vitro, the volatile oil of ginger (0.001-10 ng/mL) significantly inhibited T lymphocyte proliferation (P < 0.01), decreased the number of the total T lymphocytes and T helper cells (P < 0.01) in a concentration-dependent manner, but increased the percentage of T suppressor cells to the total T lymphocytes in the mice. In addition, the volatile oil of ginger (0.001-10 ng/mL) inhibited IL-1alpha secretion by the mice peritoneal macrophages in a concentration-dependent manner. In vivo, oral administration of the volatile oil of ginger in the doses of 0.125, 0.25 and 0.5 g/kg body weight dose-dependently weakened the delayed type of hypersensitivity response to 2,4-dinitro-1-fluorobenzene in the sensitized mice (P < 0.05). These results suggest that the volatile oil of ginger influences both cell-mediated immune response and nonspecific proliferation of T lymphocyte, and may exert beneficial effects in a number of clinical conditions, such as chronic inflammation and autoimmune diseases.

An impression on current developments in the technology, chemistry, and biological activities of ginger (Zingiber officinale Roscoe). Kubra IR, Rao LJ. Crit Rev Food Sci Nutr. 2012 Aug;52(8):651-88. Review. Ginger rhizome (Zingiber officinale Roscoe) is widely cultivated as a spice for its aromatic and pungent components. The essential oil and oleoresins from ginger are valuable products responsible for the characteristic flavor and pungency. Both are used in several food products such as soft beverages and also in many types of pharmaceutical formulations. More than 100 compounds have been reported from ginger, some of which are isolated and characterized, others are tentatively identified by GC-MS and / or LC-MS. [6]-Gingerol, the major gingerol in ginger rhizomes, has been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, and cardiotonic effects. Ginger is considered as "generally recognized as safe" (GRAS) by Food and Drug Administration (FDA), USA. Due to all these properties, ginger has gained considerable attention in developed countries in recent years, especially for its use in the treatment of inflammatory conditions. The present review is a persuasive presentation of the current information on processing, chemistry, biological activities, and medicinal uses of ginger. Further studies are required for the validation of the beneficial uses. Formulation for novel products and new usages may emerge in the years to come, based on the revealed results of various studies.

We performed a systematic review of the evidence supporting various treatments for envenomation by jellyfish (cnidarian) and related organisms in North America and Hawaii. Our review produced 19 pertinent primary articles. Current research demonstrates variable response to treatment, often with conflicting results according to species studied, which contributes to considerable confusion about what treatment is warranted and efficacious. Our review suggests that vinegar causes pain exacerbation or nematocyst discharge in the majority of species. Hot water and topical lidocaine appear more widely beneficial in improving pain symptoms and are preferentially recommended. Unfortunately, they may be difficult to obtain at the site of envenomation, such as the beach or diving sites. In these instances, removing the nematocysts and washing the area with saltwater may be considered. If the envenomation is thought to be due to the bluebottle (Physalia), vinegar may be beneficial. Copyright © 2012. Published by Mosby, Inc.

Topical anesthetics for dermatologic procedures: a review. Sobanko JF, Miller CJ, Alster TS. Dermatol Surg. 2012 May;38(5):709-21. doi: 10.1111/j.1524-4725.2011.02271.x. Epub 2012 Jan 13. Review. BACKGROUND: Practitioners are increasingly using topical anesthetics to decrease the pain associated with superficial dermatologic, aesthetic, and laser procedures. Numerous lidocaine-containing products are available, but comprehensive reviews are lacking regarding their relative safety profiles and appropriate dermatologic uses. MATERIALS AND METHODS: A literature review of currently available topical anesthetics, their safety profiles, and dermatologic uses was conducted. RESULTS: Factors that should be considered to reduce the risk of side effects associated with the use of topical anesthetics include the amount of product used, body location, size of the surface area, and duration of product application. Many case reports document adverse outcomes associated with the use of compounded products that the Food and Drug Administration has not approved that have inappropriately high anesthetic concentrations and from the use of topical anesthetics on excessively large skin surface areas during laser treatments. CONCLUSIONS: Lidocaine-containing products play an integral role in cutaneous anesthesia by providing patient comfort with minimal side effects. Careful attention must be paid to the particular anatomic location, the total surface area covered, and the duration of anesthetic skin contact. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Local anesthetic effects of Lidocaine cream: randomized controlled trial using a standardized prick pain. Herberger K, Krause K, Maier K, Zschocke I, Radtke M, Augustin M. J Dermatolog Treat. 2011 Jul 31. Abstract Background: ELA-max (4% Lidocaine) and EMLA cream (Lidocaine-Prilocaine 2.5%) are topicals used for superficial anesthesia. Only few studies have been published on their comparative effectiveness in close-to-practice pain models. Objective: 1) To evaluate the analgesic efficacy of Lidocaine cream compared with Lidocaine-Prilocaine cream and placebo. 2) To assess the safety and tolerability. Methods: Randomized, three-arm, double-blind trial in 40 healthy volunteers comparing the anesthetic effects of Lidocaine and Lidocaine-Prilocaine cream to placebo at various time points (0-120 min). A standardized pain was induced by lancet pricks and measured by a visual analogue scale. Intra-individual comparison between the test areas was performed in a cross-over design. Results: Lidocaine showed significantly reduced pain compared to placebo at all assessment points. Pain reduction was achieved significantly earlier using Lidocaine occlusively (30 min). No significant differences were found concerning the anesthetic efficacy of Lidocaine and Lidocaine-Prilocaine cream. There were no relevant adverse events. Conclusion: This study confirms that a topical preparation with 4% Lidocaine is an effective and safe treatment option for superficial anesthesia. It supports the claim that an occlusive application is more rapid in action. 4% Lidocaine is of value as a rapidly-acting local anesthetic for the treatment of minor surgical procedures.

