Hollow silica spheres with nested iron oxide particles

Patent metadata

Field	Value
Publication number	US-11957789-B2
Application number	US-202318374334-A
Country	US
Kind code	B2
Filing date	Sep 28, 2023
Priority date	May 3, 2019
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The invention pertains to a method for treating a neoplasm, such as colorectal cancer, using hollow silica spheres (“HSS”). It also is directed to a method for making uncalcined HSS, calcined HSS from which phenyl groups have been removed, and HSS incorporating particles of Fe3O4, as well as compositions containing HSS.

First claim

The invention claimed is:

1. A method for forming hollow silica spheres incorporating Fe 3 O 4 (“Fe-HSS”), comprising:
dissolving a hydrolyzable aryl silane in an aqueous solution comprising Fe 3 O 4 , water and an acid to form a hydrolyzed silane solution, wherein a molar ratio of the hydrolyzable aryl silane to the Fe 3 O 4 ranges from 100:1 to 1:100;
mixing the hydrolyzed silane solution with a hydroxide base to form a precipitate; and
calcining the precipitate using a multi-stage calcination to form the Fe-HSS;
wherein surfaces of the Fe-HSS comprise no more than 0.1 mol. % phenyl or aryl groups relative to an average uncalcined Fe-HSS,
wherein the multi-stage calcination comprises a first stage and a second stage, the first stage including heating the precipitate to a first temperature of 180° C. to 240° C. by a first ramp rate of 3° C. to 10° C. per minute, and holding at the first temperature for about 15 minutes to 45 minutes; and the second stage including heating the precipitate to a second temperature of 600° C. to 740° C. by a second ramp rate of 0.8° C. to 2.5° C. per minute, and holding at the second temperature for about 12 hours to 24 hours,
wherein the Fe-HSS have a hollow core space containing plural individual particles of Fe 3 O 4 having an average diameter in a range of from 9.5 nm to 21.3 nm and the Fe 3 O 4 has a spinel structure,
wherein the hollow silica spheres of the Fe 3 O 4 hollow silica spheres have a core-shell structure with shells larger in thickness than cores, and the hollow silica spheres have an average diameter in a range of from 415 to 615 nm,
wherein the hollow silica spheres of the Fe 3 O 4 hollow silica spheres have an average diameter less than the average diameter of the corresponding uncalcined Fe-HSS: and
wherein the particles of Fe 3 O 4 are present in an amount of from 0.1 to 10 wt. % of a combined weight of the HSS and Fe 3 O 4 in the Fe-HSS.

2. The method of claim 1 , wherein the Fe 3 O 4 particles are crystalline and present in an amount ranging from 0.1 to 10 wt % of a combined weight of the HSS and Fe 3 O 4 in the Fe-HSS.

3. The method of claim 1 , wherein the surfaces of the Fe-HSS are free of phenyl or aryl groups.

4. The method of claim 1 , wherein the hydrolyzable aryl silane is trimethoxy(phenyl) silane and the hydroxide base is NH 4 OH.

5. The method of claim 1 , wherein the Fe-HSS have a BET surface area in a range of from 350 to 450 m 2 /g.

6. The method of claim 1 , wherein the Fe-HSS has an average shell thickness in a range of from 150 to 210 nm.

7. The method of claim 1 , wherein the Fe-HSS alone is sufficient to cause nucleus condensation and nuclear augmentation in the aqueous solution in a range of from 1 to 3 mg/mL.

8. The method of claim 1 , wherein the surfaces of the Fe-HSS comprise no more than 0.05 mol. % phenyl or aryl groups, relative to an average uncalcined Fe-HSS.

9. The method of claim 1 , wherein the surfaces of the Fe-HSS comprise no more than 0.02 mol. % phenyl or aryl groups, relative to an average uncalcined Fe-HSS.

10. The method of claim 1 , wherein the surfaces of the Fe-HSS comprise no more than 0.01 mol. % phenyl or aryl groups, relative to an average uncalcined Fe-HSS.

11. The method of claim 1 , wherein the multi-stage calcination includes the first stage including heating the precipitate to a first temperature of 195° C. to 210° C. by a first ramp rate of 4° C. to 6° C. per minute, and holding at the first temperature for about 25 minutes to 35 minutes; and the second stage including heating the precipitate to a second temperature of 640° C. to 680° C. by a second ramp rate of 1° C. to 2° C. per minute, and holding at the second temperature for about 14 hours to 18 hours.

12. The method of claim 1 , wherein the multi-stage calcination includes the first stage including heating the precipitate to a first temperature of about 200° C. by a first ramp rate of about 5° C. per minute, and holding at the first temperature for about 30 minutes; and the second stage including heating the precipitate to a second temperature of about 660° C. by a second ramp rate of 1.5° C. per minute, and holding at the second temperature for about 16 hours.

Assignees

• Univ Imam Abdulrahman Bin Faisal

Inventors

• Bozkurt Ayhan
• Anil Seyda Tugba Gunday
• Khan Firdos Alam
• Akhtar Sultan

Classifications

• A61K9/16 Primary

  Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)} · CPC title

• A61K9/1682

  Processes · CPC title

• A61K33/00

  Medicinal preparations containing inorganic active ingredients · CPC title

• A61K33/26

  Iron; Compounds thereof · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title