Patent Application
20230023141
The invention provides a process for enzymatic preparation of sorbitan carboxylates, and the sorbitan carboxylates obtainable by this process.
Sorbitol carboxylates are products of interest to the food and cosmetics industries not only on account of their surfactant properties, but also because of the possibility of obtaining them from natural and renewable raw materials.
DE102009001748A describes sorbitan esters obtained from the solvent-free reaction of 1 mol of sorbitol (also called glucitol) with 1.55 mol of caprylic acid, and the use of the sorbitan esters thus obtained as thickener for aqueous surfactant systems. It is a disadvantage of the process that, under the reaction conditions described, the sorbitol is dehydrated virtually completely, but at least partially, and forms what is called sorbitan (a product mixture).
Four degradation products of sorbitol that frequently occur under such conditions are the anhydrohexitols 1,4-anhydrosorbitol, 2,5-anhydrosorbitol, 1,5-anhydrosorbitol (Advances in Carbohydrate Chemistry and Biochemistry, 1983, 41, 27-66) and isosorbide (1,4:3,6-dianhydrosorbitol; ChemSusChem. 5 (1): 167-176).
A further disadvantage of these sorbitol esters is their dark colour, which requires aftertreatment, for example with activated carbon, in order to achieve product qualities usable in the cosmetics sector.
JP63133991 describes the reaction of 1.0 equivalent of oleic acid with 1.0 equivalent of sorbitol in the presence of >9% lipase (Candida Sp) at 40-50° C. and 100 mmHg (133 mbar). A disadvantage of this process described in the prior art is that only about 70% esterification is attained. A further disadvantage is that only pure oleic acid is used, which is too costly for industrial applications in the food and cosmetics sector and hence uneconomic.
DE3430944 describes the reaction of ≥4.0 equivalents of oleic acid or stearic acid with 1.0 equivalent of sorbitol in the presence of about 7% lipase at 40° C. for 72 h, wherein the reactants and the enzyme are reacted with one another in a concentration by mass of about 28 g per 1000 ml in an aqueous buffer system. A disadvantage of this process described in the prior art is the use of aqueous phosphate buffer, the salt burden of which in the product is undesirable for use in cosmetics. A further disadvantage is that the concentration by mass of the reactants and of the lipase in the buffer system is only about 3%, which means much too low a space-time yield for industrial conversions. A further disadvantage is that only pure oleic acid and pure stearic acid are used.
Lorie et al. describe, in Biotechnol. Bioeng. 1995, 48, 214-221, the reaction of sorbitol with 1.0 equivalent of oleic acid in the presence of 15% Novozym 435 (lipase from Candida antarctica; about 494 000 PLU per mole of fatty acid) at 90° C. and a pressure of <0.7 kPa (<7 mbar). One disadvantage of the process described in the prior art is that the sorbitol used remains as a highly viscous semisolid at the base of the reaction vessel, while oleic acid is the layer above it. This behaviour additionally complicates the mixing of the reactants, which is difficult in any case.
EP1755545B1 describes a mixture of sorbitan esters and sorbitol esters, wherein the chain length of the fatty acid of the sorbitan ester is greater than the chain length of the fatty acid of the sorbitol ester, and more than 80% saturated fatty acids is always used. The sorbitan esters are at least 50% of the mixture. The sorbitol esters consist solely of mono- and diesters, with at least 40% monoesters and less than 60% diesters, and are used to influence emulsion stability and viscosity. Proceeding from lauric acid, a mixture consisting of 7% sorbitan esters, 68% C12 sorbitol esters and 25% polyol is obtained. A disadvantage of the process for preparation described in the prior art is the fact that sorbitan esters are formed here too, as a result of which the hydrophilic portion of the surfactant is reduced, and a poor colour is also obtained.
The problem addressed by the present invention was that of providing a process for preparing sorbitan esters that is capable of overcoming at least one disadvantage of the prior art processes.
It has been found that, surprisingly, the object of the invention is achieved by the sorbitol carboxylates described hereinafter and the process described hereinafter.
It is an advantage of the present invention that the sorbitol carboxylates of the invention are excellent thickeners for aqueous surfactant systems compared to the prior art.
It is a further advantage that the sorbitol carboxylates of the invention also have excellent colour and very good odour compared to the prior art.
It is an advantage of the present invention that only very small amounts of sorbitol degradation products or esters of the degradation products are obtained as reaction products.
It is an advantage of the present invention that the process according to the invention can be performed in the absence of a solvent.
It is a further advantage of the present invention that the sorbitol carboxylates are obtained in a homogeneous reaction mixture, which means that no additional process steps such as extraction, crystallization, filtration or distillation are required.
An advantage of the present invention is that the process can be carried out at elevated temperatures. This leads to better miscibility of the co-reactants, while the recyclability of the enzyme used is surprisingly high.
It is a further advantage of the present invention that the sorbitol carboxylates obtained can be incorporated very readily into formulations, particularly into cosmetic formulations.
The present invention therefore provides a process for enzymatic preparation of a sorbitol carboxylate, comprising the process steps of
A) providing sorbitol and at least one acyl group donor, preferably fatty acid acyl group donor, selected in particular from fatty acid esters and fatty acids, more preferably fatty acids,
B) reacting sorbitol with the at least one acyl group donor in the presence of a lipase at a temperature of 75° C. to 110° C., preferably of 77° C. to 100° C., even more preferably 80° C. to 95° C., to give a sorbitol carboxylate, and optionally
C) purifying the sorbitol carboxylate,
characterized in that process step A) comprises blending the sorbitol and the at least one acyl group donor within a temperature range of 80° C. to 120° C., preferably of 90° C. to 120° C., even more preferably of 95° C. to 120° C., even more preferably of 100° C. to 120° C., for at least 10 minutes, preferably at least 30 minutes, even more preferably at least 60 minutes.
