JP2021078397A - Lipid decrease promoter - Google Patents
Lipid decrease promoter Download PDFInfo
- Publication number
- JP2021078397A JP2021078397A JP2019208089A JP2019208089A JP2021078397A JP 2021078397 A JP2021078397 A JP 2021078397A JP 2019208089 A JP2019208089 A JP 2019208089A JP 2019208089 A JP2019208089 A JP 2019208089A JP 2021078397 A JP2021078397 A JP 2021078397A
- Authority
- JP
- Japan
- Prior art keywords
- pqq
- daphnia magna
- agent
- salt
- fat
- 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.)
- Pending
Links
- 150000002632 lipids Chemical class 0.000 title claims abstract description 59
- MMXZSJMASHPLLR-UHFFFAOYSA-N pyrroloquinoline quinone Chemical compound C12=C(C(O)=O)C=C(C(O)=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 MMXZSJMASHPLLR-UHFFFAOYSA-N 0.000 claims abstract description 221
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 18
- 230000001737 promoting effect Effects 0.000 claims abstract description 17
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- 230000009467 reduction Effects 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 31
- 230000001850 reproductive effect Effects 0.000 claims description 28
- 210000000577 adipose tissue Anatomy 0.000 claims description 9
- 230000004060 metabolic process Effects 0.000 claims description 5
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 241001494246 Daphnia magna Species 0.000 description 77
- 239000003795 chemical substances by application Substances 0.000 description 45
- 235000013305 food Nutrition 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 230000006870 function Effects 0.000 description 32
- 239000003925 fat Substances 0.000 description 29
- 238000009395 breeding Methods 0.000 description 25
- 230000001488 breeding effect Effects 0.000 description 25
- 230000000052 comparative effect Effects 0.000 description 20
- 241000195649 Chlorella <Chlorellales> Species 0.000 description 14
- 208000008589 Obesity Diseases 0.000 description 13
- 235000020824 obesity Nutrition 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 235000013601 eggs Nutrition 0.000 description 12
- 239000004367 Lipase Substances 0.000 description 9
- 102000004882 Lipase Human genes 0.000 description 9
- 108090001060 Lipase Proteins 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 235000019421 lipase Nutrition 0.000 description 9
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 101150022052 UCP1 gene Proteins 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- UFVBOGYDCJNLPM-UHFFFAOYSA-L disodium;9-carboxy-4,5-dioxo-1h-pyrrolo[2,3-f]quinoline-2,7-dicarboxylate Chemical compound [Na+].[Na+].C12=C(C([O-])=O)C=C(C([O-])=O)N=C2C(=O)C(=O)C2=C1NC(C(=O)O)=C2 UFVBOGYDCJNLPM-UHFFFAOYSA-L 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- -1 alkali metal salt Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 108010050258 Mitochondrial Uncoupling Proteins Proteins 0.000 description 4
- 102000015494 Mitochondrial Uncoupling Proteins Human genes 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002073 fluorescence micrograph Methods 0.000 description 4
- 235000013376 functional food Nutrition 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000037356 lipid metabolism Effects 0.000 description 4
- 238000001000 micrograph Methods 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 239000007901 soft capsule Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000238578 Daphnia Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000002123 RNA extraction Methods 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- 241000207199 Citrus Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 244000144987 brood Species 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000037081 physical activity Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- XFZJEEAOWLFHDH-UHFFFAOYSA-N (2R,2'R,3R,3'R,4R)-3,3',4',5,7-Pentahydroxyflavan(48)-3,3',4',5,7-pentahydroxyflavan Natural products C=12OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C(O)C=C(O)C=1C(C1=C(O)C=C(O)C=C1O1)C(O)C1C1=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-UHFFFAOYSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 240000009108 Chlorella vulgaris Species 0.000 description 1
- 235000007089 Chlorella vulgaris Nutrition 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 229940122858 Elastase inhibitor Drugs 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000034347 Faecal incontinence Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 101000621427 Homo sapiens Wiskott-Aldrich syndrome protein Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229940086609 Lipase inhibitor Drugs 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 244000090599 Plantago psyllium Species 0.000 description 1
- 235000010451 Plantago psyllium Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 description 1
- MOJZMWJRUKIQGL-FWCKPOPSSA-N Procyanidin C2 Natural products O[C@@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c([C@H]3[C@H](O)[C@@H](c4cc(O)c(O)cc4)Oc4c3c(O)cc(O)c4)c(O)cc(O)c2[C@@H]1c1c(O)cc(O)c2c1O[C@@H]([C@H](O)C2)c1cc(O)c(O)cc1 MOJZMWJRUKIQGL-FWCKPOPSSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000533293 Sesbania emerus Species 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 206010041969 Steatorrhoea Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 241000282887 Suidae Species 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000000386 athletic effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000001593 brown adipocyte Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- ZYWFEOZQIUMEGL-UHFFFAOYSA-N chloroform;3-methylbutan-1-ol;phenol Chemical compound ClC(Cl)Cl.CC(C)CCO.OC1=CC=CC=C1 ZYWFEOZQIUMEGL-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000002247 constant time method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 235000020805 dietary restrictions Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- LNGNZSMIUVQZOX-UHFFFAOYSA-L disodium;dioxido(sulfanylidene)-$l^{4}-sulfane Chemical compound [Na+].[Na+].[O-]S([O-])=S LNGNZSMIUVQZOX-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000000678 effect on lipid Effects 0.000 description 1
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 1
- 239000003602 elastase inhibitor Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical class C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229960000299 mazindol Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- HGVVOUNEGQIPMS-UHFFFAOYSA-N procyanidin Chemical compound O1C2=CC(O)=CC(O)=C2C(O)C(O)C1(C=1C=C(O)C(O)=CC=1)OC1CC2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 HGVVOUNEGQIPMS-UHFFFAOYSA-N 0.000 description 1
- 229920002414 procyanidin Polymers 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000037384 skin absorption Effects 0.000 description 1
- 231100000274 skin absorption Toxicity 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 208000001162 steatorrhea Diseases 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、新規な脂質減少促進剤及びその製造方法、当該脂質減少促進剤を含む組成物、及び脂質の減少促進方法に関する。 The present invention relates to a novel lipid reduction accelerator and a method for producing the same, a composition containing the lipid reduction accelerator, and a method for promoting lipid reduction.
肥満は現代社会における最も重大な疾患の一つであるが、その主たる要因は脂肪の過剰摂取である。脂肪の過剰摂取は、肥満のみならず、肥満に起因してメタボリックシンドローム、糖尿病、高脂血症、高血圧、動脈硬化などの生活習慣病を発症させることが知られている。 Obesity is one of the most serious illnesses in modern society, the main factor being fat overdose. It is known that excessive intake of fat causes not only obesity but also lifestyle-related diseases such as metabolic syndrome, diabetes, hyperlipidemia, hypertension, and arteriosclerosis due to obesity.
肥満に対する治療薬としては、食欲抑制剤であるマジンドールや、リパーゼ阻害剤であるオルリスタットなどが使用されている。しかしながら、これらの医薬では、口渇、便秘、吐き気、不眠、頭痛及び動悸など、並びにオイルスポット、鼓腸、急な便意、排便の増加、便失禁、直腸からの漏れ、上部呼吸器感染及び脂肪便などの副作用がそれぞれ報告されており、必ずしも安全性は十分であるとは言えない。 As a therapeutic agent for obesity, mazindol, which is an appetite suppressant, orlistat, which is a lipase inhibitor, and the like are used. However, these medications include dry mouth, constipation, nausea, insomnia, headache and palpitation, as well as oil spots, flatulence, fecal urgency, increased bowel movements, fecal incontinence, rectal leakage, upper respiratory infections and steatorrhea. Side effects such as these have been reported, and it cannot always be said that the safety is sufficient.
肥満を予防するためには、食事制限により摂取カロリーを減らすことが有効な手段である。しかしながら、そのためには十分な栄養指導を受けなければならず、実質的に日常生活での実施は困難である場合が多い。そのため、十分な安全性を有し、且つ効率的に肥満を解消することのできる物質が強く求められている。 In order to prevent obesity, it is an effective means to reduce calorie intake by dietary restriction. However, in order to do so, sufficient nutritional guidance must be received, and it is often difficult to implement it in daily life. Therefore, there is a strong demand for a substance having sufficient safety and capable of efficiently eliminating obesity.
ところで、ピロロキノリンキノン（以下、「ＰＱＱ」ともいう。）は、多くの食品に含まれるビタミン様の物質である。（非特許文献１）。乳酸脱水素酵素に結合してその機能を向上させることが報告されている（非特許文献２）。 By the way, pyrroloquinoline quinone (hereinafter, also referred to as "PQQ") is a vitamin-like substance contained in many foods. (Non-Patent Document 1). It has been reported that it binds to lactate dehydrogenase to improve its function (Non-Patent Document 2).
ＰＱＱはこれまでに脳機能の改善（特許文献１，２，３）に注目され、その応用がなされてきた。また、血糖値の改善効果も報告されている。 PQQ has been focused on improving brain function (Patent Documents 1, 2 and 3) and has been applied to it. In addition, the effect of improving blood glucose level has also been reported.
しかしながら、このようなＰＱＱを肥満の解消のために使用することは知られておらず、また脂質減少促進剤として利用することはこれまでに報告されていない。また、ＰＱＱを生殖機能の改善のために使用することも知られておらず、生殖機能改善剤として利用することはこれまでに報告されていない。 However, it is not known that such PQQ is used for the elimination of obesity, and it has not been reported so far that it is used as a lipid reduction promoter. In addition, it is not known that PQQ is used for improving reproductive function, and its use as a reproductive function improving agent has not been reported so far.
本発明の目的は、肥満の解消に有用な物質として上記ＰＱＱを用い、安全で、且つ効率的に脂質の減少を促進することのできる新規な脂質減少促進剤及びその製造方法、当該脂質減少促進剤を含む組成物、及び脂質の減少促進方法を提供することにある。 An object of the present invention is to use the above PQQ as a substance useful for eliminating obesity, a novel lipid reduction promoter capable of safely and efficiently promoting lipid reduction, a method for producing the same, and the lipid reduction promotion. It is an object of the present invention to provide a composition containing an agent and a method for promoting the reduction of lipids.
また、本発明の他の目的は、生殖機能の改善に有用な物質として上記ＰＱＱを用い、新規な生殖機能改善剤を提供することにある。 Another object of the present invention is to provide a novel reproductive function improving agent by using the above PQQ as a substance useful for improving reproductive function.
