Preparation method and application of oral microsphere carrying small molecular nucleic acid drug
A molecular nucleic acid and nucleic acid drug technology, which can be applied to medical preparations with non-active ingredients, non-active ingredients of polymer compounds, and medical preparations containing active ingredients, etc. It can solve the problems of complex preparation, low drug loading rate and treatment efficiency To solve the problem, to achieve the effect of simple method, optimization of size and structure characteristics, and alleviation of inflammatory diseases
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Embodiment 1
[0032]This embodiment provides an oral preparation method of small molecule nucleic acid drug microspheres, specifically the preparation method of GelMA microspheres orally loaded cKGM&TNF-αASO nano nucleic acid, the preparation process is as followsfigure 1 As shown, including the following steps:
[0033]Step 1. Preparation of cKGM&TNF-αASO composite nano medicine:
[0034]Weigh KGM in DMSO, heat and dissolve at 60°C, cool to room temperature, add excess CDI, react at room temperature for 3 hours to fully activate, then add excess ethylenediamine, continue to stir to fully react, dialyze, freeze-dry and vacuum Get cKGM. Prepare a 10% w / v cKGM solution, add a small molecule nucleic acid drug solution, and stand for 0.5h to react to obtain a stable nano nucleic acid drug. The molar ratio of KGM to DMSO is 1:106, The mass ratio of KGM to CDI is 1:2, and the molar ratio of KGM to ethylenediamine is 1:105, The mass ratio of cKGM to TNF-αASO is 1:5.
[0035]Step 2: Preparation of GelMA microsphe...
Embodiment 2
[0043]This embodiment provides a preparation method of oral small molecule nucleic acid drug microspheres, specifically the preparation of GelMA microspheres loaded cKGM&TNF-αsiRNA nano nucleic acid, including the following steps:
[0044]Step 1. Preparation of cKGM&TNF-αsiRNA composite nanomedicine:
[0045]Weigh KGM in DMSO, heat and dissolve at 60°C, cool to room temperature, add excess CDI, react at room temperature for 3 hours to fully activate, then add excess ethylenediamine, continue to stir to fully react, dialyze, freeze-dry and vacuum Get cKGM. Prepare a 10% w / v cKGM solution, add a small molecule nucleic acid drug solution, and stand for 0.5h to react to obtain a stable nano nucleic acid drug. The molar ratio of KGM to DMSO is 1:106, The mass ratio of KGM to CDI is 1:2, and the molar ratio of KGM to ethylenediamine is 1:105, The mass ratio of cKGM to TNF-αsiRNA is 1:5.
[0046]Step 2. Preparation of GelMA microspheres carrying cKGM&TNF-αsiRNA:
[0047]Prepare 15% w / v GelMA aqueous s...
Embodiment 3
[0052]This embodiment provides a method for preparing oral small molecule nucleic acid drug microspheres, specifically the preparation of methacrylate hyaluronic acid (HAMA) microspheres loaded cKGM&TNF-αASO nano nucleic acid, including the following steps:
[0053]Step 1. Preparation of cKGM&TNF-αASO composite nano medicine:
[0054]Weigh KGM in DMSO, heat and dissolve at 60°C, cool to room temperature, add excess CDI, react at room temperature for 3 hours to fully activate, then add excess ethylenediamine, continue to stir to fully react, dialyze, freeze-dry and vacuum Get cKGM. Prepare a 10% w / v cKGM solution, add a small molecule nucleic acid drug solution, and stand for 0.5h to react to obtain a stable nano nucleic acid drug. The molar ratio of KGM to DMSO is 1:106, The mass ratio of KGM to CDI is 1:2, and the molar ratio of KGM to ethylenediamine is 1:105, The mass ratio of cKGM to TNF-αASO is 1:5.
[0055]Step 2: Preparation of GelMA microspheres carrying cKGM&TNF-αASO:
[0056]Prepare a...
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