Local treatment with polykatan, a magnesium-containing drug based on bischofite mineral, promoted healing of infected skin wounds. Wound cleansing from bacteria was due to a direct antibacterial effect of the drug.

Of the ingredients in this study, Aidance products contain magnesium oxide and zinc oxide only. Interaction of mineral salts with the skin: a literature survey. Polefka TG, Bianchini RJ, Shapiro S. Int J Cosmet Sci. 2012 Oct;34(5):416-23. doi: 10.1111/j.1468-2494.2012.00731.x. Epub 2012 Jul 10. There is growing scientific evidence that the health, well-being and the attractiveness of the skin are strongly influenced by nutrition. Consumers recognize this and have supported the creation of a global cosmeceuticals market estimated in 2010 at $27.2 billion. Early in 2011, the US Department of Health and Human Services and Department of Agriculture issued the Dietary Guidelines for Americans, 2010. Twelve vitamins and nine minerals were recognized as essential. The minerals include calcium, copper, iron, magnesium, phosphorus, selenium, zinc, potassium and sodium. Although the topical benefits of several minerals such as zinc, magnesium and iron are recognized and, in some cases, approved by the FDA, the topical benefits of the others to the skin are largely unexplored and unexploited. This review attempts to summarize what has been published in the literature on the interactions of the eight of the nine essential elements with the skin. © 2012 Copyright © 2009-2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. All rights reserved.

In a well-controlled, double-blind, randomized study, 30 patients with cutaneous candidiasis were treated with a 2% miconazole nitrate lotion or its placebo control. By the 14th day, 13 of the 15 patients [87%] treated with miconazole nitrate achieved clinical and mycologic cures. Only a single patient treated with the placebo lotion would be classified as a therapeutic cure. In a second portion of the study those patients judged to be therapeutic failures were treated with the lotion containing 2% miconazole nitrate. By combining the results of both portions of the study we find that miconazole nitrate lotion produced both a clinical and mycologic cure in all patients receiving the active lotion. The miconazole lotion formula was well tolerated by all patients and no side effects were noted. The fact that miconazole nitrate acts rapidly in relieving symptoms, is well tolerated, and is highly effective against dermatophytes, yeasts and gram-positive bacteria, makes it a welcome addition to available topical therapy of skin infections.

Absorption and efficacy of miconazole nitrate 0.25% ointment in infants with diaper dermatitis. Eichenfield LF, Bogen ML. J Drugs Dermatol. 2007 May;6(5):522-6. BACKGROUND: The potential for toxicity from systemic absorption of topical miconazole in infants is a concern. OBJECTIVE: To assess the relative safety of 0.25% miconazole based on the amount absorbed through the skin of infants with diaper dermatitis after multiple applications. METHODS: Of 24 infants with moderate to severe diaper dermatitis, 19 received 0.25% miconazole nitrate ointment and 5 received 2% miconazole nitrate cream for 7 days at each diaper change and after bathing. Blood samples were collected prior to treatment and after 7 days. RESULTS: In the 0.25% treatment group, blood concentrations of miconazole were nondetectable (< 1 ng/mL) in 83% (15/18) and minimal (3.0 to 3.8 ng/mL) in 17% (3/18). Samples were missing for one patient. For the 5 infants in the 2% treatment group, miconazole concentration was nondetectable in 20% (1/5) and less than 7.4 ng/mL in 4 infants. No adverse events were noted. CONCLUSIONS: Systemic absorption of 0.25% miconazole nitrate ointment was minimal, demonstrating its safety in the treatment of moderate to severe diaper dermatitis.

Safety and efficacy of bedtime versus daytime administration of the miconazole nitrate 1200 mg vaginal ovule insert to treat vulvovaginal candidiasis.Barnhart K. Curr Med Res Opin. 2005 Jan;21(1):127-34. BACKGROUND: Most vaginal products are self-administered at bedtime. Safety, efficacy, and ' therapeutic cure with bedtime versus daytime treatment of vulvovaginal candidiasis (VVC) were assessed to potentially improve compliance and convenience with vaginal antifungal treatment. METHODS: A non-inferiority study evaluated 573 women with symptoms of WC, randomized to daytime or bedtime self-administration of single dose of miconazole nitrate 1200 mg vaginal ovule (Monistat-1). RESULTS: Subjects (n = 149) were evaluated for efficacy in the Daytime group and 163 in the Bedtime group. In the Daytime group, 86 (57.7%) participants achieved therapeutic cure, with 105 (70.5%) and 111 (74.5%) exhibiting mycologic and clinical cures, respectively. In the Bedtime group, 83 (50.9%) subjects achieved therapeutic cure, with 104 (63.8%) and 120 (73.6%) exhibiting mycologic and clinical cures, respectively (NS). There was no significant difference in the incidence of side effects between the two groups. Median estimated time to initial relief of itching, burning and irritation was similar for both. Miconazole nitrate 2% cream was also applied twice daily to the vulvar area for external symptoms for up to 7 days. Test-of-cure was assessed 21 days-30 days following administration of intra-vaginal drug. Time to vulvovaginal symptomatic relief and the effect of activity following daytime administration on therapeutic cure were also assessed. CONCLUSION: The efficacy against a broad spectrum of pathogens and acceptability of daytime and bedtime administration of miconazole nitrate 1200 mg vaginal ovule were similar. These findings offer women a convenient option for treatment for WC, whether self-managed or managed by their healthcare provider.

