EP3774757A1 - Chroman-6-ols à chaîne latérale lipophile étendue en position 2, leur fabrication et leur utilisation - Google Patents

Chroman-6-ols à chaîne latérale lipophile étendue en position 2, leur fabrication et leur utilisation

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Publication number
EP3774757A1
EP3774757A1 EP19714655.8A EP19714655A EP3774757A1 EP 3774757 A1 EP3774757 A1 EP 3774757A1 EP 19714655 A EP19714655 A EP 19714655A EP 3774757 A1 EP3774757 A1 EP 3774757A1
Authority
EP
European Patent Office
Prior art keywords
formula
oil
compound
acid
feed
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19714655.8A
Other languages
German (de)
English (en)
Inventor
Laure CLASADONTE
André DUESTERLOH
Weerasinghe INDRASENA
Thomas Netscher
René Tobias STEMMLER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DSM IP Assets BV
Original Assignee
DSM IP Assets BV
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Filing date
Publication date
Application filed by DSM IP Assets BV filed Critical DSM IP Assets BV
Publication of EP3774757A1 publication Critical patent/EP3774757A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
    • C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L13/00—Meat products; Meat meal; Preparation or treatment thereof
    • A23L13/10—Meat meal or powder; Granules, agglomerates or flakes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L17/00—Food-from-the-sea products; Fish products; Fish meal; Fish-egg substitutes; Preparation or treatment thereof
    • A23L17/10—Fish meal or powder; Granules, agglomerates or flakes

Definitions

  • the present invention is directed to the compound of formula (MI-3), as well as to the use of compounds of formula (III) as defined below, especially to the use of compound of formula (111-3) and the use of compound of formula (111-4), as antioxidants, especially in feed, such as e.g. in feed for aquatic animals, in feed for terrestrial animals (especially pet food, feed for pigs and feed for poultry) and in feed for insects, and in feed ingredients, such as in fish meal, in poultry meal, in insect meal, and in PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil.
  • the present invention is further directed towards feed and feed ingredients containing at least one compound of formula (III) as defined below, especially containing a compound of formula (MI-3) and/or a compound of formula (MI-4).
  • the present invention is also directed to a process for the manufacture of a compound of formula (III), comprising the step of reacting a compound of formula (I) with a compound of formula (II) in the presence of an acid catalyst and in a mixture of two solvents,
  • n 1 or 2
  • R 1 and R 3 are independently from each other H or Ci- 5 -alkyl, and R 2 is either H or Ci- 5 -alkyl or Ci- 5 -alkyloxy, preferably with the proviso that at least one of R 1 , R 2 and R 3 is H,
  • the first of the two solvents is selected from ethylene carbonate, propylene carbonate, 1 ,2-butylene carbonate, gamma-butyrolactone and water,
  • the second of the two solvents is selected from hexane, cyclohexane, heptane, ortho-xylene, meta-xylene, para-xylene, mesitylene, pseudocumene, methyl tert- butyl ether, and toluene.
  • n 1 or 2
  • R 1 and R 3 are independently from each other H or Ci-5-alkyl, and R 2 is either H or Ci-5-alkyl or Ci-5-alkyloxy, preferably with the proviso that at least one of R 1 , R 2 and R 3 is H,
  • the first of the two solvents is selected from ethylene carbonate, propylene carbonate, 1 ,2-butylene carbonate, gamma-butyrolactone and water,
  • the second of the two solvents is selected from hexane, cyclohexane, heptane, ortho-xylene, meta-xylene, para-xylene, mesitylene, pseudocumene, methyl tert- butyl ether, and toluene.
  • the compound of formula (111-3), 2-(4,8-dimethylnonyl)-2-methylchroman-6-ol, is a novel compound and therefore also an object of the present invention.
  • Unmodified fish meal can spontaneously combust from heat generated by oxidation of the polyunsaturated fatty acids in the fish meal.
  • factory ships have sunk because of such fires.
  • Strict rules regarding the safe transport of fish meal have been put in place by authorities and the International Maritime Organization (IMO).
  • IMO International Maritime Organization
  • fishmeal must be stabilized with antioxidants to prevent spontaneous combustion during overseas transport and storage.
  • BHT must be added in higher quantities to achieve the same efficacy as ethoxyquin. Furthermore, BHT is currently under safety evaluation by ECHA and its re-registration as feed additive is pending in Europe.
  • the compounds of formula (III), especially the compound of formula (MI-3) as well as the compound of formula (MI-4), are useful as antioxidants, especially in feed, such as e.g. in feed for aquatic animals, in feed for terrestrial animals (especially pet food, feed for pigs and feed for poultry) and in feed for insects, and in feed ingredients, such as in fish meal, in poultry meal, in insect meal, and in PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil.
  • feed such as e.g. in feed for aquatic animals, in feed for terrestrial animals (especially pet food, feed for pigs and feed for poultry) and in feed for insects, and in feed ingredients, such as in fish meal, in poultry meal, in insect meal, and in PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil.
  • PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-
  • the asterisk * marks a chiral/stereogenic center.
  • the term“compound of formula (111-4)” encompasses all possible isomers having any configuration at said center.
  • the present invention is directed towards feed and feed ingredients containing at least one compound of formula (III), especially containing a compound of formula (111-3) and/or a compound of formula (MI-4).
