EP1023040A1

EP1023040A1 - Compositions based on plant extracts

Info

Publication number: EP1023040A1
Application number: EP98949074A
Authority: EP
Inventors: Michel Dubourdeaux; Bernadette Elisabeth Fernande Verneau-Guimet
Original assignee: Laboratoire Bio Sphere 99; Institut Phytoceutic
Current assignee: Laboratoire Bio Sphere 99; Institut Phytoceutic
Priority date: 1997-10-17
Filing date: 1998-10-16
Publication date: 2000-08-02
Also published as: BR9813083A; CA2306414A1; AU9546498A; WO1999020242A1; FR2769837A1; FR2769837B1; JP2001520181A

Abstract

The invention concerns a composition comprising at least heteropolysaccharide such as pectin and a compound selected from the group consisting in carotenoids, in particular lycopene, and glucosinolate and/or sulphoraphane and mixtures thereof. The compositions are useful in medicine, dietetics and cosmetics, in particular for their curative and preventive properties relative to heavy metals and their anti-oxidant, anti-radical activity and their activity in stimulating cell turnover.

Description

COMPOSITIONS BASED ON PLANT EXTRACTS

The present invention relates to compositions, in particular for dietetic purposes (food supplement), cosmetic or medical, based on natural products, that is to say products found in plants or extracts of such plants.

We are currently witnessing considerable development in this field on the basis of very diverse compounds.

Fruit pectins have long been used as gelling agents or thickeners in the food industry. Furthermore, we now know that pectins are capable of binding heavy metals and their radionuclides and ensuring their excretion out of the body.

Carotenoids are also known and used for their pigmentary and antioxidant (anti-free radical) properties in the field of sun creams and cosmetic supplements (capsules, for example). Mention may be made of alpha- and beta-carotenes and lycopene, the most powerful of these compounds, which is extracted from tomatoes (tomato oleoresin).

Broccoli and its extracts are known for their favorable properties in carcinogenesis and cell degeneration. GB-B-1 041 890 describes emulsions which can be used in human medicine, for example as a vehicle for the administration of medicinal substances via food. These emulsions can comprise on the one hand a substance such as a fat-soluble vitamin, a fat-soluble derivative of a water-soluble vitamin, a carotenoid or their mixtures, and on the other hand a nonionic emulsifier and an ionic wetting agent, the aqueous phase. may include a hydrocolloid such as pectin.

SU-A-1 786 531 describes a drink produced from the juice of several fruits and which can therefore contain, among other things, carotene and pectin.

M. Yu Tamova et al. (Database FSTA, International Food Information Service (IFIS), Frankfurt / Main, Germany, 97-1-02-a0017, XP 002071238) have studied the ability of various pectin solutions to fix nickel and lead. The authors report that the addition of a carotene solution does not significantly affect the fixation of nickel and lead. The objective is the development of dietetic compositions for the fixation of heavy metals. The applicant has surprisingly and unexpectedly found that pectins can be very advantageously combined with carotenoids, in particular lycopene, or with broccoli or broccoli extracts. , and preferably to these two types of compounds, and that this combination allowed the different compounds to perform their above functions (fixation and elimination of heavy metals, antioxidant and anti-radical action and beneficial action on cell regeneration ) under more favorable conditions than when they are alone.

The applicant has in fact noticed that the pectins favor the availability and the transport of the associated compounds, so that the individual efficacy of the various compounds is thereby increased. From a dietetic and medical point of view, the combination administered orally allows better transport and better bioavailability of the associated compounds (carotenoid and / or broccoli or extract). On the cosmetic level, the association acts synergistically on the aggressions against the cells of the epidermis by pollution and solar rays.

The present invention therefore relates to a composition, in particular for dietetic, medical or cosmetic purposes, comprising at least one heteropolysaccharide, preferably esterified, in particular a polygalacturonic acid or ester, preferably a pectin, and a compound chosen from the group consisting of carotenoids, preferably lycopene, and glucosinolate and / or sulphoraphane, in particular plant extract, in particular from cruciferous plants, preferably broccoli, containing them, and mixtures thereof.

