Exploring the Efficacy of a Proteoglycan Mimic for Treatment of Interstitial Cystitis

 描述(申请人提供)：间质性膀胱炎(IC)是一种慢性疼痛综合征。虽然历史上IC的患病率保守地估计为52-200/100,000女性[1]，但Apostolidis和同事的评估表明，这种情况影响了超过2%的女性[2]。患IC的男性明显较少，从8-41/100,000人不等[1]。经历IC的患者有显著的发病率[3]。生活质量受到严重影响；患者表示难以维持正常的 工作安排，在人际关系中遇到挑战，经常感到沮丧，甚至有自杀倾向。在美国，仅病假一项的医疗费用在1987年就估计为4.28亿美元。关于与IC相关的直接医疗索赔费用，与非IC患者提出的费用相比，2002年每人每年增加约4,200美元[3]。因此，对社会造成了直接的医疗、社会和经济负担。这种主要是女性的疾病病因不明；然而，有明确的与膀胱壁相关的病理变化。完整的膀胱的主要功能是充当尿液的短期储存容器。膀胱壁必须在容纳尿液时不透水和废物，以防止重新吸收到血液中。膀胱壁的管腔内有上皮细胞。这些细胞彼此形成紧密的连接，并在其管腔表面分泌大量多糖，以防止尿液渗入膀胱壁内的血管。IC患者上皮细胞的病理改变包括伞状细胞之间紧密连接的丢失、多糖膜变薄、可随尿液渗入血液的上皮细胞斑块的丢失以及膀胱壁的溃疡。膀胱不通透性的丧失可导致相当大的背部和耻骨上疼痛，因为溶质迁移到周围组织并导致频繁、疼痛的排尿[4，5]。Symic Biomedical建议开发一种改进的屏障治疗方法。通过开发针对膀胱壁并结合到膀胱壁的疗法，Symic建议开发一种仿生多糖涂层，作为溶质扩散到膀胱壁的屏障，并保持结合长达一周，从而大大减少治疗频率。

 DESCRIPTION (provided by applicant): Interstitial Cystitis (IC) is a painful syndrome that is chronic in nature. While historic prevalence of IC is conservatively estimated to be 52-200/100,000 females [1], evaluations by Apostolidis and colleagues suggest that the condition affects greater than 2 % of females [2]. Significantly fewer males experience IC, with numbers ranging from 8-41/100,000 individuals [1]. Patients experiencing IC suffer significant morbidities [3]. Quality of life is significantly impacted; patients express difficulties maintaining a regular work schedule, experience challenges in relationships and are often depressed and even suicidal [3]. In the United States, estimates of medical costs for sick leave alone were $428 million in 1987. With respect to filed direct medical claims costs associated with IC as compared to those filed by patients without IC there was an increase of ~$4,200 per person per year in 2002 [3]. Thus, there is a direct medical, social and economic burden on society. This primarily female disease is of unknown etiology; however, there are well-defined pathological changes associated with the bladder wall. The primary function of the intact bladder is to serve as a short-term storage container for urine. The bladder wall must be impermeable to water and waste products while holding the urine to prevent re-adsorption into the blood stream. The lumen of the bladder wall is lined with epithelial cells. The cells form tight junctions with one another and secrete large quantities of polysaccharide on their luminal surface to prevent leakage of urine into the blood vessels within the wall of the bladder. Pathological changes observed in the epithelium of patients with IC include loss of tight junctions between umbrella cells, thinning of the polysaccharide coating, and loss of patches of epithelial cells that can lea to blood in the urine and ulcers in the bladder wall. Loss of bladder impermeability can lead to considerable back and suprapubic pain as solutes migrate into the surround tissue and lead to frequent, painful voiding [4, 5]. Symic Biomedical proposes the development of an improved barrier treatment. By developing therapies that target and bind to the bladder wall, Symic proposes to develop a biomimetic polysaccharide coating that serves as a barrier to solute diffusion into the bladder wall and remains bound for up to one week, thus greatly reducing treatment frequency.