KR102037719B1 - Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients - Google Patents
Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients Download PDFInfo
- Publication number
- KR102037719B1 KR102037719B1 KR1020180025864A KR20180025864A KR102037719B1 KR 102037719 B1 KR102037719 B1 KR 102037719B1 KR 1020180025864 A KR1020180025864 A KR 1020180025864A KR 20180025864 A KR20180025864 A KR 20180025864A KR 102037719 B1 KR102037719 B1 KR 102037719B1
- Authority
- KR
- South Korea
- Prior art keywords
- ionone
- composition
- active ingredient
- depression
- acid
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 133
- 229930002839 ionone Natural products 0.000 title claims abstract description 87
- 150000002499 ionone derivatives Chemical class 0.000 title claims abstract description 87
- 239000004480 active ingredient Substances 0.000 title claims abstract description 38
- 230000002180 anti-stress Effects 0.000 title claims abstract description 35
- 239000000935 antidepressant agent Substances 0.000 title abstract description 12
- 229940005513 antidepressants Drugs 0.000 title abstract description 11
- 239000002249 anxiolytic agent Substances 0.000 title abstract description 11
- 239000003795 chemical substances by application Substances 0.000 title abstract description 10
- 230000000949 anxiolytic effect Effects 0.000 title 1
- 229940005530 anxiolytics Drugs 0.000 title 1
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 239000002537 cosmetic Substances 0.000 claims description 44
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 claims description 35
- XMLSXPIVAXONDL-UHFFFAOYSA-N trans-jasmone Natural products CCC=CCC1=C(C)CCC1=O XMLSXPIVAXONDL-UHFFFAOYSA-N 0.000 claims description 34
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 claims description 33
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 29
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 claims description 20
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 claims description 20
- 239000008280 blood Substances 0.000 claims description 18
- 210000004369 blood Anatomy 0.000 claims description 18
- 235000013376 functional food Nutrition 0.000 claims description 16
- 239000000796 flavoring agent Substances 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 12
- XMLSXPIVAXONDL-PLNGDYQASA-N Jasmone Chemical compound CC\C=C/CC1=C(C)CCC1=O XMLSXPIVAXONDL-PLNGDYQASA-N 0.000 claims description 11
- 230000006872 improvement Effects 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 239000002304 perfume Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 235000019634 flavors Nutrition 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 9
- 208000020401 Depressive disease Diseases 0.000 claims description 6
- 230000001430 anti-depressive effect Effects 0.000 abstract description 13
- 230000000049 anti-anxiety effect Effects 0.000 abstract description 12
- PSQYTAPXSHCGMF-BQYQJAHWSA-N β-ionone Chemical compound CC(=O)\C=C\C1=C(C)CCCC1(C)C PSQYTAPXSHCGMF-BQYQJAHWSA-N 0.000 description 52
- 235000002639 sodium chloride Nutrition 0.000 description 43
- SFEOKXHPFMOVRM-UHFFFAOYSA-N (+)-(S)-gamma-ionone Natural products CC(=O)C=CC1C(=C)CCCC1(C)C SFEOKXHPFMOVRM-UHFFFAOYSA-N 0.000 description 24
- 238000004519 manufacturing process Methods 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 22
- 238000009472 formulation Methods 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 19
- -1 ketone compound Chemical class 0.000 description 19
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 230000036506 anxiety Effects 0.000 description 17
- 239000003205 fragrance Substances 0.000 description 16
- 230000036541 health Effects 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000013329 compounding Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 239000006071 cream Substances 0.000 description 14
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 14
- 239000006210 lotion Substances 0.000 description 14
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000004615 ingredient Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 235000013361 beverage Nutrition 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 235000013305 food Nutrition 0.000 description 11
- 239000008213 purified water Substances 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 235000010254 Jasminum officinale Nutrition 0.000 description 10
- 240000005385 Jasminum sambac Species 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 125000003690 ionone group Chemical group 0.000 description 10
- 239000003755 preservative agent Substances 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 235000011187 glycerol Nutrition 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 235000005911 diet Nutrition 0.000 description 8
- 230000037213 diet Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000003340 mental effect Effects 0.000 description 8
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 8
- 229940088594 vitamin Drugs 0.000 description 8
- 229930003231 vitamin Natural products 0.000 description 8
- 235000013343 vitamin Nutrition 0.000 description 8
- 239000011782 vitamin Substances 0.000 description 8
- 238000007796 conventional method Methods 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 229960000890 hydrocortisone Drugs 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 208000020016 psychiatric disease Diseases 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003246 corticosteroid Substances 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 235000016709 nutrition Nutrition 0.000 description 6
- 150000007524 organic acids Chemical class 0.000 description 6
- 235000013772 propylene glycol Nutrition 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 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 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229920001214 Polysorbate 60 Polymers 0.000 description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 238000003287 bathing Methods 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 239000004359 castor oil Substances 0.000 description 5
- 235000019438 castor oil Nutrition 0.000 description 5
- 238000004040 coloring Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 235000021590 normal diet Nutrition 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 5
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 5
- 229940113124 polysorbate 60 Drugs 0.000 description 5
- 239000000344 soap Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 150000003722 vitamin derivatives Chemical class 0.000 description 5
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 102400000739 Corticotropin Human genes 0.000 description 4
- 101800000414 Corticotropin Proteins 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- 238000011891 EIA kit Methods 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 241000700159 Rattus Species 0.000 description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 229930003427 Vitamin E Natural products 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 108060000200 adenylate cyclase Proteins 0.000 description 4
- 102000030621 adenylate cyclase Human genes 0.000 description 4
- UZFLPKAIBPNNCA-BQYQJAHWSA-N alpha-ionone Chemical class CC(=O)\C=C\C1C(C)=CCCC1(C)C UZFLPKAIBPNNCA-BQYQJAHWSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 235000015165 citric acid Nutrition 0.000 description 4
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 4
- 229960000258 corticotropin Drugs 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 229940057995 liquid paraffin Drugs 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 230000035764 nutrition Effects 0.000 description 4
- 239000003488 releasing hormone Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 230000007958 sleep Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229940032094 squalane Drugs 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 235000019165 vitamin E Nutrition 0.000 description 4
- 239000011709 vitamin E Substances 0.000 description 4
- 229940046009 vitamin E Drugs 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010010144 Completed suicide Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 244000000626 Daucus carota Species 0.000 description 3
- 235000002767 Daucus carota Nutrition 0.000 description 3
- 206010054089 Depressive symptom Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 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 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- 230000001919 adrenal effect Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- UZFLPKAIBPNNCA-UHFFFAOYSA-N alpha-ionone Natural products CC(=O)C=CC1C(C)=CCCC1(C)C UZFLPKAIBPNNCA-UHFFFAOYSA-N 0.000 description 3
- 239000003674 animal food additive Substances 0.000 description 3
- 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 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 238000007667 floating Methods 0.000 description 3
- 235000013373 food additive Nutrition 0.000 description 3
- 239000002778 food additive Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 229960001031 glucose Drugs 0.000 description 3
- 229940075529 glyceryl stearate Drugs 0.000 description 3
- 235000013402 health food Nutrition 0.000 description 3
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 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
- 239000001630 malic acid Substances 0.000 description 3
- 235000011090 malic acid Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000008450 motivation Effects 0.000 description 3
- 239000002417 nutraceutical Substances 0.000 description 3
- 235000021436 nutraceutical agent Nutrition 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 208000028173 post-traumatic stress disease Diseases 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229960002477 riboflavin Drugs 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000002453 shampoo Substances 0.000 description 3
- 208000019116 sleep disease Diseases 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000009182 swimming Effects 0.000 description 3
- 229940037128 systemic glucocorticoids Drugs 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
- 244000144725 Amygdalus communis Species 0.000 description 2
- 235000011437 Amygdalus communis Nutrition 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 206010002869 Anxiety symptoms Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 2
- 206010012239 Delusion Diseases 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 208000011688 Generalised anxiety disease Diseases 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 206010034912 Phobia Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 244000235659 Rubus idaeus Species 0.000 description 2
- 235000009122 Rubus idaeus Nutrition 0.000 description 2
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 206010042209 Stress Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000013832 Valeriana officinalis Nutrition 0.000 description 2
- 244000126014 Valeriana officinalis Species 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- 229930003451 Vitamin B1 Natural products 0.000 description 2
- 229930003471 Vitamin B2 Natural products 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 235000020224 almond Nutrition 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- IVLCENBZDYVJPA-ARJAWSKDSA-N cis-Jasmone Natural products C\C=C/CC1=C(C)CCC1=O IVLCENBZDYVJPA-ARJAWSKDSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 231100000868 delusion Toxicity 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000000686 essence Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 208000029364 generalized anxiety disease Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 2
- 235000015243 ice cream Nutrition 0.000 description 2
- 206010022437 insomnia Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 235000014380 magnesium carbonate Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- GSGDTSDELPUTKU-UHFFFAOYSA-N nonoxybenzene Chemical compound CCCCCCCCCOC1=CC=CC=C1 GSGDTSDELPUTKU-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000002884 skin cream Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229950011392 sorbitan stearate Drugs 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 2
- 229950004616 tribromoethanol Drugs 0.000 description 2
- 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 2
- 235000016788 valerian Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 235000019155 vitamin A Nutrition 0.000 description 2
- 239000011719 vitamin A Substances 0.000 description 2
- 235000010374 vitamin B1 Nutrition 0.000 description 2
- 239000011691 vitamin B1 Substances 0.000 description 2
- 235000019164 vitamin B2 Nutrition 0.000 description 2
- 239000011716 vitamin B2 Substances 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 239000011787 zinc oxide Substances 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- MXOAEAUPQDYUQM-QMMMGPOBSA-N (S)-chlorphenesin Chemical compound OC[C@H](O)COC1=CC=C(Cl)C=C1 MXOAEAUPQDYUQM-QMMMGPOBSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- LCVHZNSIAYNAGX-UHFFFAOYSA-N 2-ethylhexyl 3,5,5-trimethylhexanoate Chemical compound CCCCC(CC)COC(=O)CC(C)CC(C)(C)C LCVHZNSIAYNAGX-UHFFFAOYSA-N 0.000 description 1
- YNVZDODIHZTHOZ-UHFFFAOYSA-K 2-hydroxypropanoate;iron(3+) Chemical compound [Fe+3].CC(O)C([O-])=O.CC(O)C([O-])=O.CC(O)C([O-])=O YNVZDODIHZTHOZ-UHFFFAOYSA-K 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- BGRXBNZMPMGLQI-UHFFFAOYSA-N 2-octyldodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC BGRXBNZMPMGLQI-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- QULIOZDJZXKLNY-UHFFFAOYSA-N 3,4,5-trihydroxy-2-propylbenzoic acid Chemical compound CCCC1=C(O)C(O)=C(O)C=C1C(O)=O QULIOZDJZXKLNY-UHFFFAOYSA-N 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 240000000073 Achillea millefolium Species 0.000 description 1
- 235000007754 Achillea millefolium Nutrition 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 235000003840 Amygdalus nana Nutrition 0.000 description 1
- 244000296825 Amygdalus nana Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- VLVTUDUYHCPENC-ONYUMSKCSA-N CC(=O)\C=C\C1C(C)=CCCC1(C)C.CC(=O)\C=C\C1C(C)=CCCC1(C)C Chemical group CC(=O)\C=C\C1C(C)=CCCC1(C)C.CC(=O)\C=C\C1C(C)=CCCC1(C)C VLVTUDUYHCPENC-ONYUMSKCSA-N 0.000 description 1
- DHFUFHYLYSCIJY-WSGIOKLISA-N CCCCCCCCCCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O Chemical compound CCCCCCCCCCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DHFUFHYLYSCIJY-WSGIOKLISA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000003255 Carthamus tinctorius Nutrition 0.000 description 1
- 244000020518 Carthamus tinctorius Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 235000019973 FDA food additive Nutrition 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 235000017309 Hypericum perforatum Nutrition 0.000 description 1
- 244000141009 Hypericum perforatum Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 229930183419 Irisone Natural products 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000018330 Macadamia integrifolia Nutrition 0.000 description 1
- 235000003800 Macadamia tetraphylla Nutrition 0.000 description 1
- 240000000912 Macadamia tetraphylla Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 206010027951 Mood swings Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000011432 Prunus Nutrition 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 206010042458 Suicidal ideation Diseases 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 235000009430 Thespesia populnea Nutrition 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 235000009392 Vitis Nutrition 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 238000009825 accumulation Methods 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008649 adaptation response Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000002386 air freshener Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 150000001381 alpha-ionone derivatives Chemical class 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229960004538 alprazolam Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 230000001153 anti-wrinkle effect Effects 0.000 description 1
- 229940125713 antianxiety drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent 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
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 150000001588 beta-ionone derivatives Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229940037769 calcium carbonate 100 mg Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 235000012255 calcium oxide Nutrition 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229910021346 calcium silicide Inorganic materials 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229940047493 celexa Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940073639 ceteareth-6 Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 229960003993 chlorphenesin Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 1
- 229960004874 choline bitartrate Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- 239000002725 coal tar dye Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940086555 cyclomethicone Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 229940105990 diglycerin Drugs 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 229940008099 dimethicone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 229940100549 ethylhexyl isononanoate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 238000003958 fumigation Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 229930007090 gamma-ionone Chemical class 0.000 description 1
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 230000008571 general function Effects 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 239000008266 hair spray Substances 0.000 description 1
- 239000008269 hand cream Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 229940051250 hexylene glycol Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- ZCTXEAQXZGPWFG-UHFFFAOYSA-N imidurea Chemical compound O=C1NC(=O)N(CO)C1NC(=O)NCNC(=O)NC1C(=O)NC(=O)N1CO ZCTXEAQXZGPWFG-UHFFFAOYSA-N 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229960004391 lorazepam Drugs 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000010466 nut oil Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940073665 octyldodecyl myristate Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 235000012830 plain croissants Nutrition 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 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
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- SXBRULKJHUOQCD-UHFFFAOYSA-N propanoic acid Chemical compound CCC(O)=O.CCC(O)=O SXBRULKJHUOQCD-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940035613 prozac Drugs 0.000 description 1
- 235000014774 prunus Nutrition 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 235000018341 sodium sesquicarbonate Nutrition 0.000 description 1
- 229910000031 sodium sesquicarbonate Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- CEAYCPAHSNTNGO-UHFFFAOYSA-M sodium;ethane-1,2-diamine;acetate Chemical compound [Na+].CC([O-])=O.NCCN CEAYCPAHSNTNGO-UHFFFAOYSA-M 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 229950004959 sorbitan oleate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000002438 stress hormone Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 235000020238 sunflower seed Nutrition 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229940026510 theanine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008448 thought Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- WCTAGTRAWPDFQO-UHFFFAOYSA-K trisodium;hydrogen carbonate;carbonate Chemical compound [Na+].[Na+].[Na+].OC([O-])=O.[O-]C([O-])=O WCTAGTRAWPDFQO-UHFFFAOYSA-K 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
- SFEOKXHPFMOVRM-BQYQJAHWSA-N γ-ionone Chemical class CC(=O)\C=C\C1C(=C)CCCC1(C)C SFEOKXHPFMOVRM-BQYQJAHWSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/35—Ketones, e.g. benzophenone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q13/00—Formulations or additives for perfume preparations
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
Abstract
본 발명은 이오논을 유효성분으로 함유하는 항스트레스제, 항우울제 또는 항불안제 조성물에 관한 것으로서, 보다 구체적으로 본 발명은 이오논 또는 이의 염을 유효성분으로 포함하는 항스트레스용 조성물, 우울증 또는 불안장애의 예방, 개선 또는 치료용 조성물을 제공하는 것이다.The present invention relates to an antistress agent, antidepressant or anti-anxiety composition containing ionone as an active ingredient, and more particularly, the present invention relates to an antistress composition comprising depression or an salt thereof as an active ingredient, depression or anxiety disorder. It is to provide a composition for preventing, improving or treating.
