WO2021037656A1 - Acide folique solubilisé - Google Patents
Acide folique solubilisé Download PDFInfo
- Publication number
- WO2021037656A1 WO2021037656A1 PCT/EP2020/073310 EP2020073310W WO2021037656A1 WO 2021037656 A1 WO2021037656 A1 WO 2021037656A1 EP 2020073310 W EP2020073310 W EP 2020073310W WO 2021037656 A1 WO2021037656 A1 WO 2021037656A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solubilizate
- range
- polysorbate
- temperature
- weight
- Prior art date
Links
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims abstract description 105
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 229960000304 folic acid Drugs 0.000 title claims abstract description 53
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 53
- 239000011724 folic acid Substances 0.000 title claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 71
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 32
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 26
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 22
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 15
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 15
- 229920000053 polysorbate 80 Polymers 0.000 claims description 14
- 229940068968 polysorbate 80 Drugs 0.000 claims description 14
- 235000011187 glycerol Nutrition 0.000 claims description 13
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 11
- 239000000194 fatty acid Substances 0.000 claims description 11
- 229930195729 fatty acid Natural products 0.000 claims description 11
- 150000004665 fatty acids Chemical class 0.000 claims description 11
- 235000000346 sugar Nutrition 0.000 claims description 11
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 9
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 9
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 9
- 229940068977 polysorbate 20 Drugs 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 8
- 239000008139 complexing agent Substances 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 8
- 239000003921 oil Substances 0.000 claims description 8
- 235000019198 oils Nutrition 0.000 claims description 8
- 239000010865 sewage Substances 0.000 claims description 8
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 claims description 7
- 229920000136 polysorbate Polymers 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 229950008882 polysorbate Drugs 0.000 claims description 6
- 239000001959 sucrose esters of fatty acids Substances 0.000 claims description 6
- 238000004065 wastewater treatment Methods 0.000 claims description 6
- 235000013305 food Nutrition 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 4
- 238000010790 dilution Methods 0.000 claims description 4
- 239000012895 dilution Substances 0.000 claims description 4
- 235000015872 dietary supplement Nutrition 0.000 claims description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 3
- 239000008158 vegetable oil Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 2
- 235000013361 beverage Nutrition 0.000 claims description 2
- 230000033228 biological regulation Effects 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229940127557 pharmaceutical product Drugs 0.000 claims description 2
- 238000009472 formulation Methods 0.000 abstract description 12
- 230000000975 bioactive effect Effects 0.000 abstract description 2
- 239000012670 alkaline solution Substances 0.000 abstract 1
- 239000000693 micelle Substances 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 229940057917 medium chain triglycerides Drugs 0.000 description 7
- 230000004962 physiological condition Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 4
- -1 anion tetrahydrofolate Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- MSTNYGQPCMXVAQ-KIYNQFGBSA-N 5,6,7,8-tetrahydrofolic acid Chemical compound N1C=2C(=O)NC(N)=NC=2NCC1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-KIYNQFGBSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- OZRNSSUDZOLUSN-LBPRGKRZSA-N dihydrofolic acid Chemical compound N=1C=2C(=O)NC(N)=NC=2NCC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OZRNSSUDZOLUSN-LBPRGKRZSA-N 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- REOLHJDOUUORKY-UHFFFAOYSA-J [Na+].[Na+].[Ca+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O Chemical compound [Na+].[Na+].[Ca+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O REOLHJDOUUORKY-UHFFFAOYSA-J 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 150000004667 medium chain fatty acids Chemical class 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 210000003371 toe Anatomy 0.000 description 2
- QIZPVNNYFKFJAD-UHFFFAOYSA-N 1-chloro-2-prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1Cl QIZPVNNYFKFJAD-UHFFFAOYSA-N 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- XZAGBDSOKNXTDT-UHFFFAOYSA-N Sucrose monopalmitate Chemical compound CCCCCCCCCCCCCCCC(O)=O.OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(CO)O1 XZAGBDSOKNXTDT-UHFFFAOYSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- KGUHOFWIXKIURA-VQXBOQCVSA-N [(2r,3s,4s,5r,6r)-6-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methyl dodecanoate Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CCCCCCCCCCC)O[C@@H]1O[C@@]1(CO)[C@@H](O)[C@H](O)[C@@H](CO)O1 KGUHOFWIXKIURA-VQXBOQCVSA-N 0.000 description 1
