BIOELASTIC MATRICES FOR PREVENTION OF PRESSURE ULCERS

用于预防压疮的生物弹性基质

• 批准号: 2827009
• 负责人: DAN W URRY
• 金额: $ 10.58万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2827009
• 关键词: decubitus ulcer; disease /disorder model; disease /disorder prevention /control; dogs; elastic tissue; enzyme inhibitors; fatty acid biosynthesis; human tissue; mechanical pressure; necrosis; nonhuman therapy evaluation; peptide chemical synthesis; thromboxanes; transdermal drug delivery

Pressure-induced dermal lesions deriving from wide ranging circumstances present significant medical problems to individuals dependent on assistive devices. Because of the diverse situations under which these lesions occur, a generally applicable means of preventing the development of pressure or decubitus ulcers would be advantageous. This research proposal, in response to the RFA HD 93-012 entitled "Assistive Devices and Skin Integrity," is to develop a general purpose transdermal delivery system for the prevention of early dermal pressure pathology. It is a multidisciplinary approach combining the expertise of the biophysical and material scientist with that of the biochemist and veterinarian researcher. It is an interventional approach in which a relatively new class of biomaterials is to be used to deliver medication, to sites at risk, for the purpose of preventing the tissue necrosis that results whenever soft tissue is compressed between an assistive device and an bony prominence. The biochemical approach is to inhibit enzyme, thromboxane synthetase, which produces thromboxanes considered responsible for the tissue necrosis. The animal model is to be the greyhound dog which, because of its thin skin, angular body, limited body fat and hair, is predisposed to pressure ulcers similar to those occurring in humans. The proposed four-year research efforts is in the form of four research projects, each of which has a primary specific aim; namely: PROJECT I, to synthesize and develop elastomeric polypeptide biomaterials in the form of bioelastic matrices for the effective transdermal delivery of thromboxane synthetase inhibitor; PROJECT II, to establish in vitro the inhibitor penetration into and through the viable skin of the greyhound dog and human skin derived from breast reduction surgeries; PROJECT III, to evaluate in vivo the capacity of inhibitor doped bioelastic matrices to effect penetration of three widely different concentrations of medication into the skin of the greyhound; and PROJECT IV, to evaluate the effectiveness of each of the inhibitor-laden bioelastic matrices at the three coarsely different concentrations of inhibitor to prevent pressure dermal lesions in greyhound dogs wearing a short limb, coaptation, walking cast and then having determined which of the three coarse concentrations is most effective, to establish with a finer grained range of concentrations the most effective concentration for which the inhibitor-laden matrix will prevent the tissue necrosis leading to pressure ulcer. In general the projects are to run in sequence with PROJECT I continuing at a reduced level for years 2, 3 and 4 to provide inhibitor-loaded bioelastic matrices to PROJECTS II, III, and IV and to refine inhibitor time release profiles. PROJECT II is to use viable skin in vitro in a specially designed chamber for which considerable transdermal penetration studies have been carried out and PROJECTS III, and IV continue work on the short limb, cast model for the greyhound dog for which the thromboxane synthetase inhibitor given by mouth was found to be effective in reducing lesion formation.

压力引起的皮肤损伤来自广泛的环境 对依赖于 辅助设备。 由于这些国家在不同情况下， 病变发生时，一种普遍适用的预防发展的手段， 压迫性或褥疮性溃疡将是有利的。 本研究 建议，以响应题为“辅助设备”的RFA HD 93-012 和皮肤完整性，”是开发一种通用的透皮给药 预防早期皮肤压力病理的系统。 这是一个 多学科方法，结合生物物理和 材料科学家与生物化学家和兽医 研究员 这是一种介入性方法， 一类生物材料将用于将药物输送到 风险，目的是防止组织坏死， 每当软组织被压缩在辅助装置和 骨突 生化方法是抑制酶， 血栓素合成酶，其产生血栓素， 导致组织坏死 动物模型是 灰狗，因为它的皮肤薄，有棱角的身体，有限的身体 脂肪和头发，容易患上类似于那些 发生在人类身上。 拟议的四年研究工作是以四项研究的形式进行的 每个项目都有一个主要的具体目标，即：项目I， 合成和开发弹性多肽生物材料 用于有效透皮递送的生物弹性基质的形式 血栓素合成酶抑制剂; PROJECT II，在体外建立 抑制剂渗透到灰狗的活皮肤中并穿过灰狗的活皮肤 来自乳房缩小手术的狗和人的皮肤;项目III， 为了在体内评价掺杂抑制剂的生物弹性基质的能力 以实现三种不同浓度的 药物进入皮肤的灰狗;和项目四，以评估 每一个载有通道的生物弹性基质在 三种不同浓度的抑制剂，以防止 在穿着短肢的灰狗中的压力皮肤损伤， 然后决定这三个中的哪一个 粗浓度是最有效的，建立与较细的 颗粒浓度范围最有效的浓度 其负载的基质将防止组织坏死， 压力性溃疡 一般而言，项目将按顺序进行，项目I将继续进行 第2、3和4年降低水平， 生物弹性基质，项目II，III和IV，并完善抑制剂 时间释放曲线。 项目二是在体外使用有活力的皮肤， 专门设计的腔室， 已经开展了研究，项目III和IV继续开展工作， 短肢，铸造模型的灰狗， 口服血栓素合成酶抑制剂有效 减少损伤的形成。

项目成果

Skin concentrations of thromboxane synthetase inhibitor after topical application with bioelastic membrane.

局部应用生物弹性膜后血栓素合成酶抑制剂的皮肤浓度。

• DOI: 10.1046/j.0140-7783.2003.00544.x
• 发表时间: 2004
• 期刊: Journal of veterinary pharmacology and therapeutics
• 影响因子: 1.3
• 作者: Wang,N-Z;Urry,DW;Swaim,SF;Gillette,RL;Hoffman,CE;Hinkle,SH;Coolman,SL;Luan,C-X;Xu,J;Kemppainen,BW
• 通讯作者: Kemppainen,BW