Multicompartmentalized material for the thermostimulated delivery of substances of interest, preparation process and applications

Patent metadata

Field	Value
Publication number	US-9649277-B2
Application number	US-201314409177-A
Country	US
Kind code	B2
Filing date	Jun 20, 2013
Priority date	Jun 21, 2012
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

The present invention relates to a material in the form of solid particles with a diameter varying from 1 μm to 1 cm which are composed of a continuous shell E Ext comprising at least one silicon oxide, said shell E Ext imprisoning at least one fatty phase, said material being characterized in that said fatty phase is solid at the storage temperature of said material and predominantly comprises a crystallizable oil having a melting point (T M ) of less than 100° C. and in that said fatty phase includes at least one lipophilic substance of interest S L and at least one inclusion comprising a continuous shell E Int comprising at least one silicon oxide, said shell E Int imprisoning an aqueous phase comprising at least one hydrophilic substance of interest S H .
The invention also relates to a process for the preparation of said material, to its use for the thermostimulated delivery of active substances, and also to the compositions including it.

First claim

The invention claimed is:

1. A material in the form of solid particles with a diameter varying from 1 μm to 1 cm which are composed of a continuous shell E Ext comprising:
at least one silicon oxide, said shell E Ext imprisoning at least one fatty phase, wherein in said material said fatty phase is solid at the storage temperature of said material and comprises from 50% to 99.9% by weight, with respect to the weight of said fatty phase, of a crystallizable oil having a melting point (T M ) of less than 100° C. and in that said fatty phase includes at least one lipophilic substance of interest S L and at least one inclusion comprising a continuous shell E Int comprising at least one silicon oxide, said shell E Int imprisoning an aqueous phase comprising at least one hydrophilic substance of interest S H .

2. The 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.

3. The material according to claim 1 , wherein the crystallizable oil is chosen from paraffin waxes, triglycerides, fatty acids, rosins, waxes, hydrogenated vegetable oils and their mixtures, synthetic bitumens, and their mixtures.

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

5. The material according to claim 1 , wherein the silica shell E Ext has a thickness of 0.1 to 2 μm.

6. The material according to claim 1 , wherein the silica shell or shells E Int have a thickness varying from 0.1 to 1 μm.

7. The material according to claim 1 , wherein the shells E Ext and/or E Int additionally comprise one or more metal oxides of formula MeO 2 in which Me is a metal chosen from Zr, Ti, Th, Nb, Ta, V, W and Al.

8. The material according to claim 1 , wherein the substance of interest is chosen from medicaments, active principles which can be used in cosmetics, chemical reactants, dyes, pigments and inks.

9. The material according to claim 1 , wherein the substance or substances of interest S L represent from 0.001% to 50% by weight of the total weight of the fatty phase.

10. The material according to claim 1 , wherein the substance or substances of interest S H represent from 0.001% to 50% by weight of the total weight of the aqueous phase present in the inclusion or inclusions present within the fatty phase.