本発明者らは、上記課題を解決すべく鋭意検討した結果、驚くべきことにＰＱＱ及び／又はその塩に脂質の減少を促進する作用があることを見出した。かかる知見に基づき、本発明者らは、さらに研究を重ねることによって本発明を完成するに至った。 As a result of diligent studies to solve the above problems, the present inventors have surprisingly found that PQQ and / or a salt thereof has an action of promoting the reduction of lipids. Based on such findings, the present inventors have completed the present invention through further research.
すなわち、本発明は以下に示すとおりである。
〔１〕
ピロロキノリンキノン及び／又はその塩を有効成分として含む、脂質減少促進剤。
〔２〕
前記ピロロキノリンキノンの塩が、ピロロキノリンキノン二ナトリウム塩である、〔１〕に記載の剤。
〔３〕
運動強度３メッツ以上の運動をしているとき、または、前記運動の開始前１時間以内もしくは終了後１時間以内に摂取する、〔１〕又は〔２〕に記載の剤。
〔４〕
前記脂質減少促進が、体脂肪代謝促進である、〔１〕〜〔３〕のいずれか一項に記載の剤。
〔５〕
〔１〕〜〔４〕のいずれか一項に記載の剤を含む、組成物。
〔６〕
〔１〕〜〔４〕のいずれか一項に記載の剤を使用する、脂質の減少促進方法。
〔７〕
ピロロキノリンキノン及び／又はその塩を有効成分として含む、生殖機能改善剤。
That is, the present invention is as shown below.
[1]
A lipid reduction promoter containing pyrroloquinoline quinone and / or a salt thereof as an active ingredient.
[2]
The agent according to [1], wherein the salt of pyrroloquinoline quinone is a disodium salt of pyrroloquinoline quinone.
[3]
The agent according to [1] or [2], which is ingested when exercising with an exercise intensity of 3 mets or more, or within 1 hour before the start of the exercise or within 1 hour after the end of the exercise.
[4]
The agent according to any one of [1] to [3], wherein the promotion of lipid reduction is promotion of body fat metabolism.
[5]
A composition comprising the agent according to any one of [1] to [4].
[6]
A method for promoting lipid reduction, using the agent according to any one of [1] to [4].
[7]
A reproductive function improving agent containing pyrroloquinoline quinone and / or a salt thereof as an active ingredient.
本発明によれば、安全で、かつ効率的に脂質の減少を促進することのできる新規な脂質減少促進剤及びその製造方法、当該脂質減少促進剤を含む組成物、並びに、脂質の減少促進方法を提供することができる。 According to the present invention, a novel lipid reduction accelerator and a method for producing the same, a composition containing the lipid reduction accelerator, and a method for promoting lipid reduction, which can safely and efficiently promote the reduction of lipids. Can be provided.
また、本発明によれば、新規な生殖機能改善剤を提供することもできる。 Further, according to the present invention, it is also possible to provide a novel reproductive function improving agent.
さらに、本発明で用いられるＰＱＱ及び／又はその塩は、国内では食品に指定されており、飲食品としても使用可能であることから、本発明の剤及び組成物は、ヒト等の動物に対して十分な安全性を有しているといえる。 Furthermore, since PQQ and / or a salt thereof used in the present invention is designated as a food in Japan and can be used as a food or drink, the agent and composition of the present invention can be applied to animals such as humans. It can be said that it has sufficient safety.
以下、本発明を実施するための形態について詳細に説明するが、本発明はこれに限定されるものではなく、その要旨を逸脱しない範囲で様々な変形が可能である。なお、脂質減少促進剤を第１実施形態とし、生殖機能改善剤を第２実施形態とする。また、第１実施形態と第２実施形態を区別する必要ない箇所については、本実施形態という。 Hereinafter, embodiments for carrying out the present invention will be described in detail, but the present invention is not limited to this, and various modifications can be made without departing from the gist thereof. The lipid reduction promoter is the first embodiment, and the reproductive function improving agent is the second embodiment. Further, a portion where it is not necessary to distinguish between the first embodiment and the second embodiment is referred to as the present embodiment.
〔第１実施形態：脂質減少促進剤〕
本発明者らは、ＰＱＱの生理機能を研究する過程において、ＰＱＱを添加した条件下で微小甲殻類を生育して、ＰＱＱが脂質の減少を促進する作用を有することを見出した。すなわち、第１実施形態の脂質減少促進剤（以下、「第１実施形態の剤」ともいう。）はこの知見に基づくものであり、ピロロキノリンキノン及び／又はその塩を有効成分として含むものである。
[First Embodiment: Lipid reduction accelerator]
In the process of studying the physiological function of PQQ, the present inventors have found that PQQ has an action of promoting the reduction of lipids by growing microcrustaceans under the condition of adding PQQ. That is, the lipid reduction promoter of the first embodiment (hereinafter, also referred to as "the agent of the first embodiment") is based on this finding, and contains pyrroloquinoline quinone and / or a salt thereof as an active ingredient.
本実施形態において用いられるＰＱＱとは、化学式１に記載される化学構造を有している化合物である。また、ＰＱＱは水溶液中では化学式２に示される構造を有することもある。
また、ＰＱＱの塩は上記カルボキシル基がアルカリ金属イオン等と塩を形成したものである。ＰＱＱの塩としては、特に制限されないが、たとえば、ナトリウムやカリウムなどのアルカリ金属塩（具体的には、ＰＱＱナトリウム、ＰＱＱカリウムなど）、カルシウムやマグネシウムなどのアルカリ土類金属塩（具体的には、ＰＱＱカルシウム、ＰＱＱマグネシウムなど）、ＰＱＱアルミニウム、ＰＱＱ亜鉛、ＰＱＱマンガン及びＰＱＱ鉄などを挙げることができる。このなかでもＰＱＱの塩は、好ましくはＰＱＱナトリウム、ＰＱＱカルシウムである。特にナトリウム塩はモノナトリウム、ジナトリウム、トリナトリウムを使用でき、特にピロロキノリンキノン二ナトリウムが入手しやすく使用しやすい。尚、本実施形態においてＰＱＱの塩は水和物であってもよい。 Further, the salt of PQQ is a salt formed by the above-mentioned carboxyl group with an alkali metal ion or the like. The salt of PQQ is not particularly limited, but for example, an alkali metal salt such as sodium or potassium (specifically, PQQ sodium, PQQ potassium, etc.) or an alkaline earth metal salt such as calcium or magnesium (specifically, PQQ potassium). , PQQ Calcium, PQQ Magnesium, etc.), PQQ Aluminum, PQQ Zinc, PQQ Manganese, PQQ Iron, etc. Among these, the salt of PQQ is preferably PQQ sodium and PQQ calcium. In particular, monosodium, disodium, and trisodium can be used as the sodium salt, and pyrroloquinoline quinone disodium is particularly easy to obtain and use. In this embodiment, the salt of PQQ may be a hydrate.
ＰＱＱ及びその塩は、それらの入手方法については特に限定されず、動物や植物に由来する天然のもの、或いは化学合成法や発酵法などにより得られるもののいずれであってもよい。得られるＰＱＱ及びその塩の純度及び製造コスト等に基づき、好適なＰＱＱ及びその塩の製造方法を適宜選択することができる。また、ＰＱＱ及びその塩としては、市販されているＰＱＱ及びその塩を使用することができる。そのような市販品としては、例えば、三菱瓦斯化学株式会社で製造又は販売されている商品が挙げられる。また、本実施形態では、発酵法を利用して細菌（ＰＱＱ菌等）を培養しながら得られたＰＱＱ又はＰＱＱを含む組成物（飲食品等）をそのまま、或いは加工して使用することもできる。 The method of obtaining PQQ and its salt is not particularly limited, and it may be either a natural one derived from an animal or a plant, or one obtained by a chemical synthesis method, a fermentation method, or the like. A suitable method for producing PQQ and its salt can be appropriately selected based on the purity of the obtained PQQ and its salt, the production cost, and the like. As the PQQ and its salt, commercially available PQQ and its salt can be used. Examples of such commercial products include products manufactured or sold by Mitsubishi Gas Chemical Company, Inc. Further, in the present embodiment, PQQ or a composition containing PQQ (food and drink, etc.) obtained while culturing bacteria (PQQ bacteria, etc.) using a fermentation method can be used as it is or after being processed. ..
本明細書において、「脂質減少促進剤」とは、生体内における脂質の減少を促進する作用を有する剤を意味する。 As used herein, the term "lipid reduction promoter" means an agent having an action of promoting lipid reduction in a living body.
本明細書において「脂質」とは、生体内に存在する水不溶性の物質の総称である。また、代謝対象である脂質は、常温で固体であってもよく、或いは液体であってもよいが、固体であることが好ましい。尚、常温とは、第十六改正日本薬局方の通則に従い、通常１５〜２５℃であることを示す。脂質には、例えば、単純脂質（中性脂肪など）、複合脂質（リン脂質、糖脂質など）、誘導脂質（脂肪酸、コレステロールなど）などが含まれる。これらのうち第１実施形態で対象とされる脂質としては、単純脂質が好ましく、その中でも中性脂肪がより好ましく、最も好ましくはトリアシルグリセロール（トリグリセリド）である。 As used herein, the term "lipid" is a general term for water-insoluble substances existing in the living body. The lipid to be metabolized may be a solid at room temperature or a liquid, but is preferably a solid. The normal temperature means that the temperature is usually 15 to 25 ° C in accordance with the general rules of the 16th revised Japanese Pharmacopoeia. Lipids include, for example, simple lipids (neutral fats, etc.), complex lipids (phospholipids, glycolipids, etc.), inducible lipids (fatty acids, cholesterol, etc.) and the like. Of these, the lipid targeted in the first embodiment is preferably a simple lipid, more preferably a neutral fat, and most preferably triacylglycerol (triglyceride).
本明細書において脂質の「減少代謝」とは、主に脂質を分解することを示すが、脂質の量を減少することができる限り、特にこれに限定されるわけではない。
本発明において、「脂質代謝促進」には、生体内の脂質を減少する（「脂質代謝促進」又は「脂質の燃焼」と称する場合もある）概念と、体外より摂取される脂質を低減するなどして生体内への脂質の蓄積を抑制する概念と、が包含される。
As used herein, the term "reduced metabolism" of lipids mainly refers to the decomposition of lipids, but is not particularly limited as long as the amount of lipids can be reduced.
