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Spherical calcium alginate gel micro-particle preparation method

A calcium alginate and gel technology, which is applied in the field of medical materials, can solve the problems of easy clogging of microfluidic chips, irregular shapes of calcium alginate gel particles, etc., and achieves resistance to gravity and interface, viscosity and surface tension. increased effect

Active Publication Date: 2015-08-12
HUAZHONG UNIV OF SCI & TECH
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Problems solved by technology

[0004] In view of the above defects or improvement needs of the prior art, the present invention provides a method for preparing spherical calcium alginate gel particles, the purpose of which is to pass the pre-cross-linking in the microfluidic chip and the cross-linking in the collection solution. Cross-linking reaction to obtain spherical calcium alginate gel particles with complete shape, thus solving the technical problems that the calcium alginate gel particles prepared by the existing preparation method are not uniform in shape or easily clogged the microfluidic chip

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[0028] The preparation method of spherical calcium alginate gel particles provided by the present invention is prepared by using a microfluidic chip, comprising the following steps:

[0029] (1) Preparation of the oil phase: uniformly mix the ethanol solution of the soluble calcium salt and the continuous phase matrix containing the surfactant to obtain a homogeneous mixture; the homogeneous mixture is obtained by solvent evaporation method to obtain the in-situ-formed calcium salt-containing nano The oil phase of the grains; the oil phase per milliliter contains 0.04-0.1 mmol of calcium salt. The surfactant is a non-ionic surfactant, preferably Span 80, and its content is between 2 and 5 wt%.

[0030] When mixing, in order to be more uniform, ultrasonic mixing can be used; the calcium salt, preferably calcium chloride or calcium nitrate, ensures good solubility; the continuous phase matrix is ​​preferably liquid paraffin, salad oil, silicone oil and other non-polar organic so...

Embodiment 1

[0035] A method for preparing spherical calcium alginate gel particles is prepared by using a microfluidic chip, comprising the following steps:

[0036] (1) Preparation of oil phase: weigh 0.04g of anhydrous CaCl 2 Dissolve in about 3mL of ethanol, ultrasonically dissolve or stir to dissolve, then add to 10mL liquid paraffin containing 2wt% Span 80, ultrasonically mix or stir well, then magnetically stir overnight at 60°C to completely volatilize the ethanol, After cooling to room temperature, an oil phase containing calcium salt nanoparticles formed in situ is prepared; each milliliter of the oil phase contains 0.04 mmol of calcium salt. Determination of CaCl in the prepared oil phase by dynamic light scattering 2 The size distribution of the nanoparticles is as figure 1 As shown by the middle solid line, the average particle diameter is 50 nm, and the polydispersity index is 0.2. The photo of the oil phase before ethanol volatilization is as follows figure 2 As shown o...

Embodiment 2

[0043] A method for preparing spherical calcium alginate gel particles is prepared by using a microfluidic chip, comprising the following steps:

[0044] (1) Preparation of the oil phase: Weigh 0.11g of anhydrous Ca(NO 3 ) 2 Dissolve in about 4mL of ethanol, ultrasonically dissolve or stir to dissolve, then add to 10mL of salad oil containing 2.5wt% Span 80, ultrasonically mix or stir well, then magnetically stir overnight at 60°C to completely evaporate the ethanol , and then cooled to room temperature, the oil phase containing calcium salt nanoparticles formed in situ was prepared; the oil phase contained 0.07 mmol of calcium salt per milliliter. Ca(NO) in the prepared oil phase was determined by dynamic light scattering 3 ) 2 The size distribution of the nanoparticles is as figure 1 As shown by the middle dotted line, the average particle diameter is 110 nm, and the polydispersity index is 0.3.

[0045] (2) Preparation of spherical calcium alginate gel particles by mic...

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Abstract

The present invention discloses a spherical calcium alginate gel micro-particle preparation method, which comprises: (1) uniformly mixing an ethanol solution of a soluble calcium salt and a surfactant-containing continuous phase matrix, and evaporating to removing the solvent so as to prepare an oil phase; and (2) adopting a sodium alginate solution as a dispersed phase, adopting the oil phase as a continuous phase, carrying out a pre-crosslinking reaction in a microfluidic chip to form pre-crosslinked liquid droplets, collecting the liquid droplets into the collection liquid containing calcium ions, carrying out a crosslinking reaction, and carrying out washing separation to obtain the spherical calcium alginate gel micro-particles. According to the present invention, the method is simple and is easy to perform, and the sphere forming property is not affected by other preparation factors such as the microchannel device type, the microchannel size, the fluid flow rate, the liquid droplet size, the receiving height, and the like.

Description

technical field [0001] The invention belongs to the field of medical materials, and more specifically relates to a method for preparing spherical calcium alginate gel particles. Background technique [0002] Calcium alginate (Ca-ALG) gel particles can be used as encapsulated cells, drug delivery carriers and vascular embolization materials for interventional therapy (H.Zimmermann, et al.Curr.Diab.Rep.2007,7(4),314 -320.H.H. et al. Drug Dev. Ind. Pharm. 2002, 28(6), 621-630. T.A. Becker, et al. Neurosurgery 2007; 60:1119-1127). Calcium alginate microspheres, as an interventional vascular embolization material, can be used in the treatment of diseases such as tumors, arteriovenous malformations, and cerebral hemangiomas. For these biomedical applications, the particle size and particle size monodispersity of the gel particles, as well as a good spherical shape are crucial to their performance. [0003] Currently common methods for preparing calcium alginate gel particles, ...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08L5/04A61L31/04A61L31/14A61K47/36A61K9/16
Inventor 王芹刘珊珊杨亚江杨祥良
Owner HUAZHONG UNIV OF SCI & TECH
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