Multicompartmentalized material for the thermostimulated delivery of substances of interest, preparation method thereof and uses of the same

Abstract

A material in the form of solid particles with a diameter varying from 10 μm to 1 cm is provided, composed of a continuous solid shell having at least one silicon oxide, said shell imprisoning an aqueous phase The aqueous phase includes at least one hydrophilic substance of interest S.sub.H and at least one droplet of a fatty phase predominantly having a crystallizable oil in the solid state at the storage temperature of said material The crystallizable oil has a melting point (T.sub.M) of less than 100° C. and including at least one lipophilic substance of interest S.sub.L.

Claims

1. Material in the form of solid particles with a diameter varying from 10 μm to 1 cm which are composed of a continuous solid shell comprising: at least one silicon oxide, said shell imprisoning an aqueous phase, wherein said aqueous phase includes at least one hydrophilic substance of interest S.sub.H and at least one droplet of a fatty phase comprising from 50% to 99.9% by weight, with respect to the weight of said fatty phase, of a crystallizable oil in the solid state at the storage temperature of said material, said crystallizable oil having a melting point (T.sub.M) of less than 100° C. and including at least one lipophilic substance of interest S.sub.L, wherein said substances of interest are selected from the group consisting of antiseptics, antibiotics, anti-inflammatories, local laxatives, hormones, proteins, vitamins, sunscreens, antioxidants, agents for combating free radicals, superoxide dismutase, fragrances, odor absorbers, deodorant agents, antiperspirant agents, dyes, pigments, emollients, moisturizing agents, pH indicators, catalysts, polymerization initiators, monomers, and complexing agents.

2. Material according to claim 1, wherein the crystallizable oil is chosen from fatty substances and mixtures of fatty substances, of natural or synthetic origin, the melting point of which is greater than 15° C. and less than 100° C.

3. Material according to claim 1, wherein the crystallizable oil is a paraffin wax.

4. Material according to claim 1, wherein said material is provided in the form of a powder of spherical or substantially spherical particles.

5. Material according to claim 1, wherein the diameter of the droplet or droplets of fatty phase present in each particle of the material varies from 8 μm to 80 μm.

6. Material according to claim 1, wherein each particle of material comprises only a single droplet of fatty phase in the aqueous phase present in the silica shell and the volume of said droplet of fatty phase represents from 30% to 70% of the internal volume of the particles.

7. Material according to claim 1, wherein the silica shell has a thickness of 0.1 to 2 μm.

8. Material according to claim 1, wherein the silica shell additionally comprises one or more metal oxides of the formula ZrO.sub.2.

9. Material according to claim 1, wherein the substance or substances of interest S.sub.L represent from 0.001% to 50% by weight of the total weight of the fatty phase present in the aqueous phase.

10. Material according to claim 1, wherein the substance or substances of interest S.sub.H represent from 0.001% to 50% by weight of the weight of the aqueous phase.

11. Pharmaceutical, cosmetic or food products, wherein they include, as ingredient, at least one material as defined in claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1a-1d are optical microscopy photographs of the particles of the final material in accordance with one embodiment; and

(2) FIGS. 2a-2c are confocal microscopy images taken of the material before and after raising the temperature in accordance with one embodiment.

DETAILED DESCRIPTION

(3) The present invention is illustrated by the following implementational examples, to which, however, it is not limited.

EXAMPLES

(4) The starting materials used in the examples which follow are listed below: Paraffin 42-44 in block form, having a melting range from 42 to 44° C. (CAS No. 8002-74-2), sold by Merck; the expansion in volume of this fatty phase on changing its temperature from ambient temperature to 55° C. is approximately 13%; Tetraethoxyorthosilane, more than 99% pure (TEOS); Rhodamine B: Sigma-Aldrich; Cetyltrimethylammonium bromide (CTAB): ChemPur; Cyclic polydimethylsiloxanes, sold under the trade name DC3225C by Dow Corning (non-ionic surfactant); Silica nanoparticles with a diameter of 7 nm, sold under the name Aerosil® A380: Evonik Degussa; Hydrochloric acid, 37% by volume (Carlo Erba Reagents); PDMS DC200, viscosity 200 cSt: Aldrich.

