JP5750730B2 - ゴマ種子由来色素 - Google Patents
ゴマ種子由来色素 Download PDFInfo
- Publication number
- JP5750730B2 JP5750730B2 JP2011520496A JP2011520496A JP5750730B2 JP 5750730 B2 JP5750730 B2 JP 5750730B2 JP 2011520496 A JP2011520496 A JP 2011520496A JP 2011520496 A JP2011520496 A JP 2011520496A JP 5750730 B2 JP5750730 B2 JP 5750730B2
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- JP
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- Prior art keywords
- melanin
- reduced
- sesame
- weight percent
- reduced melanin
- 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.)
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- 229930195725 Mannitol Natural products 0.000 description 1
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- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
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- 241001494479 Pecora Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 241000238374 Sepia officinalis Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
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- 244000269722 Thea sinensis Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
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- 235000010980 cellulose Nutrition 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
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- 230000006378 damage Effects 0.000 description 1
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- 238000011156 evaluation Methods 0.000 description 1
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- 239000003925 fat Substances 0.000 description 1
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- 239000011521 glass Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000037308 hair color Effects 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
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- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
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- 239000011344 liquid material Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
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- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
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- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000002633 protecting effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000003009 skin protective agent Substances 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- ZNCPFRVNHGOPAG-UHFFFAOYSA-L sodium oxalate Chemical compound [Na+].[Na+].[O-]C(=O)C([O-])=O ZNCPFRVNHGOPAG-UHFFFAOYSA-L 0.000 description 1
- 229940039790 sodium oxalate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000003670 sublingual gland Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
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- 238000009120 supportive therapy Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B61/00—Dyes of natural origin prepared from natural sources, e.g. vegetable sources
