Retinol preparations (V)

Abstract

The present invention relates to novel formulations containing high amounts of retinol with a defined mixture of cis and trans isomers in specific solvents and in the presence of mixed tocopherols.

Description

Detailed Description of the Invention

[0001] The present invention relates to novel formulations containing high amounts of retinol with a defined mixture of cis and trans isomers in specific solvents and in the presence of mixed tocopherols.

[0002] Retinol has the formula: [ka] (stereochemistry not shown) It is a compound that exhibits very interesting properties for applications in various fields.

[0003] This is highly useful in food, feed and pharmaceutical applications, as well as personal care applications.

[0004] When used in the personal care field, it is primarily used for skin maintenance.

[0005] Benefits of applying retinol topically include: - Wrinkle minimizing effect not only prevents wrinkles but also smooths existing lines and wrinkles. - Exfoliates the skin at a cellular level to reveal brighter, smoother new skin and brighten dull skin. - Oily skin is regulated and breakouts are minimized. Dark age spots, sun spots and pigmentation are reduced, and uneven skin tone is reduced over time.

[0006] In order to produce an end market product (such as a cream), there is a need to provide a formulation containing retinol that can be incorporated into the end market product.

[0007] It is highly advantageous that the formulations used to make the end-market products contain a high amount of retinol, i.e., there are not many solvents and other ingredients present, which means that the concentrations of such solvents and other ingredients can be kept low in the end-market product, allowing the formulations of the present invention to be used in a wide range of applications.

[0008] Furthermore, such formulations containing high amounts of retinol need to be stable so that the retinol content does not decrease during storage of the formulation.

[0009] Additionally, it was a goal to avoid using antioxidants such as butylated hydroxytoluene (BHT) or butylated hydroxyanisole (BHA), as these are banned in various countries for certain applications.

[0010] It has been found that the selection of specific solvents (for retinol) and mixed tocopherols (as antioxidants) allows the production of highly concentrated and stable retinol formulations. The retinol used in the formulations according to the invention has a defined cis / trans ratio and is stable during storage.

[0011] The selection of a particular solvent is very important for the formulation according to the invention: the solvent that dissolves retinol with the defined mixture of cis and trans isomers must not contain any alcohol groups.

[0012] The solvents used are non-polar lipophilic hydrocarbons that are free of alcohol and ester groups.

[0013] The present invention relates to a formulation (F), 40 to 75 weight percent (wt%) of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation wherein at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups; Retinol is a mixture of cis and trans isomers. The cis / trans ratio in the retinol mixture is less than 0.01 (1:110), and the cis / trans ratios are 0.0099, 0.0095, 0.009, 0.0085, 0.008, 0.0075, 0.007, 0.0065, 0.006, 0.0055, 0.005, 0.0049, 0.0045, 0.0043, 0.004, 0.0035, 0.0 0.03, 0.0028, 0.0025, 0.0022, 0.002, 0.0018, 0.0015, 0.001, 0.0005 or less, for example, 0.0001 or less, and more preferably 0.0099 to 0.0001, 0.008 to 0.001, 0.007 to 0.002, 0.0099 to 0.001, 0.005 to 0.001, 0.005 to 0.000 1, 0.005~0.0005, 0.006~0.001, 0.009~0.0001, 0.008~0.0001, 0.006~0.0001, 0.0055~0.0001, 0.005~0.002, 0.007~0.0001, 0.0045~0.0001, 0.004~0.0001, 0.0035~0.0001, 0.003~0.0001 , 0.005 to 0.0025, 0.004 to 0.0005, 0.006 to 0.0005, 0.006 to 0.0008, 0.006 to 0.0015, 0.006 to 0.002, 0.006 to 0.003, 0.006 to 0.0004, 0.006 to 0.0025, and most preferably the cis / trans ratio is 0.003.

[0014] Furthermore, the formulation according to the invention may also contain up to 2% by weight (preferably 0.05-1.5% by weight) of sunflower oil, based on the total weight of the formulation.

[0015] The present invention relates to formulation (F), a ) containing up to 2% by weight (preferably 0.05 to 1.5% by weight) of sunflower oil based on the total weight of the formulation (F a ) regarding.

