CA2387858A1

CA2387858A1 - Method for supercritical fluid extraction

Info

Publication number: CA2387858A1
Application number: CA002387858A
Authority: CA
Inventors: Philippe Mengal
Original assignee: HITEX
Current assignee: Individual
Priority date: 1999-10-19
Filing date: 2000-10-06
Publication date: 2001-04-26
Also published as: WO2001028649A1; AU7795800A; ATE241412T1; FR2799660B1; EP1222008A1; DE60003057D1; EP1222008B1; JP2003516217A; FR2799660A1

Abstract

The invention relates to a method for extracting one or more active compounds from a starting material using a supercritical fluid, said compounds being for introduction into the formulation of a cosmetic, pharmaceutical or food composition containing at least one excipient. The inventive method comprises the following steps: placing said starting material containing the active compounds in the presence of at least one extraction fluid in a supercritical state and containing CO2 and at least one co-solvent; separating said extraction fluid containing at least a proportion of the active compound(s);
causing the CO2 contained in the extraction fluid to vaporize in order to obtain an extract consisting of said co-solvent and said proportion of the active compound(s); recovering the extract consisting of the co-solvent/active compound mixture. The method is characterised in that said co-solvent consists of said excipient.

Description

METHOD FOR SUPERCRITICAL FLUID EXTRACTION
The invention relates to the field of methods to extract active compounds from raw materials of natural origin, to obtain active extracts used in the 5 formulation of cosmetic, pharmaceutical or nutritional formulations.
The natural extracts particularly obtained from plants, algae, biomasses or beehive products have been used traditionally for a long time in the field of cosmetics, dermo-pharmaceuticals, pharmaceuticals or nutrition.
Numerous extraction methods are traditionally implemented to obtain said 10 extracts: hydro-distillation, organic solvent extraction, hydroglycolic maceration, leaching, decoction, etc.
These traditional methods comprise advantages, essentially related to the simplicity of the technologies used, but also drawbacks. These drawbacks include the following problems:
15 - presence of residual solvents in the case of organic solvent extraction;
poor stability of extracts obtained by means of maceration;
- very long contact time for hydroglycolic macerations;
- low selectivity of extraction in general, inducing excessively strong extract colouring.
20 Beyond the image of the "natural product", the cosmetic and dermopharmaceutical industry now seeks very stable products, selective extracts rich in active ingredients. In addition, the cost of the extracts must be optimised.
It is known in the prior art that a fluid in the supercritical state, i.e. in a state characterised either by a pressure or temperature respectively greater than 25 the critical pressure and temperature in the case of a pure substance, or by a representative point (pressure, temperature) beyond the range of critical points represented on a diagram (pressure, temperature) in the case of a mixture, has, for very numerous substances, a high solvent power, in no way comparable to that observed in the same fluid in the compressed gas state.
30 For this reason, said fluids are used in numerous extraction (solid/fluid), fractionation (liquid/fluid) analytical or preparatory chromatography and material (ceramics, polymers, etc.) processing methods.
It is important to note that the physicochemical properties of carbon dioxide (C02) and its critical co-ordinates (critical pressure: 7.4 MPa and critical 35 temperature: 31°C) make it a preferential solvent in numerous applications, in particular, it shows no toxicity and is available at a high level of purity in very large quantities at low prices.
This technology makes it possible to obtain very high-quality custom-made extracts, depending on the choice of operating parameters. Indeed, the 5 solvent power of supercritical C02 varies as a function of the extraction pressure and temperature. Oils rich in polyunsaturated fatty acids or very high-quality non-saponifiable matter-rich fractions are obtained in this way using this technology.
The drawback of supercritical C02 extraction is the high cost related to the low solvent power of pure, C02 which limits its application to a few specific 10 areas. In order to increase the solvent power of supercritical C02 and therefore increase the productivity of the method, it is possible to add to the supercritical C02 a co-solvent such as ethanol, methanol or acetone. The solvent power of supercritical C02 can then be increased by a factor of 10. Unfortunately, the gain in productivity is compensated by the need to eliminate the solvent from the 15 extract, which first of all involves an additional distillation/drying operation and, secondly, frequently induces stability problems.
The main objective of the present invention is to propose a new supercritical C02 extraction method not involving the above-mentioned drawback.
20 The objective of the present invention is also to propose such a method which is simpler than the supercritical fluid extraction methods according to the prior art.
These objectives are achieved through the invention which relates to a method of preparing a cosmetic, pharmaceutical or nutritional formulation 25 containing an excipient and one or more active compounds, said one or more active compounds having been extracted from a raw material by means of supercritical fluid, comprising steps consisting of:
- placing said raw material containing the active compounds in the presence of at least one extraction fluid in the supercritical state comprising C02 30 and at least one co-solvent, - separating said extraction fluid containing at least part of the active compound(s), - inducing the vaporisation of the C02 contained in the extraction fluid to obtain an extract composed of said co-solvent and said part of the active 35 compound(s), - recovering said extract composed of the co-solvent/active compound mixture, characterised in that, the said excipient of said formulation is composed of said co-solvent.
Therefore, the present invention is based on the discovery that certain excipients compatible with use in cosmetics, dermo-pharmaceuticals, pharmaceuticals or nutrition may be used in a mixture with supercritical COZ.
This mixture then behaves like a fluid wherein the solvent power can be adjusted by modifying the proportion of C02/excipient or by adapting the extraction 10 pressure and temperature.
Therefore, the invention use the properties of supercritical fluids or pressurised liquids, to which an excipient has been added, and comprising, under suitable temperature and pressure conditions, an increased dissolution power with respect to the active compounds to be extracted, an improved selectivity while I S limiting the risks of degradation of the active compounds considerably, said compounds being protected during the extraction method.
The excipient-active compound mixture may also correspond to the final formulation, which represents a significant advantage.
According to a preferential aspect of the invention, the method according to said 20 invention comprises an additional step consisting of recycling the vaporised COZ, at the start of the method where it can be condensed, pumped and heated to be returned to the supercritical state.
According to an alternative version, the method comprises a preliminary step consisting of adding said excipient to the C02 in the supercritical state to 25 obtain said extraction fluid.
According to another alternative version, the method comprises a preliminary step consisting of adding said excipient to the pressurised liquid and then heating the mixture obtained to change the C02 to the supercritical state and obtain said extraction fluid.
30 According to another preferential aspect of the invention, said extraction fluid comprises a temperature between approximately 31 °C and 100°C and a pressure between approximately 7.4 MPa and 50 MPa.
The excipients which may be used within the scope of the present invention may be any compound or mixture of compounds compatible with 35 cosmetic, dermo-pharmaceutical, pharmaceutical or nutritional use showing a sufficient solubility in pressurised COZ. In this way, glycerol, an excipient conventionally used in cosmetics, which is strictly insoluble in C02, cannot be selected, while other compounds showing a low but non-zero solubility, may be validly used.
Preferentially, depending on whether the formulation is intended for a 5 cosmetic, pharmaceutical, dermo-pharmaceutical or nutritional product, said excipient is selected from the group composed of propylene glycol, butylene glycol, polyethylene glycols of all molecular weights, diethylene glycol monoethylether, hexylene glycol, polyols, glyceride fatty substances, non-glyceride fatty substances, esters, waxes, silicone oils and terpenic compounds.
10 Advantageously, the method according to the invention is implemented with proportions by weight of (raw material)/(C02)/(Excipient) of (10)/10 to 2000)/( 1 to 200).
The invention also relates to any extract obtained by means of a single extraction method characterised in that it is composed of one or more active 15 compounds and of at least one excipient used in the formulation of a cosmetic, pharmaceutical or nutritional product.
The extracts obtained using the method according to the present invention may be used in any pharmaceutical form used in cosmetics or dermo-pharmaceuticals: oil in water and water in oil emulsion, shampoos and 20 conditioners, milks, lotions, gels, ointments, hair sprays, without this list being exhaustive. They may also be used in the field of nutrition and pharmaceuticals.
It is possible to incorporate the extracts obtained using the method according to the invention in cosmetic vectors such as liposomes, chylomicrons, macro, micro and nanoparticles, and macro, micro and nanocapsules. They may 25 be absorbed on powdered organic polymers, talcum powders, bentonites and other mineral substrates.
The extracts obtained using the method according to the present invention may be combined in cosmetic formulations with any other ingredient generally used in cosmetics and dermo-pharmaceuticals: lipids, gelling and viscous 30 polymers, surfactants and emulsifiers, hydro or liposoluble active ingredients, extracts of other raw materials.
The cosmetic or dermo-pharmaceutical formulations containing the extracts obtained using the method according to the present invention, are intended for all cosmetic and dermo-pharmaceutical applications, in particular:
35 care and hygiene for the skin, scalp, hair, mucous membranes, oral care, for anti-ageing treatments and sun protection, for moisturisation, smoothing effects or any other applications.
The invention and the advantages it offers will be understood more clearly using the examples of embodiments described below.

