DE1248015B - Process for the production of microcapsules from an emulsion of oil in a hydrophilic liquid - Google Patents

Description

GERMAN

PATENT OFFICE

EDITORIAL

German class 12 c - 3

Number. 1 248 015

File number U 6753IV c / 12 c

Filing date December 18, 1959

Opened on August 24, 1967

It is known to use oil droplets as such and oil droplets, which contain dissolved or dispersed substances, encapsulate by complex or simple coacetivation (See USA.-Patentschnften 2 800 457, 2 800 458) It is true that these patents describe the formation of coacervates from an oil-in-water emulsion, however, only the oil phase is encapsulated by the coacervate. The encapsulation of a Emulsion had not been tried before, and the significant advantages of one with a coacervate Coated emulsions, the phases of which contain dissolved or suspended constituents, were previously not recognized. In addition, no method was previously known by which a coacervate on a hydrophilic surface could be formed

The subject of the invention is a method of production of microcapsules, which contain an emulsion of oil in a hydrophilic liquid, by simple Coacervation with a gellable hydrophilic Colloid by adding an aqueous electrolyte solution or a water-soluble liquid, in which the colloid is less soluble than in water that The method according to the invention is characterized in that that the hydrophilic phase of the emulsion and optionally the aqueous electrolyte solution The usual thickener is added and coacervated

The inventive method opens up new ways in the production of impermeable coatings of high strength or those which allow eme slow release of water-soluble substances, a problem that could not be solved with the previously known methods of coacervation. For example, encapsulated emulsion particles can be produced which in the emulsion phases contain substances as slow-release fertilizers, plant growth hormones and pesticides such as fungicides, nematocides, bactericides, viricides and the like, for use in agriculture. Furthermore, ingredients can be added to premixed foods which normally cannot be mixed due to the drying process for foods, the encapsulated ingredients being released due to the shear force in a mixing step prior to actual use. Similarly, vitamins, especially compositions of water-soluble and oil-soluble vitamins, dry cereal preparations can be added for release in the body
liquid

Applicant.

The National Cash Register Company,

Dayton, Ohio (V St A.)

representative

Dr W Beil, A Hoeppener and Dr. H. J. Wolff,

Lawyers,

Frankfurt / M -Hochst, Adelonstr 58

Named as inventor
Everett Nelson Hiestand,
Erik Hugo Jensen,
Peter Dietrich Master,
Kalamazoo, Me (V St A)

Claimed priority
V St ν America dated December 22, 1958
(781925)

impermeable, but easily destructible coacervate shell Pharmaceuticals can be encapsulated to slow sustained release in the body after contact with a certain pH environment odei ferment system, or where stability, smell, taste or incompatibility is the problem form. Such substances can be included in top layers for oral, topical or injection administration by particle size, surface layer thickness, permeability and hardness or the composition be selected according to the top layer

For example, insecticides, which are selectively toxic to insects but are relatively non-toxic to humans, can e.g. be coated with a coacervate layer which is impermeable, with the exception of insectic ferments, which are effective against rodents when ingested, but because of their smell repellant or warning can also be covered with coacervate membranes, which are practically completely impermeable to the odor
The thickeners used here according to the invention are substances which are essentially insoluble in the oil phase of the primary emulsion and capable of removing the external hydrophilic liquid

709 638,

phase to impart surface properties that allow the coacervate to deposit on it. Examples are the natural or artificial thickeners, like acacia gum, tragacanth, methyl cellulose, Carboxymethylcellulose, Magnesiummmalumiuiumsüikat, Polyglycols, glycerin, syrups

The specific amounts of these substances can vary can be varied according to the means and system in question and can be used without difficulty Routine experiments are determined. Em range from 1 to about 20 percent by weight based on the Volume of the hydrophilic liquid phase, forms the practical measure, with 5 to about 10 percent by weight m to be preferred in most cases

example 1

An oil-in-water emulsion is prepared by emulsifying 50 ml of corn oil with 50 ml of water containing 2.5 g of methyl cellulose at 50 ° C ° C, mixed with the emulsion and slowly added to 250 ml of a 20% sodium sulfate solution, which had also been heated to 50 ° C. The sodium sulfate solution is vigorously stirred during the entire addition time. The temperature of the mixture is reduced to 5 ⁰ C to the coacervate to gel Sufficient lO ° / o aqueous sodium hydroxide solution is added to bring the pH to 9.5, followed by curing of the coacervate with 25 ml emer 37 ° / o formaldehyde solution while one hour The hardened coacervate is then removed, washed and air-dried at 80 ° C