[0016] The present invention relates to a formulation (F1), 40 to 75% by weight of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation wherein at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups; Retinol is a mixture of cis and trans isomers. The cis / trans ratio in the retinol mixture is less than 0.01 (1:100), and the cis / trans ratios are 0.0099, 0.0095, 0.009, 0.0085, 0.008, 0.0075, 0.007, 0.0065, 0.006, 0.0055, 0.005, 0.0049, 0.0045, 0.0043, 0.004, 0.0035, 0.0 0.03, 0.0028, 0.0025, 0.0022, 0.002, 0.0018, 0.0015, 0.001, 0.0005 or less, for example, 0.0001 or less, and more preferably 0.0099 to 0.0001, 0.008 to 0.001, 0.007 to 0.002, 0.0099 to 0.001, 0.005 to 0.001, 0.005 to 0.000 1, 0.005~0.0005, 0.006~0.001, 0.009~0.0001, 0.008~0.0001, 0.006~0.0001, 0.0055~0.0001, 0.005~0.002, 0.007~0.0001, 0.0045~0.0001, 0.004~0.0001, 0.0035~0.0001, 0.003~0.0001, The cis / trans ratio is in the range of 0.005 to 0.0025, 0.004 to 0.0005, 0.006 to 0.0005, 0.006 to 0.0008, 0.006 to 0.0015, 0.006 to 0.002, 0.006 to 0.003, 0.006 to 0.0004, 0.006 to 0.0025, and most preferably, the cis / trans ratio is 0.003.

[0017] The present invention relates to a formulation (F a 1) Wherein 40 to 75% by weight of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation; Sunflower oil in an amount of up to 2% by weight (preferably 0.05 to 1.5% by weight) based on the total weight of the formulation. wherein at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups; Retinol is a mixture of cis and trans isomers. The cis / trans ratio in the retinol mixture is less than 0.01 (1:100), and the cis / trans ratios are 0.0099, 0.0095, 0.009, 0.0085, 0.008, 0.0075, 0.007, 0.0065, 0.006, 0.0055, 0.005, 0.0049, 0.0045, 0.0043, 0.004, 0.0035, 0. 0.003, 0.0028, 0.0025, 0.0022, 0.002, 0.0018, 0.0015, 0.001, 0.0005 or less, for example, 0.0001 or less, and more preferably 0.0099 to 0.0001, 0.008 to 0.001, 0.007 to 0.002, 0.0099 to 0.001, 0.005 to 0.001, 0.005 to 0. 0001, 0.005~0.0005, 0.006~0.001, 0.009~0.0001, 0.008~0.0001, 0.006~0.0001, 0.0055~0.0001, 0.005~0.002, 0.007~0.0001, 0.0045~0.0001, 0.004~0.0001, 0.0035~0.0001, 0.003~0. 0.0001, 0.005 to 0.0025, 0.004 to 0.0005, 0.006 to 0.0005, 0.006 to 0.0008, 0.006 to 0.0015, 0.006 to 0.002, 0.006 to 0.003, 0.006 to 0.0004, 0.006 to 0.0025, and most preferably, the cis / trans ratio is 0.003. a Regarding 1).

[0018] The present invention relates to a formulation (F2), 40 to 75% by weight of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation wherein at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups; Retinol is a mixture of cis and trans isomers. The cis / trans ratio in the retinol mixture is less than 0.01 (1:100), and the cis / trans ratios are 0.0099, 0.0095, 0.009, 0.0085, 0.008, 0.0075, 0.007, 0.0065, 0.006, 0.0055, 0.005, 0.0049, 0.0045, 0.0043, 0.004, 0.0035, 0.0 0.03, 0.0028, 0.0025, 0.0022, 0.002, 0.0018, 0.0015, 0.001, 0.0005 or less, for example, 0.0001 or less, and more preferably 0.0099 to 0.0001, 0.008 to 0.001, 0.007 to 0.002, 0.0099 to 0.001, 0.005 to 0.001, 0.005 to 0.000 1, 0.005~0.0005, 0.006~0.001, 0.009~0.0001, 0.008~0.0001, 0.006~0.0001, 0.0055~0.0001, 0.005~0.002, 0.007~0.0001, 0.0045~0.0001, 0.004~0.0001, 0.0035~0.0001, 0.003~0.0001, The cis / trans ratio is in the range of 0.005 to 0.0025, 0.004 to 0.0005, 0.006 to 0.0005, 0.006 to 0.0008, 0.006 to 0.0015, 0.006 to 0.002, 0.006 to 0.003, 0.006 to 0.0004, 0.006 to 0.0025, and most preferably, the cis / trans ratio is 0.003.

