CH616087A5 - Dispersion of lipid spherules - Google Patents

Abstract

The spherules have a diameter of 100 to 50,000 ANGSTROM and consist of molecular layers of nonionic amphiphilic lipid compounds capable of being dispersed in water. They enclose an aqueous phase to be encapsulated. Since the lipid compounds employed are nonionic, the spherules have an electrically neutral outer surface, and this can be advantageous when the aqueous phase to be encapsulated contains pharmacologically or cosmetically active substances. To prepare such a dispersion, a polyoxyethylenated sorbitol trioleate ("Tween 85") is mixed with an aqueous solution of sorbitol, and then an aqueous solution of a polyacrylic acid crosslinked with polyallylsucrose ("Carbopol 934") is added, and vigorous agitation is applied.

Description

The object of the present invention, which aims to remedy the aforementioned drawbacks, is: a) the dispersion of lipid spherules defined in claim 1, and b) the process defined in claim 12, for obtaining such a dispersion.

The spherules of the dispersion according to the invention can encapsulate active substances with a high encapsulation yield. Within the meaning of the present description, the word encapsulate is used to indicate that there is an aqueous phase inside a capsule constituted by the lipid spherules. The method according to the invention can be applied to ionic or nonionic lipids and therefore makes it possible to include, among the lipids capable of constituting spherules, nonionic lipid compounds.

In a preferred embodiment, the spherules of the dispersion according to the invention enclose an aqueous phase to be encapsulated; the nonionic lipid compounds have a lipophilic / hydrophilic ratio such that the compound swells in the aqueous phase to be encapsulated, forming a lamellar phase; the hydrophilic groups of the nonionic lipid compounds are polyoxyethylenated, polyglycerolated groups, esters of polyols oxyethylenated or not and, for example, esters of polyoxyethylenated sorbitol; the nonionic lipid compounds are preferably taken from the group formed by:

- linear or branched polyglycerol ethers of respective formulas:

R- (OCH2CHOHCH2-) 5 OH and

R-fOCH2CH ^ OH CH2OH

n being an integer between 1 and 6, R being a linear or branched, saturated or unsaturated aliphatic chain of 12 to 30 carbon atoms; the hydrocarbon radicals of lanolin alcohols; hydroxy-2-alkyl radicals of long chain α-diols;

- polyoxyethylenated fatty alcohols;

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- esters of polyols, oxyethylenated or not and, in particular, polyoxyethylenated sorbitol esters;

- glycolipids of natural or synthetic origin, for example cerebrosides.

The continuous phase of the dispersion, which surrounds the spherules, is an aqueous phase; the aqueous phase encapsulated in the spherules is an aqueous solution of active substance, preferably iso-osmotic with respect to the continuous phase of the dispersion.

Various additives can be combined with nonionic lipid compounds in order to modify the permeability or the surface charge of the spherules. In this regard, mention may be made of the possible addition of long-chain alcohols and diols, sterols, for example cholesterol, long-chain amines and their ammonium-quaternary derivatives, dihydroxyalkylamines, polyoxyethylenated fatty amines, esters of long chain amino alcohols, their salts and ammonium-quaternary derivatives, phosphoric esters of fatty alcohols, for example sodium diketyl phosphate, alkyl sulfates, for example sodium cetyl sulfate, of certain polymers, such as polypeptides and proteins .

In a preferred embodiment, the aqueous phase to be encapsulated is an aqueous solution of active substance; the active substances of the aqueous phase to be encapsulated are products with cosmetic action; the continuous phase of the dispersion is an aqueous phase; the proportion of the weight of the spherules relative to the weight of the continuous phase of the dispersion is between 0.01 and 0.5 approximately; the continuous phase of the dispersion is advantageously iso-osmotic with respect to the aqueous phase encapsulated in the spherules.

The active substances, which can be encapsulated in the spherules of the two types of dispersion defined above, are extremely varied and correspond to those which will be indicated below for the implementation of the method according to the invention. As a result, the compositions can be used in various fields and, in particular, in pharmacy and in cosmetics.

The aqueous dispersions which have just been defined last have a very particular interest in cosmetics because of the fact that the use of large spherules makes it possible to reduce the risks of passage of these preparations through the skin.

