FR2833500A1 - New anhydrous, oily gel for use in the manufacture of e.g. cosmetics, oral dental products or pharmaceuticals - Google Patents

Abstract

Composition in the form an oily anhydrous gel comprising at least one fatty component and a non-ionic stabilizer with a melting point of greater than 40 deg C, is new. An Independent claim is also included for the preparation of the composition.

Description

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The present invention relates to an anhydrous oily gel to which its particular composition confers remarkable physical stability properties, manifested in particular by the absence of exudation at room temperature. Its production process and its low preparation cost make it suitable for all kinds of applications in fields such as cosmetics, personal hygiene or health.

There is a growing interest in the preparation of products in the form of a gel because of their texture, flexibility of touch and ease of use. This craze concerns all types of gels: aqueous gels and hydroalcoholic gels, such as anhydrous oily gels which make it possible to present fatty substances, which are fluid at room temperature, in the form of a more or less gelled pasty mass, more convenient. job.

Aqueous gels and hydroalcoholic gels are the easiest to obtain. There are a wide variety of gelling substances soluble in these hydrophilic media, such as gums, starches, pectins, cellulose derivatives, polyvinyl alcohol derivatives, or even carboxyvinyl polymers. These gelling substances have known chemistry which makes it possible to adapt the operating conditions to the characteristics desired for the final product according to the particular application envisaged. Once prepared, the aqueous gels and the hydroalcoholic gels are physically stable, that is to say that they form a homogeneous phase which does not degrade during the period of use under normal conditions of temperature and pressure.

On the other hand, obtaining anhydrous oily gels, also called "oleogels" or "lipophilic gels", raises particular difficulties. Indeed, the physical stability of these gels is not satisfactory, because a phenomenon of excision appears, which is manifested by the separation of the gel into two phases: the gelling agent and the oily phase. This phenomenon is all the more marked as the gel is not very viscous. It loses its homogeneous creamy consistency, it becomes unpleasant to the touch, and in general it is then unsuitable for any use.

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This poor stability can be explained by the fact that an anhydrous oily gel is a colloidal system which comprises a dispersed phase consisting of gelling particles 1 to 100 nm in diameter, in a medium constituting the dispersing phase: the fatty substance. It is a physical state intermediate between the solid state and the liquid state whose physical stability is fragile.

The dispersed phase and the dispersing phase ultimately form a single homogeneous phase, which distinguishes the structure of gels from that of suspensions (a liquid phase and a solid phase) and emulsions (two immiscible liquid phases). Even a slight rise in temperature can destabilize the colloidal structure, which then separates into two phases containing respectively the gelling agent and the fatty substance.

To overcome this drawback, many stabilizers have been proposed. These are substances which increase the viscosity of the oil in the colloidal suspension. These are thickeners also called gelling agents, for example - lipophilic and hydrophobic clays and silicas, which are simply mixed with the oily phase.

- waxes, characterized by their melting point, generally between 35 and 70 C, such as beeswax, whale white, cetyl alcohol, stearyl alcohol, semi-synthetic glycerides, paraffin , ceresin, ozokerite, and others. These consistency agents are mixed with the oily phase at the melting temperature of the wax, then cooled.

incorporés à la phase huileuse à haute température, comprise selon les cas entre 130 C et 160 C, ce qui nécessite une dépense énergétique importante. - various gelling agents such as aluminum or zinc soaps, ethylcellulose, or polyoxyethylene glycols of high molecular weight (approximately 20,000). These gelling agents are

incorporated into the oily phase at high temperature, between 130 C and 160 C depending on the case, which requires significant energy expenditure.

However, none of these gelling agents is fully satisfactory, since the physical stability of the gels obtained is not sufficient to ensure good preservation for several months, even a few years, the time necessary for the marketing and use of the product. In addition, the ambient temperature of the storage room can vary and greatly exceed 25 C, causing increased exudation of these oleogels which take on a dissuasive aspect for the user and become unfit for sale.

The present invention provides an unexpected solution to this well-known drawback which has not been resolved to date. It relates to a composition in the form of an anhydrous oily gel, the characteristic of which is to have good physical stability, constant throughout the storage period, usually 24 to 36 months, including when the

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 temperature exceeds 25 C. The gels according to the present invention thus have the advantage of retaining their consistency and their appearance, for long periods, whatever the ambient temperature, without any exudation of the product appearing. Another advantage of the anhydrous oily gels according to the invention lies in the simplicity of their preparation process, and its low cost.

More specifically, the subject of the present invention is a composition in the form of an anhydrous oily gel, comprising at least one fatty substance and an amphiphilic nonionic stabilizing agent having a melting temperature above 40 C.

