Tea Tree Oil for Treating Ocular Demodex Infestation

描述（由申请人提供）：蠕形螨（毛囊和短毛囊）是一种微小的体外寄生虫，通常感染皮肤的毛囊皮脂腺单位。这些螨虫不受控制的过度生长与面部酒渣鼻、眼睑炎和其他炎症相关的结膜和角膜异常有关。我们已经进行了大量的研究来证实蠕形螨在引起患者眼睛刺激和炎症方面的潜在致病性。我们已经提高了诊断蠕形螨感染的准确性，基于从患者的睫毛取样，并确定睫毛窝藏圆柱形头皮屑是蠕形螨感染的可靠标志。此外，我们已经开发了一种体外实验来筛选可能杀死成人蠕形螨的药剂。通过这个实验，我们发现婴儿洗发水没有，但是茶树油（TTO），一种从千层树中蒸馏出来的精油，可以杀死螨虫。我们进一步表明，每周用50%的TTO溶液擦洗办公室眼睑，然后每天用茶树洗发水清洁家庭眼睑，可以根除大多数患者的眼部蠕形螨。然而，该方案在大多数（但不是全部）患者中实现了根除蠕形螨感染，在一些患者中产生眼睛刺激，并且仍然不够简单，患者可以在家中自行使用。在SBIR的I期申请中，我们希望确定toto中可能在体外杀死成人蠕形螨的最有效成分，在体外细胞毒性试验和兔眼试验中检查含有该活性成分的眼科配方的安全性/毒性，并确定这些配方在不同储存条件和持续时间下的稳定性。这三个目标的实现将使我们能够收集足够的数据，以获得FDA的IND批准，以便我们可以进行II期临床研究，最终开发出第一个FDA批准的处方眼科配方，该配方含有TTO中最有效的成分，以根除这种最常见的眼部疾病的蠕形螨感染。公共卫生相关性：这项研究旨在开发第一个fda批准的处方药，其中含有茶树油中最有效的成分，以根除蠕形螨病（蠕形螨对毛囊和油腺的微观感染），通常发生在皮肤和眼睑。蠕形螨病是眼睑炎的主要原因之一，眼睑炎是一种常见的眼病，任何非处方的眼睑磨砂疗法都无法根除这种疾病。由于蠕形螨感染在老年人群中普遍存在，因此，当老龄化人口增加时，根除眼部蠕形螨病的有效治疗方法将解决一个重要的公共卫生问题，并有助于在未来开发类似的皮肤治疗方法。

DESCRIPTION (provided by applicant): Demodex (folliculorum and brevis) mites are microscopic ectoparasites that commonly infest the pilosebaceous unit of the skin. Uncontrolled overgrowth of these mites has been implicated in causing rosacea in the face, blepharitis in the eyelid, and other inflammation-associated conjunctival and corneal abnormalities. We have conducted a number of studies to substantiate the potential pathogenicity of demodex mites in causing eye irritation and inflammation in patients. We have improved the accuracy of diagnosing demodex infestation based on sampling lashes from the patient, and established that lashes harboring cylindrical dandruff are a reliable sign indicative of demodex infestation. Furthermore, we have developed an in vitro assay to screen agents that can potentially kill adult demodex mites. Using this assay, we have discovered that the Baby Shampoo does not, but tea tree oil (TTO), an essential oil distilled from Melaleuca alternifolia does, kill mites. We further showed that weekly office lid scrub with 50% TTO solution followed by daily home lid hygiene with tea tree shampoo can eradicate ocular Demodex in a majority of the suffering patients. However, this regimen achieves eradication of demodex infestation in the majority, but not all, of the patients, generates eye irritation in some patients, and is still not simple enough for patients to self administer it at home. In the SBIR Phase I application, we would like to identify the most active ingredient in TTO that may kill adult demodex mites in vitro, to examine the safety/toxicity of ophthalmic formulations containing this active ingredient in an in vitro cytotoxicity test and rabbit eyes, and to determine the stability of such formulations under different storage conditions and durations. Accomplishment of these three aims will allow us to collect sufficient data for obtaining an IND approval from the FDA so that we may conduct, in Phase II, clinical studies, eventually leading to the development of the first FDA-approved prescription ophthalmic formulation containing the most active ingredient in TTO to eradicate ocular demodex infestation in this most common eye disease. PUBLIC HEALTH RELEVANCE: This research is aimed to developing the first FDA-approved prescription drug containing the most active ingredient in tea tree oil to eradicate Demodicosis (the microscopic infestation of the hair follicle and the oil gland by Demodex mites) commonly occurring in the skin and the eyelid. Demodicosis is one of the leading causes of blepharitis, a common eye disease, for which eradication has not been achieved by any over-the-counter lid scrub regimen. Because Demodex infestation is prevalent in the older population, an effective treatment as such for eradicating Demodicosis for the eye will address an important public health concern when the aging population is increased, and help to develop a similar treatment for the skin in the future.