The term “sorbitol carboxylates” in the context of the present invention includes a composition that contains a majority of, especially at least 40% by weight, preferably at least 50% by weight, even more preferably at least 60% by weight, of carboxylic esters of sorbitol, based on the overall composition. However, as the case may be, by-products from the respective preparation processes may also be present, for example carboxylic esters of 1,4-anhydrosorbitol, carboxylic esters of 2,5-anhydrosorbitol, carboxylic esters of 1,5-anhydrosorbitol and carboxylic esters of isosorbide, and also unreacted reactants.
The terms “sorbitol carboxylates” and “sorbitan carboxylates” are used synonymously in the context of the present invention.
This use of the term is based on the common nomenclature for polyol esters, which are known to be prone to dehydration during their synthesis, and so the products are mixed compositions. Those skilled in the art will thus understand the term “sorbitan esters” to mean a mixture comprising not only esters of 1,4-anhydrosorbitol and esters of 1,5-anhydrosorbitol, but also esters of isosorbide and esters of sorbitol, and also free sorbitol; in this regard see also Food emulsifiers and their applications, 1997, page 26.
The term “carboxylic esters of sorbitol” in the context of the present invention refers to pure sorbitol compounds.
The term “carboxylic esters of 1,4-anhydrosorbitol” in the context of the present invention refers to pure 1,4-anhydrosorbitol compounds.
The term “carboxylic esters of 2,5-anhydrosorbitol” in the context of the present invention refers to pure 2,5-anhydrosorbitol compounds.
The term “carboxylic esters of 1,5-anhydrosorbitol” in the context of the present invention refers to pure 1,5-anhydrosorbitol compounds.
The term “carboxylic esters of isosorbide” in the context of the present invention refers to pure isosorbide compounds.
Unless stated otherwise, all stated percentages (%) are percentages by weight.
According to the invention, it is possible in accordance with the invention to use any acyl group donors. These include for example carboxylic esters or carboxylic acids themselves, and mixtures thereof.
It is preferable in accordance with the invention that the acyl group donor provided in process step A) provides acyl groups that derive from a carboxylic acid containing 2 to 34, preferably 4 to 24, more preferably 6 to 22, carbon atoms, especially a natural fatty acid or mixtures thereof.
Carboxylic esters used with preference in accordance with the invention as acyl group donor are selected from esters based on alkanols and polyols having up to 6 carbon atoms, particularly preferably having up to 3 carbon atoms, very particularly preferably glycerol esters.
Carboxylic esters used with particular preference in accordance with the invention as acyl group donor are selected from triglycerides, especially natural fats and oils, particularly preferably selected from the group comprising, preferably consisting of, coconut fat, palm kernel oil, olive oil, palm oil, argan oil, castor oil, linseed oil, babassu oil, rapeseed oil, algal oils, sesame oil, soya oil, avocado oil, jojoba oil, safflower oil, almond oil, cottonseed oil, shea butter, sunflower oil, cupuaçu butter and oils having a high proportion of polyunsaturated fatty acids (PUFAs). Sorbitan esters, monoglycerides and diglycerides, in particular containing the acyl groups described hereinbelow, may likewise preferably be used.
More preferably in accordance with the invention, the acyl group donor is selected from fatty acid acyl group donors that in particular provide an acyl group selected from the group of acyl groups of natural fatty acids, or mixtures thereof.
Preferred fatty acids in this connection are mixtures of natural fatty acids, especially mixtures in which no carboxylic acid chain length has a proportion in the overall chain length distribution of more than 95% by weight, especially more than 99% by weight.
Natural fatty acids can be produced on the basis of naturally occurring vegetable or animal oils and have preferably 6 to 30 carbon atoms, especially 8 to 22 carbon atoms. Natural fatty acids are generally unbranched and usually consist of an even number of carbon atoms. Any double bonds have cis configuration. Examples are: caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmifoleic acid, pelargonic acid (obtainable for example from the ozonolysis or oxidative cleavage of oleic acid), isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, undecylenic acid (obtainable for example from the pyrolysis of ricinoleic acid), oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachic acid, behenic acid, erucic acid, gadoleic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.
More preferably in accordance with the invention, the acyl group donor is selected from fatty acid acyl group donors that are characterized in that they provide an acyl group mixture containing at least two acyl groups of the carboxylic acids selected from the group of caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, pelargonic acid (obtainable for example from the ozonolysis or oxidative cleavage of oleic acid), isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, undecylenic acid (obtainable for example from the pyrolysis of ricinoleic acid), oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachic acid, behenic acid, erucic acid, gadoleic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.
Acyl group donors used with preference in accordance with the invention are carboxylic acids, especially fatty acids. Preferred fatty acids in this connection are those mentioned above in connection with the fatty acids provided with preference.
Acyl group donors used alternatively with particular preference are mixtures of fatty acids with glycerol fatty acid esters, preference being given to using those mentioned above in connection with fatty acids provided with preference, both in the case of the fatty acids and in the case of the glycerol fatty acid components, with an identical degree of preference.
The mixture of fatty acid with glycerol fatty acid ester used preferably has a weight ratio of fatty acid to glycerol fatty acid ester of 80:20 to 99:1, preferably of 90:10 to 99:1, more preferably of 95:5 to 99:1.
A process preferred in accordance with the invention is characterized in that the sorbitol and the at least one acyl group donor make up at least 80% by weight, preferably at least 90% by weight, more preferably at least 95% by weight, based on the overall reaction mixture at the start of process step B).
