JPS6357103B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing microcapsules,
In particular, it relates to a method of microencapsulating N,N-diethyl-m-toluamide, which is partially soluble in the microcapsule wall, as a core material.

Conventional technology A method of microencapsulating a lipophilic substance as a core material by a complex coacervation method is as follows.
As described in US Pat. No. 2,800,457, it basically consists of the following steps.

(a) An emulsion is obtained by emulsifying and dispersing an oily substance to be microencapsulated as a core substance in a first hydrophilic colloid aqueous solution.

(b) This emulsion is mixed with an aqueous solution of a second hydrophilic colloid having an opposite charge to that of the first colloid.

(c) Diluting the above colloidal aqueous solution mixture with water,
Alternatively, by adjusting the PH, a thick colloidal liquid, ie, a coacervate, is formed around the droplets of oily material.

(d) The colloidal aqueous solution mixture is cooled to a temperature of about 0 to 10°C to gel the coacervate.

(e) The thus gelled coacervate is cured by adding aldehydes, adjusting pH or temperature, etc.

Furthermore, in order to improve the method for producing microcapsules by such a complex coacervation method, for example, US Pat. No. 3,341,466 discloses
A method is disclosed in which the capsule wall is made thicker by lowering the temperature stepwise during the production of coacervate. Additionally, U.S. Patent No.
No. 3956172 discloses that coloring, viscosity increase, aggregation, etc. can be prevented when coacervate is cured by using a low molecular weight dialdehyde and formamide in combination.

However, with any of the above methods,
Even if the stirring conditions, viscosity, pH, temperature, etc. are carefully adjusted, the formed microcapsules may still aggregate.

In particular, N, whose core material is useful as a mosquito repellent,
When N-diethyl-m-toluamide is partially soluble in the capsule wall, the microcapsules obtained by any of the above-mentioned conventional methods do not have sufficient strength; The dry weight content of the core substance is less than 50%, and the rate at which the core substance is microencapsulated, that is, the microencapsulation rate, is also low, usually 10 to 40%.
It is only %.

Problems to be Solved by the Invention The present invention has been made in order to solve various problems as described above in a method for producing microcapsules of lipophilic core substances by a complex coacervation method. The purpose of the present invention is to provide a method for easily and quickly producing microcapsules that are stable and have a high core material content without the presence of N,N-diethyl-m, which is partially soluble in the capsule wall. - It is an object of the present invention to provide a method for producing microcapsules that can easily produce microcapsules having toluamide as a core material at a high microencapsulation rate.

Means for Solving the Problems A method for producing microcapsules by a complex coacervation method according to the present invention includes a method for producing microcapsules of N,N-diethyl-m-toluamide by a complex coacervation method. A first step of mixing N-diethyl-m-toluamide with an ionizable colloid and a coacervation aid selected from ionizable long-chain fatty acids; emulsifying and dispersing this mixture in an aqueous solution of an ionizable colloid; A second step of obtaining a hydrophilic colloid aqueous solution: A first colloid aqueous solution and a second ionizable hydrophilic colloid aqueous solution having an opposite charge to the colloid are mixed under stirring to generate coacervation. 3rd step, the colloidal aqueous solution mixture is cooled to gel the coacervate to form a capsule wall; 4th step is to add ethoxylated lanolin to stabilize the gelled capsules and prevent agglomeration. and a sixth step of curing the capsule wall, characterized in that the first and second ionizable colloids are selected from gelatin, gum arabic, casein, carrageenan and carboxymethylcellulose.

Thus, according to the present invention, before emulsifying and dispersing N,N-diethyl-m-toluamide in an aqueous hydrophilic colloid solution, an ionizable colloid or an ionizable long-chain fatty acid is added as a coacervation aid. The PH of the colloidal aqueous solution by
Coacervation can be caused quickly and efficiently without the need for adjustment or dilution, and coacervate can be gelled under milder conditions than in conventional methods, and further, By adding ethoxylated lanolin, a water-soluble wax derivative, to the aqueous colloid solution mixture after the gelation of the microcapsule walls and before their hardening, agglomeration of the microcapsules can be effectively prevented.

Below, a method for producing microcapsules having N,N-diethyl-m-toluamide as a core material by a composite coacervation method according to the present invention will be described in detail.

First, in the first step, the coacervation aid is selected from ionizable colloids and ionizable long chain fatty acids. As the ionizable colloid, for example, gelatin, gum arabic, casein, carrageenan, carboxymethylcellulose, etc. are used. Furthermore, higher fatty acids are used as the ionizable long-chain fatty acids.

