DEVELOPMENT OF A MARINE ANTI-PLAQUE COMPOUND

流行病学调查表明，平均50%的美国（US）成年人患有牙龈炎，牙龈炎可导致许多危及生命的疾病，如心脏病。由于牙龈炎是由菌斑引起的，而菌斑是由各种细菌组成的，因此理论上抗菌剂应该对牙龈炎有效。大多数抗牙菌斑化合物，例如三氯生、氯己定和氟，都是卤化的。海洋微生物可以产生整合卤素（如氯和溴）的化合物，因此可以成为发现抗牙菌斑化合物的重要资源。最近，4,800提取物来自150海洋微生物进行了筛选抗微生物活性对-放线菌共生嗜血杆菌，粘性放线菌，变形链球菌。发现一种生物的提取物APP 214对这些微生物具有优异的抑制和杀菌活性。本提案的具体目的是分离、鉴定和表征（在抗菌功效和毒性方面）来自APP 214的生物活性成分。在II期，将对候选化合物进行药物和组合化学，以最大限度地提高对口腔相关微生物的有效性和直接性。 在第三阶段，领先的抗牙菌斑化合物将与工业合作伙伴，如缅因州的汤姆，吉列或高露洁棕榄商业化。拟议的商业应用：目前还没有既方便使用又吸引消费者的真正有效的抗牙龈炎产品。 一种对口腔生物膜（牙菌斑）有效且实质性的产品将在美国和国际上具有巨大的市场潜力。

Epidemiological surveys indicate that an average of 50% of the adult population of the United States (US) has gingivitis and that gingivitis can lead to a number of life threatening illnesses such as heart disease. Since gingivitis is caused by plaque and plaque is composed of various kinds of bacteria, in theory antimicrobial agents should be effective against gingivitis. Most anti-plaque compounds, e.g. triclosan, chlorohexidene and fluorine, are halogenated. Marine microorganisms, which can generate compounds that integrate halogens such as chlorine and bromine, can thus be an important resource for the discovery of anti-plaque compounds. Recently 4,800 extracts derived from 150 marine microorganisms were screened for anti-microbial activity against - Haemophilus actinomycetemcomitans, Actinomyces viscosus, and Streptococcus mutans. The extract of one organism, APP214, was found to have excellent inhibitory and bactericidal activity against these microorganisms. The specific aims of this proposal are to isolate, identify and characterize (in terms of antimicrobial efficacy and toxicity) the bioactive components derived from APP214. In Phase II, medicinal and combinatorial chemistry will be performed on the candidate compound(s) to maximize effectiveness and substantivity against orally-relevant microorganisms. In Phase III, the lead anti-plaque compound will be commercialized with an industrial partner, such as Tom's of Maine, Gillette or Colgate-Palmolive. PROPOSED COMMERCIAL APPLICATIONS: There is currently no truly efficacious anti-gingivitis product that is also both convenient to use and appealing to the consumer. A product that is effective and substantive against oral biofilms (dental plaque) will have a significant market potential in the United States and internationally.