[0019] The present invention relates to a formulation (F a 2) Where 40 to 75% by weight of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation; Sunflower oil in an amount of up to 2% by weight (preferably 0.05 to 1.5% by weight) based on the total weight of the formulation. wherein at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups; Retinol is a mixture of cis and trans isomers. The cis / trans ratio in the retinol mixture is less than 0.01 (1:100), and the cis / trans ratios are 0.0099, 0.0095, 0.009, 0.0085, 0.008, 0.0075, 0.007, 0.0065, 0.006, 0.0055, 0.005, 0.0049, 0.0045, 0.0043, 0.004, 0.0035, 0 0.003, 0.0028, 0.0025, 0.0022, 0.002, 0.0018, 0.0015, 0.001, 0.0005 or less, for example, 0.0001 or less, and more preferably 0.0099 to 0.0001, 0.008 to 0.001, 0.007 to 0.002, 0.0099 to 0.001, 0.005 to 0.001, 0.005 to 0 .0001, 0.005~0.0005, 0.006~0.001, 0.009~0.0001, 0.008~0.0001, 0.006~0.0001, 0.0055~0.0001, 0.005~0.002, 0.007~0.0001, 0.0045~0.0001, 0.004~0.0001, 0.0035~0.0001, 0.003~0 0.0001, 0.005-0.0025, 0.004-0.0005, 0.006-0.0005, 0.006-0.0008, 0.006-0.0015, 0.006-0.002, 0.006-0.003, 0.006-0.0004, 0.006-0.0025, and most preferably, the cis / trans ratio of the formulation (F a Regarding 2).

[0020] The cis / trans ratios of retinol mixtures referred to herein refer to the weight percent ratio of each all-trans isomer of retinol to the sum of all cis isomers, determined by known methods, e.g., HPLC, and assuming equal response factors for all isomers.

[0021] The formulation according to the present invention is not an emulsion.The formulation according to the present invention is an oil formulation.This means that the water content of the formulation according to the present invention can be kept as low as possible.Water is not intentionally added to this formulation.The components of the formulation according to the present invention may contain traces of water.

[0022] While the oil formulations of retinol according to the invention using the solvents of the invention as solubilizers ensure that such solutions are easier to use and more flexible for further applications, taking the route of emulsifying such actives (which contains more ingredients) can adversely affect the end use application.

[0023] The present invention relates to formulation (F) or (F a ), which contains less than 2% by weight of water based on the total weight of the formulation.

[0024] The present invention relates to formulation (F) or (F a ), which contains less than 1% by weight of water based on the total weight of the formulation.

[0025] The present invention relates to formulation (F) or (F a ), which contains less than 0.5% by weight of water based on the total weight of the formulation.

[0026] The mixtures of cis and trans retinol used in the formulations according to the invention can be prepared either by mixing the respective all-trans form with one or more cis forms obtained by chemical or biological processes. Methods for preparing such all-trans and / or cis forms are known to those skilled in the art.

[0027] Alternatively, mixtures of said isomer ratios can be prepared by adjusting the process accordingly.

[0028] Advantageously, in all embodiments of the present invention, the retinol used in the formulations according to the present invention is biologically produced through a fermentation process, and the trans-retinol produced by fermentation can be subjected to heat treatment to form cis-retinol so as to achieve the appropriate levels set forth in all embodiments of the present invention (see, for example, McBee et al., JBC, Vol. 276, No. 51, pp. 48483-48493, 2001).

[0029] Advantageously, in all embodiments of the present invention, a mixture of cis and trans retinol having a cis-retinol to trans-retinol ratio of less than 1:100 (i.e. a ratio of less than 0.01), in particular a mixture of retinol isomers having a cis / trans ratio of about 0.003, preferably said retinoids as defined herein being biologically produced through a fermentation process, has a yellowish colour.