Unexpectedly, such a stabilizing agent entering into the composition of the anhydrous oily gel according to the invention confers its particular qualities on the gel by behaving both as a thickening agent and as an emulsifying agent. The compounds capable of exhibiting these two properties are compounds having a melting temperature comparable to that of waxes, generally between 40 and 70 ° C., and on the other hand having a non-ionic amphiphilic structure.

An amphiphilic molecule is a molecule containing both one or more hydrophilic groups and one or more lipophilic groups. A stabilizing agent entering into the composition according to the invention is therefore presented as a nonionic molecule having at least one hydrophilic pole and at least one lipophilic pole, the melting point of which is between 40 ° C. and 70 ° C.

Such a stabilizing agent can in particular be a monoester derivative of glycerol, that is to say a derivative of glycerol in which one of the hydroxyl functions is esterified while the other two remain free, or a monoester derivative of glycol, ie ie a diol derivative, one of the alcohol functions of which is esterified and the other of which is free.

For example, a stabilizing agent forming part of the composition according to the invention will advantageously be chosen from the following compounds: glycerol monostearate, glycerol monopalmitate, propylene glycol monopalmitate, ethylene glycol monostearate, polyglycerol monostearate, polyethylene glycol monostearate.

Some of these compounds are known and used for the preparation of emulsions, in which they play the role, always in combination with other emulsifiers, of stabilizing the emulsion. However, their gelling property had not hitherto been used to obtain anhydrous oily suspensions.

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The amount of stabilizing agent entering into the composition according to the invention can vary according to different parameters such as the nature of the oil and the initial consistency of the oil at room temperature, the viscosity of the gel which it is desired to obtain. , and even more.

The adjustment of this parameter is easily carried out by a person skilled in the art according to a defined specification. The proportion of stabilizing agent in the gel is generally between 1 and 20%, by weight. For example, use will be made, as stabilizing agent, of glycerol monostearate, present in the composition according to the invention at a concentration of between 1 and 20%, and preferably between 3 and 9%, by weight.

The composition according to the invention also contains a fatty substance, in general in oily form (that is to say fluid) at room temperature. Said fatty substance can be either a vegetable oil, a fatty substance of synthetic origin, a fatty substance of mineral origin, a fatty substance of animal origin. In particular, it can be chosen from: olive oil, sweet almond oil, rapeseed oil, peanut oil, castor oil, a medium chain glyceride (in general in C-12 to C-14), a polyoxyethylene glyceride, a silicone, squalane, petroleum jelly, paraffin oil, lanolin, axonge, squalene, or any other fatty substance including the gel formulation may be of interest to the user of said fatty substance.

températures sont ainsi généralement comprises entre 15 C et 25 C, mais peuvent varier occasionnellement dans un intervalle d'environ 0 C à 35 C. By ambient temperature is meant any temperature that can commonly be encountered in an industrial storage or domestic storage room, without special measures being taken to ensure particular storage conditions. These

temperatures are thus generally between 15 ° C. and 25 ° C., but may occasionally vary in the range of approximately 0 ° C. to 35 ° C.

The composition according to the invention can be used in the binary state, that is to say comprising only the two basic components described above. It then makes it possible to present certain oils having particular virtues, for example odorous, softening, disinfecting, or others, in a form that is pleasant to use and convenient to apply by friction, massage, or even by deposit in a more or less thick layer.

It may also contain a molecule of interest or other constituents having an essential or secondary role in the intended use of the oleogel. It may be a substance exhibiting a therapeutic or other activity, a substance conferring a particular property on the gel such as an adhesive polymer, or alternatively conservation additives,

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 sweeteners, flavors or colors. All these substances are known and generally used in their field of application.

A molecule of interest can be an active principle used as a medicament, such as an antibiotic, an anti-inflammatory, a local anesthetic; a food additive, such as a vitamin; or a polymeric compound, for example a hydrophilic polymeric compound. Hydrophilic polymers are well known to those skilled in the art, who may advantageously choose from the hydrophilic polymers sold, in particular, a carboxymethylcellulose, a cellulose gum, a carboxyvinyl polymer, a PVM / MA copolymer (ether copolymer polyvinylmethyl and maleic acid), or others. Likewise, a compound such as a flavoring, a sweetener, a coloring, a preservative can be added to the composition according to the invention, according to the use for which it is intended.

In the end, the composition according to the invention consists at least of a binary base, which is likely to be added in addition, one or more of the additional constituents chosen according to the destination use from those described above.

This possibility of adding additional constituents to the binary base at will is one of the original aspects of the present invention, linked in large part to the fact that the process for preparing the claimed composition is compatible with the non-destructive incorporation of said additional constituents. in the binary base. This compatibility is ultimately linked to the properties of the ingredients selected as constituents of the binary base.

