AU688920B2 - Transesterified corn oil products - Google Patents

Description

Regulation 3 2

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

(ORIGINAL)

S

Name of Applicant: Sandez-Ltd- O jar4 S AC; Actual Inventors: Address for Service: HAUER, Birgit MEINZER, Armin POSANSKI, Ulrich VONDERSCHER, Jacky DAVIES COLLISON CAVE, Patent Attorneys, 1 Little Collins Street, Melbourne, 3000.

Invention Title: "Transesterified Corn Oil Products" The following statement is a full description of this invention, including the best method of performing it known to me/us:

II

1 II'IV M I .14 7 1 I P 1A- TRANSESTERIFIED CORN OIL PRODUCTS The present invention relates to transesterified corn oil products.

In one aspect, this invention provides a transesterification product of corn oil and glycerol comprising predominately oflinoleic acid and oleic acid mono-, di and tri-glycerides, wherein the product has been treated by separative techniques and freezing procedures so as to a) reduce the saturated fatty acid component content of mono-, di- and tri-glycerides; and to b) enhance the unsaturated fatty acid component content of mono-, di- and tri-glycerides 10 so that the linoleic acid and oleic acid mono-, di- and tri-glyceride content is in total 85% by weight or more of the whole composition.

A pharmaceutical composition is disclosed in AU 18527/92 comprising a cyclosporin as active ingredient in a carrier medium comprising: *o 15 1) 1,2-propylene glycol; 2) a mixed mono-, di-, tri-glyceride; and 3) a surfactant.

Components in the compositions disclosed in AU 18527/92 comprise mixtures of

C

12 20 fatty acid mono-, di- and tri-glycerides, especially q-1 tatty acid mono-, di- and triglycerides. The fatty acid component of said mixed mono-, di- and tri-glycerides may comprise both saturated and unsaturated fatty acid residues. Preferably however they will predominantly be comprised of unsaturated fatty acid residues in particular, C18 unsaturated fatty acid residues for example linolenic, linoleic and oleic acid residues. Suitably component will comprise at least 60%, preferably at least 75%, more preferably 85% or more by weight C18 unsaturated fatty acid, e.g. linolenic, linoleic and oleic acid mono-, di- and triglycerides. Suitably they will comprise less than 20%, e.g. ca. 15% or 10% by weight of less, saturated fatty acid, e.g. palmitic and stearic acid mono-, di- and tri-glycerides.

Components in the above-mentioned compositions will preferably be predominantly comprised of mono- and di-glycerides, e.g. comprise at least 50%, more ,30 preferably at least 70%, e.g. 75%, 80%, 85% by weight or more, mono- and di-glycerides, I l)I 1 RMW 1914 )q X^ 6 I 'N -2based on the total weight of component Components in the compositions will suitably comprise from about 25 to about preferably from about 30 to about 40%, e.g. 35 to 40%, monoglycerides, based on the total weight of component Components in the composition will suitably comprise from about 30 to about preferably from about 40 to about 55%, e.g. about 48 to 50%, di-glycerides, based on the total weight of component Components in the compositions will suitably comprise at least e.g. from about 7.5 to about 15%, e.g. 9 to 12%, by weight of triglycerides.

10 Components in the compositions may be prepared by admixture ol individual mono-, di- or tri-glycerides in appropriate relative proportion. Conveniently however they will comprise transesterification products of vegetable oils, for example almond oil, ground nut oil, olive oil, peach oil, palm oil or, preferably, corn oil, sunflower oil or safflower oil and most preferably corn oil, with glycerol.

15 In another aspect, this invention provides a transesterification product of corn oil and glycerol having a saturated fatty acid content of mono-, di-, and tri-glycerides, which product is prepared by separative techniques and freezing procedures and comprises from about 25% to about 50% by weight of mono-glycerides, from about 30% to about 60% by weight of di-glycerides, and at least 5% by weight of tri-glycerides; and (ii) a linoleic acid and oleic acid mono-, di- and tri-glyceride content of at least by weight; wherein the total saturated fatty acid content of mono-, di-, and tri-glycerides is less than by weight.

Such transesterification products are generally obtained by heating of the selected vegetable oil with glycerol, at high temperature in the presence of an appropriate catalyst under an inert atmosphere with continuous agitation, e.g. in a stainless steel reactor, to effect transesterification or glycerolysis. In addition to their mono-, di and tri-glyceride ,I 3 100-'775i2/: components, such transesterification products will also generally comprise minor amounts of free glycerol. The amount of free glycerol present in components for use in the compositions of the invention will preferably be less than 100', more preferably less than most preferably ca. 1 or 2% by weight based on the total weight of free glycerol plus mono-, di- and tri-glycerides.

Preferably some of the glycerol is first removed e.g. by distillation (to give a substantially glycerol free batch), when soft gelatine capsules are to be made.