Example 1 The present example represents a comparative example between conventional supercritical C02 extraction and extraction, according to an alternative version of the method according to the present invention, of ginger 10 extract.
According to the conventional method, supercritical COZ extraction is performed with no co-solvent at 300 bar and 50°C. 9 g of extract is collected by percolating 6 kg of C02 on 30 g of previously ground ginger and 11 g of extract is collected by percolating 12 kg of C02. Under these conditions, the pasty and 15 "sticky" extract obtained has a powerful odour and flavour, characteristic of the raw material, while the residue is almost deodorised.
According to the invention, the method is then implemented under the same pressure and temperature conditions but in the presence of a co-solvent, i.e.
propylene glycol, in a mixture with COZ at a rate of 10 g per 1 kg of C02.
20 The use of a co-solvent makes it possible to increase the performance of the extraction method.
More specifically, by means of the invention, 5 kg of C02 propylene glycol mixture is sufficient to obtain a product composed of ginger extract and propylene glycol showing an aromatic power (for example according to the 25 Scoville index as defined in the publication "Epices et aromates" -editions Lavoisier - 1992) equivalent to that of the extract obtained with no co-solvent using 12 kg of C02. In addition, the product obtained using the invention contains the co-solvent as an excipient and, for this reason, has a fluid appearance, rendering it much easier to handle and formulate in a nutritional preparation.

Example 2 In this example, conventional supercritical C02 extraction of white pepper is compared to extraction according to an alternative version of the method according to the present invention.
35 In the supercritical C02 extraction with no co-solvent at 300 bar and 40°C, 10 g of extract is collected by percolating 20 kg of C02 on 500 g of crushed white pepper. Under these conditions, the resinous extract obtained has a powerful and spicy flavour, characteristic of the raw material.
Under the same pressure and temperature conditions, adding propylene glycol at a rate of 10 g per 1 kg of C02 makes it possible to increase the performance of the method. Under these conditions, 10 kg of C02 propylene glycol mixture is sufficient to obtain the same aromatic power, while the fluid extract obtained is easy to handle and formulate in a nutritional preparation.
Example 3 10 This example is an alternative version of example 2 for which propylene glycol is replaced by groundnut oil added at a rate of 5 kg per COZ. The oily extract obtained is particularly suitable for the formulation of nutritional preparations in the presence of other fatty substances.
15 Example 4 In this example, conventional supercritical C02 extraction of paprika powder is compared to extraction according to an alternative version of the method according to the present invention.
In the supercritical C02 extraction with no co-solvent at 300 bar and 20 60°C, the extract yield is very low, even for high quantities of percolated C02.
When 5% ethanol is added to the C02 to increase the solvent power, 30 kg of C02 + alcohol mixture is required to obtain a "colour yield" of 50 g of oleoresin at 110,000 CU (CU: Colour Units according to the American Spice Trade Association Analytical Methods (1986) standard / ASTAA New York 25 Method No. 20.0), per 1 kg of paprika after evaporating the alcohol.
By implementing the method according to the present invention by adding S g of propylene glycol per kg of C02, the same colour yield is achieved i:or mg of C02 propylene glycol mixture per 1 kg of paprika. The extract collected by decantation, including the co-solvent, has a colour yield of over 200,000 CU, 30 without having to evaporate the co-solvent.
Example 5 In this example, conventional supercritical C02 extraction of parthenolide from Tanacetum parthenium is compared to extraction according to an alternative 35 version of the method according to the present invention.