Indeed, an object of the present invention is a process for preparing a composition in the form of an anhydrous oily gel, comprising at least the steps consisting in a) introducing into a reactor at least one fatty substance and one amphiphilic nonionic stabilizing agent, having a melting temperature above 40 C, b) heating to a temperature close to the melting temperature of said stabilizing agent, with stirring, until a homogeneous mixture is obtained, c) allowing the mixture to cool homogeneous mixture obtained with gentle stirring until a gel is formed.

 Thus, thanks to the method according to the present invention, a binary base is obtained in the form

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 of a homogeneous mixture at a temperature close to the melting point of the chosen stabilizing agent. To this base, an additional constituent can be added from the start (step a)), provided that said additional constituent is not degraded or denatured at the melting point of the chosen stabilizing agent.

Then said homogeneous mixture cools gradually with gentle stirring until the gel forms. It is then possible to add one or more additional constituents at a desired time, during cooling. In particular, it is possible to add one or more components sensitive to heat when the temperature of said homogeneous mixture becomes compatible with the additional component or components to be incorporated into the composition.

A simple device for controlling the temperature of the reactor will make it possible to add the desired constituent (s) at the appropriate time. Those skilled in the art use well-known devices for this.

Thus, advantageously, the method according to the invention will comprise at least one additional step during which is added to said homogeneous mixture during cooling, at least one additional constituent as described, for example a molecule of interest, such as a drug, a vitamin, a hydrophilic polymer, or a flavor, a color, a preservative, a sweetener It is thus possible to obtain by a simple and inexpensive process, a large variety of anhydrous oily gels, suitable for diversified uses: the anhydrous oily composition according to the invention can be used as a fatty base, or supplemented with one or more of the constituents described. It has the great advantage of not being toxic, and of being able to be applied and absorbed without danger.

For example, it is suitable for topical use on the skin or on a mucous membrane, as a softening, emollient, occlusive cream, etc., depending on the fatty substance chosen.

It can also serve as a vehicle for various compounds stable in an anhydrous medium, and exerting their action after contact with the skin or with the aqueous medium at the time of their application or administration. By way of example, mention may be made of the vitamins which may thus be formulated for use by the oral or topical route, or alternatively antibiotics, anti-inflammatories, or anesthetics which are conveniently usable for local application.

It is also advantageous to use an oleogel according to the invention as an oral gel. In

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 Indeed, as explained above, it is possible to include in the composition according to the invention, a hydrophilic polymer. By absorption of water from the oral environment, the gel swells which causes it to adhere to the wet surface of the mucosa with which it is in contact or on which it is spread. This characteristic makes it a very suitable product as a muco-adhesive dressing, and also as an adhesive product for the fixation of dental prostheses, after possible addition of the appropriate active ingredients, flavors and preservatives.

Finally, it should be noted that in general, the oleogel according to the invention is perfectly suitable for administration by a wide range of routes: oral, cutaneous, nasal, ophthalmic, buccal, rectal, etc. This is why a composition according to the present invention can be applied perfectly to at least one of the following uses: cosmetic product, oral product, hygiene and comfort product, food supplement, pharmaceutical product.

The following examples will illustrate the invention without limiting it.

glycérol, dont la température de fusion est voisine de 60 C, et 6 parties de perhydrosqualène. On chauffe alors progressivement jusqu'à la température de 65 C environ, sous agitation, jusqu'à obtention d'un mélange homogène. Puis on laisse refroidir le mélange homogène obtenu sous faible agitation jusqu'à formation d'un gel de consistance onctueuse. EXAMPLE 1 Preparation of an emollient dermal gel 78 parts of paraffin oil, 6 parts of monostearate are introduced into a reactor.

glycerol, whose melting temperature is close to 60 C, and 6 parts of perhydrosqualene. Then heated gradually to the temperature of about 65 C, with stirring, until a homogeneous mixture is obtained. Then the homogeneous mixture obtained is allowed to cool with gentle stirring until a gel of smooth consistency is formed.

EXAMPLE 2 Preparation of a Compact Gel 87 parts of paraffin oil, 15 parts of glycerol monostearate, the melting point of which is close to 60 ° C., and 6 parts of perhydrosqualene are introduced into a reactor.

Then heated gradually to the temperature of about 65 C, with stirring, until a homogeneous mixture is obtained. Then the homogeneous mixture obtained is allowed to cool with gentle stirring until a gel of waxy and compact consistency is formed.

EXAMPLE 3 Preparation of an Antibiotic Gel for Oral Administration 70 parts of peanut oil and 3 parts of monopalmitate are introduced into a reactor.

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 glycerol, the melting point of which is close to 60 C. The mixture is then gradually heated to the temperature of approximately 65 C, with stirring, until a homogeneous mixture is obtained.

- Arôme fraise 1 partie Puis on laisse refroidir le mélange homogène obtenu sous faible agitation jusqu'à formation d'un gel. Then the homogeneous mixture thus obtained is allowed to cool with gentle stirring to a temperature of 25-30 C, and the following compounds are added to the reactor, while maintaining stirring: - Amoxicillin 25 parts - Saccharin sodium'l part

- Strawberry flavor 1 part Then the homogeneous mixture obtained is allowed to cool with gentle stirring until a gel is formed.