The compositions according to the invention have an excellent preventive action with respect to the action of pollutants such as in particular heavy metals (in particular mercury, lead, arsenic, cadmium) and their radionucleides. In vitro tests have in particular demonstrated a protective effect with respect to metals such as arsenic and cadmium which can exceed 80% and reach 100%. In vivo tests in rats have also demonstrated a very high protective and preventive protective effect against mercury. According to the preferred embodiment of the invention, the composition comprises the three types of compounds.

The applicant has found that the invention extends, with respect to pectin functionality, to heteropolysaccharides, preferably esterified to various degrees, to mixtures of such compounds, for example of various degrees of esterification, and among these heteropolysaccharides, preferably polygalacturonic acids and their esters to which pectins belong. Preferably, they are methyl, ethyl or propyl esters.

As regards broccoli or broccoli extract, the essential compounds are glucosinolates, found in particular in crucifers, and capable of transforming into sulphoraphanes.

The invention therefore extends to the use of glucosinolates and sulphoraphanes, of extraction or of synthesis, including produced by microorganisms, as well as to plants or plant extracts containing them, in particular cruciferous or extracts of cruciferous, preferably broccoli or broccoli extract.

Carotenoids and their derivatives can be used. We will prefer lycopene.

The compositions according to the invention can comprise at least one plant extract including at least one of the compounds chosen from the heteropolysaccharide, carotenoid, glucosinolate and / or sulphoraphane group. These compositions can therefore be formed, with regard to the compounds of the invention, partially or exclusively of plant extracts.

In all cases, natural extraction products can be supplemented or replaced by similar synthetic products, including those produced by microorganisms. The invention also intends to cover all derivatives and compounds equivalent to the compounds according to the invention which retain the properties used here.

The compositions according to the invention are preferably in the following forms: - for a therapeutic or non-therapeutic application, eg dietetic, preferably by oral route: in liquid or dry form or any other intermediate form comprising all extractable forms of said components: fluid extract, lyophilisate, atomiser, plant powder; formulated for example in capsules, drinks, tablets, etc. - for a cosmetic application: topical or transcutaneous route, for epidermal distribution, or oral application.

Any excipient which can be used by those skilled in the art for the preparation of aqueous solid or liquid formulas, or emulsions of any type (W / O, O / W, or triple emulsion), can be used in the context of present invention. The two-component compositions advantageously comprise in%:

- from 40 to 90, preferably from 60 to 80 of heteropolysaccharide, e.g. pectin, and

- from 10 to 60, preferably from 20 to 40 of extract containing lycopene, (such an extract contains from 3 to 6% of lycopene), or

- from 10 to 60, preferably from 20 to 40, of an extract containing glucosinolate and / or sulphorophane, e.g. broccoli extract (such an extract contains from 2000 to 5000 ppm / kg).

In the case of a three-component composition, there is advantageously in%:

from 1 to 20, preferably from 5 to 10, of extract containing carotenoid, e.g. lycopene, (such an extract contains from 3 to 6% of carotenoid), and

- from 5 to 40, preferably from 10 to 35 of extract containing glucosinolate and / or sulphorophane, e.g. broccoli extract (such an extract contains from 2000 to 5000 ppm / kg).

The present invention is intended to apply to both the therapeutic and non-therapeutic fields according to the regulations in force, methods of use and doses administered. It can in particular be used in the non-therapeutic field both in cosmetics and in dietetics, the objective then being essentially preventive and the use left to the free choice of the user. In this case, it is possible to envisage dietary compositions, in particular based exclusively or partially on plant extracts, or in the cosmetic field in the form of ointments and analogues applied to the skin, or in the form of oral hygiene products. , such as toothpaste, dental solution, etc. In the therapeutic field, these compositions may be used in curative treatment, for example in the event of intoxication with heavy metals, or also as a preventive measure in a medical context in subjects at risk, such as people working in contact with heavy metals ( eg in the paint industry) or in nuclear power plants.

The present invention therefore also relates to the use of the compositions according to the invention, preferably tri-components, for the preparation of a medicament, for example a medicament intended for trapping heavy metals, in particular lead, mercury, cadmium. , nickel and their radionucleides, especially mercury.