It should be noted that the use of the aqueous dispersions according to the invention in cosmetics, whether they are dispersions containing nonionic lipid compounds or dispersions containing ionic lipid compounds, has a considerable advantage compared to the well-known use of emulsions. Indeed, when it is desired to use preparations containing both fatty substances and water, it is necessary, to ensure the stability of the emulsion, to use amphiphilic emulsifying compounds to ensure the stability dispersions. It is known that certain emulsifiers can be relatively irritating when applied to the skin. It has been discovered, in the course of work relating to the present invention, that this effect of emulsifiers, for a given chemical structure, depends considerably on the form in which they are applied. Thus, we were able to highlight the fact that a water / oil emulsion composed of 42% perhydrosqualene, 8% emulsifier and 50% water is highly irritating, while an aqueous dispersion at 8% of the same emulsifier has a practically insignificant index of irritation and that perhydrosqualene is absolutely harmless. As a result, there is a synergy of irritation when an emulsifier and an oil phase are present. The aqueous dispersions according to the invention make it possible to avoid the simultaneous use of an emulsifier and an oil, which constitutes significant progress in the field of cosmetics.

It should be noted that it is possible to add to the dispersions of spherules according to the invention various auxiliary products intended to modify the presentation or the organoleptic characters, such as opacifiers, gelling agents, flavors, perfumes or dyes.

Generally, the advantage of the dispersions according to the invention lies in the fact that they make it possible to introduce hydrophilic substances into an essentially lipophilic medium. It follows that, under these conditions, these are hidden, hence a protective effect vis-à-vis the various possible spoilage agents: oxidants, digestive juices and more generally, reactive compounds vis-à-vis vis encapsulated substances. The penetration and / or fixation of active substances can be modulated by varying the size of the globules and their electrical charge. Their action can also be postponed (delay effect). In addition, the fact that they are masked makes it possible to suppress or substantially alter their organoleptic characters, in particular the taste. Finally, the lipids used in these preparations have, by themselves, a beneficial action, for example emollience, lubrication, polishing.

In a preferred embodiment of the method according to the invention, the weight ratio between the quantity of aqueous phase to be encapsulated brought into contact with the lipids and the quantity of lipids forming the lamellar phase is between approximately 0.1 and 3 about ; the aqueous phase to be encapsulated can be water or an aqueous solution of active product; the weight ratio of the quantity of dispersion phase, which is added, to the quantity of lamellar phase, which is dispersed, is between approximately 2 and approximately 100; the dispersion phase and the aqueous phase to be encapsulated are preferably iso-osmotic; the dispersion phase can advantageously be an aqueous solution; the agitation carried out as the last phase of the process is obtained by means of a shaker; the process is carried out at room temperature or at a higher temperature if the lipid is solid at room temperature; if it is desired that the spherules obtained have an average diameter of less than 1000 Å, the dispersion of spherules may be subjected to an ultrasound treatment.

To form the lamellar phase, a single lipid or a mixture of lipids can be used. The lipid or lipids which are used comprise a long lipophilic chain comprising from 12 to 30 carbon atoms, saturated or unsaturated, branched or linear; one can, in particular, choose oleic, lanolic, tetradecylic, hexa-decyl, isostearyl, lauric or alkylphenyl chains. As the nonionic hydrophilic group of the lipid forming the lamellar phase, it is advantageous to choose a polyoxyethylenated, a polyglycerol, an ester of polyol oxyethylenated or not, and, for example, a polyoxyethylenated sorbitol ester.

One can use an aqueous phase to be encapsulated comprising active substances of all kinds and, in particular, substances having a pharmaceutical or food interest, or substances having a cosmetic activity. The active substances can be, for example, as far as cosmetics are concerned: products intended for skin and hair care, for example humectants, such as glycerin, sorbitol, pentaerythrititol, inositol, pyrrolidonecarboxylic acid and its salts; artificial browning agents such as dihydroxyacetone, erythrulose, glyceraldehyde, γ-dialdehydes such as tartaric aldehyde (these products can possibly be combined with dyes); water-soluble sunscreen agents; antiperspirants, deodorants, astringents, refreshing, tonic, healing, keratolytic, depilatory products; scented waters; extracts of animal or plant tissues, such as proteins, Polysaccharides, amniotic fluid, water-soluble dyes, dandruff agents, antiseborrheic agents, oxidants (bleaching agents) such as hydrogen peroxide, reducers such as thioglycolic acid and its salts. As pharmaceutical active substances, mention may be made of: vitamins, hormones, enzymes (for example, super-oxydedismutase), vaccines, anti-inflammatories (hydrocortisone, for example), antibiotics, bactericides.

