Application of nano material in preparation of nasal nano preparation for brain-targeted delivery of intestinal drugs
A nano-material and nano-preparation technology, applied in the direction of drug combination, drug delivery, unknown raw materials, etc., to achieve the effect of alleviating Alzheimer's disease, easy to operate, fast and special equipment
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Embodiment 1
[0062] Example 1: Ca-MOF is the delivery of the carrier substance through the nasal cavity to the intestinal tract
[0063] 1.1. Synthesis of Curcumin Ca-MOF
[0064] Take 20 g of curcumin, dissolve it in a mixed solution of 1000 mL of ethanol and acetone (volume ratio 4:1), and incubate at 40-50 ° C for 2 h for later use. Take another 5g of anhydrous calcium chloride, dissolve it in 100mL ethanol for later use; add the calcium chloride ethanol solution to the curcumin mixed solution, keep it warm for 2-3 hours, adjust the pH of the above solution to 7-8 with ammonia water, and let it stand overnight ; The curcumin Ca-MOF precipitate was separated by filtration, washed with ethanol three times, and then dried at 70-80°C to obtain the curcumin Ca-MOF.
[0065] 1.2. Construction of Ca-MOF-BSA-Cy3 complex
[0066] with 0.1M Na 2 CO 3Adjust the pH value of BSA to between 8.5 and 9.0. Add NHS-Cy3 under the state of vortex, and mix at room temperature for 3h. After mixing, pas...
Embodiment 2
[0069] Example 2: Fe 3 o 4 For the delivery of carrier substances through the nasal cavity to the intestinal tract
[0070] 1.1, Fe 3 o 4 -BSA-Cy3 complex construction
[0071] Take 2mg Fe 3 o 4 -COOH was resuspended with 800 μL of reaction buffer (0.1M MES, 0.15M NaCl, pH 6.0), and then 200 μL of existing coupling reagent (EDC-HCl solution) was added, and vortexed at room temperature for 30 minutes, and 200 μL of BSA-Cy3 (1 mg) was added. Incubate with rotation at room temperature for 16 h, and remove the supernatant by magnetic separation. 1 mL of blocking buffer (0.2% BSA, 0.1 MES, 0.15M NaCl, pH 6.0) was added to block for 2 h at room temperature, and the supernatant was removed by magnetic separation. Wash 5 times with washing buffer (50 mM Tri-HCl, 0.15 M NaCl, pH 7.2). The specific results after coupling are attached figure 2 E in and figure 2 Shown in F.
[0072] 1.2. Nasal delivery to intestinal tract
[0073] the above Fe 3 o 4 -BSA-Cy3, the supernata...
Embodiment 3
[0074] Example 3: MSN is the delivery of a carrier substance through the nasal cavity to the intestinal tract
[0075] 1.1 Synthesis of 400nm MSN
[0076] Mix 5mL of Cetyltrimethylammonium chloride (CTAC0.274mmol) and 5mL of triethanolamine (Triethanolamine, TEA 51.1mmol) with magnetic stirring and raise the temperature to 95°C. After 1h, 0.5mL of Tetraethylorthosilicate (Tetraethylorthosilicate, TEOS 2.23mmol) was added dropwise and the temperature was maintained to continue magnetic stirring for 1h. Then, MSNs were obtained by centrifugation and washing with ethanol 3 times. The obtained MSN was stirred in 1% hydrochloric acid ethanol solution at 60° C. for 3 h, repeated three times, and centrifuged to obtain the template removing agent CTAC-MSN. Its transmission electron microscope picture is attached image 3 Shown in A.
[0077] 1.2. Loading of small molecular substances by MSN
[0078] Take 2mL of 1μg / μL MSN and 100μg Cy3 (Cy3 is an amino-reactive dye, a bright oran...
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