Example 2

Following the procedure of Example 1, but using arachidol instead of corn oil, Tragacanth in place of methyl cellulose, potassium chloride in place of sodium sulfate and fibrinogen in place from gelatin one obtains a coacervate which has essentially the same properties as the im Example 1 has produced

Example 3

An oil-in-water emulsion is made at 50 ° C by adding 33 ml of paraffin oil in 25 ml of water, the 2 g of magnesium aluminum silicate and 0.5 g of Alizanncyangrun contains, are emulsified Em Gelatineso] is made at 50 ° C from 12.5 g of gelatine and 125 ml of water prepared and mixed thoroughly with the emulsion The mixture obtained is slowly increasing 125 ml emer 2O% TNTatum sulfate solution, which Containing 37 g of acacia gum, the sodium sulfate solution was added during the entire addition time is shaken vigorously to prevent coacervate formation demand the temperature of the equilibrium liquid, which contains the coacervate-coated emulsion is reduced to 5 ° C. and 10% sodium hydroxide solution added to obtain a pH of 9.5. Then 12.5 ml of a 37% formaldehyde solution are added added to make the coacervate shell hard. After 5 hours, the resulting product is added filtered off from the mixture, washed and spray-dried at 80 ° C (exhaust temperature)

If the coacervate described above is subjected to acidic and alkaline test solutions, it can be determined that a highly impermeable coating was obtained

Example 4

Following the procedure of Example 3 using lanolin in place of paraffinol as the Oil phase in the oil-in-water emulsion, carboxymethyl cellulose instead of magnesium aluminum silicate as a thickener for the water phase of the

ίο primary emulsion, ammonium phosphate in place of the Sodium sulfate as a coacervation agent, agar-agar instead of gelatin as a coacervation colloid and Tragacanth instead of acacia gum as a thickener for the coacervation solution, one obtains a coacervate which is essentially the same Properties like that produced in Example 3 has

Example 5

An oil-m-ethanol emulsion is produced by emulsifying 33 ml of arachidol in 25 ml of ethanol containing 2 g of methylcellulose at 50 ° C. Em Fibrrnogensol wild at 50 ° C from 12.5 g of fibrinogen and 125 ml of water and thoroughly mixed with the emulsion. The resulting mixture is slowly added to 125 ml of a 20% sodium resultant solution, which contains 37 g of acacia gum, the sodium sulfate solution being vigorously shaken during the entire time of addition to encourage the formation of a coacervate Reduced to 5 ° C. to gel the coacervate, and 10% sodium hydroxide solution was added to bring the pH to 9.5. Then 12.5 ml of a 37% formaldehyde solution were added to make the coacervate shell harder The product obtained is filtered off from the mixture for 5 hours, washed and cold-dried at 40 ° C. (probably −40 ° C.) and a 0.01 mm mercury vacuum

The procedures of Examples 1 to 5 can also with other thickeners for the hydrophilic liquid, as mentioned earlier which give the outer phase the properties which give the coacervate the deposit enable Specifically, for example, equivalents Amounts of acacia, tragacanth, carboxymethyl cellulose, magnesium aluminum silicate, the Polyglycols, glycerin, syrups and the like can be used

Claims (1)

Claim Process for producing microcapsules which contain an emulsion of oil in a hydrophilic liquid by simple coacervation with a gellable hydrophilic colloid by adding an aqueous electrolyte solution. or a water-soluble liquid in which the colloid is less soluble than in water, characterized in that a customary thickener is added to the hydrophilic phase of the emulsion and optionally to the aqueous electrolyte solution and coacervated Contemplated Publications USA Patent Nos. 2,800,457, 2,800,458 When the application was announced, photomicrographs and description were laid out 709 638/481 8 67 © Bundesdruckerei Berlin