11. A process for the preparation of a material as defined in claim 1 , wherein said process comprises the following stages:
1) in a first stage, bringing a fatty phase comprising from 50% to 99.9% by weight, with respect to the weight of said fatty phase, of a solid crystallizable oil (CO) having a melting point T M of less than 100° C. to a temperature T CO such that T CO is greater than T M , in order to obtain a crystallizable oil in the liquid state;
2) in a second stage, incorporating, in the fatty phase in the liquid state, at least one lipophilic substance of interest (S L ) and solid colloidal particles P 1 ;
3) in a third stage, bringing said fatty phase in the liquid state into contact with a first aqueous phase (AP 1 ) brought beforehand to a temperature T AP1 such that T AP1 is greater than T M , said aqueous phase additionally including at least one hydrophilic substance of interest (S H );
4) in a fourth stage, subjecting the liquid mixture resulting from the third stage to mechanical stirring in order to obtain a water-in-oil (W/O) emulsion formed of droplets of aqueous phase dispersed in the continuous fatty phase in the liquid state and in which the solid colloidal particles P 1 are present at the interface formed between the continuous fatty phase and the dispersed droplets of aqueous phase AP 1 ;
5) in a fifth stage, adding the W/O emulsion obtained above in the preceding stage to a second aqueous phase (AP 2 ) brought beforehand to a temperature T AP2 such that T AP2 is greater than T M and additionally including solid colloidal particles P 2 , said W/O emulsion representing at most 20% by weight with respect to the weight of the second aqueous phase;
6) in a sixth stage, subjecting the liquid mixture resulting from the fifth stage to mechanical stirring in order to obtain a water-in-oil-in-water (W/O/W) double emulsion formed of a continuous aqueous phase (AP 2 ) including droplets of fatty phase in the liquid state, each of said droplets of fatty phase in the liquid state including at least one droplet of aqueous phase AP 1 , in which double emulsion the solid colloidal particles P 2 are present at the interface formed between the continuous aqueous phase AP 2 and the dispersed droplets of fatty phase in the liquid state;
7) in a seventh stage, bringing said W/O/W double emulsion to a temperature T W/O/W such that T W/O/W is less than T M in order to bring about the solidification of the fatty phase and to obtain a W/O/W double emulsion formed of globules of fatty phase in the solid state, each of said globules including at least one droplet of aqueous phase AP 1 , said globules being dispersed in the aqueous phase AP 2 ;
8) in an eighth stage, adding, to the aqueous phase AP 2 of the double emulsion and with mechanical stirring, at least one silicon oxide precursor and a sufficient amount of at least one acid to bring the aqueous phases AP 1 and AP 2 to a pH of less than or equal to 4;
9) in a ninth stage, leaving the W/O/W triple emulsion standing, in order to allow the silicon oxide precursor to hydrolyse and to condense in the form of a silicon oxide shell around said droplets of aqueous phase AP (mineralization of the emulsion) and to thus obtain the expected material; and
10) in a tenth stage, separating said material from the aqueous phase AP 2 .

12. The process according to claim 11 , wherein the solid colloidal particles P 1 and P 2 are metal oxides chosen from the group consisting of oxides of silicon, titanium, zirconium and iron, and their salts.

13. The process according to claim 11 , wherein the solid colloidal particles P 1 and P 2 are identical in chemical nature and are chosen from silicon oxide nanoparticles.

14. The process according to claim 11 , wherein the amount of solid colloidal particles P 1 varies from 0.01% to 10% by weight, with respect to the total weight of the aqueous phase AP 1 .

15. The process according to claim 11 , wherein the amount of solid colloidal particles P 2 varies from 0.01% to 5% by weight, with respect to the total weight of the W/O emulsion.

16. The process according to claim 11 , wherein the solid colloidal particles P 1 and P 2 are functionalized by adsorption of surfactant molecules at their surface.

17. The process according to claim 11 , wherein the silicon oxide precursors are chosen from silicon alkoxides.

18. The process according to claim 17 , wherein the silicon alkoxides are chosen from tetramethoxyorthosilane, tetraethoxyorthosilane, dimethyldiethoxysilane, (3-mercaptopropyl)trimethoxysilane, (3-aminopropyl)triethoxysilane, N-(3-trimethoxysilylpropyl)pyrrole, 3-(2,4-dinitrophenylamino)propyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, phenyltriethoxysilane, methyltriethoxysilane and their mixtures.

19. The process according to claim 11 , wherein the amount of silicon oxide precursor varies from 0.005 to 4 M/m 2 of surface area of the globules of the dispersed phase of the emulsion and of the droplets of aqueous phase AP 1 of the emulsion.

20. A thermostimulated and simulta

Assignees

• Centre Nat Rech Scient

Inventors

• Schmitt Veronique
• Nollet Maxime
• Depardieu Martin
• Backov Renal

Classifications

• A61K8/31

  Hydrocarbons · CPC title

• A61K8/361

  Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof · CPC title

• A61K2800/56

  Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms · CPC title

• A61K9/143 Primary

  with inorganic compounds · CPC title

• A61K2800/412

  Microsized, i.e. having sizes between 0.1 and 100 microns · CPC title