The Development of Inorganic Ultraviolet Filters Exhibiting Improved Topical Retention on Human Skin for The Prevention of Skin Cancer

无机紫外线滤光剂的开发可改善人体皮肤的局部保留，从而预防皮肤癌

• 批准号: 10202504
• 负责人: Steven Isaacman
• 金额: $ 100万
• 依托单位: NANOMETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202504
• 关键词: Affinity; Aldehydes; American; Award; Biological Sciences; Biotechnology; Cells; Chemistry; Cutaneous; Dermal; Development; Diagnosis; Evaluation; Excision; Exhibits; Formulation; Goals; Healthcare; Human; Immersion; Incidence; Kilogram; Knowledge; Laboratories; Legal patent; Link; Malignant Neoplasms; Market Research; Mediating; Modification; Outcome; Penetration; Performance; Phase; Phototoxicity; Preventive measure; Procedures; Process; Proteins; Reapplication; Reproducibility; Resistance; Risk; Risk Factors; Safety; Sampling; Schiff Bases; Self Care; Skin; Skin Cancer; Small Business Innovation Research Grant; Soaps; Sunlight; Sunscreening Agents; Surface; Technology; Time; Toxic effect; UV Radiation Exposure; UV protection; Ultraviolet Rays; United States; Water; Zinc Oxide; alkalinity; cancer care; commercial application; covalent bond; design; healthy volunteer; improved; interest; novel; phase 1 study; photoprotection; prevent; skin cancer prevention; skin organogenesis; success; technological innovation; titanium dioxide; ultraviolet; ultraviolet damage; volunteer

PROJECT SUMMARY / ABSTRACT This Phase II project is predicated on the NCI Phase I award 1R43CA236265-01 and is a resubmission. Problem to be Solved and Significance: Exposure to Ultraviolet radiation (UVR) is a risk factor for the development of skin cancer, and health care agencies recommend that sunscreens be used as a preventative measure. A major limitation of commercial sunscreens is the need to continually reapply to gain full benefit. This is because sunscreens contain UV filters that lack affinity with skin and are easily removed by normal wear. The development of durable filters with improved retention on skin has the potential to mitigate UV- mediated toxicities and remains a significant priority. Product and Long-Term Goal: Nanometics (d.b.a. PHD Biosciences [PHD]) is developing novel titanium dioxide and zinc oxide UV filters that contain a coating that interacts with skin proteins to improve topical retention time for up to 160 min. The novel UV filters are as photoprotective and safe as commercial UV filters and readily synthesized from inexpensive starting materials. They will be sold globally as ingredients for sunscreens and other topical products. It is anticipated that these UV filters will alleviate the need for constant product reapplication. Technological Innovation: The surface of commercial titanium dioxide and zinc oxide UV filters is covalently modified to contain a coating that interacts with skin proteins to improve topical retention time. The coating is designed to form a stable interaction at skin pH and can easily be removed by washing with soap and water. Specific Aim #1 Demonstrate that modification with HPGA does not influence the dermal penetration profile of the UV filters when evaluated on human skin explants. In this aim the dermal penetration profile of HPGA-Filters on cultured human skin will be investigated. Success Criterion: This aim will be successful upon determining that the HPGA-Filters do not penetrate to viable skin cells after a 48 h evaluation period. Specific Aim #2. Scale the chemistry, manufacturing and control processes to produce the HPGA-Filters on 75 kilogram batch sizes. The chemistry, manufacturing, and control (CMC) processes to produce HPGA-Filters in 75 kg batch sizes will be developed. Success Criterion: This aim will be successful upon optimizing the procedure to produce materials at 75 kg batch sizes with reproducible analytical profile and stability. Commercial Opportunity: The global market for UV filters is estimated to exceed $650 million by 2019. Phase II SBIR studies will include additional studies to confirm the safety on a larger number of volunteers; examine the performance against leading commercial sunscreens; and optimize the chemistry, manufacturing, and control (CMC) processes to produce the filters in multi-kilogram quantities. The technology is covered by a pending patent that protects the PHD commercial and development interests.

项目摘要 /摘要 该第二阶段项目的基于NCI I期奖项1R43CA236265-01，是重新提交的。 要解决的问题和意义：暴露于紫外线辐射（UVR）是危险因素 皮肤癌的发展和卫生保健机构建议将防晒霜用作预防性 措施。商业防晒霜的主要局限性是需要不断重新申请以获得全部利益。 这是因为防晒霜含有缺乏皮肤亲和力的UV过滤器，并且很容易通过正常去除 穿。耐用过滤器的发展具有改善对皮肤的保留率，有可能减轻紫外线 介导的毒性，并且仍然是重点。产品和长期目标：纳米学（D.B.A.博士学位 Biosciences [PhD]）正在开发新型的二氧化钛和氧化锌紫外线过滤器，其中含有涂层 与皮肤蛋白相互作用，以提高局部保留时间长达160分钟。新颖的紫外线过滤器 作为商业紫外线过滤器的光保护和安全，并且很容易从廉价的起始材料中合成。 它们将作为防晒霜和其他局部产品作为全球出售。预计这些 紫外线过滤器将减轻恒定产品重新施法的需求。技术创新：表面 商业二氧化钛和氧化锌紫外线过滤器经过共价修改，以包含相互作用的涂层 皮肤蛋白可以改善局部保留时间。涂层设计为在皮肤上形成稳定的相互作用 pH值可以通过肥皂和水清洗很容易去除。特定目的＃1证明了 使用HPGA修饰不会影响紫外线过滤器的皮肤渗透率 对人类皮肤外植体进行了评估。在此目标中，HPGA过滤器对培养 人类皮肤将被研究。成功标准：这个目标将在确定 评估期48小时后，HPGA过滤器不会渗透到可行的皮肤细胞上。特定目标＃2。缩放 化学，制造和控制过程以在75千克批次上生产HPGA过滤器 尺寸。化学，制造和控制（CMC）工艺以75千克批次生产HPGA滤波器 尺寸将开发。成功标准：在优化程序时，此目标将成功 以75千克批量的大小生产具有可重现的分析曲线和稳定性的材料。商业的 机会：到2019年，全球紫外线过滤器的全球市场估计超过6.5亿美元。II期SBIR 研究将包括其他研究，以确认对大量志愿者的安全性；检查 针对领先的商业防晒霜的性能；并优化化学，制造和控制 （CMC）过程以多售学数量生成过滤器。该技术被悬而未决 保护博士商业和发展利益的专利。