Since the overall reaction mixture in this context consists largely of the reactants, i.e. sorbitol and acyl group donor, only very little solvent—if any—can he present in the overall reaction mixture. It is clear on the basis of the above that the acyl group donor is not covered by the term “solvent” in the process according to the invention.
Possible solvents would be for example ketones, for example methyl isohutyl ketone or cyclohexanone, sterically hindered secondary alcohols such as 2-butyl-1-octanol, methylcyclohexanols, 1-methoxy-2-propanol, butane-2,3-diol, 2-octanol, diacetone alcohol, 2-methyl-2-butanol, and ethers such as 1,4-dioxane, tetrahydrofuran and Varonic APM.
Based on the overall reaction mixture, solvents are present in a maximum total amount of less than 20% by weight, preferably less than 10% by weight, especially less than 5% by weight. The expression “is present in a maximum amount of less than X % by weight” can be equated with “has a content of less than X % by weight”.
Particular preference is given to carrying out the process according to the invention in the absence of solvent.
A process preferred in accordance with the invention is thus especially characterized in that, in process step B), the water content based on the overall reaction mixture is less than 15% by weight, preferably less than 5.0% by weight, more preferably less than 1.0% by weight.
Lipases used with preference in accordance with the invention in process step B) are present immobilized on a solid support.
Lipases used with preference in accordance with the invention in process step B) are lipases selected from the group comprising the lipase from Thermomyces lanuginosus (accession number O59952), lipases A and B (accession number P41365) from Candida antarctica and the lipase from Mucor miehei (accession number P19515), the lipase from Humicola sp. (accession number O59952), the lipase from Rhizomucor javanicus (accession number S32492), the lipase from Rhizopus oryzae (accession number P61872), the lipases from Candida rugosa (accession number P20261, P32946, P32947, P3294 and P32949), the lipase from Rhizopus niveus (accession number P61871), the lipase from Penicillium camemberti (accession number P25234), the lipases from Aspergillus niger (ABG73613, ABG73614 and ABG37906) and the lipase from Penicillium cyclopium (accession number P61869), particular preference being given to lipases A and B (accession number P41365) from Candida antarctica, and their respective at least 60%, with preference at least 80%, preferably at least 90% and especially preferably at least 95%, 98% or 99%, homologues at the amino acid level.
The accession numbers listed in the context of the present invention correspond to the ProteinBank database entries of the NCBI with a date of Jan. 1, 2017; generally, in the present context, the version number of the entry is identified by “.digit”, for example “.1”.
Enzymes that are homologous at the amino acid level preferably have, by comparison with the reference sequence, at least 50%, especially at least 90%, of the enzyme activity in propyl laurate units (PLU) as defined in the context of the present invention.
To determine the enzyme activity in PLU (propyl laurate units), 1-propanol and lauric acid are mixed homogeneously in an equimolar ratio at 60° C. The reaction is started with addition of enzyme and the reaction time is measured. Samples are taken from the reaction mixture at intervals and the content of converted lauric acid is determined by titration with potassium hydroxide solution. The enzyme activity in PLU results from the rate at which 1 g of the enzyme in question synthesizes 1 μmol of propyl laurate per minute at 60° C.; cf. in this respect also US20070087418, in particular [0185].
Commercial examples, and lipases that are likewise used with preference in processes according to the invention, are the commercial products Lipozyme TL IM, Novozym 435, Lipozyme IM 20, Lipase SP382, Lipase SP525, Lipase SP523, (all commercial products from Novozymes A/S, Bagsvaerd, Denmark), Chirazyme L2, Chirazyme L5, Chirazyme L8, Chirazyme L9 (all commercial products from Roche Molecular Biochemicals, Mannheim, Germany), CALB IMMO Plus TM from Purolite, and Lipase M “Amano”, Lipase F-AP 15 “Arnano”, Lipase AY “Amano”, Lipase N “Amano”, Lipase R “Amano”, Lipase A “Amano”, Lipase D “Amano”, Lipase G “Amano” (all commercial products from Amano, Japan).
“Homology at the amino acid level” is for the purposes of the present invention understood as meaning “amino acid identity”, which can be determined with the aid of known methods. In general, use is made of special computer programs with algorithms taking into account specific requirements. Preferred methods for determining the identity first generate the closest match between the sequences to be compared. Computer programs for determining the identity include, but are not limited to, the GCG program package including
Those skilled in the art are aware that various computer programs are available for the calculation of similarity or identity between two nucleotide or amino acid sequences. For instance, the percentage identity between two amino acid sequences can be determined for example by the algorithm developed by Needleman and Wunsch (J. Mol. Biol. (48): 444-453 (1970)), which has been integrated into the GAP program in the GCG software package (available at http://www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, a gap weight of 16, 14, 12, 10, 8, 6 or 4 and a length weight of 1, 2, 3, 4, 5 or 6. Those skilled in the art will recognize that the use of different parameters will lead to slightly different results, but that the percentage identity between two amino acid sequences overall will not be significantly different. The Blossom 62 matrix is typically employed, using the default settings (gap weight: 12, length weight: 1).
In the context of the present invention, an identity of 60% according to the above algorithm means 60% homology. The same applies to higher identities.
In process step B), preference is given in accordance with the invention to using 500 PLU to 2000 PLU, preferably from 200 PLU to 1500 PLU, more preferably from 25 PLU to 1250 PLU, of lipase per gram of sorbitol to be converted.
Process step B) is in accordance with the invention preferably carried out at a pressure of less than 1 bar, preferably less than 0.5 bar and particularly preferably less than 0.1 bar.
