Preparation method for non-spherical hydrogel microparticle embolic agent

1 . A method for forming an embolic agent, comprising:

obtaining an aqueous phase solution dissolved with a polymer to be cross-linked;

obtaining an oil phase solution containing a water-soluble organic cross-linking agent;

alternately injecting the oil phase solution and the aqueous phase solution into an elongated channel to form elongated droplets of the aqueous phase solution with uniform shape and size in the elongated channel, wherein the water-soluble organic cross-linking agent in the oil phase solution diffuses from the oil phase solution into the aqueous elongated droplets in the elongated channel, such that the water-soluble organic cross-linking agent and the polymer in the elongated droplets have a cross-linking reaction in the elongated channel to obtain solidified elongated and stable non-spherical hydrogel microparticles with uniform shape and size as the embolic agent; and

discharging the embolic agent from the elongated channel.

2 . The method according to claim 1 , wherein the alternately injecting of the oil phase solution and the aqueous phase solution into the elongated channel includes:

providing a microfluidic chip of a hydrophobic material and including the elongated channel; and

alternately injecting the oil phase solution and the aqueous phase solution into the elongated channel on the microfluidic chip.

3 . The method according to claim 1 , wherein

the elongated channel is arranged in a microfluidic chip; and

the cross-linking between the organic cross-linking agent dissolved in the oil phase solution and the polymer dissolved in the aqueous phase solution in the elongated channel is carried through thermal cross-linking.

4 . The method according to claim 1 , further comprising:

immersing the embolic agent discharged from the elongated channel into a collection solution; and

heating the collection solution under stirring, wherein

the collection solution includes an oil-based solvent, and

the elongated channel includes an inlet end and an outlet end.

5 . The method according to claim 4 , wherein a cross-linking agent is dissolved in the collection solution, such that the cross-linking agent and the embolic agent continue to react.

6 . The method according to claim 4 , wherein the heating of the collection solution under stirring is carried out at a temperature of 40° C. to 85° C.

7 . The method according to claim 1 , wherein

the elongated channel includes a first passage, a second passage, and a third passage;

the third passage is respectively in communication with the first passage and the second passage; and

the oil phase solution and the aqueous phase solution are respectively injected into the elongated channel through the first passage and the second passage and contact in the third passage to enable the cross-linking reaction in the aqueous phase solution.

8 . The method according to claim 7 , wherein

the third passage includes an arched channel, and a straight channel in communication with the arched channel;

one end of the arched channel away from the straight channel respectively communicates with the first passage and the second passage; and

the embolic agent is discharged from the straight channel.

9 . The method according to claim 1 , wherein a width and a height of the elongated channel are less than 1 mm.

10 . The method according to claim 1 , wherein a ratio of an injection rate of the oil phase solution to an injection rate of the aqueous phase solution is 20:1 to 2:1.

11 . The method according to claim 1 , wherein

the aqueous phase solution further includes a catalyst; and

in the aqueous phase solution, a mass fraction of the polymer is 2.5% to 7.5%, and a concentration of the catalyst is 0.25 mol/L to 0.75 mol/L.

12 . The method according to claim 1 , wherein

the oil phase solution includes an oil-based solvent, a lipophilic emulsifier and the organic water-soluble cross-linking agent at a mass ratio of 1:(0.01-0.04):(0.075-0.3).

13 . The method according to claim 1 , wherein a volume of the polymer is reduced after solidification from the cross-linking reaction with the organic water-soluble cross-linking agent diffused from the oil phase solution into the elongated droplets.

14 . The method according to claim 1 , wherein the oil phase solution further contains an emulsifier to facilitate evenly dispersing the organic water-soluble cross-linking agent in the oil phase solution.

15 . The method according to claim 1 , wherein the organic water-soluble cross-linking agent comprises at least one of an aldehyde, an organic acid, or an organic acid anhydride.