- DPJIGBRZPUBMQJ-UHFFFAOYSA-M [OH-].[Na+].CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O Chemical compound [OH-].[Na+].CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O DPJIGBRZPUBMQJ-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011785 micronutrient Substances 0.000 description 1
- 235000013369 micronutrients Nutrition 0.000 description 1
- 235000021243 milk fat Nutrition 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003346 palm kernel oil Substances 0.000 description 1
- 235000019865 palm kernel oil Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940032085 sucrose monolaurate Drugs 0.000 description 1
- 229940035023 sucrose monostearate Drugs 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000005460 tetrahydrofolate Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/10—Foods or foodstuffs containing additives; Preparation or treatment thereof containing emulsifiers
-
- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F3/00—Biological treatment of water, waste water, or sewage
- C02F3/34—Biological treatment of water, waste water, or sewage characterised by the microorganisms used
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
- C02F1/68—Treatment of water, waste water, or sewage by addition of specified substances, e.g. trace elements, for ameliorating potable water
-
- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F2305/00—Use of specific compounds during water treatment
- C02F2305/06—Nutrients for stimulating the growth of microorganisms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
- Y02W10/00—Technologies for wastewater treatment
- Y02W10/30—Wastewater or sewage treatment systems using renewable energies
- Y02W10/37—Wastewater or sewage treatment systems using renewable energies using solar energy
Definitions
- the invention relates to a folic acid solubilizate according to claim 1. Furthermore, the invention relates to the use of such a solubilizate as
- Folic acid is a vitamin from the B complex and is chemically composed of a pteridine derivative, para-aminobenzoic acid and L-glutamic acid. It is also known as pteroglutamic acid. Folic acid is the precursor of the coenzyme tetrahydrofolic acid, which is present as an anion tetrahydrofolate under physiological conditions. In the human and animal organism as well as for some microorganisms, folic acid has an important role in the metabolism, especially in the provision of building blocks for DNA replication, or as a growth factor. Folic acid is unstable in contact with oxygen and / or UV radiation.
- folic acid formulations for the nutrition of humans and animals
- those for supporting the activity of microorganisms in biological-technical applications are known.
- One example of this is the addition of folic acid to the water to be treated in sewage treatment plants.
- DE 4213 603 CI describes a formulation which contains folic acid and / or dihydrofolic acid and / or its salts and, in connection with mixed populations of microorganisms in the so-called sewer skin, a biofilm in the sewer, is activated, whereby the degradation of the wastewater ingredients also occurs in the sewage treatment plant is improved. Since the compounds used are subject to a loss of effectiveness due to residual oxygen in the wastewater even under essentially anaerobic conditions, a protective gas is used to reduce the introduction of oxygen when the folic acid formulation is introduced.
- Folic acid preparation proposed to improve its stability in the presence of oxygen, which has a combination of dihydrofolic acid and / or at least one salt thereof and at least one hydroxypolycarboxylic acid and / or at least one salt thereof as a stabilizer.
- the dihydrofolic acid itself is sensitive to oxidation and appears to act as a kind of sacrificial substance. Their own potential for increasing metabolism or growth in the organisms that absorb them cannot be used.
- Another object of the invention is to provide an improved formulation for folic acid. Another object of the invention is to provide the highest possible proportion of the folic acid used in a bioactive manner over a period of several weeks. In particular, it is an object of the invention to provide a folic acid formulation which shows an improved bioavailability of the folic acid used compared to previously known formulations.
- folic acid in relation to the invention in the context of this application includes, in addition to folic acid, tetrahydrofolic acid and tetrahydrofolic acid as well as the derivatives and especially salts of these acids, also in dissolved form, in particular as an aqueous solution.
- the invention provides a solubilizate containing, in particular consisting of folic acid with a proportion of less than or equal to 3% by weight, preferably less than or equal to 2% by weight, particularly preferably less than or equal to 1% by weight, in particular 0.6% by weight .-%, at least one emulsifier with an HLB value in the range between 13 and 18, which is selected in particular from the group consisting of polysorbate 80, polysorbate 20,
- Sugar esters from fatty acids E 473
- at least one medium-chain triglyceride MCT
- the medium-chain triglyceride being provided in particular by at least one MCT oil and / or at least one vegetable oil, at least one alcohol, in particular glycerol and / or ethanol, at least one alkali, in particular sodium hydroxide solution, and water are available.
