US20100159013A1

US20100159013A1 - flavored clay-based therapeutic composition

Info

Publication number: US20100159013A1
Application number: US12/733,172
Authority: US
Inventors: Jerome Barra; Denis Le Hazie
Original assignee: Individual
Current assignee: Firmenich SA; Ipsen Pharma SAS
Priority date: 2007-08-13
Filing date: 2008-08-12
Publication date: 2010-06-24
Also published as: PT2194968E; AR114148A2; JP2014208715A; EP2194968B1; TWI519303B; CL2008002366A1; UA97408C2; SA08290496B1; EA201070257A1; WO2009056703A1; BRPI0814979A2; ME00975B; KR20100055460A; PL2710998T3; EP2710998B1; CA2696062A1; PT2710998T; DK2194968T3; KR101503957B1; HUE029713T2

Abstract

The subject of the present invention is a flavored therapeutic composition containing a clay as well as active principle, and characterized in that the clay is a dioctahedral smectite and the flavor is encapsulated.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the U.S. National Stage filing of International Application No. PCT/FR2008/001185, filed Aug. 12, 2008, which claims priority to EP 07291005.2, filed Aug. 13, 2007, the disclosures of which are hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

The present Application relates to a flavored pharmaceutical composition containing a smectite as active ingredient.
A therapeutic composition based on smectite known as “diosmectite” exists and is sold under the trade-mark Smecta®. But due to the particular taste of the clay which certain patients and children in particular can sometimes find unpleasant, the problem was therefore to find a novel composition which is flavored and the taste of which remains predominant vis-à-vis the taste of the clay. In order to solve this problem, the Applicant proposes a novel flavored pharmaceutical composition based on smectite and as defined below.

DETAILED DESCRIPTION OF THE INVENTION

The subject of the present invention is therefore a flavored therapeutic composition containing a clay as active ingredient, and characterized in that

- the clay is a dioctahedral smectite; and
- the flavored is encapsulated.

