Schiff base forming sunscreen filters for long-wear UV protection

描述(申请人提供)：有待解决的问题：皮肤癌是所有癌症中最常见的，占美国报告的所有癌症病例的近一半。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好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，滤镜与皮肤缺乏实质性的联系，很容易通过正常佩戴来去除。因此，消费者必须不断重复使用防晒霜，才能从产品提供的保护中受益。产品和长期目标：Nanometics已经开发出涂层无机防晒滤镜，这种滤镜可以暂时与表皮形成粘结，从而提供针对紫外线辐射的长期耐磨保护。这些过滤器在局部给药系统中用作配料，我们预计这些过滤器将减轻对产品不断重复使用的需求。这种新型过滤器将以粉末和特种分散体的形式在全球销售，并作为长效成分加入局部配方中。技术创新：一种天然存在的抗氧化剂配体，吸附在防晒级二氧化钛和氧化锌颗粒的表面，充当异质双功能连接剂，并与表皮胺形成临时共价键，以化学方式将颗粒连接到皮肤上。初步结果表明，这种新型粒子具有防水性能。到目前为止，我们已经在人类临床小组中证明了这些颗粒的初步安全性，并在已建立的体外皮肤模型中证明了它们的有效性。第一阶段假设：第一阶段假设是，配体在防晒膜上的吸附不会对(1)紫外线防护的广度和大小产生负面影响，也不会(2)增加颗粒的细胞毒性或光遗传毒性。具体目标：这一阶段SBIR的具体目标是(1)确定粒子在体外的紫外线防护宽度和在人体面板中的紫外线防护幅度，以及(2)确定粒子的体外细胞毒性和光遗传毒性潜力。第二阶段：第二阶段SBIR研究将集中于优化颗粒在体内的长期磨损属性，并在已建立的模型中展示这些颗粒的完整毒理学特征。商业机会：据估计，防晒品市场占国内97亿美元护肤品市场的13.30%。随着公众更多地了解紫外线照射的危险，防晒市场预计将比其他细分市场增长更快。与雅芳(Avon)、雅诗兰黛(Estee Lauder)等化妆品公司高管的讨论表明，有必要长期使用对人体皮肤有实质性影响的防晒霜。 公共卫生相关性：皮肤癌，如鳞癌和基底细胞癌，是美国最常见的癌症形式。暴露在紫外线(UV)下是患皮肤癌的已知危险因素，卫生保健机构建议使用局部防晒霜作为预防紫外线暴露的措施。该项目旨在促进长期佩戴防晒霜的使用，以保护消费者免受辐射的有害影响，而不需要不断重复使用。

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.