Mono-carboxyl chitosan/alkannin composite nanometer particles and preparation method thereof

A technology of composite nanoparticles and chitosan, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of long preparation cycle of nanoparticles, poor stability of nanoparticles, and cytotoxicity. And side effects and other problems, to achieve the effect of increasing accessibility and reactivity, reducing the regularity of molecular arrangement, and improving biocompatibility

Active Publication Date: 2019-10-29
ANHUI AGRICULTURAL UNIVERSITY
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Problems solved by technology

[0004] At present, the main preparation methods of chitosan drug-loaded nanoparticles include covalent cross-linking method, macromolecule compounding method, desolvation method, emulsion drop combination technology [Chinese invention patent publication number: CN1903367A], usually these methods are more loaded down with trivial details, need Organic solvents, dispersants and cross-linking agents, and the size of the prepared nanoparticles is relatively large, which limits certain routes of administration; the self-assembly construction method can self-assemble in aqueous solution to form chitosan nanoparticles with smaller particle sizes, However, chitosan must be chemically modified to make it amphiphilic, the procedure is more complicated, and the reaction cycle is longer [Chinese invention patent publication number: CN103524750B]; ion gel method is a simple method for preparing chitosan nanoparticles Rapid method, can generate particles with a particle size of tens to hundreds of nanometers under mild conditions, without using organic solvents and aldehyde crosslinking agents, simple process, high controllability of conditions, easy large-scale production, obtained chitosan Sugar nanoparticles have good stability and uniform particle size
In recent years, ion-induced gelation of chitosan with sodium tripolyphosphate (TPP) has become a hot topic to form nanoparticles. Some researchers have added TPP and citric acid to chitosan acetic acid solution. , catalyst sodium hypophosphite and surfactant Tween-80, and prepare a nano-chitosan dispersion with a particle size of 20-30 nm through ion gel crosslinking [Wang Cheng, Chen Yuyue, Lu Yanhua. Nano-chitosan Preparation and its effect on silk fiber properties. Silk, 2006(8):32-34; Lu Yanhua, Wang Lijiang, Liu Zhimei. Preparation and characterization of low molecular weight nano-chitosan for textile finishing. Journal of Liaodong University , 2009,16(2):93-96], but long-term placement is prone to sedimentation and aggregation. After standing for 12h, the particle size of nano-chitosan is greater than 70nm, the stability of nanoparticles is poor, the operation steps are more complicated, and the preparation process uses Acids and catalysts will remain in chitosan nanoparticles
Invention patent CN101766820B discloses a method for the preparation and functionalization of a novel chitosan nanocarrier, which uses acetic acid solution to dissolve chitosan, adds sodium tripolyphosphate TPP solution to obtain nanogel, and then adds glutaraldehyde Combined with excess sodium borohydride reduction, after centrifugation and dialysis, chitosan nanoparticles with a particle size between 200 and 600nm were obtained. The time for sodium borohydride reduction is 8-15 hours. The preparation period of nanoparticles is long and needs to be reacted overnight, and aldehyde chemical cross-linking agents are used, which may cause cytotoxicity and side effects (such as reactions with drug molecules, etc.)

Method used

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  • Mono-carboxyl chitosan/alkannin composite nanometer particles and preparation method thereof
  • Mono-carboxyl chitosan/alkannin composite nanometer particles and preparation method thereof
  • Mono-carboxyl chitosan/alkannin composite nanometer particles and preparation method thereof

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Embodiment 1

[0035] (1) Stir and disperse monocarboxychitosan powder with a viscosity average molecular weight of 4 to 360,000, a degree of deacetylation ≥ 88.6%, and a C6 carboxyl degree of 19.41% to 56.25% in absolute ethanol, with a working frequency of 19 Ultrasonic cell pulverizer with ~25kHz and ultrasonic power of 50~300W performs ultrasonic cavity treatment on the dispersion liquid for 5~20min, so that the monocarboxychitosan precipitate is crushed into submicron particles, and then dried to obtain monocarboxychitosan submicron particles.

