Process for obtaining microcapsules

• US 9,764,302 B2
• Filed: 05/04/2012
• Issued: 09/19/2017
• Est. Priority Date: 05/09/2011
• Status: Active Grant

• Current Assignee: Sipcam S.P.A.
• Original Assignee: Sipcam S.P.A.
• Inventors: Bernardini, Marco, Borgo, Francesca, Freschi, Giorgio, Russo, Edoardo
• Primary Examiner(s): ZIMMER, MARC S
• Application Number:
  US13/464,563
• Publication Number:
  US 20120286438A1
• Time in Patent Office: 1,964 Days
• Field of Search: 428402-40224, 428403, 428404, 428407, 4283211, 4284744, 427331, 4273899, 427212, 427213-21336, 427483, 427256, 264534, 264 5, 264 41, 264 4- 47, 424419, 424400, 424408, 424450, 424451, 424455, 424 937, 4241841, 424497, 424489, 424501, 424490, 424491, 424492, 424493, 424494, 424495
• CPC Class Codes: A01N 25/28 Microcapsules or nanocapsules
• CPC Class Codes: A01N 25/30 characterised by the surfactants
• CPC Class Codes: A01N 33/18 Nitro compounds
• CPC Class Codes: A01N 37/26 containing the group; Thio analogues thereof
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: B01J 13/16 Interfacial polymerisation

Abstract

A continuous process for preparing microcapsules containing water-insoluble active principles, comprising:

• • (1) preparing, in a first reactor, an aqueous solution containing one or more surfactants,
  • (2) preparing, in a second reactor, a solution comprising at least an active principle immiscible in an aqueous phase and a first component for preparing a polycondensation polymer for forming the microcapsule shell,
  • simultaneously feeding to a tubular reactor of a stream of aqueous solution (1) and solution (2), the ratio of solution (2)/solution (1) being between 0.5 and 2.0,
  • inletting a stream (3) of a second component for preparing the polycondensation polymer into the reactor, wherein stream (3) reacts with the first component,
  • wherein the streams are under turbulent flow conditions in the tubular reactor, and are continuously fed to the tubular reactor,
  • and wherein the ratio between the equivalents of the first component and second component are between 0.9 and 1.1.

Claims

1. A continuous process for preparing an aqueous dispersion of microcapsules with an encapsulation efficiency of the active principle ≧

98%, the microcapsules showing an homogeneous granulometric distribution as herein below defined and encapsulating water insoluble active principles to be used in the pharmaceutical and agrochemical field, comprising;

(1) preparation in a first reactor under stirring of an aqueous solution containing one or more surfactants,

(2) preparation in a second reactor under stirring of a solution comprising an active principle immiscible in an aqueous phase and a first monomeric component,

simultaneous feeding to a tubular reactor of a stream of the aqueous solution (1) and of a stream of solution (2), the ratio of stream solution (2)/stream solution (1) being between 0.5 and 2.0, the streams (1) and (2) being under turbulent flow conditions in the reactor,

then, optionally in a time of 0-10 seconds, feeding to the reactor under turbulent flow conditions stream (3) comprising a second monomeric component, the equivalent ratio between the first monomeric component and the second monomeric component being comprised between 0.9 and 1.1,

streams (1), (2) and (3) being continuously fed to the tubular reactor;

wherein the substantial homogeneous granulometric distribution of the microcapsules is defined as a b)/a) ratio, wherein b) is the average diameter determined on the smallest 90% of the microcapsules and a) is the average diameter determined on the smallest 50% of the microcapsules, being comprised between 1.5 and 2.5, b) being lower than 15 μ

m, streams (1), (2), and (3) having separate inlets into the reactor.

2. A process according to claim 1 wherein streams (1), (2) and (3) are used.

3. A process according to claim 1 wherein as first monomeric component a mixture of isocyanates is used.

4. A process according to claim 1 wherein the solution (1) and solution (2) of the active principle and of the first monomeric component are introduced into the reactor at a temperature ranging from 10°

C. up to 60°

C.

