WO2001042390A1 - Stabilisant pour composes insatures ou pate contenant ces composes et procede de stabilisation correspondant - Google Patents

Stabilisant pour composes insatures ou pate contenant ces composes et procede de stabilisation correspondant Download PDF

Info

Publication number
WO2001042390A1
WO2001042390A1 PCT/JP2000/008495 JP0008495W WO0142390A1 WO 2001042390 A1 WO2001042390 A1 WO 2001042390A1 JP 0008495 W JP0008495 W JP 0008495W WO 0142390 A1 WO0142390 A1 WO 0142390A1
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
stabilizer
amino
tocopherol
vitamin
Prior art date
Application number
PCT/JP2000/008495
Other languages
English (en)
Japanese (ja)
Inventor
Akihiko Niina
Original Assignee
Akihiko Niina
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Akihiko Niina filed Critical Akihiko Niina
Priority to AU15562/01A priority Critical patent/AU1556201A/en
Publication of WO2001042390A1 publication Critical patent/WO2001042390A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
    • C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
    • C09K15/20—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen and oxygen
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B5/00—Preserving by using additives, e.g. anti-oxidants
    • C11B5/0092—Mixtures

Definitions

  • the present invention significantly improves the chemical stability of unsaturated compounds contained in products in a wide range of fields, particularly foods, nutrients, pharmaceuticals, cosmetics, feeds, medical devices, chemicals, resins and rubbers, and the like. Effectiveness of the unsaturated compounds.
  • the present invention relates to a stabilizer which is extremely effective in improving the commercial value, such as maintaining the effectiveness of the product for an extremely long period of time and remarkably reducing the change in color and fragrance.
  • Unsaturated compounds such as retinoids, carotenoids, isoprenoids, unsaturated fatty acids, vitamin D, vitamin K, coenzyme Q, oils and fats, and essential oils are useful substances. It is contained in a wide range of products such as nutrients, pharmaceuticals, cosmetics, feed, medical devices, chemicals, resins and rubber. It is difficult to maintain the effectiveness of these unsaturated compounds for a long period of time due to instability based on their chemical structure, and stabilization with various stabilizers has been attempted in the past. Drugs and stable usage could not be established.
  • Unsaturated compounds having one or more carbon-carbon double bonds in the molecule especially the above-mentioned unsaturated compounds, such as fats and oils, essential oils, compositions, preparations, and products containing the unsaturated compound Extremely unstable, easily reacts with light, air, heat, metal ions, free radicals, and other reactive substances, depending on environmental conditions, decomposition, isomerization, polymerization, oxidation, addition, substitution, etc. Deterioration due to various reactions, losing effectiveness, and decreasing product value such as color and odor Or The present invention remarkably improves the stability of the unsaturated compounds, and maintains the effectiveness and value of the products containing the unsaturated compounds for a long period of time. Means for solving the problem
  • the present inventor has conducted intensive studies in view of such circumstances, and as a result, has found that unsaturated compounds such as retinoids, liposide tinoids, isoprenoids, unsaturated fatty acids, oils and fats, essential oils, vitamin Ds and vitamin Ks. As a means to significantly improve the stability of the compounds and those containing them, it was found that coexistence of vitamin Es and amino alcohols as essential components was extremely effective, and the present invention was completed. is there. Disclosure and structure of the invention
  • the unsaturated compounds of the present invention are a general term for compounds having at least one carbon-carbon double bond in the molecule and having high reactivity and being unstable. Among them, compounds having a structure having two or more carbon-carbon double bonds are more reactive and unstable. Particularly, highly reactive ⁇ unsaturated unsaturated compounds include retinoides, carotenoids, isoprenoids, polyunsaturated fatty acids, vitamin D, vitamin K, coenzyme Q, etc. it can. Retinoids are compounds that exhibit vitamin A activity and derivatives thereof, and are a generic name for various isomers such as retinoyl, retinal, retinoic acid, and derivatives thereof.
  • Carotenoids include various isomers such as carotene, ⁇ -carotene, r-carotene, astaxanthin, capsanthin, citranaxanthin, lycopene, bixin, rubixanthin, crocin, canthaxanthin, apocarotenil, and ana I and derivatives
  • Is a generic term for Isoprenoids include natural rubber, gata perch, synthetic polyisoprene, and screen with an isoprene polymer skeleton.
  • isomers such as cholesterols such as allene isosteric polymer, taxosterol and ergosterol, terbenoids such as abietic acid, geraniol, jasmon and ionicone, and derivatives thereof.
  • Monounsaturated fatty acids include hydrproleic acid, minderic acid, myristreic acid, and phenol. It is a general term for all other isomers and derivatives such as noremic rayic acid, oleic acid, elaidic acid, gadolinic acid, erucic acid, cetreic acid, and seracoleic acid.
  • the polyunsaturated fatty acids are a generic term for isomers and derivatives such as linoleic acid, linoleic acid, linoleic acid, arachidonic acid, eleostearic acid, eicosapentaenoic acid, docosahexaenoic acid, and the like.
  • Vitamin Ds, Vitamin Ks, and Coenzyme Qs are generic terms for compounds that exhibit each vitamin or provitamin activity and have multiple unsaturated double bonds.
  • the content of the polyunsaturated compound is a general term for substances containing one or more of the above polyunsaturated compounds, such as oils and fats, essential oils, natural pigments, foods, medicines, nutrients, cosmetics, feeds, A wide range of products of industrial value, such as chemicals, fall under this category.
