Process for producing high-grade fatty acid polyol esters, particularly fatty acid glycerol esters

Abstract

To provide an efficient method for producing triglycerides of fatty acids (that is, fatty acid glycerol triesters), particularly in high purity.SOLUTION: The present invention is to produce triglycerides of fatty acids with high purity by applying at least one or a combination of the following: (i) selective derivatization of halide-based impurities present in the reaction product and / or treating or contacting the reaction product with at least one nucleophilic agent; (ii) performing esterification at a temperature not exceeding 180°C; (iii) using glycerol as a starting material, the glycerol being free of chlorinated species; and (iv) performing esterification in the absence of any metal-based catalyst.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to the technical field of fatty acid polyol esters, in particular fatty acid glycerol esters, and related medical treatment concepts for metabolic and related disorders.

[0002] In particular, the present invention relates to a process for producing higher fatty acid polyol esters, in particular fatty acid glycerol esters (i.e., glycerides of fatty acids), as well as to the inventive reaction products (i.e., fatty acid polyol esters, in particular fatty acid glycerol esters) obtained thereby or prepared thereby, and to their respective uses and applications, in particular in pharmaceutical compositions such as drugs or pharmaceuticals, or in foods, in food compositions or nutritional compositions, in food products and / or in medical foods, and further uses or applications thereof.

[0003] Furthermore, the present invention relates to pharmaceutical compositions, particularly drugs or pharmaceutical products, comprising the reaction products of the present invention (i.e., fatty acid polyol esters, particularly fatty acid glycerol esters) obtained or produced according to the process of the present invention, usually together with physiologically acceptable excipients, as well as their respective uses or applications.

[0004] Furthermore, the present invention relates to a food, nutritional composition or food composition, a food and / or a medical food, in particular a food supplement, a functional food, a novel food, a food additive, a diet food, a power snack, an appetite suppressant and a strength and / or endurance sports supplement comprising the reaction product of the present invention (i.e., a fatty acid polyol ester, in particular a fatty acid glycerol ester) obtained or produced by the method of the present invention, as well as to applications or uses thereof.

[0005] Furthermore, the present invention relates to the use of the reaction products of the present invention (i.e. fatty acid polyol esters, in particular fatty acid glycerol esters) as additives or auxiliaries, in particular carriers or excipients, solubilizers, release agents, surface treatment agents, transport agents, lubricants, hydrophobizing agents, film-forming or protective agents, and viscosity modifiers, preferably as carriers or excipients, in pharmaceutical compositions, in particular drugs or pharmaceuticals, in foods, nutritional supplements or food compositions, food products and / or medical foods, as well as in cosmetic compositions.

[0006] Finally, the present invention also provides triglycerides of fatty acids, particularly C5-C 12 -Triglycerides of fatty acids, especially C5-C 12 - for purifying triglycerides of fatty acids and / or in organic substances, in particular triglycerides of fatty acids, in particular C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - The present invention relates to the use of nucleophiles for the preferably selective removal or derivatization of halide-based impurities present in triglycerides of fatty acids. [Background technology]

[0007] In human energy metabolism, glucose is a short-term energy carrier that is metabolized to energy in mitochondria by releasing water and carbon dioxide. Glycogen stores in the liver are already emptied during nighttime sleep. However, the human central nervous system (CNS) and heart, in particular, require a continuous energy supply.

[0008] The physiological substitute for glucose, which is mainly supplied to the central nervous system, is the so-called ketone body (also synonymously called keto body).

[0009] The term "ketone bodies" is a collective term for three compounds, primarily produced under catabolic conditions (e.g., fasting, weight-loss diets, low-carbohydrate diets), which can induce ketosis. The term specifically includes acetoacetate (also synonymously referred to as acetastate) and acetone, as well as 3-hydroxybutyric acid (hereinafter also synonymously referred to as β-hydroxybutyric acid, BHB, or 3-BHB) or its salts (i.e., 3-hydroxybutyric acid or β-hydroxybutyric acid), the latter of which is the most important of the three compounds. 3-hydroxybutyric acid or its salts occur physiologically as the (R) enantiomer, i.e., (R)-3-hydroxybutyric acid (also synonymously referred to as (3R)-3-hydroxybutyric acid, emphasizing the chirality at the 3-position) or its salts.

[0010] These ketone bodies are also physiologically supplied in large quantities from lipids accumulated in the body through lipolysis during fasting or starvation, and almost completely replace glucose, which is an energy source.

[0011] Ketone bodies are produced in the liver from acetyl-CoA (acetyl-CoA) derived from beta-oxidation; they represent the transportable form of acetyl-CoA in the human body. However, to utilize ketone bodies, the brain and muscles must first adapt by expressing the enzymes necessary to convert ketone bodies back to acetyl-CoA. Especially during fasting, ketone bodies contribute significantly to energy production. For example, after a period of time, the brain can survive on only one-third of the daily glucose intake.

[0012] Physiologically, ketone bodies are synthesized from two molecules of activated acetate in the form of acetyl coenzyme A, a common intermediate in fatty acid degradation. This is further extended to the intermediate product 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) using an acetyl coenzyme A unit and the enzyme HMG-CoA synthase, and finally cleaved to acetoacetate by HMG-CoA lyase. These three steps occur exclusively in the liver mitochondria (i.e., the hepatic cycle), and 3-hydroxybutyrate is ultimately produced in the cytoplasm by D-hydroxybutyrate dehydrogenase. HMG-CoA is also the end product of the breakdown of the amino acid leucine, while acetoacetate is produced during the breakdown of the amino acids phenylalanine and tyrosine.

[0013] Spontaneous decarboxylation converts acetoacetate to acetone, which is sometimes detected on the breath of diabetics and people on diets, and which is not further utilized by the body. However, only a small proportion of acetone is present in ketone bodies.

[0014] Acetoacetate is thus reductively converted to the physiologically relevant forms 3-hydroxybutyric acid or 3-hydroxybutyrate, but can also decompose to the physiologically unusable acetone, releasing carbon dioxide, which in severe ketosis, ketoacidosis (e.g., in type 1 diabetic patients not receiving insulin replacement), can be detected in the urine or in the breath and can be detected olfactorily.

[0015] 3-hydroxybutyric acid is currently used and sold in the weight training field as its sodium, magnesium, and calcium salts.

[0016] However, because plants do not produce 3-hydroxybutyrate, and because 3-hydroxybutyrate in animals is only present in the carcasses of animals emaciated in ketosis, 3-hydroxybutyrate is evolutionarily unknown to humans or present in very small amounts, and oral administration of 3-hydroxybutyrate causes nausea.

[0017] Furthermore, patients, especially newborns but even adults, cannot tolerate large amounts of 3-hydroxybutyrate for long periods of time due to the potential damage these compounds can cause to the kidneys.

[0018] Furthermore, the plasma half-life of 3-hydroxybutyrate and its salts is very short, with ketosis lasting only 3-4 hours even after ingestion of a few grams, which can be life-threatening in metabolic disorders.

[0019] Therefore, in the treatment of such metabolic disorders, fatty acid polyol esters, in particular fatty acid glycerol esters, in particular so-called medium chain triglycerides (i.e. so-called MCT or MCT fats / oils), are currently used in ketogenic therapy, i.e. in particular caproic, caprylic and capric acids (i.e. saturated linear C6-, C8- and C9-) from the corresponding triglycerides. 10 -fatty acids) is intended for metabolic conversion.

[0020] Medium-chain triglycerides (also synonymously known as MCTs or MCT fats / oils) are triglycerides containing two to three fatty acids, or medium-chain fatty acids (MCFAs), with a straight-chain saturated aliphatic tail of 5 to 12 carbon atoms, especially 6 to 12 carbon atoms. Abundant food sources for commercial extraction of MCTs include palm kernel oil and coconut oil.

[0021] Therefore, according to this definition, medium-chain triglycerides (MCTs) are triglycerides containing medium-chain fatty acids. Medium-chain fatty acids include, among others, caproic acid (C6:0), caprylic acid (C8:0), capric acid (C10:0), and lauric acid (C12:0). These acids are saturated fatty acids found primarily in tropical vegetable fats, such as coconut oil (approximately 60%) and palm kernel oil (approximately 55%), and butter. Small amounts are also found in milk fat (approximately 10%). Pure MCT oil does not occur in nature; it exists only as a mixture with other triglycerides. MCTs have a slightly lower calorific value or food energy (3475 kJ / 100 g) compared to fats (3852 kJ / 100 g) and a lower smoke point compared to conventional long-chain fats (LCTs, or long-chain triglycerides).

[0022] MCT fats are obtained industrially by hydrolysis of coconut or palm kernel oil, fractionation of the medium-chain fatty acids, and subsequent esterification with glycerol. Pure MCT oil is colorless to yellowish, has a neutral odor and taste, and a very low viscosity. It is designated as a vegetable oil (also known as a neutral oil or neutral fat).

[0023] The German Pharmacopoeia, 10th edition, 1991 (i.e., German Pharmacopoeia 10 or DAB10) and the corresponding European Pharmacopoeia (European Pharmacopoeia, in particular European Pharmacopoeia 10.0, Monograph No. 0868 "Triglycerides, medium chain [Triglycerida saturata media]") are as follows: 50-80% caprylic acid C8, 50-80% capric acid C 10 25-45%, lauric acid C 12 and caproic acid C6 up to 2% (Note: Hanger's Handbook of Pharmaceutical Practice, 5th edition, ISBN 978-642-63389-8, p. 1059 ff.).

[0024] MCTs have a wide range of uses and formulations. MCT fat has been industrially produced since 1955, and its unique properties have led to its diverse applications. In 1994, the U.S. Food and Drug Administration (FDA) accepted its GRAS (Generally Recognized as Safe) application, which led to MCTs gaining interest, particularly in the food industry. Due to its physical properties, industrially produced MCT fat is also used in the manufacture of cosmetics (ointments, creams, bath oils, etc.) and pharmaceuticals (tablets, coated tablets, etc.), where it plays a key role as a carrier, excipient, solubilizer, release agent, surface treatment agent, transport agent, lubricant, hydrophobic agent, film-forming agent, protectant, and viscosity modifier. Furthermore, due to its metabolic peculiarities, it is also used in diet foods (e.g., MCT oil and MCT margarine) and artificial nutrition products (e.g., enteral and parenteral). These products are classified as nutritional foods for special medical purposes (e.g. balanced diets) according to the German Dietary Products Ordinance (the so-called German "Diaetverordnung" ("everyday goods").

[0025] The physiological properties and metabolism of MCTs have also attracted considerable interest: Due to their short fatty acid chain length, MCT fats are relatively water-soluble and can be metabolized without bile acids. Furthermore, their structure does not require cleavage by pancreatic lipase (i.e., a pancreatic enzyme). Ketone bodies bypass the lymphatic system and are transported directly to the liver in the blood, where they are preferentially oxidized over conventional fats, promoting ketone body production. Transport of medium-chain fatty acids (MCFAs) to mitochondria (i.e., the site of fatty acid oxidation) occurs independently of carnitine. The tolerable daily intake varies from individual to individual, but is approximately 50 to 100 grams or more of MCT fat. To avoid side effects (e.g., diarrhea, cramps, headaches), a starting dose of approximately 20 grams of MCT fat per day is generally recommended. This amount can be gradually increased by 5 to 10 grams per day. Supplementation of fat-soluble vitamins and essential fatty acids (e.g., omega-3 and omega-6) is essential when implementing a dietary regimen using MCT fats. Fat-soluble vitamins are well absorbed when MCT fats are used.

[0026] Due to their metabolic properties, MCT fats have become valuable components of nutritional therapy in diets for a variety of clinical indications.

[0027] Because medium-chain triglycerides are highly water-soluble and absorbed more quickly by the body than traditional long-chain fats, they were first used in clinical nutrition in the 1950s as a dietary treatment for malabsorption syndromes. In cases of lymphangiectasia (dilated lymphatic vessels), Whipple's disease (a rare infection), and pneumothorax (accumulation of lymphatic fluid in the chest cavity), MCT fats help relieve lymphatic congestion. In premature infants, whose digestive systems are not yet fully developed, medium-chain fats are used to achieve weight gain.

[0028] Because MCT fats are metabolized independently of pancreatic enzymes and require only gastric lipase for degradation, their use is indicated in cases of pre-existing exocrine pancreatic insufficiency accompanied by significant fatty diarrhea (i.e., steatorrhea or the presence of fat in the feces) when enzyme supplementation fails to produce the desired effect. Exocrine pancreatic insufficiency occurs, for example, in chronic pancreatitis and cystic fibrosis. Furthermore, their use in combination with pancreatic supplementation is also effective. Another classic application of MCT fats is short bowel syndrome (SBS). In SBS, digestion of edible oils, especially fats, is impaired depending on the extent and location of intestinal resection. If the large intestine is preserved, MCT fats are adequately absorbed and can substitute for conventional fats. In rare inborn errors of metabolism, such as deficiencies in the beta-oxidation of long-chain fatty acids (LCHAD) and very-long-chain fatty acids (VLCAD), MCT fats are an essential energy source. MCT fats are also used in artificial nutrition (i.e., enteral and parenteral) for various diseases, primarily of the gastrointestinal tract.

[0029] Because MCT fats are more ketogenic than conventional fats, they are also used as a partial replacement for ketogenic diets (KDs), particularly LCT fats. Ketogenic diets have been applied to drug-resistant epilepsy and rare congenital metabolic disorders (e.g., pyruvate dehydrogenase deficiency and GLUT1 deficiency). The nutrient ratio of a classic ketogenic diet is typically 3-4 parts fat, 1 part carbohydrate, and 1 part protein. A ketogenic diet using MCT fats is considered a promising alternative to the classic diet in children and adults because the high ketogenicity of MCT fats can shift the fat-to-carbohydrate and protein ratio in favor of carbohydrates. Ketogenic diets are also being used to treat brain tumors, Parkinson's disease, migraines, Alzheimer's disease, and NAFLD (non-alcoholic fatty liver disease / hepatitis). Due to the metabolic properties of MCT fats and their lower energy content compared to conventional fats, MCT fats are also being used in the fields of weight management and metabolic syndrome.

[0030] The use of MCT fats in the nutritional therapy of various diseases should be distinguished from their use in sports nutrition, where MCT fats are known as a fast energy source and are primarily used in endurance sports.

[0031] Medium-chain fatty acids are contraindicated in patients at risk of ketoacidosis and in patients with medium-chain fatty acid oxidation disorders (MCAD deficiency, MCADD, or medium-chain acyl-CoA dehydrogenase deficiency). Due to their low smoke point, medium-chain fatty acids have limited heat tolerance, and manufacturers' information and instructions in this regard should be followed to avoid increased smoke.

[0032] Specifically, one particular fatty acid polyol ester, particularly a fatty acid glycerol ester, of particular interest in accordance with the present invention is tricaprylin (also synonymously referred to as trioctanoyl glyceride, tricaprylglycerol, glycerol trioctanoin, tricapryloylglycerol, 1,2,3-propanetriyl octanoate, glycerin tricaprylate, glycerin tricaprylate, glycerin trioctanoate, glyceryl tricaprylate, capryl triglyceride, tricaprylin, tricaprylglycerol, etc.). Tricaprylin is a triglyceride of caprylic acid, typically produced by esterification of caprylic acid with glycerin. Tricaprylin is a clear, colorless to pale yellow liquid. It forms crystals from acetone / ethanol (95%). Tricaprylin is odorless.

[0033] Tricaprylin is used, for example, as a neutral carrier or excipient, an absorption enhancer, and an active drug solubilizer in pharmaceutical formulations. It is also used as the oil phase for preparing water-in-oil multiple emulsions to incorporate water-soluble drugs and to obtain stable microcapsules. Tricaprylin also functions as a vehicle in topical creams, lotions, and cosmetic formulations. It is also used as a penetration-enhancing lipid base with excellent emollient and skin-soothing properties. Its non-greasy, low viscosity allows for excellent spreadability. Despite its skin-penetrating properties, tricaprylin does not impede natural skin respiration, making it useful in baby oils, massage oils, and face masks. It is an excellent dispersant and acts as a solubilizer, humectant, and binder in color cosmetics. Due to its compatibility with natural oils and surfactants, tricaprylin is also used as a fat component in two-phase bubble baths. Furthermore, its compatibility with organic and inorganic filter agents makes it useful in sunscreen creams and oils. It is also used as a fixative in perfumes and fragrances.

[0034] However, as already indicated herein, fatty acid polyol esters, in particular fatty acid glycerol esters, in particular the so-called medium chain triglycerides (MCTs), and especially tricaprylin, have also been used as active ingredients or compounds in pharmaceutical compositions.

[0035] Specifically, tricaprylin-containing compositions were previously marketed under the trade name "Axona" as a medical food for the clinical dietary management of impaired metabolic processes associated with mild to moderate Alzheimer's disease. The commercially available formulation consists of tricaprylin fractionated from palm kernel oil. During digestion, caprylic triglycerides are broken down into ketone bodies, which provide an alternative energy source for the brain. This use is based on the fact that in Alzheimer's disease, the brain's ability to utilize its normal energy source (i.e., glucose) is impaired.

[0036] As a result, there is a high demand and growing interest in the prior art for fatty acid polyol esters, particularly fatty acid glycerol esters such as medium chain triglycerides (MCTs), and in particular tricaprylin.In particular, there is a growing demand in the pharmaceutical and food industries for higher fatty acid polyol esters, particularly higher fatty acid glycerol esters, that are rich in active substances and low in impurities, especially harmful impurities.