Process step B) is in accordance with the invention alternatively preferably carried out in a bubble column reactor, with at least one inert gas being passed through the reaction mixture; this gas is preferably selected from the group comprising, preferably consisting of, nitrogen and argon. In this connection, it is preferable in accordance with the invention for the gas stream to be 1 to 60 kg/h, preferably 5 to 25 kg/h, yet more preferably 10 to 14 kg/h.
Process step B) is in accordance with the invention preferably characterized in that process step B) is ended no later than 180 hours, preferably 120 hours, particularly preferably 100 hours, after the lipase has been added.
A process that is preferred in accordance with the invention is characterized in that the molar ratio of sorbitol provided to acyl groups present in all acyl group donors provided is within a range from 1.00:0.50 to 1.00:5.00, preferably from 1.00:0.70 to 1.00:3.00, particularly preferably from 1.00:1.00 to 1.00:2.25, alternatively particularly preferably from 1.00:2.3 to 1.00:4.50.
A process that is preferred in accordance with the invention is characterized in that by-products formed in process step B), for example water when the acyl group donor used is an acid and the corresponding alcohol when the acyl group donor used is an ester, are removed.
This is possible by distillation for example.
Process step C) of the process of the invention comprises the purification of the sorbitol carboxylate.
All methodologies that allow the sorbitol carboxylate to be obtained in higher concentration can be employed for this purpose.
It is in accordance with the invention preferable that the process according to the invention includes the removal, in process step C), of the lipase used in the process according to the invention.
When the lipase is mmobilized on a support, it is preferable in accordance with the invention that the lipase is removed by filtration through a filter, especially a bag filter, having a fineness of 0.1 μ to 1250 μ, preferably of 0.5 μ to 100 μ.
The process of the present invention is preferably in accordance with the invention characterized in that it does not involve any use of a molecular sieve.
The process of the present invention is preferably in accordance with the invention characterized in that the substrates are not immobilized on solid supports such as silica.
The present invention further provides the sorbitol carboxylate obtainable by the process of the invention.
Preference is given in accordance with the invention to sorbitol carboxylates comprising carboxylic esters of sorbitol, carboxylic esters of 1,4-anhydrosorbitol, carboxylic esters of 2,5-anhydrosorbitol, carboxylic esters of 1,5-anhydrosorbitol, and carboxylic esters of isosorbide, where the ratio by weight of the sorbitol residues present in the sorbitol carboxylate to the sum total of all the 1,4-anhydrosorbitol residues, 2,5-anhydrosorbitol residues and 1,5-anhydrosorbitol residues and isosorbide residues present in the sorbitol carboxylate is greater than 90:10, preferably greater than 93:7, more preferably greater than 95:5, most preferably greater than 96:4, characterized in that the molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic esters of sorbitol is 80:20 to 20:80, preferably 70:30 to 30:70, even more preferably 60:40 to 40:60, even more preferably from 55:45 to 45:55.
It is clearly apparent from the expression “sorbitol carboxylates containing carboxylic esters of sorbitol, carboxylic esters of 1,4-anhydrosorbitol, carboxylic esters of 2,5-anhydrosorbitol, carboxylic esters of 1,5-anhydrosorbitol and carboxylic esters of isosorbide, where the weight ratio of the sorbitol residues present in the carboxylic esters to the sum total of all 1,4-anhydrosorbitol residues, 2,5-anhydrosorbitol residues, 1,5-anhydrosorbitol residues and isosorbide residues present in the carboxylic esters is greater than 90:10” that the content of at least one selected from carboxylic esters of 1,4-anhydrosorbitol, carboxylic esters of 2,5-anhydrosorbitol, carboxylic esters of 1,5-anhydrosorbitol and carboxylic esters of isosorbide must be non-0 (zero), since divisions by 0 are undefined.
The weight ratio of the sorbitol residues present in the sorbitol carboxylates according to the invention to the sum total of all 1,4-anhydrosorbitol residues, 2,5-anhydrosorbitol residues, 1,5-anhydrosorbitol residues and isosorbide residues present in the sorbitol carboxylate according to the invention is determined by means of high-performance liquid chromatography (HPLC). This method includes the alkaline hydrolysis of the sorbitol carboxylate to be analysed, removal of the carboxylic acids and analysis of the sorbitol and the 1,4-anhydrosorbitol, 2,5-anhydrosorbitol, 1,5-anhydrosorbitol and isosorbide degradation products thereof.
For this purpose, an initial charge of 150 mg of the sorbitol carboxylate to be analysed in 2.00 ml of 1 M aqueous KOH solution is hydrolysed at 95° C. with stirring for 30 min. The reaction solution is then cooled to room temperature and adjusted to pH 2-3 with 2 M aqueous HCl solution. The carboxylic acids that precipitate out as a result are then extracted with diethyl ether (3×3.00 ml), with removal of the organic supernatant by pipette after each extraction. After the extraction, the aqueous solution is heated to 50° C. with stirring for 20 min, which removes the rest of the ether (boiling point of diethyl ether: 34.6° C.).
The solution obtained above is made up to 10.0 ml with bidistilled H2O and then diluted 1:10, and an aliquot of the solution is analysed by HPLC. The analysis is carried out under the following conditions:
Column: Aminex HPX-87C column 300×7.8 mm
Eluent: H2O
Injected volume: 10.0 μl
Flow rate: 0.60 ml/min
Column temperature: 50° C.
Detector: G1362A/1260 RID (from Agilent), 35° C.
Run time: 30.0 min
Sorbitol and its degradation products are separated by an ion-exchange process.
For the evaluation, the peak area of sorbitol is expressed relative to the sum total of the peak areas of 1,4-anhydrosorbitol, 2,5-anhydrosorbitol, 1,5-anhydrosorbitol and isosorbide.