Especially suitable components for use in the compositions will thus comprise the following components in the indicated amounts by weight based on the total weight of component Mono-glycerides: 25 or 30 to 50%, especially 30 to Di-glycerides: 30 or 40 to 60%, especially 40 to 55%, e.g. 45 to Mono- plus di-glycerides: especially e.g. ca. Tri-glycerides: at least Free glycerol: preferably or Particularly suitable components for use in the compositions are trans-esterification products of corn oil and glycerol, for example as commercially available under the trade S name Maisine. Such products are comprised predominantly of linoleic and oleic acid mono-, di- and tri-glycerides together with minor amounts of palmitic and stearic acid mono-, di- and tri-glycerides (corn oil itself being comprised of ca. 56% by weight linoleic acid, 30% oleic acid, ca. 10% palmitic and c- 3% stearic acid constituents). Physical .characteristics for Maisine [available from the company Etablissements Gattefoss6, of 36, Chemin de Genas, P.O.Box 603, 69804 Saint-Priest, Cedex (France)] are: approximate composition free glycerol 10% max. (typically 3,9-4.9% or, in substantially glycerol free batches, ca. 0.2%) mono-glycerides ca. 35% (typically 30-40% or, in substantially glycerol free batches, e.g. 32-36%, e.g. ca.

36%) di-glycerides ca. 50% (or, in substantially glycerol free batches ca.

46-48%) -4 100 -7752/II tri-glycerides ca. 10% (or, in substantially glycerol free batches, ca.

12-15%) free oleic acid content ca. 1% Further physical characteristics for Maisine are: acid value max. ca. 2, iodine no. ca.

85-105, saponification no. ca. 150-175 (Fiedler "Lexikon der Hilfsstoffe", 3rd revised and expanded edition (1989) Vol. 2, p.768). The fatty acid content for Maisine is typically: palmitic acid ca. 11%; stearic acid ca. oleic acid ca. 29%; linoleic acid ca.

56%; others ca. It is especially preferred that the component e.g. a glycerol transesterified corn oil is clear, e.g. after keeping a sample in a refrigerator, e.g. between 2 and 8 0 C, for 24 hours, the sample is clear at room temperature 1 hour after taking the sample out of the refrigerator.

Preferably components have a low saturated fatty acid content. Components (2) meeting these requirements may, for example be obtained from commercially available products, e.g. obtained therefrom by methods such as separative techniques as known in the art, e.g. freezing procedures coupled with separative techniques, e.g. centrifugation, to remove the saturated fatty acid components/enhance the unsaturated fatty acid component content. Typically the total saturated fatty acid component content will be e.g.

or by weight based on the total weight of component A reduction of the content of saturated fatty acid component in the mono-glyceride fraction of components may be observed after the separative technique.

Components thus preferably contain lesser quantities of saturated fatty acids (e.g.

palmitic and stearic acids) and relatively greater quantities of unsaturated fatty acids (e.g.

oleic and linoleic acids) than for the starting material.

Typical preferred components preferably contain: 32-36% mono-glycerides, 45-55% di-glycerides and 12-20% tri-glycerides

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100-7752/II by weight based on the total weight of component Further preferred characteristics include the following: Fatty acid content as determined as the methyl ester by chromatography Methyl linoleate 53-63% Methyl oleate 24-34% Methyl linolenate 0- 3% Methyl arachate 0- 3% Methyl palmitate 6-12% Methyl stearate 1- 3% Relative Density 0.94-0.96 Hydroxyl Value 140-210 Iodine Value 110-120 Peroxide Value Free Glycerol Acid value max. ca. 2 Saponification no. ca. 150-185 Components complying with the above outlined features are referred to herein as "refined glycerol-transesterified corn oils". Freshly prepared components according to the preferred embodiments are of clear appearance and stay clear at storage temperature of 0 C 25 0 C for more than 20 days.

The refined glycerol-transesterified corn oils have especially been proposed for the preparation of the compositions disclosed in AU 18527/92. They may also have uses for the solubilization of other active agents and have the advantage of remaining stable, e.g. clear, for a long time.

The following example illustrates the present invention. This example is not to be construed as limiting the invention in any way.

6 100-77E2/TI EXAMPLE 1: Preparation of refined glycerol-transesterified corn oil.

Substantially-glycerol free glycerol-transesterified corn oil (if necessary after heating to give a clear mixture) is slowly cooled to a temperature of +20 0 C and kept at this temperature for one night. In a first-step centrifugation, at an acceleration of 12 000 G and a flow rate of 103 kg/h in a continuous flow centrifuge, a liquid phase (62 kg/h) and a sediment-containing phase (41 kg/h) are obtained. The liquid phase is slowly cooled to +8 0 C and kept at this temperature for one night. In a second-step centrifugation at an acceleration of 12 000 G and a flow rate of 112 kg/h a liquid phase (76.2 kg/h) and a sediment-containing phase (35.8 kg/h) are obtained. The liquid phase is "refined glycerol-transesterified corn oil". Alternatively an improved product may be obtained by effecting the centrifugation in three steps, e.g. at +20°C, +100C and The process is characterised by a slight percentage reduction in the mono-glyceride component in the refined glycerol transesterified corn oil as compared to the starting material 35.6% compared to 38.3%).