[0037] However, conventional manufacturing methods for producing fatty acid polyol esters, particularly fatty acid glycerol esters, such as medium-chain triglycerides (MCTs), and especially tricaprylin, produce relatively large amounts of impurities and by-products (such as those derived from hydrochloric acid HCl and metal-based catalysts used in the esterification step), particularly due to the high processing temperatures required, including subsequent multi-stage purification processes (multi-stage distillation at high temperatures or more), and the starting materials and reagents used, particularly halogen-containing substances. In particular, when triglycerides with low acid and hydroxyl values ​​and high degrees of esterification are required, the necessary significant esterification conditions, particularly high temperatures above 180°C and up to 230°C, the necessary subsequent multi-stage purification processes (multi-stage distillation at high temperatures or more), and the use of metal-based catalysts, lead to the formation of high amounts of toxic by-products and impurities, particularly toxic halide-based by-products and impurities.

[0038] In particular, conventional manufacturing processes for producing fatty acid polyol esters, in particular fatty acid glycerol esters, which include subsequent multi-stage purification treatments (multi-stage distillation at high temperatures or more), usually also produce relatively high levels of impurities and by-products, in particular toxic impurities and by-products such as, for example, genotoxic glycidol esters of fatty acids (also synonymously referred to as glycidyl esters of fatty acids or simply GE or GE only) and nephrotoxic fatty acid esters of monochloropropanediol (also synonymously referred to as MCPD fatty acid esters or simply MCPD esters), in particular fatty acid esters of 3-monochloropropanediol (3-MCPD fatty acid esters or 3-MCPD esters) and fatty acid esters of 2-monochloropropanediol (2-MCPD fatty acid esters or 2-MCPD esters).

[0039] The following exemplary reaction scheme illustrates the formation of the three aforementioned toxic by-products, i.e., 3-MCPD fatty acid esters, 2-MCPD fatty acid esters, and glycidol fatty acid esters, for the triglyceride tricaprylin, selected as a non-limiting example, when high temperatures (e.g., temperatures above 200°C) are applied to fatty acid triglycerides (e.g., tricaprylin) in the presence of chlorine-containing substances from the manufacturing process. The substance 3-chloro-1,2-propanediol is produced from glycerin when it reacts with 3-MCPD in the presence of chlorine-containing substances or chlorides, respectively.

[0040] [ka] Summary of the Invention [Problem to be solved by the invention]

[0041] Particularly for pharmaceutical and nutritional applications, control of impurity profiles is crucial, especially for known toxic by-products such as 3-MCPD fatty acid esters, 2-MCPD fatty acid esters, and glycidol fatty acid esters.

[0042] Although it has been well known for decades that such undesirable toxic by-products are produced due to the harsh process conditions that occur during conventional esterification / condensation methods of fats and oils, no attempt has been made to avoid such harsh conditions by improving or modifying the production process. This is because it is known that while mild esterification conditions using bio-based catalysts and low esterification temperatures reduce the production of toxic by-products such as the three aforementioned toxic by-products, i.e., 3-MCPD fatty acid esters, 2-MCPD fatty acid esters, and glycidol fatty acid esters, they also only result in triglycerides with undesirably high acid and hydroxyl values ​​and relatively low triglyceride contents at low conversions and yields.

[0043] As a result, rather than trying to avoid the production of undesired, toxic by-products, costly and burdensome pre- and / or post-treatment methods are implemented to remove these undesired, toxic by-products from the desired end product obtained under harsh esterification conditions (e.g., high temperatures exceeding 180°C and up to 230°C, the use of metal-based catalysts, etc.). Such burdensome post-treatment methods consist, inter alia, of the addition of strong alkaline reagents such as KOH, multi-stage distillation cascades, heat treatment with strong aqueous alkaline solutions, etc. (e.g., WO 2019 / 038320 A1, WO 2014 / 012548 A1, etc.), which affect and deteriorate the quality of such products, as well as the overall yield and efficiency. For example, WO 2021 / 070209 A1 discloses a complex multi-stage extraction process for the purification of triglycerides, using a saline / organic solvent two-phase extraction system with chlorinated organic solvents. However, such post-treatment methods often fail to remove the last traces of undesirable toxic by-products, which remain in the final product. This is particularly dangerous when high doses of fatty acid polyol esters, especially fatty acid glycerol esters, such as MCTs like tricaprylin, are applied in pharmaceutical and nutritional applications (especially in parenteral applications), leading to the accumulation of such undesirable traces of undesirable toxic by-products in the human body, thus exceeding the legally permitted threshold levels of undesirable toxic by-products.

[0044] Furthermore, such costly and burdensome post-treatment methods aimed solely at the reactive or retroactive removal of undesirable toxic by-products are also inefficient because they often result in undesirable entrainment of the product and do not improve or affect product quality or purity, such as the degree of esterification or the residual amount of other impurities (e.g., total halogenated substance content or total acid content).

[0045] For example, the European Union (EU) has imposed strict limits on the concentrations of such toxic by-products and impurities in food applications, especially for infants and young children, through its respective legal regulations (e.g., EU Regulations 2020 / 1322 and 2018 / 290). For example, the maximum permitted content of nephrotoxic 3-MCPD fatty acid esters in liquid infant formula, follow-on formula, special medical foods for infants and young children, and infant formula is only 15 mf / kg (i.e., 15 ppm), while the maximum permitted content of genotoxic glycidol fatty acid esters in the same formulations is only 6.0 mg / kg (i.e., 6.0 ppm). As a result, the permissible exposure levels of these toxic by-products in nutritional applications are very limited.

[0046] Therefore, it is difficult to consistently stay below maximum exposure levels, especially for monographed active pharmaceutical ingredients (i.e., pharmaceutical ingredients) such as MCT oil, where the total daily intake is well above 10 g / day. This is even more difficult for parenteral administration, where toxic substances can enter the human body directly.

[0047] Permanent or lifelong medication with fatty acid polyol esters, especially fatty acid glycerol esters, such as medium-chain triglycerides (MCTs), especially tricaprylin, can be administered or consumed in doses of up to 100 g per day. This requires particularly high purity grades. In contrast to nutritional supplements, pharmaceuticals are administered to patients suffering from serious illnesses.

[0048] It would therefore be desirable to envisage an efficient production process for directly producing high-quality fatty acid polyol esters, particularly fatty acid glycerol esters, such as MCT (e.g., tricaprylin), having high purity or minimal levels of by-products and impurities, respectively, while at the same time exhibiting a high degree of esterification and good stability, particularly storage stability, and a high active ingredient content, particularly without the need for additional cost-intensive and burdensome post-treatment operations.

[0049] As a result, the prior art has not lacked attempts to find efficient production processes, but has been unable to improve the efficiency and performance of existing processes. However, to date, no efficient manufacturing process has been considered in the prior art. Furthermore, access to such higher fatty acid polyol esters, particularly fatty acid glycerol esters such as MCT (e.g., tricaprylin), is either impossible or not easily achieved in the prior art.

[0050] The problem underlying the present invention is therefore to provide an efficient method for producing triglycerides of fatty acids (i.e. fatty acid glycerol triesters), particularly with high purity, in which the aforementioned drawbacks and / or disadvantages of the prior art should at least partially be avoided or even be at least essentially overcome.

[0051] Such a production process should in particular make available the respective fatty acid polyol esters, in particular fatty acid glycerol esters, such as MCT (e.g. tricaprylin), in an efficient manner, in particular of improved quality, without significant amounts of toxic by-products or impurities, and the production process should be feasible on an industrial level, in particular on a large scale, without the need for excessive and costly post-treatments envisaged in prior art processes. [Means for solving the problem]

[0052] The applicant has unexpectedly found that triglycerides of fatty acids, i.e., fatty acid polyol esters, in particular fatty acid glycerol esters (i.e., fatty acid glycerol triesters), such as, for example, MCT (e.g., tricaprylin), particularly with high purity, can be directly and efficiently produced, particularly in an economically and industrially feasible manner, if at least one of the following criteria is applied in the production process: (i) preferably selective derivatization of halide-based impurities present in the resulting reaction product and / or treatment or contact of the resulting reaction product with at least one nucleophile; (ii) carrying out the esterification at a temperature not exceeding 180°C; (iii) using glycerol or a protected form or precursor thereof, preferably solketal (isopropylideneglycerol), as starting material, at least essentially free of chlorinated species; and (iv) carrying out the esterification in the absence of a metal-based catalyst. It was not foreseeable that the application of at least one of these criteria, or a combination thereof, would lead to a significant improvement in the production of the aforementioned compounds.

[0053] Therefore, in order to solve the problems mentioned herein above, the present invention proposes, according to a first aspect thereof, a method for producing triglycerides of fatty acids (i.e. fatty acid glycerol triesters) having a particularly high purity according to claim 1; further particularly special and / or advantageous embodiments of the inventive method are the subject of the respective dependent claims.

[0054] Furthermore, the present invention provides, according to a second aspect thereof, C5-C which are obtainable or obtained by the inventive method according to the respective independent claim (i.e. claim 23). 12 -Triglycerides of fatty acids, especially C6-C 12 - relating to triglycerides of fatty acids C5-C according to the respective independent claim (i.e. claim 24) 12 -triglycerides of fatty acids according to the invention, in particular C6-C 12- to triglycerides of fatty acids and to the mixtures of the invention according to the respective independent claims (i.e. claim 32); further particularly special and / or advantageous embodiments of this aspect of the invention are the subject of the respective dependent claims.

[0055] Similarly, the present invention relates, according to a third aspect, to a pharmaceutical composition, in particular a medicament or pharmaceutical product, according to the respective independent claim (claim 42); further particularly special and / or advantageous embodiments of this aspect of the invention are the subject of the respective dependent claims.

[0056] Furthermore, the present invention provides, according to a fourth aspect, a C5-C 2 -antibody according to the invention for the preventive and / or therapeutic treatment of diseases of the human or animal body or for use in the preventive and / or therapeutic treatment of diseases of the human or animal body according to the respective independent claims (claims 45 and 46). 12 -Triglycerides of fatty acids, especially C6-C 12 It also relates to triglycerides of fatty acids or mixtures thereof.

[0057] Furthermore, the present invention provides, according to a fifth aspect, a compound C5-C1 according to the present invention for the manufacture of a medicament for the preventive and / or therapeutic treatment of a disease of the human or animal body or for the preventive and / or therapeutic treatment of a disease of the human or animal body, according to the respective independent claims (claims 47 to 49). 12 -Triglycerides of fatty acids, especially C6-C 12 It also relates to triglycerides of fatty acids or mixtures thereof.

[0058] Furthermore, the present invention relates, according to a sixth aspect of the invention, to a food and / or nutrient or food composition and / or food and / or medical food according to the respective independent claim (claim 50), and further particularly special and / or advantageous embodiments of the food and / or nutrient or food composition and / or food and / or medical food according to the invention are the subject of the respective dependent claims.

[0059] Similarly, according to a seventh aspect of the present invention, the present invention provides the following C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - the use of triglycerides of fatty acids, or the respective mixtures; further, particularly special and / or advantageous embodiments of the uses according to the invention are the subject of the respective dependent claims.

[0060] According to an eighth aspect of the present invention, there is further provided a method for producing a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - the use of triglycerides of fatty acids or mixtures according to the invention according to the respective independent claims (claims 54 to 58).

[0061] Finally, the present invention also relates, according to a ninth aspect, to the use of a nucleophile for purifying triglycerides of fatty acids and / or for preferably selectively removing or derivatizing halide-based impurities present in organic substances, in particular triglycerides of fatty acids, according to the respective independent claim (claim 59); further particularly special and / or advantageous embodiments of the use according to the invention are the subject of the respective dependent claims.

[0062] The following features, embodiments, advantages, etc. are described below only with respect to one aspect of the invention in order to avoid repetition, but it goes without saying that they also apply to other aspects of the invention as appropriate, without requiring separate mention.

[0063] Furthermore, it goes without saying that individual aspects and embodiments of the invention are also considered to be disclosed in any combination with other aspects and embodiments of the invention, and in particular any combination of features and embodiments resulting from backward reference to any claim is also considered to be broadly disclosed with respect to all resulting combination possibilities.

[0064] It should further be noted that with regard to all relative or percentage weight-based data provided below, in particular relative amount or weight data, within the scope of the present invention, these are selected by the skilled artisan in such a way that they always add up to 100% by weight or 100% by weight, respectively, including all components or ingredients, in particular as defined below; however, this is self-evident to the skilled artisan.

[0065] Moreover, those skilled in the art can deviate from the following range specifications as needed without departing from the scope of the present invention.

[0066] Furthermore, it applies that all values ​​or parameters etc. specified below can in principle be determined or identified by standardized or explicitly defined determination methods or by determination or measurement methods well known to those skilled in the art.

[0067] With this being said, the present invention will now be described in more detail:

[0068] The subject of the present invention is therefore, according to a first aspect thereof, a method for producing particularly pure triglycerides of fatty acids (i.e. fatty acid glycerol triesters), comprising: Formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) or a protected form or precursor thereof, preferably solketal (isopropylideneglycerol), is reacted with a radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 - alkyl radicals of general formula (II) CH2[OC(O)R 1]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (II) C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 -to produce one or more triglycerides of fatty acids, a process in which fatty acids are used as starting materials and reacted to convert them into the corresponding triglycerides of fatty acids, wherein the process comprises at least one esterification step, in particular C5-C 12 -Fatty acids, especially C6-C 12 - comprising an esterification step using fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters); wherein the method is characterized by at least one of the following features and / or conditions (i) to (iv), in particular by a combination of at least two, preferably a combination of at least three, more preferably a combination of all four of the following features and / or conditions (i) to (iv): (i) a selective derivatization of halide-based impurities present in the resulting reaction product is carried out, in particular MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids, and / or the resulting reaction product is derivatized with at least one nucleophile, in particular a nucleophile capable of removing halide-based impurities, preferably bisulfite (HSO - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- treating and / or contacting with a nucleophile selected from the group consisting of phosphines and phosphines, and combinations thereof; (ii) at least one esterification stage is operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 150°C, in particular not exceeding 120°C, preferably not exceeding 100°C, more preferably not exceeding 80°C, even more preferably not exceeding 50°C; (iii) the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol), used as starting material is at least essentially free of chlorinated species, in particular having a total chlorinated species content of at most 1 ppm, in particular at most 0.5 ppm, preferably at most 0.1 ppm, based on the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol); (iv) at least one esterification stage is operated and / or carried out in the absence of a metal-based catalyst;

[0069] As mentioned above, the Applicant has, quite surprisingly, discovered that triglycerides of fatty acids (i.e., fatty acid glycerol triesters), particularly C5-C6, such as MCTs (e.g., tricaprylin), 12 -Triglycerides of fatty acids, especially C6-C 12 It has been found that triglycerides of fatty acids can thus be produced in an efficient and economical manner, in particular with a high degree of purity and in a quality suitable in particular for nutritional but also for pharmaceutical or clinical use.

[0070] For example, triglycerides of the above-mentioned fatty acids, such as MCT (e.g., tricaprylin) i.e., fatty acid glycerol triesters), especially C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 -fatty acid triglycerides are thus for the first time available in such a high purity and in a direct and efficient manner through the production process according to the invention.

[0071] In particular, and very surprisingly, when the last one of the aforementioned features and / or conditions (i) to (iv) is applied, the formation of harmful by-products and impurities, such as, for example, genotoxic glycidyl esters of fatty acids or nephrotoxic fatty acid esters of monochloropropanediol, such as 3-MCPD and 2-MCPD fatty acid esters, can be effectively avoided or at least minimized in advance, since burdensome and costly post-processing operations for their removal, as envisaged in the prior art, are not required. Potential traces of toxic by-products and impurities are easily and efficiently removed by the aforementioned measure (I), as will be explained in more detail below.

[0072] Because, as the Applicant has surprisingly and unexpectedly found, by applying at least one, in particular a combination of at least two, preferably a combination of at least three, more preferably a combination of all four of the above-mentioned characteristics and / or conditions (i) to (iv), triglycerides of fatty acids having a high degree of purity are obtained, i.e. independently of the specific reaction pathway of these substances.

[0073] In particular, and quite surprisingly, applying at least one, particularly a combination of at least two, preferably at least three, and more preferably all four of the above-mentioned features and / or conditions (i) to (iv) results in a triglyceride of fatty acids having a high degree of purity, which simultaneously combines five purity characteristics (1) to (5): (1) very low acid value (AV), (2) very low hydroxyl value (OHV), (3) very high triglyceride content, (4) very low total content of monochloropropanediol fatty acid esters (fatty acid esters of monochloropropanediol), and (5) very low total content of glycidol esters of fatty acids. Such combinations of purity characteristics (1) to (5) were previously considered incompatible or unachievable in the prior art. However, as the applicant has surprisingly discovered, applying at least one, particularly a combination of at least two, preferably at least three, and more preferably all four of the above-mentioned features and / or conditions (i) to (iv) can achieve this purity specification regardless of the specific synthetic route.