[0030] As known in the art, color may be expressed as XYZ, RGB, CYMK, or L * a * b * (CIELAB according to EN ISO / CIE 11664-4:2019). * a * b * The definition of "yellowish" is based on the L color measurement system. Those skilled in the art will understand which instruments to use according to the different color measurement systems and how to measure the color of the mixtures described herein. As used herein, a "yellowish" color is defined as a color that is "yellowish" in the L color measurement system. * a * b * It means a color defined by a color system, especially L * a * b * is (3 <L *<100, -25 * <30, 10 * <150), for example, L * is in the range of 50 to 100, a * is in the range of -25 to 10, b * is in the range of 40 to 150, and preferably, L * is in the range of 80 to 100, a * is in the range of -22 to 1, b * is in the range of 40 to 85 or 100 to 140, and more preferably, L * is in the range of 80 to 95, a * is in the range of -17 to -1, b * is in the range of 105 to 135, and in particular, L * is about 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, and a * are approximately -24.9, -24, -23, -22, -21, -20, -19, -18, -17, -18, -17, -16, -15, -14, -13, -12, -11, -10, -9, -8, -7, -6, -5, -4, -3, -2, -1, 0, and b * is about 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 44, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135.

[0031] ​​In certain embodiments, the cis and trans forms of retinol used in the formulations according to the invention are produced in a fermentation process using suitable retinol producing host cells, such as bacterial or fungal cells (see, for example, Sun et al, ACSSynth.Biol.2019 Sep 20;8(9):2131-2140; Jang et al.,Microbial Cell Factories 2011,10:59), which express the respective enzymes, such as trans-selective enzymes, i.e., β-carotene oxidase (BCO), which is involved in the biosynthesis of retinol by converting β-carotene to retinal, which can be further enzymatically converted to retinol. The fermentation is fed with ethanol, corn sugar or corn oil, all derived from agricultural production. The fermentation product containing retinol can be extracted into an aliphatic compound phase and then purified to a crystalline form.

[0032] The present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2) or (F a 2), in which the retinol used in the formulation is biologically produced through a fermentation process.

[0033] The term "biologically produced" as used herein means that retinol is produced using a biotechnological process, such as a fermentation process, including the cultivation of a suitable (carotenoid and / or retinoid producing) host cell expressing the respective enzymes involved in the conversion of a suitable carbon source to retinal and its further conversion to retinol as defined herein, the host cell may be selected from bacteria, fungi, particularly yeast, plants or algae. "Bio-produced", "biologically derived" and "biologically produced" are used interchangeably herein. Thus, said biologically produced retinol is composed of carbon derived from atmospheric carbon dioxide (also referred to as carbon of atmospheric origin) that is converted by green plants into sugars and starches. This also includes the use of isolated and / or immobilized enzymes in the process to produce the retinol mixture as defined herein, for example the use of specific enzymes that can selectively catalyze the formation of a retinol mixture with a specific trans / cis ratio as defined herein.

[0034] As used herein, "atmospheric carbon" refers to carbon atoms of carbon dioxide molecules that have been released into the Earth's atmosphere in recent, past decades. Such carbon masses are identifiable by the presence of certain radioisotopes, as described herein. "Green carbon," "atmospheric carbon," "environmentally friendly carbon," "life cycle carbon," "non-fossil carbon," "non-petroleum carbon," "atmospheric carbon," and "bio-based carbon" are used interchangeably herein.

[0035] In all embodiments of the present invention, retinol is advantageously produced exclusively from renewable, bio-based, organic feedstocks, in particular by fermentation, since all CO2 molecules emitted during decomposition of such "fermentation-derived" or "fermentation-produced" retinol are of atmospheric origin, resulting in a zero anthropogenic CO2 emission profile during biodegradation, thus resulting in zero net emissions of CO2 to the atmosphere.

[0036] In a preferred embodiment, the mixture of cis and trans retinol used in the formulations according to the present invention consists essentially of cis and trans retinol having the ranges and all of the definitions and priorities set forth herein.

[0037] The term "consisting essentially of" as used in accordance with the present invention means that the total amounts of components in the mixture ideally total 100% by weight. However, it does not exclude the possibility that small amounts of impurities or additives may be present in the mixture, provided that the total amount of such impurities is preferably less than about 5% by weight, more preferably less than about 3, 2, 1% by weight, for example, introduced via the respective raw materials and / or processes used.

[0038] As used herein, the terms "impurities" and "additives" are used interchangeably herein and refer to coexisting components in the mixture of the present invention, and are present in the mixture of the present invention in an amount of less than 5% by weight based on the total components present in the mixture.

[0039] When the mixture according to the present invention consists essentially of retinol having a cis / trans ratio as defined herein, the purity of said mixture, i.e. the (total) amount of cis and trans retinol, as determined by known methods, such as HPLC, in particular reverse-phase C4 HPLC, is preferably at least about 95%, more preferably at least about 96, 97, 98% by weight, and most preferably at least about 98%.