Salvia officinalis L. leaves, obtained from four plant populations of different origin, were investigated for their topical anti-inflammatory properties. The n-hexane and the chloroform extracts dose-dependently inhibited the Croton oil-induced ear oedema in mice, the chloroform extracts being the most active. By contrast, the methanol extracts showed a very low effect and the essential oil was inactive. Chemical and pharmacological investigation of the most potent chloroform extract, issued from an autochthonous sage population grown in the submediterranean climatic region of Slovenia, revealed ursolic acid as the main component involved in its anti-inflammatory activity. The anti-inflammatory effect of ursolic acid (ID50 = 0.14 microMoles/cm2) was two fold more potent than that of indomethacin (ID50 = 0.26 microMoles/cm2), which was used as a reference non-steroidal anti-inflammatory drug (NSAID). The content of ursolic acid in sage and sage-based remedies for the topical treatment of inflammatory diseases is proposed as a parameter for quality control purposes.

BACKGROUND: Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. METHODS: A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. RESULTS: Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. CONCLUSIONS: Cryotherapy is more costly and no more effective than salicylic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18994246 [controlled-trials.com] and National Research Register N0484189151.

Treatment of common warts with high-potency (26%) salicylic acid. Parish LC, Monroe E, Rex IH Jr. Clin Ther. 1988;10(4):462-6. Treatment of common warts with topical keratolytic solutions is generally estimated to result in cure rates of 60% to 80% in 12 weeks. Problems with keratolytic solutions include irritation of surrounding normal skin and poor patient compliance. A product containing 26% salicylic acid in a novel polyacrylic vehicle was evaluated in 27 patients and found to cure or provide much improvement in 22 (81%) after only two weeks of treatment. This rapid response was accompanied by a low incidence of irritation. The results of this study suggest that high-potency salicylic acid promotes prompt resolution of warts, which may enhance patient compliance.

Treatment of acne vulgaris with salicylic acid pads. Zander E, Weisman S. Clin Ther. 1992 Mar-Apr;14(2):247-53. Review. Most cases of acne vulgaris are either mild or moderate in severity and well-suited for treatment with nonprescription agents that are safe, effective, and convenient to use. A review of four clinical studies and a comedolytic assay attests to the efficacy and safety of 0.5% and 2% solutions of salicylic acid for the treatment of acne vulgaris. In three placebo-controlled studies and a comedolytic assay, salicylic acid pads reduced the number of primary lesions and thereby the number and severity of all lesions associated with acne. Comparative studies of salicylic acid have shown it to be superior to benzoyl peroxide in reducing the total number of acne lesions. Adverse reactions to salicylic acid are generally limited to mild, local irritation occurring in a minority of patients.

AIM: Venous ulcers are a common, chronic medical and social problem. These ulcers are difficult to heal in most patients with sustained venous hypertension. This pilot product evaluation registry study has evaluated the efficacy and safety of an antimicrobial silver oxide wound dressing ointment ("Silver Oxide Ointment") as part of the treatment of 'difficult' venous ulcerations. METHODS: The study was conducted measuring the variations in the area of the ulceration and microcirculatory parameters. RESULTS: After four weeks, treatment with the Silver Oxide Ointment proved more effective than the 'best management' used in controls. Transcutaneous PO2 was increased (improved); Laser Doppler skin flux and transcutaneous PCO2 were improved (decreased). Also in the silver oxide group a significantly higher number of venous ulcers were completely healed at four weeks. The silver oxide ointment improved both the microcirculation and the healing rate of their ulcers. No significant tolerability problems were observed. CONCLUSION: In difficult venous ulcerations, local treatment with this Silver Oxide Ointment, as one component of the total wound dressing, improved microcirculation measurements and healing rate. Most of the treatments were done at home by the patients or by their tutors. This study indicates the important role of this type of treatment and indicates the need to plan larger and more prolonged studies.

Venous and diabetic ulcerations: management with topical multivalent silver oxide ointment. Belcaro G, Cesarone MR, Errichi BM, Ricci A, Dugall M, Pellegrini L, Ledda A, Grossi MG. Panminerva Med. 2010 Jun;52(2 Suppl 1):37-42. AIM: In addition to contemporary compression therapy, one of the therapeutic approaches is the use of a topical wound care agent. The goal of this pilot registry study is to evaluate the efficacy and safety of a uniquely designed ointment containing multivalent silver oxide (Ag4O4) in the healing of difficult diabetic or venous ulcerations. METHODS: Patients who had ulcers resulting from chronic venous insufficiency or diabetes participated in this open-label, randomized registry study. All patients were evaluated by measuring both the area of the ulceration and microcirculatory parameters. 148 patients were included in the study and categorized into two main groups: venous ulcers and diabetic ulcers. Each main group was then randomized into two sub-groups: topical treatment with silver oxide ointment and the control group (standard cleaning and compression management methods, without silver ointment). All patients were treated with accepted cleaning and compression management. RESULTS. In subjects with venous ulcers: After 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 was increased 2.1 times more than the control group (17.4% to 8.2%) and skin flux (RF) was improved 1.6 times more than the control group (-38.7% to -24.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 1.9 times the control group (-88.7% to -46.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 42% of subjects compared to 22% in the control group (P=<0.05). In subjects with diabetic ulcers: after 4 weeks, the silver treatment was more effective than the control group treatment: Skin PO2 increased 2.6 times more than the control group (23.3% to 9.1%) and skin flux (RF) was significantly improved 4.3 times more than the control group(-26.7% to -6.2%). The total surface area of the ulcer was significantly reduced in the silver treatment group by 3.7 times the control group (-89.0% to -23.9%). In addition, in the silver treatment group we observed complete closure of the ulceration in 39% of subjects compared to 16% in the control group (P</=0.05). CONCLUSION: This pilot study provides observational data on the efficacy of local treatment of ulcers with a multivalent silver oxide containing ointment. The silver ointment improved microcirculation and the healing rate of all 78 patients that were treated with multivalent silver ointment and closed twice as many ulcers in 4 weeks compared to the control groups (40.7% silver treatment compared to 19.4% for the control). This study demonstrates the feasibility of this type of treatment and provides evidence of efficacy to plan larger randomized controlled studies. The large number of patients that were helped in this study demonstrates the efficacy of multivalent silver oxide topical ointment and its important role in ulcer therapy.