In the present invention, "promotion of lipid metabolism" includes the concept of reducing lipids in the living body (sometimes referred to as "promotion of lipid metabolism" or "burning of lipids") and reduction of lipids ingested from outside the body. The concept of suppressing the accumulation of lipids in the living body is included.
第１実施形態における脂肪減少は、脂質を分解して生体内の脂質を減少する脂質代謝促進であることが好ましい。また、脂質は、生体内の場所に応じて、体脂肪（皮下脂肪、内臓脂肪など）及び血中脂質などが例示されるが、好ましくは体脂肪を分解して生体内の体脂肪を減少する体脂肪代謝促進であることが好ましい。さらに、脂質の化合物種の観点からは、第１実施形態における脂肪減少は、中性脂肪代謝促進であることが好ましい。 The fat reduction in the first embodiment is preferably a promotion of lipid metabolism that decomposes lipids and reduces lipids in the living body. Examples of the lipid include body fat (subcutaneous fat, visceral fat, etc.) and blood lipid, depending on the location in the living body, but preferably, the body fat is decomposed to reduce the body fat in the living body. It is preferable to promote body fat metabolism. Furthermore, from the viewpoint of lipid compound species, the fat reduction in the first embodiment preferably promotes triglyceride metabolism.
第１実施形態の剤は、脂質減少促進作用を通じて、肥満（「肥満症」とも称する）の予防及び治療、肝臓脂肪減少促進、体脂肪減少促進等のための食品又は医薬品として有用である。さらに、第１実施形態の剤は、肥満に起因して発症する疾患の予防及び治療のための食品又は医薬品としても有用である。そのような疾患としては、特に限定されないが、例えば、メタボリックシンドローム、脂肪肝、糖尿病（２型糖尿病を含む）、高脂血症、高血圧症、動脈硬化症などが挙げられる。 The agent of the first embodiment is useful as a food or pharmaceutical for prevention and treatment of obesity (also referred to as "obesity"), promotion of liver fat reduction, promotion of body fat reduction, etc. through a lipid reduction promoting action. Furthermore, the agent of the first embodiment is also useful as a food or pharmaceutical product for the prevention and treatment of diseases caused by obesity. Such diseases include, but are not limited to, metabolic syndrome, fatty liver, diabetes (including type 2 diabetes), hyperlipidemia, hypertension, arteriosclerosis and the like.
第１実施形態の剤は、運動と併用することが好ましい。より具体的には、運動強度３メッツ以上の運動をしているとき、または、その運動の開始前１時間以内もしくは終了後１時間以内に摂取することが好ましい。このようなタイミングで、第１実施形態の剤を投与又は摂取することにより、運動による脂質代謝をより効率的に促進することができる。 The agent of the first embodiment is preferably used in combination with exercise. More specifically, it is preferable to take it when exercising with an exercise intensity of 3 mets or more, or within 1 hour before the start of the exercise or within 1 hour after the end of the exercise. By administering or ingesting the agent of the first embodiment at such a timing, lipid metabolism by exercise can be promoted more efficiently.
「メッツ」は運動強度を示す単位であり、ある身体活動時のエネルギー消費量が、安静時エネルギー消費量の何倍にあたるかを指数化したものである。メッツは、安静状態を維持するために必要な酸素量（酸素必要量）を性別や体重に関わらず３．５ｍｌ／ｋｇ／分を１単位とする。特に制限されないが、例えば、座って安静にしている状態が１メッツ、普通の歩行が３メッツに相当し、３メッツの強度が中強度とされる。なお、第１実施形態において、剤と併用される運動の種類は、運動強度３メッツ以上の身体活動であれば、特に制限されない。 "METs" is a unit that indicates exercise intensity, and is an index of how many times the energy consumption during a certain physical activity is equivalent to the energy consumption at rest. Mets sets the amount of oxygen required to maintain a resting state (oxygen requirement) to 3.5 ml / kg / min as one unit regardless of gender or body weight. Although not particularly limited, for example, the state of sitting and resting corresponds to 1 MET, normal walking corresponds to 3 METs, and the intensity of 3 METs is medium intensity. In the first embodiment, the type of exercise used in combination with the agent is not particularly limited as long as it is a physical activity with an exercise intensity of 3 METs or more.
〔第２実施形態：生殖機能改善剤〕
本発明者らは、ＰＱＱの生理機能を研究する過程において、ＰＱＱを添加した条件下で微小甲殻類を生育して、ＰＱＱが生殖機能を改善する作用を有することを見出した。すなわち、第２実施形態の生殖機能改善剤（以下、「第２実施形態の剤」ともいう。）はこの知見に基づくものであり、ピロロキノリンキノン及び／又はその塩を有効成分として含むものである。
[Second embodiment: reproductive function improving agent]
In the process of studying the physiological function of PQQ, the present inventors have found that PQQ has an action of improving reproductive function by growing microcrustaceans under the condition of adding PQQ. That is, the reproductive function improving agent of the second embodiment (hereinafter, also referred to as "the agent of the second embodiment") is based on this finding, and contains pyrroloquinoline quinone and / or a salt thereof as an active ingredient.
なお、第２実施形態の剤で用いるピロロキノリンキノン及び／又はその塩は、第１実施形態で説明したものと同様とする。 The pyrroloquinoline quinone and / or a salt thereof used in the agent of the second embodiment is the same as that described in the first embodiment.
本明細書において、「生殖機能改善剤」とは、生体の生殖機能を改善する作用を有する剤を意味する。 As used herein, the term "reproductive function improving agent" means an agent having an action of improving the reproductive function of a living body.
本明細書において、「生殖機能」とは、種を維持するために新しい個体をつくる機能であり、卵巣に関する機能など雌に備わる生殖機能と、精巣に関する機能など雄に備わる生殖機能とが含まれる。このなかで、第２実施形態の剤の対象となる生殖機能としては、雌に備わる生殖機能が好ましく、卵巣における卵子の生産や卵子の成熟に関する生殖機能が好ましい。 In the present specification, the "reproductive function" is a function of creating a new individual to maintain a species, and includes a reproductive function of a female such as a function related to an ovary and a reproductive function of a male such as a function related to the testis. .. Among these, as the reproductive function targeted by the agent of the second embodiment, the reproductive function provided in the female is preferable, and the reproductive function related to the production of an egg in the ovary and the maturation of the egg is preferable.
本明細書において生殖機能の「改善」とは、機能の向上に当たるものであれば特に制限されないが、例えば、卵巣において生産される卵子のうち、成熟卵子数の増加などが挙げられる。 In the present specification, the “improvement” of reproductive function is not particularly limited as long as it corresponds to the improvement of the function, and examples thereof include an increase in the number of mature eggs among the eggs produced in the ovary.
〔使用態様〕
本実施形態の剤は、脂質の減少促進あるいは生殖機能の改善に用いる方法であれば特に制限されず、例えば、ヒト用又は動物用の、食品、機能性食品、医薬品又は医薬部外品として使用することができる。ここでいう機能性食品とは、健康食品、栄養補助食品、栄養機能食品、栄養保険食品等、健康の維持あるいは食事にかわり栄養補給の目的で摂取する食品を意味する。具体的な形態としてはカプセル剤、タブレット、チュアブル、錠剤、ドリンク剤等が挙げられるが、これらに限定されるものではない。
[Usage mode]
The agent of the present embodiment is not particularly limited as long as it is a method used for promoting lipid reduction or improving reproductive function, and is used, for example, as a food, functional food, pharmaceutical or quasi-drug for humans or animals. can do. The term "functional food" as used herein means foods such as health foods, nutritional supplements, nutritional functional foods, nutritional insurance foods, etc., which are ingested for the purpose of maintaining health or supplementing nutrition instead of diet. Specific forms include, but are not limited to, capsules, tablets, chewables, tablets, drinks and the like.
医薬品用途としては、本実施形態の剤は、経口投与、注射、点滴、皮膚吸収等の方法で使用することができる。経口投与の場合、本実施形態の剤はハードカプセル、ソフトカプセル、錠剤の形で他の物質と混合して用いることができる。また、本実施形態の剤は、飲料、点滴液、注射液として使用することもできる。 For pharmaceutical use, the agent of the present embodiment can be used by methods such as oral administration, injection, infusion, and skin absorption. In the case of oral administration, the agent of the present embodiment can be used in the form of hard capsules, soft capsules and tablets mixed with other substances. In addition, the agent of the present embodiment can also be used as a beverage, a drip solution, or an injection solution.
このなかで、本実施形態の剤は、飲料、ソフトカプセル、または錠剤として、経口で摂取する態様が好ましい。 Among these, the agent of the present embodiment is preferably taken orally as a beverage, soft capsule, or tablet.
本実施形態の剤は、医薬及び食品などとして有用であり、その適用対象は哺乳動物であり得る。このような哺乳動物としては、例えば、霊長類（例えば、ヒト、サル、チンパンジー）、げっ歯類（例えば、マウス、ラット、モルモット）、ペット（例、イヌ、ネコ、ウサギ）、使役動物又は家畜（例えば、ウシ、ウマ、ブタ、ヒツジ、ヤギ）が挙げられるが、本実施形態ではヒトが好ましい。尚、ヒト以外の哺乳動物に適用する場合、本実施形態の剤の投与量（摂取量）は、動物の体重又は大きさに応じて適宜加減すればよい。 The agent of the present embodiment is useful as a medicine, a food, or the like, and its application target may be a mammal. Such mammals include, for example, primates (eg, humans, monkeys, chimpanzees), rodents (eg, mice, rats, guinea pigs), pets (eg, dogs, cats, rabbits), working animals or livestock. (For example, cows, horses, pigs, sheep, goats), but humans are preferred in this embodiment. When applied to mammals other than humans, the dose (intake) of the agent of the present embodiment may be appropriately adjusted according to the body weight or size of the animal.