[0040] In one embodiment, the mixture of cis and trans retinol having a cis / trans ratio as defined herein further comprises a small amount of additives, such as dihydroretinol and / or dihydroretinoids, including retinyl dihydroacetate, in particular in the range of 0.2-0.01% by weight or less, for example 0.2, 0.18, 0.16, 0.15, 0.14, 0.12, 0.1, 0.05, 0.01% by weight or less, preferably 0.2-0.1, 0.17-0.06, 0.1-0.05, 0.04-0.01% by weight or less, more preferably 0.1% by weight or less, all based on the total components of the retinol mixture. Also preferably, the proportion of retinyl dihydroacetate is about 0.05% by weight or less, in particular about 0.01% by weight or less, based on the total components of the retinol mixture.

[0041] The present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F2), (F a 2) or (F3), comprising a small amount of an additive in a proportion of 0.2 to 0.01% by weight or less, for example, 0.2, 0.18, 0.16, 0.15, 0.14, 0.12, 0.1, 0.05, 0.01% by weight or less, preferably 0.2 to 0.1, 0.17 to 0.06, 0.1 to 0.05, 0.04 to 0.01% by weight, more preferably 0.1% by weight or less, all based on the total components of the retinol mixture.

[0042] It is understood that for all formulations disclosed in this patent application the percentages necessarily sum to 100.

[0043] The amount of retinol in the formulation according to the invention is 40-75% by weight, based on the total weight of the formulation.

[0044] Preferably, each formulation according to the present invention contains 40-70% by weight, more preferably 42-70% by weight, 42-65% by weight, 45-65% by weight, 45-60% by weight, or 45-55% by weight of retinol, based on the total weight of the formulation.

[0045] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), which contains 40 to 70% by weight of retinol based on the total weight of the formulation.

[0046] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), which contains 42 to 70% by weight of retinol based on the total weight of the formulation.

[0047] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), which contains 42 to 65% by weight of retinol based on the total weight of the formulation.

[0048] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), which contains 45 to 65% by weight of retinol based on the total weight of the formulation (F5''').

[0049] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), each of which contains 45 to 60% by weight of retinol based on the total weight of the formulation (F5'''').

[0050] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3) or (F4), which contains 45 to 55% by weight of retinol based on the total weight of the formulation (F5'''''').

[0051] As stated above, the choice of solvent is very important for the stability of the formulation according to the invention.

[0052] In the formulation according to the invention, at least one non-polar lipophilic hydrocarbon is used which is free of alcohol and ester groups.

[0053] The preferred solvents are alkanes, which may be straight or branched chain having from 8 to 42 carbon atoms.

[0054] Linear or branched chain C 10 ~C 40 Alkanes are more preferred.

[0055] In particular, the following solvents (singly or as mixtures) are preferred: decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecene, nonadecane, icosane, henicosane, docosane, tricosane, tetracosane, pentacosane, hexacosane, heptacosane, octacosane, nonacosane, triacontane, hentriacontane, dotriacontane, tritriacontane, tetratriacontane, pentatriacontane, hexatriacontane, heptatriacontane, octatriacontane, nonatriacontane and tetracontane. All of these alkanes can be linear and branched.

[0056] Most preferred are undecane, tridecane, pentadecane, hexadecane, heptadecane, octadecene, nonadecane and triacontane.

[0057] Such suitable solvents are available from a variety of suppliers (such as BASF, Seppic and Aprinnova) under trade names such as Emogreen L19, Emogreen L15, Cetiol Ultimate and Neossance Squalane.

[0058] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''') or (F5''''''), wherein at least one solvent is a C8-C 42 Concerning preparation (F6), which is an alkane.

[0059] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a Formulation (F6') is (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''') or (F5''''), in which at least one solvent is a C 10 ~C 40 Concerning preparation (F6'), which is an alkane.

[0060] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''') or (F5'''') in which the at least one solvent is selected from the group consisting of decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecene, nonadecane, icosane, henicosane, docosane, tricosane, tetracosane, pentacosane, hexacosane, heptacosane, octacosane, nonacosane, triacontane, hentriacontane, dotriacontane, tritriacontane, tetratriacontane, pentatriacontane, hexatriacontane, heptatriacontane, octatriacontane, nonatriacontane and tetracontane, these alkanes may be linear and branched.

[0061] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''') or (F5''''), in which the at least one solvent is selected from the group consisting of undecane, tridecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane and triacontane, and these alkanes may be linear and branched.