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B69/00—Dyes not provided for by a single group of this subclass
- C09B69/10—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds
- C09B69/104—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds containing an indole dye, including melanine derivates
-
- 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
Description
mおよびnで示す各単位の各Y1または各Y2の少なくとも1つは、互いに独立して、NHであり、他方はCHであり、ただし、Y1とY2の両方が共にNHまたはCHであることはなく、
mおよびnで示す各単位のQ1およびQ2は、それぞれ互いに独立して水酸基、水酸陰イオン基、水素原子、または=O基であり、
ただし、還元型メラニン内にケトン官能基が存在する場合、水酸基のケトン官能基に対するモル比は50パーセント、より特に60パーセント、さらに特に75パーセントより高く、特に少なくとも約80パーセントであり、
mは1から約40であり、
nは1から約40であり、
m+n=2から約40、より特に3、4、5、6、7、などから約40まで、およびその間のあらゆる範囲と整数であり、式中、個々の"m"および個々の"n"の単量体インドール単位はそれぞれ同一であっても異なっていてもよい。
mおよびnで示す各単位の各Y1または各Y2の少なくとも1つは、互いに独立して、NHであり、他方はCHであり、ただし、Y1とY2の両方が共にNHまたはCHであることはなく、
mおよびnで示す各単位のQ1およびQ2は、それぞれ互いに独立して、水酸基、水酸陰イオン基、水素原子、または=O基であり、
ただし、還元型メラニン内にケトン官能基が存在する場合、水酸基のケトン官能基に対するモル比は50パーセント、より特に60パーセント、さらに特に75パーセントより高く、特に少なくとも約80パーセントであり、
mは1から約40であり、
nは1から約40であり、
m+n=2から約40、より特に3、4、5、6、7、などから約40まで、およびその間のあらゆる範囲と整数であり、式中、個々の"m"および個々の"n"の単量体単位はそれぞれ同一であっても異なっていてもよい。
Y1またはY2の少なくとも一方はNHであり、他方はCHであり、ただし、Y1とY2の両方がともにNHまたはCHであることはなく、
Q1およびQ2はそれぞれ互いに独立して、水酸基、水酸陰イオン基、水素原子、または=O基であり、
ただし、還元型メラニン中にケトン官能基がもし存在していれば、そのケトン官能基に対する水酸基のモル比は50パーセント、より特に60パーセント、さらに特に75パーセントより大きく、とりわけ少なくとも約100パーセントであり、
nは少なくとも2から約40、より特に約3、4、5、6、7、などから約40まで、およびその間のあらゆる範囲と整数である。
水酸化ナトリウム5gを脱イオン水500mlに溶解し、室温まで冷却して、次に粉砕した黒ゴマ種子100gを加えた。反応混合物の温度は25℃未満に維持し、24時間撹拌して濾過した。濾過ケーキを脱イオン水100mlで洗浄した。濾液を15%塩酸塩溶液と混合して酸性化し、反応混合物の温度を25℃未満に維持しながら、最終的なpHを約1.0とした。この懸濁液を遠心分離して固形物を脱イオン水30mlで洗浄した。この生成物を集めて減圧乾燥し(−0.095MPa、60℃、4時間)、続いてP2O5上で乾燥した。この乾燥色素を石油エーテルで洗い、再び乾燥させた。還元型メラニン色素の収率は、最初の出発物質を基準として約5%であった。この試料を、後述するUV−VIS吸収によるゴマ色素の判定における実施例3の生成物とした。
図1は単離生成物TEI V1のFTIRである。
粉砕した黒ゴマ種子10gを50mlの20%グリセリン水溶液および0.9%NaOHで懸濁した。その混合物を24時間撹拌し、濾過して、石油エーテルで洗浄した。この濾液と洗浄液を15%塩酸塩溶液で酸性化し、反応混合物の温度を25℃未満に維持しながら、最終的なpHを約1.0とした。この懸濁液を遠心分離して固形物を脱イオン水30mlで洗浄した。この生成物を集めて減圧乾燥し(−0.095MPa、60℃、4時間)、続いてP2O5上で乾燥した。還元型メラニン色素の収率は、最初の出発物質を基準として約3%であった。この試料を、後述するUV−VIS吸収によるゴマ色素の判定における実施例4の生成物と称する。
図2は単離生成物TEI V2のFTIRである。
図3は試料TEI V2のゲル浸透クロマトグラフィーによる分子量を表す。
10ml容量フラスコ中で、ルテイン10mgをテトラヒドロフラン(THF)5.0mlに溶解し、その後無水エタノールで容量まで満たした。
小ビーカーにTween−80を0.5gおよび脱イオン水を15g添加した。この溶液を均質になるまで撹拌し、次に還元ゴマメラニン2mgを添加した(実施例1)。この混合物を溶液が透明になるまで超音波処理した。
上記のルテイン溶液1.0mlを小ビーカーに加え、ルテインを溶解するために軽く振った。小ビーカーから液体1.0mlを10ml容量フラスコに移して脱イオン水で容量まで満たした。
ブランク試料を、還元ゴマ色素溶液を添加せずに上記の通りに調製した。
ルテイン/還元ゴマ試料とブランク試料を両方37℃の水浴中に置き、15Wランプで3時間露光した。446nmでの吸収率をUV−VIS分光光度計で測定して、分解速度を判定した。
DHA(ドコサヘキサエン酸)25mgをジメチルホルムアミド(DMF)25mlに溶解した。還元ゴマ色素(実施例1)1mgとアルギニン1mgを脱イオン水10mlに溶解した。DHA溶液5mlをゴマ色素溶液1mlと1%H2O21mlと共に小キュベットに入れた。
ブランク試料を、還元ゴマ色素溶液を添加せずに上記の通りに調製した。
この2つのキュベットを16時間密封した。試料を取り出し、ガス相クロマトグラフィーで分析してDHAの残存率を判定した。
試料中のDHAの残存率を下の表に示す。
ホスホリルコリン(PC)25mgをジメチルホルムアミド(DMF)25mlに溶解した。還元ゴマ色素(実施例1)1mgとアルギニン1mgを脱イオン水10mlに溶解した。PC溶液5mlを還元ゴマ色素溶液1mlと1%過酸化水素1mlと共に小キュベットに入れた。
