COMPOSITION FOR MAGNETIC ULTRASOUND CONTRAST AGENT, MAGNETIC ULTRASOUND CONTRAST AGENT, MAGNETIC MICROBUBBLE ULTRASOUND CONTRAST AGENT AND PREPARATION METHOD THEREOF

1 . A composition for magnetic ultrasound contrast agent, comprising a lipid, a surfactant and a magnetic nanoparticle; wherein:

the surfactant consists of a surfactant A and a surfactant B, wherein the surfactant A is in a free state, and the surfactant B is in a bonding state and is modified on the surface of the magnetic nanoparticle;

the surfactant A is a nonionic surfactant whose HBL value is greater than 8;

the surfactant B is a citric acid-based compound; and

relative to 1 mol of the lipid, a content of the surfactant A is 0.1 mol to 1 mol, a content of the surfactant B is 0.1 mol to 1 mol, and a content of the magnetic nanoparticle is 0.05 mol to 0.5 mol.

2 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the surfactant A is a nonionic surfactant whose HBL value is greater than 15.

3 . The composition for magnetic ultrasound contrast agent according to claim 2 , wherein the surfactant A is a nonionic surfactant whose HBL value is 20 to 35.

4 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the surfactant A is any one or more selected from the group consisting of: poloxamer, poly(isobutene-maleic anhydride), and poly(maleic anhydride-alt-1-octadecene).

5 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the surfactant B is citrate and/or citrate ester.

6 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the surfactant A is poloxamer and the surfactant B is citrate.

7 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein relative to 1 mol of the lipid, the content of the surfactant A is 0.2 mol to 0.6 mol, the content of the surfactant B is 0.2 mol to 0.5 mol, and the content of the magnetic nanoparticle is 0.1 mol to 0.3 mol.

8 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the molar ratio of the magnetic particle to the surfactant B is 1:0.6 to 1:2.5.

9 . The composition for magnetic ultrasound contrast agent according to claim 1 , further comprising a drug, and relative to 100 parts by weight of a sum of the lipid, the surfactant and the magnetic nanoparticle, the content of the drug is 1 to 20 parts by weight.

10 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the lipid consists of sorbitan monostearate and polysorbate 80 in a molar ratio of 1:0.5 to 1:2.

11 . The composition for magnetic ultrasound contrast agent according to claim 1 , wherein the magnetic nanoparticle is a superparamagnetic Fe 3 O 4 nanoparticle with a particle size of 3 nm to 20 nm.

12 . A magnetic ultrasound contrast agent, wherein the magnetic ultrasound contrast agent comprises, or is prepared from, the composition for magnetic ultrasound contrast agent according to claim 1 .

13 . A method for preparing a magnetic microbubble ultrasound contrast agent, wherein raw materials comprise the composition for magnetic ultrasound contrast agent according to claim 1 , wherein the method comprises the following steps:

(1) making a first contact between the lipid and the surfactant A;

(2) mixing the drug with the resulting material obtained by step (1), pumping gases into the mixed resulting material, and processing ultrasonic cavitation to form a first microbubble suspension;

(3) processing a treatment for loading a positive charge on the first microbubble suspension to obtain a second microbubble suspension with a positive charge on the surface; and

(4) making a second contact between the magnetic nanoparticle modified with the surfactant B on the surface and the obtained second microbubble suspension with a positive charge on the surface.

14 . The method according to claim 13 , wherein the first contact conditions comprise: a temperature of 110° C. to 130° C., and a time of 8 min to 16 min.

15 . The method according to claim 13 , wherein in step (2), the mixing is processed at a temperature of 30° C. to 50° C.

16 . The method according to claim 13 , wherein the ultrasonic cavitation conditions comprise: an ultrasonic power of 8 kW to 12 kW, and a time of 1 min to 8 min.

17 . The method according to claim 13 , wherein in step (3), the process of the treatment for loading a positive charge comprises: contacting the first microbubble suspension with an aqueous solution of cationic reagent.

18 . The method according to claim 17 , wherein the volume ratio of the aqueous solution of cationic reagent and the first microbubble suspension is 0.8:1 to 1.2:1, and the concentration of the cation in the aqueous solution of the cationic reagent is 0.5 mg/L to 2 mg/L.

19 . The method according to claim 13 , further comprising: leaving the resulting material, which have contacted with the cationic reagent, to stand for stratification, taking upper layer materials, and washing the upper layer materials with buffer solution.

20 . The method according to claim 13 , wherein in step (4), the second contact conditions comprise: processing the material with ultrasonic oscillation with an ultrasonic power of 170 W to 420 W, and a time of 15 min to 50 min.