[0062] The formulation according to the invention comprises 20-55% by weight of at least one solvent, based on the total weight of the formulation.

[0063] Preferably, the amount of the at least one solvent is 25 to 55 wt %, 28 to 55 wt %, or 35 to 55 wt %, all based on the total weight of the formulation.

[0064] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (Fa 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'') or (F6'''), which comprises 25 to 55% by weight of at least one solvent, based on the total weight of the formulation.

[0065] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'') or (F6'''), which comprises 28 to 55% by weight of at least one solvent, based on the total weight of the formulation.

[0066] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5''', (F5'''', (F5''''), (F6), (F6'), (F6'') or (F6'''), which comprises 35 to 55% by weight of at least one solvent, based on the total weight of the formulation (F7'').

[0067] Formulations according to the present invention include mixed tocopherols as antioxidants.

[0068] Mixed tocopherols are made up of the following four compounds: α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol and It is a mixture of.

[0069] Mixed tocopherols are usually up to 20% by weight of α-tocopherol based on the total weight of the mixed tocopherols; up to 5% by weight of β-tocopherol based on the total weight of the mixed tocopherols; up to 75% by weight of gamma-tocopherol, based on the total weight of the mixed tocopherols; up to 35% by weight of δ-tocopherol based on the total weight of the mixed tocopherols; Includes.

[0070] Preferred mixed tocopherols are: 10 to 20% by weight of α-tocopherol based on the total weight of the mixed tocopherols; 1 to 5% by weight of β-tocopherol based on the total weight of the mixed tocopherols; 50 to 75% by weight of gamma-tocopherol based on the total weight of the mixed tocopherols; 15 to 35% by weight of δ-tocopherol based on the total weight of mixed tocopherols Includes.

[0071] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a Formulation (F8) is formulation (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7') or (F7''), wherein the mixed tocopherols are up to 20% by weight of α-tocopherol based on the total weight of the mixed tocopherols; up to 5% by weight of β-tocopherol based on the total weight of the mixed tocopherols; up to 75% by weight of gamma-tocopherol, based on the total weight of the mixed tocopherols; Up to 35% by weight of δ-tocopherol based on the total weight of mixed tocopherols The present invention relates to formulation (F8),

[0072] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a Formulation (F8') is (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7') or (F7''), wherein the mixed tocopherols are 10 to 20% by weight of α-tocopherol based on the total weight of the mixed tocopherols; 1 to 5% by weight of β-tocopherol based on the total weight of the mixed tocopherols; 50 to 75% by weight of gamma-tocopherol based on the total weight of the mixed tocopherols; 15 to 35% by weight of δ-tocopherol based on the total weight of mixed tocopherols The present invention relates to a formulation (F8') comprising:

[0073] Mixed tocopherols are commercially available from a variety of suppliers, including BASF, DuPont, Merck, and DSM.

[0074] The formulation according to the present invention does not contain any additional antioxidants other than the mixed tocopherols (i.e. BHA, BHT, etc.).

[0075] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8) or (F8'), wherein formulation (F9) does not contain any further antioxidants (other than mixed tocopherols).

[0076] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8) or (F8'), which is formulation (F9') that is (substantially) free of BHA and BHT.

[0077] The formulation according to the present invention contains 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation.

[0078] Preferably, the formulations according to the present invention contain 0.2-4.5% by weight, 0.2-4% by weight, 0.3-4% by weight, 0.4-3.5% by weight, 0.4-3% by weight, 0.4-2.5% by weight, or 0.4-2% by weight of mixed tocopherols, all based on the total weight of the formulation.

[0079] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein the formulation (F10) contains 0.2 to 4.5 wt. % mixed tocopherols based on the total weight of the formulation.

[0080] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein formulation (F10') contains 0.2 to 4 wt. % mixed tocopherols based on the total weight of the formulation.

[0081] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein formulation (F10'') contains 0.3 to 4 wt. % mixed tocopherols based on the total weight of the formulation.

[0082] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5'''', (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein the formulation (F10''') contains 0.4 to 3.5% by weight of mixed tocopherols based on the total weight of the formulation.

[0083] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein the formulation (F10'''') contains 0.4 to 3 wt. % mixed tocopherols based on the total weight of the formulation.

[0084] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''), (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein the formulation (F10'''''') contains 0.4 to 2.5 wt. % mixed tocopherols based on the total weight of the formulation.