ブランク試料を還元ゴマ色素溶液を添加せずに上記の通りに調製した。
この2つのキュベットを16時間密封放置した。試料をHPLC−ELSDで分析してPCの残存率を判定した。
試料中のホスホリルコリンの残存率を下の表に示す。
DHLAがコエンザイムQ10を保護できることが発見されており、このことはオーストリア特許AT504148A1、米国仮出願60/886,395、米国実用特許11/843,935およびPCT/IB2007/003623に記載され、その内容は全体が本明細書に組み込まれる。
驚くべき事に、還元ゴマ色素はDHLAのコエンザイムQ10を保護する効果を著しく増加できることが分かった。
試料の精製
色素試料2gをクロロホルム50ml、アセトン50mlおよびエタノール50mlで順に抽出した。その試料を室温で減圧乾燥した。ゴマ色素1gを水酸化ナトリウム1.0gと脱イオン水30mlに溶かした。クロロホルム約25mlとn−ブタノール5mlをその混合物に添加し、得られた混合物を十分に振盪し、次に遠心分離して下層を分離し、濾過した。この水層を1%水酸化ナトリウム溶液で洗浄した。全ての濾液を混合し、HClでpH値を3に調整した。この物質を濾過し、濾液のpHが約6になるまで得られたケーキを脱イオン水で洗浄した。この固体ケーキを減圧乾燥して精製色素を得た。
この全工程は温度管理をして行った。液体温度が25℃を越えることは許さず、不活性ガスを用いて反応を行うのに最良であることが分かった。
ゴマ色素20mgと水酸化ナトリウム1.0gを100ml容量フラスコ内で溶解した。この混合物を10分間超音波処理し、このフラスコを脱イオン水で容量まで満たした。試料2mlを10ml容量フラスコに移し、脱イオン水で容量まで満たした。最終溶液のUV−VIS吸収を500nmで測定した。
ヒトLDLを新鮮なヒト血液から超遠心分離によって得て、続いて4℃の暗所で24時間かけてPBS(pH7.4)10mMで透析した。LDLを異なる量のゴマ色素(pH7.4のPBSに超音波処理により溶解した)(それぞれ0,10,50,100,250,500μg/mL)と混合した。ゴマ抽出物は付録1で与えられた方法によって得られ、酸化と還元は付録1の記載通りに行った。反応はCuSO4(10μM)溶液を添加することによって開始され、試料はその後37℃で3時間保温静置された。共役ジエンの形成はUV/VIS分光光度計を用いて234nmで測定した。
色素試料の調製
およそ30gのゴマ種子を細かく粉砕し、およそ25%(m/m)HCL中で1時間煮沸した。その後、残渣を濾過により集めて105℃で乾燥した。乾燥残渣をSoxhelt抽出器で3時間(石油エーテル150mlにて)抽出し、油脂を除去した。
ゴマ色素は先に述べた工程(Horak&Gillette,1971)に従い、Ti3+で処理して還元した。ゴマ色素100mgを水に懸濁したものを、シュウ酸ナトリウム0.1Mと硫酸1Mを含む溶液20mlと混合した。次に、TiCl3を希釈硫酸(容量比で1:10)に溶解してTiCl3濃度を80mMとした液を5ml添加した。この混合物を120分間保温静置し、還元した色素を遠心により分離した。沈殿物を希釈硫酸と水で洗浄した。最後に、還元色素をミリQ水に対して24時間透析した。還元試料を蒸留水中に懸濁し、NaOHを0.1M滴下して加えてpHを7.5に調整した。このようにして得られた溶液をNalgene0.45−mmシリンジフィルターで濾過した。全ての操作はN2の下で行った。
色素の特性に対する酸化/還元の効果をさらに確認するために、ゴマ色素に酸化を施した。
アスコルビン酸5mgを0.01Mリン酸緩衝液pH=7.5に溶解し、最終容量を10mlにした。ゴマ色素(未処理試料または上記実施例4の還元試料)2mgをアスコルビン酸溶液に加えて超音波処理によって溶解した。
b)混合物を濾過し、水で洗浄して濾液を得る工程と、
c)濾液を酸性水溶液で処理する工程と、
d)ガス発生が止まって還元型メラニン色素が形成されるまで濾液に還元剤を添加する工程と、
からなる還元型メラニン色素の調製方法。
b)混合物を濾過し、水で洗浄して濾液を得る工程と、
c)濾液を酸性水溶液で室温以下で処理し、pHを約1から約7未満の間にする工程と、
d)還元型メラニン色素を集める工程と、
からなる還元型メラニン色素の調製方法。
式中、mおよびnで示す各単位のQ1およびQ2は、それぞれ互いに独立して水酸基、水酸陰イオン基、水素原子、または=O基であり、
還元型メラニン内のケトン官能基に対する水酸基のモル比は50パーセントより大きく、
式中、
式中、mは1から約40であり、
式中、nは1から約40であり、
式中、m+nは2から約40であり、
式中の各単量体単位であるmとnは同一であっても異なっていてもよい。
Claims (12)
- 濃度0.04mg/ml水溶液において500nmでのUV−VIS吸収値が約0.10から0.16のゴマ抽出物を含む組成物であって、ゴマ抽出物が還元型メラニンを含む組成物。
- 還元型メラニンの分子量が約264から約5400ダルトンの間である請求項1に記載の組成物。
- 還元型メラニンの炭素含量が約35から約57重量パーセントであり、水素含量が約5から約10重量パーセントであり、窒素含量が約5から約10重量パーセントである請求項1または2に記載の組成物。
- 還元型メラニンの硫黄含量が約1重量パーセント未満である請求項1−3のいずれかに記載の組成物。
- 還元型メラニンの赤外スペクトルが約3400cm-1、約2950cm-1、約1600から約1650cm-1、約1380から約1400cm-1、約1260cm-1、および約1170cm-1において吸収バンドを示す請求項1−4のいずれかに記載の組成物。
- 還元型メラニンの分子量が約264から約2000ダルトンの間である請求項1−5のいずれかに記載の組成物。
- 還元型メラニンの分子量が約400から約1600ダルトンの間である請求項6に記載の組成物。
- 充分な量の請求項1−7のいずれかに記載の組成物とビタミンとを混合する工程を含む、ビタミンの酸化を防止または減少させる方法。
- ビタミンがビタミンCである請求項8に記載の方法。
- LDLに対して十分な量の請求項1−7のいずれかに記載の組成物を含む、LDLの酸化を減少または阻害するための医薬組成物。
- 治療上有効量の請求項1−7のいずれかに記載の組成物を含む、循環器疾患を治療または予防するための医薬組成物。
- 循環器疾患がアテローム性動脈硬化症または冠動脈疾患である請求項11に記載の医薬組成物。
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