A subject of the invention is therefore also such a medicament, eg intended for trapping heavy metals and their radionucleides, in particular mercury, comprising a composition according to the invention, preferably tri-components, and a pharmaceutically acceptable excipient, in particular for a oral administration, this pharmaceutical excipient being able to be any usual excipient, in particular solid or liquid, preferably adapted for an oral administration. It may in particular be granules, or any other solid or liquid form, comprising from 15 to 40%, in particular from 20 to 30%, eg 25% of bi- or tri-component composition as described above, and a QSP100 excipient.

The subject of the invention is also a method of therapeutic, curative or preventive treatment, preferably curative, in particular intended to trap the heavy metals and their radionucleides, comprising the administration of such a drug.

The medicament may be administered in particular at a rate of 8 to 30 g of two- or three-component composition per day, preferably from 15 to 25 g / day. A subject of the invention is also the use of the compositions according to the invention for the preparation of external cosmetic preparations, in particular for their antioxidant and anti-radical action as well as their beneficial action on cell regeneration.

It therefore also relates to such an external cosmetic preparation comprising a composition according to the invention and an appropriate cosmetic excipient in particular suitable for topical application, in particular in the form of a lotion, ointment, body cream, etc.

It also relates to the use of the compositions according to the invention for the preparation of cosmetic products for oral hygiene, in particular mouthwashes, toothpastes, dental solutions or gels, in particular for trapping heavy metals, in particular the mercury contained in dental amalgams.

It therefore also relates to these cosmetic oral hygiene products comprising a composition according to the invention and the usual excipients of the type of product concerned (e.g. mouthwash, toothpaste, dental gel or solution). The incorporation of the compositions according to the invention, as associated active ingredient, in oral hygiene products also comes within the scope of the present invention.

It also relates to a cosmetic treatment method comprising the external or oral application to humans, of an external cosmetic or oral hygiene product according to the invention.

A subject of the invention is also the use of the compositions according to the invention for the preparation of dietetic products, in particular food supplements, for all the beneficial actions which have been mentioned above and these products will then preferably be in the form oral compositions, liquids or solids. The dietetic use essentially aims to take advantage of the preventive properties of the compositions according to the invention, eg with respect to heavy metals and their radionucleides, and antioxidant and anti-radical action. The invention therefore also relates to dietetic products comprising a composition according to the invention and optionally an excipient suitable for administration by the oral route. The incorporation of the compositions according to the invention, as associated active principle, in dietetic products, in particular food supplements, also comes within the scope of the invention. It also relates to the method consisting in administering, in particular orally, to humans, such a dietetic product.

Preferably, the dietetic products are administered orally at a rate of less than 8 g / d, eg from 1.5 to 6 g, in particular from 1.5 to 3.5 g, of bi-or tri-component composition, preferably based essentially on plant extracts as seen above, per day, in particular divided into several daily intakes. For example, take 3 to 6 capsules of 300 to 400 mg per day, the daily dose can be increased to 15 capsules.

Preferably, the cosmetic products are applied to the area to be treated at a rate of 10 to 100 mg per application, in particular at a rate of 2 to 3 applications per day.

According to a feature of the invention, the network-forming properties of heteropolysaccharides and in particular pectins can be used in other combinations of active compounds to promote their bioavailability and their transport. The invention therefore also relates to such a use of this type of compound for the production in particular of dietetic, cosmetic or medical compositions. It also relates to any dietetic, cosmetic or medical composition comprising this type of compound encapsulating one or more other active compounds.

The present invention will now be described in more detail using embodiments taken by way of nonlimiting examples. Example 1: Sources of compounds

Pectin can be obtained from any plant containing it, in particular apple, citrus, by known techniques. It is also possible to use commercially available pectins, in particular those sold by Herbstreith & Fox, in particular the pectin sold under the name Pectin Classic. AU 701 You can also use a plant extract, eg apple or citrus, naturally containing pectin which can be enriched by a supply of purified or synthesized pectin

Lycopene or psi-carotene (Cl n ° 75125, E160 (d) (trans), CAS n ° 502- 65-8) is extracted from the tomato according to methods known to those skilled in the art

One can also use a vegetable extract, in particular of tomato, naturally containing lycopene which one enriches by a contribution of lycopene or other carotenoid purified or synthesized According to a preferred mode the fresh broccoli is treated by cryogenics, then lyophilized

For the synthesis of sulphoraphane (CAS 4478-93-7), see e g J K Whitesell et al, J Org Chem 1994, 59, 597-601

Note that broccoli is also a source of beta-carotene and therefore that the use of an appropriate broccoli extract will advantageously supplement the composition according to the invention with a carotenoid.