In the supercritical C02 extraction with no co-solvent at 300 bar and 40°C, 14.8 g of resinous dark green extract is collected by percolating 8 kg of C02 on 300 g of ground drug. The extract analysed by gas chromatography has a parthenolide titre of 14.5%. Therefore, the parthenolide yield is 14.8 x 0.145/300 = 0.715%. Since the batch of plant used has a parthenolide titre of 0.8%, !~0%
can be considered to have been extracted. In order to increase its shelf life and enable the formulation of this extract in soft capsules, the raw extract must be diluted with a glyceride oil.
Under the same pressure and temperature conditions, the extraction was 10 carried out by adding to the COZ 0.5% of a capric and caprylic acid triglyceride mixture. By percolating 6 kg of this mixture successively on 300 g of drug followed by 1 kg of pure C02, 40.5 g of slightly coloured oily extract is collected.
Since this extract has a parthenolide titre of 5.5% (w/w), it can be formulated as is and packaged in soft capsules.

Example 6 In this example, conventional supercritical C02 extraction of kawa lactones from kawa-kawa (Piper methysticum) is compared to extraction according to an alternative version of the method according to the present 20 invention.
In the supercritical C02 extraction with no co-solvent at 300 bar and 40°C, 21.5 g of viscous orange yellow extract is collected by percolating 10 kg of C02 on 350 g of ground plant. The extract analysed by HPLC has a total kawa lactone titre of 85%. This extract must then be standardised to 30% kawa lactones 25 by mixing it with an excipient.
By carrying out the extraction according to the method according to the present invention by adding to the C02 2% (w/w) of capric and caprylic acid triglycerides, the oily bright yellow extract collected is standardised at 30%
kawa lactones, limiting active ingredient loss by degradation.

Example 7 In this example, conventional supercritical C02 extraction of Calendula flowers is compared to extraction according to an alternative version of the method according to the present invention.
35 With the extraction with supercritical C02 to which 3% of a capric and caprylic acid triglyceride mixture is added, extraction kinetics of the lutein used as a tracer which are twice as rapid as with the C02 extraction with no excipient are observed. In addition, the extract obtained using the method according to the present invention is much easier to use in dermo-pharmaceutical and cosmetic preparations.
Example 8 This example is an alternative of example 7 for which part of the water contained in the Calendula flowers is co-extracted. The extract offers the appearance of an emulsion wherein the properties are of interest in dermo-10 pharmaceutical and cosmetic preparations.
The embodiments of the invention described here are in no way intended to reduce the scope of the invention. Therefore, numerous modifications may be made to the invention, without leaving its scope.

Claims

9

1. Method of preparing a cosmetic, pharmaceutical or nutritional formulation containing an excipient and one or more active compounds, said one or more active compounds having been extracted from a raw material by means of supercritical fluid, comprising steps consisting of:
- placing said raw material containing the active compounds in the presence of at least one extraction fluid in the supercritical state comprising CO2 and at least one co-solvent, - separating said extraction fluid containing at least part of the active compound(s), - inducing the vaporisation of the CO2 contained in the extraction fluid to obtain an extract composed of said co-solvent and said part of the active compound(s), - recovering said extract composed of the co-solvent/active compound mixture, characterised in that, the said excipient of said formulation is composed of said co-solvent.

2. Method according to claim 1, characterised in that it comprises a step consisting of recycling the vaporised CO2.

3. Method according to any of claims 1 or 2, characterised in that it comprises a preliminary step consisting of adding said excipient to the CO2 in the supercritical state to obtain said extraction fluid.

4. Method according to any of claims 1 or 2, characterised in that it comprises a preliminary step consisting of adding said excipient to the pressurised liquid CO2 and then heating the mixture obtained to change the CO2 to the supercritical state and obtain said extraction fluid.

5. Method according to any of claims 1 to 4, characterised in that said extraction fluid comprises a temperature between approximately 31°C and 100°C
and a pressure between approximately 7.4 MPa and 50 MPa.

6. Method according to any of claims 1 to 5 characterised in that said excipient is selected from the group composed of propylene glycol, butylene glycol, polyethylene glycols of all molecular weights, diethylene glycol monoethylether, hexylene glycol, polyols, glyceride fatty substances, non-glyceride fatty substances, esters, waxes, silicone oils and terpenic compounds.

7. Method according to any of claims 1 to 6, characterised in that it is implemented with proportions by weight of (raw material)/(CO2)/(Excipient) of (10)/10 to 2000)/(1 to 200).