It is clear that, depending on the active substance contained in the aqueous phase to be encapsulated, lipids capable of stably encapsulating the aqueous phase will be chosen.

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derée. In order for the lipids constituting the lamellar phase to give stable spherules, it is necessary that there is a sufficient lateral interaction between the lipid chains which, placed side by side, constitute the layers or sheets of the spherules, that is to say -to say that the Van der Waals forces between the chains ensure sufficient cohesion of the sheets. This condition is satisfied for lipids having the characteristics indicated in the general definition of the process given above. The lipids which can be used in the process according to the invention belong to the class of emulsifiers of the water in oil type.

The method according to the invention makes it possible to obtain dispersions of spherules which consist of nonionic lipid compounds and which, therefore, form novel compositions allowing encapsulation of active substances, usable for example in pharmacy, in food or in cosmetic. The use of non-ionic compounds to constitute the encapsulation spherules is of considerable interest in the case where it is desired to prevent the spherules from having an electrically charged outer surface.

The following examples illustrate the invention.

Example 1

In a 50 ml round flask, 500 mg of oxyethylenated sorbitol trioleate containing 20 moles of ethylene oxide (Tween 85 product sold by the company ICI Atlas) are brought into contact with 0.335 ml of a 0.7M solution of sorbitol and the mixture is homogenized. The experiment is carried out at room temperature.

Then added 3 ml of an aqueous solution at 1% of the product known under the trade name of Carbopol 934 (polyacrylic acid crosslinked with polyallylsucrose, sold by the company Goodrich). The flask, placed on a shaker, is stirred vigorously for 1 h.

The dispersion obtained is gelled; the diameter of the spherules is greater than 1 | i.

Example 2

Into a 50 ml round flask, 250 mg of 10 mole oxyethylenated oleic alcohol are intimately mixed (product Brij 96 sold by the company ICI Atlas), and 250 mg of 2 mole oxyethylenated oleic alcohol (product Brij 92 sold by ICI Atlas); the mixture obtained is then brought into contact with 1 ml of a 0.5M solution of glycerol, and the mixture is homogenized. The experiment is carried out at room temperature.

20 ml of a 0.245 M solution (NaCl, KCl) are then added. The flask, placed on a shaker, is shaken vigorously for 1 h.

The dispersion obtained is fluid and milky; the diameter of the spherules is approximately 1 (i.

Example 3

In a 50 ml round flask, 500 mg of the product of general formula are brought into contact:

R-j OCH2-CH \ OH

\ CH2OH! H

R being the alkyl radical of the hydrogenated lanolin alcohols and n having a mean statistical value of 3, with 0.220 ml of a 0.5M solution of pentaeyythritol, and the mixture is homogenized. The experiment is carried out at room temperature.

Then 4 ml of water are added. The flask, placed on a shaker, is stirred vigorously for 30 min.

The dispersion obtained is milky in appearance; the diameter of the spherules is greater than 1 p ..

Example 4

In a 50 ml round flask, 500 mg of the product of general formula are brought into contact:

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R- / OCH2-CH I OH

! CH20H / n

R being the tetradecyl radical and n being equal to 2, with 0.75 ml of a 0.4M solution of sorbitol, and the mixture is homogenized. The experiment is carried out at 40 ° C.

Then 4 ml of water are added. The flask, placed on a shaker, is stirred vigorously for 30 min.

The dispersion obtained is clear, after passing through ultrasound; the diameter of the spherules is less than 1 ji.

Example 5

In a 50 ml round flask, 500 mg of the product of general formula are brought into contact:

R- / 0CH2-CH \ OH

I CH2OH jn

R being the hexadecyl radical and n being equal to 2, with 0.335 ml of a 0.3M solution of cysteine hydrochloride, and the mixture is homogenized. The experiment is carried out at 55 ° C.

Then 4.1 ml of a 0.145 M solution (NaCl, KCl) is added. The flask, placed on a shaker, is shaken vigorously for 3 h.

The dispersion obtained is practically clear at 55 ° C; the diameter of the spherules is approximately 2 (i. By slowly cooling the dispersion to room temperature, an opaque, white gel is obtained.

