Trans esterification product of the maize oil with glycerine and preparation process thereof

BACKGROUND OF THE INVENTION The present invention relates to a transesterification product, to corn oil, with glycerin and to a process for making it, a product intended for use in various drug compositions as a pharmaceutically acceptable solubilizer.

From the data in the specialized literature, transesterification products of corn oil with glycerin are known, namely products marketed under the name of Maisine.

Such products are obtained by transesterification [glycerolysis] of a vegetable oil, namely corn oil with glycerin, and are predominantly constituted by mono-, di- and triglycerides of stearic and palmitic acid.

The composition of the products is determined by the composition of corn oil containing about 56% by weight linoleic acid, 30% oleic acid, 10% palmitic acid and 3% stearic acid.

The physical characteristics of Maisine products (accessible from Establisments Gattefosse, 36 Chemin de Genas, RG Box 603, 69804, Saint-Priest Cedex, France] are as follows:

Free glycerin maximum 10% (usually 3.9 ... 4.9% or in batch without glycerin, about 0.2%] Mono-glycerides about 35% (usually 30 ... 40% or in batch without glycerin, e.g. .32 ... 36%, eg about 36%).

Di-glycerides about 50% (or in the glycerol-free batch, about 46 ... 48%).

Tri-glycerides about 10% (or in the glycerine-free batch about 12 .. 15%).

Free oleic acid content about 1%.

Other physical characteristics of these products are acidity index = maximum 2; iodine index = about 85 ... 105%; saponification index = about 150 ... 175 [Fiedler Lexikon der HilfestoffengEd.3, vol.2, pg.768, 1989). The fatty acid content of Maisine products is: palmitic acid about 11%; stearic acid about 2.5%; oleic acid about 29%; linoleic acid about 56%; others about 1.5%.

It is preferred that the transesterified product be clear, that is, after storing a sample in the refrigerator, between 2 and 8 ° C, that the sample remains clear for one hour, after being removed from the refrigerator.

Preferably transesterification products should have low saturated fatty acids content. They can be obtained from commercially accessible products, for example they can be obtained by separation methods known to those skilled in the art, by freezing processes coupled with separation techniques, by centrifugation, for removing unsaturated fatty acid components. It is desirable to be <15%, preferably <10% and especially <5% by weight, based on the total weight of the product. After using the separative technique, a reduction of the saturated fatty acid content in the mono-glyceride fraction of the product is observed.

Transesterification products, preferably, must contain lower amounts of saturated fatty acids (eg palmitic and stearic acid) and relatively higher amounts of unsaturated fatty acids (eg oleic and linoleic acids) than in the starting material.

The problem solved by the present invention is to produce a product of transesterification of the corn oil with glycerin, treated in order to increase the mono-, di- and tri-glycerides content of the unsaturated fatty acid.

The transesterification product of the corn oil with glycerin according to the invention consists of at least 85% mono-, di- and tri-glycerides of oleic and linoleic acid, less than 5%, preferably 1% free glycerin and less. of 15% mono-, di- and tri-glycerides of saturated fatty acid, respectively of stearic and palmitic acid. The transesterification product contains 30 ... 40% monoglycerides, 45 ... 55% diglycerides and at least 5% triglycerides, based on the total weight of the product.

The process for obtaining the transesterification product according to the invention consists in that the transesterified maize oil with glycerin is subjected to freezing techniques coupled with successive separations, in two or three freezing steps, at temperatures of + 20 ° C and + 8 ° C, respectively at temperatures of + 20 ° C, + 10 ° C and 5 ° C, for 12; h, followed by separation by centrifugation at an acceleration of 1 2000 G. finally obtaining a transesterification product with low mono-, tri-glyceride, saturated fatty acid content.

The transesterification product obtained according to the invention has the advantage of being stable for a longer period of time, which is why it is used for the solubilization of many therapeutically active agents.

The transesterification products which meet the respective characteristics according to the present invention are hereinafter referred to as transesterified maize oils with glycerin and refined.