〔組成物〕
本実施形態の剤は、製剤上の必要に応じて、薬学的に許容される担体を適宜用いて常法により製剤化し、組成物とすることができる（以下、「本実施形態の組成物」と称する）。これにより、本実施形態の組成物は、本実施形態の剤を含有しているということができる。本実施形態の組成物は、本実施形態の剤を含むことから、本実施形態の剤により発揮される効果をすべて有することができる。すなわち、本実施形態の組成物は、脂質減少促進作用や生殖機能改善作用を有する。ここで、「脂質減少促進」及び「生殖機能改善」とは、上記したとおりである。
〔Composition〕
The agent of the present embodiment can be formulated by a conventional method using a pharmaceutically acceptable carrier as appropriate according to the needs of the preparation (hereinafter, "composition of the present embodiment"). (Called). Thereby, it can be said that the composition of the present embodiment contains the agent of the present embodiment. Since the composition of the present embodiment contains the agent of the present embodiment, it can have all the effects exhibited by the agent of the present embodiment. That is, the composition of the present embodiment has a lipid reduction promoting action and a reproductive function improving action. Here, "promotion of lipid reduction" and "improvement of reproductive function" are as described above.
上記担体は、製剤（組成物）の剤形により適宜選択することができ、特に限定されないが、例えば、賦形剤、結合剤、滑沢剤、崩壊剤、溶剤、安定化剤、溶解補助剤、酸化防止剤、着色剤、着香剤、甘味剤等の添加剤が挙げられる。 The carrier can be appropriately selected depending on the dosage form of the preparation (composition) and is not particularly limited, but for example, an excipient, a binder, a lubricant, a disintegrant, a solvent, a stabilizer, and a solubilizing agent. , Antioxidants, colorants, flavoring agents, sweeteners and other additives.
賦形剤としては、特に制限されないが、例えば、糖類（白糖、乳糖、ブドウ糖、マンニトール等）、デンプン（コーンスターチ等）、結晶セルロース、リン酸カルシウム、硫酸カルシウム、硫酸マグネシウムなどが挙げられる。 The excipient is not particularly limited, and examples thereof include sugars (sucrose, lactose, glucose, mannitol, etc.), starch (corn starch, etc.), crystalline cellulose, calcium phosphate, calcium sulfate, magnesium sulfate, and the like.
結合剤としては、特に制限されないが、例えば、α化デンプン、ゼラチン、トラガントガム、アラビアゴム、メチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、結晶セルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、ポリビニルアルコールなどが挙げられる。 The binder is not particularly limited, and examples thereof include pregelatinized starch, gelatin, tragant gum, gum arabic, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol and the like. Can be mentioned.
滑沢剤としては、特に制限されないが、例えば、ステアリン酸マグネシウム、タルク、ポリエチレングリコール、シリカ、硬化植物油などが挙げられる。 The lubricant is not particularly limited, and examples thereof include magnesium stearate, talc, polyethylene glycol, silica, and hardened vegetable oil.
崩壊剤としては、特に制限されないが、例えば、デンプン、結晶セルロース、カルボキシメチルセルロース、寒天、クエン酸カルシウム、炭酸カルシウム、炭酸水素ナトリウム、デキストリンなどが挙げられる。 The disintegrant is not particularly limited, and examples thereof include starch, crystalline cellulose, carboxymethyl cellulose, agar, calcium citrate, calcium carbonate, sodium hydrogencarbonate, and dextrin.
溶剤としては、特に制限されないが、例えば、水、エタノール、グリセロール、生理食塩水、大豆油などが挙げられる。 The solvent is not particularly limited, and examples thereof include water, ethanol, glycerol, physiological saline, and soybean oil.
安定化剤としては、特に制限されないが、例えば、安息香酸、安息香酸ナトリウム、パラオキシ安息香酸エチル、プロピレングルコールなどが挙げられる。 The stabilizer is not particularly limited, and examples thereof include benzoic acid, sodium benzoate, ethyl paraoxybenzoate, and propylene glycol.
溶解補助剤としては、特に制限されないが、例えば、フマル酸、コハク酸、リンゴ酸などが挙げられる。 The solubilizing agent is not particularly limited, and examples thereof include fumaric acid, succinic acid, and malic acid.
酸化防止剤としては、特に制限されないが、例えば、アスコルビン酸、トコフェロール、亜硫酸水素ナトリウム、チオ硫酸ナトリウム、ピロ亜硫酸ナトリウム、クエン酸などが挙げられる。 The antioxidant is not particularly limited, and examples thereof include ascorbic acid, tocopherol, sodium bisulfite, sodium thiosulfite, sodium pyrosulfite, and citric acid.
着色剤、着香剤、及び甘味剤としては、医薬及び食品分野において通常添加することが許容されているものがそれぞれ挙げられる。 Examples of colorants, flavoring agents, and sweetening agents include those that are usually allowed to be added in the pharmaceutical and food fields, respectively.
本実施形態の組成物におけるＰＱＱ及び／又はその塩の含有量は、本実施形態の組成物の全重量に対し、好ましくは０．１０〜９９．９９質量％であり、より好ましくは０．６０〜９９．９０質量％であり、さらに好ましくは１．００〜９９．９０質量％である。本実施形態の剤におけるＰＱＱ及び／又はその塩の含有量はその物質の重量として取り扱う。したがって、ＰＱＱの塩をＰＱＱの遊離体（フリー体）に換算する必要はなく、また、ＰＱＱの塩が水和物を形成している場合は、水分子を含んだ形で重量を算出するものとする。 The content of PQQ and / or a salt thereof in the composition of the present embodiment is preferably 0.10 to 99.99% by mass, more preferably 0.60, based on the total weight of the composition of the present embodiment. It is ~ 99.90% by mass, more preferably 1.00 to 99.90% by mass. The content of PQQ and / or a salt thereof in the agent of this embodiment is treated as the weight of the substance. Therefore, it is not necessary to convert the salt of PQQ into a free form of PQQ, and when the salt of PQQ forms a hydrate, the weight is calculated including water molecules. And.
本実施形態の組成物は、医薬（即ち、医薬組成物）として使用することができる。この場合、本実施形態の医薬組成物は、肥満症に関連する疾患の予防又は治療薬として取り扱うことが可能であり、かかる疾患は上述したとおりである。また、本実施形態の組成物は、生殖機能改善に関する治療薬として取り扱うことも可能である。 The composition of this embodiment can be used as a medicine (that is, a pharmaceutical composition). In this case, the pharmaceutical composition of the present embodiment can be treated as a prophylactic or therapeutic agent for a disease related to obesity, and the disease is as described above. In addition, the composition of the present embodiment can be treated as a therapeutic agent for improving reproductive function.
本実施形態の医薬組成物の投与方法としては、特に限定されるものではなく、一般に経口投与による投与方法が挙げられるが、対象患者の状態、重症度等に応じて、非経口投与（血管内（静脈内、動脈内）投与、皮下投与、経皮投与、直腸内投与等）を適宜選択してもよい。有効成分であるＰＱＱ及び／又はその塩はいずれも飲食可能であることから、本実施形態では経口投与を採用することが好ましい。 The administration method of the pharmaceutical composition of the present embodiment is not particularly limited, and generally includes an administration method by oral administration, but parenteral administration (intravascular administration) depending on the condition, severity, etc. of the target patient. (Intravenous, intraarterial) administration, subcutaneous administration, transdermal administration, rectal administration, etc.) may be appropriately selected. Since both PQQ and / or a salt thereof, which are the active ingredients, can be eaten and eaten, it is preferable to adopt oral administration in this embodiment.
本実施形態の医薬組成物の剤形は、特に限定されず、投与方法に適した形態にすることができる。経口投与に適した形態としては、例えば、錠剤、ロゼンジ、硬質又は軟質カプセル、水性又は油性懸濁液、乳液、分散性粉末又は顆粒、シロップ又はエリキシルなどが挙げられる。非経口投与に適した形態としては、例えば、非経口注射に適した形態として、静脈内、皮下、筋肉内、血管内又は注入投与のための滅菌溶液、懸濁液、乳液などが、経皮投与に適した形態として、クリーム、軟膏、ゲル、水性又は油性の液剤（懸濁液を含む）などが挙げられる。 The dosage form of the pharmaceutical composition of the present embodiment is not particularly limited, and can be a form suitable for the administration method. Suitable forms for oral administration include, for example, tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, disperse powders or granules, syrups or elixirs and the like. As a form suitable for parenteral administration, for example, as a form suitable for parenteral injection, a sterile solution, suspension, emulsion for intravenous, subcutaneous, intramuscular, intravascular or injectable administration is percutaneously used. Suitable forms for administration include creams, ointments, gels, aqueous or oily solutions (including suspensions) and the like.
本実施形態の組成物はまた、飲食品（即ち、飲食品組成物）として使用することもできる。この場合、本実施形態の飲食品組成物は、上述した薬学的に許容される担体に加えて、飲食品の分野において通常使用される担体を用いて常法により製剤化することができる。 The composition of the present embodiment can also be used as a food or drink (that is, a food or drink composition). In this case, the food and drink composition of the present embodiment can be formulated by a conventional method using a carrier usually used in the field of food and drink in addition to the above-mentioned pharmaceutically acceptable carrier.
本実施形態における飲食品は、飲食品全般を意味するが、いわゆる健康食品を含む一般食品の他、消費者庁に規定されている特別用途食品（特定保健用食品、病者用食品、えん下困難者用食品など）や栄養機能食品をも含むものであり、さらにサプリメント、飼料等も本実施形態の飲食品に包含される。 Foods and drinks in this embodiment mean foods and drinks in general, but in addition to general foods including so-called health foods, special purpose foods (foods for specified health use, foods for the sick, and swallows) specified by the Consumer Affairs Agency. (Foods for people with disabilities, etc.) and nutritionally functional foods are also included, and supplements, feeds, etc. are also included in the foods and drinks of the present embodiment.
本実施形態の飲食品組成物は、その剤形は特に限定されず、細粒剤、顆粒剤、丸剤、錠剤（コーティング錠、糖衣錠を含む）、カプセル剤（ハードカプセル、ソフトカプセル、マイクロカプセルを含む）、飲料、ドリンク剤、液剤（シロップ剤、乳剤、懸濁剤を含む）、粉末食品、ゼリー、飴等の剤形とすることができる。 The dosage form of the food and drink composition of the present embodiment is not particularly limited, and includes fine granules, granules, pills, tablets (including coated tablets and sugar-coated tablets), and capsules (hard capsules, soft capsules, microcapsules). ), Beverages, drinks, liquids (including syrups, emulsions, capsules), powdered foods, jellies, candy and the like.