The dispersion taken at 55 ° C. can be diluted with an iso-osmotic solution or not, containing a thickener such as gums or polymers; a slightly opaque solution is obtained, the dilution ratio being chosen according to the aspect of the solution which it is desired to obtain.

Example 6

In a 50 ml round flask, placed in a water bath at 55 ° C., 500 mg of the product of general formula is brought into contact:

R- / OCH2-CH \ OH

I CH2OHL

R being the hexadecyl radical and n being equal to 2, with 10 ml of a 0.3M solution of methionine, and the mixture is homogenized. The experiment is carried out at 55 ° C.

The flask, placed on a shaker, is stirred vigorously for 3 h at 55 ° C.

The dispersion obtained is clear; the diameter of the spherules is about 1 | i. By cooling to room temperature, a white jelly is obtained.

Example 7

In a 50 ml round flask, 500 mg of the product of general formula are brought into contact: / <

R- J OCH2-CH \ OH

y CH2OH I n-

R being the alkyl radical of isostearyl alcohol, n having a mean statistical value of 2, with 5 ml of water, and the mixture is homogenized. The experiment is carried out at room temperature.

The flask, placed on a shaker, is shaken vigorously for 4 h.

The dispersion obtained is milky; the diameter of the spherules is about 5 µ.

The dispersion can be subjected to ultrasound, in order to significantly reduce the size of the spherules.

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Example 8

In a 50 ml round flask, 83.2 mg (200 (imoles) of the product of general formula) are dissolved:

R- / OCH2-CH \ OH

Œ2OH L

R being the alkyl radical of oleic alcohol and n being equal to 2, in 2 ml of a chloroform / methanol mixture in the ratio 2/1. The solvent is evaporated using a rotary evaporator, and the last traces of solvent are removed by passage through the vane pump for 1 h.

10 ml of a 0.3M glucose solution are brought into contact with the lipid. The flask, placed on a shaker, is agitated strongly during 4 h. The experiment is carried out at room temperature.

The dispersion is subjected to ultrasound for 20 min, in order to reduce the diameter of the spherules to a value less than 0.5 (x. The dispersion is then filtered through a column of Sephadex G 50 coarse swollen gel in a 0.145 M solution (NaCl, KCl) The solution obtained is slightly bluish.

Example 9

Into a 50 ml round flask, 58 mg of the product of general formula are intimately mixed:

R- / OCH2-CH \ OH CH2OH J s

R being the alkyl radical of isostearyl alcohol, n being equal to 2, with 58 mg of the product of general formula:

R- / OCH2-CH

oh

CH2OH

R- / OCH2-CH

oh

CH2OH

R being the hexadecyl radical and n having a mean statistical value of 3, with 0.5 ml of a 50 mg / ml solution of Crotein C

20

(protein with a molecular weight of approximately 10,000, sold by the company Croda).

The mixture is homogenized. The experiment is carried out at 60 ° C. Then 4 ml of a 0.145 M solution (NaCl, KCl) are added. The flask, placed on a shaker, is shaken vigorously for 3 h.

The dispersion obtained is clear; the diameter of the spherules is about 1 | i. By slow cooling to room temperature, an opaque white gel is obtained.

Example 12

In a 50 ml round flask, 300 mg of sphingomyelin is brought into contact with 0.350 ml of a 0.3M glucose solution, and the mixture is homogenized. The experiment is carried out at room temperature.

5 ml of a 0.145 M solution (NaCl, KCl) are then added. The flask, placed on a shaker, is shaken vigorously for 2 h.

The dispersion obtained is milky; the diameter of the spherules is approximately 2 (i.

The dispersion can be subjected to ultrasound for 1 hour in order to reduce the diameter of the spherules.

Example 13

In a 50 ml round flask, 300 mg of the product obtained by molecular distillation, of general formula, are intimately mixed:

R being the alkyl radical of isostearyl alcohol, n being equal to 6, and the mixture obtained is brought into contact with 10 ml of a 1M glucose solution. The experiment is carried out at room temperature. The flask, placed on a shaker, is strongly agitated for 4 h.

The dispersion obtained is very fine; the spherules have a diameter of about 1 | i. The dispersion can be subjected to ultrasound for 30 min, in order to reduce the size of the spherules to a value less than 0.5 | i.