  • Fats and oils are rapeseed oil, soybean oil, safflower oil, sesame oil, cottonseed oil, paulownia oil, linseed oil, perilla oil, other vegetable oils, shark liver oil, sardine oil, mackerel oil, bonito oil, tuna oil and other fish oils, beef tallow, pork fat, horse Oil, mink oil, tallow, lecithin, and other phospholipids and derivatives thereof.
  • Essential oil is a generic term for orange oil, rose oil, jasmine oil, geranium oil, lavender oil, turpentine oil, and derivatives thereof.
  • Natural pigment is a general term for natural products including carotenoids and derivatives thereof. Foods, nutrients, feeds, pharmaceuticals, cosmetics, medical devices, chemicals, resins and rubbers are commercial products containing one or more of the above unsaturated compounds.
  • the vitamins which are essential components of the present invention, are a general term for various compounds having a 2-methyl-6-chromanol structure having a nature as a radical scavenger, a tocopherol, ⁇ tocopherol, r tocopherol, ⁇ tocopherol, ⁇ Tocopherols and corresponding tocopherols
  • trans and cis isomers of knol There are trans and cis isomers of knol.
  • Derivatives are a general term for known compounds such as acetates, carbonates, phosphates and salts thereof, and phospholipid complexes.
  • Amino alcohols which are other essential components of the present invention, are compounds having at least one aliphatic amino group and at least one alcohol group in the molecule.
  • the molecule has at least one structure in which an amino group and an alcohol group are adjacent to each other in a molecule, and a large number of alcohol groups adjacent or adjacent to the amino group has a stabilizing effect and safety. A favorable tendency was observed in the properties and the like.
  • Specific examples of the compounds in which R 1 to R 3 are changed in the chemical formula (1) include 2-amino-1-propanol, 2-amino-2-hydroxymethyl-1,3-propanediol, and 2-amino-2- Methyl-1,3-propanediol, 2-amino-2-ethyl-1,3-propanediol, 2-amino-1,3-propanediol, 2-amino-1,3-butanediol, 2-amino-3-hydroxy Methyl-1,3,4-butanetriol, 2-amino-1-2-hydroxymethyl-1,3,4-butantriol, 3-amino-1,2,4,5-pentanetrol, 2-amino-2 '3-dihydroxymethyl-1,3,4-butanetriol, 2-amino 1,3,4,5,6-hexampen!
  • Examples of the compounds in which R 1 to R 4 are changed in the chemical formula (2) are 1-amino-12-ethanol, 1-amino-2,3-propanediol, 1-1-amino-2-propanol, and 1-amino-3- Propanol, 1-amino-2,2-dihydroxymethyl-3-propanol, 1-1-amino-2-butanol, 1-1-amino-2,3-butanediol, 1-amino-1,2,4-butanediol, 1-1-amino-2,3, 4-butanetriol, 2-aminomethyl-2-hydroxymethyl-1'3-propanediol, 1-amino-2,3,4-pentanetriol, 1-amino-2,3,4,5-pentanetrol, 1-aminopentol 2,3,4,5,6-—xampentol, structural isomers of amino alcohols including monosaccharides and polysaccharides and their deoxy structures, and amino alcohols with similar structures around the
  • Derivatives are derivatives obtained by esterification of alcohols with fatty acids, polyvalent fatty acids, nitric acid, etc., and reactions such as carboxymethylation, hydroxyethylation, hydroxypropylation, polyoxyethylation, polyoxypropylation, and etherification.
  • Amino group is a derivative of partially amidated or alkylated fatty acid or polyhydric fatty acid or the like, and is a generic term for compounds having substantially the function of stabilizing the unsaturated compound of the present invention.
  • the amino alcohols of the present invention are not limited to the above examples, provided that they are represented by the chemical formula (1) or (2). Good.
  • the type and amount of the vitamin E compound to stabilize the unsaturated compound and its content according to the present invention there is no particular limitation on the type and amount of the vitamin E compound to stabilize the unsaturated compound and its content according to the present invention, and the degree to which the desired unsaturated compound is required to be stabilized and the unsaturated compound It is freely selected according to the purpose of use of the product containing, and is usually about 0.001 to 20% by weight.
  • the amount of the amino compound and / or its derivative compounded for stabilizing the unsaturated compound and its content according to the present invention is not particularly limited, and the amount of stabilization of the target unsaturated compound is required. It is freely selected according to the purpose of use of the product containing the unsaturated compound or the unsaturated compound, but is usually about 0.001 to 20% by weight. Background technology and novelty and inventive step of the present invention
  • the chemical stability is remarkably improved, the content of the unsaturated compound as an active ingredient can be extremely effectively prevented from decreasing with time, and it is also effective for monovalent unsaturated compounds.
  • the present invention has been completed.
  • the chemical stability of unsaturated compounds to which the present invention is applied, particularly polyunsaturated compounds and their inclusions, is remarkably improved, so that the functions and effectiveness of the polyunsaturated compounds and their inclusions are extremely high. It has the effect of being retained for a long time and increasing its commercial value, and is extremely useful and innovative in a wide range of industrial fields.
  • Retinoids are useful compounds that exhibit vitamin A activity, but are extremely unstable due to the molecular structure having a high degree of conjugated double bond, and readily react with light, air, heat, metal ions, and the like.
  • the thermal stability of retinol palmitate was determined to be syrup at 60 ° C for 10 days according to the research report by Yoshioka et al. Of the National Satellite Research Laboratory (Parma ceutica IR esearch, P 388—391, Vol. 4, 1990). It has been disclosed that the residual ratio in the drug is about 760/0.