[0074] In this regard, the following finding by the Applicant is extremely surprising: in the prior art, the formation of high levels of impurities and by-products (mainly due to glycidol fatty acid esters and MCPD fatty acid esters) is primarily attributed to high-temperature workup procedures, in particular multi-stage purification treatments (multi-stage distillation at high temperatures or higher); purification treatments under heat and high temperatures are known to result in such harmful by-products. However, as the Applicant has now surprisingly discovered, when the de novo synthesis of fatty acid polyol esters, in particular fatty acid glycerol esters, such as medium-chain triglycerides (MCTs), and in particular tricaprylin, already produces large amounts of these undesirable and toxic by-products, apart from the subsequent required multi-stage purification workup (multi-stage distillation at high temperatures), more extreme esterification conditions are applied, in particular high temperatures of 180°C to 230°C in combination with the use of metal-based catalysts, and a high degree of esterification is also achieved. Therefore, the finding by the applicant that avoidance efforts regarding these toxic by-products must start very early in the process line (i.e., instead of the synthesis itself and in the upstream selection of the purity grade of the glycerol-based starting material) is quite surprising.

[0075] Although much effort has been made over the past decade to optimize the refining conditions of natural fats and oils, particularly palm oil, to reduce the content of harmful by-products, particularly MCPD and glycidol fatty acid esters, the prior art lacks a systematic attempt to identify suitable conditions for conventional condensation reactions to produce synthetic triglycerides. However, these teachings fall far short of simply transferring teachings from research related to the refining of natural oils, as they focus solely on the retroactive or retroactive reduction of impurities from by-products already formed and present in the final product, without taking into account the simultaneous need for high quality (i.e., the need to a priori prevent the formation of these undesirable toxic by-products at their source). Furthermore, these prior teachings do not provide a root-cause analysis of the origin of toxic by-products, particularly MCPD and glycidol fatty acid esters.

[0076] As a result, the applicant has unexpectedly and absolutely surprisingly found that applying at least one of the features and / or conditions (i) to (iv), in particular a combination of at least two, preferably at least three, and more preferably all four of the features and / or conditions (i) to (iv), to unify the five purity characteristics (1) to (5) described above, can efficiently reach the purity specifications defined above. Thus, according to the present invention, the features and / or conditions, in particular the features and / or conditions (ii) to (iv), prevent the formation of toxic by-products, such as glycidol fatty acid esters and MCPD fatty acid esters, at their source by avoiding the causes of their formation, while the predominant feature and / or condition (i) allows for the efficient and selective removal of any traces of these toxic by-products that are nevertheless formed or otherwise entrapped.

[0077] Thus, the applicant has been able to provide, for the very first time, a concept for producing high-purity fatty acid triglycerides with high yield and conversion, in other words, the applicant has been able to provide, for the very first time, a universal respective concept for this purpose.

[0078] by preferably selective derivatization of halide-based impurities present in the resulting reaction product and / or treatment of said resulting reaction product with at least one nucleophile, by selecting relatively mild esterification conditions in the absence of a metal-based catalyst, and / or by selecting the purity grade of the glycerol starting material, C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 It is surprisingly possible to obtain triglycerides of -fatty acids while avoiding harsh esterification conditions and burdensome and inefficient pre- and / or post-treatment procedures.

[0079] Apart from this, the process of the present invention is at the same time very flexible and compatible with known prior art production methods and plants for these substances, since the aforementioned features and / or conditions (i) to (iv) can be easily introduced into or used to modify known production methods and plants for these substances.

[0080] In contrast, the prior art production of these substances by conventional synthetic methods involving burdensome and costly workups is very complex, expensive, and inefficient, since the prior art synthetic methods produce significant amounts of the aforementioned toxic by-products and impurities, which must be separated from the respective crude products in complex and often multi-stage workup operations. In particular, the burdensome and costly workup operations do not improve the product quality in terms of a high degree of esterification and a low acidity of the final product, nor do they affect the yield of the production process in this way.

[0081] Within the scope of the present invention, triglycerides (i.e., fatty acid glycerol triesters) of fatty acids, such as MCTs (e.g., tricaprylin), in particular C5-C 12 -Triglycerides of fatty acids, especially C6-C 12-Triglycerides of fatty acids can be produced with a high content of these substances, a high degree of esterification, and very low acidity, while being free or at least essentially free from the aforementioned toxic by-products and impurities.

[0082] Furthermore, the manufacturing process according to the present invention is economical to operate and can be carried out on a large scale.

[0083] In particular, the process of the present invention uses commercially available starting compounds and is a relatively simple and manageable method for large scale implementation.

[0084] In contrast to conventional prior art manufacturing methods that require further complex post-treatment operations, the manufacturing method according to the present invention achieves excellent yields without such complex post-treatment operations, and the production of toxic by-products is minimized or completely avoided.

[0085] Furthermore, the process of the present invention is easy to carry out and economical. In particular, the process according to the present invention, in particular the esterification, is usually carried out in the absence and / or without solvent (i.e., as a bulk reaction, or as a material reaction, or as a so-called bulk reaction); as a result, the reaction product obtained is not contaminated with solvent, and after carrying out the process or reaction, there is no need to remove and dispose of the solvent or recycle it in a costly and energy-intensive manner. Furthermore, no toxic by-products are produced, or at least essentially no toxic by-products are produced.

[0086] In summary, as previously mentioned, the present invention relates to a method for producing triglycerides of fatty acids (i.e., fatty acid glycerol triesters), particularly in high purity, where formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerol, glycerin) or its protected forms or A precursor, preferably solketal (isopropylideneglycerol), is used as the starting material. and / or The reaction product is a compound represented by the general formula (II) CH2[OC(O)R 1 ]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (I) C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - converted into the corresponding triglycerides of fatty acids to produce one or more triglycerides of fatty acids. Here, in the general formula (II), the radical R 1 ,R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 represents an alkyl radical, wherein the process comprises at least one esterification step, in particular C5-C 12 -Fatty acids, especially C6-C 12 - comprising an esterification step using fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters).

[0087] As already mentioned hereinabove, the method of the present invention is characterized by at least one of the following characteristics and / or conditions (i) to (iv), in particular by a combination of at least two, preferably at least three of the following characteristics and / or conditions (i) to (iv), which are explained in more detail below: (i) Preferably, selective derivatization of halide-based impurities present in the resulting reaction product, in particular MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids, is carried out, and / or the resulting reaction product is derivatized with at least one nucleophile, in particular a nucleophile capable of removing halide-based impurities, preferably hydrogen sulfite (bisulfite, HSO - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- ) and phosphines and combinations thereof, and more preferably hydrogen sulfites (bisulfites, HSO - ), particularly for the selective derivatization of halide-based impurities, in particular MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids; (ii) at least one esterification stage is operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 150°C, in particular not exceeding 120°C, preferably not exceeding 100°C, more preferably not exceeding 80°C, even more preferably not exceeding 50°C; (iii) the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol), used as starting material is at least essentially free of chlorinated species, in particular has a total chlorinated species content of at most 1 ppm, in particular at most 0.5 ppm, preferably at most 0.1 ppm, based on the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol); (iv) At least one esterification step is carried out in the absence of a metal-based catalyst.

[0088] Regarding feature and / or condition (i), the following should be emphasized and taken into consideration: according to said feature and / or condition (i), it is envisaged that a preferably selective derivatization of halide-based impurities present in the resulting reaction product, in particular MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids, is carried out, and / or the resulting reaction product is derivatized by the addition of at least one nucleophile, in particular a nucleophile capable of removing halide-based impurities, and preferably hydrogen sulfite (bisulfite, HSO - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), bisulfite (H2PO3 - ), phosphite (HPO3 2- ) and phosphines and combinations thereof, and more preferably hydrogen sulfites (bisulfites, HSO - ), in particular for the preferably selective derivatization of halide-based impurities, especially MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids.

[0089] The applicant has surprisingly found that the use of the aforementioned nucleophiles is effective for the preferably selective derivatization of halide-based impurities, particularly MCPD fatty acid esters and glycidol esters of fatty acids. This is all the more surprising since these halide-based impurities are usually present in only small, especially trace amounts; nevertheless, treatment with the aforementioned nucleophiles usually results in the selective derivatization of these substances according to the following reaction scheme, which allows the derivatives to be subsequently easily removed or eliminated, i.e., separated from the final reaction product (see below).

[0090] The following reaction schemes show, by way of example only and not by way of limitation, the selective derivatization of halide-based impurities, namely, on the one hand, the selective derivatization of MCPD fatty acid esters (upper reaction) and, on the other hand, the selective derivatization of glycidol fatty acid esters (lower reaction), in which sodium hydrogen sulfite (sodium bisulfite, NaHSO3) is used as the nucleophile (by way of example only and not by way of limitation), and the radicals R are, independently of one another, linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radicals are preferably linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 - denotes an alkyl radical.

[0091] As can be seen from this reaction scheme, the nucleophile displaces the organically bound chlorine atom in the MCPD fatty acid ester via so-called nucleophilic substitution, preferably via a so-called SN2-like reaction mechanism, which is removed as sodium chloride and easily separated in the aqueous phase along with the substitution product (top reaction). As can be seen from this reaction scheme, the nucleophile also reacts with the glycidol fatty acid ester under ring-opening conditions to give a water-soluble product (bottom reaction). Separation of the purified triglyceride product after separation of the aqueous phase can be achieved, for example, via distillation (e.g., short-path distillation).

[0092] [ka]

[0093] As the above reaction scheme shows, halide-based impurities (i.e., MCPD fatty acid esters and glycidol fatty acid esters) can be efficiently removed by selective reaction with a nucleophile (here, e.g., bisulfite). Halide-based impurities (even trace amounts) are selectively converted to water-soluble molecules, which can be easily removed, especially by washing with water or short-path distillation.

[0094] Thus, by virtue of feature and / or condition (i) of the present invention, halide-based impurities, in particular MCPD and glycidol fatty acid esters, can be selectively removed by derivatization, but without affecting or impacting other relevant product properties such as, for example, acid value (AV), hydroxyl value (OHV) and triglyceride content.

[0095] Thus, the above feature and / or condition (i) is an efficient means for selectively removing toxic halide-based impurities, such as genotoxic glycidol esters of fatty acids and nephrotoxic fatty acid esters of MCPD. The resulting derivatized products can be easily removed by washout or short-path distillation (in the case of short-path distillation, the derivatized products are typically retained or retained in the distillation residue (sump)). As also shown in the reaction scheme above, the chlorine atoms are preferably converted to harmless sodium chloride, which is easily washed away with the aqueous phase.

[0096] Generally, the above feature and / or condition (i) is preferably carried out as a one-stage or single-stage treatment. However, it is also possible to treat and / or contact the triglycerides of fatty acids to be purified with a nucleophile repeatedly, especially in two or more cycles and / or as a multi-stage process, especially when the level of impurities is high. Nevertheless, it is preferred to treat and / or contact the triglycerides of fatty acids to be purified with a nucleophile in one stage (i.e., without repeated treatment and / or contact); as an alternative, it is also possible to use a higher amount or concentration of nucleophile instead of repeated treatment and / or contact, especially when the level of impurities is high.

[0097] As a result, feature and / or condition (i) of the present invention allows for the selective elimination or removal of low, preferably trace amounts of toxic halide-based impurities in an efficient and selective manner, i.e., without affecting other required and desired properties of the resulting product (e.g., low acid and hydroxyl values ​​and high triglyceride content, etc.).

[0098] With regard to feature and / or condition (ii), the following should be emphasized and taken into consideration: according to said feature and / or condition (ii), it is envisaged that at least one esterification stage is operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 150°C, in particular not exceeding 120°C, preferably not exceeding 100°C, more preferably not exceeding 80°C, and even more preferably not exceeding 50°C.

[0099] Surprisingly, as the Applicant has found, limiting the temperature during at least one esterification stage is also an efficient means for avoiding the formation of toxic impurities during esterification, in particular MCPD and glycidol fatty acid esters; nevertheless, high conversions, high yields and high esterification levels, in particular high triglyceride contents with low acid and hydroxyl values, are advantageously achieved with the process of the present invention, in particular when other characteristics and / or conditions are taken into account, in particular when the synthetic route described below is applied.

[0100] As a result, the process of the present invention makes it possible for the first time to operate at least one esterification stage under relatively mild conditions, in particular with a view to avoiding the formation of toxic by-products of the type mentioned above, while ensuring high esterification levels, in particular high triglyceride contents, and good conversions and yields.

[0101] In particular, in combination with at least one of the other features and / or conditions (i), (iii) and / or (iv) mentioned above, feature and / or condition (ii) of the present invention gives excellent results.

[0102] With regard to feature and / or proviso (iii), the following should be emphasized and taken into consideration: according to said feature and / or proviso (iii), the 1,2,3-propanetriol of formula (I) or its protected form, preferably solketal (isopropylideneglycerol), used as starting material is at least essentially free of chlorinated species and in particular has a total content of chlorinated species of at most 1 ppm, in particular at most 0.5 ppm, preferably at most 0.1 ppm, based on the 1,2,3-propanetriol of formula (I) or its protected form, preferably solketal (isopropylideneglycerol).

[0103] As the applicant has surprisingly found, the presence of chlorinated species, in particular the content of so-called total chlorinated species, has a decisive influence on the formation of toxic by-products in the final reaction product, namely the formation of toxic MCPD and glycidol fatty acid esters.

[0104] Therefore, the selection of starting materials for their purity grade, 1,2,3-propanetriol or its protected form, preferably solketal, plays a crucial role in avoiding the formation of toxic by-products (e.g., MCPD and glycidol fatty acid esters) during esterification, which is quite surprising. By selecting these starting materials as being at least essentially free of chlorinated species, and in particular as having the indicated total chlorinated species content, the formation of these toxic by-products is effectively prevented or at least minimized to the greatest extent.

[0105] It has never been known or realized in the prior art that the content of chlorinated species in the starting material in the form of 1,2,3-propanetriol or its protected forms (e.g., solketal) has a decisive effect on the purity of the resulting final reaction product (i.e., triglyceride).

[0106] The starting product 1,2,3-propanetriol or a protected form thereof, preferably solketal, of the required purity is generally commercially available.

[0107] The 1,2,3-propanetriol of the required purity used in the present invention can be obtained from petrochemical feedstocks, e.g., from epichlorin-hydrin, or from oleochemical feedstocks, e.g., from the hydrolysis of natural fats and oils. Petrochemically or oleochemically derived glycerol of suitable purity and quality is obtained mainly by purification using physical techniques (e.g., distillation or membrane filtration, e.g., membrane ultrafiltration).

[0108] The applicant's experimental data surprisingly show that, in contrast to the chlorinated species content of the starting glycerol or its protected derivatives (e.g., solketal), the remaining starting materials, i.e., C5-C6 used in at least the esterification step, 12 -Fatty acids, especially C6-C 12 The chlorinated species content of the fatty acids and / or their anhydrides and / or esters does not play such a significant role. C5-C with a total chlorinated species content in the range of 20 ppm to 100 ppm 12 -Fatty acids, especially C6-C 12 The esterification carried out with fatty acids and / or their anhydrides and / or esters does not at the same time result in the formation of toxic MCPD and glycidol esters during the esterification, provided that 1,2,3-propanetriol or its protected forms, preferably solketal, having the purity grade according to the invention (i.e. a total content of chlorinated species of at most 1 ppm, in particular at most 0.5 ppm, preferably at most 0.1 ppm) is used. Conversely, further experimental data by the Applicant surprisingly also show that 1,2,3-propanetriol or its protected forms, preferably solketal, having a total content of chlorinated species in the range of 20 ppm to 100 ppm, does not result in the formation of toxic MCPD and glycidol esters during the esterification. 12 -Fatty acids, especially C6-C 12 Even when the fatty acids and / or their anhydrides and / or esters are of high purity grade (i.e. total content of chlorinated species max. 1 ppm, in particular max. 0.5 ppm, preferably max. 0.1 ppm), the esterification leads to a significant formation of toxic MCPD and glycidol fatty acid esters. Without being bound by any particular theory, this surprising phenomenon may be explained by the fact that 1,2,3-propanetriol or its protected form, preferably solketal, contains at least predominantly chlorinated species in organically bound form which contribute to the formation of MCPD and glycidol fatty acid esters upon esterification, whereas C5-C 12 -fatty acids, especially C6-C 12 In the case of fatty acids and / or their anhydrides and / or esters, these substances may contain at least predominantly entrained chlorinated species in inorganic form, in particular as inorganic salts such as NaCl, which cannot contribute at all (or at best only negligibly) to the formation of MCPD and glycidol fatty acid esters upon esterification.

[0109] As a result, the purity levels of these starting materials as a whole, particularly their specific selection of their content of chlorinated species and minimization of the total chlorinated species content also play an important role in the purity and quality of the final reaction product.

[0110] With regard to feature and / or condition (iv), the following should be emphasized and taken into consideration: according to said feature and / or condition (iv), it is envisaged that at least one esterification stage is operated and / or carried out in the absence of a metal-based catalyst.

[0111] Conducting at least one esterification step without a metal-based catalyst is an important challenge in the process of the present invention because such metal-based catalysts often introduce or incorporate large amounts of undesirable halides, particularly chlorides. Such introduced or incorporated halides, particularly chlorides, can lead to the undesired production of harmful by-products during esterification, particularly MCPD and glycidol fatty acid esters. Avoiding such metal-based catalysts during esterification effectively avoids or prevents the uncontrolled and undesired introduction or incorporation of halide-based impurities.