Jojoba [Simmondsia chinensis (Link 1822) Schneider 1907] is an arid perennial shrub grown in several American and African countries. Jojoba seeds, which are rich in liquid wax, were used in folk medicine for diverse ailments. In the current study, the potential anti-inflammatory activity of jojoba liquid wax (JLW) was evaluated in a number of experimental models. Results showed that JLW caused reduction of carrageenin-induced rat paw oedema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In a test for anti-inflammatory potential utilizing the chick's embryo chroioallantoic membrane (CAM), JLW also caused significant lowering of granulation tissue formation. Topical application of JLW reduced ear oedema induced by croton oil in rats. In the same animal model, JLW also reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In addition, JLW ameliorated histopathological changes affected by croton oil application. In the lipopolysaccharide (LPS)-induced inflammation in air pouch in rats, JLW reduced nitric oxide (NO) level and tumor necrosis factor-alpha (TNF-alpha) release. In conclusion, this study demonstrates the effectiveness of JLW in combating inflammation in several experimental models. Further investigations are needed to identify the active constituents responsible for the anti-inflammatory property of JLW.

Clay jojoba oil facial mask for lesioned skin and mild acne--results of a prospective, observational pilot study. Meier L, Stange R, Michalsen A, Uehleke B. Forsch Komplementmed. 2012;19(2):75-9. Epub 2012 Apr 19. BACKGROUND: External application of clay facial masks is a cosmetic procedure generally used to reduce skin lesions and to improve overall skin condition. OBJECTIVE: Collecting pilot data about self-treatment with clay jojoba oil masks on participants with acne-prone, lesioned skin and acne. METHODS: Open, prospective, observational pilot study: Participants received written information, instructions, and questionnaires without direct contact with the study physician. For 6 weeks, they applied the masks 2-3 times per week. The primary outcome is the difference of skin lesions: baseline vs. after 6 weeks. RESULTS: 194 participants (192 female, 2 male, mean age (± SE) (32.3 ± 0.7 years) returned questionnaires and diaries. 133 of these participants returned complete and precise lesion counts (per-protocol (PP) collective). A 54% mean reduction in total lesion count was observed after 6 weeks of treatment with clay facial mask. Both inflammatory and non-inflammatory skin lesions were reduced significantly after treatment compared to baseline: Median counts (MC) of pustules per affected participant were reduced from 7.0 ± 0.9 to 3.0 ± 0.5 (mean individual reduction (MIR) = 49.4%), the MC of the papules from 3.5 ± 2.2 to 1.0 ± 0.4 (MIR = 57.3%), the MC of cysts from 2.0 ± 0.8 to 0.5 ± 0.4 (MIR = 68.6%) and the MC of comedones from 26.5 ± 6.3 to 16.0 ± 4.0 (MIR = 39.1%). DLQI-average score decreased from 5.0 ± 4.5 (mean ± SE) before to 2.1 ± 2.8 after treatment. CONCLUSIONS: The present study gives preliminary evidence that healing clay jojoba oil facial masks can be effective treatment for lesioned skin and mild acne vulgaris. Copyright © 2012 S. Karger AG, Basel.

Wound healing properties of jojoba liquid wax: an in vitro study. Ranzato E, Martinotti S, Burlando B. J Ethnopharmacol. 2011 Mar 24;134(2):443-9. Epub 2011 Jan 4. AIM OF THE STUDY: The wound healing properties of jojoba (Simmondsia chinensis) liquid wax (JLW) were studied in vitro on HaCaT keratinocytes and human dermal fibroblasts, which are involved in wounded skin repair. MATERIALS AND METHODS: JLW cytotoxicity was evaluated by the crystal violet staining and the neutral red uptake endpoint. Induction of wound healing by JLW was assessed by scratch wound assay on cell monolayers. The involvement of signaling pathways was evaluated by the use of the Ca(2+) chelator BAPTA and of kinase inhibitors, and by Western blot analysis of cell lysates using anti-phospho antibodies. Collagen and gelatinase secretion by cells were assayed by in-cell ELISA and zymography analysis, respectively. RESULTS: Cytotoxicity assays showed that the toxic effects of JLW to these cells are extremely low. Scratch wound experiments showed that JLW notably accelerates the wound closure of both keratinocytes and fibroblasts. The use of inhibitors and Western blot revealed that the mechanism of action of JLW is strictly Ca(2+) dependent and requires the involvement of the PI3K-Akt-mTOR pathway and of the p38 and ERK1/2 MAPKs. In addition, JLW was found to stimulate collagen I synthesis in fibroblasts, while no effect was detected on the secretion of MMP-2 and MMP-9 gelatinases by HaCaT or fibroblasts. CONCLUSIONS: Taken together, data provide a pharmacological characterization of JLW properties on skin cells and suggest that it could be used in the treatment of wounds in clinical settings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Essential oils extracted from flower petals of palmarosa (Cymbopogon martini), evening primrose (Primula rosea), lavender (Lavandula angustifolia) and tuberose (Polianthus tuberosa) were tested for their antibacterial activities against gram-positive and gram-negative bacteria. Different concentrations of each essential oil ranging from 10-100% were tested. Both gram-positive and gram-negative bacteria were found susceptible to the studied flower essential oils. With increase in concentration of essential oil, increase in zone of inhibition was observed thus dose-dependent response was clear for each essential oil. Essential oil extracted from Cymbopogon martini showed the highest activity against both gram positive and gram negative bacteria among the tested essential oils.