Description
본 발명은 이오논을 유효성분으로 함유하는 항스트레스제, 항우울제 또는 항불안제 조성물에 관한 것으로서, 보다 구체적으로 본 발명은 이오논 또는 이의 염을 유효성분으로 포함하는 항스트레스용 조성물, 우울증 또는 불안장애의 예방, 개선 또는 치료용 조성물을 제공하는 것이다.The present invention relates to an antistress agent, antidepressant or anti-anxiety composition containing ionone as an active ingredient, and more particularly, the present invention relates to an antistress composition comprising depression or an salt thereof as an active ingredient, depression or anxiety disorder. It is to provide a composition for preventing, improving or treating.
스트레스란 내/외부적인 자극(stressor) 또는 유발인자(trigger)에 대응하는 신체의 적응 반응이며, 의학적으로는 부신피질 자극호르몬의 분비를 촉진하는 해로운 자극이라고 정의하고 있다. 1936년 캐나다의 생리학자인 셀리(H. Selye) 박사가 네이처에 "스트레스 학설"을 발표한 이래 '스트레스'란 용어가 사용되기 시작하였다.Stress is an adaptive response of the body to internal and external stressors or triggers, and medically, it is defined as a harmful stimulus that promotes the secretion of corticosteroids. The term "stress" began to be used in 1936 when Canadian physiologist Dr. H. Selye published Nature's "Stress Theory."
스트레스의 원인이 되는 자극은 물리적, 심리적, 생리적 자극으로 분류된다. 물리적 자극은 자연계에 존재하는 기온, 자외선 등을, 심리적 자극은 정신적인 고통, 분노, 불안, 긴장 등을, 생리적 자극은 세균이나 바이러스, 알레르기 물질 등을 가리킨다. 특히 심리적 자극에 의한 우울함, 불안, 불면, 식욕감퇴 등의 증상이 반복되면 우울증(depression), 불안증(anxiety), 수면장애(sleep disorder)와 같은 질병을 유발한다. Stimulus that causes stress is classified into physical, psychological, and physiological stimuli. Physical stimulation refers to temperature, ultraviolet rays, etc. that exist in the natural world, psychological stimulation refers to mental pain, anger, anxiety, tension, and physiological stimulation refers to bacteria, viruses, and allergens. In particular, repeated symptoms such as depression, anxiety, insomnia, and loss of appetite caused by psychological stimulation cause diseases such as depression, anxiety, and sleep disorder.
우울증은 의욕 저하와 우울감을 주요 증상으로 하여 다양한 인지, 정신 또는 신체적 증상을 일으킴으로써 일상 기능의 저하를 가져오는 질환으로 생각의 과정, 동기, 의욕, 행동, 수면 등 전반적인 기능 저하로 인해 일상생활이 어려우며, 유병율, 자살률과도 높은 상관성이 있다. 불안증은 통상 6개월 이상에 걸쳐 지속적이고 회복되지 않는 신경과민, 긴장, 근심 등을 나타내는 정신적인 질환으로서, 특별한 이유 없이 사소한 사건 하나하나에도 극도의 불안을 느끼게 된다. 수면장애는 정신병적 증상인 자아해체, 환각, 망상 등을 경험하게 되며, 쥐를 대상으로 한 수면박탈 실험 결과 전신쇠약, 피부병, 체중감소, 에너지 소비 증가 및 체온하강 등의 현상이 나타났으며, 심하게는 사망에 이르는 것으로 보고되었다(Dugovic et al., 1999 High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations J. Neurosci. 19(19); 8656-8664).Depression is a disease that causes deterioration of daily functions by causing various cognitive, mental or physical symptoms due to lowered motivation and depression, and it causes a decline in daily functioning due to deterioration of overall functions such as thought, motivation, motivation, behavior, and sleep. It is difficult and has a high correlation with the prevalence and suicide rate. Anxiety is a mental disorder that usually shows persistent, unrecoverable neurological hypersensitivity, tension, and anxiety over six months, with extreme anxiety in every minor event for no particular reason. Sleep disorders include psychotic symptoms such as self-dissolution, hallucinations, and delusions. Sleep deprivation experiments in rats showed systemic weakness, skin disease, weight loss, increased energy consumption and decreased body temperature. Severe deaths have been reported (Dugovic et al., 1999 High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations J. Neurosci. 19 (19); 8656-8664).
과도한 정신적 스트레스를 받는 경우, 시상하부-뇌하수체-부신 축(hypothalamic-pituitary-adrenal axis, HPA axis)으로 이어지는 순환계(circulation system)를 통하여 혈액으로 호르몬 분비가 이루어진다. 뇌의 시상하부에서 부신피질 자극 호르몬 방출인자(corticotropin releasing factor, CRF)가 생성되고, 이는 뇌하수체에서 발현되는 CRF 수용체(CRF receptor)와 결합하여 부신피질 자극 호르몬(adrenocorticotropic hormone, ACTH)을 방출하게 한다. ACTH는 혈액 및 림프절을 통해 부신에 도착하게 되어 코르티졸(cortisol) 등 당질코르티코이드(glucocorticoid)의 분비를 촉진하며, 혈액으로 분비된 당질코르티코이드는 신체 각 기관으로 전달되게 된다. In case of excessive mental stress, hormones are secreted into the blood through a circulatory system leading to the hypothalamic-pituitary-adrenal axis (HPA axis). The corticotropin releasing factor (CRF) is produced in the hypothalamus of the brain, which binds to the CRF receptor expressed in the pituitary gland and releases adrenocorticotropic hormone (ACTH). . ACTH reaches the adrenal glands through the blood and lymph nodes, promoting the secretion of glucocorticoids such as cortisol, and the glucocorticoids secreted into the blood are delivered to each organ.
코르티졸은 스테로이드 호르몬 중 스트레스 호르몬으로 근육을 긴장시키고, 감각기관을 예민하게 만들어서 정신적인 스트레스에 대응할 수 있도록 인체를 준비시킨다. 그러나, 반복적인 정신적 스트레스로 인하여 코르티졸 호르몬이 지속적으로 분비됨으로써 이의 혈중 농도가 높아지는 경우, 신체를 늘 긴장한 상태로 유지시키고 숙면을 방해하여 수면장애를 유도한다. 이는 또다시 정신적 스트레스의 원인이 되어, 우울한 증상을 발생시키는 악순환이 계속된다. 극심한 정신적 스트레스에 의해 코르티졸 분비 조절 기능이 상실되면, 코르티졸이 과도하게 분비되어 신경계 전반에 걸쳐 뇌 위축 및 손상이 야기되고, 이로 인한 심각한 우울증 증세 및 자살 발생 가능성이 보고되고 있다.Cortisol is a stress hormone of steroid hormones that prepares the body to cope with mental stress by straining the muscles and making the sense organs sensitive. However, when the cortisol hormone is continuously secreted due to repetitive mental stress, the blood concentration of the cortisol is kept constant, causing the body to stay in a tense state and disturb sleep. This, in turn, causes mental stress, causing a vicious cycle of depressive symptoms. Loss of cortisol secretion control function by severe mental stress causes excessive cortisol release, leading to brain atrophy and damage throughout the nervous system, resulting in severe depression and suicide.
CRF 유전자가 과발현 된 마우스의 경우, 불안증 및 우울증의 행동이 증가하고 탐색 행동이 감소하는 증상을 보인다. 이는 정서장애에 연루되어 쿠싱증후군(cushing syndrome)을 유발할 수 있으며, 과도한 지방 축적, 근육 위축, 얇은 피부 및 탈모 등의 신체적 변화를 보이고, 부신피질자극호르몬(ACTH) 및 코르티졸의 혈장 수준을 상승시킨다고 알려져 있다. In mice overexpressing the CRF gene, symptoms of anxiety and depression are increased and navigational behavior is reduced. It has been implicated in emotional disorders and can cause Cushing syndrome, which causes physical changes such as excessive fat accumulation, muscle atrophy, thin skin and hair loss, and raises plasma levels of corticosteroids (ACTH) and cortisol. Known.
이러한 증상은 CRF 길항제(antagonist)의 투여에 의해 완화된다는 보고가 있다(Stenzel-poore et al., 1994). 이는 CRF 과발현에 의해 발생된 행동이 CRF와 CRF 수용체에 의해 매개된다는 것을 시사한다. CRF 수용체는 세포막에 존재하는 G 단백질 연결 수용체(G-protein coupled receptor, GPCR) 패밀리에 속하며, CRF에 의해 활성이 증가되면 그 하위에 있는 adenylyl cyclase(AC) 효소의 활성이 증가되어 cAMP 농도를 증가시킴으로서 관련된 생체반응이 일어난다고 알려져 있다. 그 반대로 길항제에 의해 CRF 수용체의 활성이 억제되면 그 하위에 있는 아데닐릴 고리화효소(adenylyl cyclase, AC)의 활성이 감소되어 cAMP 농도를 감소시킨다고 알려져 있다.These symptoms are reported to be alleviated by the administration of CRF antagonists (Stenzel-poore et al., 1994). This suggests that the behavior caused by CRF overexpression is mediated by CRF and the CRF receptor. CRF receptors belong to the family of G-protein coupled receptors (GPCRs) in the cell membrane, and when the activity is increased by CRF, the activity of adenylyl cyclase (AC) enzymes underneath is increased to increase cAMP concentration. It is known that related bioreactions occur. On the contrary, when the activity of the CRF receptor is inhibited by the antagonist, it is known that the activity of adenylyl cyclase (AC) underneath is reduced, thereby decreasing the cAMP concentration.
초기 스트레스 회복 식이보조제 시장은 고추나물(St. John's wort; 우울증, 불안장해 개선 작용)과 쥐오줌풀(Valerian; 진정 작용, 수면개선 작용)이 이끌어왔으나 최근 항스트레스 시장이 급격히 확대됨에 따라 새로운 항스트레스 물질 개발이 요구되고 있다. 다만, 가바(γ-aminobutoryl acid, GABA), 테아닌(theanine) 및 포스파티딜세린(phosphatidyl serine)과 같은 소수의 대응 상품만이 언급되고 있고, 새로 출시되는 제품들도 상기 5종의 항스트레스 물질 중 하나 이상을 배합하여 개발되고 있다. The early stress recovery diet supplement market was led by St. John's wort (depression, anxiety improvement) and Valerian (sedative, sleep improvement), but the new antistress market has recently expanded rapidly. Material development is required. However, only a few counterparts such as γ-aminobutoryl acid (GABA), theanine and phosphatidyl serine are mentioned, and newly released products are one of the five antistress substances. It is developed by mix | blending the above.
현재 허가받은 우울증 치료제로는 신경세포 말단에서 분비되는 세로토닌(serotonin)이 연접이전세포로 재흡수 되는 것을 억제하여 혈중 세로토닌 농도 및 활성도를 증가시킴으로써 일시적인 기분전환 효과를 나타내어 치료 효과를 유도하는 약물들로, 미국 FDA 승인을 받고 판매되고 있는 프로작(Prozac™, 성분명 fluoxetine)이나 세렉사(celexa™, 성분명 citalopram) 등이 있다. 그러나, 이러한 세로토닌 재흡수 억제제의 경우, 환자의 절반 정도만 증상 호전을 보이고 최소 4개월 이상의 복용기간이 요구되며, 환자에 따라서는 2년 내지 3년 동안 계속 복용하여야 하는 문제점이 있다. 또한, 상기 세로토닌 재흡수 억제제의 경우, 상기 약의 복용을 끊었을 경우 대부분 증상이 6개월 내지 12개월 이내 재발함이 관찰되었고 부작용 또한 심각한 수준인 것으로 알려져 있다. Currently approved antidepressants are drugs that induce a therapeutic effect by suppressing the reabsorption of serotonin released from neuronal ends into pre-synaptic cells, resulting in transient mood swings by increasing blood serotonin concentration and activity. Prozac ™, ingredient fluoxetine, and Celexa ™ ingredient citalopram. However, in the case of such serotonin reuptake inhibitors, only about half of patients show symptomatic improvement and a minimum period of 4 months or more is required, and depending on the patient, there is a problem of continuing to take for 2 to 3 years. In addition, in the case of the serotonin reuptake inhibitor, most of the symptoms are observed within 6 to 12 months when the drug is stopped, and side effects are also known to be serious.
