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Preparation method of mono-dispersed gelatin embolic microsphere with precisely-controlled particle size

A monodisperse, gelatin technology, used in the preparation of microspheres, microcapsule preparations, inactive components of polymer compounds, etc., can solve the residual product quality of cross-linking curing agent, the troublesome post-processing of curing methods, and the wide distribution of grade particle size, etc. To improve the clinical embolization effect, reduce the probability of false embolization, and achieve uniform particle size

Active Publication Date: 2015-08-12
ENERGY RES INST OF SHANDONG ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The particle size distribution of microspheres obtained by this method is in six ranges of 50-150 μm, 150-350 μm, 350-560 μm, 560-710 μm, 710-1000 μm, and 1000-1500 μm; It is difficult to precisely control the particle size to obtain gelatin microspheres with uniform size. In addition, the curing method of this method has post-processing troubles, and the residue of cross-linking curing agent has a serious impact on product quality.

Method used

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  • Preparation method of mono-dispersed gelatin embolic microsphere with precisely-controlled particle size
  • Preparation method of mono-dispersed gelatin embolic microsphere with precisely-controlled particle size

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Embodiment 1

[0045] Preparation mass percent concentration is 2% gelatin aqueous solution and 2% tannic acid aqueous solution as dispersed phase, preparation contains the liquid paraffin solution that mass percent concentration is 1% Span80 as continuous phase, three kinds of solutions (gelatin aqueous solution, tannic acid solution) aqueous solution, liquid paraffin solution containing Span80) into syringes respectively, and placed on three micro-injection pumps respectively, after connecting the microchannel reactor, adjust the flow of gelatin aqueous solution, tannic acid aqueous solution and liquid paraffin solution containing Span80 0.3mL / h, 0.5mL / h, and 7mL / h, respectively, to obtain W / O droplets with a particle size of 580±5μm. Collect the generated gelatin droplets and place them in an oven at 30°C for 30 minutes to solidify. The solidified gelatin microspheres sink to the bottom of the beaker, pour to remove the upper layer of liquid paraffin, add pure water, ultrasonically break t...

Embodiment 2

[0049] Preparation mass percentage concentration is 10% gelatin aqueous solution and 15% glutamine transaminase aqueous solution as dispersed phase, the preparation contains the dodecane solution that mass percentage concentration is 2% Span80 as continuous phase, three kinds of solutions are packed in the syringe respectively , and placed on three micro-injection pumps respectively, after connecting the microchannel reactor, adjust the flow rates of the gelatin aqueous solution, the transglutaminase aqueous solution and the dodecane solution containing Span80 to be 0.3mL / h and 0.5mL / h respectively, 7mL / h to obtain W / O droplets with a particle size of 510±5um; collect the generated gelatin droplets and place them in an oven at 40°C to cure for 90min. Dioxane solution, supplemented with pure water, ultrasonic demulsification, centrifugation until the liquid is clear after ultrasonication, the particle size of gelatin microspheres is 290±5μm, and after freeze-drying, the particle...

Embodiment 3

[0053] The preparation mass percentage concentration is 2% gelatin aqueous solution and 5% genipin aqueous solution as dispersed phase, preparation contains the liquid paraffin solution that mass percentage concentration is 2% EM90 as continuous phase, three kinds of solutions are packed in the syringe respectively, and Placed on three micro-injection pumps respectively, after connecting the microchannel reactor, adjust the flow rate of gelatin aqueous solution, genipin aqueous solution and liquid paraffin solution containing EM90 to 0.5mL / h, 0.7mL / h, 10mL / h respectively, W / O droplets with a particle size of 650±5um were obtained. Collect the generated gelatin droplets and place them in an oven at 30°C for 120 minutes to solidify. The solidified gelatin microspheres sink to the bottom of the beaker, pour to remove the upper layer of liquid paraffin, add pure water, ultrasonically break the emulsion, and centrifuge until the liquid is clear after ultrasonication. , the particle...

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Abstract

The invention provides a preparation method of a mono-dispersed gelatin embolic microsphere with a precisely-controlled particle size. In the provided method, micro water-in-oil liquid drops are formed in a micro channel reactor at first through a micro-fluidic liquid drop control technology, then a crosslinking agent and a gelatin water solution are taken as the dispersing phase and introduced into the water-in-oil system, and then the mixture is directly cured to form microspheres. By adjusting the flowing speeds of the continuous phase and the dispersing phase, and the flowing speeds of two dispersing phases, the particle size and sphericility can be precisely controlled. The preparation technology is simple and rapid, and the process is controllable. The prepared gelatin microsphere can be used as an embolic agent or an antitumor drug carrier, and can also be applied to cell culture.

Description

technical field [0001] The invention relates to a preparation method of monodisperse gelatin embolic microspheres with precisely controlled particle size, belonging to the technical field of interventional medical materials. Background technique [0002] Interventional therapy is a new treatment method between surgery and internal medicine. After more than 30 years of development, it has now become the three major treatment systems together with surgical treatment and internal medicine. Embolization therapy is an important part of interventional therapy. With the help of high-definition medical imaging equipment, embolic agents are introduced into tumor blood supply arteries through small incisions through catheters, guide wires and other precision instruments, and their blood supply is artificially blocked to achieve " starve the tumor". Embolization therapy has achieved good results in malignant tumors, uterine fibroids, and hemangiomas, and has gradually become an altern...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08L89/00B01J13/14A61L31/04A61L31/16A61L31/14A61K47/42A61K9/19A61P35/00
Inventor 王立秋王建梅李艳许敏孔湉湉
Owner ENERGY RES INST OF SHANDONG ACAD OF SCI
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