A composition according to the present invention can be used for the prevention and/or treatment of certain pathologies such as the symptomatic treatment of pain associated with oesogastroduodenal and colic conditions, acute and chronic diarrhoeas, coeliac disease.
Smectites represent a particular family of clay in which dioctaedral species such as montmorillonite and beidellite, and trioctaedral species such as hectorite and saponite are found.
The clay used according to the invention is a dioctahedral smectite. Preferably, the dioctahedral smectite is a montmorillonite or a beidellite or a crystallographic structure intermediate between the two crystal-chemical poles: montmorillonite and beidellite. This intermediate crystallographic structure can be close to the montmorillonite pole and even very close to the montmorillonite pole; it can also be close to the beidellite pole and even very close to the beidellite pole. Preferably, a smectite according to the invention is a montmorillonite or an intermediate structure close to the montmorillonite pole, and very preferably very close to the montmorillonite pole.
Also preferably, the clay used is the smectite known as “diosmectite” and sold under the trade-mark Smecta®.
The therapeutic composition according to the present invention comprises “a flavoring ingredient or composition”, called “flavor”. The term “flavor” as used in the present Application covers the flavoring ingredients or compositions usually used in the food industry, whether of natural or synthetic origin. It comprises single compounds or mixtures.
Specific examples of such compounds can be found in the literature, such as for example in Fenaroli's Handbook of Flavor Ingredients, 1975, CRC Press; Synthetic Food Adjuncts, 1947, M. B. Jacobs, published by Van Nostrand; or Perfume and Flavor Chemicals, 1969, S. Arctander, Montclair, N.J. (USA).
These compounds are well known to a person skilled in the art in the field of flavoring or aromatizing consumer products, i.e. traditionally flavored consumer products to which an odour, a flavor or a taste has been added, or consumer products the taste of which has been modified.
Preferably, the flavor is a hydrophobic liquid, soluble in organic solvents but only very weakly soluble in water.
Very preferably, the flavor is characterized by a Hildebrand solubility parameter 8 less than 30 MPa^1/2. The incompatibility with water of most of the flavors and perfumes can in fact be expressed by means of the Hildebrand solubility parameter which is in general less than 25 MPa^1/2while the same parameter for water is 48 MPa^1/2and for alkanes, 15-16 MPa^1/2. This parameter gives a useful polarity scale correlated with a cohesive energy density of the molecules. For mixing to take place spontaneously, the difference in solubility of the molecules to be mixed must be kept to a minimum. The handbook of solubility parameters (Handbook of Solubility Parameters, A. F. M. Barton, CRC Press, Bocca Raton, 1991) gives a list of 8 values for a large number of chemical products but also recommended group-contribution methods allowing the 8 values for complex chemical structures to be calculated.
Also preferably, the flavor is in a liquid, volatile or labile form, with a log P comprised within the range −2 to 7, and very preferably, from 2 to 6.
Also in a preferred fashion, a composition according to the present invention comprises, as flavor, natural extracts, essential oils or a mixture thereof.
As a suitable flavor, traditional flavors can be mentioned such as liquorice, exotic fruits, red fruits, extracts of citrus fruits such as lime, lemon, orange, grapefruit, or mandarin oils or coffee, tea, mint, cocoa, vanilla/caramel or essential oils from herbs and spices, or also flavors known as “modern” such as coca-cola, green tea, caramel custard.
Preferably, a composition according to the invention comprises at least one encapsulated flavor different from vanilla.
The flavors are preferably chosen from the traditional flavors such as liquorice, exotic fruits, red fruits, extracts of citrus fruits, vanilla/caramel/chocolate but also flavors known as “modern” such coca-cola, green tea, caramel custard.
Preferably, the flavor is chosen from vanilla/caramel/chocolate flavors and extracts of citrus fruits and very preferably, vanilla/caramel/chocolate and orange, lemon, grapefruit or clementine.
Also in a preferred fashion, the flavor is a mixture of flavors, and very preferably, a mixture of vanilla and orange flavors.
The flavor can be mixed with solvents, adjuvants, additives and/or other substances, for example those usually used in the flavor and/or food industry.
The flavor according to the present invention is preferably encapsulated in a glassy matrix (encapsulation matrix) of carbohydrate(s).
Any sugar or sugar derivative which can be processed by extrusion techniques can be used as constituent(s) of the encapsulation matrix, in order to form a dry extruded solid. Particular examples of suitable constituents can be chosen from the following products: sucrose, glucose, lactose, levulose, fructose, maltose, ribose, dextrose, isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol, pentatol, arabinose, pentose, xylose, galactose, hydrogenated starch hydrolysates, maltodextrin, Stabilite (trade name; origin: SPI Polyols, USA), agar, carrageenan, other gums, polydextrose and the derivatives and mixtures thereof.
Preferably, maltodextrin or mixtures of maltodextrin and at least one product chosen from: sucrose, glucose, lactose, levulose, maltose, fructose, isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol and hydrogenated starch hydrolysates are used. Very preferably, the matrix is constituted by maltodextrin or a mixture of maltodextrin and at least one product chosen from: sucrose, maltose, isomalt, maltitol and hydrogenated starch hydrolysates. Also very preferably, the matrix is constituted by maltodextrin and sucrose.
Preferably, the maltodextrin has a dextrose equivalent (DE) greater than 5 and less than 20.
An emulsifier such as lecithin, and/or a plasticizer, typically water, can be added to the mixture if necessary.
The flavored product or the flavored composition according to the invention, which are extruded, can be prepared by any standard method. For example, the methods described in U.S. Pat. Nos. 4,610,890 and 4,707,367, the content of which is incorporated by way of reference, are suitable for supplying encapsulated flavors as used in the present invention.
Also preferably, the flavor is present in a proportion of at least 10% by weight expressed as dry matter, with respect to the total weight (expressed as dry matter) of the encapsulation matrix, and preferably in a proportion comprised between 15 and 35%.
A composition according to the invention comprises preferably 70 to 90% by weight of active ingredient, and very preferably from 75 to 85%, with respect to the total weight of the composition.
Also preferably, a composition according to the invention comprises 0.1 to 3% by weight of encapsulated flavor with respect to the total weight of the composition, and very preferably 0.3 to 2.5%. Also very preferably, a composition according to the invention comprises 0.5 to 2% by weight of encapsulated flavour with respect to the total weight of the composition.
A therapeutic composition according to the present invention can be presented in different solid forms such as for example powders, granules, tablets or capsules. Appropriate solid supports can be, for example, talc, sugars, lactose, dextrin, gelatin, cellulose and its esters.
In a therapeutic composition according to the present invention, there can also be also other additives such as colouring agents, sweetening agents, lubricants, glidants. A composition according to the present invention can also contain minerals.
The colouring agent(s) used according to the present invention can be any type of colouring agents usually used in the food and/or the pharmaceutical industries. Among the sweetening agents, the following can be mentioned: saccharin, aspartame, maltodextrin, monosaccharides such as fructose or glucose, disaccharides such as saccharose. Among the lubricating agents, talc can be mentioned for example. Among the glidant agents, saccharose can be mentioned.
The mineral contribution can for example consist of the addition of metal salts such as aluminium or magnesium salts such as aluminium hydroxide, magnesium carbonate.
The administration method for a composition according to the invention is chosen, among others, according to its pharmaceutical form and the pathology to be treated. Preferably, the composition as defined above is administered by the oral route.
The daily administration dose is the usual recommended dose for this product. In the particular case of the smectite known as “diosmectite”, it can be administered at a maximum daily dose of 18 g/day.
Unless defined otherwise, all the technical and scientific terms used here have the same meaning as that usually understood by an ordinary specialist in the field to which this invention belongs.