항불안제 약물로는 디아제팜(diazepam), 로라제팜(lorazepam), 클로나제팜(clonazepam), 알프라졸람(alprazolam) 등의 벤조디아제핀(benzodiazepine) 계통들이 주로 사용되고 있고, 졸피뎀(zolpidem)과 같은 이미다조피리딘(imidazopyridine) 계통의 약물도 불안증으로 인한 단기 불면증 치료에 사용되고 있다. 그러나, 불안장애 및 정신질환에 쓰이고 있는 약물들은 중추신경의 GABA 수용체에 직접적으로 작용하여 중추신경을 억제하게 되기 때문에 과다한 진정 작용이 나타나며, 우울, 근이완, 최면 등의 중추억제 작용이 강화되어 나타날 수 있다. 또한 불안장애 및 정신질환에 사용되고 있는 약물들은 심리적, 신체적으로 의존을 하게 만들어 약물 남용이 우려되는 등의 위험성을 내포하고 있다는 문제점이 있다.As anti-anxiety drugs, benzodiazepine strains such as diazepam, lorazepam, clonazepam and alprazolam are mainly used, and imidazopyridine such as zolpidem. Drugs of the imidazopyridine family are also used to treat short-term insomnia due to anxiety. However, drugs used for anxiety disorders and mental disorders have a direct effect on the GABA receptors of the central nervous system, which inhibits the central nervous system, resulting in excessive sedation and enhanced central inhibitory effects such as depression, muscle relaxation, and hypnosis. Can be. In addition, drugs that are used for anxiety disorders and mental disorders have a problem that the psychological and physical dependence and the risk of drug abuse is included.
이에 본 출원인은 부작용이 적은 천연물에서 스트레스, 우울 증상 또는 불안 증상을 완화시키는 데 효과가 있는 소재를 개발하기 위해 노력한 결과, 이오논(ionone)이 부신피질 자극 호르몬 방출인자 수용체의 길항제(CRF receptoe anatagonist)로 작용함을 확인하였으며, 이오논과 자스몬(jasmine)을 동시에 사용하는 경우 항스트레스, 항우울 및 항불안증 효과가 현저히 상승하는 것을 확인함으로써 본 발명을 완성하였다. Accordingly, the present inventors have tried to develop a material that is effective in alleviating stress, depressive symptoms or anxiety symptoms in natural products with few side effects. As a result, ionone is an antagonist of the adrenal cortical stimulating hormone releasing factor receptor (CRF receptoe anatagonist). When the ionone and jasmine (jasmine) at the same time used to confirm that the anti-stress, anti-depressant and anti-anxiety effect is significantly increased to complete the present invention.
본 발명의 목적은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 항스트레스용 조성물을 제공하는 것이다.An object of the present invention is to provide an antistress composition comprising ionone or a salt thereof as an active ingredient.
본 발명의 또 다른 목적은 이오논 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 개선용 조성물을 제공하는 것이다.Still another object of the present invention is to provide a composition for preventing or improving depression or anxiety disorder comprising ionone or a salt thereof as an active ingredient.
본 발명의 또 다른 목적은 이오논 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder comprising ionone or a salt thereof as an active ingredient.
본 발명은 상술한 문제점을 해결하기 위한 것으로, 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 항스트레스용 조성물을 제공한다.The present invention is to solve the above problems, and provides an anti-stress composition comprising ionone or a salt thereof as an active ingredient.
본 발명의 일 양상에 따르면, 상기 조성물은 부신피질 자극 호르몬 방출인자의 활성을 저해함으로써 스트레스 증상을 완화시킬 수 있다.According to one aspect of the present invention, the composition may relieve stress symptoms by inhibiting the activity of the corticosteroid hormone releasing factor.
본 발명의 또 다른 일 양상에 따르면, 상기 조성물은 혈중 코르티코스테론 농도를 감소시킴으로써 스트레스 증상을 완화시킬 수 있다.According to another aspect of the present invention, the composition may relieve stress symptoms by reducing blood corticosterone concentration.
본 발명의 또 다른 일 양상에 따르면, 상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함함으로써 스트레스 완화 효과를 유의적으로 상승시킬 수 있다.According to another aspect of the present invention, the composition can significantly increase the stress relief effect by further comprising jasmon (jasmone) or salts thereof as an active ingredient.
본 발명의 일 구현예에 따르면, 상기 조성물은 건강기능식품 조성물, 화장료 조성물 또는 향료 조성물일 수 있다.According to one embodiment of the invention, the composition may be a nutraceutical composition, cosmetic composition or fragrance composition.
또한, 본 발명은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 개선용 조성물을 제공한다.The present invention also provides a composition for the prevention or improvement of depression or anxiety disorder comprising ionone (ionone) or a salt thereof as an active ingredient.
본 발명의 일 양상에 따르면, 상기 조성물은 부신피질 자극 호르몬 방출인자의 활성을 저해함으로써 우울증 또는 불안장애를 예방 또는 개선할 수 있다.According to an aspect of the present invention, the composition may prevent or improve depression or anxiety disorder by inhibiting the activity of the adrenal cortical stimulating hormone releasing factor.
본 발명의 또 다른 일 양상에 따르면, 상기 조성물은 혈중 코르티코스테론 농도를 감소시킴으로써 우울증 또는 불안장애를 예방 또는 개선할 수 있다.According to another aspect of the present invention, the composition may prevent or ameliorate depression or anxiety disorder by reducing blood corticosterone concentration.
본 발명의 또 다른 일 양상에 따르면, 상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함함으로써 우울증 또는 불안장애의 예방 또는 개선 효과를 유의적으로 상승시킬 수 있다.According to another aspect of the present invention, the composition may further increase the effect of preventing or improving depression or anxiety disorder by further comprising jasmone (jasmone) or a salt thereof as an active ingredient.
본 발명의 일 구현예에 따르면, 상기 조성물은 건강기능식품 조성물, 화장료 조성물 또는 향료 조성물일 수 있다.According to one embodiment of the invention, the composition may be a nutraceutical composition, cosmetic composition or fragrance composition.
또한, 본 발명은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder, including ionone (ionone) or a salt thereof as an active ingredient.
본 발명의 또 다른 일 양상에 따르면, 상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함함으로써 우울증 또는 불안장애의 예방 또는 치료 효과를 유의적으로 상승시킬 수 있다.According to another aspect of the present invention, the composition may further increase the effect of preventing or treating depression or anxiety disorder by further comprising jasmone (jasmone) or salts thereof as an active ingredient.
본 발명의 이오논을 유효성분으로 포함하는 항스트레스제, 항우울제 또는 항불안제 조성물은 부신피질 자극 호르몬 방출인자(CRF)의 활성을 저해하는 길항제로 작용할 수 있고, 혈중 코르티코스테론과 같은 당질코르티코이드의 농도를 감소시킴으로써 스트레스로 인한 증상을 완화하고, 우울증 또는 불안장애를 예방하거나, 개선 또는 치료할 수 있다. 따라서 본 발명의 조성물은 항스트레스, 항우울 또는 항불안용 건강기능식품 조성물, 화장료 조성물 등으로 사용될 수 있으며, 항우울제, 항불안제 또는 광범위한 항정신제로 이용될 수 있다.Antistress, antidepressant or anti-anxiety compositions comprising ionone of the present invention as an active ingredient may act as an antagonist that inhibits the activity of the adrenal cortical stimulating hormone releasing factor (CRF) and the concentration of glucocorticoids such as corticosteroids in the blood Reducing the symptoms can alleviate the symptoms caused by stress, prevent, ameliorate or treat depression or anxiety disorder. Therefore, the composition of the present invention can be used as antistress, antidepressant or anti-anxiety dietary supplement composition, cosmetic composition, etc., and can be used as an antidepressant, anti-anxiety agent or a wide range of antipsychotics.
도 1은 CRF 수용체가 형질주입된 HEK293 세포에서 실험 물질 처리에 따른 cAMP의 농도를 나타낸 것이다. 실험 결과는 3회 반복으로 측정한 후 평균과 표준오차(SEM)로 나타내었으며, Student's T-test를 이용한 통계처리로 유의성을 검증하여 CRF와 실험 물질(CP 154,526, 이오논, 또는 이오논 및 자스몬의 복합물)을 함께 처리한 경우와 CRF만 처리했을 때를 비교하고, p < 0.05 시에 유의한 것으로 간주하였다(평균±SEM, * p < 0.05, ** p < 0.01, *** p < 0.001).
도 2는 이오논 또는 이오논과 자스몬의 복합물을 투여시킨 마우스의 꼬리 매달기 실험(A), 강제수영 실험(B) 결과 및 혈장 코르티코스테론 지표 변화(C)를 확인한 것이다. 실험 결과는 평균과 표준오차(SEM)로 나타내었으며, Student's T-test를 이용한 통계처리로 유의성을 검증하여 이오논 투여군, 이오논과 자스몬 동시 투여군과 스트레스 대조군을 비교하고, p < 0.05 시에 유의한 것으로 간주하여 표시하였다(평균±SEM, n = 7, * p < 0.05, ** p < 0.01, *** p < 0.001).
도 3은 CRF 과발현 마우스를 대상으로 실험식이(베타이오논 포함)를 섭취시킨 마우스의 코르티코스테론 농도를 나타낸 것이다(평균±SEM, n = 7, * p < 0.05, ** p < 0.01, *** p < 0.001). Figure 1 shows the concentration of cAMP according to experimental material treatment in HEK293 cells transfected with CRF receptor. Experimental results were measured in three iterations and then expressed as mean and standard error (SEM). Complex) and when treated with CRF alone, were considered significant at p <0.05 (mean ± SEM, * p <0.05, ** p <0.01, *** p <0.001 ).
Figure 2 confirms the tail suspension experiment (A), forced swimming experiment (B) results and plasma corticosterone index change (C) of the mice administered a combination of ionone or ionon and Jasmon complex. The experimental results were expressed as mean and standard error (SEM), and statistical significance using Student's T-test was verified to compare the stress control group with the ionone group, the ionone and jasmine simultaneous group, and was significant at p <0.05. And considered as mean (mean ± SEM, n = 7, * p <0.05, ** p <0.01, *** p <0.001).
Figure 3 shows the corticosteroid concentration of mice fed the experimental diet (including betaionone) in CRF overexpressing mice (mean ± SEM, n = 7, * p <0.05, ** p <0.01, * ** p <0.001).
본 발명자들은 케톤계 화합물인 이오논이 부신피질 자극 호르몬 방출인자(CRF)의 길항제로 작용하고, 혈중 코르티코스테론 농도를 감소시키며, 동물모델에서 스트레스, 우울증 또는 불안 증상을 나타내는 행동지표를 개선시킨다는 점을 확인함으로써, 본 발명을 완성하였다.The inventors have found that the ketone compound ionon acts as an antagonist of corticosteroid-stimulating factor (CRF), reduces blood corticosteroid levels, and improves behavioral indicators of stress, depression or anxiety in animal models. By confirming the point, this invention was completed.
이하, 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 항스트레스용 조성물을 제공한다.The present invention provides an antistress composition comprising ionone or a salt thereof as an active ingredient.
구체적으로, 상기 이오논은 Rubus idaeus(Raspberry, 라즈베리), Daucus carota subsp. Sativus(Carrot, 당근), Prunus dulcis(Almond, 아몬드), Menta(Herb, 허브)에 주로 함유되어 있는 향기 성분으로 주로 꽃 향기를 내는 케톤(ketone)계 화합물이며, 구조식은 C13H20O, 분자량은 192.3 g/mol이다. 이오논은 분자구조에 따라 각각 하기 화학식 1, 2 및 3으로 표시되는 알파이오논(α-ionone), 베타이오논(β-ionone) 및 감마이오논(γ-ionone)의 이성질체를 포함한다. 알파이오논은 (3E)-4-(2,6,6-트리메틸사이클로헥스-2-엔-1-일)부트-3-엔-2-온((3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one), 사이클로시트릴리데네아세톤(cyclocitrylideneacetone), 이리손(irisone), 요논(jonon) 등의 이명으로도 불린다. 알파이오논은 옅은 황색의 투명한 액체성분이고 녹는점은 -49℃, 끓는점은 126 ~ 128℃이다.Specifically, the ionone is Rubus idaeus (Raspberry), Daucus carota subsp. Sativus (Carrot, Carrot), Prunus It is a fragrance ingredient mainly contained in dulcis (Almond, almond) and Menta (Herb, herb). It is a ketone compound which mainly gives a floral fragrance. The structural formula is C 13 H 20 O and molecular weight is 192.3 g / mol. Ionone includes isomers of alpha-ionone, beta-ionone, and gamma-ionone represented by the following
[화학식 1] [Formula 1]
[화학식 2][Formula 2]
[화학식 3][Formula 3]
이오논은 주로 샴푸, 비누, 청소용품, 바디 로션, 화장품, 샤워젤, 헤어 스프레이의 성분으로 이용되고, 한국 KFDA 및 미국 FDA 식품첨가물 데이터베이스에 착향료로 등재되어 있으며, 청량음료, 아이스크림, 츄잉껌 등에 주로 사용된다. 이오논의 생리활성에 관한 연구로는 인체에 해로운 미생물균에 대해 이오논이 강력한 항균활성을 나타낸 것이 유일한 보고(Findic et al, Synthesis of Terpenoid-Like Bischalcones from α- and β-Ionones and Their Biological Activities, Synthetic Communications, 39: 4362-4374, 2009)일 뿐, 다른 생리활성은 전혀 보고된 바가 없다.Ionone is mainly used as a component of shampoos, soaps, cleaning products, body lotions, cosmetics, shower gels, and hair sprays, and is listed as a flavoring agent in the Korean KFDA and US FDA food additive databases, and is mainly used in soft drinks, ice cream, chewing gum, etc. Used. The only report on physiological activity of ionone is that ionon showed strong antimicrobial activity against harmful microorganisms (Findic et al, Synthesis of Terpenoid-Like Bischalcones from α- and β-Ionones and Their Biological Activities, Synthetic Communications, 39: 4362-4374, 2009), but no other biological activity has been reported.
본 발명의 이오논은 상기 이오논과 동일한 효능을 갖는 범위 내에서 이오논 수화물, 이오논 유도체 등을 포함할 수 있고, 이의 용매 화합물이나 입체 이성질체 또한 포함할 수 있다.The ionone of the present invention may include an ionone hydrate, an ionone derivative, and the like within the range having the same efficacy as the ionone, and may also include a solvent compound or stereoisomer thereof.
상기 이오논의 수득방법은 특별히 한정되지 않으며, 상기 이오논을 함유하고 있는 식물로부터 분리하거나, 공지된 제법을 사용하여 화학적으로 합성하거나, 시판되는 것을 사용할 수 있다.The method for obtaining the ionone is not particularly limited, and may be isolated from the plant containing the ionone, chemically synthesized using a known manufacturing method, or commercially available.
본 발명에서, 용어 “화장품학적으로 허용 가능한 염”, “식품학적으로 허용 가능한 염”, “약학적으로 허용 가능한 염” 또는 “이의 염”은 유리산(free acid)에 의해 형성된 산 부가염일 수 있다. 산 부가염은 통상의 방법, 예를 들어 화합물을 과량의 산 수용액에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들어 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조할 수 있다. 또한, 동 몰량의 화합물 및 물 중의 산 또는 알코올 (예를 들어, 글리콜 모노메틸 에테르)을 가열하고, 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다.In the present invention, the term “cosmetic acceptable salt”, “food acceptable salt”, “pharmaceutically acceptable salt” or “salt thereof” may be an acid addition salt formed by free acid. have. Acid addition salts can be prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. In addition, equimolar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
상기 유리산으로는 무기산 또는 유기산을 사용할 수 있다. 상기 무기산의 비제한적인 예로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있으며, 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다. 상기 유기산의 비제한적인 예로는 메탄술폰산, p-톨루엔술폰산, 아세트산, 트리플루오로아세트산, 말레인산(maleic acid), 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산(fumaric acid), 만데르산, 프로피온산(propionic acid), 구연산(citric acid), 젖산(lactic acid), 글리콜산(glycollic acid), 글루콘산(gluconic acid), 갈락투론산(galacturonic acid), 글루탐산, 글루타르산(glutaric acid), 글루쿠론산 (glucuronic acid), 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 하이드로아이오딕산 등을 사용할 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다.As the free acid, an inorganic acid or an organic acid may be used. Non-limiting examples of the inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like, which may be used alone or in combination of two or more. Non-limiting examples of the organic acid are methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid (propionic acid). acid, citric acid, lactic acid, glycolic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid and the like can be used. These may be used alone or in combination of two or more thereof.
또한, 상기 이오논은 염기를 사용하여 화장품학적으로 또는 식품학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리 토금속 염은, 예를 들어 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해시키고, 비용해 화합물 염을 여과한 후 여액을 증발, 건조시켜 얻을 수 있다. 상기 금속염으로는 특히 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 바람직하나 이들에 제한되는 것은 아니다. 또한, 이에 대응하는 은염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 은염 (예를 들어, 질산은)과 반응시켜 얻을 수 있다.In addition, the ionone may use a base to make a cosmetically or food acceptable metal salt. Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compounds salt, and then evaporating and drying the filtrate. As the metal salt, it is particularly preferable to prepare sodium, potassium or calcium salts, but is not limited thereto. Corresponding silver salts can also be obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
상기 이오논의 염은, 달리 지시되지 않는 한, 상기 이오논의 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 모두 포함할 수 있다. 예를 들어 상기 이오논의 염으로는 하이드록시기의 나트륨, 칼슘 및 칼륨염 등이 포함될 수 있고, 아미노기의 기타 화장품학적으로 허용 가능한 염으로는 하드로브로마이드, 황산, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄술포네이트(메실레이트) 및 p-톨루엔술포네이트(토실레이트)염 등을 들 수 있으며 당업계에서 알려진 염의 제조 방법을 통하여 제조될 수 있다.Salts of the ionone may include all salts of acidic or basic groups which may be present in the compound of the ionon, unless otherwise indicated. For example, the salt of the ionon may include sodium, calcium and potassium salts of the hydroxy group, and other cosmetically acceptable salts of the amino group include hardbromide, sulfuric acid, hydrogen sulphate, phosphate, hydrogen phosphate, Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through the method.
본 발명에서 "항스트레스"란 신체 내적, 외적 자극으로 인한 과도한 신체적 반응의 완화 또는 정신적/육체적 피로 회복의 의미로서 구체적으로는 긴장 완화, 불안 완화 또는 집중력 향상의 의미이다.In the present invention, "anti-stress" refers to the relaxation of excessive physical reactions due to internal and external stimulation or to the recovery of mental / physical fatigue. Specifically, the term "antistress" refers to relaxation of tension, relaxation of anxiety or improvement of concentration.
본 발명에 따른 조성물은 부신피질 자극 호르몬 방출인자(corticotropin releasing factor, CRF)의 활성을 저해할 수 있다. The composition according to the present invention may inhibit the activity of corticotropin releasing factor (CRF).
본 발명의 일 실시예에 있어서, HEK293 세포에 CRF 수용체 유전자를 형질주입한 후 CRF 물질 또는 이오논을 처리하고, cAMP 농도를 측정한 결과, CRF만 처리하였을 때에 비해 CRF와 이오논을 동시에 처리하였을 때 세포의 cAMP의 농도 역시 유의적으로 감소(-48%)한 것을 확인함으로써 이오논이 CRF 수용체의 길항제로 작용함을 알 수 있었다(도 1). CRF 유전자가 과발현 된 마우스에서 발견되는 불안증 및 우울증 증상이 CRF 길항제의 투여에 의해 완화된다는 연구로부터 본 발명의 이오논이 항스트레스, 항우울 또는 항불안용 조성물로서의 활성이 있음을 알 수 있었다.In one embodiment of the present invention, CRF receptor genes were transfected into HEK293 cells and then treated with CRF material or ionone, and cAMP concentration was measured. As a result, CRF and ionone were treated simultaneously compared to CRF alone. When the concentration of cAMP of the cells was also significantly decreased (-48%), it was found that ionone acts as an antagonist of the CRF receptor (FIG. 1). Anxiety and depression symptoms found in mice overexpressed by the CRF gene have been shown to be alleviated by the administration of CRF antagonists, indicating that the ionon of the present invention is active as an antistress, antidepressant or antianxiety composition.
또한, 본 발명에 따른 조성물은 혈중 코르티코스테론(corticosterone) 농도를 감소시킬 수 있다.In addition, the composition according to the present invention can reduce the concentration of corticosterone in the blood.
본 발명의 일실시예에 있어서, 이오논을 단회 복강투여한 마우스의 스트레스 행동지표 실험 후 혈중 코르티코스테론의 농도와 CRF 과별현 마우스에 이오논을 포함한 식이를 섭취시켰을 때 혈중 코르티코스테론의 농도를 측정한 결과 각각 대조군에 비해 유의적으로 감소하는 것을 확인함(도 2C, 도 3)으로써 본 발명의 이오논에 항스트레스, 항우울 또는 항불안용 조성물로서의 활성이 있음을 알 수 있었다.In one embodiment of the present invention, blood corticosterone concentrations were obtained when dietary supplements containing ionone were ingested in blood corticosteroid concentrations and CRF over-expression mice after stress behavioral indicators in mice intraperitoneally administered with ionone. As a result of confirming that the significant reduction compared to the control group (Fig. 2C, 3), it was found that the ionone of the present invention has activity as an antistress, antidepressant or anti-anxiety composition.
본 발명의 항스트레스용 조성물은 건강기능식품 조성물, 화장료 조성물 또는 향료 조성물일 수 있다.The antistress composition of the present invention may be a health functional food composition, a cosmetic composition or a perfume composition.
본 발명에서 용어 “건강기능식품”은 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품 조성물은 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 스트레스 완화 효과를 증진시키기 위한 보조제로 섭취가 가능하다.In the present invention, the term "health functional food" refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body. Here, 'functional' means to obtain a useful effect for health purposes such as nutrient control or physiological action on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and the preparation can be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food. The health functional food composition of the present invention has the advantage that there is no side effect that may occur when taking long-term use of the drug, unlike the general medicine, food, and excellent in portability, intake as an adjuvant to enhance the stress relief effect It is possible.
본 발명에 따른 항스트레스용 건강기능식품에 있어서, 상기 이오논을 건강기능식품의 첨가물로 사용하는 경우 이를 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합양은 예방, 건강 또는 치료 등의 각 사용 목적에 따라 적합하게 결정할 수 있다.In the anti-stress health functional food according to the present invention, when the ionone is used as an additive of the health functional food, it may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. have. The mixed amount of the active ingredient can be appropriately determined depending on the purpose of use, such as prevention, health or treatment.
건강기능식품의 제형은 산제, 과립제, 환, 정제, 캡슐제의 형태뿐만 아니라 일반 식품 또는 음료의 형태 어느 것이나 가능하다.Formulations of dietary supplements may be in the form of powders, granules, pills, tablets, capsules, as well as in the form of general foods or beverages.
상기 식품의 종류에는 특별히 제한은 없고, 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸콜렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함할 수 있다.There is no restriction | limiting in particular in the kind of said food, The foodstuff which can add the said substance is a dairy product including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, etc. , Various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, etc., may include all foods in a conventional sense.
일반적으로, 식품 또는 음료의 제조시에 상기 이오논은 원료 100 중량부에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가할 수 있다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 또한 본 발명은 천연물로부터의 분획물을 이용하는 점에서 안전성 면에서 문제가 없으므로 상기 범위 이상의 양으로도 사용할 수 있다.In general, the ionone may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on 100 parts by weight of the raw material in the manufacture of food or beverage. However, in the case of long-term intake for health and hygiene or for health control, the amount may be below the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. The above amount can also be used.
본 발명에 따른 기능성식품 중 음료는 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명에 따른 음료 100 mL당 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g일 수 있다.In the functional food according to the present invention, the beverage may contain various flavors or natural carbohydrates and the like as an additional component as a general beverage. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.
상기 외에 본 발명에 따른 항스트레스용 건강기능식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제를 함유할 수 있다. 그 밖에 본 발명의 항스트레스용 건강기능식품 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 제한되지 않으나 본 발명의 기능성식품 100 중량부 대비 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above-mentioned anti-stress health functional food according to the present invention, various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, And preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages. In addition, the anti-stress health functional food composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The ratio of such additives is not limited, but is generally selected from 0.01 to 0.1 parts by weight relative to 100 parts by weight of the functional food of the present invention.
본 발명에서 사용되는 용어, "화장료 조성물"은 상기 화합물을 포함하는 조성물로서 그 제형은 어떠한 형태라도 가능하다. 이러한 제형의 예를 들면 상기 조성물을 이용하여 제조된 화장료는 영양크림, 아이크림, 마사지크림, 클렌징 크림과 같은 크림류, 팩류, 영양로션과 같은 로션류, 에센스류, 유연화장수, 영양화장수와 같은 화장수류, 파우더류, 파운데이션류 및 메이크업 베이스류 등이고, 본 발명의 목적을 달성하기 위하여 이러한 제형 중 어떠한 형태로도 제조되어 상용화될 수 있으며, 상기 예들에 한정되지 않는다. 또한, 본 발명에 따른 화장료 조성물에는 통상의 화장료 제조 방법으로 제형화할 수 있다. 구체적으로 본 발명의 화장료는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 맛사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 팩, 마스크팩, 마스크시트, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 및 아이섀도로 구성된 그룹에서 선택된 어느 하나의 제형을 가지는 것일 수 있다.As used herein, the term "cosmetic composition" is a composition comprising the compound, the formulation may be in any form. Examples of such formulations include cosmetics prepared using the composition, such as nutrition creams, eye creams, massage creams, creams such as cleansing creams, packs, lotions such as nutrient lotions, essences, soft cosmetics, and nutrient cosmetics. , Powders, foundations, makeup bases, and the like, and may be prepared and commercialized in any of these formulations to achieve the object of the present invention, and are not limited to the above examples. In addition, the cosmetic composition according to the present invention can be formulated by a conventional cosmetic preparation method. Specifically, the cosmetics of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, pack, mask pack, mask sheet It may be one having a formulation selected from the group consisting of, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder and eye shadow.
본 발명의 화장료 조성물은 이오논 또는 이의 염에 더하여 부형제, 담체 등 기타 첨가제를 포함할 수 있으며, 일반 피부 화장료에 배합되는 보통의 성분을 필요한 만큼 적용 배합하는 것이 가능하다.The cosmetic composition of the present invention may include other additives such as excipients, carriers, etc., in addition to ionone or salts thereof, and it is possible to apply and blend as needed the usual ingredients formulated into general skin cosmetics.
구체적으로, 본 발명의 화장료 조성물은 경피 침투 강화제를 추가로 포함할 수 있다. 본 발명에서 사용되는 용어, 경피 침투 강화제란 피부의 혈관세포 내로 원하는 성분이 높은 흡수율로 침투할 수 있게 해주는 조성물이다. 바람직하게는 레시틴 화장품에 사용되는 다른 인지질 성분, 리포좀 성분 등이 포함되지만 이에 국한되지는 않는다.Specifically, the cosmetic composition of the present invention may further include a transdermal penetration enhancer. As used herein, the term transdermal penetration enhancer is a composition that allows a desired component to penetrate into the blood vessel cells of the skin at a high absorption rate. Preferably other phospholipid components, liposome components and the like used in lecithin cosmetics are included, but are not limited to these.
또한, 유상 성분으로서 주로 사용될 수 있는 오일로는 식물성 오일, 광물성 오일, 실리콘유 및 합성유 중에서 선택된 하나 이상을 사용할 수 있다. 보다 구체적으로, 미네랄오일, 사이크로메치콘, 스쿠알란, 옥틸도데실 미리스테이트, 올리브오일, 비티스 비니페라 씨드 오일, 마카다미아너트오일, 글리세릴옥타노에이트, 캐스터오일, 에칠헥실 이소노나노에이트, 디메치콘, 사이크로펜타실록산 및 선플라워씨드 오일 등을 사용할 수 있다.In addition, as the oil which can be mainly used as an oil phase component, one or more selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis binifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dimethicone Chicon, cyclopentasiloxane, sunflower seed oil and the like can be used.
또한, 유화 능력을 보강하기 위하여 계면활성제, 고급 알콜 등을 0.1 내지 5 중량% 첨가할 수 있다. 이러한 계면 활성제로는 비이온 계면활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제, 인지질 등과 같은 통상적인 계면활성제를 사용할 수 있으며, 구체적으로, 소르비탄세스퀴놀리에이트, 폴리솔베이트 60, 글리세릴 스테아레이트, 친유형 글리세릴스테아레이트, 소르비탄올리에이트, 소르비탄 스테아레이트, 디이에이-세틸포스페이트, 소르비탄스테아레이트/ 슈크로스코코에이트, 글리세릴스테아레이트/폴리에틸렌글라이콜-100 스테아레이트, 세테아레스-6 올리베이트, 아라키딜알코올/ 베헤닐알코올/아라키딜 글루코사이드, 폴리프로필렌글라이콜-26-부테스-26/ 폴리에틸렌글라이콜-40 하이드로제네이티드 캐스터오일 등을 사용할 수 있다. 고급 알콜로는 탄소수가 12 내지 20인 알코올, 예컨대 세틸알코올, 스테아릴 알코올, 옥틸도데칸올, 이소스테아릴 알코올 등을 단독으로 또는 1종 이상 혼합하여 사용할 수 있다.In addition, 0.1 to 5% by weight of a surfactant, a higher alcohol, and the like may be added to reinforce the emulsifying ability. Such surfactants may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids, and the like, specifically, sorbitan sesquinolate, polysorbate 60 , Glyceryl stearate, lipophilic glyceryl stearate, sorbitan oleate, sorbitan stearate, die-cetyl phosphate, sorbitan stearate / sucrosecoate, glyceryl stearate / polyethylene glycol-100 Stearate, ceteareth-6 oleate, arachidyl alcohol / behenyl alcohol / arachidyl glucoside, polypropylene glycol-26-butes-26 / polyethylene glycol-40 hydrogenated castor oil, etc. have. As the higher alcohol, alcohols having 12 to 20 carbon atoms, such as cetyl alcohol, stearyl alcohol, octyldodecanol, isostearyl alcohol, etc. may be used alone or in combination of one or more thereof.
수상 성분은 수상의 점도 또는 경도를 조절하기 위하여 카보머, 잔탄검, 벤토나이트, 마그네슘알루미늄실리케이트, 셀룰로오스검, 덱스트린 팔미테이트 등과 같은 1종 이상의 점증제를 0.001 내지 5 중량% 더 첨가할 수 있다.The aqueous phase component may further add 0.001 to 5% by weight of one or more thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
또한, 본 발명의 화장료 조성물에는 필요에 따라 고급 지방산, 비타민 등의 약효 성분과 자외선 차단제, 산화 방지제(부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산, 토코페릴아세테이드, 부틸레이티드하이드록시톨루엔 등), 방부제(메칠파라벤, 부틸파라벤, 프로필파라벤, 페녹시에탄올, 이미다졸리디닐우레아, 클로르페네신 등), 착색제, pH 조절제(트리에탄올아민, 씨트릭애씨드, 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등), 보습제(글리세린, 솔비톨, 프로필렌 글라이콜, 부틸렌 글라이콜, 헥실렌 글라이콜, 디글리세린, 베타인, 글리세레스-26, 메칠글루세스-20 등), 윤활제 등의 성분을 더 첨가할 수 있다.In addition, the cosmetic composition of the present invention, if necessary, active ingredients such as higher fatty acids, vitamins, sunscreens, antioxidants (butylhydroxyanisole, propyl gallic acid, elixolic acid, tocopheryl acetate, butylated hydroxy) Toluene), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorants, pH adjusters (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, Sodium malic acid, fmaric acid, sodium pramate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc., moisturizers (glycerine, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin , Betaine, glycerin-26, methylgluse-20 and the like), lubricants and the like can be further added.
또한, 본 발명의 화장료 조성물은 피부에 필수 영양소를 보조적으로 제공할 수 있는 물질을 추가로 포함하는데, 바람직하게는 천연향, 화장품향, 또는 한약재가 포함되지만 이들에 국한되지 않는 보조제를 함유할 수 있다.In addition, the cosmetic composition of the present invention further comprises a substance capable of auxiliaryly providing essential nutrients to the skin, and may preferably contain auxiliary agents including, but not limited to, natural flavors, cosmetic flavors, or herbal medicines. have.
본 발명의 화장료 조성물에서 이오논 또는 이의 화장품학적으로 허용 가능한 염의 유효 함량은 특별히 제한되지 않으며, 조성물 전체 중량에 대하여 0.0001 내지 20 중량%로 포함되는 것일 수 있다. 화장료 내에 0.0001 중량% 미만의 이오논 또는 이의 염은 그 용량이 소량이어서 주름 개선 효과가 없을 수 있으며, 20 중량% 이상의 이오논 또는 이의 염은 기존에 알려진 독성을 나타낼 수 있다.The effective amount of ionone or a cosmetically acceptable salt thereof in the cosmetic composition of the present invention is not particularly limited and may be included in 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of ionone or its salt in the cosmetics may have a small amount of anti-wrinkle effect, and more than 20% by weight of ionone or its salt may exhibit known toxicity.
본 발명의 용어 "향료 조성물"은 향수, 화장품, 입욕제 등의 피부 외용 기제나 식품, 의약품 등에 배합될 수 있고, 배합량은 당업계에 통상적인 기술에 따라, 목적하는 효과를 이루기 위해 적절하게 선택하여 배합할 수 있다.The term "fragrance composition" of the present invention may be blended into skin-based bases such as perfumes, cosmetics, bathing agents, foods, pharmaceuticals, and the like, and the blending amount may be appropriately selected to achieve a desired effect according to techniques conventional in the art. It can mix.
본 발명의 향료 조성물의 제형은 특별하게 제한되지 않지만, 분말, 과립, 액상 스프레이, 고형 및 젤 타입의 제형 중에서 선택된 어느 하나일 수 있다. The formulation of the fragrance composition of the present invention is not particularly limited, but may be any one selected from powder, granule, liquid spray, solid and gel type formulations.
상기 향료 조성물은 향수를 포함하는 화장용품, 목욕비누를 포함하는 비누세정용품, 유리 크리너를 포함하는 실내청소용품, 자동차용 방향제를 포함하는 방향용품, 허브타입 입욕제를 포함하는 목욕용품, 문구류를 포함하는 향기상품, 오피스용 방향제를 포함하는 환경용품 또는 합성수지를 포함하는 공업용품을 제조하는데 사용할 수 있다.The fragrance composition includes a cosmetic article including perfume, a soap cleaning article including a bath soap, a room cleaning article including a glass cleaner, a fragrance article including a car air freshener, a bath article containing a herb-type bathing agent, and stationery It can be used to manufacture industrial products including fragrance products, environmental products containing office fragrances or synthetic resin.
본 발명의 향료 조성물은 향료 조성물 전체 중량을 기준으로 할 때 그 유효성분인 이오논을, 본 발명의 향료 조성물이 구체화되는 제품 형태에 따라 0.00001 중량% 내지 10 중량%, 바람직하게는 0.00001 중량% 내지 1.0 중량%, 더 바람직하게는 0.00001 중량% 내지 0.5 중량%의 범위로 함유할 수 있다.Perfume composition of the present invention is based on the total weight of the perfume composition, the active ingredient of the ionon, 0.00001% to 10% by weight, preferably 0.00001% to 10% by weight depending on the product form in which the perfume composition of the present invention is specified 1.0 wt%, more preferably 0.00001 wt% to 0.5 wt%.
상기에서 향료 조성물이 구체화되는 제품 형태는 비누, 화장품, 입욕제, 아로마 오일 등을 포함하며, 구체적으로 바디 로션, 샴푸, 헤어 린스, 헤어 컨디셔너, 헤어 트리트먼트, 발한 억제제, 스킨 로션, 스킨 크림, 방취제, 향수(스프레이제 또는 훈증제), 립스틱, 립크림, 입욕제 등을 포함하나, 이들에 한정되는 것은 아니다.Product forms in which the fragrance composition is embodied include soaps, cosmetics, baths, aroma oils, and the like, specifically, body lotions, shampoos, hair rinses, hair conditioners, hair treatments, antiperspirants, skin lotions, skin creams, deodorants , Perfumes (spray or fumigation), lipsticks, lip creams, baths and the like.
이들 제품은 혈행 촉진제, 소염제, 보습제, 수렴제, 무기 염, 유기 염, 오일성 성분, 계면활성제, 생약류, 색소, 향료, 황, 탕화(sinter deposit), 살균제 등과 같은 각종 부가제를 함유할 수 있다.These products may contain various additives such as blood circulation promoters, anti-inflammatory agents, humectants, astringents, inorganic salts, organic salts, oily ingredients, surfactants, herbal medicines, pigments, perfumes, sulfur, sinter deposits, fungicides and the like. .
특히 본 발명의 향료 조성물은 메이크업 제품, 스킨 로션, 스킨 크림 등의 화장품 제형의 피부 외용제로 사용되는 경우가 일반적일 것인데, 이 경우에는 이들 화장품 제형에 통상적으로 사용되는 성분들을 함유할 수 있다.In particular, the fragrance composition of the present invention will generally be used as a skin external preparation of cosmetic formulations, such as makeup products, skin lotions, skin creams, in which case it may contain components commonly used in these cosmetic formulations.
특히 본 발명의 향료 조성물은 그 유효성분인 이오논이 항스트레스 활성을 가진다는 점에서 입욕제에 혼입되어 사용되는 것이 바람직하나. 이 경우 유효성분은 입욕제 총 중량을 기준으로 할 때 바람직하게는 0.00001 중량 내지 1 중량%, 더 바람직하게는 0.0001 내지 0.1 중량%의 범위로 포함될 수 있다. 본 발명의 향료 조성물이 입욕제에 혼입되어 사용되는 경우 그 입욕제는 목욕물에 0.015 내지 15 ppm의 농도로 첨가되어 사용될 수 있다.In particular, the fragrance composition of the present invention is preferably used incorporating into a bathing agent in that ionone, the active ingredient, has antistress activity. In this case, the active ingredient may be included in the range of preferably 0.00001 to 1% by weight, more preferably 0.0001 to 0.1% by weight based on the total weight of the bath. When the fragrance composition of the present invention is incorporated into a bath and used, the bath may be added to the bath water at a concentration of 0.015 to 15 ppm.
입욕제는 본 발명의 향료 조성물의 유효성분 이외에 무기염, 유기산, 오일성 성분 등을 함유할 수 있다.Bathing agent may contain an inorganic salt, an organic acid, an oily component, etc. in addition to the active ingredient of the fragrance composition of this invention.
무기 염으로서는 염화나트륨, 탄산수소나트륨, 탄산나트륨, 붕사, 황산나트륨, 황화나트륨, 세스퀴탄산나트륨, 질산나트륨, 티오황산나트륨, 폴리인산나트륨, 인산나트륨, 산화칼슘, 산화마그네슘, 탄산칼슘, 탄산마그네슘, 염화칼륨, 황화칼륨 등을 예시할 수 있으며, 이들은 단독으로 또는 2종 이상의 혼합물로서 사용될 수 있다. 이들 무기염은 입욕제 총 중량을 기준으로 5 중량% 이상, 바람직하게는 10 중량% 이상으로 입욕제에 첨가될 수 있다.Inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, borax, sodium sulfate, sodium sulfide, sodium sesquicarbonate, sodium nitrate, sodium thiosulfate, sodium polyphosphate, sodium phosphate, calcium oxide, magnesium oxide, calcium carbonate, magnesium carbonate, potassium chloride, sulfide Potassium and the like, and these may be used alone or as a mixture of two or more thereof. These inorganic salts may be added to the bath at least 5% by weight, preferably at least 10% by weight based on the total weight of the bath.
유기산으로서는 석신산, 푸마르산, 말산, 타르타르산, 시트르산, 벤조산 등을 예시할 수 있으며, 이들은 단독으로 또는 2종 이상의 혼합물로 사용될 수 있다. 이들 유기산은 입욕제 총 중량을 기준으로 할 때 0.1 내지 50 중량%의 범위로 입욕제에 첨가될 수 있다.Examples of the organic acid include succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, and the like, which may be used alone or in a mixture of two or more thereof. These organic acids can be added to the bath in the range of 0.1 to 50% by weight, based on the total weight of the bath.
오일성 성분으로서는 왁스, 탄화수소, 고급 지방산, 고급 알콜, 에스테르, 실리콘 오일 등을 들 수 있다.Examples of the oily component include waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicone oils, and the like.
입욕제는 또한 당해 기술분야에서 통상적으로 사용되는 기타 성분들을 추가로 함유할 수 있다. 이러한 성분들로서는 (a) 붕산, 메타규산, 규산 무수물과 같은 무기산, (b) 회향풀, 은행, 생강, 감귤 껍질, 쥐오줌풀 뿌리, 박하, 인삼, 귀리 등의 생약재 분말, (c) 콜타르 염료, 클로로필, 리보플라빈, 사프플라워, 안트라퀴논와 같은 인체에 무해한 것으로 확인된 천연 색소, (d) 비타민 A, 비타민 C, 비타민 D, 비타민 E 등의 비타민류, (e) 황, 운모 분말, 백토 분말, 황토 분말, 쌀겨 탄화물, 살균제, 방부제 등을 들 수 있다.The bath may also further contain other ingredients conventionally used in the art. These components include (a) inorganic acids such as boric acid, metasilicic acid, silicic anhydride, (b) medicinal powders such as fennel, ginkgo, ginger, citrus peel, Valerian root, peppermint, ginseng, oats, (c) coal tar dye, Natural pigments identified as harmless to the human body, such as chlorophyll, riboflavin, saffflower, anthraquinone, (d) vitamins such as vitamin A, vitamin C, vitamin D, vitamin E, (e) sulfur, mica powder, clay powder, Ocher powder, rice bran carbide, fungicides, and preservatives.
이러한 입욕제는 과립, 정제, 액제, 산제 등의 임의의 성상으로 제조될 수 있다.Such bathing agents can be prepared in any form, such as granules, tablets, solutions, powders and the like.
또한, 본 발명은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 개선용 조성물을 제공한다. The present invention also provides a composition for the prevention or improvement of depression or anxiety disorder comprising ionone (ionone) or a salt thereof as an active ingredient.
상기 이오논의 구체적인 내용은 전술한 바와 같다.Details of the ionone are as described above.
본 발명에서 사용되는 용어 "우울증(depression)"은 정신 질환의 일종으로서 주로 슬픔, 무미, 감정의 상실, 무쾌감증(쾌감의 결여), 비탄, 동요 또는 지체, 죄의식과 무가치하다는 생각을 특징으로 하며 심각한 경우에는 자살, 환각 및 망상 등의 증상을 동반한다. As used herein, the term "depression" is a type of mental illness characterized primarily by sadness, tastelessness, loss of feelings, numbness (lack of pleasure), grief, agitation or delay, guilt and worthlessness. Serious cases are accompanied by symptoms such as suicide, hallucinations and delusions.
또한, 본 발명에서 사용되는 용어 "불안장애(anxiety disorder)"는 병적인 불안으로 인하여 과도한 심리적 고통을 느끼거나 현실적인 적응에 심각한 어려움을 겪는 경우를 말한다. 이는 정신 질환의 일종으로서 실제적인 위험에 기인하지 않고 공격(공황 장애)이나 지속적인 상태(일반화된 불안장애)로서 나타나는 심리적이고 육체적인 불안 징후들의 다양한 조합과 관련이 있다. 구체적으로 불안장애에는 범불안장애(generalized anxiety disorder), 공포증(phobia)(특정 공포증, 사회공포증, 광장공포증), 공황장애(panic disorder), 강박장애(Obsessive-Compulsive Disorder), 외상 후 스트레스 장애(Post-traumatic stress disorder, PTSD) 등이 있다.In addition, the term "anxiety disorder" used in the present invention refers to a case in which excessive psychological pain or severe difficulty in realistic adaptation is caused by pathological anxiety. It is a type of mental illness and is associated with various combinations of psychological and physical “anxiety symptoms” that are not attributable to actual risk but appear as an attack (panic disorder) or persistent state (generalized anxiety disorder). Specifically, anxiety disorders include generalized anxiety disorder, phobia (specific phobias, social phobias, agoraphobia), panic disorders, obsessive-compulsive disorders, and post-traumatic stress disorders ( Post-traumatic stress disorder (PTSD).
우울증과 불안장애는 가장 보편적인 정신적 기능 장애로서 우울증은 일차적으로는 만성적인 우울상태를 나타내며 대부분이 수면장애, 낮은 자존감, 수치심, 자살 성향 등을 동반한다. 따라서 우울증은 복합적인 장애로 여겨지며, 이의 발병원인과 관련된 메커니즘은 불명확하다. 불안장애는 주로 불안한 감정으로 드러나는 정신 질병이다. 불안장애의 주된 특징은 자율 신경계 장애(autonomic nerves disturbance), 근육 경직(muscle rigidity), 운동 장애(exercise disturbance) 등과 같은 증후군(syndromes)과 결합한 발동 혹은 불안, 긴장증(catatonia), 두려움 등과 같은 계속적인 긴장 정서들이다. Depression and anxiety disorders are the most common mental dysfunction disorders. Depression is primarily a chronic depressive state, most of which is accompanied by sleep disorders, low self-esteem, shame, and suicidal tendencies. Depression is therefore considered a complex disorder, and the mechanisms associated with its pathogenesis are unclear. Anxiety disorders are often mental illnesses manifested by anxious feelings. The main features of anxiety disorders are continuations such as actuation or anxiety, catatonia and fear combined with syndromes such as autonomic nerves disturbance, muscle rigidity, and exercise disturbance. Tense emotions.
우울증과 불안장애는 거의 서로 함께 나타난다고 보고된 바 있다(Mineka, S., and R. Zinbarg. 2006. A contemporary learning theory perspective on the etiology of anxiety disorders: it's not what you thought it was. Am. Psychol. 61: 10-26).(Mineka, S., and R. Zinbarg. 2006. A contemporary learning theory perspective on the etiology of anxiety disorders: it's not what you thought it was.Am Psychol 61: 10-26).
본 발명의 우울증 또는 불안장애의 예방 또는 개선용 조성물은 건강기능식품 조성물, 화장료 조성물 또는 향료 조성물일 수 있다.The composition for preventing or improving the depression or anxiety disorder of the present invention may be a nutraceutical composition, cosmetic composition or perfume composition.
상기 건강기능식품 조성물, 화장료 조성물 또는 향료 조성물의 구체적인 내용은 전술한 바와 같다.Specific contents of the health functional food composition, cosmetic composition or perfume composition are as described above.
또한, 본 발명은 이오논(ionone) 또는 이의 염을 유효성분으로 포함하는 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of depression or anxiety disorder, including ionone (ionone) or a salt thereof as an active ingredient.
상기 이오논의 구체적인 내용은 전술한 바와 같다.Details of the ionone are as described above.
본 발명에 따른 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물은 이오논 또는 이의 약학적으로 허용 가능한 염을 포함하는 것이라면 그 함량을 특별히 제한하지는 않는다. 바람직하게 상기 이오논의 용량은 0.1 μM 내지 1000 μM의 농도로 포함할 수 있으나, 이에 한정되지 않는다. 이때, 이오논이 상기 농도 범위 미만인 경우, 효과적으로 우울증상, 불안장애 증상 또는 이와 관련된 질환의 예방 또는 치료 효과를 발휘하기 어려운 문제점이 있고, 이오논이 상기 농도 범위를 초과하는 경우, 세포독성을 포함한 독성의 우려사항이 있을 수 있다.The pharmaceutical composition for preventing or treating depression or anxiety disorder according to the present invention is not particularly limited as long as it contains ionone or a pharmaceutically acceptable salt thereof. Preferably, the dose of ionone may be included in a concentration of 0.1 μM to 1000 μM, but is not limited thereto. At this time, when the ionone is less than the concentration range, there is a problem that it is difficult to effectively prevent or treat the depressive symptoms, anxiety disorder symptoms or related diseases, and when the ionone exceeds the concentration range, including cytotoxicity There may be toxicity concerns.
본 발명에 따른 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구제 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화되어 사용할 수 있고, 제형화를 위하여 약학 조성물의 제조에 통상적으로 사용되는 적절한 담체, 부형제 또는 희석제를 포함할 수 있다.Pharmaceutical compositions for the prophylaxis or treatment of depression or anxiety disorders according to the present invention are powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterilization, respectively, according to conventional methods. It may be formulated and used in the form of injectable solutions, and may comprise suitable carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions for formulation.
상기 담체 또는, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리게이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화합물 혹은 혼합물을 들 수 있다.The carrier or excipient or diluent may be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicide, cellulose, methyl cellulose, undetermined. And various compounds or mixtures including vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
제제화할 경우에는 보통 사용하는 충진제, 중량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조할 수 있다.When formulated, it may be prepared using diluents or excipients such as fillers, weights, binders, wetting agents, disintegrating agents, and surfactants that are commonly used.
경구 투여를 위한 고형제제는 상기 이오논에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 제조할 수 있다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용할 수 있다.Solid preparations for oral administration may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like in the ionone. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
경구를 위한 액상 제제로는 현탁액, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용하는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등을 포함할 수 있다.Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to commonly used simple diluents such as water and liquid paraffin. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수용성제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등을 사용할 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤젤라틴 등을 사용할 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol,
본 발명에 따른 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물의 바람직한 투여량은 환자의 상태, 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서는 1일 0.0001 내지 2,000 mg/kg으로, 바람직하게는 0.001 내지 2,000 mg/kg으로 투여할 수 있다. 투여는 하루에 한 번 투여할 수도 있고, 수회 나누어서 투여할 수도 있다. 다만, 상기 투여량에 의해서 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the pharmaceutical compositions for preventing or treating depression or anxiety disorders according to the present invention vary depending on the patient's condition, weight, degree of disease, drug form, route of administration, and duration, and may be appropriately selected by those skilled in the art. have. However, for the desired effect, it may be administered at 0.0001 to 2,000 mg / kg, preferably at 0.001 to 2,000 mg / kg. Administration may be once a day or may be divided several times. However, the scope of the present invention is not limited by the above dosage.
본 발명에 따른 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물은 쥐, 생쥐, 가축, 인간 등의 포유 동물에 다양한 경로로 투여할 수 있다. 투여의 모든 방식은 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해서 투여할 수 있다.The pharmaceutical composition for preventing or treating depression or anxiety disorder according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of administration may be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명의 상기 항스트레스용 조성물, 우울증 또는 불안장애의 예방 또는 개선용 조성물, 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함함으로써 스트레스 완화 효과, 우울증 또는 불안장애의 예방, 개선 또는 치료 효과를 유의적으로 상승시킬 수 있다.The anti-stress composition of the present invention, the composition for preventing or improving depression or anxiety disorder, the pharmaceutical composition for preventing or treating depression or anxiety disorder further comprises a jasmine (jasmone) or salts thereof as an active ingredient to alleviate stress Can significantly increase the effectiveness of preventing, improving or treating depression, anxiety or anxiety disorders.
구체적으로, 상기 자스몬은 자스민(Jasmin) 및 서양톱풀(Yarrow) 등의 식물에 함유되어 있는 화합물로서, 구조식은 C11H16O이고, 분자량은 164.248 g/mol이다. 자스몬은 하기 화학식 1로 표시될 수 있으며, 시스-자스몬(cis-jasmone)으로도 불린다.Specifically, the jasmine is a compound contained in plants such as jasmine and yarrow, the structural formula is C 11 H 16 O, the molecular weight is 164.248 g / mol. Jasmon can be represented by the following formula (1), it is also called cis-jasmone (cis-jasmone).
[화학식 1][Formula 1]
자스몬은 FDA(Food and Drug Administration) 및 KFDA(Korea Food and Drug Administration) 식품첨가물 데이터베이스에 착향료로 사용가능한 물질로 등재되어 있으며, Joint FAO/WHO Expert Committe on Food Additives(JECFA)에 식품첨가물로 안전하다고 승인되어 있다. Jasmon is listed as a flavoring agent in the Food and Drug Administration (FDA) and Korea Food and Drug Administration (KFDA) food additive databases and is safe as a food additive in the Joint FAO / WHO Expert Committe on Food Additives (JECFA). Approved.
자스몬의 생리활성 및 일반기능으로 칼슘 흡수를 도와주는 기능이 보고되어 있다. 자스몬을 개의 골격근의 마이크로솜에 처리시 마이크로솜의 칼슘 흡수율 및 칼슘 함량이 높아졌다는 보고가 있다(Antipenko et al., Journal of Biological Chemistry 272.5, 1997). 자스몬의 LD50 값은 랫트에게 경구투여시 5,000 mg/kg 이상으로 안전한 것으로 보고되었다(Jenner, et al., Food and Cosmetics Toxicology 2 (1964): 327-343.).Jasmon's physiological and general functions have been reported to help calcium absorption. Jasmon has been reported to increase calcium absorption and calcium content of microsomes when treated with microsomes of skeletal muscle in dogs (Antipenko et al., Journal of Biological Chemistry 272.5, 1997). Jasmon's LD 50 value has been reported to be more than 5,000 mg / kg safe for oral administration to rats (Jenner, et al., Food and Cosmetics Toxicology 2 (1964): 327-343.).
본 발명의 자스몬은 상기 자스몬과 동일한 효능을 갖는 범위 내에서 자스몬 수화물, 자스몬 유도체 등을 포함할 수 있고, 이의 용매 화합물이나 입체 이성질체 또한 포함할 수 있다.Jasmon of the present invention may include a jasmon hydrate, a Jasmon derivative, and the like within the range having the same efficacy as the Jasmon, and may also include a solvent compound or stereoisomer thereof.
상기 자스몬의 수득방법은 특별히 한정되지 않으며, 상기 자스몬을 함유하고 있는 식물로부터 분리하거나, 공지된 제법을 사용하여 화학적으로 합성하거나 또는 시판되는 것을 사용할 수 있다.The method for obtaining the jasmine is not particularly limited, and may be isolated from a plant containing the jasmine, chemically synthesized using a known manufacturing method, or commercially available.
이하, 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Below, Through the examples will be described in more detail the present invention. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.
실시예Example 1. One. HEK293HEK293 세포를 이용한 이오논의 Ionon Using Cells CRFCRF 길항제 활성 측정 Antagonist Activity Measurement
이오논 및 자스몬이 CRF 수용체의 길항제(antagonist)로 작용하는지 여부를 확인하기 위하여 HEK293 세포에 CRF 수용체 유전자를 형질주입한 후 실험 대상 물질을 처리하고, cAMP 농도를 측정하였다. In order to confirm whether ionone and jasmine act as antagonists of the CRF receptor, transfected with CRF receptor gene in HEK293 cells, the test subjects were treated, and cAMP concentration was measured.
1-1) 1-1) HEK293HEK293 세포 배양 및 Cell culture and CRFCRF 수용체 유전자 형질주입 Receptor Gene Transfection
구체적으로, HEK293 세포(American Type Culture Collection, Manassas, VA, USA)를 6 웰 플레이트(well plate)에서 10% FBS(fetal bovine serum; Gibco, BRL, NY, USA), 1% 비필수아미노산(non-essential amino acid) 및 1% 페니실린/스트렙토마이신(penicillin/streptomycin, Pen/Strep; Gibco, Grand Island, NY)이 포함된 DMEM(Dulbecco's Modified Eagle's Medium; Hyclone, UT, USA) 배지를 사용하여 37℃, 5% CO2 배양기에서 배양시켰다. 그 후, 70% 융합성(confluent) 상태로 자란 HEK293 세포에 혈청이 없는(serum-free) DMEM 배양액을 넣고, 리포펙타민(lipofectamin 2000; Invitrogen, Massachusetts, USA)을 이용하여 CRF 수용체 벡터(Origene, Maryland, USA)를 24시간 동안 형질주입 시켰다. 그 후, 10% FBS를 포함하는 DMEM 배양액에 CRF 20 μM, 알려진 CRF 길항제(CP 154,526; Sigma, Missouri, USA) 1 μM, 베타 이오논 100 μM, 또는 베타 이오논(100 μM)과 자스 몬(100 μM) 혼합물을 처리하여 24시간 더 배양시켰다. 사용된 베타 이오논과 자스몬은 시그마-알드리치(Sigma-Aldrich, Missouri, USA)에서 구입하였다.Specifically, HEK293 cells (American Type Culture Collection, Manassas, VA, USA) were prepared in a 10-well plate in 10% FBS (fetal bovine serum; Gibco, BRL, NY, USA), 1% non-essential amino acids (non 37 ° C. using DMEM (Dulbecco's Modified Eagle's Medium; Hyclone, UT, USA) medium containing essential amino acid) and 1% penicillin / streptomycin, Pen / Strep; Gibco, Grand Island, NY , 5% CO 2 incubator. Subsequently, serum-free DMEM culture was added to HEK293 cells grown at 70% confluent, and the CRF receptor vector (Origene) was obtained using lipofectamine (lipofectamin 2000; Invitrogen, Massachusetts, USA). , Maryland, USA) was transfected for 24 hours. Subsequently, 20 μM CRF, 1 μM known CRF antagonist (CP 154,526; Sigma, Missouri, USA), 100 μM beta ionone, or beta ionone (100 μM) and
1-2) 1-2) cAMPcAMP 농도 측정 Concentration measurement
상기 실험 물질을 처리한지 24시간 후, 배양 중인 세포의 배양액을 제거하고 0.1 M HCl을 웰(well)당 0.5 ml씩 분주하고 30분 간 상온에서 방치하였다. 그 후 혼합액을 600 × g, 10분, 20 조건으로 원심분리한 후 상층액을 취하여 분석에 사용하였다. cAMP 활성은 상업용 키트(Enzo Life Sciences, NY, USA)를 이용하여 측정하였으며, 제조사의 프로토콜에 따라 수행하였다.After 24 hours of treatment with the test substance, the culture medium of the cells in culture was removed, 0.1 M HCl was dispensed at 0.5 ml per well, and left at room temperature for 30 minutes. The mixture was then centrifuged at 600 x g, 10 minutes, 20 conditions, and the supernatant was taken and used for analysis. cAMP activity was measured using a commercial kit (Enzo Life Sciences, NY, USA) and performed according to the manufacturer's protocol.
결과는 3반복으로 측정되어 평균과 표준오차로 나타내었으며, Student's T-test를 이용한 통계처리로 유의성을 검증하여 CRF만 처리한 경우와 CRF와 실험물질(CP 154,52, 베타 이오논, 베타 이오논+자스몬)을 함께 처리한 경우를 비교하고, p < 0.05 시에 유의한 것으로 간주하여 표시하였다(* p < 0.05, ** p < 0.01, *** p < 0.001).The results were measured in three repetitions and expressed as mean and standard error.The results were statistically verified using Student's T-test, and the results were statistically significant. Non-jasmon) was compared and treated as being significant at p <0.05 (* p <0.05, ** p <0.01, *** p <0.001).
그 결과, 도 1에 나타낸 바와 같이 HEK293 세포의 cAMP 농도는 CRF만 처리했을 때에 비해 CRF와 알려진 CRF 길항제(CP154,526)를 함께 처리한 경우 유의적으로 감소(-61%)하였다. 또한 CRF만 처리하였을 때에 비해 CRF와 베타 이오논을 동시에 처리하였을 때 세포의 cAMP의 농도 역시 유의적으로 감소(-48%)하였고, CRF와 베타 이오논만 처리한 경우보다, 베타 이오논과 자스몬을 동시에 처리하였을 때 더 크게 감소(-54%)한 것을 확인하였다. 이를 통해 베타 이오논이 CRF 수용체의 길항제로 작용하며, 베타 이오논과 자스몬을 함께 처리했을 때 시너지 효과를 나타내는 것을 알 수 있었다. As a result, as shown in FIG. 1, the cAMP concentration of HEK293 cells was significantly reduced (-61%) when CRF and known CRF antagonists (CP154,526) were treated with CRF alone. In addition, when treated with CRF and beta ionone at the same time, the concentration of cAMP in the cells was also significantly decreased (-48%), compared with only CRF and beta ionone. At the same time, it was confirmed that the reduction was greater (-54%). It was found that beta ionone acts as an antagonist of the CRF receptor and synergistic effect of beta ionone and jasmine together.
실시예Example 2. 마우스에서 이오논의 2. Ionone in the Mouse 항스트레스Anti-stress , 항우울, , Antidepressive, 항불안Anti-anxiety 효과 확인 Check the effect
2-1) 실험동물 사육 및 실험식이2-1) Breeding experimental animals and diet
실험동물로 사용된 7주령 수컷 C57BL/6 마우스는 ㈜ 오리엔트바이오(경기도, 한국)에서 공급받아 사용하였다. 실험동물은 사육실에서 1주간의 적응기간을 거친 후, 대조군(CON, n=6)과 베타 이오논 투여군(IO, n=6), 베타 이오논 및 자스몬 투여군(IO+JA, n = 6)으로 나누었다. 대조군은 올리브 오일을, 베타 이오논 투여군은 베타 이오논 4 mg/kg body weight을, 베타 이오논 및 자스몬 투여군은 베타 이오논 2 mg/kg body weight와 자스몬 2 mg/kg body weight을 올리브 오일에 녹여 하기 스트레스 행동지표 실험 1시간 전에 단회 복강투여 하였다. 사용된 베타 이오논과 자스몬은 씨그마-알드리치 사(Missouri, USA)에서 구입하였다. 실험동물은 온도 23±1℃, 습도 50±10% 내외, 12시간 명암주기로 일정하게 유지된 공간에서 사육되었고, 자당선호실험 이전에 실시하는 음수 박탈 이외에는 Chow(오리엔트바이오)와 음수를 자유로이 섭취하였다. Seven-week-old male C57BL / 6 mice used as experimental animals were supplied from Orient Bio Co., Ltd. (Gyeonggi-do, Korea). The experimental animals were acclimated for one week in the rearing room, and then the control group (CON, n = 6), beta ionone group (IO, n = 6), beta ionone and jasmon group (IO + JA, n = 6). Divided by. Olive oil for the control group, beta-ionone 4 mg / kg body weight for beta-ionone, and beta-ionone and jasmon for 2 mg / kg body weight and 2 mg / kg body weight for olive-ion. One hour before the dissolution of the stress behavioral indicator experiment was dissolved. The beta ionone and jasmon used were purchased from Sigma-Aldrich (Missouri, USA). The experimental animals were kept in a constant space with a temperature of 23 ± 1 ℃ and a humidity of 50 ± 10% and kept for 12 hours in a light and dark cycle. The animals were freely fed Chow (orient bio) and negative water, except for the negative deprivation conducted before sucrose preference experiment. .
2-2) 행동지표 실험 1: 꼬리 2-2) Behavior Indicator Experiment 1: Tail 매달기실험Hanging experiment (tail suspension test, (tail suspension test, TSTTST ))
꼬리 매달기 실험은 Steru 등(1985)의 방법을 이용하였다. 실험용 마우스의 꼬리 끝 1 ㎝ 정도에 고정 장치를 장착한 후 지면에서 50 ㎝ 떨어진 위치에 매달고, 영상추적시스템(video tracking system, smart v.2.5.21)을 이용하여 실험동물의 부동상태(immobility) 시간을 측정하였다. 마우스가 매달려 있는 상태에서 아무런 움직임 없이 완전히 멈춰 있는 경우를 부동상태로 간주하였으며, 2분 간의 적응 시간을 거친 후 4분 동안의 행동 상태를 측정하였다. 일반적으로 스트레스가 유도되면 불안감이 커지고 우울감이 증가해 활동량이 적어지므로, 부동시간이 길수록 스트레스가 심한 상태로 보았다.Tail hanging experiments were performed using the method of Steru et al. (1985). After attaching the fixed device about 1 cm to the tail of the experimental mouse, it is suspended 50 cm from the ground, and the immobilization of the experimental animal using a video tracking system (smart v.2.5.21) The time was measured. When the mouse was suspended and completely stopped without any movement, it was considered as a floating state, and after 2 minutes of adaptation time, the behavioral state was measured for 4 minutes. In general, when stress is induced, anxiety increases and depression increases, resulting in less activity.
그 결과, 도 2A에 나타낸 바와 같이 대조군(CON)에 비하여 베타 이오논군(IO)에서 유의적으로 부동시간이 감소(-37%)하는 것을 확인하였으며, 베타 이오논과 자스몬을 동시에 투여한 경우(IO+JA) 부동시간이 현저히 감소(-63%)하는 것을 확인할 수 있었다. 이를 통해 이오논이 항스트레스, 항우울, 항불안 효과를 나타낼 뿐만 아니라 자스몬과 동시에 사용한 경우 시너지 효과가 나타나는 것을 알 수 있었다.As a result, as shown in FIG. 2A, it was confirmed that the dead time was significantly decreased (-37%) in the beta-ionone group (IO) compared to the control group (CON), and when beta-ionone and jasmon were simultaneously administered (IO + JA) it was confirmed that the dead time is significantly reduced (-63%). This resulted in the anti-stress, anti-depressive and anti-anxiety effects of ionone as well as synergistic effects when used simultaneously with Jasmon.
2-3) 행동지표 실험 2: 강제수영 실험(forced swimming test, FST)2-3) Behavior Indicator Test 2: Forced swimming test (FST)
강제수영 실험은 Porsolt 등(1997)의 방법을 이용하였다. 높이 40 cm, 직경 20 cm인 수조에 온도 25±1℃의 물을 30 cm 채운 후 실험용 쥐를 한 마리씩 수조에 넣고 영상추적시스템(video tracking system, smart v.2.5.21)을 이용하여 실험동물의 부동상태(immobility) 시간을 측정하였다. 마우스가 수면 위에 얼굴만 나온 채로 똑바로 서서 움직이지 않고 떠 있는 경우를 부동상태로 간주하였으며, 2분 간의 적응 시간을 거친 후 4분 동안의 상태를 측정하였다. 일반적으로 스트레스가 유도되면 불안감이 커지고 우울감이 증가해 활동량이 적어지므로, 부동시간이 길수록 스트레스가 심한 상태로 보았다.Forced swimming experiments were performed using Porsolt et al. (1997). Fill a water tank with a temperature of 25 ± 1 ℃ with 30 cm in a water tank of 40 cm in height and 20 cm in diameter, and then put the mice in the tank one by one and use a video tracking system The immobility time of was measured. The mouse was considered to be floating when the mouse was standing upright with only a face on the water and floating. The state was measured for 4 minutes after 2 minutes of adaptation time. In general, when stress is induced, anxiety increases and depression increases, resulting in less activity.
그 결과, 대조군(CON)에 비하여 베타 이오논군(IO)에서 유의적으로 부동시간이 감소(-29%)하는 것을 확인할 수 있었으며, 베타 이오논과 자스몬을 동시에 투여한 경우(IO+JA) 부동시간이 현저히 감소(-72%)하는 것을 확인할 수 있었다. 이를 통해 이오논이 항스트레스, 항우울, 항불안 효과를 나타낼 뿐만 아니라 자스몬과 동시에 사용한 경우 시너지 효과가 나타나는 것을 알 수 있었다(도 2B).As a result, it was confirmed that the dead time was significantly reduced (-29%) in the beta ionone group (IO) compared to the control group (CON), and when beta ionone and jasmon were simultaneously administered (IO + JA) This markedly decreased (-72%). Through this, it was found that the ionon not only exhibited antistress, antidepressant and anti-anxiety effects but also synergistic effects when used simultaneously with Jasmon (FIG. 2B).