(5) These starting materials were used as received from the manufacturers, without additional purification.

(6) The critical micelle concentration (CMC) of the CTAB in pure water at ambient temperature is 0.92 mM.

(7) The materials obtained were characterized using an inverted optical microscope sold under the trade name Axiovert® X100 by Zeiss and equipped with a heating stage from Mettler which makes it possible to control the temperature and also the heating and cooling rates.

(8) The size distribution of the emulsions was studied using a particle sizer sold under the trade name Mastersizer Hydro MS2000 by Malvern Instrument. The particle size measurements were carried out at 25° C. in pure water. The intensity of the scattering as a function of the angle which was collected was converted using the Mie-Lorenz theory. The distribution in the size of the particles was expressed by their weighted mean diameter (D) and their polydispersity (P) by applying the following equations (1) and (2):

(9) $\begin{array}{cc}D=\frac{\underset{i}{.Math.}{N}_i{D}_i^3}{\underset{i}{.Math.}{N}_i{D}_i^2}& \left(1\right)\\ \mathrm{and}P=\frac{1}{\stackrel{\_}{D}}\frac{\underset{i}{.Math.}{N}_i{D}_i^3.Math.\stackrel{\_}{D}-D_i.Math.}{\underset{i}{.Math.}{N}_i{D}_i^3}& \left(2\right)\end{array}$

(10) in which: D.sub.i is the diameter of the particles, N.sub.i is the total number of droplets with the diameter D.sub.i, D is the median diameter, that is to say the theoretical opening of the sieve such that 50% of the particles, by weight, have a greater diameter and 50% have a smaller diameter.

(11) These formulae are applied in the particle sizers from Malvern Instrument.

Example 1: Preparation, Characterizations and Study of a Material in Accordance with the Invention

(12) In this example, the preparation, the characterization and the study of a material in accordance with the invention, composed of a silica shell including an aqueous phase comprising a fatty phase in the form of a droplet of crystallizable oil, are illustrated.

(13) It should be noted that, in this example, the fatty and aqueous phases do not include substances of interest, this example being given to demonstrate the structural feasibility of the compartmentalized material according to the process in accordance with the invention.

(14) It is easy to extrapolate the process below to fatty and aqueous phases respectively including at least one lipophilic substance of interest and at least one hydrophilic substance of interest, their use not in any way modifying the process in accordance with invention or the structure of the material obtained.

(15) 1) Preparation of the Material

(16) i): Functionalization of the Silica Particles

(17) 72 mg of Aerosil® A380 silica nanoparticles were dispersed in 7 ml of distilled water using an ultrasonic bath. 0.66 mg of CTAB/g of particles were subsequently added to this dispersion, this amount representing approximately ⅕ of the critical micelle concentration (CMC=0.92 mM). As the surface of the silica nanoparticles is negatively charged, the CTAB (cationic surfactant) is adsorbed at the surface of the silica particles and thus makes it possible to confer on them an amphiphilic nature. An aqueous phase including a dispersion of silica nanoparticles functionalized at the surface was obtained.

(18) The amount of CTAB was adjusted to the weight of the silica particles in order to obtain a specific coverage of 25 nm.sup.2/CTAB molecule at the silica/water interface, all the CTAB used being regarded as adsorbed at the surface of the silica particles.

(19) ii) Preparation of the O/W Emulsion

(20) 3 g of paraffin wax were added to a receptacle containing 7 g of water including 72 mg of silica particles as functionalized above in i).

(21) The receptacle was brought to a temperature of 60° C. in order to bring about the melting of the paraffin wax (fatty phase).