EXPERIMENTAL PART

Example 1

Preparation of an Encapsulated Orange (Oil) Flavor

A syrup is prepared from maltodextrin, sucrose, water and flavor. The mixture is then heated to 123° C. in order to reduce the moisture content of the syrup. Then, the emulsifier is mixed with the concentrated syrup under high shear conditions in order to form a uniform melt. The melt is then extruded under a pressure of 2×10⁵Pa through an extrusion die plate with holes of 0.8 mm diameter in a cold solvent for chilling and breaking of the extrudates.


Ingredients	in grams (g)	% dry matter

Maltodextrin 18DE	1505	44.55
Sucrose	1505	44.55
Cold-pressed oil of Valencia orange	350	10.36
Soya lecithin¹⁾	18	0.54
Water	400	—
Total		100.00

¹⁾origin: Central Soya, Strong Wayne, Indiana, USA

Example 2

Preparation of an Encapsulated Vanilla Flavor

Example 1 is reproduced by using a vanilla extract (ex Firmenich) instead of the orange flavor.

Example 3

Preparation of an Encapsulated Caramel Flavor

Example 1 is reproduced by using a caramel flavor (ex Firmenich) instead of the orange flavor.

Example 4

Preparation of a Flavored Therapeutic Composition

The compositions below are prepared by gently mixing all the substances together in the proportions indicated, until they are dispersed in a homogenous fashion. In the table below, all the quantities are expressed in mg.


	Example	Example	Example
Ingredients	4a	4b	4c

Diosmectite	3000	3000	3000
Encapsulated orange flavor	—	—	10
(flavor prepared according to
Example 1) ¹
Encapsulated vanilla flavor	50	50	50
(flavor prepared according to
Example 2) ²
Encapsulated caramel ® flavor	10	—	—
(flavor prepared according to
Example 3) ³
Soluble saccharine + hydrated	700	710	700
glucose
Water	100	100	100

¹ex Firmenich, ref. 501289 TD 0990B;
²ex Firmenich, ref. 501465 TD1591;
³ex Firmenich, ref. 501403 TD 1094

Example 5

Stability of a Composition According to the Invention

Clay being a stable product naturally, the stability of a composition according to the invention is measured both as regards the organoleptic characteristics of the flavor and for its inertia vis-à-vis the clay.
The stability of the organoleptic characteristics of the flavor is established by testers (panel of 7 experts) on the basis of a number of criteria (sugary, fruity, acidic, bitterness, etc.) over a period of at least 6 months.
Moreover, it is noted that the flavor shows no deterioration in the presence of the clay over this same period.