Dispersions having either spherules with a diameter greater than 1 μm or spherules with a diameter less than 0.5 (j. Are filtered on a column of Sephadex G 50 coarse gel swollen in a 0.475 M solution (NaCl KCl).

Example 10

In a 50 ml round flask, 500 mg of tetraethylene glycol monolauryl ether are brought into contact with 0.4 ml of a 0.3M glucose solution, and the mixture is homogenized. The experiment is carried out at room temperature.

5 ml of a 0.145 M solution (NaCl, KCl) are then added.

The flask, placed on a shaker, is stirred vigorously for 15 min.

The dispersion obtained is clear; the diameter of the spherules is approximately 1 | x.

Example 11

In a 50 ml round flask, 500 mg of the product of general formula are brought into contact:

R-

OCH2-CH

OH

CH2OH

R being the alkyl radical of oleic alcohol and n being equal to 2; 150 mg of cholesterol; 50 mg of an amine of general formula:

C2H5

RC00 (CH2CH20) n-CH2CH2N;

/

\

C2H5

RÇOO being the remainder of the copra and n being a number between 2 and 5, and the mixture obtained is brought into contact with 0.5 ml of a 0.3M sorbitol solution; the mixture is homogenized. The experiment is carried out at room temperature.

Then 4 ml of a 0.145 M solution (NaCl, KCl) is added. The flask, placed on a shaker, is shaken vigorously for 4 h.

The dispersion obtained is opalescent; the diameter of the spherules is about 2 | i.

Example 14

In a 50 ml round flask, 425 mg of the product, of general formula:

R- / OCH2-CH \ OH

CH2OH J n

R being the alkyl radical of oleic alcohol and n being a number equal to 2, and 75 mg of an amine of the following formula:

R-

OCH2-CH

I

CH2OH

-OCH, CHOH-CH.

\ _ / °

R being the oleyl radical and n having a mean statistical value of 1, with 0.5 ml of a 0.3M solution of glucose, and the mixture is homogenized. The experiment is carried out at room temperature.

Then 4 ml of a 0.145 M solution (NaCl, KCl) is added. The flask, placed on a shaker, is shaken vigorously for 4 h.

The dispersion obtained is opaque; the diameter of the spherules is greater than 2 (d ..

The dispersion can be subjected to ultrasound, the size of the spherules then becoming less than 1 (i.

Example 15

In a 50 ml round flask, 300 mg of sphingomyelin are brought into contact with 0.350 ml of a 0.3M solution of ascorbic acid, and the mixture is homogenized. The experiment is carried out at room temperature.

2.650 ml of a 0.145M solution (NaCl, KCl) are then added. The flask, placed on a shaker, is shaken vigorously for 4 h.

The dispersion obtained is milky; the diameter of the spherules is approximately 2 (i.

If desired, the dispersion can be filtered on a column of Sephadex G 50 coarse gel swollen in a 0.145 M solution (NaCl, KCl).

Example 16

In a 50 ml round flask, 142 mg of the Na salt of N2- (alkylsulf) -N-dodecyl-N (N ', N'-diethylaminoethyl) -asparagine are dissolved in 2 ml of a chloroform / methanol mixture in report 2/1. The solvent is evaporated using a rotary evaporator, then the last traces of solvent are removed by subjecting the product for 1 h to the reduced pressure given by a vane pump.

10 ml of a 0.3M glucose solution are brought into contact with the lipid.

The flask, placed on a shaker, is strongly agitated for 4 h. The experiment is carried out at room temperature. The size of the spherules is approximately 1 | i. The dispersion is then filtered on a column of Sephadex G 50 coarse gel swollen in a 0.145 M solution (NaCl, KCl).

Example 17

80 mg of the product of general formula are dissolved in a 50 ml flask: / \

R- j OCH2-CH j OH

\ CH2OHJ n

R being the hexadecyl radical and n being equal to 2.10 mg of cholesterol and 10 mg of diketylphosphate in 2 ml of a chloroform / methanol mixture in the ratio 2/1.

The solvent is evaporated using a rotary evaporator and the last traces of solvent are removed by passage through the vane pump for 1 h.

10 ml of a 0.15M solution of the sodium salt of pyroglutamic acid are brought into contact with the lipids. The flask, placed on a shaker, is stirred vigorously for 2 h in a water bath at 55 ° C.,

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then gradually cooling until it returns to room temperature.

