WO2008142175A1 - Procedimiento de obtencion de escualeno - Google Patents

Procedimiento de obtencion de escualeno Download PDF

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Publication number
WO2008142175A1
WO2008142175A1 PCT/ES2008/000083 ES2008000083W WO2008142175A1 WO 2008142175 A1 WO2008142175 A1 WO 2008142175A1 ES 2008000083 W ES2008000083 W ES 2008000083W WO 2008142175 A1 WO2008142175 A1 WO 2008142175A1
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WO
WIPO (PCT)
Prior art keywords
squalene
saponification
carried out
base
unsaponifiable fraction
Prior art date
Application number
PCT/ES2008/000083
Other languages
English (en)
Spanish (es)
French (fr)
Inventor
Manuel Aguado Ramos
Antonio Martin Martin
Arturo Chica Perez
Maria Angeles Martin Santos
Mónica BERRIOS CABALLERO
Jose Angeles Siles Lopez
Original Assignee
Universidad De Cordoba
Pradomudo, S.L.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universidad De Cordoba, Pradomudo, S.L. filed Critical Universidad De Cordoba
Publication of WO2008142175A1 publication Critical patent/WO2008142175A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C7/00—Purification; Separation; Use of additives
    • C07C7/005—Processes comprising at least two steps in series
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C11/00—Aliphatic unsaturated hydrocarbons
    • C07C11/21—Alkatrienes; Alkatetraenes; Other alkapolyenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C7/00—Purification; Separation; Use of additives
    • C07C7/04—Purification; Separation; Use of additives by distillation