Claims

1. A flavored therapeutic composition comprising a clay as an active ingredient, wherein

the clay is a dioctahedral smectite; and

the flavor is encapsulated.

2. The composition according to claim 1, wherein the dioctahedral smectite is a montmorillonite or a beidellite or an intermediate crystallographic structure between montmorillonite and beidellite crystal-chemical poles.

3. The composition according to claim 1, wherein the dioctahedral smectite is a montmorillonite or an intermediate crystallographic structure close to the montmorillonite pole.

4. The composition according to claim 1, wherein the dioctahedral smectite is a montmorillonite or an intermediate crystallographic structure very close to the montmorillonite pole.

5. The composition according to claim 1, wherein the dioctahedral smectite is a diosmectite.

6. The composition according to claim 1, wherein the flavor is a hydrophobic liquid.

7. The composition according to claim 1, wherein the flavor has a Hildebrand solubility parameter less than 30 MPa^1/2.

8. The composition according to claim 1, wherein the flavor is in liquid form with a log P comprised within the range −2 to 7.

9. The composition according to claim 1, wherein the flavor has a log P comprised within the range 2 to 6.

10. The composition according to claim 1, wherein the flavor is a natural extract, an essential oil or a mixture thereof.

11. The composition according to claim 1, wherein the composition comprises at least one encapsulated flavor different from vanilla.

12. The composition according to claim 1, wherein the flavor is liquorice, exotic fruits, red fruits, extracts of citrus fruits, vanilla, caramel, chocolate, coca-cola, green tea, caramel custard, or mixtures thereof.

13. The composition according to claim 1, wherein the flavor is vanilla, caramel, chocolate, extracts of citrus fruits, or mixtures thereof.

14. The composition according to claim 1, wherein the flavor is vanilla, caramel, chocolate, orange, lemon, grapefruit, clementine, or mixtures thereof.

15. The composition according to claim 1, wherein the flavor is a mixture of flavors.

16. The composition according to claim 1, wherein the flavor is a mixture of vanilla and orange flavors.

17. The composition according to claim 1, wherein the flavor is encapsulated in a glassy matrix of carbohydrates.

18. The composition according to claim 17, wherein the matrix comprises maltodextrin or a mixture of maltodextrin and at least one of sucrose, glucose, lactose, levulose, maltose, fructose, isomalt, sorbitol, mannitol, xylitol, lactitol, maltitol or hydrogenated starch hydrolysates.

19. The composition according to claim 17, wherein the matrix comprises maltodextrin or a mixture of maltodextrin and at least one of sucrose, maltose, isomalt, maltitol, or hydrogenated starch hydrolysate.

20. The composition according to claim 17, wherein ene the matrix comprises maltodextrin and sucrose.

21. The composition according to claim 18, wherein the maltodextrin has a dextrose equivalent greater than 5 and less than 20.

22. The composition according to claim 1, wherein the flavor is present in a proportion of at least 10% by weight expressed as dry matter, with respect to the total weight of the encapsulation matrix expressed as dry matter.

23. The composition according to claim 1, wherein the flavor is present in a proportion comprised between 15 and 35% by weight expressed as dry matter, with respect to the total weight of the encapsulation matrix expressed as dry matter.

24. The composition according to claim 1, wherein the composition comprises from 70 to 90% by weight of active ingredient.

25. The composition according to claim 1, wherein the composition comprises from 75 to 85% by weight of active ingredient.

26. The composition according to claim 1, wherein the composition comprises from 0.1 to 3% by weight of encapsulated flavor.

27. The composition according to claim 1, wherein the composition comprises from 0.3 to 2.5% by weight of encapsulated flavor.

28. The composition according to claim 1, wherein the composition comprises from 0.5 to 2% by weight of encapsulated flavor.