本実施形態の剤及び組成物の投与量（摂取量）は、特に限定されず、体内において脂質減少促進作用や生殖機能改善作用が発現することができる有効量の範囲内であればよく、対象の個人差、症状、投与方法等に応じて適宜設定することができる。また、１日あたりの投与量（摂取量）は、一度にもしくは数回（例えば、２、３回）に分けて投与（摂取）することができる。本実施形態の剤及び組成物の投与（摂取）は、食前、食後及び食間を問わず、またその期間は、本実施形態の効果が奏される限りにおいて特に限定されない。以下、本明細書において用語「投与」が使用される場合は、該用語は「摂取」の概念も包含することを意味する。 The dose (intake) of the agent and the composition of the present embodiment is not particularly limited as long as it is within an effective amount capable of exhibiting a lipid reduction promoting action and a reproductive function improving action in the body. It can be appropriately set according to individual differences, symptoms, administration methods, and the like. In addition, the daily dose (intake) can be administered (ingested) at one time or divided into several times (for example, two or three times). The administration (ingestion) of the agent and composition of the present embodiment may be performed before, after, and between meals, and the period thereof is not particularly limited as long as the effects of the present embodiment are exhibited. Hereinafter, when the term "administration" is used in the present specification, the term means that the concept of "ingestion" is also included.
上述したとおり、ＰＱＱ及び／又はその塩は別個の製剤に製剤化することができ、その場合、本実施形態において両製剤は併用されることができる。ＰＱＱ及び／又はその塩及びカフェインは同時に投与されてもよく、或いはいずれかの順序で逐次的に投与されることもできる。 As described above, PQQ and / or a salt thereof can be formulated into separate formulations, in which case both formulations can be used together in this embodiment. PQQ and / or a salt thereof and caffeine may be administered simultaneously, or may be administered sequentially in any order.
本実施形態の剤及び組成物を使用する場合はまた、脂質減少促進作用や生殖機能改善作用を有する既存の成分と併用することも可能である。そのような場合、本実施形態の剤及び組成物と上記既存の成分とを投与する順序は、同時又は別々であってもよい。別々の場合、本実施形態の剤及び組成物の投与は、上記既存の成分の前又は後のいずれでもよい。 When the agent and composition of the present embodiment are used, they can also be used in combination with existing components having a lipid reduction promoting action and a reproductive function improving action. In such cases, the order of administration of the agent and composition of the present embodiment and the existing components may be simultaneous or separate. In separate cases, administration of the agents and compositions of this embodiment may be before or after the existing ingredients.
脂質減少促進作用に関する既存の成分としては、特に制限されないが、例えば、茶抽出物、カカオ抽出物、コーヒー豆マンノオリゴ糖、りんご由来プロシアニジン、糖転移ヘスペリジン、レスベラトロール、グリーンシトラスエキス、シトラスナリジニン、グルコサミン、キノコキトサン、キトサン、ジアシルグリセロール、中鎖脂肪酸、ＥＰＡ、ＤＨＡ、大豆蛋白、植物ステロール（β−シトステロール等）、サイリウム種皮由来食物繊維、低分子化アルギン酸ナトリウム、ガラナ、ショウキョウ、ガルシニア、グロビン蛋白分解物、カルニチン、α−リポ酸、植物スタノールエステル、リン脂質結合大豆ペプチド又はこれらの組み合わせ等が挙げられるが、特にこれらに限定されない。 The existing components related to the lipid reduction promoting action are not particularly limited, but for example, tea extract, cacao extract, coffee bean manno-oligosaccharide, apple-derived procyanidin, glycosylated hesperidin, resveratrol, green citrus extract, citrus naridinin. , Glucosamine, mushroom chitosan, chitosan, diacylglycerol, medium-chain fatty acid, EPA, DHA, soy protein, plant sterol (β-citosterol, etc.), psyllium seed coat-derived dietary fiber, low molecular weight sodium alginate, galana, shokyo, garsina, Examples thereof include, but are not limited to, globin proteolytic products, carnitine, α-lipoic acid, plant stanol esters, phospholipid-binding soybean peptides or combinations thereof.
以下に実施例を挙げて本発明をさらに具体的に説明するが、これらは単なる例示であって、本発明の範囲を何ら限定するものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but these are merely examples and do not limit the scope of the present invention in any way.
本実施例で用いるピロロキノリンキノン二ナトリウム塩は、三菱瓦斯化学製ＢｉｏＰＱＱ（以下、「ＰＱＱ」ともいう。）を使用した。また、その他の化合物については、特に断りのない限り和光純薬工業株式会社製の試薬を使用した。 As the pyrroloquinoline quinone disodium salt used in this example, BioPQQ manufactured by Mitsubishi Gas Chemical Company (hereinafter, also referred to as “PQQ”) was used. For other compounds, reagents manufactured by Wako Pure Chemical Industries, Ltd. were used unless otherwise specified.
本実施例では、脂質減少促進試験にオオミジンコ（学名：Daphnia magna）を使用した。オオミジンコの餌となるクロレラ(学名：Chlorella vulgaris)は有限会社日海センターの製品を使用した。具体的には、親のオオミジンコを、ライト条件８時間、暗条件１６時間を一日のサイクルとして、水温２２度の水槽中で育成した。餌となるクロレラは、月、水、金曜日に８×１０7個を与えた。水槽の飼育水は一週間に一回の頻度で交換した。そして、このような飼育条件下において、親のオオミジンコから生まれた子のオオミジンコを以下の実施例において用いた。 In this example, Daphnia magna (scientific name: Daphnia magna) was used for the lipid reduction promotion test. Chlorella (scientific name: Chlorella vulgaris), which is the food for Daphnia magna, used the products of Nikkai Center Co., Ltd. Specifically, the parent Daphnia magna was cultivated in a water tank having a water temperature of 22 ° C. with a light condition of 8 hours and a dark condition of 16 hours as a daily cycle. The prey chlorella was fed 8 x 10 7 pieces on Monday, Wednesday and Friday. The breeding water in the aquarium was changed once a week. Then, under such breeding conditions, the offspring Daphnia magna born from the parent Daphnia magna was used in the following examples.
〔実施例１〕高い餌濃度−ＰＱＱ存在下での飼育
子のオオミジンコ２０匹を、ライト条件８時間、暗条件１６時間を一日のサイクルとして、５００ｍＬのミネラル水（水温２２度）で飼育した。餌となるクロレラは、オオミジンコ一匹当たり、８×１０5〜９×１０5個／日となるように、毎日与えた。飼育開始から４８時間後（２日後）に、濃度１５ｍｇ／Ｌとなるように、飼育水にピロロキノリンキノン二ナトリウムを添加し、引き続き餌となるクロレラもオオミジンコ一匹当たり８×１０5〜９×１０5個／日与え続けた。飼育水にピロロキノリンキノン二ナトリウムを添加し始めてから４日後、ナイルレッドを使用してオオミジンコの脂肪を染色した。
[Example 1] Breeding in the presence of high food concentration-PQQ 20 Daphnia magna were bred in 500 mL of mineral water (water temperature 22 degrees) with a daily cycle of 8 hours under light conditions and 16 hours under dark conditions. .. The food chlorella was given daily so as to be 8 × 10 5 to 9 × 10 5 pieces / day per Daphnia magna. 48 hours after the start of feeding (after 2 days), concentration 15 mg / L and such that, added pyrroloquinoline quinone disodium in breeding water, continue to be a food Chlorella also flea one animal per 8 × 10 5 ~9 × Continued to give 10 5 pieces / day. Four days after starting the addition of pyrroloquinoline quinone disodium to the breeding water, Daphnia magna fat was stained with Nile Red.
〔比較例１〕高い餌濃度−ＰＱＱなし条件下での飼育
子のオオミジンコ２０匹を、ライト条件８時間、暗条件１６時間を一日のサイクルとして、５００ｍＬのミネラル水（水温２２度）で飼育した。餌となるクロレラは、オオミジンコ一匹当たり、８×１０5〜９×１０5個／日となるように、毎日与えた。飼育開始から６日後、ナイルレッドを使用して脂肪を染色した。
[Comparative Example 1] Breeding under conditions of high food concentration-no PQQ 20 Daphnia magna were bred in 500 mL of mineral water (water temperature 22 degrees) with a daily cycle of 8 hours under light conditions and 16 hours under dark conditions. did. The food chlorella was given daily so as to be 8 × 10 5 to 9 × 10 5 pieces / day per Daphnia magna. Six days after the start of breeding, the fat was stained with Nile Red.
〔実施例２〕
餌となるクロレラを、オオミジンコ一匹当たり、２×１０5個／日となるように、毎日与えたこと以外は、実施例１と同様にしてオオミジンコを飼育し、ナイルレッドを使用してオオミジンコの脂肪を染色した。
[Example 2]
The Daphnia magna was bred in the same manner as in Example 1 except that the food chlorella was given daily so as to be 2 × 10 5 per day, and the Daphnia magna was used with Nile Red. The fat was stained.
〔比較例２〕
餌となるクロレラを、オオミジンコ一匹当たり、２×１０5個／日となるように、毎日与えたこと以外は、比較例１と同様にしてオオミジンコを飼育し、ナイルレッドを使用してオオミジンコの脂肪を染色した。
[Comparative Example 2]
The Daphnia magna was bred in the same manner as in Comparative Example 1 except that the food chlorella was given daily so as to be 2 × 10 5 pieces / day per Daphnia magna, and the Daphnia magna was used with Nile Red. The fat was stained.
〔実施例３〕
餌となるクロレラを、オオミジンコ一匹当たり、４×１０4個／日となるように、毎日与えたこと以外は、実施例１と同様にしてオオミジンコを飼育し、ナイルレッドを使用してオオミジンコの脂肪を染色した。
[Example 3]
The Daphnia magna was bred in the same manner as in Example 1 except that the feed chlorella was given daily to 4 × 10 4 per day, and the Daphnia magna was used with Nile Red. The fat was stained.
〔比較例３〕
餌となるクロレラを、オオミジンコ一匹当たり、４×１０4個／日となるように、毎日与えたこと以外は、比較例１と同様にしてオオミジンコを飼育し、ナイルレッドを使用してオオミジンコの脂肪を染色した。
[Comparative Example 3]
The Daphnia magna was bred in the same manner as in Comparative Example 1 except that the food chlorella was given daily to 4 × 10 4 per day, and the Daphnia magna was used with Nile Red. The fat was stained.