  • Japanese Patent Application Laid-Open No. 2-289513 Japanese Patent Application Laid-Open No. 3-38519
  • Japanese Patent Application Laid-open No. Hei 4-26670 Japanese Patent Application Laid-Open No. Hei 210-1990
  • Japanese Patent Laid-open No. Hei 4-1702210 Japanese Patent Application Laid-Open No. Hei 5-4991 8
  • Japanese Patent Application Laid-Open No. 5-173050 Japanese Patent Application Laid-Open No. 5-111366, Japanese Patent Application Laid-Open No. 5-124967, Japanese Patent Application Laid-Open No. 5-132321, Japanese Patent Application Laid-Open No. 5-139955, Japanese Patent Application Laid-open No.
  • butylhydroxytoluene BHT
  • butylhydroxydisole BHA
  • ascorbic acid AA
  • propyl gallate 8 carotene, tocopherol, ethylenediaminetetraacetate (EDTA salt), an ultraviolet absorber, Nordihydroguaiaretic acid (NDGA), ascorbyl fatty acid, isoascorbic acid, benzophenone compounds, cyclodextrin, basic amino acids (arginine, lysine, hydroxy lysine, orditin), acidic amino acids (asparaginate, glutamic acid, Pyrrolidone carboxylic acid) pentaerythritol Fatty acid esters, trimethylolpropane fatty acid esters and water-swellable clay minerals, citrates, imidazoles (ketoconazole, miconazole, econazole, itraconazole, fficonazole, terconazole, clotrimazo
  • JP-A-9-111777, JP-A-9-11-1237, JP-A-11-96779, JP-A-11-21 5968, JP-A-11-285359, JP-T-10-509590 There are disclosed examples such as Tokuheihei 1 1-506925.
  • BHA BHA, BHT, ascorbic acid, isoascorbic acid, ascorbic acid fatty acid ester, sorbic acid, sucrose fatty acid ester, propyl gallate, guaiac, nordihydroguaiaretic acid, isopropyl citrate, vitamin Class A, iS carotene, 2,2,5,7,8-pentamethyl-6-chromanol, Tocopherol, tocopheryl hydroquinone, catechin, tea extract, sesame extract, southern extract, grape extract, grape seed extract, proanthocyanidin, peach extract, 0-glycosylisovitexin, sufingomyelin, lecithin,
  • a stabilizing technique has been disclosed in which butter, phospholipids, vinegar, citrus juice, sesame oil, cottonseed oil and the like are blended with polyunsaturated fatty acids
  • the specification of the invention discloses a stabilization technique in which BHT, BHA, tocopherol, ascorbic acid, ⁇ -carotene, propyl gallate, 0-glycosylisovitexin, and the like are mixed with vitamins D and tamins. .
  • Coenzymes Q JP-A-53-56315, JP-A-55-81813, JP-A-57-106627, JP-A-58-92609, JP-A-58-113127, JP-A-58-113127 58-1113127, JP-A-60-1125, JP-A-60-25918, JP-A-60-25918, JP-A-60-89442, JP-A-2-28953, JP-A-41 26670, Tokuhyohei 10-51 0523, etc.
  • tocopherol phytonadione, polyoxyethyl-hardened castor oil, lecithin, soybean oil, corn oil, sorbitan monolaurate, vitamin ⁇ 2, pyrogallol, hydrogenated lecithin and neutral amino acid, polyglycerin fatty acid
  • a stabilizing technique has been disclosed in which a powder of ester and a water-soluble polymer, 7 "cyclodextrin, cyclic mono-, 6-D-glucan and the like are mixed with coenzymes Q.
  • BHA ascorbic acid
  • isoascorbic acid fatty acid ester of ascorbic acid
  • fatty acid ester of sucrose propyl gallate
  • guaiac nordihydroguaiaretinic acid
  • isopropyl citrate vitamin A, Vitamin A acetate, ⁇ -carotene, tocopherol, 1,2-diasyl-glycerol 3-phospho-2-hydroxyethyl-2,5,7,8-tetramethyl-6-hydroxychroman, catechin, tea extract, Sesame extract, Nanten extract, Grape extract, Yamato extract, Lignin, Lecithin, Lipid, Glutathione, 4,4'-Methylenebis (2,6-di-tert-butylphenol), 2,6-Di
  • Foods, nutrients, feed, pharmaceuticals, cosmetics, medical devices, etc. are intended for oral or intravenous injection, injection, mucous membrane, oral cavity, tissue, skin, etc.
  • Safety is considered important along with the nature.
  • the tocopherols and amino alcohols, which are essential components of the present invention are safe compounds from the general level of safety, and can be selected from them according to the purpose of use.
  • products including natural compounds, compressed oils, refined products, processed products, blended compositions, additives, and other substances containing unsaturated compounds, but the present invention can be applied to any form. is there. It can be applied at various stages such as the production stage, processing stage, distribution stage, and consumption stage.
  • the physical form and embodiment of the application of the present invention in the above-mentioned industrial fields are not limited, and any form is possible.
  • solid state, liquid state, gaseous state and coexistence thereof, hydrophobic phase, hydrophilic state Phase, organic solvent phase and its coexisting state, solubilized form, suspended form, emulsified form, gel form and coexisting state are also possible.
  • the reactivity of unsaturated compounds is high and deteriorates due to various reactions such as decomposition reaction, isomerization reaction, polymerization reaction, oxidation reaction, addition reaction and substitution reaction depending on the environmental conditions. Is likely to be different, and which elementary reactions are important to inhibit is important.
  • the stabilization efficiency is increased by the presence of the unsaturated compound and one or more of the components of the present invention in close proximity, the design of the type and ratio of the components of the present invention is changed according to the physical form. It is important to apply.
  • an additive in the case of an additive, it may vary depending on the acceptance conditions in each of the above fields, the physical form of the additive, the required attributes, and the like.
  • Solubilized compositions, suspension compositions, dispersion compositions, emulsified compositions, dry fine powders, microcapsules, gel compositions, solubilized, suspended, emulsified, solubilized compositions containing high concentrations of the unsaturated compounds to facilitate gelation A well-known method for making a solid or the like can be used. It is known that unsaturated compounds contain highly volatile low-molecular compounds generated by the reaction, and these low-molecular compounds cause sequential reactions and odors.