Similarly, we can choose to take advantage of the other chemical compounds included in broccoli and known to have anti-carcinogenic activity or against cell degeneration flavonoids and polyphenolic derivatives, other glucosinolate derivatives (eg glucobrassicin), S- methylcysteine sulfoxide and its derivatives

In general, for the carotenoid, in particular lycopene, and broccoli, it will be preferable to use natural plant extracts, according to the process described below. Method of obtaining:

Broccoli is a vegetable belonging to the cruciferous family, which contains substances very sensitive to the phenomenon of redox as well as to the phenomenon of enzymatic lysis. Like its sisters in the cruciferous family, it has the particularity of containing sulfur glucosides (glucosinolates) which under the attack of certain enzymes (myrosinases, catalases) transform this compound into isothyocyanates or derivatives (sulphoraphanes) which are responsible for very characteristic smell of this family. These compounds are very volatile and oxidize quickly, making any preparation of dry plants ineffective.

The applicant was able to develop an appropriate procurement process.

The principle of this process of obtaining consists in:

- use fresh broccoli and freeze it so that the cells burst

- pre-grind this plant in an appropriate device - perform a cryogenic grinding using any cryogenic source, e.g. liquid nitrogen

- a micronized powder is obtained which is then lyophilized.

The broccoli powder is then collected and mixed with the other ingredients of the preparation. The evaporation water from the freeze-dryer freeze trap is then recovered, it is concentrated by reverse osmosis at a temperature not exceeding 15 ° C. The volume of concentrated solution is reduced to the proportion of 1/100 (1 liter of concentrate for 100 liters of RO water).

This water contains part of the volatile substances of the plant; it is then reintroduced into the final preparation according to the process described below.

Preparation of the final mixture:

The mixing of pectins of various esterifications is carried out in a band mixer (Comia Fao type) or any other type of mixer; when the mixture is homogeneous, the tomato oleoresin is added in small portions, then the broccoli osmosis water. This addition has the particularity of creating a network at the fiber level which very advantageously leads to an encapsulation of the active substances (which in particular makes it possible to ensure the bioavailability of the added compounds (eg carotenoid and / or glucosinolate and / or sulphoraphane, etc.). .) and their transport); the lyophilized broccoli powder is then added, then finally a colloidal silica-type substance (eg AEROSIL) allowing the preparation to be dehydrated.

The mixture thus prepared is ready for the various applications.

Example 2: Dietary composition

Anti-free radical product

%

Pectins of varying degree of esterification 65

Concentrated tomato extract 10

Broccoli lyophilisate 20

Raw carrot concentrate 2

Rosa gallica extract 2

Acerola powder 1

Example 3: Dietary composition

Product with depolluting action

% Pectins of varying degree of esterification 65 Concentrated tomato extract 10

Broccoli lyophilisate 25

EXAMPLE 4 Dietetic Composition

Product for cholesterol-lowering purposes% Pectins of varying degree of esterification 65

Concentrated tomato extract 5

Broccoli lyophilisate 15

Inulin 15 Example 5: Cosmetic composition Product with depolluting action and cellular protector

%

Water QSP 100

Carbomer 0.5

0.7 xanthan gum

Glycerin 5

Mixture of parahydroxybenzoate esters 0.5

Pectins of varying degree of esterification 3.25

Concentrated tomato extract 0.5

Broccoli lyophilisate 1, 25

Fragrance 0.2

Example 6 Composition of Oral Hygiene Product (Toothpaste)

Water QSP 100

Glycerin 25

Silica 22

0.22 sodium fluoride

Saccharin 0.1

Menthane 0.05

Pectin of various degrees of esterification 1,625

Concentrated tomato extract 0.250

Broccoli extract 0.625

Sodium lauryl sulfate 0.2 Preservative 0.5

Example 7 Effect of a composition according to the invention on the toxicity of mercury in rats.

