GB1594603A

GB1594603A - Hydrogenation of lipids

Info

Publication number: GB1594603A
Application number: GB2999776A
Authority: GB
Original assignee: Individual
Current assignee: Individual
Priority date: 1977-10-18
Filing date: 1977-10-18
Publication date: 1981-08-05

Description

(54) HYDROGENATION OF LIPIDS (71) I, DENNIS CHAPMAN of 103 Gregories Road, Beaconsfield, Buckinghamshire, a British Subject, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The invention relates to catalytic hydrogenation of lipids.

I and my co-inventors have looked for selective, readily applied methods of hydrogenation for lipids and consider that homogeneous catalysts have a number of advantages over heterogeneous catalysts.

As is known, all the metal atoms of homogeneous catalysts are potentially available as catalytic centres. Such catalysts are therefore likely to be more efficient in terms of the amount of catalyst required to sustain a given rate of hydrogenation.

Further, we have found that homogeneous catalysts have a selectivity with regard to the manner in which polyenoic lipid substrates can be hydrogenated and since they have a definiete stoichiometry and structure the hydrogenation process is more reproducible.

Lipids such as phospholipids and glycolipids exist naturally in bilayer form in polar media, with the polar ends of the molecules forming the surfaces of the bilayer and the non-polar ends directed inwards to form a non-polar zone. The bilayers may form a multilamellar structure, each lamella being constituted by an essentially.planar bilayer, or be present as vesicles each enclosing a quantity of the medium and formed of a single closed bilayer.

Our proposal is to use homogeneous catalysts directly in heterogeneous systems of lipids and polar media, particularly bilayer systems, thus 'heterogenising' the catalysts and allowing their easy introduction into the system, essentially without alteration of it.

Specifically the invention provides a process for the hydrogenation of an unsaturated lipid material, in which a twophase system of the material and water or other polar medium, is subjected to the action of molecular hydrogen in the presence of a catalytic transition metal complex soluble in the polar medium but having an affinity for the non-polar phase of the system so as to present a catalytically active site therein, until hydrogenation has taken place.

The lipid may be for example a triglyceride fat, of which very large quantities are commercially hydrogenated in the well known 'hardening' process, or for example a phospholipid or glycolipid.

The catalyst according to its nature may partition into the non-polar phase of the lipid/polar medium system, and diffuse therein, or it may preferentially remain at the phase boundary. The latter kind, where the free end of a ligand of the metal atom is polar in nature and for example remains in the polar zone of a bilayer, is particularly desirable as the lipid after being acted on can for example he removed free of catalyst by extraction with a non-polar solvent or, in a system capable of settling cleanly into polar and non-polar layers, even by simple decantation.

The process of the invention offers a new freedom in hydrogenation of phospholipids and other lipid materials in that it is no longer necessary to operate in a singlephase, generally non-polar medium. Thus for example natural materials, which exist in aqueous environments, can be acted on in their natural form.

Further a desirable selectivity may be shown, and higher degrees of unsaturation removed at relative rates different from those hitherto available, to give a required degree of unsaturation in for example phospolipids such as soya lecithin.

Thus trienoic fatty acid residues (i.e.

residues containing three ethylenic unsaturations) can be completely converted to dienoic (containing two such unsaturations), and resulting or pre-existing dienoic residues at least partly converted to monoenoic (containing one such unsaturation), without complete hydrogenation. This selectivity, which is the basis of the modification of physical properties, removes rancidity problems arising in natural materials from the polyunsaturated acids.

Hitherto in particular only synthetic phospholipids on the one hand and natural phospholipids on the other have been available. Now many degrees of unsaturation between the composition of natural materials and that of wholly saturated materials can be made available. The invention includes as novel products natural unsaturated phospholipids or other lipid materials forming bilayers in polar media, selectively freed wholly or in part from multiple unsaturations in the carbon chain by catalytic hydrogenation.

Desired physical characteristics, as followed for example by calorimetric, X-ray and permeability measurements, can therefore be achieved, and in particular a desired fluidity at physiological temperatures, the fluidity decreasing as the degree of hydrogenation increases.

Calorimetric curves for example show, for hydrogenated material, a sharp lipid phase transition endotherm that does not exist beforehand, the endotherm lying for example at 430C for completely saturated egg yolk phosphatidylcholine. The transition temperature itself provides a reference for the fluidity characteristics, since the hydrocarbon chains go from rigid relatively immobile condition to a fluid structure when heated above this temperature.