[0036] (2) stirring and dissolving the dried monocarboxychitosan submicron particles in ultrapure water (deionized water filtered 2 to 3 times with a 0.22 to 0.45 μm filter membrane) to prepare a solution with a mass concentration of 0.1 to 1.0%, Then add emulsifier and shikonin, and fully emulsify by magnetic stirring for 1-3 hours to obtain a stable emulsion system. The emulsifier is polysorbate-80, polyvinylpyrrolidone, fatty alcohol polyoxy...

Embodiment 2

[0041] (1) Stir and disperse monocarboxychitosan powder with a viscosity-average molecular weight of 80,000, a deacetylation degree of 90%, and a C6 carboxyl degree of 26.74% in absolute ethanol, with a working frequency of 20kHz and an ultrasonic power of 100W Ultrasonic cell pulverizer is used to ultrasonically treat the dispersion liquid for 10 minutes, so that the monocarboxychitosan precipitate is crushed into submicron particles, and then dried to obtain monocarboxychitosan submicron particles.

[0042] (2) Stir and dissolve the dried monocarboxyl chitosan submicron particles in ultrapure water (deionized water filtered through a 0.22 μm filter membrane 3 times) to prepare a solution with a mass concentration of 0.4%, add emulsifier fatty alcohol polyoxygen Vinyl ether and shikonin were fully emulsified by magnetic stirring for 2 hours to obtain a stable emulsion system. The mass ratio of the emulsifier fatty alcohol polyoxyethylene ether to monocarboxy chitosan is 1:1; ...

Embodiment 3

[0047] (1) Stir and disperse monocarboxychitosan powder with a viscosity-average molecular weight of 80,000, a deacetylation degree of 90%, and a C6 carboxyl degree of 43.61% in absolute ethanol, with a working frequency of 20kHz and an ultrasonic power of 100W Ultrasonic cell pulverizer is used to ultrasonically treat the dispersion liquid for 15 minutes, so that the monocarboxychitosan precipitate is crushed into submicron particles, and then dried to obtain monocarboxychitosan submicron particles.

[0048] (2) the monocarboxyl chitosan submicron particle after drying is stirred and dissolved in ultrapure water (0.22 μm filter membrane filter 3 times of deionized water) and is formulated with a mass concentration of 0.4% solution, adding emulsifying agent polyvinylpyrrolidone and Shikonin was fully emulsified by magnetic stirring for 2 hours to obtain a stable emulsion system. The mass ratio of emulsifier polyvinylpyrrolidone and monocarboxychitosan is 2:1; the purity of shi...

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Abstract

The invention discloses mono-carboxyl chitosan/alkannin composite nanometer particles and a preparation method thereof. Alkannin coated nanometer particles are prepared through ion gel coagulation effects of water-soluble mono-carboxyl chitosan and sodium tripolyphosphate, and then mutual cross-linking and assembling of hydrophilic macromolecule addition agents and the mono-carboxyl chitosan, composite nanometer particle being small in particle diameter, homogeneous in size, high in stability and good in biological activity are prepared. The method disclosed by the invention is simple and easyto operate, low in cost, mild in reaction condition, environmentally-friendly, safe and non-toxic, the obtained composite nanometer particles are resistant to gastric acid and high in stability, andthe orally-taken absorption and utilization rate of a Chinese herbal medicine namely alkannin and the target medicine release properties are effectively improved.

Description

technical field [0001] The invention relates to a monocarboxyl chitosan / shikonin composite nano particle and a preparation method thereof, in particular to a preparation technology of a highly active chitosan nano carrier, which belongs to the technical field of functional nano material preparation. Background technique [0002] Chitosan (Chitosan) is a deacetylated derivative of chitin, which is derived from the shell of crustaceans, insects and other invertebrates or the cell wall of fungal yeast. Its annual biosynthesis can reach 200 billion tons, and it is the only natural cation in nature. Basic amino polysaccharides. Chitosan has a wide range of sources, is renewable, and is biocompatible, non-irritating, non-sensitizing, non-toxic, easy to degrade, tissue repair, immune regulation, hemostasis, antibacterial, anti-cancer, blood lipid lowering, anti-oxidation, moisturizing and emollient It has broad application prospects in the fields of medicine and health care, biolo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/36A61K47/04A61K31/122
CPCA61K9/5115A61K9/5161A61K31/122
Inventor 许云辉郑宏飞杜兆芳朱莹
Owner ANHUI AGRICULTURAL UNIVERSITY
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