The invention provides a process for the enzymatic preparation of sugar esters and/or sugar alcohol esters and also provides mixture compositions containing sugar esters and/or sugar alcohol esters.
Fatty acid esters of sugars and sugar alcohols have surfactant properties and due to their natural raw material basis and sustainability are in particular suitable for applications in the food sector and in the cosmetics industry.
Fatty acid esters of sugars or sugar alcohols are conventionally synthesized by reaction of the sugars or sugar alcohols with fatty acid chlorides in the presence of pyridine (Surfactants, K. Kosswig in Ullmann's Encyclopedia of Industrial Chemistry, Online, Wiley-VCH, Weinheim, 2000, https://doi.org/10.1002/14356007.a25_747).
However, a disadvantage of this process described in the prior art is that the use of such solvents for applications in the food or cosmetics sector is not acceptable and in addition a corresponding removal of the solvents requires additional process steps such as crystallization, filtration or distillation. A further disadvantage of this process described in the prior art is the quantitative release of HCl when using fatty acid chlorides, since HCl can lead to corrosion of the metallic surfaces of the reactors.
An alternative prior art process which is used in particular on an industrial scale reacts the sugars or sugar alcohols with the free fatty acids or the fatty acid alkyl esters in the absence of a solvent at temperatures of 200-250° C. in the presence of basic catalysts such as sodium hydroxide (Römpp, Georg Thieme Verlag K G, 2019 under the heading “Sorbitans” and Surfactants, K. Kosswig in Ullmann's Encyclopedia of Industrial Chemistry, Online, Wiley-VCH, Weinheim, 2000, https://doi.org/10.1002/14356007.a25_747). However, a disadvantage of this process described in the prior art is that, during the reaction for example of sorbitol under the conditions mentioned, dehydration of the sugars or sugar alcohols occurs as a side reaction. This side reaction occurs in the presence of acidic catalysts even from temperatures as low as approx. 140° C. For example, sorbitol is dehydrated first to sorbitan (by the loss of a molecule of water) and further to isosorbide (by the loss of a further molecule of water). The sugars or sugar alcohols used thus lose hydrophilicity and are thus increasingly less suitable as hydrophilic head groups for surfactants. A further disadvantage of this process described in the prior art is that the side reactions occurring lead to a dark colouration of the products obtained, which possibly requires a further treatment, for example with bleaching agents such as hydrogen peroxide or activated carbon, in order to be able to use the products obtained in cosmetic formulations, for example. This process described in the prior art has the further disadvantage that the side reactions occurring lead to an unpleasant odour in the products obtained, which can interact undesirably with the perfume used in cosmetic formulations.
The enzyme-catalyzed preparation of fatty acid esters of sugars or sugar alcohols in dilute solutions in organic solvents such as 2-methyl-2-butanol, pyridine, dimethylformamide or 2-pyrrolidone has been described (A. Ducret, A. Giroux, M. Trani, and R. Lortie, Characterization of enzymatically prepared biosurfactants, J. Am. Oil Chem. Soc. 1996, 73, 109-113, doi: 10.1007/BF02523456; M. Therisod, A. M. Klibanov, Facile enzymatic preparation of monoacylated sugars in pyridine, J. Am. Chem. Soc., 1986, 108 (18), pp 5638-5640; J. Chem. Soc., Perkin Trans. 1, 1939,0, 1057-1061, 10.1039/P19890001057; A. E. M. Janssen, C. Klabbers, M. C. R. Franssen, K. van't Riet, Enzymatic synthesis of carbohydrate esters in 2-pyrrolidone, Enzyme and Microbial Technology, 1991, 13 (7), 565-572). However, a disadvantage of these processes described in the prior art is that the use of such solvents for applications in the food or cosmetics sector is not acceptable and in addition a corresponding removal of the solvents requires additional process steps that consume large amounts of energy, such as crystallization, filtration or distillation.
An enzymatic synthesis of fatty acid esters of sugars or sugar alcohols using dilute aqueous solutions of enzymes is described in A. E. M. Janssen, A. G. Lefferts, K. van't Riet, Enzymatic synthesis of carbohydrate esters in aqueous media, Biotechnology Letters 1990, 12 (10), 711-716, DOI https://doi.org/10.1007/BF01024726; H. Seino, T. Uchibori, T. Nishitani, et al., Enzymatic synthesis of carbohydrate esters of fatty acid (I) esterification of sucrose, glucose, fructose and sorbitol, J. Am, Oil Chem. Soc. 1984, 61 1761-1765, https://doi.org/10.1007/BF02582144 and in WO9412651. Disadvantages of this process described in the prior art are the energy-demanding process steps additionally required for isolating the products from the aqueous systems, such as crystallization, filtration or distillation, and additionally in the case of buffered aqueous systems the removal of the salt load. A further disadvantage here is that the presence of water when using fatty acids as acyl donor impedes the shifting of the equilibrium position toward the products. A further disadvantage is that enzymes usually exhibit a performance maximum at a particular water activity.
T. Itoh, Ionic Liquids as Tool to Improve Enzymatic Organic Synthesis, Chemical Reviews 2017, 117, 10567-10607 discloses the enzyme-catalyzed preparation of fatty acid esters of sugars or sugar alcohols in ionic liquids as solvents. However, a disadvantage of these processes described in the prior art is that at least one additional, energy-intensive process step such as crystallization, filtration or distillation is required for removing the ionic liquids, since the ionic liquids cannot remain in the product for downstream applications in the food sector or in the cosmetics industry. A further disadvantage of these processes described in the prior art is that the ionic liquids are produced from petrochemical raw materials and hence their use is undesirable for natural and sustainable applications in the food sector or in the cosmetics industry. A further disadvantage of the processes described in the prior art is the use of fatty acid vinyl esters as acyl donor, since these release toxicologically hazardous acetaldehyde during the reaction, which complicates handling on an industrial scale and in addition is undesirable for applications in the food sector or in the cosmetics industry. In addition, the fatty acid vinyl esters are prepared from petrochemical raw materials such as acetylene or ethylene in the presence of toxicologically hazardous metal catalysts such as mercury, cadmium, palladium or silver salts (G. Roscher, Vinyl Esters in Ullmann's Encyclopedia of Industrial Chemistry, Online, Wiley-VCH, Weinheim, 2012, DOI: 10.1002/14356007.a27_419), which precludes use of these raw materials for natural and sustainable applications in the food sector or in the cosmetics industry.