5. A process according to claim 1 wherein solution (2) is prepared by mixing solution (2a) containing the active principle and optionally an organic solvent, and solution (2b) comprising the first monomeric component, optionally dissolved in organic solvent, (2a) and (2b) being continuously premixed and then fed into the tubular reactor.

6. A process according to claim 1 wherein the viscosity of solution (2), optionally diluted with an organic solvent, is in the range 400 and 1000 cps.

7. A process according to claim 1 wherein the surfactants of solution (1) are selected from anionic and nonionic surfactants.

8. A process according to claim 7 wherein the anionic surfactants are selected from the group consisting of sodium ligninsulphonates, calcium ligninsulphonates and sodium polycarboxylates, the nonionic surfactants are selected from block copolymers formed by ethoxylated and propoxylated units.

9. A process according to claim 1 wherein the active principles are selected from herbicides, acaricides, insecticides, fungicides, biocides, plant and insect growth regulators, antidotes.

10. A process according to claim 9, wherein the active principles are selected from the following classes:

herbicides, selected from the following classes;

dinitroanilines;

pendimethalin and trifluralin

chloroacetamides;

alachlor, acetochlor, dimethenamide, metolachlor, pethoxamide, pretilachlor

carbammates;

molinates, triallates, EPTC;

diphenylethers;

oxyfluorfen, or

flurochloridone, clomazone, dichlobenil,

acaricides of the METI class, selected from fenazaquin, pyridaben, hexythiazox,

insecticides, selected from those belonging to the following classes;

pyrethroids;

bifenthrin, α

-cypermethrin, cypermethrin, deltamethrin, imiprothrin, λ

-cyhalothrin, prallethrin, tetramethrin, preferably bifenthrin, α

-cypermethrin, deltamethrin e λ

-cyhalothrin, ethofenprox

phosphoorganic compounds;

phosmet, chlorpyriphos, naled, fenitrothion;

neonicotinoids;

imidachloprid, acetamiprid

carbammates;

carbosulfan, pirimicarb, aldicarb, thiodicarb, carbofuran and propoxur, preferably carbosulfan,

fungicides, selected from those belonging to the following classes of imidazoles, triazoles, anilinopyrimidine.

11. A process according to claim 10 wherein the herbicide is pendimethalin.

12. A process according to claim 1 wherein the polymeric shell of the microcapsule is obtainable by polycondensation or by reacting the second monomeric component formed in situ with the first monomeric component.

13. A process according to claim 12 wherein the polymer shell is selected from the group of polyamides, polyesters, polyurethanes, polyureas.

14. A process according to claim 12 wherein the polymer is a polyurea or a polyurethane and the first monomeric component is selected between di- and tri-isocyanates wherein the isocyanate groups are linked to an aliphatic or aromatic group and the second component is an aliphatic diamine having C₂-C₇ carbon atoms.

15. A process according to claim 1 wherein during the preparation of the microcapsule or after the microcapsule formation, ammonium salts, or inorganic alkaline metal salts selected from the following ones are added:

lithium chloride, sodium chloride, potassium chloride, lithium nitrate, sodium nitrate, potassium nitrate, lithium sulphate, sodium sulphate, potassium sulphate, sodium monohydrogen-phosphate, potassium monohydrogen phosphate, sodium dihydrogen-phosphate, potassium dihydrogen-phosphate;

alkaline-earth metal salts selected from magnesium chloride, calcium chloride, magnesium nitrate, calcium nitrate, magnesium sulphate; and

alkaline metal salts of acetic acid.

16. A process according to claim 15 wherein the salt is calcium nitrate.

17. The process of claim 15, wherein the ammonium salts are selected from the group consisting of:

ammonium chloride, ammonium sulphate, ammonium monohydrogen phosphate, and ammonium dihydrogen-phosphate.