The dispersion is subjected to ultrasound for 1 h at a temperature maintained near room temperature. The dispersion is then filtered on a column of Sephadex G 50 coarse gel swollen in distilled water.

The dispersion obtained is fluid and clear after passage through ultrasound; the diameter of the spherules is less than 1 [i.

Example 18

240 mg of the product of general formula are intimately mixed in a 50 ml round flask:

R- / OCH2-CH \ OH I CH2OH L

R being the alkyl radical of the hydrogenated lanolin alcohols and n having a mean statistical value of 3, and 60 mg of cholesterol.

The mixture obtained is brought into contact with 0.4 ml of a 0.15M solution of the sodium salt of pyroglutamic acid and the mixture is homogenized. The experiment is carried out at 45 ° C. 4.6 ml of a 9% sodium chloride solution o- is then added.

The flask, placed in a water bath, is vigorously agitated using a shaker for 2 h at 45 ° C, then gradually cooling until it returns to room temperature.

The dispersion obtained is fluid and milky; the diameter of the spherules is greater than 1 | x.

Example 19

In a 50 ml round flask, 200 mg of the product of general formula are intimately mixed:

R- / OCH2-CH \ OH I CH2OH ln

R being the hexadecyl radical and n being equal to 2.25 mg of cholesterol and 25 mg of diketylphosphate; the mixture obtained is brought into contact with 0.3 ml of a 10% tartaric aldehyde solution and the mixture is homogenized. The experiment is carried out at 55 ° C. 4.7 ml of a 0.145M solution (NaCl, KCl) is then added.

The flask, placed in a water bath, is stirred vigorously using a shaker for 2 h at 55 ° C, then gradually cooling until it returns to room temperature.

The dispersion obtained is gelled and slightly bluish in appearance.

The simultaneous application to the skin of this dispersion of niosomes and of an aqueous solution with the same final concentration of tartaric aldehyde, makes it possible to appreciate two effects of the niosomes, which, considerably reinforcing the developed coloration, clearly improve the behavior of this coloration in water washes and detergents.

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Claims (24)