Next, as the ionizable colloid used in the first step, second step, and third step, conventionally known colloids can be used, and specific examples include gelatin, casein, carrageenin,
gum arabic, carboxymethyl cellulose,
Examples include sodium alginate.
The first colloid in the second step and the second colloid in the third step are selected to have charges of opposite signs. In particular, in the method of the present invention, gelatin is preferably used on the one hand and gum arabic on the other hand.

The first and second steps are carried out at room temperature or higher temperature, preferably in the range of 35 to 50°C, for example. The third step is carried out at a temperature above the gelation of the colloid, in the range of 35-50°C.
Furthermore, the time for mixing the aqueous colloid solution in the third step is not limited at all and can be varied over a wide range. In the first step, after mixing the core material and the coacervation aid to obtain an emulsion, the emulsion is depressurized to remove dissolved air to make it even stronger. Microcapsules with capsule walls can be obtained.

In the fourth step, the aqueous colloid mixture is cooled to gel the coacervate and form the capsule wall. In this case, the cooling rate is not limited in any way, but the cooling temperature must be 20°C or less, preferably in the range of 15 to 20°C,
Compared to conventional methods, coacervate can be gelled under milder conditions.

According to the method of the present invention, in the fifth step, ethoxylated lanolin, which is a water-soluble wax derivative, is added to stabilize the gelled capsules and prevent agglomeration. This step is carried out at the cooling temperature mentioned above.

The gelled capsule wall is then hardened, insolubilized and stabilized in a sixth step. Hardening of the capsules is accomplished by adding formaldehyde, glutaraldehyde, glyoxal or mixtures thereof and then increasing the temperature preferably to 20-40° C. to accelerate hardening, as already known from the above-mentioned literature and elsewhere. This can be done by doing.

Hardening of the capsule walls can also be achieved by adding tannic acid at a temperature of 15-25° C. and then leaving the mixture to stand for several hours. Tannic acid may be added either before or after the addition of ethoxylated lanolin. When the capsule wall is hardened with tannic acid without using aldehyde, the resulting microcapsules melt at a temperature of 30°C or higher;
- Diethyl-m-toluamide can be released, but it can be suitably used in applications where it is not released at temperatures lower than 30°C.

Effects of the Invention As described above, according to the method of the present invention, there is no need to adjust the pH or dilute the colloidal aqueous solution mixture when forming coacervate, and the coacervate can be gelled under milder conditions than conventional methods. can be done. Furthermore, according to the method of the present invention, since aggregation of microcapsules does not occur,
Microcapsules can be efficiently microencapsulated using N,N-diethyl-m-toluamide, which is soluble in the capsule wall, as a core material, which has conventionally been difficult to microencapsulate. That is, according to the method of the present invention, in the production of microcapsules having N,N-diethyl-m-toluamide as a core material, stable microcapsules containing 60% or more of the core material by dry weight are
% or more.

EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 14 g of gelatin was dissolved in 175 ml of water at a temperature of 40°C. Separately, 4.2 g of stearic acid was dissolved in 100 ml of N,N-diethyl-m-toluamide, and this solution was added to the above gelatin colloid with stirring at a temperature of 40 DEG C. to emulsify and disperse. 9.3g of gum arabic in water
Add the solution dissolved in 135 ml to the emulsion obtained above, and stir for 3 hours with constant stirring.
Cooled to ℃.

After this, 140 ml of a 30% by weight aqueous ethoxylated lanolin solution (Ethoxylan 100 manufactured by Emery) was added.
After 10 minutes, add 50% glutaraldehyde aqueous solution by volume.
735μ was added. The resulting mixed solution was gently stirred for 1.5 hours and then left overnight at room temperature.

The precipitated microcapsules were centrifuged at 2800 rpm for 15 min to obtain 42-44% N,N by wet weight.
About 220 ml of microcapsules containing -diethyl-m-toluamide were obtained without agglomeration. When the wet microcapsules were dried at room temperature for 4 hours, the content of N,N-diethyl-m-toluamide was 75-80% by dry weight. Also, N, N-
The microencapsulation rate of diethyl-m-toluamide was about 94%.

In this example, gelatin is the negatively charged first ionizable colloid, stearic acid is the negatively charged coacervation aid, N,N-diethyl-m-toluamide is the lipophilic core material, and gum arabic is the positively charged coacervation colloid. It is a second ionizable colloid that has an electric charge.

