Schiff base forming sunscreen filters for long-wear UV protection

描述（由申请人提供）：待解决的问题：皮肤癌是所有癌症中最常见的，占美国所有报告的癌症病例的近一半。根据美国癌症协会（ACS）的说法，降低非黑色素瘤皮肤癌风险的最佳方法是通过使用广谱防晒霜来“实践防晒安全”。商业防晒霜的一个主要缺点是过滤器与皮肤缺乏实质性的接触，并且很容易通过正常佩戴而去除。因此，消费者必须不断地重新涂抹防晒霜，以受益于产品提供的保护。产品和长期目标：Nanometics开发了涂层无机防晒过滤器，与表皮形成临时粘合，提供长期佩戴保护免受紫外线辐射。该过滤器可用作局部给药系统的成分，我们预计这些过滤器将满足不断重复使用产品的需要。新型过滤器将作为粉末和特种分散体在全球销售，并作为局部配方中的长效成分。技术创新：一种天然存在的抗氧化剂配体，吸附在防晒级TiO 2和ZnO颗粒的表面，作为一种异双功能连接剂，与表皮胺形成临时共价键，将颗粒化学“连接”到皮肤上。初步结果表明，新的颗粒表现出防水性能。到目前为止，我们已经证明了这些颗粒在人类临床小组中的初步安全性及其在已建立的体外皮肤模型中的实用性。第一阶段假设：第一阶段假设是，配体吸附到防晒过滤器上不会对（1）紫外线防护的广度和强度产生负面影响，并且不会（2）增加颗粒的细胞毒性或光遗传毒性。具体目标：本I期SBIR的具体目的是（1）确定微粒的体外紫外线防护宽度和人体样本组的紫外线防护强度，以及（2）确定微粒的体外细胞毒性和光遗传毒性潜力。第二阶段：第II阶段SBIR研究将重点关注优化颗粒在体内的长期磨损属性，并证明这些颗粒在已建立模型中的完整毒理学特征。商业机会：防晒市场估计占97亿美元国内护肤品市场的13.30%。随着公众对紫外线照射的危险性越来越了解，预计防晒市场的增长速度将超过其他领域。与化妆品公司（雅芳、雅诗兰黛）高管的讨论表明，需要对人体皮肤有实质性作用的长效防晒过滤器。 公共卫生相关性：皮肤癌，如鳞状细胞癌和基底细胞癌，是美国最常见的癌症形式。暴露于紫外线（UV）光是已知的皮肤癌发展的风险因素，并且卫生保健机构建议使用局部防晒霜作为预防UV暴露的措施。该项目旨在促进使用长效防晒过滤器，保护消费者免受辐射的有害影响，而无需不断重复使用。

DESCRIPTION (provided by applicant): Problem to be solved: Skin cancer is the most common of all cancers, accounting for nearly half of all reported cancer cases in the USA. According to the American Cancer Society (ACS), the best way to lower the risk of non-melanoma skin cancer is "to practice sun safety" by applying broad-spectrum sunscreens. One major disadvantage of commercial sunscreens is that the filters lack substantively with the skin and are easily removed by normal wear. As a consequence, the consumer must constantly reapply the sunscreen to benefit from the protection offered by the product. Product and Long-Term Goal: Nanometics has developed coated inorganic sunscreen filters that form temporary bonds with the epidermis, providing for long-wear protection from UV radiation. The filters are useful as ingredients in topical delivery systems and we anticipate that these filters will alleviae the need for constant product reapplication. The novel filters will be sold globally as powders and specialty dispersions, to be incorporated as long-wear ingredients in topical formulas. Technical Innovation: A naturally occurring anti-oxidant ligand, adsorbed to the surface of sunscreen grade TiO2 and ZnO particles, acts as a hetero bifunctional linker and forms temporary covalent bonds with epidermal amines, chemically "linking" the particles to the skin. Preliminary results have demonstrated that the novel particles exhibit water resistant properties. Thus far we have demonstrated the preliminary safety of these particles in a human clinical panel and their utility in an established in vitro skin model. Phase I Hypothesis: The Phase I hypothesis is that adsorption of the ligand onto the sunscreen filter does not negatively impact (1) the breadth and magnitude of UV protection and will not (2) increase the cytotoxicity or photogenotoxicity of the particles. Specific Aims: The specific aims of this Phase I SBIR are to (1) determine the particles breadth of UV protection in vitro and magnitude of UV protection in a human panel and (2) To determine the cytotoxic and photogenotoxic potential of the particles in vitro. Phase II: Phase II SBIR studies will focus on optimizing the long-wear attributes of the particles in vivo and demonstrating the complete toxicological profile of these particles in established models. Commercial Opportunity: The sun care market is estimated to represent 13.30% of the $9.7 billion domestic skin care market. As the public becomes more educated about the dangers of UV exposure, the sun care market is expected to grow more rapidly than other segments. Discussions with executives at cosmetic companies (Avon, Estee Lauder) indicate a need for long-wear sunscreen filters that are substantive on human skin. PUBLIC HEALTH RELEVANCE: Skin cancers, such as squamous and basal cell carcinomas, represent the most common form of cancer in the United States. Exposure to ultraviolet (UV) light is a known risk factor for the development of skin cancer and health care agencies recommend that topical sunscreens be used as preventative measures against UV exposure. This project seeks to advance the use of long-wear sunscreen filters that will protect the consumer from the harmful effects of radiation, without the need for constant reapplication.