[0085] Thus, the present invention relates to formulation (F10'''''') which is formulation (F), (F'), (F'', (F'''), (F1), (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''', (F5''''), (F6), (F6'), (F6'', (F6'''), (F7), (F7'), (F7''), (F8), (F8'), (F9) or (F9'), wherein formulation (F10'''''') comprises 0.4 to 2% by weight of mixed tocopherols, based on the total weight of the formulation.

[0086] The formulations according to the invention are manufactured using generally known methods and with commonly used equipment.

[0087] A general method for preparing a formulation according to the invention is as follows: Retinol and mixed tocopherols are mixed at high temperature (usually between 40 and 65°C), Heating at least one solvent to a temperature similar to that of the retinol / mixed tocopherol mixture (usually in the temperature range of 40-65°C); adding at least one solvent to the retinol / mixed tocopherol mixture (or vice versa) at an elevated temperature (usually in the temperature range of 40-65° C.) and mixing it at this temperature; Allow the mixture to cool slowly.

[0088] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a 2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5'''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9), (F9'), (F10), (F10'), (F10'', (F10'''), (F10''''), (F10'''') or (F10''''''); mixing retinol and mixed tocopherols at high temperature (usually in the range of 40-65°C); heating at least one solvent to a temperature similar to that of the retinol / mixed tocopherols mixture (usually in the temperature range of 40-65° C.); adding at least one solvent to the retinol / mixed tocopherols mixture (or vice versa) at an elevated temperature (usually in the temperature range of 40-65° C.) and mixing it at this temperature; Slowly cooling the mixture The present invention relates to a process comprising:

[0089] It is also possible to first mix the retinol in a solvent (usually at a temperature range of 40-65°C) and then mix it with the mixed tocopherols (usually at a temperature range of 40-65°C) and slowly cool the mixture.

[0090] It is also possible to first mix the mixed tocopherols in a solvent (usually at a temperature range of 40-65°C) and then mix it with the retinol (usually at a temperature range of 40-65°C) and slowly cool the mixture.

[0091] The formulations according to the invention can be used in a variety of areas of application, such as food, feed, pharmaceutical and personal care.

[0092] Preferably, the formulations according to the invention are used for incorporation into personal care products (creams, lotions, etc.).

[0093] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a The present invention also relates to the use of at least one of the following in food, feed, drug and personal care products: (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9), (F9'), (F10), (F10'), (F10'', (F10'''), (F10''''), (F10'''') or (F10'''''').

[0094] Thus, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F aThe present invention also relates to the use of at least one of the following compounds in a personal care product (cream, lotion, etc.): (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9), (F9'), (F10), (F10'), (F10'', (F10'''), (F10''''), (F10'''') or (F10'''''').

[0095] Furthermore, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a The present invention also relates to food, feed, drug and personal care products containing at least one of: (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5'''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9), (F9'), (F10), (F10'), (F10'', (F10'''), (F10''''), (F10'''') or (F10'''''').

[0096] Furthermore, the present invention relates to formulations (F), (F a ), (F'), (F''), (F'''), (F1), (F a 1), (F2), (F a The present invention also relates to personal care products (creams, lotions, etc.) comprising at least one of: (F2), (F3), (F4), (F5), (F5'), (F5'', (F5'''), (F5''''), (F5''''), (F6), (F6'), (F6'', (F6''), (F6''', (F7), (F7'), (F7''), (F8), (F8'), (F9), (F9'), (F10), (F10'), (F10'', (F10'''), (F10''''), (F10'''') or (F10'''''').

[0097] As mentioned above, one advantage of the formulation according to the invention is the high amount of retinol (and therefore the reduced amount of other ingredients), another important advantage is that the formulation is oily and not in the form of a classical emulsion.

[0098] When incorporated into end market products (food, feed, pharmaceutical and personal care products), the amount of formulation will vary depending on the amount of retinol required in those end products.

[0099] The following examples serve to illustrate the invention.

[0100] [Example] All of the following examples are carried out by the following method: Melt and mix retinol and mixed tocopherols in nitrogen at a temperature of 63°C to 65°C for approximately 5 to 10 minutes; The solvent is then heated to a temperature of 63°C to 65°C. The retinol / mixed tocopherol mixture and solvent are then mixed (with stirring) at 63° C.-65° C. for several minutes, ie, 2-5 minutes, and the formulation is allowed to cool slowly to room temperature.