Antimicrobial action of palmarosa oil (Cymbopogon martinii) on Saccharomyces cerevisiae. Prashar A, Hili P, Veness RG, Evans CS. Phytochemistry. 2003 Jul;63(5):569-75. The essential oil extracted from palmarosa (Cymbopogon martinii) has proven anti-microbial properties against cells of Saccharomyces cerevisiae. Low concentrations of the oil (0.1%) inhibited the growth of S. cerevisiae cells completely. The composition of the sample of palmarosa oil was determined as 65% geraniol and 20% geranyl acetate as confirmed by GC-FTIR. The effect of palmarosa oil in causing K(+) leakage from yeast cells was attributed mainly to geraniol. Some leakage of magnesium ions was also observed. Blocking potassium membrane channels with caesium ions before addition of palmarosa oil did not change the extent of K(+) ion leakage, which was equal to the total sequestered K(+) in the cells. Palmarosa oil led to changes in the composition of the yeast cell membrane, with more saturated and less unsaturated fatty acids in the membrane after exposure of S. cerevisiae cells to the oil. Some of the palmarosa oil was lost by volatilization during incubation of the oil with the yeast cells. The actual concentration of the oil components affecting the yeast cells could not therefore be accurately determined.

The antimicrobial and antiplasmid activities of essential oils (orange oil, eucalyptus oil, fennel oil, geranium oil, juniper oil, peppermint oil, rosemary oil, purified turpentine oil, thyme oil, Australian tea tree oil) and of menthol, the main component of peppermint oil, were investigated. The antimicrobial activities were determined on the Gram (+) Staphylococcus epidermidis and the Gram (-) Escherichia coli F'lac K12 LE140, and on two yeast Saccharomyces cerevisiae 0425 delta/1 and 0425 52C strains. The antiplasmid activities were investigated on E. coli F'lac bacterial strain. Each of the oils exhibited antimicrobial activity and three of them antiplasmid action. The interaction of peppermint oil and menthol with the antibiotics was studied on the same bacterial strain with the checkerboard method. Peppermint oil and menthol displayed additive synergy with oxytetracycline. A new mechanism of plasmid curing was established for one of the oil components.

A novel treatment of postherpetic neuralgia using peppermint oil. Davies SJ, Harding LM, Baranowski AP. Clin J Pain. 2002 May-Jun;18(3):200-2. BACKGROUND: Postherpetic neuralgia remains a difficult problem to treat. A number of therapies have been shown to be effective, but some patients have intractable pain. PATIENT: The case of a 76-year-old woman whose pain had been resistant to standard therapies is described. The pattern of quantitative sensory testing results for this patient led the authors to believe that she had an "irritable nociceptor" type of pathophysiology. INTERVENTION: The patient was instructed to apply neat peppermint oil (containing 10% menthol) to her skin, resulting in an almost immediate improvement in her pain. This pain relief persisted for 4-6 hours after application of the oil. RESULTS: The patient was successfully treated with topical peppermint oil. During 2 months of follow-up she has had only a minor side effect, with continuing analgesia. The authors believe this is the first evidence of peppermint oil (or menthol) having a strong analgesic effect on neuropathic pain. The possible mechanisms of action of peppermint oil are discussed.

Virucidal effect of peppermint oil on the enveloped viruses herpes simplex virus type 1 and type 2 in vitro. Schuhmacher A, Reichling J, Schnitzler P. Phytomedicine. 2003;10(6-7):504-10. The virucidal effect of peppermint oil, the essential oil of Mentha piperita, against herpes simplex virus was examined. The inhibitory activity against herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) was tested in vitro on RC-37 cells using a plaque reduction assay. The 50% inhibitory concentration (IC50) of peppermint oil for herpes simplex virus plaque formation was determined at 0.002% and 0.0008% for HSV-1 and HSV-2, respectively. Peppermint oil exhibited high levels of virucidal activity against HSV-1 and HSV-2 in viral suspension tests. At noncytotoxic concentrations of the oil, plaque formation was significantly reduced by 82% and 92% for HSV-1 and HSV-2, respectively. Higher concentrations of peppermint oil reduced viral titers of both herpesviruses by more than 90%. A clearly time-dependent activity could be demonstrated, after 3 h of incubation of herpes simplex virus with peppermint oil an antiviral activity of about 99% could be demonstrated. In order to determine the mode of antiviral action of the essential oil, peppermint oil was added at different times to the cells or viruses during infection. Both herpesviruses were significantly inhibited when herpes simplex virus was pretreated with the essential oil prior to adsorption. These results indicate that peppermint oil affected the virus before adsorption, but not after penetration into the host cell. Thus this essential oil is capable to exert a direct virucidal effect on HSV. Peppermint oil is also active against an acyclovir resistant strain of HSV-1 (HSV-1-ACV(res)), plaque formation was significantly reduced by 99%. Considering the lipophilic nature of the oil which enables it to penetrate the skin, peppermint oil might be suitable for topical therapeutic use as virucidal agent in recurrent herpes infection.