  • the low molecular compound can be removed during the production process of the additives.
  • powdering methods are possible for powdering. First, a solution, suspension, emulsified liquid, gelling liquid, etc. are produced, and then powdered by spray drying, spraying in a coagulating liquid or other methods You can also. Accordingly, a microstructured coexisting composition manufacturing method of the unsaturated compound and the component of the present invention by solubilization, suspension, emulsification, gelation, or the like is applied to the basic technology.
  • the polarity of the unsaturated compound changes from hydrophobic to hydrophilic depending on the structure and ratio of the hydrophobic portion and the hydrophilic portion in the molecule.
  • the polarity of the coexisting substance with the unsaturated compound may fluctuate in a wide range from hydrophobicity to hydrophilicity due to required attributes and the like.
  • the present invention is not limited by this, and a preferable micro-distribution state can be obtained by changing the polarity of the components of the present invention. That is, the polarity can be controlled by introducing a hydrophobic or hydrophilic group into the vitamin Es, amino alcohols, and polyphenols of the present invention.
  • Non-derivative vitamin Es are compounds in which the phenolic hydroxyl group is hydrophilic and the isoprenide group is hydrophobic.In a two-phase system, the phenol group is present in the vicinity of the aqueous phase, and it is considered that there is a high probability that the isoprenide group develops in the oil phase. It is possible.
  • Non-derivative amino alcohols are generally considered to be highly hydrophilic and have a high probability of moving around the aqueous phase unless they themselves have large non-polar groups in the molecule. It is considered that the vicinity of the unsaturated compound varies depending on the polarity and the probability that the unsaturated compound is present is high. Regardless of the physical form, it is desirable to make the constituent molecules easily collide with each other.
  • an amphiphilic dispersing agent or a surfactant is required to coexist with a wide range of polar variations of unsaturated compounds, vitamin Es, amino alcohols, and polyphenols. Is preferred.
  • amphiphilic substance There is no restriction on the amphiphilic substance, and the design is selected from a combination that can stabilize the compatibility with the constituents and the physical form of the system.Also, the safety, required attributes, and easy handling that are acceptable in the field Select considering pod cost It is possible to
  • OZW Oil-in-water
  • WZO water-in-oil
  • WZ O ZW water-in-oil-in-water
  • O ZWZ O oil-in-water-in-oil
  • a known nonionic or ionic compound can be used as the surfactant, but in an emulsified system, the presence of an anionic surfactant that attracts an amino alcohol to the interface is preferable for improving the chemical stability of the unsaturated compound.
  • a trend was identified. In particular, coexistence of a polymer compound having an anionic dissociation group and a hydrophobic group was found to be favorable for improving the chemical stability of the unsaturated compound and the stability of the emulsion system. If the degree of polymerization of both the amino alcohol and the anionic polymer is extremely large, the resulting ion complex may gel or precipitate, and in such a case, it is necessary to control the gel and apply the gel.
  • Catechins and tannins are polyphenol mixtures extracted from plants, and there is no limitation in the present invention depending on condensed type, non-condensed type, monomer, degree of polymerization and origin.
  • unsaturated compounds are mutually used as stabilizers for other unsaturated compounds, and in the above-mentioned industrial fields, the functions of various unsaturated compounds can be combined and used. It is often a mixture for handling, and it is common for natural products to coexist with various unsaturated compounds. Since these various embodiments cannot be illustrated, only a few representative examples of mixtures are given. Hereinafter, specific embodiments will be described as examples, but the present invention is not limited thereto.
  • Unsaturated compounds are very reactive compounds, and the reaction products contain highly volatile off-flavor substances, which is one factor that degrades the quality. Analyzing volatile substances is one of the evaluation methods.
  • Vitamin A is a very responsive compound, one of the main reaction products is ionone with very low threshold level and fern or raspberry fragrance, to determine the quality of vitamin A Can be used for Vitamin A is tasteless and odorless. Spray-dried Vitamin A is more stable, but reacts over time to become odorous of zionone. As a specific example, stabilization of retinoyl palmitate in corn oil was performed.
  • Example 1 Example 1
  • retinyl palmitate (BAS FZ100 I UZg content 55%) 100 g.
  • Em ix 80 (Eisaino 80% soybean tocopherol mouth) 15 g, sufingosine (content 90%) 3 Add O g.
  • the round bottom flask is equipped with a dip tube, which can be used to sparg the vessel with nitrogen. Volatile materials are collected on the cold finger capacitor. The sample is first degassed under a vacuum of 0.1 mm mercury. A nitrogen sparge is then introduced at a flow rate of 100 ml. Sample is 1
  • Example 2 Purification, storage and analysis were carried out in the same manner as in Example 1 except that sphingosine was used in Comparative Example 1, tocopherol was used in Comparative Example 1, and tocopherol and sphingosine were not used in Comparative Example 3.