A typical analytical comparison between the sediment and clear solution is as follows: Compound Sediment Clear Solution 1. Mono palmitate 19.1 3.4 2. Mono linoleate 23.4 27.0 Mono oleate 3. Mono stearate 5.7 <2 4. Dilinoleate 35.4 44.7 Dioleate 5. Other di-glycerides 7.7 10.4 6. Tri-glycerides 8.7 12.5 Typical contents of components in the refined product obtained from these preparations are listed in the following Table: COMPOSITION OF COMPONENTS w/w) Components refined glycerol-transesterified corn oil Glycerides: mono 33.3 di 52.1 tri 14.6 Fatty acids: palmitic acid (C16) 7.8 stearic acid (C18) 1.7 oleic acid (C18:1) 31.6 linoleic acid (C18:2) 57.7 Glycerol content <1% Throughout this specification and claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

Claims (17)

1. A transesterification product of corn oil and glycerol comprising predominately of linoleic acid and oleic acid mono-, di and tri-glycerides, wherein the product has been treated by separative techniques and freezing procedures so as to a) reduce the saturated fatty acid component content of mono-, di- and tri-glycerides; and to b) enhance the unsaturated fatty acid component content of mono-, di- and tri-glycerides so that the linoleic acid and oleic acid mono-, di- and tri-glyceride content is in total 85% by 10 weight or more of the whole composition.

S"2. A product as claimed in claim 1 having 30% to 40% by weight of mono-glycerides.

3. A product as claimed in claim 1 or claim 2 having 45% to 55% by weight of di- 15 glycerides.

4. A product as claimed in any one of the preceding claims having 12 to 20% by weight of tri-glycerides.

5. A product as claimed in any one of the preceding claims having a free glycerol content of less than 5% by weight.

6. A product as claimed in any one of the preceding claims having a free glycerol content of less than 2% by weight.

7. A product as claimed in any one of the preceding claims having a total palmitic acid and stearic acid content of mono-, di- and tri-glycerides of less than 10% by weight.

8. A transesterification product of corn oil and glycerol having a saturated fatty acid content of mono-, di-, and tri-glycerides, which product is prepared by separative techniques and freezing procedures and comprises )4 S'oiTN'IJ('2R33'79iX6 ,1,94 -9- i) from 25% to 50% by weight of mono-glycerides, from 30% to 60% by weight of di- glycerides, and at least 5% by weight of tri-glycerides; and ii) a linoleic acid and oleic acid mono-, di- and tri-glyceride content of at least 85% by weight; wherein the total saturated fatty acid content of mono-, di- and tri-glycerides is less than by weight.

9. A product as claimed in claim 8 having 30% to 40% by weight of mono-glycerides.

10 10. A product as claimed in claim 8 or claim 9 having 45% to 55% by weight of di- S glycerides.

11. A product as claimed in any one of claims 8 to 10 having 12 to 20% by weight of tri- glycerides. S ooee•

12. A product as claimed in any one of claims 8 to 11 having a free glycerol content of less than 5% by weight. *0

13. A product as claimed in any one of claims 8 to 12 having a free glycerol content of less than 2% by weight.

14. A product as claimed in any one of claims 8 to 13, having a total palmitic acid and stearic acid content of mono-, di- and tri-glycerides of less than 10% by weight.

15. A process for obtaining a refined glycerol-transesterified corn oil according to any one of the preceding claims, comprising heating of corn oil with glycerol at high temperature in the presence of a suitable catalyst under an inert atmosphere with continuous agitation to effect glycerol-transesterification, and refining said product by freezing procedures coupled with separative techniques. 11 01T MWl 2,317 'A Wit, i 1 1;4

16. A transesterified corn oil substantially as hereinbefore described with reference to Example 1.

17. A purification process substantially as hereinbefore described with reference to Example 1. DATED this 5th day of January 1998 Sandoz Ltd. 10 By Its Patent Attorneys DAVIES COLLISON CAVE 0 e 0 0 *o 11 10-7752/II ABSTRACT A trans-esterification product of corn oil and glycerol comprising predominately of linoleic acid and oleic acid mono-, di- and tri-glycerides, wherein the product has been treated so as to reduce the saturated fatty acid component content of mono-, di- and tri-glycerides; and to enhance the unsaturated fatty acid component content of mono-, di- and tri-glycerides so that the linoleic acid and oleic acid mono-, di- and tri-glyceride content is in total 85% or more of the whole composition. *A e