The preventive and curative properties of a composition according to the invention (comprising 70.8% pectin, 5.2% concentrated tomato extract and 24% broccoli lyophilisate) were evaluated with respect to mercury. in rats. The preventive properties were evaluated by simultaneously administering HgCI ₂ and the composition. The healing properties were evaluated by administering HgCI ₂ alone to rats for 2 weeks, then by treating with the composition for the following 2 weeks.

Duration of treatment: 28 days. Non-lethal doses of mercury were administered and no direct deaths were observed. On the other hand, mortality was observed during anesthesia performed on certain rats not treated with the composition. The composition, on the other hand, protected the treated rats; the action of mercury on anesthesia was inhibited by the composition.

The blood mercury concentrations were measured on D15 for the animals of groups 2 and 3, then on D28 for the animals of the 4 groups. The average values are given below: - at D 15:

Group 2: 308.0 μg Hg / I

Group 3: 147.33 μg Hg / I, ie a reduction of 51.47% in the presence of the composition according to the invention (significance p <0.001)

at D 28

Conclusion: The composition significantly reduces blood mercury concentrations, both preventive and curative.

Claims

1. Composition comprising at least one heteropolysaccharide and a compound chosen from the group consisting of carotenoids and glucosinolate and / or sulphoraphane and mixtures thereof.

2. Composition according to claim 1, characterized in that the carotenoid is lycopene.

3. Composition according to claim 1 or 2, characterized in that it comprises at least one heteropolysaccharide, a carotenoid, preferably lycopene, and glucosinolate and / or sulphoraphane.

4. Composition according to any one of claims 1 to 3, characterized in that the heteropolysaccharide is a polygalacturonic acid or an ester of polygalacturonic acid.

5. Composition according to Claim 4, characterized in that the polygalacturonic acid is a pectin.

6. Composition according to any one of claims 1 to 5, characterized in that it comprises at least one plant extract including at least one of the compounds chosen from the heteropolysaccharide, carotenoid, glucosinolate and / or sulphoraphane group.

7. Composition according to claim 6, characterized in that it comprises broccoli or a broccoli extract.

8. Composition according to one of claims 1 to 7, characterized in that it is in two-component form and comprises in%: - from 40 to 90, preferably from 60 to 80 of heteropolysaccharide and

- from 10 to 60, preferably from 20 to 40 of extract containing lycopene, or

- from 10 to 60, preferably from 20 to 40 of extract containing glucosinolate and / or sulphoraphane.

9. Composition according to one of claims 1 to 7, characterized in that the composition has three components and comprises in%:

- from 40 to 90, preferably from 60 to 80 of heteropolysaccharide

from 1 to 20, preferably from 5 to 10, of extract containing carotenoid, preferably lycopene, and

- from 5 to 40, preferably from 10 to 35 of extract containing glucosinolate and / or sulphoraphane.

10. A medicament comprising a composition according to any one of claims 1 to 9, and a pharmaceutically acceptable excipient.

11. Medicament according to claim 10. characterized in that it comprises a solid or liquid excipient suitable for oral administration.

12. Medicament according to claim 10 or 11, characterized in that it is intended to trap heavy metals and their radionucleides, in particular mercury.

13. Use of a composition according to any one of claims 1 to 9, for the preparation of a medicament intended to trap heavy metals and their radionucleides.

14. Use according to claim 13 for the preparation of a medicament intended to trap mercury.

15. Oral care product, comprising a composition according to one any of claims 1 to 9 and a suitable cosmetic excipient.

16. Product according to claim 15, characterized in that it is in the form of a shower bath, toothpaste, or dental solution or gel.

17. External cosmetic product comprising a composition according to any one of claims 1 to 9 and an appropriate cosmetic excipient.

18. Dietetic product comprising a composition according to any one of claims 1 to 9.