(2004; 358 pages)
Aetheroleum Melaleucae Alternifoliae
Aetheroleum Melaleucae Alternifoliae is the essential oil obtained by steam distillation of the leaves and terminal branchlets of Melaleuca alternifolia (Maiden and Betche) Cheel (Myrtaceae) (1-3).
No information available.
Selected vernacular names
Australian tea tree, tea tree (1-5).
Indigenous to Australia, where it is grown commercially (6, 7).
A narrow-leaved tree not exceeding 6 m. Entire plant glabrous; leaves alternate. Flowers scattered in an interrupted spike; stamens more than 12mm long united at their bases to form 5 distinct bundles; capsule persisting within fruiting hypanthium (6-8).
Plant material of interest: essential oil
A colourless to pale-yellow liquid (1-3).
Odour: myristic (1, 2).
Powdered plant material
General identity tests
Physico-chemical properties, thin-layer and gas chromatography (1, 2).
Tests for specific microorganisms and microbial contamination limits are as described in the WHO guidelines on quality control methods for medicinal plants (9).
Refractive index: 1.475-1.482 (1-3);
Optical rotation: +5° to +15° (1-3);
Relative density: 0.885-0.906 (1-3);
Solubility in alcohol: soluble in two volumes of 85% ethanol at 20°C (1-3).
The recommended maximum limit of aldrin and dieldrin is not more than 0.05mg/kg (10). For other pesticides, see the European pharmacopoeia (10), and the WHO guidelines on quality control methods for medicinal plants (9) and pesticide residues (11).
For maximum limits and analysis of heavy metals, consult the WHO guidelines on quality control methods for medicinal plants (9).
Where applicable, consult the WHO guidelines on quality control methods for medicinal plants (9) for the analysis of radioactive isotopes.
Contains not less than 30% (w/w) of terpinen-4-ol (4-terpineol) and not more than 15% (w/w) of 1,8-cineole (also known as cineol, cineole or eucalyptol) (1, 2). The oil must contain: not less than 3.5% sabine; 1-6% α-terpinene; 10-28% γ-terpinene; 0.5-12.0% p-cymene; not less than 30% terpinen-4-ol; and 1.5-8.0% α-terpineol, as measured by gas chromatography (1-3).
Major chemical constituents
The major constituents are terpinen-4-ol (29-45%), γ-terpinene (10-28%), α-terpinene (2.7-13.0%) and 1,8-cineole (4.5-16.5%) (8, 12-15). Other mono-terpenes present in significant quantities (1-5%) include α-pinene, limonene, p-cymene and terpinolene. The structures of the major monoterpenes are presented below.
and enantiomer terpinen-4-ol (4-terpineol)
Uses supported by clinical data
Topical application for symptomatic treatment of common skin disorders such as acne, tinea pedis, bromidrosis, furunculosis, and mycotic onychia (onychomycosis), and of vaginitis due to Trichomonas vaginalis or Candida albicans, cystitis and cervicitis (16-23).
Uses described in pharmacopoeias and in traditional systems of medicine
As an antiseptic and disinfectant for the treatment of wounds (5).
Uses described in folk medicine, not supported by experimental or clinical data
Symptomatic treatment of burns, colitis, coughs and colds, gingivitis, impetigo, nasopharyngitis, psoriasis, sinus congestion, stomatitis and tonsillitis (24, 25).
Aetheroleum Melaleucae Alternifoliae inhibited the growth in vitro of Escherichia coli, vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, metacillin-resistant Staphylococcus aureus, and a variety of Streptomyces species (MIC 0.04-0.50%) (26-30). It also inhibited the growth in vitro of Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, Malassezia furfur, Candida albicans, Cryptococcus neoformans, Pityrospermum ovale and Trichosporon cutaneum (MIC 1.1-2.2mg/ml) (31-35). The susceptibility of 32 strains of Propionibacterium acnes to the essential oil was determined using a broth dilution method. The MIC was 0.25% for five strains, and 0.50% for the other strains (36). Several chemical constituents of the oil, linalool, terpinen-4-ol, α-terpineol, α-terpinene, terpinolene and 1,8-cineole, inhibited the growth in vitro of a wide variety of microorganisms, including Candida albicans, Escherichia coli and Staphylococcus aureus (MIC 0.06-0.50% v/v) (27).
The dermal median lethal dose (LD50) of the essential oil in rabbits is >5.0mg/kg body weight, since 5.0mg/kg resulted in the deaths of two out of 10 treated rabbits (37). The oral LD50 in rats is 1.9g/kg body weight (range of doses 1.4-2.7 g/kg) (24, 25, 37, 38). The signs of severe toxicity are respiratory distress, and coma with diarrhoea (26, 38). A few cases of toxicosis after topical application of high doses of the essential oil to dogs and cats have been reported. Symptoms included central nervous system depression, weakness, and lack of coordination and muscle tremors that were resolved within 2-3 days after supportive treatment (39).
Vaginitis and cervicitis
A study without controls assessed the safety and efficacy of a 40% emulsified solution of Aetheroleum Melaleucae Alternifoliae in 13% isopropyl alcohol in the treatment of 130 women with cervicitis or vaginitis due to Trichomonas vaginalis or vaginitis due to Candida albicans. Intravaginal application of tampons saturated with a 20% emulsified solution healed cervicitis due to Trichomonas vaginalis after four weekly treatments. In patients with vaginitis due to Trichomonas vaginalis, intravaginal application of a 1% emulsified solution using a saturated tampon, as well as vaginal douching, resulted in clinical cures and restoration of the cervix (21). In another study without controls, 28 women with vaginitis due to Candida albicans were treated with vaginal pessaries (containing 0.2 g essential oil) every night for 90 days. After 30 days of treatment, 24 patients were already free of symptoms such as leukorrhoea and burning sensation, and 21 were free of Candida albicans (17).
