English:
[0001] This invention relates generally to the treatment of disorders, diseases, and other adverse medical conditions, including the adverse ocular conditions often associated with aging. More particularly, the invention pertains to the treatment of conditions associated with the presence of macromolecular aggregates such as may be present in the eye. The invention finds utility in a variety of fields, including ophthalmology and geriatrics.
[0002] Progressive, age-related changes of the eye, including normal as well as pathological changes, have always been an unwelcome but inevitable part of extended life in humans and other mammals. Many of these changes seriously affect both the function and the cosmetic appearance of the eyes. These changes include: development of cataracts; hardening, opacification, reduction of pliability, and yellowing of the lens; yellowing and opacification of the cornea; presbyopia; clogging of the trabeculum, leading to intraocular pressure build-up and glaucoma; increased floaters in the vitreous humor; stiffening and reduction of the dilation range of the iris; age-related macular degeneration (AMD); formation of atherosclerotic deposits in retinal arteries; dry eye syndrome; and decreased sensitivity and light level adaptation ability of the rods and cones of the retina. Age-related vision deterioration includes loss in visual acuity, visual contrast, color and depth perception, lens accommodation, light sensitivity, and dark adaptation. Age-related changes also include changes in the color appearance of the iris, and formation of arcus senilis. The invention is, in large part, directed toward a formulation and method for preventing and treating a multiplicity of age-related ocular disorders and diseases.
[0003] All parts of the eye, including the cornea, sclera, trabeculum, iris, lens, vitreous humor, and retina are affected by the aging process, as explained below.
[0008] Another common ocular disorder that adversely affects the cornea as well as other structures within the eye is keratoconjunctivitis sicca, commonly referred to as "dry eye syndrome" or "dry eye." Dry eye can result from a host of causes, and is frequently a problem for older people. The disorder is associated with a scratchy sensation, excessive secretion of mucus, a burning sensation, increased sensitivity to light, and pain. Dry eye is currently treated with "artificial tears," a commercially available product containing a lubricant such as low molecular weight polyethylene glycol. Surgical treatment, also, is not uncommon, and usually involves insertion of a punctal plug so that lacrimal secretions are retained in the eye. However, both types of treatment are problematic: surgical treatment is invasive and potentially risky, while artifical tear products provide only very temporary and often inadequate relief.
[000119] Contrast sensitivity: Measurements are shown in Table 4.
[000181] Results. FIG. 10 shows the percent of cell viability under each condition. The oxidants decreased cell viability between 30% (Fenton) and almost 45% (ascorbate + H2O2). The addition of 4 mM MSM increased the percent cell viability for all oxidants, while the addition of 4 mM MSM with 0.5 mM EDTA gave a greater increase in the percentage of viable cells. A Chi Square test was performed to determine whether the protective effects of MSM/EDTA were statistically significant. For those wells containing an oxidant plus the MSM/EDTA mixture, statistically significant results (P value of less than 0.05) were obtained for all oxidants except Fenton.

中文:
[0001]本发明一般涉及紊乱、疾病和其它不良医学病症,包括常常与衰老有关的不良眼睛病症的治疗。更具体地说,本发明涉及与大分子聚集体(macromolecular aggregates)的存在,例如可存在于眼中的大分子聚集体有关的病症的治疗。本发明在多个领域,包括眼科学和老年病学中发现其效用。
[0002]与衰老有关的进行性的眼睛变化,包括正常的以及病理性变化,总是令人讨厌的但却是人和其它动物延长生命中不可避免的部分。许多这样的变化严重影响眼睛的功能和美观。这些变化包括:白内障的发展;晶状体的硬化、混浊、柔韧性降低和变黄;角膜泛黄和混浊;远视眼;小梁(trabeculum)堵塞,导致眼内压增加和青光眼;玻璃体液中悬浮物(floaters)增加;虹膜的扩张范围僵硬和缩减;与衰老有关的黄斑变性(AMD);视网膜动脉中的动脉粥样硬化的沉积物的形成;干眼综合症和视网膜的视杆细胞和视锥细胞的敏感性以及光水平适应能力降低。与衰老有关的视觉退化包括视敏度、视觉对比、色觉和深度感觉、晶状体调节、光敏感性和暗适应的丧失。与衰老有关的变化还包括虹膜颜色外观的变化和老年环的形成。本发明主要涉及用于预防和治疗与衰老有关的眼睛病症和疾病的制剂和方法。
[0003]如下说明的,眼的所有部分,包括角膜、巩膜、小梁、虹膜、晶状体、玻璃体液和视网膜均受到衰老过程的影响。
[0008]另一个常见的对角膜以及眼中其它结构产生不良影响的眼科疾患是角膜结膜炎,通常指如“干眼综合征”或“干眼”。干眼可由许多原因引起,是老人常见的问题。该疾患与刺痒感、粘液过度分泌、灼烧感、对光变得更敏感和疼痛相关联。目前,用“人工泪液”治疗干眼,“人工泪液”是含润滑剂诸如低分子量的聚乙二醇的、商业上可获得的产品。手术治疗也是常用的,通常包括插入泪点塞(punctal plug),这样使泪腺分泌液保留在眼中。然而,两类治疗均存在问题:手术治疗是侵入性的并且具有潜在危险,而人工泪液产品仅提供非常短暂的并且经常是不足以缓解。
[000119]对比敏感度:测量值示于表4中。
[000181]结果.图10显示每种条件下的细胞生存能力的百分比。氧化剂降低细胞生存能力30%(Fenton)至几乎45%(抗坏血酸盐+H2O2)之间。加入4mM MSM增加对所有氧化剂的百分细胞生存能力,而加入4mM MSM和0.5mM EDTA使细胞生存能力百分比增加更多。卡方检验证明,MSM/EDTA的保护作用具有统计学上的显著意义。对于那些含氧化剂加上MSM/EDTA混合物的孔,除了Fenton外,得到对于所有氧化剂的具有统计学显著意义的结果(P值小于0.05)。