Reference substances for the sorbitol degradation products are commercially available or can alternatively be obtained by heating sorbitol in neat form in the presence of acidic (>140° C.) or basic (>180° C.) catalysts.
The molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic esters of sorbitol is determined by 13C NMR spectroscopy. For sample preparation, 50-70 mg of substance is dissolved in 1 ml of a deuterated solvent to which has been added a relaxation agent (chromium(III) acetylacetonate, 1%). DMSO-d6, CDCl3 and methanol-d4 have been found to be suitable solvents, according to product properties. If the sample does not dissolve completely in one of the solvents, a solvent mixture must be found. The prepared sample solution is transferred to a 5 mm NMR tube and introduced into the NMR spectrometer.
The NMR spectroscopy investigations can in principle be carried out with any commercial NMR instrument. For the present NMR spectroscopy investigations, a Bruker Avance 400 instrument was used. The spectra were recorded with the following parameters:
Temperature: T=295 K, Time delay: D1=2 s. Number of scans: NS=2048, Transmitter frequency offset: O1P=110 ppm, Sweep width: SW=300 ppm, Probe: PA BBI 400 S1 H-BB-D-05-Z.
The resonance signals were recorded against the chemical shift of tetramethylsilane (TMS=0 ppm) as internal standard. Other commercial NMR instruments give comparable results with the same operating parameters. The signals are quantified by determining the area under the respective resonance signals, i.e. the area enclosed by the signal from the baseline. In the present NMR spectroscopy investigations, the spectra were integrated using the “TOPSPIN” software, version 3.0.
For more accurate identification of the esterified primary and esterified secondary hydroxyl groups, a DEPT spectrum is first recorded. The molar ratio of esterified primary to esterified secondary hydroxyl groups is determined by subtracting the integral value P (group of signals for the esterified primary hydroxyl groups) from integral value C (group of signals for the ester carbonyl groups).
This gives an internal value S for the group of signals for the esterified secondary hydroxyl groups, which cannot be determined directly because of superimposition with other signals.
P=Integral value of the esterified primary hydroxyl groups [R—CH2—OC(O)R groups]
C=Integral value of the ester carbonyl groups
S=C−P=Integral value of the esterified secondary hydroxyl groups [R2—CH—OC(O)R groups]
The ratio of P to S ascertained corresponds to the molar ratio of esterified primary hydroxyl groups to esterified secondary hydroxyl groups in the carboxylic esters of sorbitol.
Preference is given in accordance with the invention to sorbitol carboxylates that are characterized in that the average degree of esterification of the carboxylic esters of sorbitol present is from 0.3 to 4.0, preferably from 1.0 to 3.0, more preferably from 1.1 to 2.7, especially preferably from 1.3 to 2.6. Preference is alternatively given in accordance with the invention to sorbitol carboxylates that are characterized in that the average degree of esterification of the carboxylic esters of sorbitol present is from 2.7 to 4.0.
The average degree of esterification of the carboxylic esters of sorbitol present in the sorbitol carboxylate according to the invention is determined, for example, by first determining the content of free sorbitol and of its 1,4-anhydrosorbitol, 2,5-anhydrosorbitol, 1,5-anhydrosorbitol and isosorbide degradation products in a sample of the sorbitol carboxylate in question. It is additionally necessary to determine the saponification value, acid value and content of free and neutralized fatty acids (for example via GC as described hereinbelow under “Determination of the content of free carboxylic acid”). The determination of the carboxylic acid composition after alkaline saponification gives an average molar mass of the carboxylic acid mixture that has been esterified.
This value can then be used to calculate the average degree of esterification.
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that the carboxylic esters of sorbitoi present comprise monoesters of sorbitol, diesters of sorbitol and triesters of sorbitol, where the triesters of sorbitol are present preferably in an amount, based on all carboxylic esters of sorbitol present, of 10% to 50% by weight, preferably of 15% by weight to 45% by weight, more preferably of 20% by weight to 40% by weight. In this connection, it is further preferable in accordance with the invention that the carboxylic esters of sorbitol present comprise monoesters of sorbitol, diesters of sorbitol, triesters of sorbitol and tetraesters of sorbitol.
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that it contains 0.05% to 40% by weight, preferably 0.2% to 25% by weight, more preferably 0.5% to 10% by weight, of free sorbitol,
where the percentages by weight are based on the overall sorbitol carboxylate.
For determination of the sorbitol present in the sorbitol carboxylate of the invention by GC, a portion of the sample is dissolved in pyridine:chloroform (4:1). 0.25 ml of this solution is mixed with 0.5 ml of MSTFA [N-methyl-N-(trimethylsilyl)trifluoroacetamide] and 0.5 ml of a mixture of N-trimethylsilylimidazole and pyridine (11:39).
The alcohols are quantitatively converted into their trimethylsilyl ethers by reaction at 80° C. (30 minutes) and then analysed by GC/FID.
This is performed in a gas chromatograph equipped with a split/splitless injector, a capillary column and a flame ionization detector, under the following conditions:
Injector: 290° C., split 30 ml
Injected volume: 1 μl
Column: 50 m*0.32 mm HP5 1.05 μm
Carrier gas: Hydrogen, constant flow, 2 ml/min
Temperature program: 100° C. to 140° C. at 10° C./min, then 140° C. to 300° C. at 5° C./min, then conditioning at 300° C. for 5 minutes.
Detector: FID at 310° C. Hydrogen 30 min Air 400 ml/min Make-up gas 12 ml/min
The sorbitol is separated off and its proportion by mass determined by an internal standard method. For this purpose, the GC system is calibrated by analysing mixtures of sorbitol and of the internal standard of known composition.
