Spherical porous hydroxyapatite sorbent and methods thereof

Patent metadata

Field	Value
Publication number	US-10914712-B2
Application number	US-201515123307-A
Country	US
Kind code	B2
Filing date	Mar 3, 2015
Priority date	Mar 3, 2014
Publication date	Feb 9, 2021
Grant date	Feb 9, 2021

Abstract

Highly spherical sorbents of porous hydroxyapatite materials and methods of producing these sorbents are disclosed. The sorbents of the present invention have good mechanical stability and are useful as chromatography media for the separation of biomolecules, such as proteins and nucleic acids.

First claim

The invention claimed is:

1. A method of preparing hydroxyapatite of formula Ca 10 (PO 4 ) 6 (OH) 2 for use as a chromatography medium, comprising the following steps:
(a) reacting an aqueous suspension comprising calcium hydroxide powder with an aqueous solution comprising phosphoric acid and an ammonium phosphate salt by adding the aqueous solution into the aqueous suspension while stirring to obtain a hydroxyapatite suspension comprising nanostructured primary particles of hydroxyapatite, wherein use of the aqueous solution comprising both phosphoric acid and the ammonium phosphate salt enables control of temperature through avoiding heat excursion of the reaction and forms a buffer to maintain the pH of the resultant hydroxyapatite suspension in the range of 8 to 11 in order to minimize formation of dicalcium phosphate (DCP) and tricalcium phosphate (TCP) impurities;
(b) milling the primary particles of hydroxyapatite in the suspension;
(c) spray-drying the suspension to obtain consolidated secondary particles of hydroxyapatite having an average pore size of about 50 to 100 nm and an average pore volume of about 0.1-0.5 cm 3 /g; and
(d) sintering the consolidated secondary particles to obtain sintered hydroxyapatite particles having a bulk density in the range of about 0.5 to 0.9 g/cm 3 .

2. The method of claim 1 , further comprising (e) classifying the sintered hydroxyapatite particles to obtain hydroxyapatite particles having a desired particle size range or desired median particle size.

3. The method of claim 1 , further comprising addition of a dispersant into the suspension to obtain a homogenized suspension before said spray-drying.

4. The method of claim 1 , wherein said ammonium phosphate salt is ammonium phosphate monobasic.

5. The method of claim 3 , wherein the dispersant is an inorganic compound, a short-chain organic compound, a polymer, or a combination thereof.

6. The method of claim 5 , wherein said inorganic compound is selected from phosphates, silicates and carbonates; said short-chain organic compound is selected from organic electrolytes and surfactants; and said polymer is selected from polymer electrolytes and polymer nonelectrolytes.

7. The method of claim 1 , wherein said milling comprises ball milling.

8. The method of claim 1 , wherein the mean particle size of the hydroxyapatite particles obtained from said milling is in the range of about 1.0 to 5.0 μm.

9. The method of claim 1 , wherein the temperature used for said sintering is in the range of about 450 to 800° C.

10. The method of claim 2 , wherein said classifying comprises ultrasonic sifting.

Assignees

• Bio Rad Laboratories

Inventors

• Xu James W

Classifications

• B01J20/048 Primary

  containing phosphorus, e.g. phosphates, apatites, hydroxyapatites · CPC title

• B01J20/282

  Porous sorbents (ion exchange B01J39/00 - B01J41/00) · CPC title

• B01J20/28011

  Other properties, e.g. density, crush strength · CPC title

• B01J20/3085

  Chemical treatments not covered by groups B01J20/3007 - B01J20/3078 · CPC title

• B01J20/28004

  Sorbent size or size distribution, e.g. particle size · CPC title