[0101] The solvents used are shown below. Emogreen L19 (from Seppic): This is a 15 ~C 19 Alkane mixture Cetiol Ultimate (from BASF): This is a mixture of undecane and tridecane. Cetiol 5 (from BASF): This is a coco-octanoate (comparative example) Eutanol G (from BASF): This is octyldodecanol (comparative example) Mixed tocopherols are Mixed Tocopherols 95 (from DSM)

[0102] [Table 1]

[0103] To determine the stability of these formulations, they were stored (at 40° C.) for 2 and 6 weeks, and the loss of retinol was measured (initial value taken as 100%).

[0104] [Table 2]

[0105] From this table, it can be seen that the stability of the formulation according to the invention is very high. It can also be seen how the stability of Comparative Examples 3 and 4 is lower than that of one of the formulations according to the invention. The cis / trans ratio of retinol was also stable.

[0106] As noted above, the inventive retinol formulations according to the present invention may be incorporated into a variety of compositions.

[0107] For example, the following personal care compositions are listed in the table below (all values ​​are given in weight percent based on the total weight of the composition):

[0108] [Table 3]

[0109] [Table 4]

[0110] [Table 5]

Claims

1. 1. A formulation comprising: 40 to 75 weight percent (wt%) retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation; wherein the at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups, The retinol is a mixture of cis and trans isomers, A formulation characterized in that the cis / trans ratio in the retinol mixture is less than 0.

01.

2. 1. A formulation comprising: 40 to 75% by weight of retinol based on the total weight of the formulation; 20 to 55% by weight of at least one solvent, based on the total weight of the formulation; 0.1 to 5% by weight of mixed tocopherols based on the total weight of the formulation; wherein the at least one solvent is a non-polar lipophilic hydrocarbon having no alcohol or ester groups, The retinol is a mixture of cis and trans isomers, A formulation characterized in that the cis / trans ratio in the mixture is less than 0.

01.

3. 3. The formulation of claim 1 or 2, wherein the retinol is biologically produced through a fermentation process.

4. 3. The formulation according to claim 1, comprising 40 to 70% by weight of retinol, based on the total weight of the formulation.

5. The at least one solvent is a C ８ ~C ４２ 3. The formulation of claim 1 or 2, which is an alkane.

6. 3. The formulation of claim 1 or 2, wherein the at least one solvent is selected from the group consisting of decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecene, nonadecane, icosane, henicosane, docosane, tricosane, tetracosane, pentacosane, hexacosane, heptacosane, octacosane, nonacosane, triacontane, hentriacontane, dotriacontane, tritriacontane, tetratriacontane, pentatriacontane, hexatriacontane, heptatriacontane, octatriacontane, nonatriacontane, and tetracontane, and the alkane can be linear or branched.

7. 3. The formulation of claim 1, comprising 25 to 55% by weight of said at least one solvent, based on the total weight of the formulation.

8. The mixed tocopherols are up to 20% by weight of α-tocopherol, based on the total weight of the mixed tocopherols; up to 5% by weight of β-tocopherol, based on the total weight of the mixed tocopherols; up to 75% by weight of gamma-tocopherol, based on the total weight of the mixed tocopherols; up to 35% by weight of δ-tocopherol, based on the total weight of the mixed tocopherols; 3. The formulation of claim 1 or 2, comprising:

9. 3. The formulation of claim 1 or 2, which does not contain any additional antioxidants (other than the mixed tocopherols).

10. 3. The formulation of claim 1, comprising 0.2 to 4.5% by weight of mixed tocopherols, based on the total weight of the formulation.

11. 3. A process for producing the formulation of claim 1 or 2, comprising: - mixing the retinol and the mixed tocopherols at elevated temperature (temperature range of 40-65°C); heating said at least one solvent to a temperature similar to that of the retinol / mixed tocopherol mixture (temperature range of 40-65°C); adding said at least one solvent to said retinol / mixed tocopherol mixture (or vice versa) at an elevated temperature (temperature range of 40-65°C) and mixing it at said temperature; - slowly cooling the mixture A process involving:

12. 3. Use of the formulation according to claim 1 or 2 in food, feed, pharmaceutical and personal care products, preferably personal care products.

13. 3. Food, feed, pharmaceutical and personal care products comprising the formulation of claim 1 or 2.

14. A personal care product comprising the formulation of claim 1 or 2.