Spray dry method for encapsulation of biological moieties and chemicals in polymers cross-linked by multivalent ions for controlled release applications

Patent metadata

Field	Value
Publication number	US-9700519-B2
Application number	US-201414288110-A
Country	US
Kind code	B2
Filing date	May 27, 2014
Priority date	Dec 23, 2011
Publication date	Jul 11, 2017
Grant date	Jul 11, 2017

Abstract

Microencapsulation of bioactive and chemical cargo in a stable, cross-linked polymer matrix is presented that results in small particle sizes and is easily scaled-up for industrial applications. A formulation of a salt of an acid soluble multivalent ion, an acid neutralized with a volatile base and one or more monomers that cross-link in the presence of multivalent ions is atomized into droplets. Cross-linking is achieved upon atomization where the volatile base is vaporized resulting in a reduction of the pH of the formulation and the temporal release of multivalent ions from the salt that cross-link the monomers forming a capsule. The incorporation of additional polymers or hydrophobic compounds in the formulation allows control of hydration properties of the particles to control the release of the encapsulated compounds. The operational parameters can also be controlled to affect capsule properties such as particle-size and particle-size distribution.

First claim

We claim:

1. A method for producing microcapsules, comprising:
(a) providing a formulation comprising:
(i) monomer molecules;
(ii) at least one acid neutralized with a volatile base; and
(iii) an insoluble salt of a multivalent ion;

(b) atomizing said formulation to form droplets; and
(c) volatilizing said volatile base of said droplets, thereby lowering the pH of the formulation, which dissolves the otherwise insoluble salt, thereby making available said multivalent ion to cross-link monomer molecules, forming microcapsules.

2. The method as recited in claim 1 , further comprising adding a cargo to said formulation prior to atomization.

3. The method as recited in claim 1 , wherein said formulation further comprises a copolymer.

4. The method as recited in claim 1 , wherein said formulation further comprises a hydrophobic compound.

5. The method as recited in claim 4 , wherein said hydrophobic compound comprises latex.

6. The method as recited in claim 1 , wherein said monomer is selected from the group of monomers consisting of alginates, polygalacturonates, chitosan, collagen, soy proteins and whey proteins.

7. The method as recited in claim 1 , wherein said insoluble salt is selected from the group of salts consisting of dicalcium phosphate, calcium carbonate, calcium oxalate, calcium phosphate, calcium meta-silicate and calcium tartrate.

8. The method as recited in claim 1 , wherein said acid is an organic acid selected from the group of acids consisting of adipic acid, acrylic acid, glutaric acid, succinic acid, ascorbic acid, gallic acid and caffeic acid.

9. The method as recited in claim 1 , wherein said volatile base is a base selected from the group of bases consisting of ammonia, methylamine, trimethylamine, ethylamine, diethylamine, and triethylamine.

10. A method for producing microcapsules, comprising:
(a) providing a formulation comprising:
(i) a plurality of at least one type of monomer molecule;
(ii) citrate;
(iii) at least one acid neutralized with a volatile base;
(iv) a salt of an acid soluble multivalent ion; and
(v) a hydrophobic compound;

(b) atomizing said formulation to form droplets; and
(c) volatilizing said volatile base of said droplets, thereby lowering the pH of the formulation, which dissolves the otherwise insoluble salt, thereby making available said multivalent ion to cross-link monomer molecules, forming microcapsules;
(d) wherein the hydrophobic compound modifies hydration properties of the microcapsules to retard release of an encapsulated cargo.

11. The method as recited in claim 10 , wherein said hydrophobic compound comprises a compound selected from the group of compounds comprising polymer latexes, wax emulsions and surfactants.

12. The method as recited in claim 10 , wherein said monomer is selected from the group of monomers consisting of alginates, polygalacturonates, chitosan, collagen, soy proteins and whey proteins.

13. The method as recited in claim 10 , wherein said salt is selected from the group of salts consisting of dicalcium phosphate, calcium carbonate, calcium oxalate, calcium phosphate, calcium meta-silicate and calcium tartrate.

14. The method as recited in claim 10 , wherein said acid is an organic acid selected from the group of acids consisting of adipic acid, acrylic acid, glutaric acid, succinic acid, ascorbic acid, gallic acid and caffeic acid.

Assignees

• Univ California

Inventors

• Zicari Tina Jeoh
• Scher Herbert B
• Santa-Maria Monica C
• Strobel Scott

Classifications

• C08J2389/00

  Characterised by the use of proteins; Derivatives thereof · CPC title

• C08J2305/06

  Pectin; Derivatives thereof · CPC title

• C08J2305/04

  Alginic acid; Derivatives thereof · CPC title

• C08J3/24

  Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K) · CPC title

• C08J3/122

  Pulverisation by spraying · CPC title