ORAL DISSOLUTION OF KIDNEY STONES WITH DRUGS FROM MEDICINAL PLANTS

用药用植物药物口服溶解肾结石

• 批准号: 6107153
• 负责人: FERNANDO A SOUTO
• 金额: $ 5.66万
• 依托单位: UNIVERSITY OF PUERTO RICO MAYAGUEZ
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107153
• 关键词: United States; chemical structure function; clinical research; data collection; diuretics; drug design /synthesis /production; drug discovery /isolation; drug screening /evaluation; field study; gas chromatography; gas chromatography mass spectrometry; high performance liquid chromatography; human data; kidney disorder chemotherapy; laboratory rat; medicinal plants; nephrocalcinosis; nephrolithiasis; oral administration; plant extracts; thin layer chromatography; ultracentrifugation; ultraviolet spectrometry

Kidney stones are one of the most painful disorders to afflict humans. In the United States, urinary stone disease is a common clinical problem with a high risk of recurrence. One out of every ten Americans suffer kidney stone disease sometime during their lifetime. It is the third leading cause of hospitalization in this country and the seventh leading cause for visits to urologists. Clinical treatment of stone related disorders is estimated to cost over $2 billion per year. Current medical treatment will not dissolve symptomatic kidney stones. Since most stones will not pass out of the body spontaneously, comminution with high intensity shock waves (SWL) has become nearly a standard procedure for stones in the upper urinary tract. However, compelling clinical data now suggests that SWL may cause acute renal injury, a rise in diastolic blood pressure, a decrease in renal function, and an increase in stone recurrence. This proposal seeks an alternative to SWL for kidney stone treatment. Oral dissolution therapy of kidney stones with diuretic medicinal plants has been known for millennia by the indigenous people of America, India, and Arabia. The objective of this proposal is to place in scientific perspective the ethnopharmacological use of medicinal plants in Middle America as diuretics for the treatment of kidney stones. Numerous herbal treatments of this disease seem to cure the patients. However, little evaluation of diuretic medicinal plants has been performed using objective scientific methods and the pharmacology of their phytomedicinals is still unclear. The hypothesis is that effective medicinal plants may contain a) natural diuretics that decrease Ca ion excretion, b) organic inhibitors of CaOx (oxalate) crystallization from naturally super-saturated urine, c) Ca ion chelating agents capable to further reduce the free Ca concentration, d) amphiphilic agents or enzymes that digest the organic matrix of large stones, and e) anti-inflammatory agents and urinary muscle relaxants that facilitate the passage of smaller stones. This hypothesis will be tested by 1) clinical studies with patients treated for kidney stones in Puerto Rico, 2) physicochemical in vitro studies with medicinal plant extracts, and 3) selected in vivo tests with an animal model. The specific aims will be: a) collection and study of clinical records to find whether patients use medicinal plants to break and expel kidney stones, b) botanical identification of plants likely to posses biological activity, c) field collection of plant material, and d) characterization of plant extracts using both in vitro and in vivo models for kidney stone dissolution. Screens will be conducted with crude plant extracts to test for comminution activity against CaOx and CaP stones and low levels of free Ca ions. When crude extracts prove positive in either test, biodirected assays with animals will allow to identify active fractions with biodynamic compounds. Isolation and characterization of these principles will provide chemical which could be developed into new pharmaceutical of substantial of substantial to human health.

肾结石是困扰人类的最痛苦的疾病之一。在美国，尿石疾病是一个常见的临床问题，复发的风险很高。在他们一生中的某个时候，每十分之一的美国人中有一个患有肾脏石头疾病。这是该国住院的第三大主要原因，也是访问泌尿科医生的第七主要原因。相关疾病的临床治疗估计每年成本超过20亿美元。当前的医疗不会溶解有症状的肾结石。由于大多数石头不会自发地从体内传播，因此高强度冲击波（SWL）几乎已成为上尿路中石头的标准程序。但是，引人注目的临床数据现在表明SWL可能会导致急性肾脏损伤，舒张压升高，肾功能降低以及石材复发的增加。该建议寻求SWL的替代肾脏石材治疗。美国土著人民，印度和阿拉伯对肾结石的口服溶解疗法已在数千年中闻名。该提议的目的是从科学角度置于中美洲药用植物作为肾结石治疗的利尿剂的民族药物使用。这种疾病的许多草药治疗似乎可以治愈患者。但是，使用客观的科学方法对利尿剂植物进行了几乎没有评估，其植物医学的药理学仍不清楚。假设是有效的药用植物可能含有a）自然排泄的天然利尿剂，b）自然超饱和尿液中Caox（草酸盐）结晶的有机抑制剂，c）Ca离子螯合剂，能够进一步降低CA的浓度，d）较大的有机物，d）较大的有机物，digement and eNzemient nimik intrix intrix nimix intrix intrix nigrix nigrix themix intrix themix and eyzemix trix trix trix an药物和尿肌松弛剂促进较小的石头的通过。该假设将通过1）在波多黎各接受肾结石的患者的临床研究，2）用药物植物提取物进行物理化学的体外研究，以及3）用动物模型选择的体内测试。具体目的是：a）收集和研究临床记录，以发现患者是否使用药用植物破裂和驱除肾结石，b）植物鉴定可能具有生物学活性的植物，c）植物材料的现场收集，d）植物提取物的表征，使用体外和体外和体内的肾脏石材溶解的植物提取物。将使用粗植物提取物进行筛选，以测试针对Caox和Cap Stones以及低水平的自由Ca离子的粉碎活性。当任何测试中的原油提取物均为阳性时，用动物的生物方向测定将允许鉴定具有生物动力化合物的活性馏分。这些原理的隔离和表征将提供化学物质，可以发展为新的药物，以实质性对人类健康。