(22) The emulsification of the fatty phase and of the aqueous phase was carried out using a stirrer sold under the name Ultra-Turrax® T25 by Janke & Kunkel, equipped with an S25 KV-25F dispersing device, at 9000 revolutions/min for 30 seconds. The resulting monodisperse O/W emulsion thus obtained (mean size of the droplets of fatty phase centred at a diameter of 20 μm) was maintained at 60° C. in a thermostatically controlled bath without stirring in order to allow the phenomenon of limited coalescence to occur (adsorption of the silica particles at the surface of the dispersed droplets of fatty phase, which makes it possible to improve the homogeneity of the distribution in the size of the oil droplets dispersed in the water).

(23) iii) Preparation of the O/W/O Emulsion

(24) The pH of the continuous aqueous phase of the O/W emulsion obtained above in the preceding stage was subsequently adjusted to a value of approximately 0 by addition of hydrochloric acid. This very low pH value subsequently makes it possible to catalyse the hydrolysis of the TEOS and its condensation in the form of silicon oxide at the FP2/AP interface.

(25) 0.8 g of the O/W emulsion thus acidified was subsequently added to a fatty phase FP2 containing 8.2 g of PDMS, 0.3 g of DC3225C surfactant and 0.5 g of TEOS.

(26) The emulsification of the O/W emulsion in the fatty phase FP2 was carried out using the same stirrer as above in stage ii), finishing by stirring at 3500 revolutions/min for 10 seconds. The O/W/O double emulsion thus obtained was subsequently stored at ambient temperature without stirring for 24 hours in order to bring about the solidification of the fatty phase and to allow the hydrolysis of the TEOS and its condensation in the form of a silica shell to occur around the droplets of aqueous phase.

(27) After 24 hours, the material obtained and sedimented at the bottom of the receptacle was recovered and dispersed again in PDMS in order to remove any residue of non-encapsulated crystallizable oil and any droplet of aqueous phase also non-encapsulated or not containing encapsulated fatty phase.

(28) 2) Results and Characterizations

(29) The appended FIG. 1 represents an optical microscopy photograph of the particles of the final material thus obtained: FIG. 1a is a view of several particles after sedimentation, FIG. 1b is centred on a single particle and FIGS. 1c and 1d show the particles of the material after application of a mechanical pressure using a spatula at ambient temperature to the slide covering the drop observed with the microscope, this mechanical pressure having brought about the rupture of the silica shells. In these figures, the white arrows mark off the silica shells, the black arrows mark off the droplets of solid fatty phase after rupture of the shell and the white circles in dotted lines show that the space reserved for the fatty phase is filled with a fatty phase in FIG. 1b whereas it is empty of fatty phase after rupture of the silica shell in FIG. 1d.

(30) It was subsequently confirmed that an increase in the temperature brought about the rupture of the silica shells and the release of the aqueous phase and of the molten fatty phase.

(31) The material was incorporated in an oily phase composed of PDMS and including 20% by weight of DC3225C. The composition obtained was brought to a temperature of 44° C. by gradually raising the temperature at the rate of 5° C. per minute on the heating stage of the microscope. The composition was observed in confocal microscopy before and after raising the temperature. The corresponding photos are given in the appended FIG. 2. In this figure, FIG. 2a corresponds to the image taken before raising the temperature, whereas FIGS. 2b and 2c correspond to images taken after raising the temperature. It is found that raising the temperature brings about the melting of the fatty phase present in the aqueous phase, the rupture of the silica shell (white arrow in FIG. 2c) and the expulsion of the molten fatty phase into the oily phase (PDMS) of the composition, where it dissolves, and also the expulsion of the aqueous phase in the form of a few droplets (black arrows).

(32) It is thus possible to simultaneously release lipophilic and hydrophilic substances which would be respectively present in the fatty phase and in the aqueous phase AP by simple raising of the temperature of the materials in accordance with the invention.