[0112] Furthermore, in contrast to the enzyme-based catalysts used during esterification according to certain embodiments of the methods of the present invention, metal-based catalysts (e.g., tetrabutyl titanate, etc.) require relatively high temperatures (e.g., 190°C to 230°C) for esterification, thus resulting in the undesirable and uncontrolled formation of the aforementioned toxic by-products, particularly MCPD and glycidol fatty acid esters.

[0113] Consequently, feature and / or condition (iv) of the present invention also significantly contributes to obtaining a final reaction product with desirable properties in terms of excellent purity and other properties, such as low acid number, low hydroxyl number and high triglyceride content.

[0114] According to the present invention, the method of the present invention produces highly pure fatty acid triglycerides (i.e., fatty acid glycerol triesters).

[0115] In particular, according to the method of the present invention, General formula (II) CH2[O-(O)R 1 ]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (II) Here, in the general formula (II), the radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -reaction products which represent alkyl radicals, especially C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 one or more triglycerides of fatty acids, in each bond, characterized by and / or exhibiting the following properties (1) to (5) and / or meeting the following manufacturing specifications: (1) Acid value (AV), in particular as measured according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (2) hydroxyl value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (3) triglyceride content, as determined by European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0): ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%, based on the reaction product; and (4) the total content of MCPD fatty acid esters, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fatty Acids): each based on the reaction product, is ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm; and (5) Total glycidol content of fatty acids, determined in particular by the method of DGF C-VI 18(10) (German Fat Society standard method): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on the reaction product.

[0116] In particular, in other words, according to the present invention, the process is carried out in such a way that the features and / or conditions (i) to (iv), in particular a combination of at least two, preferably at least three of the features and / or conditions (i) to (iv), are applied and / or implemented, with the proviso that the reaction product, in particular the product of the general formula (II) General formula (II) CH2[O-(O)R 1 ]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (II) Here, in the general formula (II), the radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11-Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -reaction products which represent alkyl radicals, especially C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 provided that one or more triglycerides of fatty acids are characterized and / or exhibit, in each bond, the following properties (1) to (5) and / or meet the following manufacturing specifications: (1) Acid value (AV), in particular as measured according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (2) hydroxyl value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (3) triglyceride content, as determined by European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0): ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%, based on the reaction product; and (4) the total content of MCPD fatty acid esters, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fatty Acids): each based on the reaction product, is ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm; and (5) Total glycidol content of fatty acids, determined in particular by the method of DGF C-VI 18(10) (German Fat Society standard method): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on the reaction product.

[0117] Surprisingly, the reaction product of the present invention integrates in an overall combination the five aforementioned properties (1) to (5), which have previously been considered mutually exclusive, since, according to prior art methods, increasing the triglyceride content and decreasing the acid and hydroxyl values ​​usually leads to a high total content of MCPD and glycidol fatty acid esters and is favored by aggressive esterification conditions; whereas, according to prior art, decreasing the total content of MCPD and glycidol fatty acid esters leads to a relatively low triglyceride content with a high acid and hydroxyl value.

[0118] In contrast to this prior art, the present invention makes it possible for the first time to combine all five of the aforementioned properties (1) to (5) in one and the same product, resulting in an inventive reaction product that is highly suitable for food and pharmaceutical applications, even for parenteral use at high doses and / or concentrations.

[0119] According to the present invention, the inventive reaction products obtained from the inventive process have a very low acid value (AV), i.e., an acid value (AV) of ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g, as measured in particular according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0). The so-called acid value parameter indicates the residual free acid resulting from the esterification. The lower the acid value, the higher the product quality. In particular, the very low acid value envisaged in the present invention results in high stability of the resulting reaction products (i.e., triglycerides), in particular excellent long-term and / or storage stability and excellent preservation stability.

[0120] As indicated above, according to the present invention, the acid value (AV) is usually determined according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0). The acid value (also synonymously referred to as neutralization value, acid value, or acidity) is the mass (in milligrams) of potassium hydroxide (KOH) required to neutralize one gram of a chemical substance, and the acid value is a measure of the number of carboxylic acid groups in a chemical compound (here, triglycerides). The indicated standard of European Pharmacopoeia 2.5.1 is based on the titration method.

[0121] Apart from the acid value (AV) parameter, the hydroxyl value (OHV) of the inventive reaction product obtained from the process of the present invention also plays an important role. According to the present invention, the inventive reaction product also has a very low hydroxyl value (OHV), i.e., a hydroxyl value (OHV) of ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g, measured in particular according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0). In this case, the hydroxyl value (OHV) is an indicator of the degree of esterification, and indicates a very high degree of esterification of the inventive reaction product.

[0122] According to the present invention, the hydroxyl value (OHV) is determined in particular according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0). The hydroxyl value measured according to this method is defined as the number of milligrams of potassium hydroxide (KOH) required to neutralize the acetic acid incorporated during the acetylation of one gram of a chemical substance (here, a triglyceride) containing free hydroxyl groups. Thus, the hydroxyl value is a measure of the content of free hydroxyl groups in a chemical substance (here, a triglyceride), and is usually expressed as the mass of potassium hydroxide (KOH) in milligrams corresponding to the hydroxyl group content in one gram of the chemical substance. The measurement method specified in European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0) involves acetylating the free hydroxyl groups of the reaction product (here, a triglyceride) with acetic anhydride in pyridine solvent. After the reaction is complete, water is added to convert the remaining unreacted acetic anhydride to acetic acid, which is then titrated with potassium hydroxide to determine the OHV.

[0123] Thus, in the case of the reaction products of the present invention, the triglycerides of the present invention, apart from a very low acid value (AV), also contain at the same time a very low hydroxyl value (OHV), as indicated herein above, corresponding to a high degree of esterification.

[0124] Furthermore, as a third parameter and / or property (3), the reaction products of the present invention exhibit a very high triglyceride content, i.e., a triglyceride content determined in particular according to European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0), in particular ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%, based on the reaction product. These extremely high triglyceride content values ​​also indicate a high purity grade of the reaction products of the present invention. The triglyceride content of the products of the present invention is determined in particular according to European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0). This method is based on quantification by gas chromatography.

[0125] Apart from the parameters and / or properties of low acid value (AV), low hydroxyl value (OHV) and high triglyceride content, the reaction products of the invention are also characterized by an extremely low total content of MCPD fatty acid esters and glycidol fatty acid esters: the total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), determined in particular according to the method DGF C-VI 18(10) (German Fatty Society standard method), is ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, respectively, based on the reaction product, and; the total content of glycidol esters of fatty acids, determined in particular according to the method DGF C-VI 18(10) (German Fatty Society standard method), is ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, respectively, based on the reaction product.

[0126] The indicated method for measuring DGF C-VI1 18(10) allows for reliable quantification of these toxic impurities. In particular, the reaction product of the present invention obtained from the process of the present invention, as shown herein, combines a high triglyceride content level with a very low total content of these toxic esters with low acid and hydroxide values.

[0127] As a result, the five combinations of the aforementioned properties and / or parameters (1)-(5) are unique characteristics of the reaction products obtained from the process of the present invention, distinguishing these reaction products from similar prior art reaction products. Thus, the process of the present invention provides, for the first time, high purity grades of C6-C4 exhibiting low acid numbers and low hydroxyl numbers. 12 -Triglycerides of fatty acids can be produced with a very high triglyceride content and at the same time with a very low total content of toxic MCPD and glycidol fatty acid esters.

[0128] According to a particular embodiment, the present invention relates to a method for producing triglycerides of fatty acids (i.e. fatty acid glycerol triesters) of particularly high purity, in particular as described or defined herein above, where formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerin, glycerol) or a protected form thereof, preferably solketal (isopropylideneglycerol), is used as the starting material to react, and / or Radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 - alkyl radicals of general formula (II) CH2[OC(O)R 1 ]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (II) C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - converted into the corresponding triglycerides of fatty acids to produce one or more triglycerides of fatty acids, The process comprises at least one esterification step, in particular C5-C 12 -Fatty acids, especially C6-C 12 - comprising an esterification step using fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters); The method is characterized by at least one of the following features and / or conditions (i) to (iv), in particular by a combination of at least two, preferably at least three, of the following measures (i) to (iv): (i) a preferably selective derivatization of halide-based impurities present in the resulting reaction product, in particular MCPD fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids, is carried out, and / or the resulting reaction product is derivatized with at least one nucleophile, in particular with a nucleophile capable of removing halide-based impurities, preferably hydrogen sulfite (bisulfite, HSO - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- ) and phosphines and combinations thereof, more preferably hydrogen sulfites (bisulfites, HSO - ) for the preferably selective derivatization, in particular of MCPED fatty acid esters (fatty acid esters of monochloropropanediol) and glycidol esters of fatty acids; (ii) at least one esterification stage is operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 150°C, in particular not exceeding 120°C, preferably not exceeding 100°C, more preferably not exceeding 80°C, even more preferably not exceeding 50°C; (iii) the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol), used as starting material is at least essentially free of chlorinated species, in particular having a total chlorinated species content of at most 1 ppm, in particular at most 0.5 ppm, preferably at most 0.1 ppm, based on the 1,2,3-propanetriol of formula (I) or a protected form thereof, preferably solketal (isopropylideneglycerol); (iv) at least one esterification step is carried out in the absence of a metal-based catalyst; wherein the method is carried out in such a way that the features and / or conditions (i) to (iv), in particular a combination of at least two, preferably at least three of the features and / or conditions (i) to (iv), are applied and / or implemented, provided that the reaction product, one or more triglycerides of C5-C12 fatty acids of general formula (II) above, in particular one or more triglycerides of C6-C12 fatty acids, in combination thereof, is characterized by the following properties (1) to (5) and / or meets the following product specifications: (1) Acid value (AV), in particular as measured according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 ppm KOH / g; and (2) hydroxyl value (OHV), in particular as measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 ppm KOH / g; and (3) triglyceride content, in particular as determined by European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%; and (4) The total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), determined in particular by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): ≦0.5 ppm, in particular ≦0.2 ppm, based on the respective reaction products, preferably ≦0.1 ppm; and (5) Total content of glycidol esters of fatty acids, in particular as determined by the DGF C-VI18(10) method (German Fat Society standard method): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on the respective reaction products.

[0129] According to a further particular embodiment of the present invention, the method of the present invention is carried out and / or a combination of at least two, preferably at least three, of the features and / or conditions (i) to (iv), in particular of the features and / or conditions (i) to (iv), is applied and / or implemented, with the proviso that said reaction product, in particular one or more triglycerides of C5-C12 fatty acids, in particular C6-C 12 provided that one or more triglycerides of fatty acids, of general formula (II) above, in their combination are characterized by and / or exhibit the following properties (1) to (5) and / or meet the following product specifications: (1) In particular, the acid value (AV) as determined by European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): 0.1 ppm KOH / g; and (2) Hydroxylic acid value (OHV) measured in particular according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.1 ppm KOH / g; and (3) triglyceride content, in particular as determined by European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≥ 99.5%, in particular ≥ 99.6%, preferably ≥ 99.8%; and (4) The total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), as determined in particular by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): ≦0.1 ppm based on the reaction product; and (5) Total content of glycidol esters of fatty acids, determined in particular by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): ≦0.1 ppm based on the reaction product.

[0130] Such reaction products, in particular C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12- one or more triglycerides of fatty acids are particularly suitable for applications requiring high purity grades and at the same time high levels of active ingredients, such as nutritional and especially pharmaceutical applications and uses (e.g. even parenteral applications at high doses and / or concentrations).

[0131] As mentioned above, the process of the present invention includes at least one esterification step, particularly C5-C 12 -Fatty acids, especially C6-C 12 - an esterification step using fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters).

[0132] According to a particular embodiment of the process of the present invention, the C5-C esters used in at least one esterification step 12 -Fatty acids, especially C6-C 12 fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters) of the general formula (III) R 4 -C(O)OH (III) It is expressed as: Here, in the general formula (III), the radical R 4 is a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 12 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 - represents alkyl radicals, their anhydrides and esters (preferably C1-C4-alkyl esters) and combinations thereof.

[0133] According to a further particular embodiment of the present invention, the C5-C 12 -Fatty acids, especially C6-C 12 - fatty acids and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters) are straight-chain saturated C5-C 12 -Fatty acids, especially straight chain saturated C6-C 12fatty acids, and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters).

[0134] According to yet another particular embodiment of the process of the invention, the C5-C esters used in at least one esterification step 12 -Fatty acids, especially C6-C 12 fatty acids, and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters), such as valeric acid (pentanoic acid), caproic acid (hexanoic acid), enanthic acid (heptanoic acid), caprylic acid (octanoic acid), pelargonic acid (nonanoic acid), capric acid (decanoic acid), undecylic acid (undecanoic acid), lauric acid (dodecanoic acid) and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters), in particular caproic acid (hexanoic acid), enanthic acid (heptanoic acid), caprylic acid (octanoic acid), pelargonic acid (nonanoic acid), capric acid (decanoic acid), undecylic acid (undecanoic acid), Lauric acid (dodecanoic acid) and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters), preferably caproic acid (hexanoic acid), enanthic acid (heptanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid), lauric acid (dodecanoic acid) and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters), more preferably caproic acid (hexanoic acid), enanthic acid (heptanoic acid), caprylic acid (octanoic acid), capric acid (decanoic acid) and / or their anhydrides and / or esters (preferably C1-C4-alkyl esters).

[0135] As already described in detail, the method of the present invention provides the following reaction products: Radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11-Alkyl radicals, especially C5-C 11 - alkyl radicals of general formula (II) CH2[OC(O)R 1 ]-CH[OC(O)R 2 ]-[CH2[OC(O)R 3 ] (II) C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - one or more triglycerides of fatty acids are provided and / or produced.

[0136] In this regard, according to a particular embodiment of the process of the invention, the reaction product is a C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - one or more triglycerides of fatty acids are envisaged, provided that all radicals R 1 , R 2 and R 3 The condition is that they are the same.

[0137] According to a further particular embodiment of the method of the present invention, the reaction product is triheptanoin (1,3-di(heptanoyloxy)propan-2-ylheptanoate); and / or In the above general formula (II), the radical R 1 , R 2 and R 3 each represents a linear saturated aliphatic C6-alkyl radical; and / or It is envisaged that in at least one esterification step, heptanoic acid (enanthic acid) and / or its anhydrides and / or esters (preferably C1-C4-alkyl esters) are used.

[0138] Furthermore, according to yet another particular embodiment of the method of the present invention, the reaction product is tricaprylin; and / or In the above general formula (II), the radical R 1 , R2 and R 3 each represents a linear saturated aliphatic C7-alkyl radical; and / or It is envisaged that in at least one esterification step, octanoic acid (caprylic acid) and / or its anhydrides and / or esters (preferably C1-C4-alkyl esters) are used.

[0139] Additionally, in accordance with an alternative embodiment of the present invention, it is contemplated that the reaction product is not tricaprylin.

[0140] Furthermore, according to yet another alternative embodiment of the process of the present invention, the reaction product is a C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - one or more triglycerides of fatty acids, provided that the radical R 1 , R 2 and R 3 The condition is that at least two of the above are different from each other.

[0141] Finally, according to yet another alternative embodiment of the process of the invention, the reaction product is a C5-C 12 -One or more triglycerides of fatty acids, especially C6-C 12 - one or more triglycerides of fatty acids are envisaged, provided that all radicals R 1 , R 2 and R 3 The condition is that they are different from each other.

[0142] This indicates that the method of the present invention can produce triglycerides of many different fatty acids (i.e., fatty acid glycerol triesters).

[0143] As already detailed herein, according to the present invention, the method of the present invention is characterized by at least one of the above-defined features and / or conditions (i) to (iv), in particular by a combination of at least two, preferably a combination of at least three, more preferably a combination of all four of the above-defined features and / or conditions (i) to (iv).

[0144] In this regard, it is envisaged that, according to a particular embodiment of the method of the invention, the method of the invention is characterized by a combination of at least two, preferably a combination of at least three, more preferably a combination of all four of the above-defined features and / or conditions (i) to (iv).

[0145] According to another particular embodiment of the method of the invention, it is envisaged that the method of the invention is characterized by a combination of at least two, preferably at least three, of the above-defined features and / or conditions (ii) to (iv), optionally in further combination with the above-defined feature and / or condition (i).

[0146] Furthermore, according to yet another particular embodiment of the method of the present invention, it is envisaged that the method of the present invention is characterized by a combination of the above-defined feature and / or condition (i) and at least two of the above-defined features and / or conditions (ii) to (iv).

[0147] Finally, according to further particular embodiments of the method of the invention, it is envisaged that the method of the invention is characterized by all combinations of the above-defined features and / or conditions (i) to (iv).

[0148] As stated above, according to the present invention, by applying the above-defined characteristics and / or conditions (i) and / or (ii) and / or (iii) and / or (iv), particularly pure triglycerides of fatty acids (i.e. fatty acid glycerol triesters) are obtained in accordance with the above-mentioned reference product specifications.

[0149] According to a particular embodiment of the method of the present invention, it is particularly preferred that the entire and / or all stages, including any pre-treatment and / or post-treatment stages (if any), are operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 160°C, in particular not exceeding 150°C, preferably not exceeding 120°C.