The uses of the modified lipids are various, soya lecithin for example being widely used as an emulsifier. A particular use we have in mind however is the preparation of materials of controlled fluidity and hence controlled permeability to incorporated drugs, hormones, enzymes, enzyme co-factors or other materials, for release for action on the human or animal body after administration thereto.

Another application is in the entrapment and controlled release of flavouring agents or other food additives or preservatives.

Emulsifiers, as mentioned above, are used in the food, drug, cosmetic and chemical industries, and the preparation of materials of modified physical properties is a valuable feature of the invention, particularly as biological safety clearance problems may be expected to be restricted to ensuring that catalyst residues are absent.

As mentioned above the invention allows hydrogenation of unsaturated lipids including fats, phospholipids and glycolipids, in their natural form and particularly in situ in the natural materials in which they are found, even if required in the living organism. Micro-organisms have been hydrogenated but remained living, their lipids being shown subsequently to be in the hydrogenated state.

Such treatment allows unstable polyunsaturated lipids to be partially hydrogenated in the natural invironment, where they are protected against deterioration by natural means not fully understood, and subsequently extracted in stable form. Removal of the catalyst can take place during or subsequent to the extraction.

This application of the invention in natural material, relies upon the ability of the catalyst to pass the lipid barrier of the cell walls of natural material by virtue of its solubility in lipids as well as aqueous media, and then act not only on the lipids of the cell wall but on lipids, particularly fats, within the cell.

An application of this aspect of the invention is in food technology, where rancidity problems due to polyunsaturations in fats can be attacked at source, by modification of the fat before the extraction and resulting increased accessibility to deteriorative processes.

Modification of the fat in foods to be consumed as such is also possible.

Apart from the chemical modification of materials subsequently to be extracted, modification of cell-wall lipids that will take place will fundamentally affect the physical and hence metabolic properties of the cell wall, by affecting its fluidity, and will give a means of controlling biological processes in industrially important micro-organisms dependent on these properties.

The rate of reaction, as seen in the examples below, can be such as to give useful results in hours and, combined with the selectivity that can be shown, is highly advantageous. After reaction, the product can be separated with ease where suitable catalysts have been used by non-polar extraction of the lipid, leaving the catalyst in the polar phase. The method of Bligh & Dyer, Canadian J. Biochem, 37 911 (1959), is for example suitable, and such extractions generally are familiar technology.

Bilayer forming lipids are preferably acted on in the form of vesicles, produced in per se known manner by sonication of dispersions of the lipid in a polar medium.

The catalyst then has to pass only one interface to reach the whole of the substrate, rather than the successive interfaces in multilamellar bilayer dispersions. Soya lecithin vesicles for example, treated with 6 moles RhCl(dpm)3 per 100 moles of the lecithin, at 370C and 6 atm pressure of hydrogen gas, are 80% hydrogenated after 2 hours and substantially completely hdrogenated after 4 hours. Under otherwise identical conditions an unsonicated dispersion is only 40% hydrogenated after 4 hours, and takes 24 hours for complete hydrogenation. (The abbreviation dpm stands for sodium diphenyl-phosphino benzene-msulphonate).

The hydrogen is preferably present at a few atmospheres pressure, up to say ten atmospheres. Soya lecithin for example, reacted in vesicle form for 2 hours at 370C in the presence of 6 moles RhCl(dpm)3 per 100 moles of the lecithin, shows a substantially greater reaction rate under 2 atmospheres hydrogen pressure than at atmospheric pressure, and a substantially greater rate again at 4 atmospheres.

Pressures of 6 and 8 atmospheres give however little further increase in rate with this preparation, though with the lecithin in multibilayer form the rate increases continuously at these successive pressures.

The effect of the catalyst concentration varies according to the physical form of the lipid. Soya lecithin for example, reacted in vesicle form for 2 hours at 370C under 6 atmospheres hydrogen pressure shows the same reaction rate with 4 mole % of catalyst as with 6 mole %, though the rate doubles as between 1 mole % and 2 mole % and triples as between I mole % and 4 mole Multilamellar bilayer dispersions in contrast show a linear increase in reaction rate with 1, 2, 4 and 6 mole % amounts of catalyst. Partition of the whole of the catalyst into the lipid is readily demonstrated, for example by high speed centrifuging over a sucrose gradient followed by rhodium analysis of the supernatant lipid by atomic absorption spectroscopy.

