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: 10080275
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080275
• 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; 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.

项目概要/摘要 该第二阶段项目以 NCI 第一阶段奖项 1R43CA236265-01 为基础，是重新提交的项目。 待解决的问题及意义：暴露于紫外线辐射（UVR）是导致皮肤病的危险因素 皮肤癌的发生，医疗保健机构建议使用防晒霜作为预防措施 措施。商业防晒霜的一个主要限制是需要不断地重新涂抹才能获得充分的功效。 这是因为防晒霜含有与皮肤缺乏亲和力的紫外线过滤剂，很容易被正常去除。 穿。开发具有更好的皮肤保留能力的耐用过滤器有可能减轻紫外线- 介导的毒性，仍然是一个重要的优先事项。产品和长期目标：纳米学（d.b.a. PHD Biosciences [PHD]）正在开发新型二氧化钛和氧化锌紫外线过滤剂，其涂层可 与皮肤蛋白质相互作用，提高局部保留时间长达 160 分钟。新型紫外线过滤剂如下 与商业紫外线过滤剂一样具有光保护性和安全性，并且很容易由廉价的起始材料合成。 它们将作为防晒霜和其他外用产品的成分销往全球。预计这些 紫外线过滤器将减少不断重复使用产品的需要。技术创新：表面 商用二氧化钛和氧化锌紫外线过滤剂经过共价修饰，含有相互作用的涂层 与皮肤蛋白质一起改善局部保留时间。该涂层旨在与皮肤形成稳定的相互作用 pH 值，可以通过用肥皂和水清洗轻松去除。具体目标#1 证明 当使用 HPGA 进行改性时，不会影响紫外线过滤剂的皮肤渗透特性 在人类皮肤外植体上进行评估。在此目标下，HPGA 过滤器对培养物的皮肤渗透特性 将对人体皮肤进行研究。成功标准：当确定以下目标时，该目标将会成功 经过 48 小时的评估期后，HPGA 过滤器不会渗透到活的皮肤细胞。具体目标#2。规模化 批量生产 75 公斤 HPGA 过滤器的化学、制造和控制流程 尺寸。批量生产 75 公斤 HPGA 过滤器的化学、制造和控制 (CMC) 工艺 将开发尺寸。成功标准：通过优化程序来实现这一目标 生产批量为 75 千克的材料，具有可重复的分析曲线和稳定性。商业的 机遇：到 2019 年，全球紫外线过滤器市场预计将超过 6.5 亿美元。第二阶段 SBIR 研究将包括额外的研究，以确认更多志愿者的安全性；检查 与领先的商业防晒霜相比的性能；并优化化学、制造和控制 (CMC) 工艺可生产公斤级的过滤器。该技术涵盖在一个待定的项目中 保护 PHD 商业和开发利益的专利。