Mentha piperita (peppermint). Herro E, Jacob SE. Dermatitis. 2010 Dec;21(6):327-9. PEPPERMINT (Mentha piperita) is a popular herb that can be used in numerous forms (ie, oil, leaf, leaf extract, and leaf water). Peppermint oil has the most uses, and use data on the oil are considered relevant to the leaf extract formulations as well. This herbal preparation is used in cosmeceuticals, personal hygiene products, foods, and pharmaceutical products for both its flavoring and fragrance properties. Peppermint oil possesses a fresh sharp menthol odor and a pungent taste followed by a cooling sensation. It also has a variety of therapeutic properties and is used in aromatherapy, bath preparations, mouthwashes, toothpastes, and topical preparations. Topical preparations of peppermint oil have been used to calm pruritus and relieve irritation and inflammation. Their frequent application to impaired skin could contribute to the sensitization rates seen. Numerous allergic contact dermatitis reactions to peppermint oil have been described, many of which are linked to both perioral and intraoral disorders. Although peppermint oil is known for its many properties, its role as a sensitizer should be recognized so as to aid in the diagnosis of both dermatitis and oral conditions and to allow the initiation of proper avoidance measures.

Background: Tea tree oil is the essential oil steam-distilled from Melaleuca alternifolia, an Australian native plant. In recent years it has become increasingly popular as an antimicrobial for the treatment of conditions such as tinea pedis and acne. Objectives:: To investigate the anti-inflammatory properties of tea tree oil on histamine-induced weal and flare. Methods: Twenty-seven volunteers were injected intradermally in each forearm (study and control assigned on an alternating basis) with histamine diphosphate (5 microg in 50 microL). Flare and weal diameters and double skin thickness were measured every 10 min for 1 h to calculate flare area and weal volume. At 20 min, 25 microL of 100% tea tree oil was applied topically to the study forearm of 21 volunteers. For six volunteers, 25 microL paraffin oil was applied instead of tea tree oil. Results: Application of liquid paraffin had no significant effect on histamine-induced weal and flare. There was also no difference in mean flare area between control arms and those on which tea tree oil was applied. However, mean weal volume significantly decreased after tea tree oil application (10 min after tea tree oil application, P = 0.0004, Mann-Whitney U-test). Conclusions: This is the first study to show experimentally that tea tree oil can reduce histamine-induced skin inflammation.

Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: a randomized, placebo-controlled, blinded study. Australas J Dermatol. 2002 Aug;43(3):175-8. PubMed PMID: 12121393. Tea tree oil has been shown to have activity against dermatophytes in vitro. We have conducted a randomized, controlled, double-blinded study to determine the efficacy and safety of 25% and 50% tea tree oil in the treatment of interdigital tinea pedis. One hundred and fifty-eight patients with tinea pedis clinically and microscopy suggestive of a dermatophyte infection were randomized to receive either placebo, 25% or 50% tea tree oil solution. Patients applied the solution twice daily to affected areas for 4 weeks and were reviewed after 2 and 4 weeks of treatment. There was a marked clinical response seen in 68% of the 50% tea tree oil group and 72% of the 25% tea tree oil group, compared to 39% in the placebo group. Mycological cure was assessed by culture of skin scrapings taken at baseline and after 4 weeks of treatment. The mycological cure rate was 64% in the 50% tea tree oil group, compared to 31% in the placebo group. Four (3.8%) patients applying tea tree oil developed moderate to severe dermatitis that improved quickly on stopping the study medication.

Buck DS, Nidorf DM, Addino JG. Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. J Fam Pract. 1994 Jun;38(6):601-5. PubMed PMID: 8195735. Background: The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis. Methods: A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy. Results: The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%). Conclusions: All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy.

Tong MM, Altman PM, Barnetson RS. Tea tree oil in the treatment of tinea pedis. Australas J Dermatol. 1992;33(3):145-9. PubMed PMID: 1303075. Abstract Tea tree oil (an essential oil derived primarily from the Australian native Melaleuca alternifolia) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections; however, to date, the evidence for its efficacy in fungal infections is still largely anecdotal. One hundred and four patients completed a randomized, double-blind trial to evaluate the efficacy of 10% w/w tea tree oil cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis. Significantly more tolnaftate-treated patients (85%) than tea tree oil (30%) and placebo-treated patients (21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no statistically significant difference between tea tree oil and placebo groups. All three groups demonstrated improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching and burning. The tea tree oil group (24/37) and the tolnaftate group (19/33) showed significant improvement in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018 respectively). Tea tree oil cream (10% w/w) appears to reduce the symptomatology of tinea pedis as effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure. This may be the basis for the popular use of tea tree oil in the treatment of tinea pedis.

Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust. 1990 Oct 15;153(8):455-8. PubMed PMID: 2145499. Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions. We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower. Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.