The temperature at which hydrogenation is carried out, e.g. 20 , 300 or 40"C, can be used to a degree to control the hydrogenation, in that when fatty acid triglyceride oils are being acted on the rate of reaction is much reduced once a solid fat has been formed.

Further the hydrogenation can be influenced by the ionic strength and pH of the polar medium, which change the charge on the catalyst molecule and hence its partition coefficient between lipid and polar medium. The RhCl(dpm)3 catalyst for example shows a many-fold increase in hydrogenation rate as the sodium chloride content of a water medium is raised, up to 7% or 8% NaCI. The catalyst is seen as being driven into the lipid phase; conversely when removal of the catalyst is required replacing such a brine medium by water alone facilitates the removal.

For the catalyst itself, in principle, all transition metals can be formed into complexes with hydrogenation activity. One of the most active of these complexes is chloro-tris (triphenylphosphine) rhodium(I). Another is the chlorotris(sodium diphenylphosphino benzene-msulphonate) rhodium(I) mentioned above which has the further advantage of solubility in water and ready separation from the hydrogenated product by nonpolar solvent extraction to remove the lipid.

A proposed mechanism for the hydrogenation process has been described in detail for the triphenyl phosphine and related catalyst by Osborn et al J. Chem.

Soc. A 1711-1732 (1966).

Preparation and use of two rhodium (I) complexes is now described in detail by way of example, but without any limitation to this particular metal or these particular complexes.

Preparation of Catalyst Chloro - tris - (triphenylphosphine) rhodium(I) was prepared by the method of Osborn et al, J. Chem. Soc. A 1711-1732 (i66), as follows: 0.2g Rh Cl3.3H2O (Johnson Matthey Chemicals Ltd.) was dissolved with gentle warming in 15 ml of 95% aqueous ethanol in a two-necked, 50cm3 pear-shaped flask provided with a nitrogen inlet and a reflux condenser protected by a silica gel guard tube. A stream of nitrogen, presaturated with ethanol, was passed through the solution for 15 min before further reaction.

Triphenylphosphine (1.2 g), freshly recrystalliied from 95% ethanol, was dissolved in 35 ml of hot, deoxygenated, 95% ethanol. The rhodium trichloride solution was heated to boiling point and the triphenylphosphine solution added via the reflux condenser. The mixture was refluxed vigorously under a moderate flow of nitrogen gas. Within a few minutes an orange brown precipitate formed which on further refluxing darkened to deep purple.

After 30 mins the hot mixture was filtered and the crystals of Rh(PPh3)3Cl were washed with diethylether, dried by aspiration and vacuum desiccated. The yield was approximately 0.6 g.

Preparation of Alternative Catalyst Chlorotris(sodiumdiphenyl - phosphino benzene-m-sulphonate) rhodium (I) tetrahydrate is readily prepared by direct exchange of sodium diphenyl-phosphino benzene-m-sulphonate (dpm) for triphenylphosphine (PPh3) in chlorotris (triphenylphosphine) rhodium (I) prepared as described previously.

The reaction is as follows: take 1.2g Ph2P(C6H4SO3Na) 1.0g RhCl(PPh3)3 and add to 40 ml of degassed tetrahydrofuran containing 1.0 ml of water.

Stir for 1 hour at room temperature (200 C) under nitrogen. A plate orange microcrystalline solid is formed which is collected under nitrogen and washed with two 10 ml aliquots each of tetrahydrofuran, dichloromethane and tetrahydrofuran before drying in vacuo. The yield is over 90% The amount of water present is important both for the recovery of the product and the extent of its hydration. The anhydrous complex which is formed when no water is present in the reaction mixture has different properties from the tetrahydrate, including greater instability to storage exposed to air. Distinguishing features of the infra red spectrum are that the anhydrous complex shows two broad peaks centred at 1223cm-' and 1192cm-1 and a sharper peak at 1029cm-' all associated with S=O vibration of the sulphonate residue. The tetrahydrate complex has only two absorbances in this region 1200cm-' (sbr) and 1030cm-'.

