title: Terpinen-4-ol is the Most Active Ingredient of Tea Tree Oil to KillDemodexMites.
abstract: OBJECTIVE
  To determine the active ingredient in tea tree oil (TTO) responsible for its reported killing effect onDemodexmites, the most common ectoparasite found in the human skin extending to the eye.
  
  
  METHODS
  Using a reported in vitro killing assay to measure the survival time of adultDemodex folliculorumup to 150 minutes, we have screened serial concentrations of 13 of the 15 known ingredients of TTO (ISO4730:2004) that were soluble in mineral oil and examined their synergistic relationships in killing mites. The most potent ingredient was then tested for its efficacy in killingDemodexin vivo.
  
  
  RESULTS
  All ingredients exhibited a dose-dependent killing effect. Besides Terpinen-4-ol, the order of relative potency did not correlate with the order of relative abundance in TTO for the remaining 12 ingredients. Terpinen-4-ol was the most potent ingredient followed by α-Terpineol, 1,8-Cineole and Sabinene. Terpinen-4-ol, the most abundant ingredient in TTO, was more potent than TTO at equivalent concentrations and its killing effect was even observable at a mere concentration of 1%. Terpinen-4-ol exhibited a significant synergistic effect with Terpinolene, but an antagonistic effect with α-Terpineol in killing mites (bothP< 0.05). In vivo, Terpinen-4-ol was shown to eradicate mites.
  
  
  CONCLUSIONS
  The above finding suggests that deployment of Terpinen-4-ol alone should enhance its potency in killingDemodexmites by reducing the adverse and antagonistic effects from other ingredients in TTO.
  
  
  CONCLUSIONS
  Terpinen-4-ol can be adopted in future formulations of acaricides to treat a number of ocular and cutaneous diseases caused by demodicosis.
authors.affiliation: TissueTech, Inc. and Ocular Surface Center, Miami, FL.
authors.forename: Sean
authors.initials: S
authors.lastname: Tighe
authors.affiliation: TissueTech, Inc. and Ocular Surface Center, Miami, FL ; Department of Ophthalmology, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Gao
authors.affiliation: TissueTech, Inc. and Ocular Surface Center, Miami, FL.
authors.forename: Scheffer C G
authors.initials: SC
authors.lastname: Tseng
keywords: acaricide; demodex; ocular drug delivery; tea tree oil; terpinen-4-ol