〔脂肪量の測定〕
非特許文献３に準じて脂肪量の測定をした。実施例１〜３及び比較例１〜３で飼育したオオミジンコを、ナイルレッド０．５ｍｇ／Ｌを含む水溶液２ｍＬに加え、２時間処理した。その後、水洗いをして各オオミジンコを取り出した。そして、オオミジンコ一匹当たり３００μＬの水を加え、１５分超音波を当てることにより粉砕した。粉砕液を遠心分離して上澄みを取り出した。これをプレートリーダーにより４８５ｎｍ励起／５３５ｎｍ検出により蛍光強度を測定した。この測定作業をオオミジンコ２０匹に対して行った。その結果を図１に示す。
[Measurement of fat mass]
The amount of fat was measured according to
図１に示すように、餌の量にかかわらず、飼育途中からＰＱＱを添加した飼育水を用いて飼育したオオミジンコの脂肪量は低い値であることが分かった。特に、高程度の餌の量（実施例１、比較例１）と中程度の餌の量（実施例２、比較例２）では、ＰＱＱの添加により脂肪量が優位に減少していた。 As shown in FIG. 1, it was found that the fat content of Daphnia magna bred using the breeding water to which PQQ was added from the middle of breeding was low regardless of the amount of food. In particular, in the high food amount (Example 1, Comparative Example 1) and the medium food amount (Example 2, Comparative Example 2), the fat mass was significantly reduced by the addition of PQQ.
また、ＰＱＱの添加が脂肪減少に関与していることを確かめるために、Ｓｔｕｄｅｎｔ−Ｔ検定を行った。具体的には、ＰＱＱを添加して育てたオオミジンコの脂肪量と、同量の餌量でＰＱＱを添加せずに育てたオオミジンコの脂肪量とに差がないという帰無仮説を設定し、Ｓｔｕｄｅｎｔ−Ｔ検定を行った。その結果、実施例１と比較例１、実施例２と比較例２、実施例３と比較例３のいずれの場合においても、ｐ＜０．０５となり、ＰＱＱを添加せずに育てたオオミジンコに対して、ＰＱＱを添加して育てたオオミジンコの脂肪量減少には、統計的に有意な差がみられることが確認された。なお、図１中の「Ｎ．Ｓ．」は、ｎｏｔ ｓｉｇｎｉｆｉｃａｎｔの略であり、「＊」は０．０１≦ｐ＜０．０５であることを示し、「＊＊」はｐ＜０．０１であることを示す。以上の結果より、ＰＱＱは体内の脂肪を分解する、即ち、体脂肪の減少作用を有することが示唆された。 In addition, a Student-T test was performed to confirm that the addition of PQQ was involved in fat loss. Specifically, we set the null hypothesis that there is no difference between the fat content of Daphnia magna grown with PQQ and the fat content of Daphnia magna grown with the same amount of food without adding PQQ. -T test was performed. As a result, in any of the cases of Example 1 and Comparative Example 1, Example 2 and Comparative Example 2, and Example 3 and Comparative Example 3, p <0.05, and the Daphnia magna grown without adding PQQ On the other hand, it was confirmed that there was a statistically significant difference in the decrease in fat mass of Daphnia magna grown with the addition of PQQ. In addition, "NS" in FIG. 1 is an abbreviation for not significant, "*" indicates that 0.01 ≤ p <0.05, and "**" is p <0.01. Indicates that. From the above results, it was suggested that PQQ decomposes fat in the body, that is, has an action of reducing body fat.
なお、上記試験においてオオミジンコは常に運動をしている状態であり、ヒトの運動強度に例えると３メッツ以上の運動をしている状態と考えられる。 In the above test, Daphnia magna is in a state of being constantly exercising, and is considered to be in a state of exercising 3 mets or more in comparison with human exercise intensity.
〔蛍光顕微鏡写真〕
実施例１〜３と比較例１〜３で飼育したオオミジンコの蛍光顕微鏡写真を図２に示す。なお、図２（ａ）と（ｂ）は同じ視野の顕微鏡写真であって、図２（ａ）は、ナイルレッドによる蛍光を撮影した蛍光顕微鏡写真であり、図２（ｂ）は、通常の顕微鏡写真である。図２に示されるように、餌の量が多くなるにつれ、オオミジンコの個体の大きさが大きく、蓄えられる脂肪量も多くなることが分かる。また、図２（ａ）と（ｂ）の対比から、餌の量が同一である場合には、ＰＱＱを添加して育てたオオミジンコの方が染色される脂肪量は少なくなることが分かる。この顕微鏡写真から得られた結果は、上記プレートリーダーの結果と同様であった。
[Fluorescence micrograph]
Fluorescence micrographs of Daphnia magna bred in Examples 1 to 3 and Comparative Examples 1 to 3 are shown in FIG. Note that FIGS. 2 (a) and 2 (b) are micrographs of the same field of view, FIG. 2 (a) is a fluorescence micrograph of fluorescence by Nile Red, and FIG. 2 (b) is a normal micrograph. It is a micrograph. As shown in FIG. 2, it can be seen that as the amount of food increases, the size of the individual Daphnia magna increases and the amount of fat stored also increases. Further, from the comparison between FIGS. 2 (a) and 2 (b), it can be seen that when the amount of food is the same, the amount of fat stained by Daphnia magna grown by adding PQQ is smaller. The results obtained from this micrograph were similar to those of the plate reader described above.
〔体長測定〕
実施例１〜３比較例１〜３で飼育したオオミジンコの体長測定を行った。その結果を図３に示す。また、オオミジンコの体長においてもＰＱＱの添加が関与しているか否かを確かめるために、Ｓｔｕｄｅｎｔ−Ｔ検定を行った。その結果、体長に関してはＰＱＱ添加の有無にかかわらず、有意差は存在しないことが分かった（ｐ＞０．０５）。図３中の「Ｎ．Ｓ．」は、ｎｏｔ ｓｉｇｎｉｆｉｃａｎｔの略である。また、ＰＱＱによってオオミジンコの体長に有害な影響は確認されなかった。
[Measurement of body length]
The body length of the Daphnia magna bred in Examples 1 to 3 and Comparative Examples 1 to 3 was measured. The result is shown in FIG. In addition, a Student-T test was performed to confirm whether or not the addition of PQQ was involved in the body length of Daphnia magna. As a result, it was found that there was no significant difference in body length with or without PQQ addition (p> 0.05). “NS” in FIG. 3 is an abbreviation for not significant. In addition, PQQ did not confirm any adverse effect on the length of Daphnia magna.
〔ＰＱＱ添加有無による生存率と卵の量〕
オオミジンコの産卵する卵の量は個体の健康状態と比例する。そこで、オオミジンコの生存率と卵の量を測定した。
[Survival rate and amount of eggs with or without PQQ addition]
The amount of eggs laid by Daphnia magna is proportional to the health status of the individual. Therefore, the survival rate of Daphnia magna and the amount of eggs were measured.
〔実施例４〕
子のオオミジンコを一匹ずつ、ライト条件８時間、暗条件１６時間を一日のサイクルとして、５０ｍＬのミネラル水（水温２２度）で飼育した。飼育開始から７日間は、餌となるクロレラを、オオミジンコ一匹当たり、１×１０5個／日となるように、毎日与えた。そして、飼育開始から８〜１４日間は、クロレラの量を、オオミジンコ一匹当たり、５×１０5個／日に増やして、毎日与えた。また、飼育開始から８〜１４日間は、濃度１．５ｍｇ／Ｌとなるように、飼育水にピロロキノリンキノン二ナトリウムも添加した。なお、飼育水の交換は、週３回行った。
[Example 4]
The pups, Daphnia magna, were bred one by one in 50 mL of mineral water (water temperature 22 ° C) with a daily cycle of 8 hours under light conditions and 16 hours under dark conditions. For 7 days from the start of breeding, chlorella to be fed was given daily so as to be 1 × 10 5 per day for each Daphnia magna. Then, for 8 to 14 days from the start of breeding, the amount of chlorella was increased by 5 × 10 5 cells / day per Daphnia magna and given daily. In addition, pyrroloquinoline quinone disodium was also added to the breeding water so that the concentration was 1.5 mg / L for 8 to 14 days from the start of breeding. The breeding water was exchanged three times a week.
〔比較例４〕
飼育開始から８〜１４日間において、飼育水にピロロキノリンキノン二ナトリウムを添加しなかったこと以外は、実施例４と同様の条件でオオミジンコを育てた。
[Comparative Example 4]
Daphnia magna was grown under the same conditions as in Example 4 except that pyrroloquinoline quinone disodium was not added to the breeding water for 8 to 14 days from the start of breeding.
実施例４及び比較例４の条件でオオミジンコを１４日間飼育し、オオミジンコの生存と卵の数を確認した。オオミジンコの生存を図４に示し、卵の数を図５に示す。図４に示すように、ＰＱＱ添加の有無にかかわらずオオミジンコの生存率は１００％であった。また、図５に示すように、ＰＱＱを添加した飼育水で飼育されたオオミジンコの方が、卵の数が多くなることが分かった。このことから、ＰＱＱを添加した飼育水で飼育されたオオミジンコの固体はより健康な状態であることが分かる。また、オオミジンコの健康状態においてもＰＱＱの添加が関与しているか否かを確かめるために、Ｓｔｕｄｅｎｔ−Ｔ検定を行った。その結果、ＰＱＱを添加せずに育てたオオミジンコに対して、ＰＱＱを添加して育てたオオミジンコの健康状態の向上には、統計的に有意な差がみられることが確認された。図５中の「＊＊」はｐ＜０．０１であることを示す。また、図５中の1st brood 及び2nd broodは、それぞれ一回目と二回目の産卵を意味する。 Daphnia magna was bred for 14 days under the conditions of Example 4 and Comparative Example 4, and the survival of Daphnia magna and the number of eggs were confirmed. The survival of Daphnia magna is shown in FIG. 4, and the number of eggs is shown in FIG. As shown in FIG. 4, the survival rate of Daphnia magna was 100% with or without the addition of PQQ. Further, as shown in FIG. 5, it was found that the number of eggs of Daphnia magna bred in the breeding water to which PQQ was added was larger than that of Daphnia magna. From this, it can be seen that the solids of Daphnia magna bred in the breeding water to which PQQ was added are in a healthier state. In addition, a Student-T test was performed to confirm whether or not the addition of PQQ was involved in the health condition of Daphnia magna. As a result, it was confirmed that there was a statistically significant difference in the improvement of the health condition of Daphnia magna grown with PQQ compared with that of Daphnia magna grown without PQQ. “**” in FIG. 5 indicates that p <0.01. In addition, 1st brood and 2nd brood in FIG. 5 mean the first and second spawning, respectively.