Hydrogenation Procedure Generally Samples (e.g. 0.5g) of phospholipids i.e.

phosphatidylcholine purified from the stated sources (soya bean lecithin, Sigma Type II-S, or egg yolk lecithin, Lipid Products, South Nutfield, Surrey) were hydrogenated in the presence of catalyst in the apparatus illustrated in Fig. 1 with a magnetic stirrer 1, water bath 2, reaction flask 3, 100 ml gas syringe 4,1 ml sampling syringe 5, gas inlet 6 and presaturation vessel 7. The reactions were performed in a total volume of 10 ml medium consisting of water or various combinations of water: tetrahydrofuran constituting polar media for the triphenyl phosphine catalyst (95:5, 90:10, 80:20, 70:30, 60:40, 50:50 by volume).

The tetrahydrofuran (Ralph Emanuel Ltd.

Wembley London) was redistilled and dried before use. Rhodium catalyst (50 mg unless otherwise stated) dissolved in hydrogensaturated tetrahydrofuran was added to the reaction mixture pregassed with hydrogen and stirred vigorously with a magnetic stirrer. Hdrogenations unless otherwise stated were at pH 4.5 and 35"C under 1 atm.

hydrogen, in this Fig. 1 apparatus.

Where the medium was water alone and the RhCe(PPh3)3 complex was used, lipid and catalyst were for convenience predissolved in tetrahydrofuran and the solvent removed by vacuum desiccation. The lipid and catalyst were then dispersed in degassed water and the reaction started by flushing the apparatus with hydrogen.

Hydrogenations carried out in this way, are not within the appended -claims since this particular catalyst is not soluble in water, but are included to aid ill the description of the invention and to show that the added solvent is in no way essential to the catalytic action per se.

The rate of the reactions was monitored by change in volume of the system, recorded by the gas syringe, and samples of the reaction mixture were withdrawn at intervals for fatty acid analysis. Hydrogen uptake values gave good agreement with theoretical values subsequently calculated from changes in the fatty acid composition.

Further analysis by thin layer chromatography showed that there was no significant alteration of the product other than by hydrogenation.

Where single bilayer vesicles were required they were prepared by sonicating samples of soya licithin (lOmg) in 10ml deoxygenated water for 5 min with a Kerry's Ultrasonic Ltd. System 150 ultrasonicator.

Hydrogenations in these instances were performed in the presence of 0.6 mg rhodium catalyst added in 60,u1 tetrahydrofuran and the reaction was monitored by gas chromatographic analyses of the constituent fatty acids.

Following the Progress of Hydrogenation In the following the results of all the reactions phospholipids were extracted from samples, removed at intervals, by the method of Kates 'Laboratory Techinques in Biochemistry and Molecular Biology' 3 3512 (1972) (ed. T. S. Work and E. Work: North Holland, Amsterdam). Extracted fatty acids were methyl'ated in a solution of 14% BF3 in methanol by heating at 700C for 2 min. The resulting methyl esters were extracted into light petroleum ether, dried over anhydrous Na2SO4 and separated by gas chromatography. The instrument was a Pye Trade Mark series 104 gas chromatograph using a stationary phase of 10% polyethylene glycol adipate on a support of diatomite C-AN (100120 mesh) with a carrier gas of nitrogen and a temperature of 197"C. Retent on times of authentic fatty acid methyl esters were used to identify fatty acids derived from phospholipid samples.

Hydrogenation Results The initial rate and the time taken to achieve 95% hydrogenation of soya lecithin in multibilayer form with the.RhCe(PPh3)3 complex as catalyst is shown in Fig. 2 the plots being extrapolated to join results for tetrahydrofuran used alone for comparison.

The initial rate of hydrogen uptake decreased as the proportion of water in the system increased and the time required to achieve 95% hydrogenation of the phospholipid increased accordingly. (At 100% water a result for 95% hydrogenation is not plotted; as stated above, such a system is not according to the invention with this catalyst). The low rate of hydrogenation shown in this particular example is much increased by working at higher than 1 atm hydrogen pressure.

It is found that when soya lecithin is hydrogenated in this way in water containing increasing proportions of tetrahydrofuran changes in the relative proportions of the various fatty acids are similar irrespective of the proportion of water present in the system.