  • Volatile substances at 50 ° C were analyzed by gas chromatography using the following method. Approximately 0.10 g of test substance is weighed directly into a cooled sparge tube and placed immediately on a Te kmar unit. The sample is heated to 50 ° C. and purged with nitrogen at a volume flow of 10-20 mI for 4 minutes. Volatiles are collected in traps containing Tena X GC adsorbent. When complete, pre-heat the trap to 100 ° C for 2 minutes.
  • Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Elapsed time (days) 90 90 60 60 Total peak area 21 52 9487 49907 685793 Zionone area 1 02 798 2579 9968 Although the stability is slightly improved, this is the effect according to the present invention.
  • Example 2 Comparative Example 3 Elapsed time (days) 90 90 60 60 Total peak area 21 52 9487 49907 685793 Zionone area 1 02 798 2579 9968 Although the stability is slightly improved, this is the effect according to the present invention.
  • Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Elapsed time (days) 90 90 60 60 60 Total peak area 21 52 9487 49907 685793 Zionone area 1 02 798 2579 9968 Although the stability is slightly improved, this is the effect according to the present invention.
  • Example 2 Comparative Example 3 Elapsed time (days) 90 90 60 60 60 Total peak area 21 52 9487 49907 685793 Zionone area 1 02 798 2579 99
  • An emulsion was produced using the oil-based additive of Example 1 as a part of the oil phase.
  • a vacuum emulsifier 30 g of the purified product of Example 1, Pemu Ien TR2 (good drastic polyacrylic polymer surfactant) 0.4 g, suspension of 0.02 g of butyl paraben ultrasonically dispersed
  • the solution was vacuumed and gum arabic 5 g gelatin A 100 bloom 5 g oleinated COS—PN (Kimitsu Chemical Chitosan 35% oleic oxide of rigo sugar) 1.5 g 1-amino-1-deoxyglucitol 0.5 g polyglycerin fatty acid ester (Polyme K-30) 1.5 g disodium ethylenediaminetetraacetate 0.01 g g methylparaben 0 .03 g Dehydroacetic acid 0.05 g While adding dropwise to a solution of 50 g of purified water, stir and emulsify with a homomix
  • Comparative Example 4 the oily additive of Example 1 was replaced with the oily additive of Comparative Example 1, and triethanolamine was used in place of oleinated COS-PN and 1-amino-1-dexoxyglucitol.
  • Comparative Example 5 the oily additive of Comparative Example 2 was used instead of the oily additive of Example 1, and in Comparative Example 6, the oily additive of Comparative Example 3 was used instead of the oily additive of Example 1.
  • an emulsion was prepared in the same manner as in Example 2 except that no amino alcohol was added.
  • Example 2 Comparative Example 4 Comparative Example 5 Comparative Example 6 Elapsed period (days) 1 20 1 20 90 90 Retinyl palmitate 93 52 21 ⁇ 10 Residual rate (%)
  • Example 2 has a higher residual ratio of retinyl palmitate as compared with the others, and thus has improved stability. This is an effect according to the present invention.
  • Example 3
  • Example 2 After mixing and stirring 100 g of the emulsion of Example 2 and 100 g of an aqueous solution containing 20% dextrin and 10% gelatin, the mixture was stirred at a temperature of 60 ° C using a single-component nozzle at a high pressure to remove hydrophobic silica from the spray tower. Sprayed in the fog. The still damp powder was dried in a fluidized drier at room temperature to a water content of 4.2% to produce a powder dosage form additive. Comparative Examples 7 to 9
  • Example 3 In the same manner as in Example 3 except that the emulsion of Example 2 was changed to the emulsions of Comparative Examples 4 to 6, a powder without addition of vitamin Es and a powder without addition of amino acids were not added. A powder was produced.
  • Example 3 Comparative Example 7 Comparative Example 8 Comparative Example 9 Elapsed period (days) 1 20 1 20 90 90 Retinyl palmitate 96 62 28 ⁇ 10 Residual rate (%)
  • Example 3 has a higher retinyl palmitate residual ratio and improved stability than the others, but this is an effect according to the present invention. Carotenoids are very unstable and a variety of stabilization methods have been tried but are not satisfactory.
  • Example 4
  • the sample is quickly heated to a temperature of 120 ° C by immersing the container in an oil bath maintained at 120 ° C.
  • the product is heated for 30 minutes under these conditions while maintaining a vacuum of 0.1-0.2 mm mercury. Then saturate with nitrogen and cool to 30 ° C.
  • the ratio of S-carotene: tocopherol: sphinganine: fat is 1: 0.27: 0.6: 2.5 by weight.
  • the oil-type additive produced in this manner was dispensed in 8 g portions into 10 10 ml brown bottles with aluminum foil laminated polyethylene sheets sandwiched between the lids, and stored in a 45 ° C constant temperature bath. We analyzed the progress. Comparative Example 10 0 to "!
  • Example 2 Purification, preservation and analysis were performed in the same manner as in Example 4 except that sphinganine was used in Comparative Example 10, tocopherol in Comparative Example 11, and tocopherol and sphinganine were not used in Comparative Example 12.
  • sphinganine was used in Comparative Example 10
  • tocopherol in Comparative Example 11
  • tocopherol and sphinganine were not used in Comparative Example 12.
  • the gas chromatographic analysis of Example 1 and Comparative Examples 1 to 3 the following results were obtained using a highly volatile odor component, which is a reaction product, as an indicator of stability.
  • Table 1-4 Analysis results of volatile substances
  • Example 4 Comparative Example 1 0 Comparative Example 1 1 Comparative Example 1 2 Elapsed time (days) 90 90 60 60 Total peak area 1 650 8591 35942 489793 Example 4 has less volatile matter generation and stability compared to others. This is an effect according to the present invention.
  • Example 4 Comparative Example 1 0 Comparative Example 1 1 Comparative Example 1 2 Elapsed time (days) 1 20 1 20 90 90 ⁇ -carotene 94 56 25 ⁇ 10 Residual rate (%)