EXAMPLE 4: Composition of a rectal gel - Paraffin oil 80 parts - Vaseline 13 parts - Propylene glycol palmitostearate 6 parts - Ruscus aculeatus dry extract 2 parts EXAMPLE 5: Composition of an antibiotic ophthalmic ointment - Paraffin oil 53 parts - Vaseline 40 parts - Glycerol monostearate 6 parts - Auréomycin 1 part EXAMPLE 6: Composition of an anti-inflammatory muco-adhesive dressing - Paraffin oil 75 parts - Glycerol monostearate 4 parts - Carboxymethylcellulose 20 parts - Triamcinolone acetonide, 05 part - QS aroma

EXAMPLE 7 Composition of an adhesive paste for dental prosthesis

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 - Paraffin oil 40 parts - Vaseline 10 parts - Glycerol monostearate 3 parts - Cellulose gum 20 parts - PVM / MA copolymer 25 parts - Enoxolone 0.5 parts - Colorant Q. S.

 - Q. S. aroma

- Curator Q. S.

EXAMPLE 8 Stability tests Stability tests were carried out, demonstrating the absence of excision in anhydrous oily gels. The tests presented here were carried out on the one hand on samples prepared according to the indications given in Example 1 (binary basis) and on the other hand on an adhesive paste for dental prosthesis prepared according to Example 7.

The samples are introduced into 50 ml containers opaque to light and placed in rooms thermostatically controlled at 40 ° C., 50 ° C. and 60 ° C. (3 repetitions for each batch). The results of visual observations are taken daily for 3 months. The results are as follows: - Binary base: At 40 ° C., the binary base is has not changed in consistency or appearance, no phenomenon of excision is visible. At 50 ° C., a slight fluidization is observed without demixing.

500 um). - Dental adhesive paste: Storage at 40 C under the conditions defined above for 3 months does not reveal any modification of the dental paste. At 60 ° C., fluidization of the medium and sedimentation of the insoluble constituents (cellulose gum and PVM / MA copolymer) are observed at the end of the sixth day. This phenomenon is slowed down by the use for said insoluble constituents, of powders of finer particle size (10-50 μm, rather than 200-

500 µm).

By comparison, samples of oily gels taken from commercially available products show a phase shift at 30 C after a few days or a few weeks depending on the products.

Claims (11)

1-Composition in the form of an anhydrous oily gel, comprising at least one fatty substance and an amphiphilic nonionic stabilizing agent having a melting temperature above 40 C.

" 2-Composition according to claim 1, characterized in that said stabilizing agent is chosen from monoester derivatives of glycerol and monoester derivatives of glycol.  3-Composition according to claim 1 or 2, characterized in that said stabilizing agent is chosen from the following compounds: glycerol monostearate, glycerol monopalmitate, propylene glycol monopalmitate, ethylene glycol monostearate, polyglycerol monostearate, polyethylene glycol monostearate .  4-Composition according to one of the preceding claims, characterized in that said stabilizing agent is glycerol monostearate present at a concentration of 1 to 20%, preferably 3 to 9% by weight.  5-Composition according to one of the preceding claims, characterized in that said fatty substance is chosen from a vegetable oil, a fatty substance of synthetic origin, a fatty substance of mineral origin, a fatty substance of animal origin.  6-Composition according to one of the preceding claims, characterized in that it further comprises, a molecule of interest.  7-Composition according to one of the preceding claims, characterized in that it further comprises at least one compound chosen from a vitamin, an antibiotic, an anti-inflammatory, a local anesthetic, a hydrophilic polymeric compound, a sweetener, a flavor, color, preservative.  8-Composition according to one of the preceding claims, characterized in that it further comprises at least one hydrophilic polymeric compound chosen from carboxymethylcellulose, cellulose gum, the PVMIMA copolymer, a polymer <Desc / Clms Page number 11>  carboxy.  9-A method of preparing a composition according to one of the preceding claims, comprising at least the steps of a) introducing into a reactor at least one fatty substance and an amphiphilic nonionic stabilizing agent, having a melting temperature above 40 C b) heating to a temperature close to the melting point of said stabilizing agent, with stirring, until a homogeneous mixture is obtained, b) allowing the homogeneous mixture obtained to cool with gentle stirring until a gel is formed .  10-A method according to the preceding claim, wherein is further added to said homogeneous mixture during cooling, at least one of the following compounds: a molecule of interest, a sweetener, a flavor, a color, a preservative.  11- Application of a composition according to one of the preceding claims to the preparation of at least one of the following products: cosmetic product, oral product, hygiene and comfort product, food supplement, pharmaceutical product.