Definitions

  • the present invention falls within the chemical and agri-food sector, more specifically the invention relates to a process for obtaining squalene from distillates of physical refining of olive oil.
  • Squalene is a precursor of cholesterol and this in turn of the hormone Dehydroepiandrosterone (DHEA), which gives an important role in restoring the normal values of this hormone, which with age or significantly decrease in humans.
  • DHEA Dehydroepiandrosterone
  • This hormone is attributed with properties such as the improvement of neurological performance, concentration, memory and the decrease in fat accumulation at the abdominal level. Squalene also has antioxidant properties and the ability to repolarize cell membranes, controlling their repair. 5
  • Olive oil is made up of a saponifiable fraction, which represents more than 98% of the oil and an unsaponifiable fraction constituted between 1.5% and 0.5%.
  • the constituents of the saponifiable fraction are triglycerides, diglycerides, terpenic alcohols and free fatty acids.
  • the constituents of the unsaponifiable fraction are sterols, terpene dialcohols, triterpenic alcohols, aliphatic alcohols, tocopherols, steroidal hydrocarbons, terpenic hydrocarbons (squalene), phenolic and flavonoid compounds, pigments, volatile compounds responsible for the aromas of the oils.
  • Squalene is the main constituent of the unsaponifiable fraction and can reach up to 40% of the total weight.
  • Patent ES2162742 describes a process for obtaining squalene from the by-product obtained from the physical refining (neutralizing distillation / deodorization) of olive oil, which consists in extracting the physical refining fatty acids, with water, an apolar solvent. and another polar, to obtain two miscelas: one polar and one non-polar. Then the polar miscela is decomposed to produce two miscelas: one of alcohol / water and the other of alcohol / polar solvent / fatty acids.
  • the solvents of the said miscelas are recovered to obtain a squalene concentrate from the non-polar miscellany and a fractional distillation of the squalene concentrate thus obtained is carried out, to obtain three fractions: one light, one squalene and another heavy Finally, the fraction rich in squalene is cooled for purification.
  • Patent ES2186380 describes a process for obtaining phytosqualane from a residue from the process of obtaining various vegetable oils. The residue is subjected to an esterification step of the fatty acids it presents, to a distillation and is hydrogenated. Finally it is treated with various reagents, washed and deodorized to obtain high purity phytosqualane.
  • Patent ES8602102 refers to a process for obtaining squalene and squalene from by-products of physical refining and / or deodorization of vegetable oils.
  • the described procedure consists in subjecting the by-products of the physical refining and / or deodorization of olive and pomace vegetable oils, previously catalytically hydrogenated, to an alkaline saponification followed by a continuous extraction with solvents of squalene and / or squalane from the mass of soap.
  • US2004015033 the same raw material is used as in the aforementioned patents, differentiating the procedure in which an extraction is carried out under supercritical conditions.
  • Patent ES2238183 describes a process for obtaining compounds of high added value from the olive leaf.
  • the sheets are subjected to solid-liquid extraction with organic solvents, preferably hexane or ethanol, and the crude extract obtained is concentrated in vacuo.
  • organic solvents preferably hexane or ethanol
  • the crude extract obtained is concentrated in vacuo.
  • a fractionation of the crude extract is performed by countercurrent extraction in column with supercritical carbon dioxide. This procedure allows to extract from the olive leaf natural products such as waxes, squalene, oleuropein, hydroxytyrosol and other phenolic compounds and terpenic alcohols.
  • the invention provides a process for obtaining squalene, from distillates of physical refining of olive oil.
  • this provides a process for obtaining squalene from the distillation of physical refining of olive oil as a raw material, characterized in that it comprises the steps of: a) alkaline saponification of the raw material: b) physical separation of the saponifiable and unsaponifiable fraction; and c) molecular distillation of the unsaponifiable fraction.
  • reaction times between 1 and 6 hours, with a time between 1 and 3 hours being more preferred.
  • an excess of base is used in the alkaline saponification stage with respect to the saponification index of the oil used.
  • oils with a saponification index of between 175 and 240 mg base / g fat are used. More preferred are oils with a saponification index of between 180 and 210 mg base / g fat.
  • the raw material used to obtain squalene is the oleins from the physical refining of olive oil.
  • said oleins have the analytical characteristics indicated in Table 1.
  • a base weight / fat ratio of between 0.2 and 1 is used, 0.5 being more preferred.
  • the weight / total water / fat ratio preferably said ratio is between 1 and 12, with 5 being more preferred.
  • alkaline saponification is carried out using a base selected from the group consisting of NaOH, KOH, Ca (OH) 2 , Mg (OH) 2 .
  • a base selected from the group consisting of NaOH, KOH, Ca (OH) 2 , Mg (OH) 2 .
  • KOH being particularly preferred.
  • the saponification process is carried out at a temperature between 40 and 100 0 C.
  • the temperature is between 70 and 90 0 C.
  • the saponification stage (a) is performed in the presence of a hydrotrope.
  • Hydrotropy is the property that various compounds (alkaline and alkaline earth salts of organic acids) possess in whose concentrated aqueous solutions certain organic compounds that are otherwise insoluble or hardly soluble (for example proteins, carbohydrates, aniline, nitrobenzene) are well solubilized. ).
  • the hydrotropic compounds reduce the surface tension of the water, thus facilitating the dispersion of the substances to be dissolved.
  • the dissolved substance can be separated by hydrotropic dilution.
  • Hydrotropic compounds find a wide scope of application in the chemical industry as solvents. They are fireproof, harmless and easily regenerable.
  • the hydrotrope is selected from the group consisting of sodium xylenesulfonate, ammonium xylenesulfonate, metaxylenesulfonate, ethylbenzene sulfonate, urea, sodium eumene sulfonate, ammonium sulfonate, paratoluen sulfonic acid and sodium toluene sulfonate.
  • sodium xylenesulfonate, metaxylenesulfonate and ethylbenzene sulfonate Particularly preferred is the use of a 45% solution of sodium xylenesulfonate (w / w) in water.
  • any suitable method for the physical separation of the saponifiable and unsaponifiable fractions can be employed.
  • said separation can be carried out by centrifugation.
  • the percentage of squalene wealth in the unsaponifiable fraction after stage b) is at least 75%; while the percentage of squalene richness after the molecular distillation process is at least 90%, preferably more than 95%, and particularly preferred more than 98%.
  • successive liquid-liquid extractions of the fat-soluble impurities present in the unsaponifiable are performed, which are preferably carried out with water in a 1/1 ratio (VA /) regarding the unsaponifiable.
  • a stage of purification of the unsaponifiable fraction is carried out by the use of adsorbent materials for the elimination of undesirable materials.
  • said adsorbent material is an adsorbent clay or non-activated earth ( ⁇ 10% by weight).
  • said purification is carried out under vacuum at a temperature between 40 and 100 0 C.
  • the oleins (2) together with the base (4), the hydrotrope (3) and the water (5), are added to the reactor (1) and once the saponification process is finished, the saponifiable fraction (7A) and unsaponifiable fraction are separated (6A).
  • the saponifiable fraction is centrifuged to recover the unsaponifiable 6B occluded therein, the majority of the squalene present in the starting sample remaining in the unsaponifiable fraction (6A + 6B).
  • the unsaponifiable fraction is centrifuged (8) to remove the remains of soap (9) it contains and then it is subjected to successive liquid-liquid extractions, in a discontinuous full-mix extractor (10), with water (11) to remove water-soluble impurities (12).
  • the sample is centrifuged again (13) to remove the aqueous remains it contains (14). In this way the fraction of unsaponifiable free of water-soluble substances is obtained.
  • the unsaponifiable fraction enriched in squalene is subjected to an adsorption purification process, preferably on an adsorbent clay (15) to remove undesirable substances (16).
  • the molecular distillation process (17) is carried out.
  • fractions with a squalene richness between 95 and 99% by weight (18 and 19) are obtained.
  • the determination of the percentage by weight of the squalene present in the fractions obtained has been determined by chromatographic techniques (20).
  • a method of determining the percentage of squalene applicable is by means of the gas chromatography, using the technique proposed by the European Union for the joint determination of squalene and waxes, separating the apolar fraction in the column and using a squalane solution as an internal standard (J European Union Commission, Regulation EEC / 183/93, Off. J. Eur. Common. L248 1993).
  • HPSEC high performance liquid exclusion liquid chromatography
  • refractive index detector which allows quantifying the remaining triglycerides in the sample, as well as the main groups of intermediate reaction compounds, monoglycerides and diglycerides , due to their differences in molecular weights.
  • Free fatty acids are also included in the hydrocarbon peak when the proportion found in the sample is very low (Standard IUPAC Method 2,508).
  • the quantification of the different groups of compounds is carried out based on their percentage over the total area obtained, since each of the chromatographic peaks corresponds to a complex group of compounds and the equality of the response factors is assumed.
  • Example 1 Procedure for obtaining squalene. Laboratory scale and pilot plant.
  • the experimental equipment used on a laboratory scale for the realization of the saponification was composed of a discontinuous stirred tank reactor that operated under isothermal conditions.
  • the reactor used was made of glass, cylindrical, of 2 L of useful volume and provided with a lid with a hermetic closing system.
  • the cover had several holes; one of them allowed the extraction of samples and another was connected to a condenser that minimized the loss of compounds by volatilization.
  • the condensation system was connected to a Frigiterm Selecta ® thermostatic bath through which water circulated at low temperature (5-8 0 C).
  • the thermostatization of the reactor was carried out through a jacket through which glycerin circulated from a thermostatic bath identical to the previous one, which allowed the heating of the internal contents of the reactor.
  • the process temperature was measured with a Testo 946 temperature probe.
  • the experimental equipment used consisted of a discontinuous full-mix reactor that was thermostated.
  • the reactor was metallic, 15 L capacity and had a hole in the upper part, where the reagents were added, and a lower opening, whereby the sample extraction was carried out.
  • the reactor had a jacket connected to a closed circuit through which glycerin circulated, which allowed the heating of the reaction medium.
  • Said heating system consisted of a 5 L capacity tank where the heating fluid was heated, a pump that allowed the circulation of the glycerin and several temperature probes.
  • the homogenization of the internal content of the reactor was achieved by a blade agitator that rotated by the action of an engine.
  • the reactor also presented several baffle partitions inside.
  • the set was equipped with a closet where the measuring devices and temperature control and degree of agitation were located.
  • the unsaponifiable fraction prewashed to remove soluble impurities enriched squalene he was subjected to a purification process by adsorption with not activated earth ( ⁇ 10 wt%), under vacuum and at a temperature between 40 and 100 0 C to remove substances undesirable
  • the distillation system consisted of a KDL 5 Short Route / Molecular Distillation distillation unit of UIC GMBH, whose characteristics are:
  • the determination of the percentage of squalene was carried out by gas chromatography, using the technique proposed by the European Union for the "Joint determination of squalene and waxes", separating the apolar fraction in a column and using a squalane solution as an internal standard [ J. European Union Commission, Reg ⁇ lation EEC / 183/93, Off, J. Eur. Commun, L248 (1993)]. The determination was made in duplicate, with a coefficient of variation of less than 5% in all cases.
  • samples were also analyzed by high efficiency liquid exclusion liquid chromatography (HPSEC) with refractive index detector, which allows quantifying the remaining triglycerides in the sample, as well as the main groups of intermediate reaction compounds, monoglycerides and diglycerides , due to their differences in molecular weights. Free fatty acids are also included in the hydrocarbon peak when the proportion found in the sample is very low (Standard IUPAC Method 2,508).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Water Supply & Treatment (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/ES2008/000083 2007-05-18 2008-02-14 Procedimiento de obtencion de escualeno WO2008142175A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES200701369A ES2308924B1 (es) 2007-05-18 2007-05-18 Procedimiento de obtencion de escualeno.
ESP200701369 2007-05-18

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WO2008142175A1 true WO2008142175A1 (es) 2008-11-27

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013156720A3 (fr) * 2012-04-16 2014-01-09 Roquette Freres Procédé de raffinage du squalène produit par microalgues
US9199897B2 (en) 2010-05-12 2015-12-01 Novartis Ag Methods for preparing squalene

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES8602102A1 (es) * 1985-01-25 1985-11-16 Derivan Sa Procedimiento para la obtencion de escualeno y escualano a partir de subproductos de la refinacion fisica y-o desodori-zacion de aceites vegetales
ES8706592A1 (es) * 1986-05-19 1987-07-16 Tadeval S A Procedimiento para la obtencion de escualano
ES2002428A6 (es) * 1986-10-21 1988-08-01 Hispano Quimica Procedimiento para la obtencion del 2,6,10,15,19,23-hexametiltetracosano
JP2005255746A (ja) * 2004-03-10 2005-09-22 Chikuno Shokuhin Kogyo Kk 米糠油脱臭スカム不ケン化物濃縮物製造法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES8602102A1 (es) * 1985-01-25 1985-11-16 Derivan Sa Procedimiento para la obtencion de escualeno y escualano a partir de subproductos de la refinacion fisica y-o desodori-zacion de aceites vegetales
ES8706592A1 (es) * 1986-05-19 1987-07-16 Tadeval S A Procedimiento para la obtencion de escualano
ES2002428A6 (es) * 1986-10-21 1988-08-01 Hispano Quimica Procedimiento para la obtencion del 2,6,10,15,19,23-hexametiltetracosano
JP2005255746A (ja) * 2004-03-10 2005-09-22 Chikuno Shokuhin Kogyo Kk 米糠油脱臭スカム不ケン化物濃縮物製造法

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9867877B2 (en) 2010-05-12 2018-01-16 Novartis Ag Methods for preparing squalene
EP2620423B2 (en) † 2010-05-12 2019-07-31 Novartis AG Improved methods for preparing squalene
US9199897B2 (en) 2010-05-12 2015-12-01 Novartis Ag Methods for preparing squalene
US11077186B2 (en) 2010-05-12 2021-08-03 Novartis Ag Methods for preparing squalene
US10517947B2 (en) 2010-05-12 2019-12-31 Novartis Ag Methods for preparing squalene
EP2620423B1 (en) 2010-05-12 2016-07-20 Novartis AG Improved methods for preparing squalene
EP2569267B2 (en) † 2010-05-12 2017-03-22 Novartis AG Improved methods for preparing squalene
EP3489211B1 (en) 2010-05-12 2020-07-15 Novartis AG Improved methods for preparing squalene
US9545440B2 (en) 2010-05-12 2017-01-17 Novartis Ag Methods for preparing squalene
WO2013156720A3 (fr) * 2012-04-16 2014-01-09 Roquette Freres Procédé de raffinage du squalène produit par microalgues
CN104245076A (zh) * 2012-04-16 2014-12-24 罗盖特兄弟公司 用于精炼微藻产生的角鲨烯的方法
US9346722B2 (en) 2012-04-16 2016-05-24 Roquette Freres Method for refining squalene produced by microalgae
CN104245076B (zh) * 2012-04-16 2017-03-01 罗盖特兄弟公司 用于精炼微藻产生的角鲨烯的方法
CN105296552A (zh) * 2012-04-16 2016-02-03 罗盖特兄弟公司 用于精炼微藻产生的角鲨烯的方法

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ES2308924B1 (es) 2009-11-02
ES2308924A1 (es) 2008-12-01

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