Tea tree oil as a novel antipsoriasis weapon. Pazyar N, Yaghoobi R. Skin Pharmacol Physiol. 2012;25(3):162-3. doi: 10.1159/000337936. Epub 2012 Apr 3. Psoriasis is a clinical skin disease that is characterized by erythematous scaling plaques and involves the extensor site of the extremities, the scalp and other surfaces of the skin. Tea tree oil (TTO) is considered an essential oil, obtained by steam distillation of the leaves and terminal branchlets of Melaleuca alternifolia. Notably,terpinen-4-ol, the major TTO constituent, has been found to have potent anti-inflammatory properties. It is suggested that terpinen-4-ol may be a novel potential agent against psoriasis. This article draws attention to the antipsoriatic effect of TTO and provides a theoretical molecular approach.

Tea tree oil attenuates experimental contact dermatitis. Wallengren J. Arch Dermatol Res. 2011 Jul;303(5):333-8. doi: 10.1007/s00403-010-1083-y. Epub 2010 Sep 24. Herbs and minerals have been used in clinical dermatology for hundreds of years and herbal ingredients are becoming increasingly popular with the public in treatment of various dermatological conditions characterised by inflammation and pruritus. The aim of this study was to compare the efficacy of traditional topical therapeutic agents with a moderate potency topical glucocorticoid on experimental contact dermatitis and contact urticaria. The effects of ichthammol 10% pet, zinc oxide 20% pet, camphor 20% pet, levomenthol 10% pet, tea tree oil 20 or 50% and clobetason butyrate 0.05% ointment were studied in the following experimental models: elicitation of allergic contact dermatitis to nickel, irritant contact dermatitis to benzalkonium chloride, and in immediate reactions to histamine and benzoic acid (non-immunological contact utricaria) respectively. Delayed reactions were evaluated using a clinical scoring system and immediate reactions were estimated by planimetry. Histamine-induced pruritus was evaluated using VAS. Tea tree oil reduced allergic contact dermatitis by 40.5% (p = 0.003), zinc oxide by 17.4% (p = 0.04) and clobetason butyrate by 23.5% (p = 0.01). Zinc oxide reduced histamine induced flare by 18.5% (p = 0.01), ichthammol by 19.2% (p = 0.02) and clobetason butyrate by 44.1% (p = 0.02). Irritant contact dermatitis and non-immunological contact urticaria were not influenced by the pre-treatments. Pruritus induced by histamine also remained unchanged. In conclusion, tea tree oil seems to be a more effective anti-eczematic agent than zinc oxide and clobetasone butyrate, while clobetasone butyrate is superior to both ichthammol and zinc oxide in topical treatment of urticarial reactions.

Nenoff, P., Haustein, U. F., and Brandt, W. Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro. Skin Pharmacol 1996;9(6):388-394. The in vitro antifungal activity of tea oil, the essential oil of Melaleuca alternifolia, has been evaluated against 26 strains of various dermatophyte species, 54 yeasts, among them 32 strains of Candida albicans and other Candida sp. as well as 22 different Malassezia furfur strains. Minimum inhibitory concentrations (MIC) of tea tree oil were measured by agar dilution technique. Tea tree oil was found to be able to inhibit growth of all clinical fungal isolates. For the investigated dermatophytes MIC values from 1,112.5 to 4,450.0 micrograms/ml with a geometric mean of 1,431.5 micrograms/ml were demonstrated. Both C. albicans strains and the other strains belonging to the genus Candida and Trichosporon appeared to be slightly less susceptible to tea tree oil in vitro. However, their MIC values, which varied from 2,225.0 to 4,450.0 micrograms/ml (geometric mean 4,080 micrograms/ml), indicated moderate susceptibility to the essential oil of M. alternifolia. The lipophilic yeast M. furfur seemed to be most susceptible to tea tree oil. MIC values between 556.2 and 4,450.0 micrograms/ml (geometric mean 1,261.5 micrograms/ml) were found against the tested M. furfur strains. However, when calculated as percentage tea tree oil of the agar, the above-mentioned concentrations correspond to 0.5-0.44% tea tree oil content. These values are far below the usual relatively high therapeutic concentrations of the agent; approximately 5-10% solution or even the concentrated essential oil are used for external treatment. In comparison with tea tree oil, in vitro susceptibility against miconazole, an established topical antifungal, was tested. As expected, very low MIC values for miconazole were found for dermatophytes (geometric mean 0.2 microgram/ml), yeasts (geometric mean 1.0 microgram/ml), and M. furfur (geometric mean 2.34 micrograms/ml). It is suggested that the in vivo effect of tea tree oil ointment in the therapy of fungal infections of the skin and mucous membranes as well as in the treatment of dandruff, a mild form of seborrheic dermatitis, may be at least partly due to an antifungal activity of tea tree oil.

Successful topical treatment of hand warts in a paediatric patient with tea tree oil (Melaleuca alternifolia). Millar BC, Moore JE. Complement Ther Clin Pract. 2008 Nov;14(4):225-7. Epub 2008 Jul 11. Tea tree oil (TTO) (Melaleuca alternifolia) has been used recently as an effective topical application for the treatment of skin infections due to a variety of aetiological microbial agents, including mainly bacterial infections. We detail the first report in the peer-reviewed literature of the successful treatment with TTO of a paediatric patient with warts on her right middle finger. TTO was applied topically once daily to the lesions for 12 days, with a successful outcome, including complete re-epithelization of the infected areas. The case highlights the potential use of TTO in the treatment of common warts due to human papilloma virus.

Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children. Zinc in combination with antioxidants may be modestly effective in slowing the progression of intermediate and advanced age-related macular degeneration. Zinc is an effective treatment for Wilson disease. Current data do not support zinc supplementation as effective for upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc is well tolerated at recommended dosages. Adverse effects of long-term high-dose zinc use include suppressed immunity, decreased high-density lipoprotein cholesterol levels, anemia, copper deficiency, and possible genitourinary complications. Copyright (c) 2009 American Academy of Family Physicians.