また、上記試験において、ＰＱＱを添加した飼育水で飼育されたオオミジンコの卵の数が有意に増えていることから、ＰＱＱには生殖機能の改善効果があることも分かった。 In addition, in the above test, the number of eggs of Daphnia magna bred in the breeding water to which PQQ was added was significantly increased, and thus it was also found that PQQ has an effect of improving reproductive function.
（実施例５）肥満関連遺伝子解析
脂質減少促進の予想されているメカニズムとしてはミトコンドリアを豊富に新生し、ミトコンドリア脱共役タンパク質（ＵＣＰ１）の高発現により熱産生を行い、脂肪を分解するというものである。ＵＣＰ１は主に褐色脂肪細胞に存在し、ミトコンドリア内での脂肪燃焼（熱産生）に必要なタンパク質である。本検討では、オオミジンコを用いてＰＱＱの影響によるＵｃｐ１の発現変化を調べた。
(Example 5) Analysis of obesity-related genes The expected mechanism for promoting lipid reduction is that mitochondria are abundantly regenerated, heat is produced by high expression of mitochondrial uncoupling protein (UCP1), and fat is decomposed. is there. UCP1 is mainly present in brown adipocytes and is a protein required for fat burning (heat production) in mitochondria. In this study, the expression change of Ucp1 due to the influence of PQQ was investigated using Daphnia magna.
遺伝子発現を測定するリアルタイムＰＣＲ実験のため、ターゲット遺伝子（Ｕｃｐ１）のプライマー配列を設計した。ホモサピエンスのＵＣＰ１タンパク配列はNational Center for Biotechnology Information (NCBI)のウェブサイトから収得した。その配列を利用してオオミジンコのゲノムデータベース（wFleaBase: Daphnia Water Flea Genome Database）でミジンコにあるＵｃｐ１遺伝子を検索した。表１に記載した配列はPCR primer design tool （https://www.eurofinsgenomics.eu/en/ecom/tools/pcr-primer-design/）を使ってオオミジンコのＵｃｐ１遺伝子に対応したプライマーの配列である。Ｂ−ａｃｔｉｎ遺伝子はリアルタイムＰＣＲ分析の内部参照遺伝子として利用した。 Primer sequences for the target gene (Ucp1) were designed for real-time PCR experiments to measure gene expression. The UCP1 protein sequence of Homo sapiens was obtained from the National Center for Biotechnology Information (NCBI) website. The sequence was used to search the Daphnia Water Flea Genome Database (wFleaBase) for the Ucp1 gene in Daphnia magna. The sequences shown in Table 1 are the sequences of primers corresponding to the Ucp1 gene of Daphnia magna using the PCR primer design tool (https://www.eurofinsgenomics.eu/en/ecom/tools/pcr-primer-design/). .. The B-actin gene was used as an internal reference gene for real-time PCR analysis.
ＲＮＡ抽出サンプル：
ＰＱＱ存在下での飼育とＰＱＱなし条件下での飼育（コントロール）を行った。ＰＱＱ存在下での飼育では子のオオミジンコ１０匹を、ライト条件８時間、暗条件１６時間を一日のサイクルとして、３００ｍＬのミネラル水（水温２２度）で飼育した。餌となるクロレラは、オオミジンコ一匹当たり、１×１０6個／日となるように、毎日与えた。７日後に、濃度２０ｍｇ／Ｌとなるように、飼育水にＰＱＱを添加し、引き続き餌となるクロレラもオオミジンコ一匹当たり１×１０6個／日与え続けた。飼育水にＰＱＱを添加し始めてから３日後、１匹ずつ２ｍＬチューブ移し、水を抜いた。Ｔｏｔａｌ ＲＮＡ抽出実験まで−８０℃に保存した。
RNA extraction sample:
Breeding in the presence of PQQ and breeding (control) under the condition without PQQ were carried out. In the breeding in the presence of PQQ, 10 offspring Daphnia magna were bred in 300 mL of mineral water (water temperature 22 ° C.) with a daily cycle of 8 hours under light conditions and 16 hours under dark conditions. The prey chlorella was given daily at a rate of 1 × 10 6 per day for each Daphnia magna. After 7 days, PQQ was added to the breeding water so as to have a concentration of 20 mg / L, and chlorella, which was continuously used as food, was continuously fed at 1 × 10 6 cells / day per Daphnia magna. Three days after starting to add PQQ to the breeding water, 2 mL tubes were transferred one by one and the water was drained. It was stored at -80 ° C until the Total RNA extraction experiment.
ＰＱＱなし条件下では子のオオミジンコ１０匹を、ライト条件８時間、暗条件１６時間を一日のサイクルとして３００ｍＬのミネラル水（水温２２度）で飼育した。餌となるクロレラは、オオミジンコ一匹当たり、１×１０6個／日となるように、毎日与えた。飼育開始から１０日後、ナイルレッドを使用して脂肪を染色した。１匹ずつ２ｍＬチューブ移し、水を抜いた。Ｔｏｔａｌ ＲＮＡ抽出実験まで−８０℃に保存した。 Under the condition without PQQ, 10 offspring Daphnia magna were bred in 300 mL of mineral water (water temperature 22 ° C.) with a daily cycle of 8 hours under light conditions and 16 hours under dark conditions. The prey chlorella was given daily at a rate of 1 × 10 6 per day for each Daphnia magna. Ten days after the start of breeding, the fat was stained with Nile Red. 2 mL tubes were transferred one by one and the water was drained. It was stored at -80 ° C until the Total RNA extraction experiment.
ＰＱＱなし条件下で飼育したオオミジンコ（コントロール）とＰＱＱ存在下で飼育したオオミジンコの３つのサンプルからＲＮＡをそれぞれ抽出した。サンプルを入れた２ｍＬチューブに１ｍＬ Sepasol-RNA I Super G（ナカライ）を加え、プラスチックのホモジナイザーペッスルでオオミジンコをつぶした。室温で５分間を放置した後、２００ｕＬフェノールクロロホルムイソアミルアルコール（ナカライ）を加え、３０秒間激しく振盪して混和した。室温で３分間放置した後、遠心（12,000×g，15分間，4°C）して上清を新しいチューブに移した。上清に対して、上清と同じ容量のイソプロパノールを加えてゆっくりで混和した。室温で１０分間放置した後、さらに遠心（12,000×g，5分間，4°C）して上清を除去し、沈殿したＲＮＡを得た。ＲＮＡの沈殿物は７０％エタノール１ｍＬで洗い、もう一度遠心（12,000×g，5分間，4°C）して上清を除去した。数分ＲＮＡを風乾して２５μＬ純水（RNAse-free water）で懸濁した。各サンプルにはオオミジンコ１匹から得られたＴｏｔａｌ ＲＮＡ２〜６ｕｇが含まれていた。各サンプルよりＲＮＡ１０〜５０ｎｇを用い、１ステップリアルタイムＰＣＲを行った。 RNA was extracted from three samples of Daphnia magna (control) bred under the condition of no PQQ and Daphnia magna bred in the presence of PQQ. 1 mL Sepasol-RNA I Super G (Nacalai) was added to a 2 mL tube containing the sample, and Daphnia magna was crushed with a plastic homogenizer pestle. After leaving to stand at room temperature for 5 minutes, 200 uL phenol chloroform isoamyl alcohol (Nacalai) was added, and the mixture was vigorously shaken for 30 seconds to mix. After leaving at room temperature for 3 minutes, the supernatant was transferred to a new tube by centrifugation (12,000 × g, 15 minutes, 4 ° C). To the supernatant, the same volume of isopropanol as the supernatant was added and mixed slowly. After leaving to stand at room temperature for 10 minutes, the supernatant was further removed by centrifugation (12,000 × g, 5 minutes, 4 ° C) to obtain precipitated RNA. The RNA precipitate was washed with 1 mL of 70% ethanol and centrifuged again (12,000 xg, 5 minutes, 4 ° C) to remove the supernatant. RNA was air dried for a few minutes and suspended in 25 μL pure water (RNAse-free water). Each sample contained 2-6 ug of Total RNA obtained from one Daphnia magna. One-step real-time PCR was performed using 10 to 50 ng of RNA from each sample.
遺伝子発現を測定するため、One Step TB Green PrimeScript RT-PCR Kit II (タカラバイオ（株）)のリアルタイム ＲＴ−ＰＣＲ 専用キットを利用した。プライマーセットを使ってＵｃｐ１の発現量を測定した。ＰＣＲ反応（ｎ＝２）はキットマニュアル通りに実施し、反応チューブを軽く遠心後、Thermal Cycler Dice Real Time System (タカラバイオ（株）)にセットし、下記の反応条件を行った。
・Pattern 1：逆転写反応（Ｈｏｌｄ；４２℃ ５分→９５℃ １０秒）
・Pattern 2：ＰＣＲ反応（４０Ｃｙｃｌｅｓ；９５℃ ５秒→６０℃ ３０秒）
・Pattern 3：Ｄｉｓｓｏｃｉａｔｉｏｎ
In order to measure gene expression, a real-time RT-PCR dedicated kit of One Step TB Green PrimeScript RT-PCR Kit II (Takara Bio Inc.) was used. The expression level of Ucp1 was measured using a primer set. The PCR reaction (n = 2) was carried out according to the kit manual, the reaction tube was lightly centrifuged, set in the Thermal Cycler Dice Real Time System (Takara Bio Inc.), and the following reaction conditions were carried out.
-Pattern 1: Reverse transcription reaction (Hold; 42 ° C. 5 minutes → 95 ° C. 10 seconds)
-Pattern 2: PCR reaction (40 Cycles; 95 ° C. 5 seconds → 60 ° C. 30 seconds)
・ Pattern 3: Dissociation
遺伝子発現解析においてＣｔ値はＲＴ−ＰＣＲから求めて２-ΔΔCT法により遺伝子発現相対比を計算した。結果、Ｂ−ａｃｔｉｎを参照遺伝子として設定すると、ＰＱＱを与えたサンプルにはコントロールと比較して目的遺伝子Ｕｃｐ１の発現量が１．２５倍増加した（ｐ−ｖａｌｕｅ＝０．３）。ＰＱＱがオオミジンコのＵｃｐ１発現増加を行うことと考えられる。 In the gene expression analysis, the Ct value was obtained from RT-PCR, and the relative gene expression ratio was calculated by the 2- ΔΔ CT method. As a result, when B-actin was set as the reference gene, the expression level of the target gene Ucp1 was increased 1.25 times in the sample given PQQ as compared with the control (p-value = 0.3). It is considered that PQQ increases the expression of Ucp1 in Daphnia magna.