The enzyme-catalyzed preparation of fatty acid esters of sugars or sugar alcohols in the presence of choline chloride (or other ammonium or phosphonium salts) to form deep eutectic mixtures has also been described (S. Siebenhaller, C. Muhle-Goll, B. Luy, F. Kirschhöfer, G. Brenner-Weiss, E. Hiller, et al., Sustainable enzymatic synthesis of glycolipids in a deep eutectic solvent system, J. Mol. Catal. B Enzym. 2016, 133, 281-287, doi:10.1016/j.molcatb.2017.01.015). However, a disadvantage of this process described in the prior art is that choline chloride or other ammonium or phosphonium salts as a result of their salt character can negatively affect the use profiles of fatty acid esters of sugars or sugar alcohols, if they remain in the product. A further disadvantage of this process described in the prior art is that the industrially available quality of choline chloride is a petrochemical raw material, the presence of which in the product is therefore undesirable for natural and sustainable applications in the food sector or in the cosmetics industry. It is thus a further disadvantage of this process described in the prior art that at least one additional process step such as crystallization, filtration or distillation is necessary for removing the choline chloride or other ammonium or phosphonium salts.
The enzyme-catalyzed esterification of an individual sugar present in honey or agave syrup with fatty acid vinyl esters as acyl donor is described in S. Siebenhaller, J. Gentes, A. Infantes, C. Muhle-Goll, F. Kirschhöfer, G. Brenner-Weiß, K. Ochsenreither, C. Syldatk, Lipase-Catalyzed Synthesis of Sugar Esters in Honey and Agave Syrup, Front. Chem. 2018, 6, Article 24, 1-9, doi: 10.3389/fchem.2018.00024). A disadvantage of this process described in the prior art is the use of fatty acid vinyl esters as acyl donor, since these release toxicologically hazardous acetaldehyde during the reaction, which complicates handling on an industrial scale and in addition is undesirable for applications in the food sector or in the cosmetics industry. In addition, the fatty acid vinyl esters are prepared from petrochemical raw materials such as acetylene or ethylene in the presence of toxicologically hazardous metal catalysts such as mercury, cadmium, palladium or silver salts (G. Roscher, Vinyl Esters in Ullmann's Encyclopedia of Industrial Chemistry, Online, Wiley-VCH, Weinheim, 2012, DOI: 10.1002/14356007.a27_419), which precludes use of these raw materials for natural and sustainable applications in the food sector or in the cosmetics industry. A further disadvantage of this process described in the prior art is the use of at most only 0.066 equivalents of the acyl donor based on the total amount of sugars and sugar alcohols. A further disadvantage of this process described in the prior art is that the large excess of the sugars and sugar alcohols used necessitates at least one further additional process step such as extraction, crystallization, filtration or distillation for isolation of the fatty acid esters of the sugars and sugar alcohols. A further disadvantage of this process described in the prior art is that the large excess of the sugars and sugar alcohols used is uneconomical on an industrial scale and in addition necessitates complex recycling of the sugars and sugar alcohols used. A further disadvantage of this process described in the prior art is that, in the case of honey as substrate, only glucose esters are detected and, in the case of agave syrup as substrate, only fructose esters are detected, that is to say in each case only one of the sugar components present in the honey or agave syrup is actually esterified.
JPS58116688 discloses the enzymatically catalyzed esterification of mixtures of polysaccharides and/or monosaccharides and oligosaccharides: oligosaccharides and/or polysaccharides are thus always present. The reactions are carried out in water or hexane as solvent; the comparative examples show that, without solvent or with only small quantities of solvent, barely any conversion can be achieved.
KR20180007129 discloses a process for preparing mixtures of sucrose esters, fructose esters and glucose esters by enzymatic esterification of sucrose.
The process is carried out in solutions which have been diluted with water to such an extent that lauric acid employed is present in dissolved form. Owing to the aqueous, acidic conditions, sucrose is split into the corresponding monosaccharides and esterified during the course of the reaction.
The acyl groups are always employed in deficiency, in relation to esterified saccharides obtained, so that the product always contains unreacted saccharides. The sucrose esters always make up the majority of esters obtained.
A further disadvantage of this prior art process is that the ratio of the different saccharide esters obtained cannot be predicted or controlled.
The object of the invention was to provide a process for preparing sugar esters and/or sugar alcohol esters which contain in particular 4 to 12, preferably 4 to 6, carbon atoms in the sugar moiety or sugar alcohol moiety, which is able to overcome at least one disadvantage of the processes of the prior art. In particular, the sugar esters and/or sugar alcohol esters are to be represented by the readily available sugars or sugar alcohols having 4 to 12, preferably 4 to 6, carbon atoms.
Surprisingly, it has been found that the process described hereinafter is able to achieve the object of the invention.
The present invention provides a process for the enzymatic preparation of a mixture composition comprising at least two selected from sugar esters and/or sugar alcohol esters which contain 4 to 12, preferably 4 to 6, carbon atoms in the sugar moiety or sugar alcohol moiety, comprising the process step
B) reacting a mixture containing at least two selected from sugars and sugar alcohols, wherein the sugars and sugar alcohols contain in particular 4 to 12, preferably 4 to 6, carbon atoms,
with at least one acyl group donor, preferably fatty acid acyl group donor, especially selected from fatty acid esters and fatty acids, particularly preferably fatty acids,
in the presence of a lipase.