[0150] In other words, according to this particular embodiment of the method of the invention, it is particularly preferred that said method is characterized by the further feature and / or proviso (v): (v) In particular, the entire and / or all steps, including any optional pre-treatment and / or post-treatment steps (if any), are operated and / or carried out at a temperature not exceeding 180°C, in particular not exceeding 160°C, in particular not exceeding 150°C, preferably not exceeding 120°C.

[0151] This measure (v) allows to effectively prevent the formation of toxic by-products such as MCPD and glycidol fatty acid esters.

[0152] According to another particular embodiment of the process of the invention, it is particularly preferred that the entire and / or entire step, including also any pre-treatment and / or post-treatment steps (if any), is operated and / or carried out in the absence of a metal-based catalyst.

[0153] In other words, according to this particular embodiment of the method of the present invention, said method may further comprise the further feature and / or condition (vi) (vi) In particular, the entire process and / or the entire step, including any pre-treatment and / or post-treatment steps, if any, is operated and / or carried out in the absence of a metal-based catalyst.

[0154] It is also an important objective of the process of the present invention that all and / or all steps, particularly any pre- and / or post-treatment steps, are carried out without the use of metal-based catalysts, since such metal-based catalysts often introduce or incorporate large amounts of undesirable halides, especially chlorides. The halides, especially chlorides, thus introduced or incorporated can lead to the undesired formation of harmful by-products, especially MCPD and glycidol fatty acid esters, during esterification. By avoiding such metal-based catalysts throughout all and / or all process steps, particularly including any pre- and / or post-treatment steps (if any), the uncontrolled and undesired introduction or incorporation of halide-based impurities is thus effectively avoided or prevented.

[0155] As mentioned above, the process of the present invention includes at least one esterification step.

[0156] Generally, the at least one esterification step can be carried out and / or performed as a single-step esterification or, alternatively, as a two-step or multi-step esterification.

[0157] According to a particular embodiment of the process of the present invention, at least one esterification step comprises a C5-C 1,2,3-propanetriol of formula (I) or a protected form or precursor thereof, preferably solketal, which is reacted with the 1,2,3-propanetriol of formula (I) or a protected form or precursor thereof, preferably solketal. 12 Preferably, the esterification step is carried out and / or performed as a one-stage esterification (using an anhydride of a fatty acid). Alternatively, according to another particular embodiment of the method of the invention, at least one esterification step is also carried out and / or performed as a two-stage or multi-stage esterification (i.e., in a first stage, a C5-C ester is reacted with 1,2,3-propanetriol of formula (I) or a protected form or precursor thereof, preferably solketal). 12 - use of fatty acids and / or their esters, followed in a subsequent step by further esterification, in particular by further esterification of free and / or remaining OH groups, preferably C5-C12 -Esterification using fatty acid anhydrides is carried out).

[0158] Generally, according to certain embodiments of the method of the present invention, it is preferred if at least one esterification step is carried out and / or performed in the absence and / or without a solvent. This means that at least one esterification step is carried out as a mass reaction / esterification, a material reaction / esterification, a so-called bulk reaction (bulk esterification). This has the advantage that the resulting reaction product is not contaminated with solvent, and after at least one esterification step is carried out, there is no need to remove and discard the solvent or recycle it in a cost- and energy-intensive manner. Surprisingly, the at least one esterification step nevertheless proceeds with high conversion and yield, and at least essentially without the production of significant by-products. In addition, the absence of a solvent during the at least one esterification step facilitates the recycling of the esterification catalyst, if one is used, and in particular ensures that the esterification catalyst can be recycled without reactivation, since solvents can deactivate or poison such esterification catalysts.

[0159] The temperature range applied to the at least one esterification stage can vary over a wide range. Generally, according to the present invention, it is preferred that the at least one esterification stage is carried out and / or performed at a moderate temperature, i.e., in the range of 5°C to 95°C, in particular in the range of 10°C to 85°C, preferably in the range of 15°C to 80°C, more preferably in the range of 20°C to 75°C, and even more preferably in the range of 25°C to 70°C. This moderate temperature regime applied to the at least one esterification stage effectively prevents the formation of particularly toxic by-products and ensures efficient esterification. However, those skilled in the art can deviate from these range specifications if necessary or in single or exceptional cases without departing from the scope of the present invention.

[0160] The pressure range applied in the at least one esterification stage may also vary over a wide range. Generally, according to the present invention, it is preferred that the at least one esterification stage is carried out and / or performed at a pressure in the range of 0.0001 bar to 10 bar, in particular in the range of 0.001 bar to 5 bar, preferably in the range of 0.01 bar to 2 bar, more preferably in the range of 0.05 bar to 1 bar, and even more preferably at a pressure of about 1 bar. This pressure regime applied in the at least one esterification stage ensures efficient esterification. However, those skilled in the art can deviate from these range specifications if necessary or in single or exceptional cases without departing from the scope of the present invention.

[0161] Basically, according to the present invention, at least one esterification step can be carried out and / or performed in the absence of a catalyst, or alternatively, at least one esterification step can be carried out and / or performed at least partially in the presence of an enzyme as a catalyst and / or at least partially in the presence of an enzyme-based catalyst. When an enzyme as a catalyst and / or an enzyme-based catalyst is used, it is preferred that the catalyst is recycled after at least one esterification step; this increases efficiency and process economics, especially when the method of the present invention is carried out on a large scale or industrial level.

[0162] As used herein, the expressions or formulations "enzyme (used) as a catalyst" and "enzyme-based catalyst" are used synonymously.

[0163] In this regard, according to a particular embodiment of the method of the present invention, a C5-C 1,2,3-propanetriol of formula (I) or a protected form or precursor thereof, preferably solketal, is reacted with 12When using an anhydride of a fatty acid, at least one esterification step can be carried out and / or performed in the absence of a catalyst. Alternatively, according to another alternative particular embodiment of the method of the present invention, a C5-C 1,2,3-propanetriol of formula (I) or a protected form or precursor thereof, preferably solketal, is reacted with 12 When using fatty acids and / or esters thereof, at least one esterification step can also be carried out and / or performed at least in part in the presence of an enzyme as catalyst and / or at least in part in the presence of an enzyme-based catalyst; as mentioned above, when an enzyme as catalyst and / or an enzyme-based catalyst is used, it is preferred that the catalyst is recycled after at least one esterification step.

[0164] As mentioned above, according to a particular embodiment of the present invention, at least one esterification step can be carried out and / or performed at least partially in the presence of an enzyme as a catalyst and / or at least partially in the presence of an enzyme-based catalyst (preferably, as indicated above, in the absence and / or without a solvent), which ensures high esterification efficiency, in particular high conversion and yield due to an excellent degree of esterification under mild esterification conditions and low acid and hydroxyl values.

[0165] Generally, when at least one esterification step is carried out at least in part in the presence of an enzyme as a catalyst and / or in the presence of an enzyme-based catalyst, it is preferred that the enzyme is selected in particular from synthetases (ligases), catalases, esterases, lipases and combinations thereof.

[0166] In particular, the enzyme is selected from the group consisting of Candida antarctica, Mucor miehei (Rhizomucor miehei), Thermomyces lanuginosus, Candida rugosa, Aspergillus oryzae, Pseudomonas cepacia, Pseudomonas fluorescens, Rhizopus delemar, Pseudomonas sp. It is preferred to use Candida Antarctica, Mucor miehei (Rhizomucor miehei) and Thermomyces lanuginosus as the starting material, and combinations thereof, preferably Candida Antarctica. These species provide particularly good esterification results.

[0167] Furthermore, the enzymes can be used in immobilized form, in particular on a support, preferably a polymeric support, more preferably a polymeric organic support, more preferably a hydrophobic support, even more preferably a poly(meth)acrylic resin support, which greatly improves the handling and use as well as the recycling of the enzymes as catalysts.

[0168] In particular, as mentioned above, it is preferred that the enzyme is recycled after at least one esterification step for the reasons stated above.

[0169] Generally, when at least one esterification step is carried out at least in part in the presence of an enzyme as a catalyst and / or at least in part in the presence of an enzyme-based catalyst, the temperature range applied to the at least one esterification step can vary over a wide range. In particular, in that case, the at least one esterification step can be carried out and / or performed at a temperature in the range of 5° C. to 95° C., in particular in the range of 10° C. to 85° C., preferably in the range of 15° C. to 80° C., more preferably in the range of 20° C. to 75° C., and even more preferably in the range of 25° C. to 70° C. However, a person skilled in the art can deviate from these range specifications if necessary or in single or exceptional cases without departing from the scope of the present invention.

[0170] Furthermore, if at least one esterification step is carried out at least partially in the presence of an enzyme as a catalyst and / or at least partially in the presence of an enzyme-based catalyst, the amount of enzyme applied in at least one esterification step can vary within wide limits. In particular, in this case, the enzyme is used in an amount ranging from 0.0001 to 25% by weight, in particular from 0.001 to 20% by weight, preferably from 0.01 to 15% by weight, more preferably from 0.05 to 10% by weight, based on the total amount of all starting compounds. However, a person skilled in the art can deviate from these ranges if necessary or in single or exceptional cases without departing from the scope of the invention.

[0171] In particular, according to a particular embodiment of the present invention, the enzyme is present in an amount of 1×10 based on the total amount of all starting compounds. -6 Within the range of ~5 mol%, especially 1 × 10 -6 Within the range of 2.5 mol%, preferably 1 × 10 -4 in the range of up to 1.5 mol%, more preferably 1 × 10 -3 % to 1 mol %, however, those skilled in the art can deviate from these ranges if necessary or in single or exceptional cases without departing from the scope of the invention.

[0172] Furthermore, if at least one esterification stage is carried out at least partially in the presence of an enzyme as a catalyst and / or at least partially in the presence of an enzyme-based catalyst, the pressure range applied to the at least one esterification stage may also vary over a wide range. In particular in that case, the at least one esterification stage can be carried out and / or performed at a pressure in the range of 0.0001 bar to 10 bar, in particular in the range of 0.001 bar to 5 bar, preferably in the range of 0.01 bar to 2 bar, more preferably in the range of 0.05 bar to 1 bar, and even more preferably at about 1 bar. However, those skilled in the art can deviate from these range specifications if necessary or in single or exceptional cases without departing from the scope of the present invention.

[0173] As stated above, the present invention is based on a general concept / method for producing high purity triglycerides of fatty acids in high yield and high conversion, which concept / method is independent of any particular synthetic route, and therefore Applicant's concept is general in its applicability for this purpose.

[0174] As a result, numerous synthetic routes are applicable within the scope of the present invention, and these possible synthetic routes are described in more detail below.

[0175] According to a particular embodiment of the present invention, the reaction product obtained or obtainable from the process of the present invention can be prepared, for example, via one of the following synthetic routes (A) to (F): (A) According to the (first) overall route (A), a compound of formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerol, glycerin), preferably in the presence of an enzyme as a catalyst and / or in the presence of an enzyme-based catalyst (especially as defined above), is converted to at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acids or esters thereof, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12-fatty acids or their esters, preferably linear saturated aliphatic C5-C 12 -fatty acids or their esters, in particular linear saturated aliphatic C6-C 12 - first reacting with a fatty acid or an ester thereof to produce a diglyceride, more preferably a 1,3-diglyceride, This is followed by the addition of at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12 - fatty acid anhydrides, preferably at least one linear saturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear saturated aliphatic C6-C 12 - reacting with a fatty acid anhydride, producing a reaction product of general formula (II) as defined above; Otherwise , (B) According to the (second) synthetic route (B), a compound of formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerol, glycerin) Preferably in the presence of an enzyme as a catalyst and / or in the presence of an enzyme-based catalyst (especially as defined above), at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acids or esters thereof, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12 -fatty acids or their esters, preferably linear saturated aliphatic C5-C 12 -fatty acids or their esters, in particular linear saturated aliphatic C6-C 12 - first reacting with a fatty acid or an ester thereof to produce a diglyceride, more preferably a 1,3-diglyceride, Subsequently, preferably in the presence of an enzyme as a catalyst and / or in the presence of an enzyme-based catalyst (more preferably an enzyme such as Pseudomonas fluorescens lipase or Burkholderia cepacia lipase for the regioselective esterification of 1,3-diglycerides at the 2-position), at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acids or their esters, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12 - fatty acids or esters thereof, preferably at least one linear saturated aliphatic C5-C 12 - fatty acids or their esters, in particular at least one linear saturated aliphatic C6-C 12 reacts with fatty acids or their esters, producing a reaction product of general formula (II) as defined above; Otherwise, (C) According to the (third) synthetic route (C), a compound of formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerin, glycerin) is Preferably, in the absence of a catalyst, at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear or branched, saturated or unsaturated aliphatic C-C 12 - fatty acid anhydrides and preferably at least one linear saturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear saturated aliphatic C6-C 12 - reacting with a fatty acid anhydride, producing a reaction product of general formula (II) as defined above; Otherwise, (D) According to the (fourth) synthetic route (D), a protected form or precursor of 1,2,3-propanetriol of formula (I) above, preferably solketal (isopropylideneglycerol), is converted to at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12 - fatty acid anhydrides and preferably at least one linear saturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear saturated aliphatic C6-C 12 reacting with a fatty acid anhydride, In particular, a deprotection reaction, in particular a ring-opening (preferably acid-induced) and optionally acetone removal, is carried out after monoesterification of the free OH groups of the protected form or precursor of 1,2,3-propanetriol of formula (I) above, followed by the addition of at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 with fatty acid anhydrides, in particular with at least one linear or branched, saturated or unsaturated aliphatic C-C 12 with fatty acid anhydrides, preferably at least one linear saturated aliphatic C5-C 12 with fatty acid anhydrides, in particular with at least one linear saturated aliphatic C6-C 12 a further esterification with a fatty acid anhydride is carried out, producing a reaction product of general formula (II) as defined above; Otherwise, (E) According to the (fifth) synthetic route (E), The protected form or precursor of 1,2,3-propanetriol of formula (I), preferably solketal (isopropylideneglycerol), is preferably converted to at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acids or their esters, in particular at least one linear or branched, saturated or unsaturated aliphatic C6-C 12- fatty acids or esters thereof, preferably at least one linear saturated aliphatic C5-C 12 - fatty acids or their esters, in particular at least one linear saturated aliphatic C6-C 12 with a fatty acid or an ester thereof, followed by a deprotection reaction, in particular a ring-opening reaction (preferably acid-induced) and removal of acetone, to preferably produce a monoglyceride, more preferably a terminal monoglyceride and / or a 1-monoglyceride, This is followed by the addition of at least one linear or branched, saturated or unsaturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear or branched, saturated or unsaturated aliphatic C-C 12 - fatty acid anhydrides and preferably at least one linear saturated aliphatic C5-C 12 - fatty acid anhydrides, in particular at least one linear saturated aliphatic C6-C 12 - reacts with fatty acid anhydrides, producing a reaction product of general formula (II) as defined above; Otherwise, (F) According to the (sixth) combined route (F), the compound of formula (I) CH2(OH)-CH(OH)-CH2(OH) (I) 1,2,3-propanetriol (glycerin, glycerol), optionally in the presence of an enzyme as a catalyst and / or in the presence of an enzyme-based catalyst (as specifically defined herein), is converted to at least one linear or branched, mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C5-C 12 fatty acids and / or their esters and / or anhydrides, in particular at least one linear or branched, mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C-C 12 - fatty acids and / or their esters and / or anhydrides, preferably mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C5-C 12 - fatty acids and / or their esters and / or anhydrides, in particular mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C6-C 12- fatty acids and / or their esters and / or anhydrides with at least one linear mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C-C 12 - reacts with fatty acids and / or their esters and / or anhydrides, preferably mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C5-C 12 - producing triglycerides of fatty acids, This is followed by a hydrogenation reaction, preferably in the presence of at least one hydrogenation catalyst, to convert the mono- or poly-unsaturated (preferably mono-unsaturated) aliphatic C5-C6 of the triglyceride. 12 -Hydrogenation of the double bond of the fatty acid radical, Producing a reaction product of general formula (II) as defined above.

[0176] The above (first) synthetic route (A) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0177] [ka]

[0178] The above (second) synthetic route (B) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0179] [ka]

[0180] The above (third) synthetic route (C) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0181] [ka]

[0182] The above (fourth) synthetic route (D) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0183] [ka]

[0184] The above (fifth) synthetic route (E) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0185] [ka]

[0186] The above (sixth) synthetic route (F) can be illustrated in a non-limiting manner and for visualization purposes only by the following simplified reaction scheme showing the preparation of an exemplary inventive reaction product, tricaprylin.

[0187] [ka]

[0188] Overall, the applicant has been able to provide a general concept and method, respectively, for producing high-purity fatty acid triglycerides with high yield and high conversion. Therefore, the applicant's concept is universally applicable for this purpose. The method of the present invention simultaneously has high flexibility and compatibility with known prior art production methods and plants for these substances, since the aforementioned features and / or conditions (i) to (iv) of the present invention can be easily implemented in or used to modify known production methods and plants for these substances.

[0189] In particular, the method of the present invention produces high purity triglycerides of fatty acids that simultaneously combine a combination of at least five purity characteristics: (1) very low acid value (AV), (2) very low hydroxyl value (OHV), (3) very high triglyceride content, (4) very low total MCPD fatty acid ester content, and (5) very low total glycidol ester content of fatty acids, where the purity specifications can be achieved independently of a particular synthetic route. While this combination of purity characteristics (1) through (5) was previously thought to be incompatible or impossible to achieve, applicants have surprisingly discovered that the method of the present invention makes this combination of purity characteristics possible for the first time.