〔実施例６〕脂質取り込みへの影響評価
体脂肪の蓄積は脂肪の取り込みを阻害することによっても防ぐことができる。脂質は体に取り込まれるとき、体内の酵素（リパーゼ）によって分解される。そのため、ＰＱＱがリパーゼの阻害作用を有しているのであれば、ＰＱＱは体内への脂肪の取り込みを抑制していると推察される。そこでＰＱＱを使用してリパーゼ阻害試験を行った。
[Example 6] Evaluation of effect on lipid uptake Accumulation of body fat can also be prevented by inhibiting fat uptake. When lipids are taken up by the body, they are broken down by enzymes (lipases) in the body. Therefore, if PQQ has an inhibitory effect on lipase, it is presumed that PQQ suppresses the uptake of fat into the body. Therefore, a lipase inhibition test was conducted using PQQ.
試験には、リパーゼ（豚膵臓由来：東京化成 ＲＮ＝９００２−６２−１）を使用した。ＳＢバイオサイエンス製のリパーゼキットＳを使用して実験した。以下、溶液名、プロトコールはキットのスケール１／２でリパーゼと試験サンプルの混合を評価する方法にモディファイした。 Lipase (derived from porcine pancreas: Tokyo Kasei RN = 9002-62-1) was used in the test. Experiments were performed using Lipase Kit S manufactured by SB Bioscience. Below, the solution name and protocol have been modified to evaluate the mix of lipase and test sample on a scale 1/2 of the kit.
リン酸バッファー（ＰＢＳ：ＧＩＢＣＯ製ｐＨ７．２）を使用し、ＰＱＱを所定量溶かし、試験液を調製した。リパーゼ１０ｍｇ／Ｌ水溶液４０μＬと試験液２５μＬを混合し、さらに、発色液５００μＬエラスターゼ阻害剤１０μＬを混合した。３０℃５分処理したのち、基質液５０μＬ加えた。これを３０分間インキュベートした。阻害液１ｍＬをさらに加え、吸光度４１２ｎｍで測定した。盲検としてリパーゼと試験液を阻害液投入後に加えるものを準備した。試験液をＰＱＱなし（ＰＢＳ）のみの吸光度を１００％として酵素活性を評価した。 A test solution was prepared by dissolving a predetermined amount of PQQ using a phosphate buffer (PBS: pH 7.2 manufactured by GIBCO). 40 μL of a lipase 10 mg / L aqueous solution and 25 μL of a test solution were mixed, and further, 500 μL of a color-developing solution and 10 μL of an elastase inhibitor were mixed. After treating at 30 ° C. for 5 minutes, 50 μL of the substrate solution was added. This was incubated for 30 minutes. 1 mL of the inhibitor was further added, and the absorbance was measured at 412 nm. As a blind study, we prepared a lipase and test solution to be added after the inhibitor was added. The enzyme activity was evaluated with the absorbance of the test solution without PQQ (PBS) as 100%.
以上の結果から、ＰＱＱにより酵素反応の阻害は見られなかった。また、高濃度のＰＱＱを使用した場合においても盲検では３%の影響で測定への影響はほとんどないことが分かった。この試験により、ＰＱＱのリパーゼ阻害活性は確認されず、ＰＱＱが直接的に脂肪吸収を阻害しているとは考えられないことが分かった。 From the above results, no inhibition of the enzyme reaction was observed by PQQ. It was also found that even when a high concentration of PQQ was used, there was almost no effect on the measurement with a blind effect of 3%. In this test, the lipase inhibitory activity of PQQ was not confirmed, and it was found that PQQ is not considered to directly inhibit fat absorption.
（実施例７） 運動能力評価
実施例５で記載したＰＱＱなし条件下で飼育したオオミジンコ（コントロール）とＰＱＱ存在下で飼育したオオミジンコを利用した。二つの１００ｍｍプラスチックシャーレに１５ｍＬのミネラルウォーターをそれぞれを入れ、そこにそれぞれのＰＱＱなし条件下で飼育したオオミジンコ（コントロール）とＰＱＱ存在下で飼育したオオミジンコを１匹ずつ移した。シャーレは隣同士に置き、１分間のミジンコの動きを録画した。これを違う個体を用いて３回繰り返した。そしてＫｉｎｏｖｅａ動画分析ソフトを用いてミジンコの３０秒間移動距離を分析した。
(Example 7) Evaluation of athletic ability The Daphnia magna (control) bred under the condition without PQQ and the Daphnia magna bred in the presence of PQQ described in Example 5 were used. 15 mL of mineral water was placed in each of two 100 mm plastic petri dishes, and one Daphnia magna (control) bred under the condition of no PQQ and one Daphnia magna bred in the presence of PQQ were transferred thereto. The petri dishes were placed next to each other and the movement of the daphnia was recorded for one minute. This was repeated 3 times with different individuals. Then, the movement distance of Daphnia was analyzed for 30 seconds using Kinovea video analysis software.
上記のとおり、ＰＱＱ摂取によりオオミジンコの運動量の減少は見られず、寧ろＰＱＱ摂取により約１．２倍の運動量の向上が認められた。これによれば、ＰＱＱ摂取によってオオミジンコの運動機能が向上した可能性がある。また、脂肪減少は運動量が増えた影響と代謝活性の複合的な効果とも考えられる。なお、オオミジンコの動き自体は通常の運動であり、ヒトでいうところの通常の歩行と見做せるものと考えられる。 As described above, the intake of PQQ did not reduce the amount of exercise of Daphnia magna, but rather the intake of PQQ improved the amount of exercise by about 1.2 times. According to this, it is possible that the motor function of Daphnia magna was improved by ingesting PQQ. In addition, fat loss is considered to be a combined effect of increased exercise and metabolic activity. In addition, the movement of Daphnia magna itself is a normal movement, and it is considered that it can be regarded as a normal walking in humans.
本発明の剤は、脂質の減少促進剤あるいは生殖機能の改善剤として、産業上の利用可能性を有する。 The agent of the present invention has industrial applicability as a lipid reduction promoter or a reproductive function improving agent.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019208089A JP2021078397A (en) | 2019-11-18 | 2019-11-18 | Lipid decrease promoter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019208089A JP2021078397A (en) | 2019-11-18 | 2019-11-18 | Lipid decrease promoter |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2021078397A true JP2021078397A (en) | 2021-05-27 |
Family
ID=75961580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019208089A Pending JP2021078397A (en) | 2019-11-18 | 2019-11-18 | Lipid decrease promoter |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2021078397A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113813261A (en) * | 2021-09-15 | 2021-12-21 | 常州市妇幼保健院 | Application of pyrroloquinoline quinone in preventing and/or treating female reproductive dysfunction |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012001507A (en) * | 2010-06-18 | 2012-01-05 | Osaka Prefecture Univ | Ptp1b inhibitor, and diabetes treatment agent, skin external pharmaceutical preparation and food containing the same |
| JP2019077640A (en) * | 2017-10-25 | 2019-05-23 | 三菱瓦斯化学株式会社 | Herb tea drink |
-
2019
- 2019-11-18 JP JP2019208089A patent/JP2021078397A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012001507A (en) * | 2010-06-18 | 2012-01-05 | Osaka Prefecture Univ | Ptp1b inhibitor, and diabetes treatment agent, skin external pharmaceutical preparation and food containing the same |
| JP2019077640A (en) * | 2017-10-25 | 2019-05-23 | 三菱瓦斯化学株式会社 | Herb tea drink |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113813261A (en) * | 2021-09-15 | 2021-12-21 | 常州市妇幼保健院 | Application of pyrroloquinoline quinone in preventing and/or treating female reproductive dysfunction |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5145035B2 (en) | Use of β-cryptoxanthin | |
| EP1785132A1 (en) | Constitutional function-improving agents | |
| EP2050444B1 (en) | Fatigue-reducing agent | |
| CN102781438A (en) | Anaplerotic therapy for alzheimer's disease and the aging brain | |
| ES2314485T3 (en) | COMPOSITIONS THAT INCLUDE PANTOTENIC ACID OR DERIVATIVES OF THE SAME AND ITS USE TO STIMULATE THE APPETITE. | |
| WO2001087291A1 (en) | Compositions normalizing circadian rhythm | |
| EA025256B1 (en) | Composition useful for the treatment of lipid metabolism disorders | |
| EP2532351B1 (en) | Agent for improving motility function | |
| KR101695848B1 (en) | A composition comprising ginsenoside f2 for preventing or treating non-alcoholic liver disease | |
| WO2007119588A1 (en) | Brain function-improving agent, and functional food containing the improving agent | |
| JP5547486B2 (en) | Composition containing sesamin and arachidonic acid | |
| JP2021078397A (en) | Lipid decrease promoter | |
| JP5922862B2 (en) | Mitochondrial function improver | |
| JP2010222284A (en) | Blood gip increase inhibitor | |
| EP1327443A1 (en) | Therapeutic or preventing agent for the diseases caused by a decrease in the expression level of the klotho protein | |
| JP2007070253A (en) | Agent for preventing and treating obesity and diabetes | |
| JP2008056628A (en) | Sleep inducer and stress insomnia ameliorating agent | |
| WO2020218148A1 (en) | Lipid peroxide production inhibitor | |
| JP2007230954A (en) | Sleep inducer and stress insomnia-improving agent | |
| JP7344661B2 (en) | Method for producing food composition | |
| JP6391959B2 (en) | Non-alcoholic steatohepatitis ameliorating agent and ameliorating nutrition composition | |
| WO2022224776A1 (en) | Lipid decrease promoter | |
| CN110831587A (en) | Betaine for preventing obesity | |
| JP2000302677A (en) | Medicine and food/feed composition having improving action on carnitine self production ability | |
| JP2021028311A (en) | Liver glycogen accumulation promoter |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200701 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221014 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230922 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230926 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231116 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240117 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240411 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20240418 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20240712 |