A randomized, double-blind, placebo-controlled trial assessed the efficacy of the essential oil in the treatment of 26 women with chronic ideopathic colibacilli cystitis. Patients were treated with 8 mg essential oil, in an enteric capsule form, orally three times daily for 6 months. After treatment, 54% of the essential oil-treated group were free of symptoms, compared with only 15% in the placebo group. However, approximately 50% of the asymptomatic patients still showed evidence of colibacilli and leukocytes in their urine (17).
A randomized, single-blind, comparison trial evaluated the safety and efficacy of topical application of a gel containing either 5% essential oil or 5% benzoyl peroxide in the treatment of mild to moderate acne in 119 patients. The results demonstrated that both preparations significantly reduced the number of inflamed and non-inflamed lesions (open and closed comedones) after 3 months of daily treatment (P < 0.001), although the onset of action of the gel containing the essential oil was slower than that of the gel containing benzoyl peroxide. Patients treated with the oil-containing gel reported fewer side-effects than those treated with the benzoyl peroxide-containing gel (16).
A randomized double-blind, placebo-controlled clinical trial evaluated the efficacy of a cream containing either 10% (w/w) essential oil, 1% tolnaftate or a placebo in the treatment of 104 patients with tinea pedis due to Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum. After application of the cream twice daily for 4 weeks, 30% of the essential oil-treated patients, 85% of the tolnaftate-treated patients and 21% of the placebo-treated patients showed conversion to a negative culture (P < 0.001). Both the essential oiltreated group and tolnaftate-treated group demonstrated significant improvement in the clinical symptoms of scaling, inflammation, itching and burning sensation, compared with the placebo group (P < 0.001). The cream containing the essential oil reduced symptomatology of tinea pedis as effectively as that containing tolnaftate, but was no better than the placebo in achieving a mycological cure (22). A study without controls assessed the efficacy of three products in the treatment of 60 patients with tinea pedis due to Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum, as well as other conditions such as bromidrosis, inflamed corns, calluses, bunions, fissures and mycotic onychia (onychomycosis) of the toenails. Eight patients were treated with 100% essential oil, 40 patients were treated with a 40% emulsified solution of the essential oil in 13% isopropyl alcohol and 12 were treated with an ointment containing 8% essential oil, twice daily for 3 weeks to 4 years. The 100% essential oil was assessed as fair to poor in the treatment of mycotic onychia. The 40% emulsified solution reduced the symptoms of bromidrosis, and inflammation of corns, calluses and bunions. The 8% ointment was effective in the symptomatic treatment of tinea pedis due to T. mentagrophytes and Epidermophyton floccosum, but was less effective against T. rubrum (23).
A randomized, double-blind, multicentre comparison trial assessed the efficacy of 100% essential oil or 1% clotrimazole in the treatment of 117 patients with distal subungual mycotic onychia. Patients received twice-daily applications for 6 months, and debridement and clinical assessment were performed at 0, 1, 3 and 6 months. After 3 months, approximately 50% of each group reported improvements. After 6 months, clinical assessment showed partial or full resolution in approximately 60% of each group (19).
The efficacy of the essential oil was assessed in an open study of 35 patients with furuncles on the axilla, back, ear, face, forearm, neck and scalp. The furuncles were painted with the essential oil two or three times daily, after thorough cleaning. In the group treated with the essential oil, only one furuncle required incision, and in 15 patients, the furuncles were completely cured after 8 days of treatment. The only adverse reaction was slight temporary stinging reported by three patients. In the untreated control group, furuncles on five of the 10 patients required incision and the infected site of the furuncles was still apparent after 8 days (20).
Aetheroleum Melaleucae Alternifoliae is contraindicated in cases of known allergy to plants of the Myrtaceae family.
Not for internal use. Keep out of reach of children (see Adverse reactions).
No information available on general precautions or precautions concerning drug interactions; drug and laboratory test interactions; carcinogenesis, mutagenesis, impairment of fertility; teratogenic and non-teratogenic effects in pregnancy; nursing mothers; or paediatric use. Therefore, Aetheroleum Melaleucae Alternifoliae should not be administered during pregnancy or lactation or to children without medical supervision.
Allergic contact dermatitis after external application and ingestion of Aetheroleum Melaleucae Alternifoliae has been reported (26, 40-44). No adverse reactions were reported in two patch tests using preparations containing up to 5% essential oil (45, 46). Accidental ingestion of 10 ml essential oil caused confusion, disorientation and loss of coordination in a 23-month-old child (47). Ingestion of 2.5 ml essential oil by a 60-year-old man resulted in a severe rash and a general feeling of malaise (48). Induction of a comatose state lasting 12 hours, followed by 36 hours of a semi-conscious state accompanied by hallucinations, was reported in one patient after ingestion of approximately half a cup (120 ml) of the essential oil. Abdominal pain and diarrhoea lasting up to 6 weeks were also reported (38).
Essential oil (1, 2). Store in a well-filled, airtight container, protected from heat and light.
(Unless otherwise indicated)
External application of the essential oil at concentrations of 5-100%, depending on the skin disorder being treated (16-23).
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