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that it contains less than 25% by weight, preferably from 0.01% by weight to 20% by weight, more preferably from 0.05% by weight to 10% by weight, of at least one free carboxylic acid, the percentages by weight being based on the overall sorbitol carboxylate.
The at least one free carboxylic acid may be in protonated or neutralized form.
To determine the content of free carboxylic acid in the sorbitol carboxylate of the invention, the acid value is first determined. Through the acid value and molecular weight of the fatty acid concerned, it is possible to determine the proportion by weight.
Suitable methods for determining the acid number are particularly those according to DGF C-V 2, DIN EN ISO 2114, Ph. Eur. 2.5.1, ISO 3682 and ASTM D 974.
It is known to those skilled in the art that, where there is a mixture of carboxylic acids, a GC analysis can also additionally be carried out after saponification of the sorbitol carboxylate, in order to determine an average molecular weight of the carboxylic acid mixture present.
For this purpose, 0.6 g of the sorbitol carboxylate of the invention is boiled under reflux in 25 ml of 0.5 M ethanolic KOH solution for 4 hours. The pH is then adjusted to 2-3 with sulfuric acid and the liberated carboxylic acids are separated by extracting three times with a volume of petroleum ether.
The combined extracts are concentrated to about 10 ml by evaporation.
Suitable methods for determining the fatty acid distribution are in particular those according to DGF C VI 11a, DGF C-VI 10 a and GAT ring test 7/99.
A 0.5 ml aliquot of the petroleum ether extract obtained as described above is mixed in an autosampler vial with 0.5 ml of MTBE and 1 ml of trimethylanilinium hydroxide (0.2 M in methanol) and analysed by GC. This is performed in a gas chromatograph equipped with a split/splitless injector, a capillary column and a flame ionization detector, under the following conditions:
Injector: 290° C., split 30 ml
Injected volume: 1 μl
Column: 30 m*0.32 mm HP1 0.25 μm
Carrier gas: Helium, head pressure 70 kPa
Temperature program: 80° C.-300° C. at 8° C./min, then conditioning for 20 minutes at 300° C.
Detector: FID at 320° C. Hydrogen 35 ml/min Air 240 ml/min Make-up gas 12 ml/min
The carboxylic acids are separated according to length of their carbon chain in the form of their methyl esters. By evaluating the peak areas it is possible to determine the mass ratio of these carboxylic acid methyl esters to one another and from this—via their respective molecular weights—their molar ratio, which corresponds to the molar ratio of the associated carboxylic acids. it is in addition possible to determine an average molecular weight of this fatty acid mixture:
where ai=Normalized proportion by mass of carboxylic acid methyl ester i in the mixture of all carboxylic acid methyl esters [%]. Ai=Peak area of carboxylic acid methyl ester i in the GC chromatogram [%].
where ni=Molar amount [mol] of carboxylic acid methyl ester i in 100 g of carboxylic acid methyl ester mixture; from this, the ratios of the individual ni values to one another are obtained, which correspond to the ratios of the molar amounts of the associated carboxylic acids in the sorbitol carboxylate; thus it is possible for the total molar amount ns [mol] of carboxylic acids in 1 g of sorbitol carboxylate, as obtained from the saponification value (see below), to be split into its components according to said ratios. Mi=Molecular weight of the carboxylic acid corresponding to methyl ester i [g/mol].
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that the total monoester component of the carboxylic ester of sorbitol contains from 5% by weight to 25% by weight, preferably from 7% by weight to 15% by weight, more preferably from 9% by weight to 13% by weight, of secondary ester regiolsomers.
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that the total monoester component of the carboxylic ester of sorbitol and the total diester component of the carboxylic ester of sorbitol each comprise at least two regioisomers.
Preference is given in accordance with the invention to a sorbitol carboxylate that is characterized in that the total diester component of the carboxylic ester of sorbitol contains from 25% by weight to 45% by weight, preferably from 28% by weight to 39% by weight, more preferably from 30% by weight to 37% by weight, of regioisomers in which at least one secondary hydroxyl group has been esterified.
The determination of the content of secondary ester regiolsomer in the total monoester component of the carboxylic ester of sorbitol of the invention, the determination of the content of triester species based on the sum total of all carboxylic esters of sorbitol that are present, and the determination of the content of regioisorners in the total diester component in which at least one secondary hydroxyl group has been esterified can be performed by gas chromatography, optionally coupled with mass spectrometry (GC-FID and GC-MS):
10 mg of a sample of the corresponding sorbitol carboxylates is first dissolved in 1.5 ml of trichloromethane, and then 0.15 ml of N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) is added. The derivatization is carried out at 80° C. for 30 minutes. A sample of the clear solution thus obtained is analysed by GC-FID and GC-MS. The parameters of the analysis method are:
Gas chromatograph: Agilent MSD 7890
Column: Agilent HP-5 (50 m, 0.32 mm, 0.5 μm),
Flow rate: constant 2 ml/min with hydrogen (GC-MS: helium)
Thermal equilibration at 80° C., 8° C./min; 300° C., 30 min, injector 1 μl, split 1:20, detector at 310° C.
Detector: FID, 310° C./GC-MS scan 35-650 d
In the GC-FID analysis, the esters present in the sample are separated according to their total chain length. The ratios of the individual ester species to one another are determined via the respective area percentage of the GC-FID peak. The peaks are identified/assigned to the individual ester species via GC-MS, if appropriate also via a comparison of retention time of separately prepared and isolated standards, for example for the mono- and diesters esterified exclusively at primary hydroxyl groups.
This method can likewise be used to detect the content of free protonated and also free neutralized carboxylic acids, since these are likewise derivatized.
The present invention further provides for the use of the sorbitol carboxylates according to the invention as viscosity regulator, care active ingredient, foam booster or solubilizer, antimicrobial, antistat, binder, corrosion inhibitor, dispersant, emulsifier, film former, humectant, opacifier, oral care agent, preservative, skincare agent, hydrophilic emollient, foam stabilizer and nonionic surfactant, preferably as viscosity regulator, emulsifier, antimicrobial and hydrophilic emollient, particularly preferably as viscosity regulator, especially as thickener, especially in cleansing or care formulations.
The examples that follow describe the present invention by way of example, without any intention to limit the invention, the scope of application of which is apparent from the entirety of the description and the claims, to the embodiments specified in the examples.
Various sorbitol carboxylates were synthesized as described hereinafter.
A 25% solution of the sample to be analysed was prepared in a mixture of concentrated acetic acid and toluene (3:1), and filtered if necessary to give a clear solution. An aliquot (approx. 10 g; so that the cuvette is sufficiently filled) was measured in a Lica 690 spectral colorimeter at room temperature in an 11 mm round cuvette, and the colour numbers reported in each case were recorded.
A mixture of sorbitol (96.5 g, 0.529 mol, 1.00 eq.) and caprylic acid (acid number=389 mg KOH/g, >98%, 118.34 g, 0.821 mol, 1.55 eq.) was heated to 100° C. while stirring and passing N2 through. After 1 h, the mixture was cooled down to 85° C., immobilized Candida antarctica lipase B enzyme (6.44 g; Purolite D5619, corresponding to 55747 PLU) was added, and stirring of the mixture was continued at 85° C. and 15 mbar for 24 h, during which time the water formed was distilled off continuously. The mixture was then filtered at 80° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 3.0 mg KOH/g.
A mixture of sorbitol (70% aqueous solution, 390.45 g, 1.50 mol, 1.00 eq.), phosphoric acid (2.9 g) and sodium hydroxide (5.0 g) was dehydrated at 140° C. for 30 min. Subsequently, caprylic acid (acid number=389 mg KOH/g, >93%, 334.8 g, 2.32 mol, 1.55 eq.) was added, and the mixture was stirred at 200° C. until an acid number of 8.1 mg KOH/g had been attained.
A mixture of sorbitol (96.5 g, 0.529 mol, 1.00 eq.), caprylic acid (acid number=389 mg KOH/g, >98%, 118.34 g, 0.821 mol, 1.55 eq.) and Novozym 435 (57.9 g, 405475 PLU) was stirred at 90° C. and <7 mbar for 24 h, and the water formed was distilled off continuously. The mixture was then filtered at 85° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 2.0 mg KOH/g.
A mixture of sorbitol (51.3 g, 0.282 mol, 1.00 eq.) and oleic acid (acid number=200 mg KOH/g, iodine number=92.3 g I2/100 g, 157.9 g, 0.563 mol, 2.00 eq.) was heated to 100° C. while stirring and passing N2 through. After 1 h, the mixture was cooled down to 85° C., immobilized Candida antarctica lipase B enzyme (6.28 g; Purolite D5619, corresponding to 54361 PLU) was added, and stirring of the mixture was continued at 85° C. and 20 mbar for 24 h, during which time the water formed was distilled off continuously. The mixture was then filtered at 80° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 4.2 mg KOH/g.
A mixture of sorbitol (100.1 g, 0.549 mol, 1.00 eq.), oleic acid (>99%, 155.1 g, 0.549 mol, 1.00 eq.) and Novozym 435 (38.7 g, 271126 PLU) was stirred at 90° C. and <7 mbar for 24 h, and the water formed was distilled off continuously. The mixture was then filtered at 85° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 12.8 mg KOH/g.
A mixture of sorbitol (62.6 g, 0.344 mol, 1.00 eq.) and stearic acid (acid number=198 mg KOH/g, ≥92%, 146.7 g, 0.516 mol, 1.50 eq.) was heated to 115° C. while stirring and passing N2 through.
After 1 h, the mixture was cooled down to 90° C., immobilized Candida antarctica lipase B enzyme (6.28 g; Purolite D5619, corresponding to 54350 PLU) was added, and stirring of the mixture was continued at 90° C. and <7 mbar for 24 h, during which time the water formed was distilled off continuously. The mixture was then filtered at 85° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 6.5 mg KOH/g.
A mixture of sorbitol (62.6 g, 0.344 mol, 1.00 eq.), stearic acid (acid number=198 mg KOH/g, ≥92%, 146.7 g, 0.516 mol, 1.50 eq.) and Novozym 435 (7.77 g, 54393 PLU) was stirred at 90° C. and <7 mbar for 24 h, and the water formed was distilled off continuously. The mixture was then filtered at 85° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 10.4 mg KOH/g.
A mixture of sorbitol (71.4 g, 0.392 mol, 1.00 eq.) and lauric acid (acid number=280 mg KOH/g, ≥99%, 141.3 g, 0.705 mol, 1.80 eq.) was heated to 100° C. while stirring and passing N2 through. After 1 h, the mixture was cooled down to 95° C., immobilized Candida antarctica lipase B enzyme (6.38 g; Purolite D5619, corresponding to 55227 PLU) was added, and stirring of the mixture was continued at 95° C. and 20 mbar for 24 h, during which time the water formed was distilled off continuously. The mixture was then filtered at 80° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 3.5 mg KOH/g.