[0190] A further subject matter, according to a second aspect of the invention, is a reaction product obtained or obtainable by the process according to the invention. In other words, according to this aspect of the invention, the invention relates to a C5-C olefin obtained or obtainable by the process according to the invention as defined above. 12 -Triglycerides of fatty acids, especially C6-C 12 - relating to triglycerides of fatty acids.

[0191] In particular, the subject of the present invention is, according to this aspect of the invention, C5-C 12 -Triglycerides of fatty acids Celides, especially C6-C 12-Triglycerides of fatty acids, especially those obtained by the method of the present invention triglycerides obtained or obtainable by C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 -Triglycerides of fatty acids contain the radical R 1 , R 2 and R 3 are each independently a linear or branched, saturated or unsaturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 -Alkyl radical, preferably a linear saturated aliphatic C4-C 11 -Alkyl radicals, especially C5-C 11 - alkyl radicals of general formula (II) CH2[OC(O)R 1 ]-CH[OC(O)R 2 ]-CH2[OC(O)R 3 ] (II) corresponds to Here, C5-C of general formula (II) 12 -Triglycerides of fatty acids, especially C6-C 12 The triglycerides of fatty acids, in their combination, are characterized by and / or exhibit the following properties (1) to (5) and / or meet the following product specifications: (1) Acid value (AV), in particular as determined according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (2) Hydroxylic acid value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (3) Triglyceride content as determined by European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0): ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%, based on triglycerides; and (4) total content of MCPD fatty acid esters, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on triglycerides; and (5) Total glycidol content of fatty acids, determined in particular by the method of DGF C-VI 18(10) (German Society of Fatty Acids Standard Method): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on triglycerides, respectively.

[0192] In particular, the subject of the present invention is triglycerides of C5-C12 fatty acids, in particular triglycerides of C6-C12 fatty acids, according to the above definition, The triglycerides of C5-C12 fatty acids of general formula (II), in particular triglycerides of C6-C12 fatty acids, are characterized by and / or exhibit the following properties (1) to (5) in their bonds and / or meet the following product specifications: (1) Acid value (A), measured in particular according to the European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0) V):≦0.1mgKOH / g; and (2) Hydroxylic acid value (OH) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0) V): 0.1mgKOH / g; and (3) Triglycerides measured according to European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0) Lithium content: ≥ 99.5%, in particular ≥ 99.6%, preferably based on the reaction product or ≥ 99.8%; and (4) In particular, by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science) The total content of MCPD fatty acid esters measured: each based on the reaction product ≦0.1ppm; and (5) In particular, by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science) The total glycidol content of the fatty acids measured: each based on the reaction product is ≦ 0.1 ppm.

[0193] According to a particular embodiment of the invention, the subject of the invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - a triglyceride of fatty acids, in which in the general formula (II) all radicals R 1 , R 2 and R 3 are identical.

[0194] According to a further particular embodiment of the invention, the subject of the invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 -triglycerides of fatty acids, where C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 The triglyceride of the fatty acid is triheptanoin (=1,3-di(heptanoyloxy)propan-2-ylheptanoate).

[0195] According to yet another particular embodiment of the invention, the subject of the invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - Triglycerides of fatty acids, C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 -The triglyceride of fatty acid is tricaprylin.

[0196] Furthermore, according to yet another, but alternative, particular embodiment of the present invention, the subject of the present invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 -triglycerides of fatty acids, where C5-C 12 -Triglycerides of fatty acids, especially C6-C 12-Triglycerides of fatty acids are not tricaprylin.

[0197] Furthermore, according to yet another embodiment of the present invention, the subject of the present invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - a triglyceride of fatty acids, in which the radical R 1 , R 2 and R 3 At least two of the triglycerides are different from each other (i.e., mixed triglycerides).

[0198] According to yet another embodiment of the present invention, the subject of the present invention is a C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - a triglyceride of fatty acids, in which in the general formula (II) all radicals R 1 , R 2 and R 3 However, they are different from each other (i.e., mixed triglycerides).

[0199] According to this aspect of the invention, and according to a particular embodiment of the invention, the subject of the invention also relates to a mixture of triglycerides, wherein the mixture of the invention is a mixture of C5-C as defined above. 12 - at least two different triglycerides of fatty acids, especially C6-C 12 - Containing at least two different triglycerides of fatty acids.

[0200] In this respect, according to a particular embodiment of the present invention, the mixture of the present invention may be, for example, As defined in 12 - two, three or more different triglycerides of fatty acids, especially C6-C 12 -Contains triglycerides of fatty acids.

[0201] Typically, the mixture of the present invention is obtainable or obtained by the process of the present invention as defined above.

[0202] According to a particular embodiment of the present invention, the mixture of the present invention preferably comprises triheptanoin (i.e. 1,3-di(heptanoyloxy)propan-2-ylheptanoate).

[0203] According to yet another particular embodiment of the invention, the mixture of the invention preferably comprises tricaprylin.

[0204] According to yet another particular, but alternative, embodiment of the present invention, the mixture of the present invention does not comprise tricaprylin.

[0205] Furthermore, according to another particular embodiment of the invention, the mixture of the invention has the following characteristics: total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), determined in particular according to the method of DGF C-VI 18(10) (standard method of the German Society of Fatty Acids): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, in each case based on the mixture; and The total content of glycidol esters of fatty acids, determined in particular according to the method of DGF C-VI 18(10) (standard method of the German Society of Fatty Acids): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, each based on the mixture.

[0206] Furthermore, according to yet another particular embodiment of the present invention, the mixture of the present invention has the following characteristics: Total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), determined specifically according to the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science): ≤ 0.1 ppm, based on the mixture; and The total content of glycidol esters of fatty acids, determined in particular according to the method of DGF C-VI 18(10) (standard method of the German Fat Society): ≦0.1 ppm, based on the mixture.

[0207] Likewise, according to yet another particular embodiment of the present invention, the mixtures of the present invention are typically characterized in that all triglycerides present in the mixture are characterized by and / or exhibit, in combination, the following properties (1) to (5) and / or meet the following product specifications: (1) Acid value (AV), in particular as determined according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (2) Hydroxylic acid value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g, in particular ≦0.2 mg KOH / g, preferably ≦0.1 mg KOH / g; and (3) Triglyceride content as determined by European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0): ≥ 99%, in particular ≥ 99.2%, preferably ≥ 99.5%, based on triglycerides; and (4) total content of MCPD fatty acid esters, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science): each based on triglycerides ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm; and (5) Total glycidol content of fatty acids, determined in particular by the method of DGF C-VI 18(10) (German Society of Fatty Acids Standard Method): ≦0.5 ppm, in particular ≦0.2 ppm, preferably ≦0.1 ppm, based on the triglycerides.

[0208] Finally, according to yet another particular embodiment of the present invention, the mixtures of the present invention are typically characterized in that all the triglycerides present in the mixture are characterized by and / or exhibit, in combination, the following properties (1) to (5) and / or meet the following product specifications: (1) Acid value (AV) determined specifically according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≤ 0.1 mg KOH / g; and (2) Hydroxylic acid value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≤ 0.1 mg KOH / g; and (3) Triglyceride content as determined according to European Pharmacopoeia 2.2.28 (European Pharmacopoeia 10.0): ≥ 99.5%, in particular ≥ 99.6%, preferably ≥ 99.8%, each based on triglycerides; and (4) Total content of MCPD fatty acid esters, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science): ≤ 0.1 ppm based on triglycerides; and (5) Total content of glycidol of fatty acids, determined in particular by the method of DGF C-VI 18(10) (standard method of the German Society of Fat Science): ≦0.1 ppm based on triglycerides.

[0209] The reaction product of the present invention, i.e., the C5-C 12 -triglycerides of fatty acids, in particular C6-C 12 - triglycerides of fatty acids and their mixtures are linked and combined with a number of advantageous and specific properties and characteristics, which have already been explained in detail above in connection with the process of the invention; therefore, reference can be made to these above explanations in order to avoid unnecessary repetition.

[0210] In particular, the reaction product of the present invention, i.e., C5-C 12 - the inventive triglycerides of fatty acids, in particular C6-C 12 The inventive triglycerides of -fatty acids and mixtures thereof are particularly suitable for applications requiring high purity grades and at the same time high levels of active ingredients, such as nutritional applications, and especially pharmaceutical applications and uses (e.g. even parenteral applications at high doses and / or concentrations).

[0211] Furthermore, the reaction product of the present invention, i.e., the C5-C 12 -Triglycerides of fatty acids, especially C6-C 12The triglycerides of fatty acids and their mixtures unite, in an overall combination, the five aforementioned properties (1) to (5), which have previously been considered mutually exclusive. This is because, according to prior art methods, increasing the triglyceride content and decreasing the acid and hydroxyl values ​​typically leads to a high total content of MCPD and glycidol fatty acid esters due to drastic esterification conditions. Conversely, according to prior art methods, decreasing the total content of MCPD and glycidol fatty acid esters leads to a relatively low triglyceride content with a high acid and hydroxyl value. In contrast to this prior art, the present invention makes it possible for the first time to combine all five aforementioned properties (1) to (5) in one and the same product. As a result, the inventive reaction product obtained by the inventive method is highly suitable for food and pharmaceutical applications, even in parenteral applications at high doses and / or concentrations.

[0212] For further details relating to the second aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first aspect of the present invention (i.e., the method of the present invention), which explanations and remarks apply mutatis mutandis accordingly to this second aspect of the present invention.

[0213] Similarly, the present invention provides, according to a third aspect thereof, at least one inventive C5-C 12 - triglycerides of fatty acids, in particular at least one C6-C 12 - a pharmaceutical composition, in particular a drug or medicinal product, comprising a triglyceride of fatty acids and / or a mixture of the invention as defined above, in particular together with a physiologically acceptable excipient.

[0214] In particular, according to this aspect of the invention, the present invention provides a method for treating diseases of the human or animal body, in particular cardiovascular diseases such as brain trauma, stroke, hypoxia, and myocardial infarction, diseases related to disorders of energy metabolism, in particular ketone body metabolism, such as refeeding syndrome, anorexia, and epilepsy, neurodegenerative diseases such as dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, lipid metabolism diseases such as glucose transporter deficiency (GLUT1 deficiency) and long-chain fatty acid dysregulation (VL-FAOD), and mitochondrial diseases such as mitochondrial thiolase deficiency, cancers such as Huntington's disease, T-cell lymphoma, astrocytoma, and glioblastoma, HIV, rheumatic diseases such as rheumatoid arthritis and arthritis, and gastrointestinal diseases such as chronic inflammatory bowel disease, The present invention relates to pharmaceutical compositions for or for use in the prophylactic and / or therapeutic treatment of gastrointestinal diseases, in particular ulcerative colitis and Crohn's disease, rhizal storage diseases, such as glycosphingolipidosis, in particular Niemann-Pick disease, diabetes, migraines and migraines, epilepsy, in particular infantile spasms, and the effects and side effects of chemotherapy.

[0215] In particular, according to this aspect of the invention, the invention relates to a pharmaceutical composition for or for use in the preventive and / or therapeutic treatment of diseases of the human body selected from among Alzheimer's disease, in particular mild to moderate Alzheimer's disease; migraine and migraine headaches; and epilepsy, in particular infantile convulsions.

[0216] For further details relating to the third aspect of the invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first and third aspects of the invention, which explanations and remarks apply mutatis mutandis accordingly to this third aspect of the invention.

[0217] Furthermore, according to a fourth aspect of the present invention, the present invention provides a method for treating diseases of the human or animal body, particularly cardiovascular diseases such as brain trauma, stroke, hypoxia, and myocardial infarction, diseases associated with disorders of energy metabolism, particularly ketone body metabolism, such as renutation syndrome, anorexia, and epilepsy, neurodegenerative diseases such as dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, lipid metabolism diseases such as glucose transporter deficiency (GLUT1 deficiency) and VL-FAOD, and mitochondrial diseases such as mitochondrial thiolase deficiency, cancers such as Huntington's disease, T-cell lymphoma, astrocytoma, and glioblastoma, rheumatic diseases such as HIV, rheumatoid arthritis, and arthritis, and gastrointestinal diseases such as chronic inflammatory bowel disease, The present invention relates to inventive triglycerides of C5-C12 fatty acids as defined above, in particular inventive triglycerides of C6-C12 fatty acids and / or inventive mixtures as defined above for or use in the preventive and / or therapeutic treatment of gastrointestinal diseases, in particular ulcerative colitis and Crohn's disease, glycosphingolipidosis, lysosomal storage diseases, in particular Niemann-Pick disease, diabetes, migraines and migraines, epilepsy, in particular infantile spasms, the effects and side effects of chemotherapy, etc.

[0218] In particular, according to this aspect of the invention, the present invention relates to a compound of the invention C5-C6 as defined above for use in the preventive and / or therapeutic treatment or in the preventive and / or therapeutic treatment of a disease of the human body selected from Alzheimer's disease, in particular mild to moderate Alzheimer's disease, migraine and migraine headache; and epilepsy, in particular infantile convulsions. 12 -Triglycerides of fatty acids, especially C6-C 12 - relates to triglycerides of fatty acids and / or mixtures of the invention as defined above.

[0219] For further details relating to the fourth aspect of the invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second and third aspects of the invention, which explanations and remarks apply mutatis mutandis accordingly to this fourth aspect of the invention.

[0220] Furthermore, according to a fifth aspect of the present invention, there is provided a method for producing a cyclohexane- ... 12 - the inventive triglycerides of fatty acids, in particular of at least one C6-C 12 - the use of the inventive triglycerides of fatty acids and / or the inventive mixtures as defined above in diseases of the human or animal body, in particular cardiovascular diseases such as brain trauma, stroke, hypoxia, myocardial infarction, diseases associated with disorders of energy metabolism, in particular ketone body metabolism, such as refeeding syndrome, anorexia, epilepsy, neurodegenerative diseases such as dementia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, lipid metabolism diseases such as glucose transporter deficiency (GLUT1 deficiency), VL-FAOD, mitochondrial diseases such as mitochondrial thiolase deficiency, cancers such as Huntington's disease, T-cell lymphoma, astrocytoma, glioblastoma, HIV, rheumatic diseases such as rheumatoid arthritis and arthritis, gastrointestinal diseases such as chronic inflammatory bowel disease, It also relates to the use of the invention for the prophylactic and / or therapeutic treatment of, or for the manufacture of a medicament for, the prophylactic and / or therapeutic treatment of, gastrointestinal diseases, in particular ulcerative colitis and Crohn's disease, rhizal storage diseases, such as glycosphingolipidosis, in particular Niemann-Pick disease, diabetes, migraines and migraines, epilepsy, in particular infantile spasms, the effects and side effects of chemotherapy, etc.

[0221] In particular, according to this aspect of the invention, the present invention relates to a compound of formula (I) or (II) comprising a C5-C agonist as defined above for the manufacture of a medicament for the preventive and / or therapeutic treatment of a disease of the human body selected from Alzheimer's disease, in particular mild to moderate Alzheimer's disease, migraine and migraine headache; and epilepsy, in particular infantile convulsions. 12 - at least one triglyceride of the invention of a fatty acid, in particular C6-C 12 - the inventive use of at least one inventive triglyceride of fatty acids and / or an inventive mixture as defined above.

[0222] In particular, according to this aspect of the invention, the present invention provides a C5-C 12 at least one triglyceride of fatty acids according to the invention, in particular C6-C 12- the inventive use of at least one inventive triglyceride of a fatty acid according to the above definition and / or of an inventive mixture according to the above definition for the preventive and / or therapeutic treatment or for application in catabolic metabolic conditions such as starvation, dieting or low-carbohydrate nutrition, for the preventive and / or therapeutic treatment or for the manufacture of a medicament.

[0223] For further details relating to the fifth aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second, third and fourth aspects of the present invention, which explanations and remarks apply mutatis mutandis accordingly to this fifth aspect of the present invention.

[0224] Furthermore, according to a sixth aspect of the present invention, there is provided a method for producing a hydroxybenzoate comprising the steps of: 12 - inventive triglycerides of fatty acids, in particular of at least one C6-C 12 - a food and / or nutritional or food composition and / or food product and / or medical food comprising the inventive triglycerides of fatty acids, and / or a mixture of the invention according to the above definition.

[0225] In particular, according to this aspect of the invention, the food and / or nutritional or food composition and / or food product and / or medical food is preferably, for example, a dietary supplement, a functional food, a novel food, a food additive, a food supplement, a diet food, a power snack, an appetite suppressant, or a strength and / or endurance sports supplement.

[0226] For further details relating to the sixth aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second, third, fourth and fifth aspects of the present invention, which explanations and remarks apply mutatis mutandis accordingly to this sixth aspect of the present invention.

[0227] Similarly, the present invention provides, according to a seventh aspect of the present invention, at least one C5-C12 of the triglycerides of the invention of fatty acids, in particular C6-C 12 - the use of at least one inventive triglyceride of a fatty acid and / or of an inventive mixture as defined above in a food product and / or in a nutritional or food composition and / or in a food product and / or in a medical food.