Total hydrogenation of the lipid is also achieved with the lipid in a completely aqueous system. Thus for example a g.l.c.

trace of the fatty acid methyl esters prepared from soya lecithin so hydrogenated shows a single strong 18:0 peak (with one at 16:0), replacing a strong 18:2 peak and minor 18:3, 18:1 and 18:0 peaks of the starting material.

Changes in fatty acid composition related to hydrogen uptake during hydrogenation in an aqueous system, are illustrated in Fig. 3.

The lipid is again soya lecithin (soya phosphatidylcholine), 0.5g, in multibilayer form, and the catalyst is 20 mg of the RhCe(PPh3)3 complex. Only the C18 fatty acids are plotted: palmitic acid (Cl6.0) however forms 23wt % of the total fatty acid component of the material.

It can be seen that hydrogenation is markedly selective in that saturation of the polyenioc fatty acids, linoleic and linolenic acids, takes place predominantly during the initial stages of hydrogenation whereas conversion of oleate to stearate remains constant throughout the incubation. In quantitative terms most of the polyenoic fatty acids are hydrogenated at a faster rate than oleic acid although a proportion of these acids are hydrogenated at a slower rate during the latter half of the reaction.

An indication of selectivity of the degree to which the C18:i curve goes above 40%.

Thus 0.5g soya lecithin took up approx.

43 ml hydrogen. After uptake of approx. 20 ml hydrogen C,83 acid was absent. The curve for C,8.2 acid showed a rapid conversion until approx. 25 ml hydrogen had been taken up, at which stage C,82 acid was present as under 5 mole % of total C,8 acids; there was then a much slower conversion of Cm8.2 acid during the rest of the hydrogen uptake. The proportion of C18:i acid rose while the rapid conversion of Cm8;2 acid was taking place, then fell steadily.

The increase in the proportion of C18.0 acid present was steady throughout, indicating a steady conversion of C18:i acid whether initially present or produced from the polyenoic acids.

As stated, the above results relate specifically to an aqueous medium in which the RhCe(PPh3)3 complex is not soluble.

Essentially the same results are however obtained in the systems where the polar medium is thf/water in which in contrast this complex is soluble.

In Fig. 4 the wt % of the different C,8 acids is plotted against the hydrogenation time, giving a similar picture, the catalyst again being the RhCe(PPh3)3 complex. The C,83 acid (linolenic acid) goes in two hours.

The C18:2 acid (linolenic acid) drops rapidly over the first hour then more slowly, but has largely gone in four hours. The proportion of C,8., acid (oleic acid) rises rapidly over the first hour, stays level for two hours, then starts to fall towards complete conversion.

These results are for systems in which the lipid is present as multi bilayer structures.

Results with soya lecithin vesicles and egg yolk lecithin were quantitatively similar to those with the soya lecithin preparations described in detail above, and were also confirmed by fatty acid analyses. Thus Fig.

5 of the accompanying drawings shows the progress of hydrogenation of 50 mg sonicated soya lecithin vesicles at 370C under 6 atm pressure of hydrogen in 10 ml water. The catalyst was 6 moles Rh Cl (dpm)3 per 100 moles phospholipid. The general position is very similar to Figs 3 and 4.

Example of Hydrogenation of Non-Bilayer System 2 mg Rh Cl (dpm)3 catalyst were added to 5 ml saline and degassed with hydrogen, and 25 mg soyabean oil were introduced into the surface. The pressure of hydrogen increased to 10 atm and incubation continued for 16 hours without stirring. The product was separated by decantation. Fatty acid analysis of the triglyceride before and after hdyrogenation was as follows: % by weight* Fatty Hydro acid Control genated 18:0 3.8 27.4 18:1 22.8 34.2 18:2 55.3 23.2 18:3 7.0 1.4 *Mean of two runs at 350C.

The amount of hydrogenation during the reaction was about 50%, and analysis confirmed that the only change was hydrogenation. The colour of catalyst in the aqueous phase was observed to change from a pale yellow-orange to a light brown during the course of the reaction.

Presence of Multi Bilayer Structures in Materials Hydrogenated In relation to the water/tetrahydrofuran systems, experiments were carried out to ascertain whether lipid bilayer structures were retained in water as the proportion of THF to water in the system was increased.

