組成物用於治療高血壓的用途

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

110138970

專利證號

I 785853

專利獲證名稱

組成物用於治療高血壓的用途

專利所屬機關 (申請機關)

輔仁大學學校財團法人輔仁大學

獲證日期

2022/12/01

技術說明

高血壓是全世界重要的疾病之一，它的盛行率約占全人口25%，50歲以上約占30%，65歲以上約占50%。在台灣高人口死亡率疾病中，它在第九位，與第二位心臟病，第三位的腦中風息息相關。 本發明即在發現小分子化合物Y16與Rhosine是治療高血壓的藥物。Y16與Rhosine可抑制血管收縮素II型受器訊息傳遞練下游的小G蛋白Rho GEF中的LARG分子，使得其下游的Rho A/Rho Kinase去活化，而進一步抑制血管平滑肌細胞心肌蛋白輕鏈磷酸酶(MCLP)的磷酸化，使Actin與Myosin無法鍵結、收縮，而失去張力，降低了血壓。 Abstract Background/Purpose: The small-molecule compounds Y16 and Rhosin can inhibit the activation of leukemia-associated Rho guanine nucleotide exchange factor (LARG) and small G-protein RhoA, respectively, as well as suppress the activity of the calcium sensitization pathway in vascular smooth muscle cells (VSMCs). However, it remains unclear whether they can decrease the blood pressure (BP) in organism. Methods: The spontaneously hypertensive rats (SHRs) were anesthetized and then attached to a physiological signal recording device. The Y16 and Rhosin were administered to them by intravenous injection. The electrocardiography (ECG), heart rate (HR), and BP measurements were taken. After recording the physiological signals, blood was drawn for tests of complete blood cell count and liver function. The rats were then sacrificed. Their heart, lungs, liver, and kidneys were removed and were fixed in 4% paraformaldehyde overnight and then embedded in paraffin for histological examination. The transverse sections (4 μm) were incubated at 75~85°C for 10 minutes, followed by stained with hematoxylin/eosin (HE), and examined under a light microscope. Results: Both Y16 and Rhosin can dose-dependently reduce the BP of SHRs. However, high doses (20mg/kg) of the drugs could lower HR, but the difference was not statistically significant. A lower dose of Y16 combined with a lower dose of Rhosin, Y16 (3mg/kg) + Rhosin (7mg/kg) or Y16 (5mg/kg) + Rhosin (10mg/kg), has the same BP reduction effects as a high single dose of Y16 or Rhosin without having any effects on HR. None of the doses could cause overt injuries to the rats’ organs or cells within a short period of time (90 minutes of observation). Conclusion: Small-molecule compounds Y16 and Rhosin can decrease BP, respectively, in the SHRs. In addition, Y16 can also cooperate with Rhosin to produce better antihypertensive effect. The combination of Y16 and Rhosin at lower doses can achieve the antihypertensive effect that higher doses are needed when they are used separately

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