[0228] In particular, according to this aspect of the invention, the food and / or nutritional or food composition and / or food product and / or medical food is preferably, for example, a dietary supplement, a functional food, a novel food, a food additive, a food supplement, a diet food, a power snack, an appetite suppressant, or a strength and / or endurance sports supplement.

[0229] For further details relating to the seventh aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second, third, fourth, fifth and sixth aspects of the present invention, which explanations and remarks apply mutatis mutandis accordingly to this seventh aspect of the present invention.

[0230] The present invention also provides, according to an eighth aspect of the present invention, further comprising at least one C5-C hydroxybenzoate according to the above definition, as an additive or auxiliary, in particular as a carrier or excipient, as a solubilizer, release agent, surface treatment agent, transport agent, lubricant, hydrophobizing agent, film-forming or protecting agent or viscosity modifier, preferably as a carrier or excipient, in pharmaceutical compositions, in particular in drugs or pharmaceuticals, in foods, nutritional or food compositions, food products and / or in medical foods and cosmetic compositions. 12 -triglycerides of fatty acids according to the invention, in particular C6-C 12 - the inventive use of at least one inventive triglyceride of fatty acids and / or an inventive mixture as defined above.

[0231] In particular, according to this aspect of the invention, the present invention provides at least one C5-C hydroxybenzoate according to the above definition as a carrier or excipient in a pharmaceutical composition, in particular in a drug or medicament. 12-triglycerides of fatty acids according to the invention, in particular C6-C 12 - the inventive use of at least one inventive triglyceride of fatty acids and / or an inventive mixture as defined above.

[0232] Further, according to this aspect of the invention, the present invention also provides a compound having at least one C5-C 12 -triglycerides of fatty acids according to the invention, in particular C6-C 12 - the inventive use of at least one inventive triglyceride of a fatty acid and / or the use of an inventive mixture as defined above as an active substance in a pharmaceutical composition, in particular a drug or pharmaceutical, in a food, nutritional or food composition, a food product and / or a medical food, or in a cosmetic composition, in particular together with an excipient, in particular together with a physiologically acceptable excipient.

[0233] Further, according to this aspect of the invention, the present invention provides a method for producing a cycloaliphatic polysaccharide comprising at least one C5-C 12 -triglycerides of fatty acids according to the invention, in particular C6-C 12 - relating to the inventive use of at least one inventive triglyceride of a fatty acid and / or relating to the inventive use of an inventive mixture according to the above definition as an active substance (i.e. active ingredient, API) in a pharmaceutical composition.

[0234] Further, according to this aspect of the invention, the present invention also provides a C5-C 12 - at least one triglyceride of the invention of a fatty acid, in particular C6-C 12 - the inventive use of at least one inventive triglyceride of a fatty acid and / or the use of an inventive mixture according to the above definition, in particular together with a physiologically acceptable excipient, as an active substance (i.e. active ingredient, API) in a pharmaceutical composition, in particular a drug or medicinal product.

[0235] For further details relating to the eighth aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second, third, fourth, fifth, sixth and seventh aspects of the present invention, which explanations and remarks apply mutatis mutandis accordingly to this eighth aspect of the present invention.

[0236] Finally, the present invention provides, according to a ninth aspect, triglycerides of fatty acids, in particular C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 It also relates to the use of nucleophiles for purifying triglycerides of fatty acids, preferably triglycerides of general formula (II) as defined above, and / or for purifying organic substances, in particular triglycerides of fatty acids, in particular C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - for the preferably selective removal or derivatization of halide-based impurities present in triglycerides of fatty acids, preferably triglycerides of general formula (II) as defined above.

[0237] In particular, according to this aspect of the invention, the nucleophile may be, for example, a nucleophile capable of removing halide impurities. It is a nucleophilic agent that can be removed by hydrogen sulfite (bisulfite, HSO3 - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- ) and phosphines and combinations thereof, more preferably hydrogen sulfites (bisulfites, HSO - )

[0238] Typically, according to certain embodiments of this aspect of the invention, the triglycerides of fatty acids to be purified are treated with and / or contacted with a nucleophilic agent.

[0239] Generally, it is preferred that the treatment and / or contact of the triglycerides of fatty acids to be purified with a nucleophilic agent is carried out in one step or a single-step process. However, it is also possible to repeatedly treat and / or contact the triglycerides of fatty acids to be purified with a nucleophilic agent, particularly in cases where the level of impurities is high, and in particular in two or more cycles and / or as a multi-step process. Nevertheless, it is preferred that the treatment and / or contact of the triglycerides of fatty acids to be purified with a nucleophilic agent is carried out in one step (i.e., without repeated treatment and / or contact); in particular in cases where the level of impurities is high, as an alternative embodiment, it is also possible to use a higher amount or a higher concentration of nucleophilic agent instead of repeated treatment and / or contact.

[0240] In particular, according to another particular embodiment of this aspect of the invention, the nucleophile is used to purify triglycerides of fatty acids from halide-based, particularly chlorine-based, impurities and / or to remove halide-based, particularly chlorine-based, impurities from triglycerides of fatty acids, in particular to remove chlorine-based impurities selected from the group consisting of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), glycidol esters of fatty acids, and combinations thereof.

[0241] In particular, according to yet another particular embodiment of this aspect of the invention, the halide-based impurities are chlorine-based impurities, particularly chlorine-based impurities selected from the group consisting of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), glycidol esters of fatty acids, and combinations thereof.

[0242] In particular, according to further particular embodiments of this aspect of the invention, the triglycerides of fatty acids to be purified are usually treated and / or contacted with a nucleophilic agent, particularly preferably with an aqueous solution of the nucleophilic agent.

[0243] In particular, the triglycerides of fatty acids to be purified are treated and / or contacted with a nucleophile under reaction conditions, particularly reaction temperature and / or reaction time, sufficient to remove the impurities.

[0244] In particular, the fatty acid triglycerides to be purified are treated and / or contacted with the nucleophile at a temperature in the range of 10°C to 175°C, preferably in the range of 25°C to 120°C, more preferably in the range of 50°C to 100°C, and / or for a time in the range of 0.001 to 50 hours, preferably in the range of 0.01 to 30 hours, more preferably in the range of 0.1 to 20 hours.

[0245] Therefore, overall, hydrogen sulfite (bisulfite, HSO3 - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- Nucleophiles such as phosphines and combinations thereof are useful for the synthesis of triglycerides of fatty acids, particularly C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - an excellent reagent for purifying triglycerides of fatty acids, and in particular for removing halide-based impurities, particularly chlorine-based impurities, from triglycerides of fatty acids, in particular for removing chlorine-based impurities selected from the group consisting of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), glycidol esters of fatty acids, and combinations thereof (i.e., via selective derivatization of the halide-based impurities).

[0246] For further details relating to the ninth aspect of the present invention, in order to avoid unnecessary repetition, reference may be made to the above explanations and remarks relating to the first, second, third, fourth, fifth, sixth, seventh and eighth aspects of the present invention, which explanations and remarks apply mutatis mutandis accordingly to this ninth aspect of the present invention.

[0247] Further embodiments, modifications and variations of the invention will be readily apparent to or realizable by those skilled in the art upon reading this specification, without departing from the scope of the invention. DETAILED DESCRIPTION OF THE INVENTION

[0248] The present invention is illustrated by the following examples, which are not intended to limit the invention in any way, but are intended to illustrate exemplary and non-limiting implementations and configurations of the invention. [Example]

[0249] Manufacturing example The process according to the invention is illustrated by the following examples, in which different synthetic modes are applied, as explained in detail below. In all inventive examples, the starting materials 1,2,3-propanetriol (glyceol, glycerin) and solketal (isopropylideneglycerin) used, respectively, are each at least essentially free of chlorinated species, i.e., each contains a maximum total chlorinated species content of 0.1 ppm (based on 1,2,3-propanetriol or solketal, respectively). Furthermore, the concentration of the sum of MCPD fatty acid esters and glycidol fatty acid esters is below the detection limit (the sum of MCPD and glycidol esters, based on glycerol or solketal, respectively, is 0.1 ppm or less). Furthermore, in all inventive examples, the esterification is carried out at a temperature not exceeding 100°C, preferably not exceeding 80°C. In addition, in all of the examples of the present invention, the esterification is carried out in the absence of a metal-based catalyst. Finally, all of the inventive examples include selective derivatization, i.e., chemical treatment with nucleophiles, to remove traces of halide-based impurities, particularly MCPD fatty acid esters and glycidol fatty acid esters. While all of the inventive examples meet the purity requirements of the product without such treatment, such selective derivatization, i.e., chemical treatment with nucleophiles, selectively removes even trace impurities that may be present, thereby further increasing the purity grade.

[0250] 1. Total Route(A) Tricaprylin is prepared according to the aforementioned synthetic route (A). For this purpose, the following procedure is applied: Caprylic acid (i.e., saturated linear C8 fatty acid or octanoic acid) is reacted with glycerol at 80°C under vacuum (<100 mbar) in the presence of a CALB lipase on a polymeric support from Candida Antarctica (e.g., Novozym® 435 from Sigma-Aldrich or Merck or Lipozym® 435 from Strem Chemicals; 1% by weight based on the reaction mixture). Caprylic acid is used in amounts of up to 300 mol-%, preferably up to 100 mol-%, based on the OH groups of glycerol. Excess caprylic acid is then removed using short-path distillation (<180°C, preferably 120-130°C; <0.1 mbar, preferably <2 mbar). Dicaprylin, especially 1,3-dicaprylin (1,3-diglyceride of caprylic acid), is obtained.

[0251] Dicaprylin is then reacted with caprylic anhydride at a temperature below 180° C., preferably between 80° C. and 150° C., until the hydroxyl value (OHV) is less than 0.1 mg KOH / g. The resulting product is treated in the usual manner (i.e., short path distillation, etc.) to remove the caprylic acid by-product.

[0252] The resulting tricaprylin product is analyzed as follows: Acid value (AV) measured according to European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≤ 0.1 mg KOH / g; Hydroxylic acid value (OHV) measured according to European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.1 mg KOH / g; Triglyceride content determined according to European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≥ 99.4% based on reaction products (so-called tricaprylin), Total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol) determined according to the method DGF C-VI 18(10) (standard method of the German Fat Society): 0.14 ppm based on reaction products (i.e. tricaprylin), Total content of glycidol esters of fatty acids determined according to the method DGF C-VI 18(10) (standard method of the German Fat Society): 0.12 ppm based on reaction products (i.e. tricaprylin).

[0253] The tricaprylin product is further treated with sodium bisulfite (NaHSO3) in aqueous solution (80°C, 6 hours) as a nucleophile (selective derivatization of halide-based impurities, i.e., MCPD fatty acid esters and glycidol fatty acid esters). After separating the aqueous phase and drying the resulting tricaprylin product, the triglyceride content increases to a value of 99.5% or more, and the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids are each below the detection limit (i.e., 0.1 ppm or less), further improving the overall quality of the product. Optionally, the thus-treated product is further treated with bleaching earth and / or activated carbon, followed by optional subsequent deodorization (e.g., using pressurized steam). The resulting tricaprylin product, after treatment with sodium bisulfite (NaHSO3) and optional further processing, is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0254] Equivalent results are obtained when other nucleophiles (i.e., sodium hydrogen thiosulfate (NaHS2O3), sodium hydrogen phosphite (NaH2PO3), and phosphines) are used in place of sodium hydrogen sulfite (NaHSO3).

[0255] The above preparation procedure was repeated in a similar manner using different starting materials, namely the respective C1-C4-esters of caprylic acid, with comparable results.

[0256] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10 ) are produced with comparable results (characterization after bisulfite treatment for triheptanoin and MCT respectively: acid number: ≦0.1 mg KOH / g; hydroxyl number: ≦0.1 mg KOH / g; triglyceride content: ≧99.5%; total content of MCPD fatty acid esters: ≦0.1 ppm; total content of glycidol esters: ≦0.1 ppm).

[0257] Comparative Procedure (Not According to the Invention) In a non-inventive method, synthetic route (A) for tricaprylin is carried out with the following deviations: the glycerol used as starting material has a total chlorinated species content of about 30 ppm. The esterification catalyst used is a metal-based catalyst based on tetrabutyl titanate (TBT). The esterification is carried out in the temperature range of 190°C to 230°C.

[0258] The tricaprylin obtained is analyzed as follows: acid value (European Pharmacopoeia 2.5.1): >0.6 mg KOH / g, hydroxyl value (European Pharmacopoeia 2.5.3): >0.7 mg KOH / g, triglyceride content (European Pharmacopoeia 2.2.28): 97.5% based on tricaprylin, total content of MCPD fatty acid esters (DGF C-VI 18(10)): 0.9 ppm based on tricaprylin, total content of glycidol esters of fatty acids (DGF C-VI 18(10)): 0.7 ppm based on tricaprylin.

[0259] Subsequent treatment with sodium bisulfite (NaHSO) in the form of an aqueous solution (80°C, 6 hours) is able to reduce both the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids to values ​​of about 0.4 ppm, respectively, but does not improve or affect the parameters of acid number, hydroxyl number and triglyceride content.

[0260] 2. Synthetic Route (B) Tricaprylin is prepared according to the aforementioned synthetic route (B). For this purpose, the following procedure is applied: Caprylic acid (i.e., saturated linear C8 fatty acid or octanoic acid) is reacted with glycerol under vacuum (<100 mbar) at 80°C in the presence of an immobilized enzyme (CALB lipase on a polymeric support from Candida Antarctica, e.g., Novozym® 435 from Sigma-Aldrich or Merck or Lipozym® 435 from Strem Chemicals; 1% by weight based on the reaction mixture) as a catalyst. Caprylic acid is used in amounts up to 300 mol-%, preferably up to 100 mol-%, based on the OH groups of glycerol. Excess caprylic acid is then removed using short-path distillation (180°C, preferably 120-130°C; 0.1 mbar, preferably 2 mbar). Dicaprylin, specifically 1,3-dicaprylin (1,3-diglyceride of caprylic acid), is obtained.

[0261] Dicaprylin is then reacted with caprylic acid in the presence of an enzyme, specifically an enzyme that regioselectively esterifies the 2-position of 1,3-diglycerides (e.g., Pseudomonas fluorescens lipase in the first approach, or Burkholderia cepacia lipase in the alternative second approach, each immobilized on chitosan), at 50°C until the hydroxyl value (OHV) is less than 0.1 mg KOH / g.

[0262] The resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.17 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤0.19 ppm based on tricaprylin.

[0263] The tricaprylin product is further treated with aqueous sodium bisulfite (NaHSO) as a nucleophile (80°C, 6 hours) (selective derivatization of halide-based impurities, i.e., MCPD fatty acid esters and glycidol fatty acid esters). After separating the aqueous phase and drying the resulting tricaprylin product, the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids are each below the detection limit (i.e., ≦0.1 ppm each), further improving the overall quality of the product. Optionally, the thus-treated product can be further treated with bleaching earth and / or activated carbon, optionally followed by deodorization (e.g., using pressurized steam).

[0264] The tricaprylin product after treatment with sodium bisulfite (NaHSO3) and optional further processing is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0265] The above preparation procedure was repeated in a similar manner using different starting materials, namely the respective C1-C4-esters of caprylic acid, with comparable results.

[0266] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10 Medium-chain triglycerides (MCT) based on MCPD are also produced with comparable results (properties after bisulfite treatment for triheptanoin and MCT, respectively: acid number: ≦0.1 mg KOH / g; hydroxyl number: ≦0.1 mg KOH / g; triglyceride content: ≧99.5%; total MCPD fatty acid ester content: ≦0.1 ppm; total glycidol ester content: ≦0.1 ppm).

[0267] 3. Synthetic Route (C) Tricaprylin is prepared according to the aforementioned synthetic route (C). For this purpose, the following procedure is applied: Caprylic anhydride (i.e., a straight-chain saturated C8-fatty acid anhydride or octanoic anhydride) is reacted with glycerol at a temperature of up to 180°C, preferably between 80°C and 150°C, until the hydroxyl value (OHV) is less than 0.1 mgKOH / g. The formed caprylic acid (by-product) is then removed using short-path distillation (<180°C, preferably 120°C to 130°C; <0.1 mbar, preferably <2 mbar).The formed caprylic acid (by-product) is then removed using short-path distillation (<180°C, preferably 120°C to 130°C; <0.1 mbar, preferably <2 mbar).

[0268] The resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.16 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.12 ppm based on tricaprylin.

[0269] The tricaprylin product is further subjected to treatment with sodium bisulfite (NaHSO) in aqueous solution (80°C, 6 hours) as a nucleophile (selective derivatization of halide-based impurities, i.e., MCPD fatty acid esters and glycidol fatty acid esters). After separating the aqueous phase and drying the resulting tricaprylin product, the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids are each below the detection limit (i.e., each ≦0.1 ppm), further improving the overall quality of the product. Optionally, the product thus treated can be further treated with bleaching earth and / or activated carbon, optionally followed by deodorization (e.g., using pressurized steam).

[0270] After treatment with sodium bisulfite (NaHSO3) and optional further processing, the resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0271] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10 Medium-chain triglycerides (MCT) based on MCPD are also produced with comparable results (properties after bisulfite treatment for triheptanoin and MCT, respectively: acid number: ≦0.1 mg KOH / g; hydroxyl number: ≦0.1 mg KOH / g; triglyceride content: ≧99.5%; total content of MCPD fatty acid esters: ≦0.1 ppm; total content of glycidol esters: ≦0.1 ppm).