- the solubilizate according to the invention is a colloidally formulated mixture in which folic acid is contained as a bioactive agent.
- a solubilizate can be created with stable micellar structures, even under physiological conditions.
- a prerequisite for the absorption of fat-soluble micronutrients by the human or animal body is the formation of so-called "physiological mixed micelles" with the help of bile acids, bile salts and enzymes from the digestive tract.
- the solubilizate according to the invention therefore has analogous to this natural principle and against the background of optimization
- the bioavailability of folic acid has a stable micellar structure, and bioavailability can be improved in this way if the micelle is stable under physiological conditions - that is, at a temperature of 37 ° C and pH 1.1 reaches the small intestine undamaged.
- At least one sugar ester of a fatty acid or a mixture of several sugar esters of fatty acids can also be used as an emulsifier.
- Individual sugar esters of fatty acids (E 473) or mixtures of at least two sugar esters of fatty acids can be used as sugar esters of fatty acids (E 473).
- Suitable sugar esters of fatty acids are, in particular, sucrose mono-laurate, sucrose-di-laurate, sucrose-mono-palmitate, sucrose-di-palmitate, sucrose-mono-stearate and sucrose-di-stearate.
- polysorbate 20 can also be used as an emulsifier within the scope of the invention.
- the inventor has found that the mixture of polysorbate 80 or polysorbate 20 or a mixture of polysorbate 80 and polysorbate 20 with at least one sugar ester of an edible fatty acid can also be used as an emulsifier within the scope of the invention.
- Vegetable oils for example, sunflower oil and / or safflower oil can be used.
- the invention offers the advantage of being able to adjust the composition depending on which other components are to be contained in the solubilizate and in what proportions, its properties with regard to optimizing bioavailability and storage stability and preventing or reducing interactions between folic acid and other substances in the stomach contents of humans and / or animals as well as in the wastewater to be treated is to be provided.
- the folic acid formulation according to the invention provides folic acid enclosed in micelles.
- the micelles are mechanically stable. This micellation also protects the folic acid against oxidation. Micellation generally enables a reduction or even suppression of reactions of folic acid with other substances. In this way, when the formulation according to the invention comes into contact with the cells of the organism that absorbs the folic acid, the folic acid can be available undamaged and thus develop its full effectiveness.
- the formulation of folic acid according to the invention enables, when used in sewage treatment plants, a reduction in sludge formation from biological wastewater treatment and an optimization of biogas production.
- the emulsifier component in particular the polysorbate component, is at least 45% by weight, preferably in the range between 60% by weight and 95% by weight, particularly preferred is in the range between 73% by weight and 90% by weight. With these values, very stable micelles can be achieved.
- the at least one lye comprises an aqueous solution of sodium hydroxide solution, the ratio of sodium hydroxide solution to water being in particular 1: 3.
- the solubilizate or an aqueous solution of the solubilizate has, in particular, a basic pH.
- a significant improvement in the stability of the micelles in which the folic acid according to the invention is enclosed is achieved according to the invention by adding at least one complexing agent to the solubilizate, in particular ethylenediaminetetraacetic acid and / or ethylenediaminetetraacetate (EDTA) and / or
- the solubilizate contains up to 25% by weight, preferably up to 12% by weight, glycerol.
- glycerine By adding glycerine, the proportion of polysorbate in particular can be reduced, depending on the application.
- the invention offers the possibility that the solubilizate contains up to 20% by weight, preferably up to 15% by weight, of ethanol.
- the amount of polysorbate can also be reduced by adding ethanol.
- a reduction in the polysorbate content of a solubilizate is an advantage with regard to the ADI value for polysorbate.
- the easily accessible determination of the turbidity of the solubilizate provides an indication of the good bioavailability.
- the turbidity of the solubilizate is preferably less than 10 FNU, preferably less than 5 FNU, as a result of the formulation according to the invention, is measured by measuring scattered light with infrared light according to the regulations of the ISO 7027 standard with a dilution of the solubilizate in a ratio of 1:50 in water at pH 1 1 and 37 ° C.
- the solubilizate according to the invention can also be incorporated into other fluids, in particular liquids, within the scope of the invention.
- the small micelles filled with the active ingredient are retained.