Comparative Example 1 Microcapsules were prepared in exactly the same manner as in Example 1 above, except that ethoxylated lanolin was not added. However, the microcapsules agglomerated significantly, and despite high-speed stirring, the entire solution turned into a gel.

Example 2 20 g of gelatin was dissolved in 200 ml of water at a temperature of 40°C. Separately, 8 g of gum arabic was dispersed in 80 ml of N,N-diethyl-m-toluamide, and this was added to the gelatin aqueous solution and stirred vigorously at 45°C to form an emulsion. Add a solution of 20g of gum arabic dissolved in 200ml of water to the emulsion obtained above,
The mixture was then cooled to 25° C. with constant stirring. After this, an aqueous solution of 8 g of tannic acid dissolved in 80 ml of water was added, and the same 30% by weight as above was added.
200 ml of ethoxylated lanolin aqueous solution was added. The mixture was stirred for 3 hours and then left at room temperature overnight.

The precipitated microcapsules were centrifuged at 2700 rpm for 10 minutes to obtain approximately 350 ml of microcapsules without agglomeration. The microcapsules contain 16-20% N by wet weight and about 60% by dry weight.
It contained N-diethyl-m-toluamide.
Further, the microencapsulation rate of N,N-diethyl-m-toluamide was about 80%.

In this example, the initially added gum arabic acts as a coacervation aid, and the tannic acid acts as a curing agent.

Example 3 30 g of gelatin was dissolved in 440 ml of water at room temperature. Separately, add 5.4 g of stearic acid to N,N-diethyl-m
- It was dissolved in 157.5 ml of toluamide, and this solution was emulsified and dispersed in the gelatin aqueous solution at room temperature using a blender. The emulsion was degassed under reduced pressure for 20 minutes with stirring, after which it was added to an aqueous solution of 20 g of gum arabic dissolved in 360 ml of water at a temperature of 45°C. The mixture was cooled to 19°C while stirring for 3 hours.

Next, 540 ml of the same 30% by weight aqueous ethoxylated lanolin solution as above was added over 20 minutes. After this, add 4.5 ml of 50% by volume glutaraldehyde aqueous solution.
Add 0.3ml of 36% formaldehyde aqueous solution,
The temperature was raised to 35° C. over 1 hour while stirring. The solution was then left at room temperature overnight.

The precipitated microcapsules were centrifuged at 3000 rpm for 35 min to remove microcapsules without agglomeration.
Obtained 390g. The microcapsules contain about 30% by wet weight and about 70% by dry weight N,N.
-diethyl-m-toluamide. Further, the microencapsulation rate of N,N-diethyl-m-toluamide was about 75%.

Reference Example 1 To 91 parts by weight of the microcapsules obtained in Example 3, the methyl vinyl ether-maleic anhydride copolymer solution as an excipient was 9 parts by weight, so that 47.5% of this copolymer was added. mixed with solution. The resulting cream was applied to human skin, and N,N-diethyl- remained on the skin for 12 hours.
The amount of m-toluamide was measured.

After 2 hours, 40% of the applied amount has been applied, and after 6 hours, 20% of the applied amount has been applied.
% and 15% remained after 10 hours. Here, the amount of N,N-diethyl-m-toluamide remaining on the skin is determined by
- Diethyl-m-toluamide was collected by rinsing off the skin and weighed.

Further, as a result of examining the mosquito repellent effect of the cream containing N,N-diethyl-m-toluamide obtained in this reference example in an experiment using rabbits, it was confirmed that it lasted for more than 8 hours.

Claims (1)

[Claims] 1. A method for producing microcapsules of N,N-diethyl-m-toluamide by a complex coacervation method, in which N,N-diethyl-m-toluamide is combined with an ionizable colloid and an ionizable long-chain fatty acid. a first step of mixing with a coacervation aid selected from the following; a second step of emulsifying and dispersing this mixture in an aqueous solution of an ionizable colloid to obtain a first aqueous hydrophilic colloid solution; a first aqueous colloid solution; A third step in which this colloid and a second ionizable hydrophilic colloid aqueous solution having an opposite charge are mixed with stirring to cause coacervation, and this colloid aqueous solution mixture is cooled to gel the coacervate. , a fourth step of forming a capsule wall, a fifth step of adding ethoxylated lanolin to stabilize the gelled capsule and prevent agglomeration, and a sixth step of hardening the capsule wall, and a second ionizable colloid selected from gelatin, gum arabic, casein, carrageenan and carboxymethyl cellulose.