The invention further provides mixture compositions containing particular sugar esters and/or sugar alcohol esters which contain in particular 4 to 12, preferably 4 to 6, carbon atoms in the sugar moiety or sugar alcohol moiety.
An advantage of the present invention is that the process according to the invention can be carried out in the absence of a solvent.
Another advantage of the present invention is that the process according to the invention can be carried out using natural and sustainable synthesis components.
A further advantage of the present invention is that the sugar esters and/or sugar alcohol esters according to the invention are obtained in homogeneous reaction mixtures, and this property can be achieved even at low degrees of esterification.
A further advantage of the present invention is that the sugar esters and/or sugar alcohol esters according to the invention have outstanding colour properties.
A further advantage of the present invention is that the sugar esters and/or sugar alcohol esters according to the invention have low odour, in particular a caramel-typical odour is barely perceptible.
An advantage of the present invention is that substrates in a mixture can be successfully converted, whereas their conversion alone in the absence of a solvent is not successful.
A further advantage of the present invention is that no undesired byproducts are formed from the employed sugars/sugar alcohols by elimination of water, such as sorbitans from sorbitol.
A further advantage of the present invention is that the sugar esters and/or sugar alcohol esters obtained can be incorporated very readily into formulations, especially into cosmetic formulations.
A further advantage of the present invention is that gentle formulations can be prepared using the sugar esters and/or sugar alcohol esters obtained.
A further advantage of the present invention is that formulations having a particularly good skin feel can be prepared using the sugar esters and/or sugar alcohol esters obtained.
A further advantage of the present invention is that sustainable formulations without petrochemical components can be prepared using the sugar esters and/or sugar alcohol esters obtained.
A further advantage of the present invention is that the sugar esters and/or sugar alcohol esters obtained can be prepared without the quantitative release of HCl or acetaldehyde.
A further advantage of the present invention is that the reaction can be effected in a bubble column on account of the good miscibility of the reaction mixture, as a result of which relatively long catalyst lifetimes can be achieved.
A further advantage of the present invention is that a large amount of acyl donors can be used, based on the total molar amount of sugars and/or sugar alcohols.
A further advantage of the present invention is that the esters of the sugars and sugar alcohols used are obtained in a homogeneous reaction mixture, so that no additional process steps such as extraction, crystallization, filtration or distillation are required.
A further advantage of the present invention is that during the reaction more than just one of the sugar and sugar alcohol components used is esterified.
A further advantage of the present invention is that homogeneous melts are obtained when reacting at relatively low degrees of esterification.
The present invention provides a process for the enzymatic preparation of a mixture composition comprising at least two selected from sugar esters and/or sugar alcohol esters which contain in particular 4 to 12, preferably 4 to 6, carbon atoms in the sugar moiety or sugar alcohol moiety, comprising the process step
B) reacting a mixture containing at least two selected from sugars and sugar alcohols with at least one acyl group donor, preferably fatty acid acyl group donor, especially selected from fatty acid esters and fatty acids, particularly preferably fatty acids,
in the presence of a lipase.
The term “two selected from sugar esters and/or sugar alcohol esters” in the context of the present invention should be understood to mean that the two esters differ in terms of their sugars and/or in terms of their sugar alcohols. Esters must therefore be present which have two different residues in terms of sugar and/or sugar alcohol residue.
Unless stated otherwise, all percentages (%) given are percentages by mass.
In accordance with the invention, all of the sugars and sugar alcohols, such as for example agarose, amylopectin, amylose, cellulose, chitin, cyclodextrins, dextrans, fructans, glycogen, hyaluronic acid, inulin, isomelizitose, maltohexose, maltopentose, maltotetrose, maltotriose, melizitose, pectins, raffinose, stachyose, starch, starch hydrolysate, umbelliferose, cellobiose, isomalt, isomaltulose, lactitol, lactose, lactulose, maltitol, maltose, maltulose, sucrose, trehalose, trehalulose,
allitol, allulose, altritol, arabinitol, arabinose, deoxyribose, erythritol, fructose, fucose, galactitol, galactose, glucose, iditol, mannitol, mannose, rhamnose, ribitol, ribose, sorbitol, sorbose, threitol, xylitol and xylose, can be employed.
Preferably in accordance with the invention, the sugars and sugar alcohols are selected from the group of sugars and sugar alcohols containing 4 to 12, preferably 4 to 6, carbon atoms.
Preferably in accordance with the invention, the sugars and sugar alcohols from the group of sugars and sugar alcohols containing 4 to 12 carbon atoms are selected from
cellobiose, isomalt, isomaltulose, lactitol, lactose, lactulose, maltitol, maltose, maltulose, sucrose, trehalose, trehalulose,
allitol, allulose, altritol, arabinitol, arabinose, deoxyribose, erythritol, fructose, fucose, galactitol, galactose, glucose, iditol, mannitol, mannose, rhamnose, ribitol, ribose, sorbitol, sorbose, threitol, xylitol and xylose,
wherein allitol, allulose, altritol, arabinitol, arabinose, cellobiose, deoxyribose, erythritol, fructose, fucose, galactitol, galactose, glucose, iditol, isomalt, isomaltulose, lactitol, lactose, lactulose, maltitol, maltose, maltulose, mannitol, mannose, rhamnose, ribitol, ribose, sorbitol, sorbose, threitol, trehalulose, xylitol and xylose are particularly preferred and
erythritol, fructose, glucose, isomalt, isomaltulose, lactitol, lactose, maltitol, maltose, maltulose, mannitol, sorbitol, sorbose, xylitol and xylose are very particularly preferred.