A mixture of sorbitol (70% aqueous solution, 390.0 g, 1.50 mol, 1.00 eq.), lauric acid (acid number=280 mg KOH/g, ≥99%, 330.0 g, 1.65 mol, 1.10 eq.) and K2CO3 (16 g) were heated to 180° C. while stirring and passing N2 through, and the water formed was distilled off continuously until an acid number of 3.5 mg KOH/g had been attained.
A mixture of sorbitol (99.0 g, 0.54 mol, 1.00 eq.), methyl laurate (140.0 g, 0.65 mol, 1.20 eq.) and K2CO3 (6 g) was heated to 160° C. at 50 mbar while stirring for 5 h, during which time the methanol formed was distilled off continuously.
A mixture of sorbitol (71.4 g, 0.392 mol, 1.00 eq.), lauric acid (acid number=280 mg KOH/g, ≥99%, 141.3 g, 0.705 mol, 1.80 eq.) and Novozym 435 (49.8 g, 348253 PLU) was stirred at 90° C. and <7 mbar for 24 h, and the water formed was distilled off continuously. The mixture was then filtered at 85° C. through a Büchner funnel with black band filter to remove the enzyme. The product obtained had an acid number of 2.8 mg KOH/g.
Table 1 compares the parameters determined for the examples according to the invention and the noninventive examples.
More particularly, it is apparent from Examples 4, 4B and 4C that the sorbitol carboxylates prepared by the process according to the invention have a better colour than those from the conventional chemical synthesis.
The thickening action of the inventive examples was evaluated by comparison with the corresponding noninventive examples in two different formulations:
Formulation 1 consisted of 9% SLES, 3% Cocamidopropyl Betaine and 0.7% NaCl in water. The pH of formulation 1 was adjusted to 5.2 with citric acid. Subsequently incorporated into this formulation in each case was 1.1% of the example substances mentioned above by stirring at 60° C. for 30 min, and the viscosities were measured using a Brookfield viscometer (spindle 62, 30 rpm, in Examples 1, 1B, 1C, 2, 2B; spindle 2, 60 rpm, in Examples 3, 3B, 4, 4B, 4C, 4D) at 22° C.
Formulation 2 consisted of 5.6% AM C, 4.4% Lauryl Glucoside, 1.2% Coco-Glucoside and 3.6% Glutamate in water. The pH of formulation 2 was adjusted to 5.2 with citric acid. Subsequently incorporated into this formulation in each case was 1.0% of the example substances mentioned above by stirring at 60° C. for 30 min, and the viscosities were measured using a Brookfield viscometer (spindle 62, 30 rpm, in Examples 1, 1B, 1C, 2, 2B; spindle 2, 60 rpm, in Examples 3, 3B, 4, 4B, 4C, 4D) at 22° C.
The results of the viscosity measurements are shown in Table 2.
§Example 3B was not fully soluble in formulation 2, which is a further disadvantage of this noninventive example.
The results from Table 2 show that higher viscosities are achieved with the inventive Example 1 in both formulations than with the noninventive Examples 1B and 1C, The same is found for the inventive Example 2 compared to the noninventive Example 2B, and for 3 versus 3B and 4 versus 4B, 4C and 4D.
The literature Biotechnol Bioeng 1995 48 214-221 describes the use of extremely high amounts of enzyme, namely about 494 000 PLU per mole of fatty acid used. Such a high enzyme load is uneconomic. Loads of interest are around 100 000 PLU per mole of fatty acid used or lower. In the case of Examples 3 (inventive) and 3B (noninventive), after the reaction had ended and after the enzyme had been removed, the acid number was determined and an aliquot (about 30 g) in a 100 ml glass measuring cylinder was left in a heated cabinet at 90° C. for 24 h and then, after the phases had separated, the ratio (v/v) of the upper ester phase to the lower sorbitol phase was determined.
Table 2 presents the results.
It becomes clear from the data shown in Table 2 that the process according to the invention has the advantage compared to the process described in the prior art that, after a reaction time of 24 h, a low acid number has already been attained, which is desirable, and the sorbitol phase that separates in the melt likewise represents a smaller proportion.
A further advantage of the process according to the invention is found in a comparison of Example 1 with 1C. In spite of seven times the amount of lipase, after a reaction time of 24 h, in the prior art process, the conversion rate measured by the acid number is within the same range as in the process according to the invention.
A similar picture is found in a comparison of Example 2 with 2B. With the same amount of lipase, after a reaction time of 24 h, in the prior art process, the conversion rate measured by the acid number is actually clearly lower than in the process according to the invention.
A similar picture is found in a comparison of Example 4 with 4D. With the same amount of lipase, after a reaction time of 24 h, in the prior art process, the conversion rate is within the same range as in the process according to the invention.
Persea Gratissima (avocado) Oil
Prunus Amygdalus Dulcis (sweet almond) Oil
Terminalia Arjuna Bark Extract;
Persea Gratissima (avocado) Oil
Persea Gratissima (avocado) Oil
Butyrospermum Parkii Butter (shea butter)
Primus Amygdalus Dulcis (sweet almond) Oil
Prunus Amygdalus Dulcis (sweet almond) Oil
Helianthus Annuus Seed Oil (AEC Sunflower Oil, A & E
Lavandula Angustifolia (lavender) Oil
Argania spinosa oil (Argan Oil, DSM Nutritional Products Ltd.)
Mangifera Indica (mango) Fruit Extract (Mango Extract, Draco
Olea Europaea Fruit Oil (Cropure Olive, Croda Europe, Ltd.)
Formulation 51: Micellar Water for Makeup Removal
Aloe Barbadensis Leaf Extract (Aloe-Con UP 40, Florida Food
| Number | Date | Country | Kind |
|---|---|---|---|
| 19218421.6 | Dec 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/086739 | 12/17/2020 | WO |