  • Example 4 has a higher carotene residual rate and improved stability compared to the other forces. This is an effect according to the present invention.
  • Example 5 100 g fish oil 100 g Em ix 80 (containing Eza Z80% soybean tocopherol) in a 100 ml round-bottom flask equipped for use on a rotary evaporator protected from light 22 g DL sphingosine (content 90%) Insert The round bottom flask is equipped with a dip tube, which can be used to sparg the vessel with nitrogen. Volatile materials are collected on a cold finger condenser. The sample is first degassed under a vacuum of 0.1 mm mercury. Then a nitrogen sparge is introduced at a flow rate of 100 mI.
  • Comparative Example 10 was DL sphingosine
  • Comparative Example 11 was tocopherol
  • Comparative Example 12 was to purify and preserved and analyzed in the same manner as in Example 5 except that tocopherol and D-sphingosine were not blended. I did it.
  • the following results were obtained using a highly volatile odor component, which is a reaction product, as an indicator of stability. Table 1 6 Analysis results of volatile substances
  • Example 5 Comparative Example 13 Comparative Example 14 Comparative Example 15 Elapsed period (days) 90 90 60 60 Total peak area 1 369 7638 42896 482879
  • Example 5 produces less volatile substances and improves stability compared to the others, but this is an effect according to the present invention.
  • Example 6
  • Example 16 In Comparative Example 16, dalcosamine 2.0 g was replaced with triethanolamine 1.65 g. In Comparative Example 17, human tocopherol 0.8 g was not added. In Comparative Example 18, glucosamine 2.0 g. Example 6 except that triethanolamine was changed to 1.65 g and 0.8 g of tocopherol was not added. In the same manner as in Example 1, a skin external preparation was produced.
  • the above external preparation for skin was dispensed at a rate of 10 g into an aluminum tube coated with an epoxy resin on the inner surface, and sealed while excluding air.
  • the samples were stored in a thermostat at 45 ° C and analyzed with the progress. The analysis was carried out by extracting a soluble component from the sample with an organic solvent and performing liquid chromatography under the following conditions.
  • Detector UV370-380.
  • Table 1 7 Residual rate of coenzyme Q10 in skin external preparation
  • Example 6 Example 7 Comparative Example 16 Comparative Example 17 Comparative Example 18 Elapsed time (say) 1 50 1 50 1 50 90 90 Coenzyme Q10 89 96 55 1 9 ⁇ 10 Residual rate ( 0/0 )
  • Example 6 and Example 7 have a higher coenzyme Q10 retention rate and improved stability as compared with the others, but this is an effect according to the present invention.
  • Example 7 is more stable than Example 6, which is the effect according to the present invention.
  • Example 8 is more stable than Example 6, which is the effect according to the present invention.
  • An oily additive of retinol palmitate was produced in the same manner as in Example 1 except that tris (hydroxymethyl) aminoamino was used instead of sphingosine.
  • Comparative Example 19 Tocopherol in Comparative Example 20; Comparative Example 20: a partial isosuryl ether of tris (hydroxymethyl) aminomethane; Comparative Example 21: Partial iso-isomer of tocopherol and tris (hydroxymethyl) aminomethane Except that the steryl ether compound was not blended, it was produced, stored and analyzed in the same manner as in Example 7.
  • Example 8 and Comparative Examples 19 The analysis results of the volatile substances of the compositions of Examples 9 to 21 were similar to those of Example 1 and Comparative Examples 1 to 3, and are shown in the table below. Table 1 8 Analysis results of volatile substances
  • Example 8 Comparative Example 19 Comparative Example 20 Comparative Example 21 Elapsed period (days) 90 90 60 60 Total peak area 2480 9850 557 1 6 705469 Ionone area 1 09 889 351 1 1 0737
  • Example 8 compared with other volatile substances Although the generation of small amounts is improved and the stability is improved, this is the effect according to the present invention.
  • Example 9 Comparative Example 2 2 Comparative Example 2 3 Elapsed time (say) 1 80 90 90 Retinol 94 4 1 ⁇ 10 Residual rate (%)
  • Example 9 has a higher retinol residual ratio than the others and has improved stability. This is an effect according to the present invention.
  • the sensory change of the fragrance was compared with that of the sample which had been separately refrigerated at 2 ° C.
  • the sensory evaluation showed that no change was observed in Example 9, but a marked change was observed in the comparative example.
  • This is the effect according to the present invention.
  • the inventors of the present invention pursued intensive research in order to verify the novelty and usefulness of the present invention, and from the fact that they capture radicals that cannot be captured by tocopherol alone under the conditions of the present invention, etc.
  • the remarkable stabilizing effect of the stabilizer of the present invention is thought to be the result of a mechanism that can very effectively prevent elemental reactions of the degradation of unsaturated compounds that cannot be prevented by tocopherol alone.
  • the present invention relates to unsaturated compounds contained or blended in various products in a wide range of industrial fields such as foods, nutrients, pharmaceuticals, cosmetics, feeds, medical tools, chemicals, resins and rubbers, and particularly polyunsaturated compounds.
  • the function and effectiveness of the unsaturated compound and its contents are maintained for an extremely long time, and the change in color and fragrance is significantly reduced, thereby improving the commercial value. It provides extremely effective stabilizers and stabilization methods. This technology is especially valuable in the above fields where high safety is required.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Materials Engineering (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