Light microscopy showed birefringent structures in water and as the proportion of tetrahydrofuran was increased these became progressively less distinct and were not visible when equal amounts of water and tetrahydrofuran were used. X-ray studies on a Joel DX-LS-1 low angle gonimeter showed that phospholipid bilayer structures were retained at least until the ratio of water to tetrahydrofuran was 80:20. Differential scanning calorimetric heating curves taken at 5 Clmin on Perkins Elmer DSC-2 for pure lecithin e.g. dimyristoyl lecithin (Fluka Puriss Flurochem, Glossop, Derbyshire) dispersed in similar mixtures i.e. 90:10 and 80:20 water:tetrahydrofuran, all showed a sharp main co-operative endothermic transition similar to that which is observed in aqueous dispersions and consistent with the retention of a bilayer structure.

It is in fact believed that the bilayer structures are present down to 50:50 water:tetrahydrofuran mixtures.

WHAT I CLAIM IS: 1. Natural unsaturated phospholipids or other lipid materials forming bilayers in polar media, selectively freed wholly or in part from multiple unsaturation in the carbon chain by catalytic hydrogenation.

2. A process for the hydrogenation of a natural unsaturated phospholipid or other lipid material, in which a two-phase system of the material and water or other polar medium is subjected to the action of molecular hydrogen in the presence of a catalytic transition metal complex soluble in the polar medium but having an affinity for the nonpolar phase of the system so as to present a catalytically active site therein, until hydrogenation has taken place.

3. A process according to claim 2, in which the lipid is of a kind forming bilayers in polar media and is hydrogenated in multilamellar or vesicular bilayer form.

4. A process according to claim 2 or 3, in which the catalyst has a moiety, carrying the catalytically active site, with an affinity for the non-polar phase of the system and a moiety with an affinity for the polar phase and thus tending to remain in the phase boundary during the reaction.

5. A process according to claim 4, in which after hydrogenation the lipid is extracted in a non-polar solvent, leaving the catalyst in the polar medium.

6. A process according to any of claims 2 to 5 applied to lipids containing polyunsaturated fatty acids, in which the duration of hydrogenation is controlled to selectively free the fatty acids wholly or in part from multiple unsaturation in the carbon chain.

7. A process according to claim 6, carried out to give a predetermined fluidity in the hydrogenated product.

8. A process according to any of claims 2 to 7 where the catalyst is a rhodium (I) complex.

9. A process according to any of claims 2 to 8, wherein the catalyst comprises a sulphonated ligand.

10. A process according to claim 9, in which the catalyst comprises a diphenylphosphino benzene-m-sulphonate ligand.

11. A process according to claim 2, for the hydrogenation of unsaturated lipids, substantially as herein described in relation to any one of Figures 2 to 5 of the drawings or otherwise by way of particular example.

12. A phospholipid or other lipid material, when hydrogenated by the process of any of claims 2 to 11.

13. A phospholipid or other lipid material according to claim 1 or 12, incorporating a drug, enzyme or other material for release for action on the human or animal body after administration thereto.

14. A phospholipid or other lipid material according to claim 1 or 12, incorporating a flavouring agent or other food additive or preservative.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. Presence of Multi Bilayer Structures in Materials Hydrogenated In relation to the water/tetrahydrofuran systems, experiments were carried out to ascertain whether lipid bilayer structures were retained in water as the proportion of THF to water in the system was increased. Light microscopy showed birefringent structures in water and as the proportion of tetrahydrofuran was increased these became progressively less distinct and were not visible when equal amounts of water and tetrahydrofuran were used. X-ray studies on a Joel DX-LS-1 low angle gonimeter showed that phospholipid bilayer structures were retained at least until the ratio of water to tetrahydrofuran was 80:20. Differential scanning calorimetric heating curves taken at 5 Clmin on Perkins Elmer DSC-2 for pure lecithin e.g. dimyristoyl lecithin (Fluka Puriss Flurochem, Glossop, Derbyshire) dispersed in similar mixtures i.e. 90:10 and 80:20 water:tetrahydrofuran, all showed a sharp main co-operative endothermic transition similar to that which is observed in aqueous dispersions and consistent with the retention of a bilayer structure. It is in fact believed that the bilayer structures are present down to 50:50 water:tetrahydrofuran mixtures. WHAT I CLAIM IS:

1. Natural unsaturated phospholipids or other lipid materials forming bilayers in polar media, selectively freed wholly or in part from multiple unsaturation in the carbon chain by catalytic hydrogenation.