  • Feed encompasses feed for aquatic animals, feed for terrestrial animals (especially pet food, feed for pigs and feed for poultry) and feed for insects.
  • Feed ingredients encompass especially fish meal, poultry meal, insect meal, and PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil.
  • PUFA(s) means polyunsaturated fatty acid(s) such as docosahexaenoic acid (“DHA”) and/or eicosapentaenoic acid (“EPA”) and/or docosapentaenoic acid (“DPA”) and/or oleic acid and/or stearidonic acid and/or linoleic acid and/or alpha- linolenic acid (“ALA”) and/or gamma-linolenic acid and/or arachidonic acid (“ARA”) and/or the esters of all of them, whereby the term “esters” encompasses monoglycerides, diglycerides and triglycerides as well as Ci- 6 -alkyl esters such as especially the methyl esters and the ethyl esters, whereby the triglycerides are often dominant. DHA, EPA, ALA and stearidonic acid are omega-3 fatty acids, whereas linoleic acid,
  • DPA encompasses two isomers, the omega-3 fatty acid clupanodonic acid (7Z,10Z,13Z,16Z,19Z-docosapentaenoic acid) and the omega-6 fatty acid osbond acid (4Z,7Z, 10 Z, 13Z, 16Z-docosapentaenoic acid).
  • the polyunsaturated fatty acid is preferably DHA and/or EPA and/or DPA and/or any ester thereof, more preferably the polyunsaturated fatty acid (PUFA) is preferably DHA and/or EPA and/or any ester thereof.
  • - marine oil such as preferably fish oil
  • microbial oil preferably containing high amounts of docosahexaenoic acid (“DHA”) and/or eicosapentaenoic acid (“EPA”) and/or
  • DPA docosapentaenoic acid
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • DPA docosapentaenoic acid
  • PUFA- containing plant oil such as e.g. canola seed oil, linseed /flaxseed oil, hempseed oil, pumpkin seed oil, evening primrose oil, borage seed oil, blackcurrent seed oil, sallow thorn/sea buckthorn oil, chia seed oil, argan oil and walnut oil.
  • PUFA- containing plant oil such as e.g. canola seed oil, linseed /flaxseed oil, hempseed oil, pumpkin seed oil, evening primrose oil, borage seed oil, blackcurrent seed oil, sallow thorn/sea buckthorn oil, chia seed oil, argan oil and walnut oil.
  • feed such as especially feed for aquatic animals, feed for terrestrial animals such as poultry, pigs and pets, and feed for insects, comprising such compounds of formula (III) and
  • the present invention is directed to feed ingredients, such as especially poultry meal, fish meal, insect meal and PUFA enriched oil, comprising such compounds of formula (III).
  • feed ingredients such as especially poultry meal, fish meal, insect meal and PUFA enriched oil
  • the present invention is directed to feed for aquatic animals comprising such compounds of formula (III) with the preferences as given above.
  • the present invention is also directed to feed for insects and terrestrial animals, e.g. pigs, poultry and pets, comprising such compounds of formula (III) with the preferences as given above.
  • Aquatic animals in the context of the present invention encompass farmed
  • Crustacea such as shrimp and carnivorous species of farmed fish such as salmons, rainbow trout, brown trout (Salmo trutta) and gilthead seabream.
  • the feed for aquatic animals comprising the compounds of formula (III) are especially fed to the aquatic animals as cited above.
  • Feed ingredients are broadly classified into cereal grains, protein meals, fats and oils, minerals, feed additives, and miscellaneous raw materials, such as roots and tubers.
  • the compounds of formula (III) can be used in combination with one or more other antioxidants as described below.
  • the feed ingredients of the present invention additionally comprise a mixture of 2-tert-butyl-4-methoxyphenol and 3- tert-butyl-4-methoxyphenol, which is known under the name “BHA” (butylated hydroxyanisole).
  • the feed ingredients of the present invention additionally comprise ascorbyl palmitate. In another embodiment of the present invention the feed ingredients of the present invention additionally comprise BHA and ascorbyl palmitate.
  • esters of ascorbic acid such as the esters of ascorbic acid with linear C 12-20 alkanols, preferably the esters of ascorbic acid with linear C 14-18 alkanols, may also be used, so that further embodiments of the present invention are directed to feed ingredients that additionally comprise esters of ascorbic acid with linear C 12-20 alkanols, preferably esters of ascorbic acid with linear C 14-18 alkanols, more preferably ascorbyl palmitate, whereby optionally BHA may also be present.
  • the feed ingredients may also comprise additionally alpha-tocopherol and/or gamma-tocopherol, whereby either an ester of ascorbic acid with a linear C 12-20 alkanol with the preferences as given above or BHA or both may additionally be present.
  • PUFAs polyunsaturated fatty acids
  • DHA docosahexaenoic acid
  • EPA eicosapentaenoic acid
  • DPA docosapentaenoic acid
  • - oil containing high amounts of PUFAs especially containing high amounts of DHA and/or EPA and/or DPA and/or their esters extracted from microbial biomass as e.g. , fungi (“fungal oil”) or algae (“algal oil”);
  • PUFA-containing plant oil such as e.g. canola seed oil, linseed /flaxseed oil, hempseed oil, pumpkin seed oil, evening primrose oil, borage seed oil, blackcurrent seed oil, sallow thorn/sea buckthorn oil, chia seed oil, argan oil and walnut oil.
  • DHA does not only encompass the acid but also derivatives thereof such as monoglycerides, diglycerides and triglycerides as well as Ci- 6 -alkyl esters such as the methyl and ethyl esters.
  • EPA monoglycerides
  • DPA dihydroxy-3-methylethyl esters
  • feed ingredients may not only be used as alternative of fish oil and algal oil, but also in addition.
  • suitable marine oils include, but are not limited to, Atlantic fish oil, Pacific fish oil, or Mediterranean fish oil, or any mixture or combination thereof.
  • a suitable fish oil can be, but is not limited to, pollack oil, bonito oil, pilchard oil, tilapia oil, tuna oil, sea bass oil, halibut oil, spearfish oil, barracuda oil, cod oil, menhaden oil, sardine oil, anchovy oil, capelin oil, herring oil, mackerel oil, salmonid oil, tuna oil, and shark oil, including any mixture or combination thereof.
  • marine oils suitable for use herein include, but are not limited to, squid oil, cuttle fish oil, octopus oil, krill oil, seal oil, whale oil, and the like, including any mixture or combination thereof.
  • the other PUFA-containing oils such as microbial oil, algal oil, fungal oil and PUFA-containing plant oil.
  • a commercially available example of marine oil is the fish oil“MEG-3” (Bleached 30S TG Fish oil) from DSM Nutritional Products, LLC (US) whose specification and composition is shown in Tables I and II below:
  • the peroxide value is defined as the amount of peroxide oxygen per 1 kilogram of oil. Traditionally this is expressed in units of milliequivalents or meq/kg. Winterization is part of the processing of fish oil, and it is performed to remove solid fat in the oil. The“cold test” is performed to check if any solid fat is present and precipitated in the oil when cooled to 0°C within a specific period of time. In this fish oil (Product Code: FG30TG), any such precipitation is checked for 3 hours at 0°C.
  • Algal oil is an oil containing high amounts of DHA and/or EPA and/or DPA and/or their esters extracted from algae as microbial source/biomass.
  • algal oil is the commercially available“Algal oil containing EPA+DPA” from DSM Nutritional Products, LLC (US) whose composition is shown in the Table III below:
  • a further example of a crude oil containing high amounts of DHA and/or EPA extracted from microbial sources as e.g., algae, is the oil extracted from Algae Schizochytrium Biomass, whose specification is given in the following Table IV.
  • the biomass preferably comprises cells which produce PUFAs heterotrophically.
  • the cells are preferably selected from algae, fungi, particularly yeasts, bacteria, or protists.
  • the cells are more preferably microbial algae or fungi.
  • Suitable cells of oil-producing yeasts are, in particular, strains of Yarrowia, Candida, Rhodotorula, Rhodosporidium, Cryptococcus, Trichosporon and
  • Oil produced by a microorganism or obtained from a microbial cell is referred to as “microbial oil”.
  • Oil produced by algae and/or fungi is referred to as an algal and/or a fungal oil, respectively.
  • microorganism refers to organisms such as algae, bacteria, fungi, protist, yeast, and combinations thereof, e.g., unicellular organisms.
  • a microorganism includes but is not limited to, golden algae (e.g., microorganisms of the kingdom Stramenopiles); green algae; diatoms; dinoflagellates (e.g., microorganisms of the order Dinophyceae including members of the genus
  • Crypthecodinium such as, for example, Crypthecodinium cohnii or C. cohnii); microalgae of the order Thraustochytriales; yeast ( Ascomycetes or
  • Basidiomycetes Basidiomycetes ); and fungi of the genera Mucor, Mortierella, including but not limited to Mortierella alpina and Mortierella sect, schmuckeri, and Pythium, including but not limited to Pythium insidiosum.
  • the microorganisms of the kingdom Stramenopiles may in particular be selected from the following groups of microorganisms: Hamatores, Proteromonads, Opalines, Developayella, Diplophrys, Labrinthulids,
  • the microorganisms are from the genus Mortierella, genus Crypthecodinium, genus Thraustochytrium, and mixtures thereof.
  • the microorganisms are from Crypthecodinium Cohnii.
  • the microorganisms are from Mortierella alpina.
  • the microorganisms are from Schizochytrium sp.
  • the microorganisms are selected from Crypthecodinium Cohnii, Mortierella alpina, Schizochytrium sp., and mixtures thereof.
  • the microorganisms include, but are not limited to, microorganisms belonging to the genus Mortierella, genus Conidiobolus, genus Pythium, genus Phytophthora, genus Penicillium, genus Cladosporium, genus Mucor, genus Fusarium, genus Aspergillus, genus Rhodotorula, genus
  • Entomophthora genus Echinosporangium, and genus Saprolegnia.
  • microorganisms are from microalgae of the order Thraustochytriales, which includes, but is not limited to, the genera
  • Thraustochytrium (species include arudimentale, aureum, benthicola, globosum, kinnei, motivum, multirudimentale, pachydermum, proliferum, roseum, striatum); the genera Schizochytrium (species include aggregatum, limnaceum, mangrovei, minutum, octosporum); the genera Ulkenia (species include
  • amoeboidea kerguelensis, minuta, profunda, radiate, sailens, sarkariana, schizochytrops, visurgensis, yorkensis); the genera Aurantiacochytrium; the genera Oblongichytrium; the genera Sicyoidochytium; the genera Parientichytrium; the genera Botryochytrium; and combinations thereof. Species described within Ulkenia will be considered to be members of the genus Schizochytrium.
  • the microorganisms are from the order Thraustochytriales.
  • the microorganisms are from Thraustochytrium.
  • the microorganisms are from Schizochytrium sp.
  • the oil can comprise a marine oil.
  • suitable marine oils are the ones as given above.
  • the biomass according to the invention preferably comprises cells, and preferably consists essentially of such cells, of the taxon Labyrinthulomycetes ( Labyrinthulea , net slime fungi, slime nets), in particular, those from the family of Thraustochytriaceae.
  • the family of the Thraustochytriaceae includes the genera Althomia, Aplanochytrium, Aurantiochytrium, Botryochytrium, Elnia, Japonochytrium, Oblongichytrium, Parietichytrium, Schizochytrium, Sicyoidochytrium, Thraustochytrium, and Ulkenia.
  • the biomass particularly preferably comprises cells from the genera Aurantiochytrium, Oblongichytrium, Schizochytrium, or Thraustochytrium, more preferably from the genus
  • the polyunsaturated fatty acid is preferably DHA and/or EPA and/or their esters as defined above.
  • the cells present in the biomass are preferably distinguished by the fact that they contain at least 20 weight-%, preferably at least 30 weight-%, in particular at least 35 weight-%, of PUFAs, in each case based on cell dry matter.
  • cells in particular a Schizochytrium strain, is employed which produces a significant amount of EPA and DHA, simultaneously, wherein DHA is preferably produced in an amount of at least 20 weight-%, preferably in an amount of at least 30 weight-%, in particular in an amount of 30 to 50 weight-%, and EPA is produced in an amount of at least 5 weight-%, preferably in an amount of at least 10 weight-%, in particular in an amount of 10 to 20 weight-% (in relation to the total amount of lipid as contained in the cells, respectively).
  • Preferred species of microorganisms of the genus Schizochytrium, which produce EPA and DHA simultaneously in significant amounts, as mentioned before, are deposited under ATCC Accession No.
  • DHA and EPA producing Schizochytrium strains can be obtained by consecutive mutagenesis followed by suitable selection of mutant strains which demonstrate superior EPA and DHA production and a specific EPA:DHA ratio.
  • Any chemical or nonchemical (e.g. ultraviolet (UV) radiation) agent capable of inducing genetic change to the yeast cell can be used as the mutagen. These agents can be used alone or in combination with one another, and the chemical agents can be used neat or with a solvent.
  • UV radiation ultraviolet
  • a biomass which comprises cells containing lipids, in particular PUFAs, particularly of the order Thraustochytriales are described in detail in the prior art (see e.g. WO 91 /07498, WO 94/08467, WO 97/37032, WO 97/36996, WO 01 /54510).
  • the production takes place by cells being cultured in a fermenter in the presence of a carbon source and a nitrogen source, along with a number of additional substances like minerals that allow growth of the microorganisms and production of the PUFAs.
  • biomass densities of more than 100 grams per litre and production rates of more than 0.5 gram of lipid per litre per hour may be attained.
  • the process is preferably carried out in what is known as a fed-batch process, i.e. the carbon and nitrogen sources are fed in incrementally during the fermentation.
  • lipid production may be induced by various measures, for example by limiting the nitrogen source, the carbon source or the oxygen content or combinations of these.
  • the cells are grown until they reach a biomass density of at least 80 or 100 g/l, more preferably at least 120 or 140 g/l, in particular at least 160 or 180 g/l (calculated as dry-matter content).
  • a biomass density of at least 80 or 100 g/l, more preferably at least 120 or 140 g/l, in particular at least 160 or 180 g/l (calculated as dry-matter content).
  • Such processes are for example disclosed in US 7,732,170.
  • the cells are fermented in a medium with low salinity, in particular, so as to avoid corrosion.
  • This can be achieved by using chlorine-free sodium salts as the sodium source instead of sodium chloride, such as, for example, sodium sulphate, sodium carbonate, sodium hydrogen carbonate or soda ash.
  • chloride is used in the fermentation in amounts of less than 3 g/l, in particular, less than 500 mg/l, especially preferably less than 100 mg/l.
  • PUFA-containing plant oils Plant oils with relatively high amounts of PUFAs. especially with high amounts of DHA and/or EPA such as e.g. , canola seed oil
  • the plant cells may, in particular, be selected from cells of the families
  • the cells of the family Brassicaceae may be selected from the genus Brassica, in particular, from oilseed rape, turnip rape and Indian mustard; the cells of the family Elaeagnaceae may be selected from the genus Elaeagnus, in particular, from the species Oleae europaea ; the cells of the family Fabaceae may be selected from the genus Glycine, in particular, from the species Glycine max.
  • - Canola seed oil with a content of EPA of at least 9% by weight, of at least 12% by weight, of at least 15% by weight, or of at least 20% by weight, based on the total weight of the canola seed oil.
  • PUFA-containing plant oils containing high amounts of other PUFAs than EPA and/or DHA and/or DPA and/or their esters are linseed /flaxseed oil, hempseed oil, pumpkin seed oil, evening primrose oil, borage seed oil, blackcurrent seed oil, sallow thorn/sea buckthorn oil, chia seed oil, argan oil and walnut oil.
  • Poultry meal is a high-protein commodity used as a feed ingredient. It is made from grinding clean, rendered parts of poultry carcasses and can contain bones, offal, undeveloped eggs, and some feathers. Poultry meal quality and composition can change from one batch to another.
  • Chicken meal like poultry meal, is made of "dry, ground, rendered clean parts of the chicken carcass" according to AAFCO and may contain the same ingredients as poultry meal. Chicken meal can vary in quality from batch to batch. Chicken meal costs less than chicken muscle meat and lacks the digestibility of chicken muscle meat.
  • Poultry meal contains preferably not less than 50 weight-% of crude protein, not less than 5 weight-% of crude fat, not more than 5 weight-% of crude fiber, not more than 40 weight-% of ash and not more than 15 weight-% of water, each based on the total weight of the poultry meal, whereby the total amount of all ingredients sums up to 100 weight-%. More preferably poultry meal contains from 50 to 85 weight-% of crude protein, and from 5 to 20 weight-% of crude fat, and from 1 to 5 weight-% of crude fiber, and from 5 to 40 weight-% of ash, and from 5 to 15 weight-% of water, each based on the total weight of the poultry meal, whereby the total amount of all ingredients sums up to 100 weight-%.
  • Fish meal contains preferably not less than 50 weight-% of crude protein, and not more than 20 weight-% of crude fat, and not more than 10 weight-% of crude fibers, and not more than 25 weight-% of ash, and not more than 15 weight-% of water, each based on the total weight of the fish meal, whereby the total amount of all ingredients sums up to 100 weight-%. More preferably fish meal contains from 50 to 90 weight-% of crude protein and from 5 to 20 weight-% of crude fat, and from 1 to 10 weight-% of crude fibers, and from 5 to 25 weight-% of ash, and from 5 to 15 weight-% of water, each based on the total weight of the fish meal, whereby the total amount of all ingredients sums up to 100 weight-%.
  • Fish meal is a commercial product made from fish that is used primarily as a protein supplement in compound feed, especially for feeding farmed fish, Crustacea, pigs and poultry, and companion animals such as cats and dogs.
  • a portion of the fish meal is made from the bones and offal left over from processing fish used for human consumption, while the larger percentage is manufactured from wild-caught, small marine fish. It is powder or cake obtained by drying the fish or fish trimmings, often after cooking, and then grinding it. If the fish used is a fatty fish it is first pressed to extract most of the fish oil.
  • fish meal The uses and need of fish meal are increasing due to the rising demand for fish, because fish has the best feed conversion rate of all farmed animals, can be produced well in developing countries and has a small size, i.e. can be slaughtered for preparing a meal, so that there is no need to store the fish. Furthermore, there are no religious constraints concerning the consumption of fish, fish is a source of high quality protein and it is easy to digest.
  • Fish meal is made by cooking, pressing, drying, and grinding of fish or fish waste to which no other matter has been added. It is a solid product from which most of the water is removed and some or all of the oil is removed. About four or five tons of fish are needed to manufacture one ton of dry fish meal.
  • Cooking A commercial cooker is a long, steam-jacketed cylinder through which the fish are moved by a screw conveyor. This is a critical stage in preparing the fishmeal, as incomplete cooking means the liquid from the fish cannot be pressed out satisfactorily and overcooking makes the material too soft for pressing. No drying occurs in the cooking stage.
  • Pressing A perforated tube with increasing pressure is used for this process. This stage involves removing some of the oil and water from the material and the solid is known as press cake. The water content in pressing is reduced from 70% to about 50% and oil is reduced to 4%.
  • the two main types of dryers are:
  • Indirect A cylinder containing steam-heated discs is used, which also tumbles the meal.
  • the fish meal has to be transported long distances by ship or other vehicles to the various locations, where it is used.
  • Unmodified fish meal can spontaneously combust from heat generated by oxidation of the polyunsaturated fatty acids in the fish meal. Therefore, it has to be stabilized by antioxidants.
  • antioxidants Especially advantageous for this purpose are the compounds of formula (III) of the present invention.
  • Insect meal has a high content of protein and is therefore, a valuable source of protein.
  • insects of special interest in the context of the present invention encompass black soldier flies (Hermetia species, commonly called BSF), mealworms (Tenebrio molitor), lesser mealworms (Alphitobius diaperinus), house cricket (Acheta domesticus, grasshoppers (Locusta migratoria), buffaloworms (Alphitobius diaperinus), cockroaches and domestic flies, whereby black soldier flies (Hermetia species, commonly called BSF), mealworms (Tenebrio molitor) and lesser mealworms (Alphitobius diaperinus) are more preferred.
  • the compounds of formula (III) with the preferences as given above are not only suitable for stabilizing fish meal, but also for stabilizing feed ingredients and feed. Preferences for feed ingredients and feed are given above and also apply here.
  • Feed means any substance or product, including additives, whether processed, partially processed or unprocessed, intended to be used for oral feeding to animals. Feed in the context of the present invention is feed for aquatic animals and for terrestrial animals, as well as feed for insects.
  • At least one compound of formula (III) ranging from 10 to 500 ppm, preferably ranging from 30 to 300 ppm, more preferably ranging from
  • the compounds of formula (III) can be used in combination with one or more other antioxidants as described below.
  • the feed of the present invention additionally comprises a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl- 4-methoxyphenol, which is known under the name “BHA” (butylated hydroxyanisole).
  • BHA butylated hydroxyanisole
  • the feed of the present invention additionally comprises ascorbyl palmitate. In another embodiment of the present invention the feed of the present invention additionally comprises BHA and ascorbyl palmitate.
  • esters of ascorbic acid such as the esters of ascorbic acid with linear C12-20 alkanols, preferably the esters of ascorbic acid with linear C14-18 alkanols, may also be used, so that further embodiments of the present invention are directed to feed that additionally comprises esters of ascorbic acid with linear C12-20 alkanols, preferably esters of ascorbic acid with linear C14-18 alkanols, more preferably ascorbyl palmitate, whereby optionally BHA may also be present.
  • the feed may also comprise additionally alpha-tocopherol and/or gamma- tocopherol, whereby either an ester of ascorbic acid with a linear C12-20 alkanol with the preferences as given above or BHA or both may additionally be present.
  • alpha-tocopherol and/or gamma- tocopherol whereby either an ester of ascorbic acid with a linear C12-20 alkanol with the preferences as given above or BHA or both may additionally be present.
  • the feed for poultry differs from region to region.
  • Tables V and VI typical examples for diets in Europe and Latin America are given. These diets include cereals such as wheat, rye, maize/corn, minerals such as NaCl, vegetable oils such as soya oil, amino acids and proteins.
  • Table V European diet
  • Pet foods are formulated to meet nutrient specifications using combinations of multiple ingredients to meet the targeted nutrient specification.
  • Poultry meal e.g. is an ingredient that is commonly found in Dog and Cat foods.
  • a typical example of feed for fish comprises the following ingredients, whereby all amounts are given in weight-%, based on the total weight of the feed for fish:
  • - binders mainly starch, in an amount ranging from 9 to 12 weight-%;
  • micro-ingredients such as vitamins, choline, minerals, mono calcium phosphate (“MCP”) and/or amino acids in an amount ranging from 3 to 6 weight-%;
  • - marine oil in an amount ranging from 5 to 10 weight-%, preferably marine oil in said amount comprising the compounds of formula (III) of the present invention
  • - vegetable oil in an amount ranging from 20 to 25 weight-%, preferably vegetable oil in said amount comprising the compounds of formula (III) of the present invention
  • alkyl and“alkoxy” in the context of the present invention encompass linear alkyl and branched alkyl, and linear alkoxy and branched alkoxy, respectively.
  • R 1 and R 3 are independently from each other H or methyl or ethyl, and R 2 is either H or methyl or ethyl or methoxy or ethoxy, preferably with the proviso that at least one of R 1 , R 2 and R 3 is H.
  • R 1 and R 3 are independently from each other H or methyl, and R 2 is either H or methyl or methoxy, preferably with the proviso that at least one of R 1 , R 2 and R 3 is H.
  • Fig. 1 shows the synthesis of 2,5,7,8-tetramethyl-2-(4-methylpentyl)chroman-6-ol (compound of formula (MI-1 )) starting from 2,3,5-trimethyl-1 ,4-hydroquinone (compound of formula (1-1 )) and 3,7-dimethyloct-1 -en-3-ol (compound of formula (11-1 )) .
  • Fig. 2 shows the synthesis of 2-methyl-2-(4-methylpentyl)chroman-6-ol (compound of formula (MI-2)) starting from 1 ,4-hydroquinone (compound of formula (I-2)) and 3,7-dimethyloct-1 -en-3-ol (compound of formula (11-1 )).
  • Fig. 3 shows the synthesis of 2-(4,8-dimethylnonyl)-2-methylchroman-6-ol
  • the molar ratio of the compound of formula (I) to the compound of formula (II) is in the range of 6.0:1 to 1 .1 :1 , preferably in the range of 4.0:1 to 1 .2:1 , more preferably in the range of 3.0:1 to 1 .3:1 , most preferably in the range of 2.0:1 to 1.5: 1.
  • the first of the two solvents is selected from ethylene carbonate, propylene carbonate, 1 ,2-butylene carbonate, and gamma-butyrolactone,
  • the second of the two solvents is selected from hexane, cyclohexane, heptane, ortho-xylene, meta-xylene, para-xylene, mesitylene, pseudocumene, methyl tert- butyl ether, and toluene, whereby this preference is preferably combined with another preference, some other preferences or all preferences of the process according to the present invention .
  • the first of the two solvents is ethylene carbonate or propylene carbonate
  • the second of the two solvents is selected from either hexane, cyclohexane or heptane, preferably the first of the two solvents is ethylene carbonate and the second of the two solvents is heptane.
  • hexane encompasses n-hexane, as well as any mixture of the isomers of hexane. The same applies for heptane.
  • the volume ratio of the first solvent to the second solvent during the reaction is in the range of 1 :4 to 4: 1 , preferably the volume ratio of the first solvent to the second solvent is in the range of 1 :3 to 3:1 , more preferably the volume ratio of the first solvent to the second solvent is in the range of 1 :2 to 2: 1.
  • the total amount of the two solvents is in the range of 1 to 10 kg, preferably in the range of 2 to 7 kg, more preferably in the range of 2.5 to 6 kg, per kg of the compound of formula (I).
  • Suitable acid catalysts are Bronsted acids and Lewis acids and any mixture thereof.
  • Bronsted acids are sulfuric acid, phosphoric acid, acidic ion-exchange resins (e.g. Amberlyst 15), acidic clays (e.g. Montmorillonite K-10), zeolites (e.g. HSZ-360), hydrochloric acid, trifluoroacetic acid, trichloroacetic acid, acetic acid, formic acid, methanesulfonic acid, benzenesulfonic acid, para-toluenesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, bis(perfluoroalkyl- sulfonyl)methanes (R’S0 2 )(R”S0 2 )CH 2 wherein R’ and R” each signify independently from each other a perfluoroalkyl group of the formula C n F 2n+i where n is an integer from 1 to 10, tris(perfluorosulfonyl)methane
  • pentafluorophenyl group (-C 6 F5) and R” and R’” each signify an identical perfluoroalkyl group of the above formula C n F 2n+i , methanetrisulfonic acid, and bis(trifluormethylsulfonyl)imide, and any mixture thereof, whereby the use of single catalysts is preferred.
  • Lewis acids are Al(OTf) 3 , Sc(OTf)3, Sc(NTf 2 ) 3 , ScCl 3 , Yb(OTf) 3 , YbCl 3 , Cu(OTf) 2 , FeCl 2 , Fe(OTf) 2 , ZnCl 2 , Zn(OTf) 2 , Zn(NTf 2 ) 3 , YCl 3 , Y(OTf) 3 , lnCl 3 , lnBr 3 , ln(OTf) 3 , ln(NTf 2 ) 3 , La(OTf) 3 , Ce(OTf) 3 , Sm(OTf) 3 , Gd(OTf) 3 , and Bi(OTf) 3 in the presence or absence of 2,2-bipyridine, and any mixture thereof, whereby the use of single catalysts is preferred.
  • the acid catalyst is para-toluenesulfonic acid, sulfuric acid,
  • the acid catalyst is para-toluenesulfonic acid or Al(OTf) 3 or any mixture thereof.
  • the use of single catalysts is preferred.
  • the more preferred acid catalyst is para-toluenesulfonic acid, sulfuric acid, methanesulfonic acid, Al(OTf) 3 , Sc(OTf) 3 , or ln(OTf) 3
  • the most preferred acid catalyst is para-toluenesulfonic acid or Al(OTf) 3 .
  • the amount of the acid catalyst is in the range of 0.001 to 5 mol equivalents, preferably in the range of 0.005 to 1 mol equivalents, more preferably in the range of 0.01 to 0.1 mol equivalents, relative to the amount of the compound of formula (II).
  • the acid catalyst is recyclable which is a further advantage of the present invention.
  • the reaction is preferably carried out at a temperature in the range of 70 to 160°C, more preferably in the range of 80 to 130°C, most preferably in the range of 90-105°C.
  • the reaction is preferably carried out at a pressure in the range of 0.8 to 20 bar (absolute), more preferably at a pressure in the range of 0.8 to 10 bar (absolute), most preferably at a pressure in the range of 0.8 to 5 bar (absolute).
  • the compounds of formulae (MI-3) and (111-4) have been tested.
  • MNT are mixed natural tocopherols commercially available as e.g.,“Tocomix 70 IP” from AOM (wholesome Aires, Argentina). Tocomix 70 IP comprises d-alpha- tocopherol, d-beta-tocopherol, d-gamma-tocopherol and d-delta-tocopherol, whereby the total amount of tocopherols is at least 70.0 weight-% and the amount of non-alpha tocopherols is at least 56.0 weight-%.
  • the compounds of formulae (111-3) and (MI-4) were evaluated primarily for their oxidative stability by the Oil Stability Index (OSI) measurements. Two different levels of these antioxidants (0.5 and 2 mg/g) were used in 5 g of natural fish oil (Product code: FG30TG) and used in the Oxidative Stability Instrument at 80°C with the air flow rate of 40 psi.
  • OSI Oil Stability Index
  • Crude algal oil (Lot# VY00010309) contained about 1 .6 mg/g of MNT prior to use in these experiments whereas fish oil did not contain any antioxidants.
  • Oil Stability Indices (OSI) for these compounds at 500 and 2000 ppm levels, in comparison with the same amounts of MNT, are shown in Tables 2-3.
  • Table 8 Improvement of the Protection Factors of compound of formula (MI-4) with AP in FG30TG fish oil
  • Tables 1 1 , 12 and 13 show the PV peroxide value), p- AV (g-anisidine value) and CD (conjugated dienoic acid %) of the fish oil samples stabilized with compounds of formulae (MI-3) and (MI-4), respectively.
  • Table 1 1 Variation of PV (peroxide value) with compounds of formulae (MI-3) and (MI-4) in FG30TG
  • Table 12 Variation of p- AV (p-anisidine value) with compounds of formulae (MI-3) and (MI-4) in FG30TG
  • Protection Factors of the compounds of formulae (MI-3) and (MI-4), including MNT, in fish oil could be improved by the addition of AP (Tables 8-9) indicating the possibility of combining AP with compounds of formulae (MI-3) and (MI-4) to improve the oxidative stability of matrices containing high amounts of unsaturated fatty acids such as marine oil.
  • AP AP
  • a combination of complex, polymeric compounds generated at the end of the oxidation cascade of unsaturated fatty acids indicate the levels of overall oxidation of the matrix.
  • the generation of such polymers in fish oil containing these novel antioxidant compounds could be reduced considerably when AP was added as a synergistic compound (Table 10).
  • the oxidative stability of fish oil with compound of formula (III-4) is comparable to the antioxidative effect of MNT.

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Abstract

La présente invention concerne un procédé de fabrication d'un composé de formule (III), comprenant une étape consistant à faire réagir un composé de formule (I) avec un composé de formule (II) en présence d'un catalyseur acide et dans un mélange de deux solvants, n étant 1 ou 2, et R1 et R3 sont indépendamment l'un de l'autre H ou un alkyle en C1-5, et R2 représente soit H soit un alkyle en C1-5 ou alkyloxy en C1-5, de préférence à condition qu'au moins l'un de R1, R2 et R3 soit H, et le premier des deux solvants étant choisi parmi le carbonate d'éthylène, carbonate de propylène, carbonate de 1,2-butylène, gamma-butyrolactone et l'eau, et le second des deux solvants étant choisi parmi l'hexane, cyclohexane, heptane, ortho-xylène, méta-xylène, para-xylène, mésitylène, pseudocumène, méthyl tert-butyle éther et toluène. La présente invention concerne également un composé de formule (III-3), ainsi que l'utilisation des composés de formule (III), en particulier l'utilisation d'un composé de formule (III-3) et l'utilisation du composé de formule (III-4), en tant qu'antioxydants, en particulier dans des aliments pour animaux, tels que, par exemple, dans des aliments pour animaux aquatiques, dans des aliments pour animaux terrestres (en particulier des aliments pour animaux de compagnie, des aliments pour porcs et des aliments pour volailles) et dans des aliments pour insectes, ainsi que dans des ingrédients alimentaires, tels que dans la farine de poisson, dans la farine de volaille, dans la farine d'insectes, et dans des huiles contenant des PUFA telles que l'huile marine, l'huile microbienne, l'huile fongique, l'huile d'algale et l'huile végétale contenant des PUFA. La présente invention concerne en outre des aliments pour animaux et des ingrédients d'aliments pour animaux contenant au moins un composé de formule (III), contenant en particulier un composé de formule (III-3) et/ou un composé de formule (III-4).
EP19714655.8A 2018-03-29 2019-03-29 Chroman-6-ols à chaîne latérale lipophile étendue en position 2, leur fabrication et leur utilisation Withdrawn EP3774757A1 (fr)

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WO2022078924A1 (fr) 2020-10-12 2022-04-21 Dsm Ip Assets B.V. Nouveaux additifs alimentaires de vitamines liposolubles
WO2022112586A1 (fr) 2020-11-30 2022-06-02 Dsm Ip Assets B.V. Nouvelles formulations sans sucre, leur production et leur utilisation
WO2022112585A1 (fr) 2020-11-30 2022-06-02 Dsm Ip Assets B.V. Nouvelles formulations sans sucre, leur fabrication et leur utilisation
EP4250961A1 (fr) 2020-11-30 2023-10-04 DSM IP Assets B.V. Nouvelles formulations à teneur réduite en antioxydant, leur production et leur utilisation
WO2022112592A1 (fr) 2020-11-30 2022-06-02 Dsm Ip Assets B.V. Nouvelles formulations à teneur réduite en antioxydant, leur fabrication et leur utilisation
CN116669565A (zh) 2020-12-18 2023-08-29 帝斯曼知识产权资产管理有限公司 包含脂溶性维生素的无动物制剂的代乳品
WO2022129433A1 (fr) 2020-12-18 2022-06-23 Dsm Ip Assets B.V. Lait de remplacement comprenant des formulations sans matière animale de vitamines liposolubles

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US5130242A (en) 1988-09-07 1992-07-14 Phycotech, Inc. Process for the heterotrophic production of microbial products with high concentrations of omega-3 highly unsaturated fatty acids
US5340742A (en) 1988-09-07 1994-08-23 Omegatech Inc. Process for growing thraustochytrium and schizochytrium using non-chloride salts to produce a microfloral biomass having omega-3-highly unsaturated fatty acids
JP3839071B2 (ja) * 1993-12-07 2006-11-01 有限会社ケムフィズ クロマン誘導体
JP4545235B2 (ja) 1996-03-28 2010-09-15 ディーエスエム アイピー アセッツ ビー．ブイ． 顆粒状微生物バイオマスの製造法とそのバイオマスからの貴重化合物の単離法
EP2280062A3 (fr) 1996-03-28 2011-09-28 DSM IP Assets B.V. Preparation d'acide gras polyinsature microbien a partir d'huile contenant une biomasse pasteurisee
KR20090064603A (ko) 2000-01-28 2009-06-19 마텍 바이오싸이언스스 코포레이션 발효기 내에서 진핵 미생물의 고밀도 배양에 의한 고도불포화 지방산을 함유하는 지질의 증진된 생산 방법
WO2004046127A1 (fr) * 2002-11-21 2004-06-03 Dsm Ip Assets B.V. Production de $g(a)-tocopherol

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