Cette invention se rapporte à un stabilisant pour composés insaturés, qui comprend à la fois une vitamine E et un amino-alcool et qui produit sur les composés insaturés un effet stabilisant remarquablement accru. L'amino-alcool est de préférence un composé représenté par la formule générale (1) ou (2), et des composés insaturés sont notamment des rétinoïdes, des caroténoïdes, des isoprénoïdes, des acides gras polyinsaturés, des matières grasses et des huiles. Dans ces formules (1) et (2), les éléments R1 à R5 représentent chacun hydrogène, un hydrocarbure, un alcool, un sucre, un hydrate de carbone ou une amine.
PCT/JP2000/008495 1999-12-06 2000-12-01 Stabilisant pour composes insatures ou pate contenant ces composes et procede de stabilisation correspondant WO2001042390A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU15562/01A AU1556201A (en) 1999-12-06 2000-12-01 Stabilizer for unsaturated compounds or stuff containing the compounds and method of stabilization

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP11/376245 1999-12-06
JP37624599 1999-12-06

Publications (1)

Publication Number Publication Date
WO2001042390A1 true WO2001042390A1 (fr) 2001-06-14

Family

ID=18506818

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/008495 WO2001042390A1 (fr) 1999-12-06 2000-12-01 Stabilisant pour composes insatures ou pate contenant ces composes et procede de stabilisation correspondant

Country Status (2)

Country Link
AU (1) AU1556201A (fr)
WO (1) WO2001042390A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003306690A (ja) * 2002-02-18 2003-10-31 Nooburu:Kk 多価不飽和脂肪酸含有油脂組成物
JP2005529993A (ja) * 2002-06-11 2005-10-06 オリックス エナージー インターナショナル， インコーポレイティッド 炭化水素を含むディーゼル燃料にセタン価向上剤として安定化ベータカロチンを使用する方法および組成物
JP2006249050A (ja) * 2005-03-14 2006-09-21 Cyclochem:Kk 安定化された複合体及びその製造方法
JP2013147636A (ja) * 2011-12-22 2013-08-01 Snow Brand Milk Products Co Ltd 酸化抑制剤およびこれを用いた油脂含有飲食品
JP2013241406A (ja) * 2012-04-26 2013-12-05 Mikimoto Pharmaceut Co Ltd Ｏ／ｗ型エマルション組成物及び皮膚外用剤
JP2015119647A (ja) * 2013-12-20 2015-07-02 太陽化学株式会社 色素退色防止剤
WO2016148238A1 (fr) * 2015-03-19 2016-09-22 国立大学法人北海道大学 Inhibiteur d'oxydation et aliment et boisson contenant des graisses et des huiles l'utilisant

