可同時口服傳遞疏水性小分子藥物和親水性小分子藥物的醫藥組合物

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

109117920

專利證號

I 739450

專利獲證名稱

可同時口服傳遞疏水性小分子藥物和親水性小分子藥物的醫藥組合物

專利所屬機關 (申請機關)

國立清華大學

獲證日期

2021/09/11

技術說明

口服投藥對病患來說，是一最舒適且易被接受的給藥方式。然而小分子疏水藥物在小腸絨毛處由於分子間的聚集現象無法有效地被吸收，造成了這類藥物的口服生體可利用率都相當的低。因此目前臨床上，是以靜脈注射來投遞藥物。然而注射投藥所造成的疼痛以及心理恐懼，往往讓病人產生極大的排斥感。本研究擬研發一自我乳化脂質油珠奈米載體平台技術，用於口服吸收疏水性小分子藥物，經淋巴系統以標的胰臟相關疾病。疏水性藥物在腸道內可自我乳化載入脂質油珠內，增加其溶解性、避免藥物分子自我聚集失去活性，且配方內無需添加高毒性的Cremophor EL。 The oral route is a preferred route for drug administration because it does not cause the pain or contamination that are associated with injections. Increasing the oral absorption of drugs that have poor oral bioavailability to a therapeutically acceptable level has long been an elusive goal. This work proposes an oral drug delivery platform for forming oil-structured nanoemulsions containing hydrophobic drugs that are self-emulsified in the intestinal tract. The proposed oral platform is based on a bubble-carrier system that comprises a mixture of an acid initiator (citric acid), a foaming agent (sodium bicarbonate), a surfactant (capric acid), and a poorly water-soluble drug (paclitaxel), all in a gelatin capsule that is then coated with an enteric polymer. Following oral administration of the enteric-coated capsule and its dissolution in the small intestine, its citric acid is exposed to the intestinal fluid, forming an acidic environment, in which sodium bicarbonate decomposes to generate CO2 bubbles that are stabilized by a monolayer of surfactant molecules (capric acid). The lipophilic tails of these surfactant molecules cause them to self-assemble into a nanofilm into which is incorporated the poorly water-soluble paclitaxel. As the CO2 bubbles expand, rise, and approach the water/air interfaces in the intestinal lumen, this self-assembled monolayer carrier system becomes double-layer nanoassemblies. After the bubbles burst in the air, the surfactant molecules (capric acid) readily convert the nanoassemblies into oil-structured nanoemulsions that contain paclitaxel (paclitaxel-loaded lipid oil drops) via self-emulsification. A drug that is delivered through the lymphatic system can bypass the hepatic first-pass metabolism and eliminate the need for the toxic formulation vehicle Cremophor EL®, making oral delivery a favorable noninvasive means of administering drugs. The proposed oral platform enables a broad spectrum of poorly water-soluble drugs to be effectively self-emulsified in the intestinal tract, increasing their solubility and thereby greatly enhancing their oral bioavailability. As the preparation of the described self-emulsified lipid oil drop system is quite straightforward, involving simply filling an enteric-coated capsule with a mixture of the ingredients, the delivery platform can be readily scaled-up for industrial purposes.

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