- the invention thus also provides a fluid containing an above-described solubilizate, the fluid being selected from the group which includes additives for wastewater treatment in sewage treatment plants, as well as food, beverages, cosmetics and pharmaceutical products.
- the fluid can comprise an aqueous dilution of the solubilizate.
- the invention thus also enables, in particular, the use of a solubilizate or fluid described above as an additive for wastewater treatment in sewage treatment plants or as a food supplement.
- the invention further provides a method for producing a solubilizate described above with the following steps a) providing a mixture of alcohol, in particular of glycerol and / or ethanol, and water, b) adding the at least one lye and the at least one medium-chain triglyceride, c) adding folic acid, d) adding the emulsifier, in particular polysorbate 80, polysorbate 20, sugar esters from fatty acids
- step a) heating to a temperature in the range from 50 ° C to 65 ° C, preferably to a temperature in
- step d) heating to a temperature in the range from 80 ° C to 95 ° C, preferably to a temperature im
- At least one complexing agent in addition to the alkali, at least one complexing agent, in particular ethylenediaminetetraacetic acid and / or ethylenediaminetetraacetate (EDTA) and / or ethylenediaminetetraacetate calcium disodium complex (EDTA CaNa2-2 H 2 O), is added in step b).
- EDTA ethylenediaminetetraacetic acid and / or ethylenediaminetetraacetate
- EDTA CaNa2-2 H 2 O ethylenediaminetetraacetate calcium disodium complex
- ethylenediaminetetraacetate calcium disodium complex (EDTA CaNa 2 ⁇ 2 H 2 0) is added as a complexing agent, it has proven helpful to heat to a temperature in the range from 50 ° C. to 70 ° C., preferably to one temperature in the range from 55 ° C to 65 ° C, particularly preferably at a temperature in the range from 58 ° C to 62 ° C.
- step b) bl) the at least one complexing agent is dissolved in the at least one alkali, in particular in an aqueous solution of the at least one alkali.
- the folic acid used in the exemplary embodiments described below was obtained from Welding GmbH & Co. KG, Hamburg, Germany, from Koninklijke DSM N.V., Heerlen, Netherlands, from Zhejiang
- TEGO SMO 80 V FOOD The material "TEGO SMO 80 V FOOD” from Evonik Nutrition & Care GmbH, Essen, Germany, was used as the source for polysorbate 80.
- the product complies with the EU requirements for the food additive E 433 mentioned TEGO SMO 80 V from Evonik as polysorbate 80, for example also Crillet 4 / Tween 80-LQ- (SG) from CRODA GmbH, Nettetal, Germany or Lamesorb SMO 20 and Kotilen-O / 1 VL from Univar or Kolb Distributions AG, Hedingen, Switzerland can be used.
- glycerine from CREMER OLEO GmbH & Co. KG was used as the glycerine. According to the manufacturer, the glycerine content of this product is at least 99.5%. Alternatively, for example, the product “Glycamed 99.7%” from Glaconchemie GmbH, Merseburg, Germany can also be used.
- MCTs Medium-chain triglycerides
- the medium-chain fatty acids include caproic acid, caprylic acid, capric acid and lauric acid. These are saturated fatty acids, which occur naturally in tropical vegetable fats such as coconut oil and palm kernel oil. To a small extent, they are also contained in milk fat. There is no pure MCT oil in nature, but pure MCT oils can be obtained synthetically. In the context of the invention, individual MCTs or a mixture of different MCTs can be used as medium-chain triglycerides.
- EDTA-NaOH solution was used for the exemplary embodiments described below. This corresponds to a composition of sodium hydroxide solution (1: 3) and ethylenediaminetetraacetate (EDTA), AppliChem GmbH, Darmstadt, Germany, or ethylenediaminetetraacetate calcium disodium complex (EDTA CaNa2 2 H2O) as the product Solvitar® from Nouryon, Amsterdam, Netherlands, formerly AkzoNobel Specialty Chemicals.
- the sodium hydroxide solution was prepared from one part of NaOH pellets and three parts of water. The NaOH toes were obtained from Spolchemie, Usti nad Labern, Czech Republic.
- Distilled water was used as the water.
- the 15% EDTA-NaOH solution corresponds to 1.5 g EDTA and 8.5 g sodium hydroxide solution.
- the sodium hydroxide solution consists of one part of NaOH toes and three parts of water.