616,087 2 1. Dispersion of spherules consisting of organized molecular layers of lipid compounds, characterized in that the lipid compounds are non-ionic amphiphilic compounds capable of being dispersed in water and that the spherules have a diameter of between 100 and 50,000 Å . 2. Dispersion according to claim 1, characterized in that the spherules enclose an aqueous phase to be encapsulated. 3. Dispersion according to one of claims 1 or 2, characterized in that the nonionic lipid compounds have a lipophilic / hydrophilic ratio such that the compound swells in the aqueous phase to be encapsulated by forming a lamellar phase. 4. Dispersion according to claim 3, characterized in that the hydrophilic groups of the nonionic lipid compounds are polyoxyethylenated, polyglycerolated groups, esters of polyol oxyethylenated or not and, in particular, polyoxyethylenated sorbitol esters. 5. Dispersion according to claim 3, characterized in that the nonionic lipid compounds are taken from the group formed by: - linear or branched polyglycerol ethers of respective formulas: R- (OCH2CHOHCH2-) n OH and R-fOCKbCH ^ OH CH2OH n being an integer between 1 and 6, R being a linear or branched, saturated or unsaturated aliphatic chain, comprising from 12 to 30 carbon atoms; the hydrocarbon radicals of lanolin alcohols; hydroxy-2-alkyl radicals of long chain α-diols; - polyoxyethylenated fatty alcohols; - esters of polyols, oxyethylenated or not and, in particular, polyoxyethylenated sorbitol esters; - glycolipids of natural or synthetic origin, for example cerebrosides. 6. Dispersion according to one of claims 1 to 5, characterized in that the nonionic lipid compounds are associated with additives taken from the group formed by long chain alcohols and diols, sterols, for example cholesterol, from amines to long chain and their ammonium-quaternary derivatives, dihydroxyalkylamines, polyoxyethylenated fatty amines, esters of long-chain amino alcohols, their ammonium-quaternary salts and derivatives, phosphoric esters of fatty alcohols, for example dicetylphosphate sodium, alkyl sulfates, for example sodium cetyl sulfate, certain polymers, such as polypeptides and proteins. 7. Dispersion according to one of claims 1 to 6, characterized in that the continuous phase of the dispersion, which surrounds the spherules, is an aqueous phase. 8. Dispersion according to one of claims 1 to 7, characterized in that the spherules enclose an aqueous phase to be encapsulated, this aqueous phase being an aqueous solution of active substance, preferably iso-osmotic with respect to the continuous phase of the dispersion. 9. Dispersion according to claim 8, usable in cosmetics, characterized in that the aqueous phase encapsulated in the spherules contains at least one product taken from the group formed by humectants, such as glycerin, sorbitol, penta-erythritol , inositol, pyrrolidonecarboxylic acid and its salts; artificial browning agents such as dihydroxyacetone, erythrulose, glyceraldehyde, γ-dialdehydes such as tartaric aldehyde (these products can possibly be combined with dyes); water-soluble sunscreen agents; antiperspirants, deodorants, astringents, refreshing, tonic, healing, keratolytic, depilatory products; scented waters; extracts of animal or plant tissues, such as proteins, Polysaccharides, amniotic fluid; water-soluble dyes, anti-dandruff agents, antiseborrhoeic agents, oxidants such as hydrogen peroxide, reducers such as thioglycolic acid and its salts. 10. Dispersion according to claim 8, usable in pharmacy or in the food industry, characterized in that the aqueous phase encapsulated in the spherules contains at least one pharmaceutically active agent or a food adjuvant. 11. Dispersion according to one of claims 1 to 10, characterized in that it contains at least one product chosen from opacifiers, gelling agents, flavors, perfumes and dyes. 12. A method of obtaining a dispersion of spherules according to claim 1 containing an aqueous phase to be encapsulated, characterized in that one brings into contact, on the one hand, at least one liquid lipid dispersible in water and having the general formula: X-Y formula in which X represents a nonionic hydrophilic group and Y represents a lipophilic group and, on the other hand, the aqueous phase to be encapsulated in the spherules, the lipophilic / hydrophilic ratio of the lipid being such that the latter swells in the aqueous phase to encapsulate, to form a lamellar phase; that is stirred to ensure mixing and to obtain a lamellar phase; that a dispersion liquid is then added in an amount greater than the amount of lamellar phase obtained and that is vigorously shaken for a time varying from 15 min to 4 h. 13. Method according to claim 12, characterized in that the weight ratio between the quantity of aqueous phase to be encapsulated brought into contact with the lipids and the quantity of lipids forming the lamellar phase, is between 0.1 and 3. 14. Method according to one of claims 12 or 13, characterized in that the aqueous phase to be encapsulated is water. 15. Method according to one of claims 12 or 13, characterized in that the aqueous phase to be encapsulated is an aqueous solution of active product. 16. Method according to one of claims 12 to 15, characterized in that the weight ratio of the amount of dispersion phase, which is added, to the amount of lamellar phase, which is dispersed, is included between 2 and 100. 17. Method according to one of claims 12 to 16, characterized in that the dispersion phase and the aqueous phase to be encapsulated are iso-osmotic. 18. Method according to one of claims 12 to 17, characterized in that the dispersion phase is an aqueous solution. 19. Method according to one of claims 12 to 18, characterized in that it is implemented at a temperature at least equal to the melting temperature of the lipid. 20. Method according to one of claims 12 to 19, usable when it is desired that the spherules have an average diameter less than 1000 Â, characterized in that the dispersion of the spherules obtained is subjected to an ultrasonic treatment . 