[0272] 4. Synthetic Route (D) Tricaprylin is prepared according to the aforementioned synthetic route (D). For this purpose, the following procedure is applied: Solketal and caprylic anhydride (a linear saturated C8-fatty acid anhydride or octanoic anhydride) are combined in a flask and the system is evacuated. The mixture is reacted for 6 hours at a temperature of up to 180°C, preferably 80°C to 150°C. The caprylic acid formed as a by-product is then distilled off at <20 mbar and 130°C. Solketal monoester of caprylic acid is obtained with a purity of less than 95%.

[0273] The solketal monoester of caprylic acid is then subjected to an acidic deprotection reaction (i.e., ring opening). Either dilute sulfuric acid or dilute phosphoric acid is used to adjust the pH to a value, preferably about 1, and acetone, which is produced as a by-product from the deprotection, is removed.

[0274] The resulting glycerol monoester of caprylic acid (i.e., the monoglyceride of caprylic acid) is then further reacted with caprylic anhydride at 80°C for 90 minutes to produce the triglyceride (i.e., tricaprylin). After the reaction is complete, the caprylic acid produced as a by-product is distilled at less than 20 mbar and 130°C.

[0275] The resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.2% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.15 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.13 ppm based on tricaprylin.

[0276] The tricaprylin product is further treated with aqueous sodium bisulfite (NaHSO) as a nucleophile (80°C, 6 hours) (selective derivatization of halide-based impurities, i.e., MCPD fatty acid esters and glycidol fatty acid esters). After separating the aqueous phase and drying the resulting tricaprylin product, the triglyceride content increases to 99.5% or more, and the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids are each below the detection limit (i.e., 0.1 ppm or less), further improving the overall quality of the product. Optionally, the thus-treated product is preferably further treated with bleaching earth and / or activated carbon, optionally followed by subsequent deodorization (e.g., using pressurized steam). After treatment with sodium bisulfite (NaHSO) and optional further processing, the resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0277] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10 Medium-chain triglycerides (MCT) based on MCPD are also produced with comparable results (properties after bisulfite treatment for triheptanoin and MCT, respectively: acid number: ≦0.1 mg KOH / g; hydroxyl number: ≦0.1 mg KOH / g; triglyceride content: ≧99.5%; total content of MCPD fatty acid esters: ≦0.1 ppm; total content of glycidol esters: ≦0.1 ppm).

[0278] 5. Total Routes (E) Tricaprylin is prepared according to the aforementioned synthetic route (E). For this purpose, the following procedure is applied: Solketal and caprylic acid (i.e., linear saturated C8-fatty acid or octanoic acid) are mixed with an immobilized enzyme (CALB lipase on a polymeric support from Candida Antarctica, e.g., Novozym® 435 from Sigma-Aldrich or Merck or Lipozym® 435 from Strem Chemicals; 1% by weight based on the reaction mixture) as a catalyst and reacted at 80°C for 6 hours under a N2 atmosphere. The enzyme is then filtered. Solketal monoester of caprylic acid is obtained.

[0279] The solketal monoester of caprylic acid is then subjected to an acid-induced deprotection reaction (i.e., ring-opening): either dilute sulfuric acid or dilute phosphoric acid is used to adjust the pH value, preferably to about 1, and acetone formed as a by-product of the deprotection is removed.

[0280] The resulting glycerol monoester of caprylic acid (i.e., caprylic acid monoglyceride) is then further reacted with caprylic anhydride at 80°C for 90 minutes to obtain the triglyceride (i.e., tricaprylin). After the reaction is complete, caprylic acid produced as a by-product is distilled off at less than 20 mbar and 130°C.

[0281] The resulting tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.4% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.15 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.12 ppm based on tricaprylin.

[0282] The tricaprylin product is then further treated with aqueous sodium bisulfite (NaHSO) as a nucleophile (80°C, 6 hours) (selective derivatization of halide-based impurities, i.e., MCPD fatty acid esters and glycidol fatty acid esters). After separating the aqueous phase and drying the resulting tricaprylin product, the triglyceride content increases to a value of 99.5% or more, and the total content of MCPD fatty acid esters and the total content of glycidol esters of fatty acids are each below the detection limit (i.e., 0.1 ppm or less), further improving the overall quality of the product. Optionally, the thus-treated product can be further treated with bleaching earth and / or activated carbon, and optionally followed by deodorization (e.g., using pressurized steam). After sodium bisulfite (NaHSO) and optional further treatment, the tricaprylin product is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0283] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10Medium-chain triglycerides (MCT) based on MCPD have also been produced with comparable results (properties after bisulfite treatment for triheptanoin and MCT, respectively: acid number: ≦0.1 mg KOH / g; hydroxyl number: ≦0.1 mg KOH / g; triglyceride content: ≧99.5%; total MCPD fatty acid ester content: ≦0.1 ppm; total glycidol ester content: ≦0.1 ppm).

[0284] 6. Synthetic Route (F) Tricaprylin is prepared according to the aforementioned synthetic route (F). For this purpose, the following procedure is applied: 2-Octenoic acid is esterified with glycerol (MCPD fatty acid esters and glycidol esters total ≤0.1 ppm; total chlorinated species ≤0.1 ppm) using excess 2-octenoic acid (≤50 mol%, preferably ≤30 mol%, based on OH groups of glycerol) in the presence of an immobilized enzyme as catalyst (CALB lipase from Candida Antarctica on a polymeric support, e.g., Novozym® 435 from Sigma-Aldrich or Merck or Lipozym® 435 from Strem Chemicals; ≤0.5 wt.%, preferably ≤0.1 wt.%, based on the reaction mixture) at 70°C under vacuum (≤100 mbar). Water produced as a reaction by-product is continuously removed. The esterification is carried out until the hydroxyl value (OHV) is ≤0.1 mg KOH / g.

[0285] The excess 2-octenoic acid is then removed using short-path distillation (<180°C, <10 mbar, preferably 120-130°C, <2 mbar). The triglyceride of 2-octenoic acid is obtained.

[0286] The triglyceride of 2-octenoic acid is then hydrogenated using a conventional hydrogenation catalyst (i.e., a transition metal catalyst, preferably Pd, Pt, Ru, Rh, Ni, etc., on a catalyst support) at a concentration of 10% by weight or less, based on the triglyceride of 2-octenoic acid. The hydrogenation is carried out at a temperature between 50°C and 180°C, preferably between 80°C and 120°C, and at a hydrogen pressure of 50 bar or less, preferably 5 bar to 30 bar. The hydrogenation is continued until the iodine value of the reaction mixture is 1.0 g / 100 g or less. The catalyst is then filtered and the reaction product is chemically washed / treated with bleaching earth / activated carbon, then filtered. The chemical washing / treatment is carried out as described above using sodium bisulfite (NaHSO) in the form of an aqueous solution (80°C, 6 hours).

[0287] The product is then deodorized using pressurized steam (HOW-steam) to remove any remaining 2-octenoic acid at a temperature of 120°C to 180°C and a pressure of 10 mbar or less.

[0288] The tricaprylin product after treatment with sodium bisulfite (NaHSO3) is analyzed as follows: Acid value (European Pharmacopoeia 2.5.1): ≦0.1 mg KOH / g, Hydroxyl value (European Pharmacopoeia 2.5.3): ≦0.1 mg KOH / g; Triglyceride content (European Pharmacopoeia 2.5.28): ≥ 99.5% based on tricaprylin; Total content of MCPD fatty acid esters (DGF C-VI 18(10)): ≤0.1 ppm based on tricaprylin; Total content of glycidol esters of fatty acids (DGF C-VI 18(10)): ≤ 0.1 ppm based on tricaprylin.

[0289] However, the above-described preparation procedure has been repeated using different starting materials, namely 4-octenoic acid and 7-octenoid acid, and a triple mixture of 2-octenoid acid, 4-octenoid acid, and 7-octenoid acid, with comparable results obtained with each approach.

[0290] In a similar manner, triheptanoin on the one hand and caproic (C6) / caprylic (C8) / capric (C 10 Medium-chain triglycerides (MCT) based on MCPD are also produced with comparable results (properties after treatment with bisulfite for triheptanoin and MCT: acid value: ≦0.1 mg KOH / g, hydroxyl value: ≦0.1 mg KOH / g, triglyceride content: ≧99.5%, total content of MCPD fatty acid esters: ≦0.1 ppm, total content of glycidol esters: ≦0.1 ppm).

[0291] Inventive feature and / or condition (i): Selective derivatization / treatment with at least one nucleophile To demonstrate the effectiveness of measurement (i) of the present invention, in particular the selective derivatization of halide impurities, i.e., the selective removal of halide impurities (in particular MCPD and glycidol fatty acid esters), a commercially available triglyceride is subjected to treatment according to measurement (i) of the present invention.

[0292] A commercial product based on MCT oil (triglycerides) has a glycidol ester content of 70 ppm. After 6 hours of treatment with aqueous sodium bisulfite at 80° C., the glycidol ester content is reduced to 9.11 ppm; this achieves a reduction of approximately 7.5 times.

[0293] Another commercial product (MCT60 / 40) based on MCT oil (triglycerides) has a 3-MCPD fatty acid ester content of 8 ppm. After 6 hours of treatment with aqueous sodium bisulfite at 80°C, the 3MCPD content was reduced to 2.21 ppm; this represents a reduction of approximately 3.5 times.

[0294] Further commercially available products (Miglyol® 812N, C8 / C 10The triglycerides have a 3-MCPD fatty acid ester content of 1.56 ppm. After 15 hours of treatment with 12% aqueous sodium bisulfite at 8°C, the 3-MCPD content was reduced to 0.16 ppm; this represents a reduction of approximately 9.7 times.

[0295] Equivalent results can be obtained by using other nucleophiles (i.e., sodium hydrogen thiosulfate NaHS2O3, sodium hydrogen phosphite NaH2PO3, or phosphines) in place of sodium hydrogen sulfite (NaHSO3).

[0296] Therefore, the feature and / or condition (i) of the present invention effectively reduces the content of halide-based impurities, particularly MCPD and glycidol fatty acid esters. However, based solely on the condition (i) of the present invention, it is not always sufficient to meet the overall product specifications having a five-fold purity / grade requirement of the aforementioned characteristics (1) to (5), except when starting from low-purity commercial triglycerides or prior art triglycerides. However, in particular, at least the characteristics of (4) a total content of MCPD fatty acid esters of less than 0.1 ppm and (5) a total content of glycidol esters of less than 0.1 ppm can be efficiently adjusted and / or achieved by this measure (1).

[0297] conclusion The applicant has been able to provide a general concept / method for producing high purity fatty acid triglycerides with high yield and high conversion, and therefore the applicant's concept is general in application for this purpose.

[0298] The process of the present invention is at the same time very flexible and compatible with known prior art methods and plants for producing these substances, since the aforementioned features and / or conditions (i) to (iv) of the present invention can be easily implemented in or used to modify known methods and plants for producing these substances.

[0299] In particular, the method of the present invention produces high purity fatty acid triglycerides while simultaneously achieving a combination of at least five purity characteristics: (1) very low acid value (AV), (2) very low hydroxyl value (OHV), (3) very high triglyceride content, (4) very low total MCPD fatty acid ester content, and (5) very low total glycidol fatty acid ester content, where the purity specifications can be achieved independently of a particular synthetic route. While this combination of purity characteristics (1) through (5) was previously thought to be incompatible or impossible to achieve, applicants have surprisingly discovered that the method of the present invention makes this combination of purity characteristics possible for the first time.

[0300] Furthermore, for example, hydrogen sulfite (bisulfite, HSO3 - ), sulfite (SO3 2- ), hydrogen thiosulfate (HS2O3 - ), thiosulfate (S2O3 2- ), hydrogen phosphite (H2PO3 - ), phosphite (HPO3 2- Nucleophiles such as phosphines and phosphines and combinations thereof are useful for the synthesis of triglycerides of fatty acids, particularly C5-C 12 -Triglycerides of fatty acids, especially C6-C 12 - is an excellent reagent for purifying triglycerides of fatty acids, in particular for removing halide-based impurities, in particular chlorine-based impurities (i.e., selective derivatization of halide-based impurities), from triglycerides of fatty acids, in particular chlorine-based impurities, selected from the group consisting of MCPD fatty acid esters (fatty acid esters of monochloropropanediol), glycidol esters of fatty acids, and combinations thereof.

Claims

1. 1. A method for purifying triglycerides of fatty acids containing halide-based impurities, comprising: The method comprises at least one step of selectively removing and derivatizing halide-based impurities present in the triglycerides of fatty acids to be purified by treatment with at least one nucleophilic agent; The nucleophile is selected from the group consisting of bisulfites, sulfites, hydrogen thiosulfates, thiosulfates, hydrogen phosphites, phosphites, and phosphite, and combinations thereof.

2. 10. The purification method of claim 1, wherein the halide-based impurities are selected from the group consisting of fatty acid esters of monochloropropanediol, glycidol esters of fatty acids, and combinations thereof.

3. The overall process, including any pre-treatment and post-treatment steps, is carried out at a temperature not exceeding 180°C; and 3. A purification process according to claim 1 or 2, characterized in that the entire process, including any pre-treatment and post-treatment steps, is carried out in the absence of metal-based catalysts.

4. at least one esterification step is carried out in the absence of a solvent; and 3. The method according to claim 1, wherein at least one esterification step is carried out in the absence of a catalyst or, alternatively, in the presence of an enzyme as at least a partial catalyst.

5. The fatty acid triglycerides to be purified are C ５ -C １２ - the triglycerides of fatty acids are of the general formula (II) CH ２ [O-C(O)R １ ]-CH[O-C(O)R ２ ]-CH ２ [O-C(O)R ３ ] (II) be expressed as: In the general formula (II), the radical R １ , R ２ , and R ３ are each independently a linear or branched, saturated or unsaturated aliphatic C ４ -C １１ -representing an alkyl radical; C ５ -C １２ - the triglycerides of fatty acids exhibit the following properties (1) to (5) in combination thereof; and (1) Acid value as measured by European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g; and (2) hydroxyl value measured by European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.5 mg KOH / g; and (3) Triglyceride content as measured by European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≧99%; and (4) The total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol) measured by the DGF C-VI 18(10) method (German Fatty Acid Society standard method): ≦0.5 ppm based on triglycerides of C5-C12 fatty acids; and (5) Total content of glycidol esters of fatty acids measured by the DGF C-VI 18 (10) method (standard method of the German Society of Fatty Acids): C ５ -C １２ - ≦0.5 ppm based on triglycerides of fatty acids; 3. The purification method according to claim 1, wherein the product specification is satisfied.

6. Said C ５ -C １２ - the triglycerides of fatty acids are of the general formula (II) CH ２ [O-C(O)R １ ]-CH[O-C(O)R ２ ]-CH ２ [O-C(O)R ３ ] (II) be expressed as: In the general formula (II), the radical R １ , R ２ , and R ３ are each independently a linear or branched, saturated or unsaturated aliphatic C ４ -C １１ -representing an alkyl radical; C ５ -C １２ - the triglycerides of fatty acids exhibit the following properties (1) to (5) in combination thereof; and (1) Acid value as measured by European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.2 mg KOH / g; and (2) hydroxyl value measured by European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.2 mg KOH / g; and (3) Triglyceride content as measured by European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≧99.2%; and (4) The total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol) measured by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): ≦C ５ -C １２ ≦0.2 ppm based on triglycerides of fatty acids; and (5) Total content of glycidol esters of fatty acids measured by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): C ５ -C １２ ≦0.2 ppm based on triglycerides of fatty acids; The purification method according to claim 5, wherein the product specification is satisfied.

7. Said C ５ -C １２ - the triglycerides of fatty acids are of the general formula (II) CH ２ [O-C(O)R １ ]-CH[O-C(O)R ２ ]-CH ２ [O-C(O)R ３ ] (II) be expressed as: In the general formula (II), the radical R １ , R ２ , and R ３ are each independently a linear or branched, saturated or unsaturated aliphatic C ４ -C １１ -representing an alkyl radical; C ５ -C １２ - the triglycerides of fatty acids exhibit the following properties (1) to (5) in combination thereof; and (1) Acid value measured by European Pharmacopoeia 2.5.1 (European Pharmacopoeia 10.0): ≦0.1 mg KOH / g; and (2) hydroxyl value measured by European Pharmacopoeia 2.5.3 (European Pharmacopoeia 10.0): ≦0.1 mg KOH / g; and (3) Triglyceride content as measured by European Pharmacopoeia 2.5.28 (European Pharmacopoeia 10.0): ≧99.5%; and (4) The total content of MCPD fatty acid esters (fatty acid esters of monochloropropanediol) measured by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): ≦C ５ -C １２ ≦0.1 ppm based on triglycerides of fatty acids; and (5) Total content of glycidol esters of fatty acids measured by the DGF C-VI18(10) method (standard method of the German Society of Fatty Acids): C ５ -C １２ - ≤ 0.1 ppm based on triglycerides of fatty acids; The purification method according to claim 5, wherein the product specification is satisfied.

8. In the general formula (II), all radicals R １ , R ２ and R ３ The purification method according to claim 5, wherein

9. In the general formula (II), the radical R １ , R ２ and R ３ 6. The method of claim 5, wherein at least two of the above are different from each other.

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