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1193027A (en) * 1967-10-27 1970-05-28 Hoffmann La Roche Antioxidant Compositions
JPS617382A (ja) * 1984-06-20 1986-01-14 Yuki Gosei Yakuhin Kogyo Kk 抗酸化組成物
JPH0496992A (ja) * 1990-08-15 1992-03-30 Kao Corp 酸化防止剤組成物
JPH05320048A (ja) * 1992-05-19 1993-12-03 Shiseido Co Ltd 抗酸化剤
US5648377A (en) * 1993-12-21 1997-07-15 Indena S.P.A. Formulations containing carotenoids an procarotenoids combined with polyphenols in the prevention of the damages due to an abnormal production of free radicals
JPH11335284A (ja) * 1998-05-21 1999-12-07 Isehan:Kk レチノイド類を含有する皮膚外用剤

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1193027A (en) * 1967-10-27 1970-05-28 Hoffmann La Roche Antioxidant Compositions
JPS617382A (ja) * 1984-06-20 1986-01-14 Yuki Gosei Yakuhin Kogyo Kk 抗酸化組成物
JPH0496992A (ja) * 1990-08-15 1992-03-30 Kao Corp 酸化防止剤組成物
JPH05320048A (ja) * 1992-05-19 1993-12-03 Shiseido Co Ltd 抗酸化剤
US5648377A (en) * 1993-12-21 1997-07-15 Indena S.P.A. Formulations containing carotenoids an procarotenoids combined with polyphenols in the prevention of the damages due to an abnormal production of free radicals
JPH11335284A (ja) * 1998-05-21 1999-12-07 Isehan:Kk レチノイド類を含有する皮膚外用剤

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003306690A (ja) * 2002-02-18 2003-10-31 Nooburu:Kk 多価不飽和脂肪酸含有油脂組成物
JP2005529993A (ja) * 2002-06-11 2005-10-06 オリックス エナージー インターナショナル， インコーポレイティッド 炭化水素を含むディーゼル燃料にセタン価向上剤として安定化ベータカロチンを使用する方法および組成物
JP2006249050A (ja) * 2005-03-14 2006-09-21 Cyclochem:Kk 安定化された複合体及びその製造方法
JP2013147636A (ja) * 2011-12-22 2013-08-01 Snow Brand Milk Products Co Ltd 酸化抑制剤およびこれを用いた油脂含有飲食品
JP2013241406A (ja) * 2012-04-26 2013-12-05 Mikimoto Pharmaceut Co Ltd Ｏ／ｗ型エマルション組成物及び皮膚外用剤
JP2015119647A (ja) * 2013-12-20 2015-07-02 太陽化学株式会社 色素退色防止剤
WO2016148238A1 (fr) * 2015-03-19 2016-09-22 国立大学法人北海道大学 Inhibiteur d'oxydation et aliment et boisson contenant des graisses et des huiles l'utilisant
JP2016175983A (ja) * 2015-03-19 2016-10-06 国立大学法人北海道大学 酸化抑制剤及びこれを用いた油脂含有飲食品
US11252974B2 (en) 2015-03-19 2022-02-22 National University Corporation Hokkaido University Oxidation inhibitor, and food and drink containing fats and oils using same

Also Published As

Publication number Publication date
AU1556201A (en) 2001-06-18

Similar Documents

Publication Publication Date Title
Barouh et al. Tocopherols as antioxidants in lipid‐based systems: The combination of chemical and physicochemical interactions determines their efficiency
Farooq et al. A comprehensive review on polarity, partitioning, and interactions of phenolic antioxidants at oil–water interface of food emulsions
EP2727580B1 (fr) Composition contenant de l'astaxanthine, son procédé de fabrication, et produit cosmétique associé
US8722104B2 (en) Composition containing organic substance having double bond with improved oxidative stability
CN104800119B (zh) 一种薰衣草精油脂质体及其制备方法
NZ279952A (en) Oil-in-water emulsion comprising digalactosyldiacylglycerols as carrier
CN105287666A (zh) 一种沙棘籽油的制备方法
TW200902072A (en) Emulsion-containing composition, food and topical product, and method of preventing coagulation of polyphenol compound
Chen et al. Lipid oxidation in base algae oil and water-in-algae oil emulsion: Impact of natural antioxidants and emulsifiers
DE102005031464A1 (de) Emulgatorsystem, Emulsion und deren Verwendung
JP3770922B2 (ja) 皮膚外用剤
JP2023086983A (ja) 水中油型乳化組成物、並びに、これを含む食品及び飲料
CN113038928A (zh) 防止香料原料和食品原料的氧化
Eisinaitė et al. Freeze‐drying of black chokeberry pomace extract–loaded double emulsions to obtain dispersible powders
WO2001042390A1 (fr) Stabilisant pour composes insatures ou pate contenant ces composes et procede de stabilisation correspondant
Ma et al. Antioxidant properties of lipid concomitants in edible oils: A review
EP2835055A2 (fr) Composition pour l'encapsulation d'acides gras polyinsaturés et procédé de préparation
JPH11335284A (ja) レチノイド類を含有する皮膚外用剤
KR20110044968A (ko) 식물 추출물 및 ｐｕｆａ 조합물
MX2012014872A (es) Compuesto activo estabilizado.
JP2000026270A (ja) レチノイド類を含有する皮膚外用剤
JP2001151664A (ja) レチノイド類を含有する皮膚外用剤
JP5007417B2 (ja) 会合物形成剤
JP4320798B2 (ja) 肝油、精製方法および用途
JP2007016000A (ja) チオクト酸含有組成物

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 543676

Kind code of ref document: A

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase