GB2183635A - 1-mono-glyceride ester of gamma-linolenic acid - Google Patents

Abstract

The 1-mono-glyceride ester of gamma-linolenic acid (GLA) is disclosed together with its preparation by esterification of the acid (or ester forming derivative thereof) with glycerol. The GLA may be obtained from a naturally occurring source, e.g. Evening Primrose Oil, Common Borage Seed Oil, or Blackcurrant Seed Oil. The 1-mono-glyceride ester may be used in pharmaceutical compositions, cosmetic compositions or in food.

Description

SPECIFICATION Glycercide ester The present invention relates to a glycercide ester of gamma-linolenic acid.

Gamma Linolenic Acids, (GLA), or cis - 6,9,12-Octadecatrienoic Acid occurs rarely in natural sources. It is one of the family of 6 fatty acids, each have n-6 unsaturation, some or all of which are designated essential fatty acids being related to the prostaglandins which are required for human metabolic processes.

Evening Primrose Oil (Oenothera biennis or O.Lamarkiana), Common Borage seed Oil (Borago Officinalis), and Blackcurrant seed Oil are naturally occuring sources of GLA. More particularly, these oils comprise triglyceride esters of various long chain unsaturated acids, one of which is GLA. The triglyyceride esters will generally have, at most, one acid residue derived from GLA, the remainder being derived from the other long chain acids. The proportion of G LA (expressed as free acid) based on the total acids of the abovementioned oils are as follows: Evening Primrose Seed Oil 8-11% Borage Seed Oil 20-22% Blackcurrant Seed Oil 15-20% In order to provide a source of GLA in the human diet, Evening Primrose Oil, Borage Oil and Blackcurrant Seed Oil are currently marketed for medical use, as a direct dietary supplement and also for cosmetic formulations.The oils are usually sold commercially contained in small retail bottles or in soft gelatin capsules.

Whilst these oils are regarded as being beneficial, and are highly valued, they suffer from several disadvantages: (a) The oils have to be broken down by the digestive system to release either free GLA or its monoglycercide from in which the fatty acid is combined with glycerine in the 2 position, since it is in these forms that the GLA can pass across the intestinal wall.

(b) The oils cannot be readily emulsified with water, without the addition of an emulsification agent.

(c) The GLA content of the oil cannot readily be increased thereby inhibiting commercial marketing of the GLA in a more concentrated form.

(d) The naturally occuring, GLA-containing oils, may in some cases contain fatty acids which are not desirable.

Attempts have been made to overcome these disadvantages; one attempt has been to make commercially available the free fatty acid from these oils which can be readily obtained from the parent oil by methods such as hydrolysis, or saponification and re-acidification.

The free fatty acids can then be purified to give higher concentrations of GLA by methods such as fractional vacuum distillation, fractional low-temperature crystailisation and urea-adduct formation.

Such free fatty acids, whilst having the advantage of permitting purification and concentration, suffer from 2 main disadvantages.

(a) The free fatty acids are more unstable to oxidation than the esters.

(b) The free acids are not palatable as food due to unpleasant taste.

Further attempts to overcome these disadvantages have been made by combining fatty acid mixtures, with various concentrations of GLA, to an esterification procedure to produce ethyl esters.

Whilst these products are more oxidation-stable than the free acids and whilst they are more palatable they suffer from the following disadvantages: (a) Ethyl esters of GLA have not been found to occur from natural sources.

(b) Ethyl esters give rise to ethyl alcohol when broken down by the human digestive system, which may not be desirable.

It is an object of the present invention to obviate or mitigate the abovementioned disadvantages.

According to the present invention there is provided the 1 -mono-glyceride ester of GLA, i.e. the ester derived from GLA and glycerol in which the ester function is at the 1 -position of the glycerine residue.

The ester of the invention may be obtained by a number of techniques. For example, the tryglyceride esters of a naturally occuring source of GLA (e.g. Evening Primrose Oil, Common Borage Seed Oil, Blackcurrant Seed oil) may be hydrolysed or saponified and reacidified to produce glycerol (which may then be separated) and a mixture of free acids. The G LA may then be separated from this mixture by known techniques (e.g. fractional vacuum distillation, low temperature fractional crystallisation, urea adduct formtion) for subsequent esterification with glycerol. Such esterification may be effected by conventional techniques, e.g. with an acid catalyst (e.g.

para-toluene suphonic acid). The resultant product can be purified by distillation in a molecular still, e.g. to remove any tri or di-glyceride ester by-products of the reactions. Use of in excess of glycerol will however ensure minimum formation of such by products.

Alternatively, a mixture of the free acids as derived from the naturally occuring source of GLA may be esterified with glycerol as described above and the ester mixture used without separation of the 1 -mono-glyceride ester of GLA (although di- and tri-glyceride by products may be separated in molecular still).

We have found that the 1 -mono-glyceride ester of the invention has the following advantages: (a) GLA 1 -mono-glyc & de products are attainable with 0.1% to 99.1% GLA content depending on the concentration of GLA in the fatty acid mixture used for manufacture.

(b) GLA 1 -mono-glyceride products are readily purified by distillation in a molecular distillation apparatus.

(c) GLA 1 -mono-glyceride products require less action by the human or animal digestive systems, than the naturally occuring GLA oils, to release the GLA.

(d) GLA 1 -mono-glyceride products are more palatable as food than the free fatty acids or the ethyl esters.

(e) When GLA 1 -mono-glyceride products are digested they yield only free fatty acid and glycerol similar to the products when the human or animal body digests the naturally occuring oils.

(f) GLA 1 -mono-glyceride will emulsify water and water-containing solutions of other nutrients and can therefore be used in other water-containing foods, pharmaceuticals and cosmetics such as creams, lotions, pastes, dairy products or synthetic dairy products and the like.

(g) GLA 1 -mono-glyceride finds application when added to naturally occuring oils to render those oils more water absorptive, more water emulsifiable, for use in foods, pharmaceuticals or cosmetics such as creams, pastes, lotions, dairy products or synthetic dairy products and the like.

The 1 -mono-glyceride ester of GLA may thus be used (possibly in admixture with other esters) for a variety of purposes.

Examples are: (a) for medical use in which case the ester is formulated with a pharmaceutically acceptable carrier (b) for cosmetic use which case the ester is formulated with a cosmetically acceptable carrier; and (c) as a food or as a dietary supplement in which case the ester is formulated with an acceptable carrier.

A non-limiting Example for the manufacture of the ester of the invention is given below.

Example In a typical manufacture, 90 kilos of Evening Primrose Oil fatty acids (as obtained by hydrolysis or saponification and reacidification of Evening Primrose Oil followed by separation of glycerine) together with 30 kilos of Glycerol and 400 grams of para-toluene sulphonic acid were heated together at 130"C in a stainless-steel reactor, whilst passing a steady steam of oxygen-free nitrogen through the reaction mixture, in order to give agitation, prevent oxidation and to assist in removal of the water reaction product. This was continued for 4 hours when the reaction was subsequently complete; free fatty acid content of the product being 5.2%. The reaction product was passed through a molecular distillation apparatus, with a vacuum at 10 microns and at a temperature of 95-1 00 C in order to strip off residual fatty acids. A first distille fraction, of 36% free fatty acid content was separated, weight 16 kilos. This fraction was retained to be introduced into a succeeding manufacturing batch. The stripped product was re-passed through the molecular distillation apparatus at 8 microns vacuum and at a 130-1 35 C temperature to substantially distill the 1 -mono-glyceride product.

1 -mono-glyceride product was collected as a pale yellow clear oil, weight 61 kilos. The residue, 26 kilos, was retained for subsequent hydrolysis and distillation, in order to introduce the recovered fatty acids in the successive manufactured batch of 1-mono-glyceride.

Claims (13)

1. The 1-mono-glyceride ester of gamma linolenic acid.

2. An ester mixture comprising the ester as claimed in claim 1 and glycerides of other long chain acids.

3. A mixture as claimed in claim 2 wherein the acid residue content of the mixture is derived from Evening Primrose Oil, Common Borage Seed Oil or Blackcurrant Seed Oil.

4. A method of preparing the ester of claim 1 comprising esterifying gamma-linolenic acid or an ester forming derivative thereof with glycerol.

5. A method of preparing the ester of claim 1 comprising liberating from a triglyceride ester in which at least one of the acid residues is gamma-linolenic acid and esterifying the gamma-linolenic acid with glycerol.

6. A method as a claimed in claim 5 wherein the triglyceride ester is obtained from a naturally occuring source.

7. A method as claimed in claim 6 wherein the naturally occuring source is Evening Primrose Oil, Common Borage Seed Oil, or Blackcurrant Seed Oil.

8. A method as claimed in any one of claims 5 to 7 wherein the gamma-linolenic acid is separated from other free acids liberated from the tryglyceride ester prior to esterification with glycerol.

9. A method as claimed in any one of claims 5 to 7 wherein the gamma-linolenic acid is not separated from other free acids liberated from triglyceride ester and esterified in admixture therewith.

10. A method as claimed in any one of claims 4 to 9 wherein di and/or triglyceride by-products are separated from the 1 -mono-glyceride ester.

11. A pharmaceutical composition comprising an ester as claimed in claim 1 together with a pharmaceutically acceptable carrier.

12. A cosmetic composition comprising an ester as claimed in claim 1 together with a cosmetically acceptable carrier.

13. A food or food supplement which includes an ester as claimed in claim 1.