21. Method according to one of claims 12 to 20, characterized in that the lipid or lipids used comprise a lipophilic chain comprising from 12 to 30 carbon atoms. 22. Method according to claim 21, characterized in that the lipid or lipids used are chosen from the group formed by lipids comprising an oleic, lanolic, tetradecylic, hexadecylic, isostearyl, lauric or alkylphenyl chain. 23. Method according to one of claims 21 or 22, characterized in that the nonionic hydrophilic group of the lipid forming the lamellar phase is a polyoxyethylenated group, polyglycerol, polyol ester oxyethylenated or not and, for example, an ester of polyoxyethylenated sorbitol. 24. Method according to one of claims 12 to 20, characterized in that one uses as lipids forming the lamellar phase at least one nonionic compound taken from the group formed by: s 10 15 20 25 30 35 40 45 50 55 60 65 3 616,087 - linear or branched polyglycerol ethers of respective formulas: R- (OCH2CHOHCH2-) j OH and R-fOCH2CH ^ OH CH2OH n being an integer between 1 and 6, R being a linear or branched, saturated or unsaturated aliphatic chain, comprising from 12 to 30 carbon atoms; the hydrocarbon radicals of lanolin alcohols; hydroxy-2-alkyl radicals of long chain α-diols; - polyoxyethylenated fatty alcohols; - esters of polyols, oxyethylenated or not and, for example, polyoxyethylenated sorbitol esters; - glycolipids of natural or synthetic origin, for example cerebrosides. It is known that certain lipids have the property of forming, in the presence of water, mesomorphic phases whose state of organization is intermediate between the crystalline state and the liquid state. Among the lipids which give rise to mesomorphic phases, it has already been indicated that some can swell in aqueous solution to form spherules dispersed in the aqueous medium, these spherules being constituted by multimolecular layers and, preferably, by bimolecular layers having a thickness of approximately 30 to 100 Â [see, in particular, the article by Bangham, Standish and Watkins, “J. Mol. Biol. ”, 13, 238 (1965)]. Until now, it has been possible to obtain lipid spherules consisting of concentric sheets only by using lipids comprising an ionic hydrophilic group and a lipophilic group, and the preparation methods which have been described entail obtaining spherules with an average diameter of less than 1000 Å. The process for obtaining these spherules consists in producing a dispersion, the dispersed phase of which contains the lipid substance capable of forming the spherules, and in subjecting this dispersion to an ultrasound treatment; to produce the dispersion which is subjected to ultrasound, it is possible, firstly, to produce on a wall, by evaporation, a thin film of the lipid substance to be dispersed, then, secondly, to bring into contact with the wall thus coated , the continuous phase of the dispersion to be carried out and finally, thirdly, stir to obtain the dispersion to be subjected to ultrasound. In another process described in French patent application No. 2221122, it is also possible, to obtain the dispersion to be subjected to ultrasound, adding the lipid intended to form the walls of spherules to an aqueous phase, then heat slightly and stir vigorously with shaking. Spherules made up of concentric sheets thus obtained, and which have a maximum diameter of approximately 1000 Å, are generally called liposomes. It has already been proposed to use liposomes to enclose aqueous solutes containing active substances in the aqueous compartments between the lipid double layers and thus to protect the encapsulated substances against external conditions [see, in particular, the article Sessa and Weismann, "J. Lipid Res.", 9.310 (1968) and the article Mageeet Miller, "Nature", vol. 235 (1972)]. Since liposomes can have variable sizes in the range of less than 1000 Å, their penetration power can be varied in the human body, which has made it possible to envisage numerous uses from the pharmaceutical point of view, all the more so as their charge electric outdoor can allow to choose their fixing site ("Biochem. J." (1971), 124, p. 58 P). However, cosmetically, the use of spherules with a diameter of less than 1000 Å is likely to cause some disadvantages due to the risk of penetration of the products through the skin. It is therefore clear that at least for this type of application, it would be desirable to be able to produce spherules with concentric lipid sheets having a diameter greater than 1000 Å. In addition, the methods currently known for obtaining liposomes containing active substances between their concentric lipid sheets have considerable drawbacks: first, the active substance placed in the continuous phase of the dispersion which is subjected to ultrasound n 'is encapsulated between the lipid sheets of the liposomes only for a very small part, because a very small part of the continuous phase of the dispersion is trapped between said sheets. When it is desired to isolate the encapsulation liposomes, it is necessary to pass the dispersion, which has been subjected to ultrasound, over a separation column of the Sephadex type, in which case the liposomes are found in the form of an extremely dilute dispersion. It follows that, on the one hand, it is practically not possible, with known methods, to obtain a high concentration of liposomes and that, on the other hand, the active substance is encapsulated only in a low proportion and is lost in the elution of the separation column without it being practically possible to recover it in a simple manner, which leads to a significant increase in the price of the active ingredients encapsulated in the liposomes. It is therefore desirable to have a process for manufacturing spherules with concentric sheets which allows obtaining a dispersion with a high concentration of spherules with a reduced loss of the product encapsulated between the sheets of spherules. Finally, the methods for manufacturing liposomes which have been described to date mention that only certain well-defined categories of lipids can be used: in the state of the art cited above, the use of phospho-lipids, lipids comprising an ionic hydrophilic group and a lipophilic group, and unsaturated fatty acids.