Preferably in accordance with the invention, the sugars and sugar alcohols from the group of sugars and sugar alcohols containing 4 to 6 carbon atoms are selected from
allitol, allulose, altritol, arabinitol, arabinose, deoxyribose, erythritol, fructose, fucose, galactitol, galactose, glucose, iditol, mannitol, mannose, rhamnose, ribitol, ribose, sorbitol, sorbose, threitol, xylitol and xylose, wherein erythritol, fructose, glucose, sorbitol, xylitol and xylose are particularly preferred.
Particularly preferably in accordance with the invention, the sugars and sugar alcohols are selected from the group.
A process which is preferred according to the invention is characterized in that in process step B), as mixture containing at least two selected from sugars and sugar alcohols, mixtures containing glucose, fructose and maltose with, in each case based on all sugars and sugar alcohols present in the mixture, a glucose content of 40% by weight to 50% by weight and a fructose content of 47% by weight to 57% by weight, and
glucose, fructose and sucrose with, in each case based on all sugars and sugar alcohols present in the mixture, a glucose content of 5% by weight to 24% by weight and a fructose content of 75% by weight to 94% by weight
are excluded.
Any acyl group donors may be used according to the invention. These are, for example, carboxylic esters or carboxylic acids themselves and mixtures thereof.
Preferably in accordance with the invention, carboxylic esters used 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 preferably glycerol esters.
Especially preferably in accordance with the invention, carboxylic esters used 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 hereinafter, may likewise preferably be used.
Preferably in accordance with the invention, the acyl group donor is selected from fatty acid acyl group donors which in particular provide an acyl group selected from the group of acyl groups of natural fatty acids. Natural fatty acids can be produced on the basis of naturally occurring vegetable or animal oils and have preferably 6-30 carbon atoms, especially 8-22 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, palmitoleic acid, pelargonic acid (obtainable from the ozonolysis of oleic acid), isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, undecylenic acid (obtainable from the pyrolysis of ricinoleic acid), oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachic acid, behenic acid, erucic acid, gadoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.
Preferably in accordance with the invention, acyl group donors used are carboxylic acids, especially fatty acids, with particular preference being given to using the fatty acids specifically mentioned hereinabove.
It is preferable in accordance with the invention for vinyl esters as acyl group donors to be excluded, because these release toxicologically hazardous acetaldehyde during the reaction, which complicates handling on an industrial scale and in addition is undesirable for applications in the food sector or in the cosmetics industry. In addition, the fatty acid vinyl esters are prepared from petrochemical raw materials such as acetylene or ethylene in the presence of toxicologically hazardous metal catalysts such as mercury, cadmium, palladium or silver salts (G. Roscher, Vinyl Esters in Ullmann's Encyclopedia of Industrial Chemistry, Online, Wiley-VCH, Weinheim, 2012, DOI: 10.1002/14356007.a27_419), which precludes use of these raw materials for natural and sustainable applications in the food sector or in the cosmetics industry.
According to the invention, it is in particular preferable for the sugars and sugar alcohols to be selected from erythritol, fructose, glucose, sorbitol, xylitol and xylose and for the acyl group donor to be selected from at least one from the group of caproic acid, caprylic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachic acid, behenic acid, erucic acid, gadoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.
A process which is preferred in accordance with the invention is characterized in that the mixture used in process step B) and containing at least two selected from sugars and sugar alcohols comprises substances selected from the group consisting of choline salts, ammonium salts and phosphonium salts in an amount of less than 2% by weight, preferably less than 1% by weight, particularly preferably less than 0.1% by weight, especially does not comprise any of these substances, where the weight percentages relate to all sugar and sugar alcohols in process step B) in the mixture containing at least two selected from sugars and sugar alcohols.
A process which is preferred in accordance with the invention is characterized in that in process step B) the molar ratio of all sugars and sugar alcohols to acyl groups present in all acyl group donors is in a range from 1.00:0.08 to 1.00:10.00, preferably from 1.00:0.50 to 1.00:7.00, particularly preferably from 1.00:1.25 to 1.00:2.25, alternatively particularly preferably from 1.00:2.00 to 1.00:4.50.
A process which is preferred in accordance with the invention is characterized in that in process step B) the molar ratio of all primary hydroxyl groups in all sugars and sugar alcohols to acyl groups present in all acyl group donors is in a range from 1.00:0.10 to 1.00:3.00, particularly preferably from 1.00:1.25 to 1.00:2.25.
A process which is preferred in accordance with the invention is characterized in that in process step B) a mixture containing sugars and/or sugar alcohols having 4 to 6 carbon atoms is employed and the molar ratio of all primary hydroxyl groups in all sugars and sugar alcohols having 4 to 6 carbon atoms to acyl groups present in all acyl group donors is in a range from 1.00:0.20 to 1.00:1.5.
Lipases used with preference in accordance with the invention 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), and their respective at least 60%, with preference at least 80%, preferably at least 90%, particularly preferably at least 95%, 98% or 99%, homologues at the amino acid level.
The enzymes that are homologous at the amino acid level, by comparison with the reference sequence, preferably have at least 50%, especially at least 90%, enzyme activity in propyl laurate units as defined in the context of the present invention.
Commercial examples, and carboxylic ester hydrolases 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 “Amano”, 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” in the context of the present invention is understood to mean “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 initially generate the greatest alignment between the sequences to be compared. Computer programs for determining the identity include, but are not limited to, the GCG program package including
The person skilled in the art is 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. The person 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 used applying 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.
Preferably in accordance with the invention, process step B) is conducted at reaction temperatures in the range between 20° C. and 160° C., preferably 35° C. and 130° C., in particular between 50° C. and 110° C.
Preferably in accordance with the invention, process step B) is conducted at a pressure of less than 1 bar, preferably less than 0.5 bar and particularly preferably less than 0.05 bar.
Alternatively preferably in accordance with the invention, process step B) is conducted 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 context, 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.
A process which is preferred in accordance with the invention is characterized in that in process step B) the mixture containing at least two selected from sugars and sugar alcohols and the acyl group donor make up in total at least 10% by weight, preferably at least 86% by weight, particularly preferably at least 90% by weight, of the overall reaction mixture.
The abovementioned high proportions by weight of the starting materials leave correspondingly little room for the presence of solvents, such as for example water or hexane.
A process which is preferred in accordance with the invention is characterized in that, in the process, solvent, in particular water or hexane, is added in an amount of at most 5% by weight, preferably at most 2% by weight, particularly preferably is not added at all, where the weight percentages relate to the overall reaction mixture.
A process which is preferred in accordance with the invention is characterized in that byproducts forming in process step B), for example water in the case where the acyl group donor used is an acid, the corresponding alcohol in the case where the acyl group donor used is an ester, are removed.
This is possible for example by distillation.
Preferably in accordance with the invention, the process according to the invention comprises process step A) providing the at least two selected from sugars and sugar alcohols spatially separately from each other in solid form or in a form dissolved in water and mixing them to give the mixture used in process step B) and containing at least two selected from sugars and sugar alcohols. It may be especially preferable here to concentrate the mixture containing at least two selected from sugars and sugar alcohols and the acyl group donor by means of removing water, in order for the abovementioned mixture and acyl group donor to reach in total at least 10% by weight, preferably at least 86% by weight, particularly preferably at least 90% by weight, of the overall reaction mixture.
In this context, it is especially preferable for process step A) to comprise a reduction of the water content of the mixture used in process step B) and containing at least two selected from sugars and sugar alcohols to less than 17% by weight, preferably less than 14% by weight, particularly preferably less than 10% by weight, where the weight percentages relate to the total mixture used in process step B) and containing at least two selected from sugars and sugar alcohols.
Preferably in accordance with the invention, the process according to the invention comprises process step C) removing the lipase.
Likewise preferably in accordance with the invention, the process according to the invention comprises process step D) filtering the mixture composition comprising at least two selected from sugar esters and/or sugar alcohol esters through a filter, especially a bag filter, having a fineness of 0.1μ to 1250μ, preferably from 0.5μ to 100μ.
Preferably in accordance with the invention, process step D) is conducted in a temperature range of from 20° C. to 150° C., especially 40° C. to 120° C.
Preferably in accordance with the invention, process step D) is conducted in a pressure range of from 1 bar to 25 bar, especially of from 1.5 bar to 10 bar.
Preferably in accordance with the invention, the process according to the invention does not comprise any further purification step besides process steps C) and D), if these are present.
The present invention further provides a mixture composition comprising at least two selected from sugar esters and sugar alcohol esters obtainable by the process according to the invention which contain in particular 4 to 12, preferably 4 to 6, carbon atoms in the sugar moiety or sugar alcohol moiety.
The present invention also provides a mixture composition containing sugar esters and/or sugar alcohol esters, characterized in that the sugar and/or sugar alcohol residue of the sugar ester and/or of the sugar alcohol ester is selected from at least two sugar and/or sugar alcohol residues selected from the group of the residues of allitol, allulose, altritol, arabinitol, arabinose, cellobiose, deoxyribose, erythritol, fructose, fucose, galactitol, galactose, glucose, iditol, iditol, isomalt, isomaltulose, lactitol, lactose, lactulose, maltitol, maltose, maltulose, mannitol, mannose, rhamnose, ribitol, ribose, sucrose, sorbitol, sorbose, threitol, trehalose, trehalulose, xylitol and xylose,
preferably from erythritol, fructose, glucose, isomalt, isomaltulose, lactitol, lactose, maltitol, maltose, maltulose, mannitol, sucrose, sorbitol, sorbose, xylitol and xylose, especially preferably from erythritol, fructose, glucose, sorbitol, xylitol and xylose, and
the ester residue is selected from at least one acyl group of the group of acid residues of the fatty acids,
preferably of caproic acid, caprylic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, isostearic acid, stearic acid, 12-hydroxystearic acid, dihydroxystearic acid, oleic acid, linoleic acid, linolenic acid, petroselinic acid, elaidic acid, arachic acid, behenic acid, erucic acid, gadoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonic acid.
Mixture compositions that are preferred in accordance with the invention contain preferably 4 to 6 carbon atoms in the sugar moiety or sugar alcohol moiety.
Mixture compositions that are preferred in accordance with the invention contain the sugar ester and/or the sugar alcohol ester in an amount of at least 50% by weight, preferably at least 80% by weight, particularly preferably at least 95% by weight, where the percentages by weight relate to the overall mixture composition.
Mixture compositions that are preferred in accordance with the invention are characterized in that the sugar esters and/or sugar alcohol esters present have a degree of esterification of 1.00 and above, in particular of 1.00 to 7.00, particularly preferably of 1.25 to 2.25, alternatively particularly preferably of 2.00 to 4.50.
The examples which follow describe the present invention by way of example, without any intention of restricting the invention, the scope of application of which is apparent from the entirety of the description and the claims, to the embodiments cited in the examples.
Method for Determining the Acid Number
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.
Method for Determining the Specific Activity of the Enzyme Used in PLU
To determine the enzymatic 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 is timed. Samples are taken from the reaction mixture at intervals, and the content of lauric acid converted is determined by means of titration with potassium hydroxide solution. Enzyme activity in PLU is found 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, especially [0185].
Method for Determining the Colour Numbers
An aliquot (approx. 10 g; so that the cuvette is sufficiently filled), was measured in a Lico 690 spectral colorimeter at 90° C. in an 11 mm round cuvette, and the colour numbers reported in each case were recorded.
A mixture of xylitol (60.0 g, 0.394 mol, 1.00 eq.) and caprylic acid (acid number=389 mg KOH/g, >98%, 113.70 g, 0.788 mol, 2.00 eq.) was heated to 80° C. with stirring and while passing N2 through, and after 1 h immobilized Candida antarctica lipase B enzyme (5.21 g; Purolite D5619, corresponding to 45110 PLU) was added. The mixture was stirred at 80° C. and 15 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme.
The product obtained was homogeneous in the melt, colourless and had an acid number of 1.8 mg KOH/g.
A mixture of fructose (83.31 g, 0.462 mol, 1.00 eq.) and caprylic acid (acid number=389 mg KOH/g, >98%, 133.36 g, 0.925 mol, 2.00 eq.) was heated to 80° C. with stirring and while passing N2 through, and after 30 min immobilized Candida antarctica lipase B enzyme (6.50 g; Fermenta BIOCATALYST CALBTA 10000 NLT 95%, corresponding to 63788 PLU) was added. The mixture was stirred at 80° C. and 20 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was inhomogeneous in the melt, reddish coloured and had an acid number of approx. 140.5 mg KOH/g (due to the inhomogeneity the acid number could not be determined unambiguously).
A mixture of an ester obtained as described in Example 1 (42.00 g) and an ester as described in Example 2 (18.00 g) was heated to 80° C. for 1 h with stirring and while passing N2 through. The product obtained was inhomogeneous in the melt, cloudy, orange and had an acid number of approx. 40 mg KOH/g (due to the inhomogeneity the acid number could not be determined unambiguously).
A mixture of xylitol (42.00 g, 0.276 mol), D-(−)-fructose (18.00 g, 0.100 mol) and caprylic acid (acid number=389 mg KOH/g, >98%, 108.40 g, 0.752 mol, 2.00 eq. based on the total initial weight of xylitol and fructose) was heated to 80° C. with stirring and while passing N2 through, and after 1 h immobilized Candida antarctica lipase B enzyme (5.05 g; Purolite D5619, corresponding to 43724 PLU) was added. The mixture was stirred at 80° C. and 15 mbar for 27 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and yellowish and had an acid number of 2.4 mg KOH/g.
A mixture of xylitol (89.14 g, 0.586 mol, 1.00 eq.) and caprylic acid (acid number=389 mg KOH/g, >98%, 126.7 g, 0.879 mol, 1.50 eq.) was heated to 80° C. with stirring and while passing N2 through, and after 30 min immobilized Candida antarctica lipase B enzyme (6.47 g; Fermenta BIOCATALYST CALBTA 10000 NLT 95%, corresponding to 63493 PLU) was added. The mixture was stirred at 80° C. and 20 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and colourless and had an acid number of 1.3 mg KOH/g.
A mixture of sorbitol (98.09 g, 0.538 mol, 1.00 eq.) and caprylic acid (acid number=389 mg KOH/g, >98%, 116.47 g, 0.808 mol, 1.50 eq.) was heated to 100° C. with stirring and while passing N2 through, and after 30 min immobilized Candida antarctica lipase B enzyme (6.44 g; Purolite D5619, corresponding to 55759 PLU) was added. The mixture was subsequently stirred at 90° C. and 50 mbar for 24 during which time the water formed was continuously distilled off. The product obtained was, after 24 h, inhomogeneous, pale yellow and had an acid number of approx. 10-11 mg KOH/g (due to the inhomogeneity the acid number could not be determined unambiguously).
A mixture of an ester obtained as described in Example 5 (42.00 g) and of an ester as described in Example 6 (18.00 g) was heated to 80° C. for 1 h with stirring and while passing N2 through. The product obtained was inhomogeneous in the melt and had an acid number of 3.7 mg KOH/g.
A mixture of xylitol (64.15 g, 0.421 mol), sorbitol (27.49 g, 0.151 mol) and caprylic acid (acid number=389 mg KOH/g, >98%, 123.81 g, 0.859 mol, 1.50 eq. based on the total initial weight of xylitol and sorbitol) was heated to 80° C. with stirring and while passing N2 through, and after 30 min immobilized Candida antarctica lipase B enzyme (6.02 g; Fermenta BIOCATALYST CALBTA 10000 NLT 95%, corresponding to 59077 PLU) was added. The mixture was subsequently stirred at 80° C. and 20 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and colourless and had an acid number of 1.6 mg KOH/g.
A mixture of xylitol (11.72 g, 0.077 mol), sorbitol (6.01 g, 0.033 mol) and oleic acid (acid number=200 mg KOH/g, iodine number=92.3 g I2/100 g, 61.7 g, 0.22 mol, 2.00 eq. based on the total initial weight of xylitol and sorbitol) was heated to 90° C. with stirring and while passing N2 through, and after 30 min immobilized Candida antarctica lipase B enzyme (2.3 g; Fermenta BIOCATALYST CALBTA 10000 NLT 95%, corresponding to 59077 PLU) was added. The mixture was subsequently stirred at 80° C. and 10 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, slightly cloudy and pale yellow and had an acid number of 2.0 mg KOH/g.
A mixture of xylitol (28.0 g, 0.184 mol), sorbitol (12.0 g, 0.066 mol) and oleic acid (acid number=200 mg KOH/g, iodine number=92.3 g I2/100 g, 140.2 g, 0.50 mol, 2.00 eq. based on the total initial weight of xylitol and sorbitol) was heated to 80° C. with stirring and while passing N2 through, and after 1 h immobilized Candida antarctica lipase B enzyme (5.40 g; Purolite D5619, corresponding to 46754 PLU) was added. The mixture was subsequently stirred at 80° C. and 25 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, slightly cloudy and pale yellow and had an acid number of 1.9 mg KOH/g.
A mixture of xylitol (40.00 g, 0.263 mol, 1.00 eq.) and stearic acid (acid number=198 mg KOH/g, >92%, 148.18 g, 0.526 mol, 2.00 eq.) was heated to 90° C. with stirring and while passing N2 through, and after 1 h immobilized Candida antarctica lipase B enzyme (5.65 g; Purolite D5619, corresponding to 48919 PLU) was added. The mixture was subsequently stirred at 90° C. and 15 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 80° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear, pale yellow and had an acid number of 1.3 mg KOH/g.
A mixture of fructose (42.00 g, 0.233 mol, 1.00 eq.) and stearic acid (acid number=198 mg KOH/g, >92%, 132.42 g, 0.482 mol, 2.00 eq.) was heated to 90° C. with stirring and while passing N2 through, and after 1 h immobilized Candida antarctica lipase B enzyme (5.18 g; Fermenta BIOCATALYST CALBTA 10000 NLT 95%, corresponding to 50834 PLU) was added. The mixture was subsequently stirred at 90° C. and 15 mbar for 51 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 90° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear, orange-red and had an acid number of 14.7 mg KOH/g.
A mixture of an ester obtained as described in Example 11 (42.00 g) and an ester as described in Example 12 (18.00 g) was heated to 80° C. for 1 h with stirring and while passing N2 through. The product obtained was homogeneous in the melt, clear, orange and had an acid number of 5.1 mg KOH/g.
A mixture of xylitol (28.0 g, 0.184 mol) and fructose (12.0 g, 0.067 mol) was heated to 130° C. with stirring and after 2 h was cooled down to 90° C. Subsequently, stearic acid (acid number=198 mg KOH/g, approx. 95%, 142.14 g, 0.501 mol, 2.00 eq.) was added with stirring and while passing N2 through. After stirring for 30 min at 90° C., immobilized Candida antarctica lipase B enzyme (Puri)lite D5619, 5.46 g, corresponding to 47274 PLU) was added. The mixture was subsequently stirred at 90° C. and 10 mbar for 24 h, during which time the water formed was continuously distilled off. The mixture was subsequently filtered at 80′C and 2 bar N2 pressure through a filter press with a Seitz T-750 depth filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and had an acid number of 3.2 mg KOH/g.
A mixture of xylitol (39.59 g, 0.260 mol), sorbitol (19.80 g, 0.109 mol), fructose (19.80 g, 0.110 mol) and caprylic acid (acid number=389 mg KOH/g, >98%, 138.05 g, 0.957 mol, 1.91 eq. based on the total initial weight of xylitol, sorbitol and fructose) was heated to 100° C. with stirring and while passing N2 through and stirred for 1 h. Subsequently, the mixture was cooled down to 80° C., immobilized Candida antarctica lipase B enzyme (5.92 g; Purolite D5619, corresponding to 51257 PLU) was added and the mixture was stirred further at 80° C. and 20 mbar for 24 h, during which time the water formed was continuously distilled off, Subsequently, the mixture was filtered at 90° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and yellow and had an acid number of 3.1 mg KOH/g.
A mixture of xylitol (52.12 g, 0.342 mol), sorbitol (20.05 g, 0.110 mol), glucose (8.02 g, 0.045 mol) and caprylic acid (acid number=389 mg KOH/g, >98%, 136.91 g, 0.949 mol, 1.91 eq, based on the total initial weight of xylitol, sorbitol and glucose) was heated to 100° C. with stirring and while passing N2 through and stirred for 1 h. Subsequently, the mixture was cooled down to 80° C., immobilized Candida antarctica lipase B enzyme (5.91 g; Purolite D5619, corresponding to 51170 PLU) was added and the mixture was stirred further at 80° C. and 20 mbar for 24 h, during which time the water formed was continuously distilled off, Subsequently, the mixture was filtered at 90° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, clear and pale yellow and had an acid number of 10.0 mg KOH/g.
A mixture of xylitol (51.7 g, 0.340 mol), sorbitol (22.16 g, 0.122 mol) and lauric acid (acid number=280 mg KOH/g, >99%, 138.60 g, 0.692 mol, 1.50 eq. based on the total initial weight of xylitol and sorbitol) was heated to 100° C. with stirring and while passing N2 through, and after 60 min immobilized Candida antarctica lipase B enzyme (6.02 g; Purolite D5619, corresponding to 52122 PLU) was added. The mixture was subsequently stirred at 95° C. and 50 mbar for 24 h, during which time the water formed was continuously distilled off. Subsequently, the mixture was filtered at 90° C. through a Büchner funnel with black ribbon filter in order to remove the enzyme. The product obtained was homogeneous in the melt, slightly cloudy and pale yellow to virtually colourless and had an acid number of 0.8 mg KOH/g.
The examples which follow are intended to illustrate the subject matter of the invention in detail, without restricting said subject matter to these examples. These examples are intended to show that the process according to the invention has advantages with respect to the prior art. In this case, the representatives for the prior art selected were the examples not in accordance with the invention.
Technical Effect: Homogeneity & Odour
Table 1 compares Example 4 according to the invention with Examples 1, 2 and 3 not in accordance with the invention in terms of reaction course, homogeneity and odour.
As can be seen from Table 1, Example 2 not in accordance with the invention after 24 h reaction time is inhomogeneous, still has a high residual acid number of approx. 140.5 mg KOH/g and in addition still has a pronounced odour of fatty acid, which is perceived as unpleasant in the case of the short-chain fatty acids such as caprylic acid. In contrast, although Example 1 not in accordance with the invention after 24 h reaction time is homogeneous and has a residual acid number of just <1.3 mg KOH/g, a pronounced odour of fatty acid can also be detected for this example. The same applies to the physical mixture of Example 1 and Example 2 (example 3). Only in Example 4 according to the invention are a low residual acid number (i.e. a high conversion of the fatty acid), a homogeneous product and a pleasant odour (popcorn-like) achieved after 24 h reaction time.
Technical Effect: Homogeneous Even at Relatively Low Degrees of Esterification
Table 2 compares Example 8 according to the invention with Examples 5 and 6 not in accordance with the invention in terms of reaction course and homogeneity.
As can be seen from Table 2, Example 5 not in accordance with the invention at 80° C. exhibits phase separation in the melt in the form of a sediment. This phenomenon is even more pronounced in Example 6 not in accordance with the invention and also occurs in the physical mixture of Example 5 and Example 6 (Example 7). Only Example 8 according to the invention at 80° C. is homogeneous in the melt and exhibits no phase separation, despite the comparatively low degree of esterification of 1:1.5 (sugar/fatty acid molar ratio).
Technical Effect: Colour and Reactivity (i.e. Degree of Conversion of the Fatty Acid)
Table 3 compares Example 14 according to the invention with Example 13 not in accordance with the invention in terms of reaction course and colour.
As can be seen from Table 3, the physical mixture (Example 13) exhibits a much poorer colour than a process product according to the invention (Example 14).
Formulation Examples
The examples which follow are intended to show that the compositions according to the invention can be used in a large number of cosmetic formulations.
Formulations 1a, 1b and 1c: Aluminium Salt-Containing Antiperspirant/Deodorant Formulations
Formulations 2a, 2b and 2c: Aluminium-Free Deodorant Formulation without Antiperspirant Active Ingredients
Formulations 3a, 3b and 3c: O/W Deodorant Emulsion Containing Potassium Alum
Formulation 4a and 4b: Antiperspirant/Deodorant Lotion
Formulations 5a, 5b and 5c: Antiperspirant/Deodorant Creams
Formulation 6a and 6b: Sun Care Spray SPF 30
Formulations 7a, 7b and 7c: Sunscreen Spray
Formulations 8a, 8b and 8c: Sunscreen Lotion, SPF 30
Formulations 9a, 9b and 9c: Sunscreen Lotion SPF 30, High UVA Protection
Formulations 10a, 10b and 10c: Sunscreen Lotion, SPF 30
Formulations 11a, 11b and 11c: Sunscreen Lotion SPF 50, High UVA Protection
Formulations 12a, 12b and 12c: Sunscreen Lotion, SPF 50
Formulations 13a, 13b and 13c: Sunscreen Lotion SPF 50+
Formulation 14a and 14b: Body Lotion
Formulation 15a and 15b: Natural Care Cream
Formulation 16a and 16b: Anti-Aging Cream
Formulation 17a and 17b: O/W Foundation
Formulations 18a, 18b, 18c and 18d: Lotions with Cosmetic Active Ingredients
Formulations 19a, 19b and 19c: Lotion with Low Oil Phase Content
Formulations 20a, 20b, 20c and 20d: O/W Serums 1
Formulations 20e 20f, 20g and 20h: O/W Serums 2
Formulations 21a, 21b and 21c: O/W Blemish Balm Lotion
Formulations 22a, 22b, 22c and 22d: Lotion for Sensitive Skin
Formulations 23a, 23b, 23c and 23d: Care Lotion for Dry Skin 1
Formulations 23e, 23f, 23g and 23h: Care Lotion for Dry Skin 2
Formulations 24a, 24b and 24c: Preservative-Free Lotions 1
Formulations 24d, 24e and 24f: Preservative-Free Lotions 2
Formulation 25a and 25b: W/O Lotion
Formulation 26a and 26b: W/O Cream
Formulation 27a and 27b: Quick-Breaking Cream
Formulations 28a, 28b and 28c: Cooling Body Lotion
Formulations 29a, 29b and 29c: W/O Cream Based on Natural Ingredients
Formulations 30a, 30b and 30c: Cold-Preparable Lotion
Formulations 31a, 31b and 31c: Moisturizing Lotion Containing Urea
Formulations 32a, 32b, 32c and 32d: W/O Lotion with Light-as-Silk Skin Feel
Formulations 33a, 33b and 33c: Baby-Care Product
Formulations 34a, 34b and 34c: Foot-Care Product
Formulations 35a and 35b: Sunscreen Lotion SPF 30 UVA with Insect Repellent
Formulations 36a and 36b: Sunscreen Lotion SPF 30 UVA in Accordance with Exocet Criteria
Formulations 37a, 37b, 37c and 37d: Sunscreen Spray SPF 30 UVA
Formulations 38a, 38b, 38c and 38d: Sunscreen Lotion SPF 50 UVA
Formulations 39a, 39b and 39c: Sunscreen Lotion SPF 50 in Accordance with FDA Criteria
Formulations 40a, 40b, 40c, 40d, 40e and 40f: Foundation
Formulations 41a, 41b, 41c, 41d, 41e, 41f and 41g: CC (Colour Control) Fluid
Formulations 42a, 42b, 42c, 42d and 42e: Antiperspirant/Deodorant Spray or Aerosol Spray
Formulations 43a, 43b, 43c and 43d: Sunscreen Aerosol SPF 50 UVA
Formulation 44: Shower Cream
Formulation 45: Body Shampoo
Formulation 46: Shampoo
Formulation 47a and 47b: Shampoo
Formulation 48: Liquid Soap
Formulation 49: Cream Soap
Formulation 50: Oil Bath
Formulation 51: Micellar Water for Make-Up Removal
Formulation 52a and 52b: Solution for Wet Wipes
Formulation 53: Antiperspirant Deodorant
Formulation 54: Mouthwash
Formulation 55: Toothpaste
Number | Date | Country | Kind |
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19218421.6 | Dec 2019 | EP | regional |
Filing Document | Filing Date | Country | Kind |
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PCT/EP2020/086736 | 12/17/2020 | WO |