The invention provides in a first aspect a product of transesterification of the corn oil with glycerin which contains predominantly

RO 111110 Glycerine and refined maize wheat, compared to the starting material (eg

35.6% compared to 38.3%).

mono-, di- and tri-glycerides of the linoleic and oleic acid treated to increase the content of unsaturated fatty acid component of mono-, di- and tri-glycerides so that the mono-, di- and tri-glyceride content of of oleic acid and 5 linoleic acids is 85% or more, based on the entire composition.

A second aspect of the invention is the process of obtaining the product of transesterification of corn oil with 10 glycerine, refined.

The following is an example of an embodiment of the invention.

Example. Preparation of transesterified corn oil with glycerin and refined 15

Corn oil transesterified with glycerin and without free glycerin content is cooled slowly, to a temperature of + 2 ° C and left at this temperature overnight. After a first centrifugation step, at 20 12OOO G and a flow rate of 103 kg / h, in a continuous flow centrifuge, a liquid phase [62 kg / h) was obtained and a phase containing a sediment [41 kg / h). The liquid phase cools slowly to + 8 ° C and is left at this temperature overnight. In a second centrifugation step at an acceleration of 12000 G and at a flow rate of 112 kg / h, a liquid phase (76.2 kg / h) and a phase containing sediment (35.8 kg / h) were obtained. Liquid phase 30 is corn oil, which is transesterified with glycerin and refined. It can be obtained in three stages, ie at + 2 ° C, + 1 ° C and + 5 ° C.

The process is characterized by a slight reduction of monoglyceride in the oil of 35

Preferred transesterification products according to the present invention contain:

... 36% .... mono-glyceride;

... 55% ....... di-glyceride;

... 20% ....... tri-glyceride;

by weight, based on the total weight of the product.

Other preferred features include the following:

- The fatty acid content determined as methyl ester by chromatography:

<td>Methyl linoleate</td><td> 53 ..</td>

<td>Methyl oleate. .</td><td> 24 ..</td>

<td>Methyl linoleate</td><td> . . 0</td>

<td>Methyl arachnite</td><td> . . 0</td>

<td>Methyl palmitate</td><td> . 6 ..</td>

<td>Methyl stearate</td><td> . . . 1</td>

<td>- Relative density.</td><td> 0,94 .</td>

- Hydroxyl index

-Iodine index. .

- Peroxide index ....... &lt;4.0;

-Glycerin free ......... &lt;1.0;

-Acid index, max ..... about 2;

- Saponification index 150 ... 185.

The freshly prepared products are clear and retain their clarity over 20 days, at a temperature of 20 ... 25 ° C.

The analytical results of the sediment and the clear solution are presented comparatively in the table below:

<td></td><td>Compound</td><td>Sediment (%]</td><td>Clear solution (%]</td>

<td> 1</td><td>Palmitate monkey</td><td> 19,1</td><td> 3.4</td>

<td> 2</td><td>Linoleat money + Oleat money</td><td> 23,4</td><td> 27,0</td>

<td> 3</td><td>Mono stearate</td><td> 5,7</td><td> &lt; 2</td>

<td> 4</td><td>Dilinoleat + Dioleat</td><td> 35,4</td><td> 44,7</td>

<td> 5</td><td>Other di-glycerides</td><td> 7,7</td><td> 10,4</td>

<td> 6</td><td>Tri-glycerides</td><td> 8,7</td><td> 12,5</td>

The content of the components in the refined product is presented in the following table:

RO 111110 Bl

Composition of components (%, w / w)

<td>components</td><td>Maize oil transesterified with glycerin and refined</td>

<td>Glyceride: mono</td><td> 33,3</td>

<td>di</td><td> 52,1</td>

<td>tri</td><td> 14,6</td>

<td>Fatty acids:</td><td></td>

<td>palmitic acid (C_1B)</td><td> 7,8</td>

<td>stearic acid (C_takes)</td><td> 1,7</td>

<td>oleic acid (C_1S : 1)</td><td> 31,6</td>

<td>linoleic acid (C_1S : 2]</td><td> 57.7</td>

<td>Glycerin content</td><td> &lt; 1</td>

claims