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Nano granules adhesive to mucous membrane, preparation method and application

A nanoparticle and adhesive technology, applied in the fields of botanical equipment and methods, applications, chemical instruments and methods, etc., can solve the problems that cannot improve the oral bioavailability of protein and polypeptide drugs, inactivation of protein and polypeptide drugs, and inactivation of nanoparticles. Stability and other issues, to achieve the effect of convenient preparation, uniform particle size, and increased penetration

Inactive Publication Date: 2006-04-19
FUDAN UNIV
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0003] Takeucki et al. improved the oral bioavailability of calcitonin by coating polylactide copolymer nanoparticles with chitosan (Mucoahesive DL-Lactide / glycolide copolymer nanospheres coated with chitosan to improve oraldelivery of elcatonin, Pharm.Dev. Tech.2000(5): 77-85), in the preparation process of the above-mentioned nanoparticles, organic solvents such as methanol and chloroform were used and ultrasound was carried out, these methods could easily cause the inactivation of protein and polypeptide drugs
Studies have shown that chitosan cannot improve the oral bioavailability of protein peptide drugs under high pH conditions
Xu Yongmei et al. formed adhesive nanoparticles by ionically cross-linking chitosan and chitosan quaternary ammonium salt with sodium tripolyphosphate (Effect of molecular structure of chitosan nanoparticles Int.J.Pharm.2003, 25(1) : 215-226), although the destruction of the active ingredient by the organic solvent is avoided, the pH instability of the nanoparticle limits its application as an oral delivery carrier for protein and polypeptide drugs

Method used

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  • Nano granules adhesive to mucous membrane, preparation method and application
  • Nano granules adhesive to mucous membrane, preparation method and application
  • Nano granules adhesive to mucous membrane, preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0051] Embodiment 1: N, N, the synthesis of N-trimethyl chitosan quaternary ammonium salt

[0052] Disperse 2g of chitosan (30,000, 100,000-300,000, greater than 300,000) in 50ml of dimethyl sulfoxide in an eggplant-shaped bottle, soak and stir at room temperature for 24 hours, then add 4.8g of potassium iodide, 2g of sodium hydroxide and A solution made of 6ml of double distilled water was stirred slowly at 36°C for 16h. Then use four times the volume of the mixed solution of absolute ethanol and absolute ether to precipitate the crude product of the reaction, i.e. iodide N, N, N-trimethyl chitosan quaternary ammonium salt. Due to the poor stability of the iodized salt, it was dissolved in water, converted into N, N, N-trimethyl chitosan quaternary ammonium chloride by ion exchange, and then precipitated with absolute ethanol and anhydrous ether, and then After filtration and vacuum drying, the pure product was obtained, which was used for the following synthesis of mucoadhe...

Embodiment 2

[0053] Embodiment 2: chitosan coated nanoparticles

[0054] Weigh 1g of chitosan (greater than 300,000), place it in an Erlenmeyer flask, add 98ml of 1% acetic acid solution, stir, heat to 25°C, dissolve, then add 1.6ml of methyl methacrylate to it, after 20min Ammonium persulfate was added, the temperature rose to 75°C, and the reaction was continued for 12 hours. The resulting suspension was dialyzed against a semipermeable membrane with a molecular size of 12,000 Daltons. After the suspension was diluted 100 times with water, the particle size and Zeta potential under different conditions were measured with a particle size analyzer (Nicomp 380 / ZLS, Santa Barbara, Calif., USA), see accompanying drawings 1 and 3.

Embodiment 3

[0055] Embodiment 3: chitosan coated nanoparticles

[0056] Weigh 0.5g of chitosan (greater than 300,000), place it in a Erlenmeyer flask, add 98ml of 1% acetic acid solution, stir, heat to 40°C, dissolve, then add 1.1ml of methyl methacrylate to it for 10min Then ammonium persulfate was added, the temperature rose to 80°C, and the reaction was continued for 14 hours. The resulting suspension was dialyzed against a semipermeable membrane with a molecular size of 12,000 Daltons. After the suspension was diluted 100 times with water, the particle size and Zeta potential under different conditions were measured with a particle size analyzer (Nicomp 380 / ZLS, Santa Barbara, Calif., USA), see accompanying drawings 1 and 3.

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PUM

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Abstract

A mucosa adhesive nanoparticle for medicine, food and cosmetics is prepared from skeleton (alkyl polyacrylate, alkyl polymethylacrylate, or polycyanoacrylate) and coating (mucosa adhesive polymer) through dissolving the coating, adding skeleton and trigger, heating while reaction, continuous reaction and purifying.

Description

technical field [0001] The invention belongs to the technical field of adhesive nanomaterials, and in particular relates to a mucoadhesive nanoparticle and a preparation method and application thereof. Background technique [0002] Protein and polypeptide drugs have short biological half-lives, poor biofilm permeability, and are easily degraded by gastrointestinal enzymes. Improving their oral bioavailability has become one of the current research hotspots in pharmacy. Mucoadhesive nanoparticles, which have been researched in recent years, can prolong the residence time of drugs at the absorption site to promote drug absorption; some preparation materials also have enzyme inhibition and permeation promotion effects, which can prevent enzymatic degradation of drugs and promote transmembrane transport of drugs. Thereby improving the bioavailability of protein peptide drugs. At present, there are relatively few studies on mucoadhesive nanoparticles at home and abroad. [0003...

Claims

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Application Information

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IPC IPC(8): C08F251/00C07K17/08A01N25/10A61K8/64A61Q1/00
Inventor 印春华崔福英钱锋唐翠
Owner FUDAN UNIV
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