- glycerine and water are mixed and heated to a temperature in the range from 53 ° C to 57 ° C.
- the EDTA solution and the MCT oil are then added and the mixture is homogenized while maintaining the temperature in the range from 53 ° C. to 57 ° C. while stirring. This means that it is stirred so vigorously that the components initially mixed with one another combine with one another homogeneously, with in particular essentially no residues remaining.
- the folic acid is then added while maintaining the temperature in the range from 53 ° C to 57 ° C and.
- the folic acid is incorporated with stirring and homogenized with the other components.
- Polysorbate 80 is then added.
- the temperature is increased to a value in the range from 83 ° C. to 87 ° C. and the product is homogenized.
- the mixture is cooled to a temperature below 60 °.
- the folic acid solubilizate is yellow and transparent.
- the turbidity is a maximum of 1.5 FNU under physiological conditions, the measurement being carried out as described above.
- the folic acid solubilisate is then bottled and stored in a dark and cool place, i.e. below 25 ° C.
- Ethyldiamine tetraacetate calcium disodium complex (EDTA CaNa2 ⁇ 2 H2O) and NaOH solution are used.
- the NaOH solution is prepared as described in embodiment 1. 8.5 g of this NaOH solution are mixed with 1.5 g
- Ethyldiamine tetraacetate calcium disodium complex used as 10 g of the 15% (EDTA CaNa2 ⁇ 2 H2O) -NaOH solution.
- the temperature is increased to a value in the range from 58.degree. C. to 62.degree.
- the further processing corresponds to that described above.
- This folic acid solubilizate is also yellow and transparent.
- the turbidity is a maximum of 1.5 FNU under physiological conditions, the measurement being carried out as described above.
- the clarity of the solubilizate according to the invention is retained; when heated further, it becomes cloudy the solubilizate. On cooling, the cloudiness is reversible and the solubilizate becomes clear again.
- Whether a sufficiently complete homogenization of the components to form a solubilizate according to the invention has been completed is checked during production by measuring the clarity of the product with the aid of a laser beam.
- a laser beam measurement can be carried out, for example, by illuminating the sample with the aid of a commercially available laser pointer, in particular with a wavelength in the range between 650 nm and 1700 nm (spectral color red), and subsequent visual inspection of the illuminated or transilluminated solubilizate.
- the control is not carried out by taking samples and thus outside the reaction vessel, but in the reaction vessel.
- the laser beam is directed through a sight glass, which is located on the front of the reaction vessel, perpendicular to the reaction vessel. If only one point of light appears on the rear inner side of the reaction kettle, completely free of scattering, the resulting particle structures in the reaction kettle are smaller than the wavelength of visible light and thus an optical confirmation that the micellation process has been completed.
- the folic acid content in the solubilizate can also be set significantly higher than in the examples shown, depending on the application.
- this effectiveness can be attributed to the improved bioavailability of the folic acid solubilized according to the invention compared to known formulations and can already be read from the particularly low turbidity of the solubilizate, which can be understood as a kind of parameter for bioavailability. It is evident to the person skilled in the art that the invention is not restricted to the examples described above, but rather can be varied in many ways. In particular, the features of the individually illustrated examples and embodiments or developments can also be combined with one another or exchanged for one another.