Aidance does not test on animals and did not conduct this study. It is referenced as scientific evidence of the effectiveness of ingredients in our products. Studies on zinc in wound healing. Agren MS. Acta Derm Venereol Suppl (Stockh). 1990;154:1-36. Topical zinc is widely used in wound treatment although the beneficial effect of zinc has only been documented in zinc-deficient patients who were given zinc orally. The main purpose of this study was to investigate the effect of topically applied zinc on leg ulcer healing and examine its effect on some mechanisms in wound healing using standardized animal models. Additionally, absorption of zinc into wounds and intact skin treated topically with zinc was studied. In a double-blind trial involving 37 leg ulcer patients with low serum zinc levels, topical zinc oxide promoted cleansing and re-epithelialization. Infections and deteriorations of ulcers were less common in zinc oxide treated patients. Re-epithelialization, an important mechanism in the closure of leg ulcers, was enhanced with zinc oxide applied topically on partial-thickness wounds in pigs with normal zinc status. Zinc sulfate at three different concentrations did not, however, result in this beneficial effect on the resurfacing of wounds. The inflammatory reaction was diminished in zinc treated wounds except when a high zinc sulfate concentration was applied. Bacterial growth and concomitant diseases such as diabetes can complicate wound healing. In normal rats, bacterial growth in full-thickness wounds was reduced with topical zinc oxide but not in hyperglycemic diabetic rats. The anti-bacterial mechanism of zinc oxide seemed to be more indirect and to be mediated via local defense systems rather than being directly toxic to the bacteria. Healing of 21-day-old skin incisions was impaired in zinc deficiency, as measured by a significantly decreased wound breaking strength in zinc-deficient rats compared with that of pair-fed controls. The decreased breaking strength did not seem to be due to differences in collagen concentration of the wounds. Zinc oxide was slowly but continuously solubilized when applied on open wounds in rats. On the other hand, with zinc sulfate, the zinc concentrations, either locally or systemically, did not maintain a constant level for the 48-hour post-operative treatment period as they did with zinc oxide. Zinc absorption in and through normal human forearm skin was demonstrated after treatment with a zinc oxide medicated occlusive dressing by increased zinc levels in epidermis, interstitial fluid and dermis compared with the non-zinc control dressing. In conclusion, topical zinc may stimulate leg ulcer healing by enhancing re-epithelialization, decreasing inflammation and bacterial growth. When zinc is applied on wounds it not only corrects a local zinc deficit but also acts pharmacologically.

Enhanced healing of surgical wounds of the lower leg using weekly zinc oxide compression dressings. Stebbins WG, Hanke CW, Petersen J. Dermatol Surg. 2011 Feb;37(2):158-65. doi: 10.1111/j.1524-4725.2010.01844.x. Epub 2011 Jan 26. BACKGROUND: Management of lower extremity wounds after Mohs micrographic surgery can pose a challenge to the surgeon. Postoperative reactive edema and inflammation can lead to a painful and protracted healing course. Unna boots deliver zinc oxide to the wound bed and surrounding skin while providing compression and occlusion of the wound. OBJECTIVE: To evaluate the utility of weekly Unna boot therapy in decreasing postoperative edema, inflammation, and morbidity; minimizing postoperative wound care; and improving the rate of wound healing in patients with lower leg surgical defects. METHODS: Ten patients (6 men, 4 women) aged 72 to 91 with postoperative defects on the distal lower extremity were treated with weekly Unna boots until wounds had sufficiently granulated or re-epithelialized. RESULTS: In all 10 patients, weekly Unna boot therapy was well tolerated, with high satisfaction levels relating to minimal postoperative wound care, rapid granulation, minimal pain, and excellent esthetic outcome of postoperative wounds. No infections or other complications were noted during the healing process. LIMITATIONS This was not a randomized, controlled trial. CONCLUSIONS: In patients with postoperative wounds of the lower leg, weekly Unna boots significantly improve the healing process, decrease postoperative pain, and minimize wound care. © 2011 by the American Society for Dermatologic Surgery, Inc.

Zinc in wound healing: theoretical, experimental, and clinical aspects. Lansdown AB, Mirastschijski U, Stubbs N, Scanlon E, Agren MS. Wound Repair Regen. 2007 Jan-Feb;15(1):2-16. Review. Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.

Electrometric assessment of the effect of a zinc oxide paste in diaper dermatitis. Xhauflaire-Uhoda E, Henry F, Piérard-Franchimont C, Piérard GE. Int J Cosmet Sci. 2009 Oct;31(5):369-74. Epub 2009 May 13. Diaper dermatitis affects nearly 50% of infants as well as some bed-ridden adults particularly in the elderly people. This condition is induced by irritation and maceration, and may be further exacerbated by Candida sp. colonization and infection. A key factor in the pathogenesis is the alteration in both the barrier function and the water-holding capacity of the stratum corneum. The purpose of this study was to assess the effects of an unmedicated zinc oxide-petrolatum paste and to observe for possible shielding and restoring effects on the water-holding capacity of the stratum corneum altered by diaper dermatitis. The paste appeared to load the hollow skin microrelief. It was inferred that this effect was responsible for a reticulated shielding effect. Compared with healthy skin and untreated diaper dermatitis, the application of the anhydrous paste resulted in a trend to normalize electrometric properties of skin reflecting the combination of transepidermal water loss and the water-holding capacity of the stratum corneum.