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Abstract
La présente invention concerne une formulation améliorée d'acide folique qui peut libérer comme pourcentage élevé de l'acide folique utilisé sous une forme bioactive sur une période de plusieurs semaines. L'invention concerne un solubilisat contenant de l'acide folique avec un pourcentage inférieur ou égal à 3 % en pds, au moins un agent émulsifiant ayant une valeur HLB dans la plage de 13 et 18, au moins un triglycéride à chaîne moyenne (MCT), au moins un alcool, au moins une solution alcaline et de l'eau. L'invention concerne également un procédé de préparation d'un tel solubilisat.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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EP20761181.5A EP4021412A1 (fr) | 2019-08-29 | 2020-08-20 | Acide folique solubilisé |
CN202080061116.XA CN114364268A (zh) | 2019-08-29 | 2020-08-20 | 叶酸增溶物 |
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DE202019104734.8 | 2019-08-29 | ||
DE202019104734.8U DE202019104734U1 (de) | 2019-08-29 | 2019-08-29 | Folsäure-Solubilisat |
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PCT/EP2020/073310 WO2021037656A1 (fr) | 2019-08-29 | 2020-08-20 | Acide folique solubilisé |
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EP (1) | EP4021412A1 (fr) |
CN (1) | CN114364268A (fr) |
DE (1) | DE202019104734U1 (fr) |
WO (1) | WO2021037656A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023139105A1 (fr) | 2022-01-20 | 2023-07-27 | Solmic Biotech GmbH | Composition pour application topique contenant des solubilisats de substances actives lipophiles |
EP4275694A1 (fr) | 2022-05-13 | 2023-11-15 | Solmic Biotech GmbH | Utilisation de solubilisats dans des articles destinés à l'application topique |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0319598B1 (fr) | 1987-12-07 | 1991-09-25 | Holger Blum | Préparation stabilisée aqueuse d'acide folique |
DE4213603C1 (en) | 1992-04-24 | 1993-06-03 | Allied Colloids Mfg. Gmbh, 2000 Hamburg, De | Treating waste water by addn. of (di:hydro)folic acid or salts - activating bio:film on inner wall of pipes to accelerate breakdown of components in the water |
US20080249191A1 (en) * | 2007-03-30 | 2008-10-09 | Nof Corporation | Solubilizing composition |
WO2011066937A1 (fr) * | 2009-12-01 | 2011-06-09 | Aquanova Ag | Composition agissant comme émulsifiant pour des composés hydrophobes de solubilisats solubles dans l'eau |
EP3216443A1 (fr) * | 2016-03-10 | 2017-09-13 | Athenion AG | Capsule de préparation de boisson d'un solubilisate |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19936545A1 (de) * | 1999-08-03 | 2001-02-08 | Hexal Ag | Neue pharmazeutische Zusammensetzung zur nasalen Anwendung von wasserlöslichen Wirkstoffen |
DE102004045622A1 (de) * | 2004-09-17 | 2006-03-30 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Konservierungsmittel-Zusammensetzungen |
DK2192160T3 (en) * | 2008-12-01 | 2016-12-12 | Aquanova Ag | INTEGRATED oxidation of micelles FOR NATURAL DYES |
DE202012012130U1 (de) * | 2012-12-19 | 2014-03-21 | Aquanova Ag | Curcuminsolubilisat |
CA3148455A1 (fr) * | 2017-07-11 | 2019-01-17 | Aquanova Ag | Solubilisat contenant de la curcumine et optionnellement au moins une autre substance active |
-
2019
- 2019-08-29 DE DE202019104734.8U patent/DE202019104734U1/de active Active
-
2020
- 2020-08-20 CN CN202080061116.XA patent/CN114364268A/zh active Pending
- 2020-08-20 EP EP20761181.5A patent/EP4021412A1/fr active Pending
- 2020-08-20 WO PCT/EP2020/073310 patent/WO2021037656A1/fr unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0319598B1 (fr) | 1987-12-07 | 1991-09-25 | Holger Blum | Préparation stabilisée aqueuse d'acide folique |
DE4213603C1 (en) | 1992-04-24 | 1993-06-03 | Allied Colloids Mfg. Gmbh, 2000 Hamburg, De | Treating waste water by addn. of (di:hydro)folic acid or salts - activating bio:film on inner wall of pipes to accelerate breakdown of components in the water |
US20080249191A1 (en) * | 2007-03-30 | 2008-10-09 | Nof Corporation | Solubilizing composition |
WO2011066937A1 (fr) * | 2009-12-01 | 2011-06-09 | Aquanova Ag | Composition agissant comme émulsifiant pour des composés hydrophobes de solubilisats solubles dans l'eau |
EP3216443A1 (fr) * | 2016-03-10 | 2017-09-13 | Athenion AG | Capsule de préparation de boisson d'un solubilisate |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023139105A1 (fr) | 2022-01-20 | 2023-07-27 | Solmic Biotech GmbH | Composition pour application topique contenant des solubilisats de substances actives lipophiles |
EP4275694A1 (fr) | 2022-05-13 | 2023-11-15 | Solmic Biotech GmbH | Utilisation de solubilisats dans des articles destinés à l'application topique |
Also Published As
Publication number | Publication date |
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EP4021412A1 (fr) | 2022-07-06 |
CN114364268A (zh) | 2022-04-15 |
DE202019104734U1 (de) | 2020-12-01 |
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