2-4) 혈장 2-4) plasma 코르티코스테론Corticosterone (( corticosteronecorticosterone ) 농도 측정A) concentration measurement
스트레스 행동지표 실험이 끝나고 45분이 경과한 후 실험동물을 아베르틴(avertin)으로 마취한 상태에서 혈액을 채취하였다. 복부대동맥으로부터 채혈한 혈액은 2000 ×g에서 15분간 원심분리하여 혈장(plasma)을 분리하였다. 코르티코스테론 농도는 일반적으로 사용하는 EIA 키트(Corticosterone EIA kit; Enzo Life Sciences, NY, USA)를 이용하여 측정하였다. 기본적인 실험 방법은 제조사의 지시에 따라 수행하였다. 45 minutes after the stress behavioral indicators were over, blood was collected under anesthesia with an avertin. Blood collected from the abdominal aorta was centrifuged at 2000 xg for 15 minutes to separate plasma. Corticosterone concentrations were measured using a commonly used EIA kit (Corticosterone EIA kit; Enzo Life Sciences, NY, USA). Basic experimental methods were performed according to the manufacturer's instructions.
그 결과, 도 2C에 나타낸 바와 같이, 대조군(CON)에 비하여 베타 이오논군(IO)에서 혈장 코르티코스테론 농도가 유의하게 감소하였고(-14%), 베타 이오논과 자스몬을 동시에 투여한 경우(IO+JA) 혈장 코르티코스테론 농도가 현저히 감소(-35%)하는 것을 확인할 수 있었다. 이를 통해 이오논이 항스트레스, 항우울, 항불안 효과를 나타낼 뿐만 아니라 자스몬과 동시에 사용한 경우 시너지 효과가 나타남을 알 수 있었다.As a result, as shown in FIG. 2C, the plasma corticosterone concentration was significantly decreased (-14%) in the beta ionone group (IO) compared to the control group (CON), and beta ionone and jasmon were simultaneously administered (IO). + JA) the plasma corticosterone concentration was found to be significantly reduced (-35%). Through this, it was found that the ionon not only exhibited antistress, antidepressant and anti-anxiety effects but also synergistic effects when used simultaneously with Jasmon.
실시예Example 3. 3. CRFCRF 과발현 마우스에서 이오논의 Ionone in Overexpressed Mice 항스트레스Anti-stress , 항우울, , Antidepressive, 항불안Anti-anxiety 효과 확인 Check the effect
3-1) 실험동물 사육 및 실험식이3-1) Experiment Animal Breeding and Experimental Diet
본 실험은 CRF 과발현 마우스 28마리(수컷 n = 14, 암컷 n = 14)와 야생형(wild type) 마우스 14마리(수컷 n = 7, 암컷 n = 7) 를 대상으로 12주간 실시하였다. 구체적으로, CRF 과발현 마우스는 CRF 과발현 마우스(hemizygous)와 야생형 마우스(littermate)를 Jackson lab(Bar Harbor, Maine, USA)으로부터 입고한 후, 3세대에 걸쳐 교배하여 사육한 7주령의 암수 14쌍을 실험에 사용하였다. This experiment was conducted for 12 weeks in 28 CRF overexpressing mice (male n = 14, female n = 14) and 14 wild-type mice (male n = 7, female n = 7). Specifically, CRF overexpressing mice received 14 pairs of male and female 7-week-old males and females bred for three generations after wearing CRF overexpressing mice (hemizygous) and wild type mice (littermate) from Jackson lab (Bar Harbor, Maine, USA). It was used for the experiment.
야생형 마우스는 정상식이(Normal diet, ND)를 섭취시켰고, CRF 과발현 마우스는 두 군으로 나누어 각각 ND(n = 14)와 베타 이오논이 보충된 식이(IO)(n = 14)를 섭취시켰다. 베타 이오논이 보충된 식이는 ND와 조성이 동일하되 베타 이오논이 0.2% 수준으로 포함되었다(하기 표 1 참조). 사용된 베타 이오논은 씨그마-알드리치 사(Missouri, USA)에서 구입하였다. 실험동물 사육은 온도 23±1℃, 습도 50±10% 내외, 12시간 명암주기의 환경에서 실시되었다. Wild-type mice were fed a normal diet (ND), and CRF overexpressing mice were divided into two groups and ND (n = 14) and beta-ionone supplemented diet (IO) (n = 14), respectively. The diet supplemented with beta ionone had the same composition as ND but contained 0.2% of beta ionone (see Table 1 below). The beta ionone used was purchased from Sigma-Aldrich (Missouri, USA). Experimental animal breeding was carried out in a environment of 12 hours light and dark cycles with a temperature of 23 ± 1 ℃ and a humidity of 50 ± 10%.
(g/kg diet)Normal diet
(g / kg diet)
(g/kg diet)Beta Ionone Supplements
(g / kg diet)
실험 기간 동안 실험동물의 체중은 주 1회 일정한 시간에 측정하였고, 식이 섭취량은 매일 측정하였다. During the experiment, the body weight of the test animals was measured at a regular time once a week, and the dietary intake was measured every day.
3-2) 혈액 채취 및 혈장 3-2) Blood Collection and Plasma 코르티코스테론Corticosterone 측정 Measure
실험동물 사육이 완료되는 시점에 마우스를 6시간 금식시킨 후, 아베르틴으로 마취한 상태에서 혈액을 채취하였다. 복부대동맥으로부터 채혈한 혈액은 2000 ×g에서 15분 간 원심분리하여 혈장(plasma)을 분리하였다. 코르티코스테론 농도는 일반적으로 사용하는 EIA 키트(Corticosterone EIA kit; Enzo Life Sciences, NY, USA)를 이용하여 측정하였다. 기본적인 실험 방법은 제조사의 지시에 따라 수행하였다.The mice were fasted for 6 hours at the completion of experimental animal breeding, and blood was collected under anesthesia with avertin. Blood collected from the abdominal aorta was centrifuged at 2000 xg for 15 minutes to separate plasma. Corticosterone concentrations were measured using a commonly used EIA kit (Corticosterone EIA kit; Enzo Life Sciences, NY, USA). Basic experimental methods were performed according to the manufacturer's instructions.
그 결과, 도 3에 나타낸 바와 같이 CRF 과발현 마우스의 혈장 코르티코스테론은 WT 마우스에 비해 수컷과 암컷에서 모두 유의적으로 증가하였으며(수컷, +284%; 암컷, +289%), 베타 이오논을 섭취한 CRF 과발현 마우스의 경우 혈장 코르티코스테론이 유의적으로 감소하엿다(수컷, -32%; 암컷, -26%). 이로부터 베타 이오논은 만성적으로 증가한 혈장 코르티코스테론의 농도를 개선하는 효과가 있음을 알 수 있었다.As a result, as shown in FIG. 3, the plasma corticosterone of CRF overexpressing mice was significantly increased in both males and females compared to WT mice (male, + 284%; female, + 289%). Plasma corticosterone was significantly reduced in CRF overexpressing mice (male, -32%; female, -26%). From this, beta ionone was found to have an effect of improving the concentration of chronically increased plasma corticosterone.
하기에 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.
제제예Formulation example 1. One. 산제의Powder 제조 Produce
이오논 20 ㎎Ionone 20 mg
유당수화물 100 ㎎
탈크 10 ㎎
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in an airtight cloth to prepare a powder.
제제예Formulation example 2. 정제의 제조 2. Preparation of Tablets
이오논 10 ㎎
옥수수전분 100 ㎎
유당수화물 100 ㎎
스테아르산마그네슘 2 ㎎Magnesium stearate 2mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Manufacture of capsule
이오논 10 ㎎
미결정셀룰로오스 3 ㎎ 3 mg of microcrystalline cellulose
유당수화물 14.8 ㎎Lactose carb 14.8 mg
스테아르산마그네슘 0.2 ㎎Magnesium Stearate 0.2 mg
상기의 성분을 혼합한 후, 통상의 캅셀제의 제조방법에 다라서 젤라틴캡슐에 충전하여 캅셀제를 제조하였다.After mixing the above components, it was filled in gelatin capsules according to the conventional method for producing a capsule to prepare a capsule.
제제예Formulation example 4. 주사제의 제조 4. Preparation of Injectables
이오논 10 ㎎
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎Sterile distilled water for injection 2974 mg
인산일수소나트퓸 26 ㎎Monohydrogen phosphate 26 mg
상기의 성분을 혼합한 후, 통상의 주사제의 제조방법에 따라 1앰플당(2mL) 상기의 성분 함량으로 제조하였다.After mixing the above components, it was prepared in the above ingredient content per ampoules (2 mL) according to the conventional method for preparing injections.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
이오논 10 ㎎
이성화당 10 ㎎
만니톨 5 ㎎Mannitol 5 mg
정제수 적량Purified water
레몬향 적량Lemon flavor
상기의 성분을 통상의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 정제수를 가하여 전체 100mL로 조절한 후 멸균시켜 갈색병에 충진하여 액제를 제조한다. The above components are dissolved in purified water according to a conventional preparation method, dissolved in purified water, and then lemon juice is added in an appropriate amount, and then adjusted to 100 mL by adding purified water.
제제예Formulation example 6. 6. 기능성식품의Functional food 제조 Produce
이오논 10 ㎎
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이드 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 30 ㎎Potassium citrate 30 mg
탄산칼슘 100 ㎎
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예Formulation example 7. 건강음료의 제조 7. Manufacture of health drinks
이오논 10 mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g0.3 g of vitamin B2
정제수 정량Purified Water Quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2l 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 l container, sealed sterilization and refrigerated and then stored in the present invention Used to prepare healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
하기에 본 발명의 추출물을 함유하는 화장료 조성물의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of preparation of a cosmetic composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.
제조예Production Example 1. 영양화장수( 1. Nutritional Cosmetics ( 밀크로션Milk Croissant ))
이오논 2.0 중량%Ionone 2.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
밀납 4.0 중량%Beeswax 4.0 wt%
폴리솔베이트60 1.5 중량%Polysorbate60 1.5 wt%
솔비탄세스퀴올레이트 1.5 중량%Sorbanthesquioleate 1.5 wt%
유동파라핀 0.5 중량%0.5% by weight of liquid paraffin
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / Capric Triglycerides 5.0 wt%
글리세린 3.0 중량%Glycerin 3.0 wt%
부틸렌글리콜 3.0 중량%Butylene Glycol 3.0 wt%
프로필렌글리콜 3.0 중량%Propylene Glycol 3.0 wt%
카르복시비닐폴리머 0.1 중량%Carboxy vinyl polymer 0.1 wt%
트리에탄올아민 0.2 중량%0.2% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량%Purified water to 100% by weight
상기의 배합비는 비교적 영양화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nutritional longevity in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
제조예Production Example 2. 유연화장수(스킨로션) 2. Softening Cosmetics (Skin Lotion)
이오논 2.0 중량 %Ionone 2.0% by weight
글리세린 3.0 중량 %Glycerin 3.0 wt%
부틸렌글리콜 2.0 중량 %Butylene glycol 2.0% by weight
프로필렌글리콜 2.0 중량 %Propylene Glycol 2.0 wt%
카르복시비닐폴리머 0.1 중량 %Carboxy vinyl polymer 0.1 wt%
PEG 12 노닐페닐에테르 0.2 중량 %PEG 12 nonylphenylether 0.2% by weight
폴리솔베이트80 0.4 중량 %
에탄올 10.0 중량 %Ethanol 10.0 wt%
트리에탄올아민 0.1 중량 %Triethanolamine 0.1% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 유연화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed and formulated in a preferred embodiment with a component suitable for a relatively softening longevity, the compounding ratio may be arbitrarily modified, and can be prepared according to the manufacturing method in the general cosmetic field.
제조예Production Example 3. 영양크림 3. Nutrition Cream
이오논 2.0 중량 % Ionone 2.0% by weight
폴리솔베이트60 1.5 중량 %Polysorbate 60 1.5% by weight
솔비탄세스퀴올레이트 0.5 중량 %Sorbitan sesquioleate 0.5% by weight
PEG60 경화피마자유 2.0 중량 %PEG60 Cured Castor Oil 2.0% by weight
유동파라핀 10 중량 %10% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량 %Caprylic / Capric Triglycerides 5.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제 적량Preservative
색소 적량Pigment amount
향료 적량Spices
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 영양크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nourishing cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
제조예Production Example 4. 마사지크림 4. Massage Cream
이오논 1.0 중량 %Ionone 1.0% by weight
밀납 10.0 중량 %Beeswax 10.0 weight%
폴리솔베이트60 1.5 중량 %Polysorbate 60 1.5% by weight
PEG 60 경화피마자유 2.0 중량 %PEG 60 Cured Castor Oil 2.0% by weight
솔비탄세스퀴올레이트 0.8 중량 %Sorbanthesquioleate 0.8 wt%
유동파라핀 40.0 중량 %40.0% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 4.0 중량 %Caprylic / Capric Triglyceride 4.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 마사지크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a massage cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
제조예Production Example 5. 팩 5. Pack
이오논 1.0 중량 %Ionone 1.0% by weight
폴리비닐알콜 13.0 중량 %Polyvinyl alcohol 13.0 wt%
소듐카르복시메틸셀룰로오스 0.2 중량 %Sodium Carboxymethylcellulose 0.2% by weight
글리세린 5.0 중량 %Glycerin 5.0 wt%
알란토인 0.1 중량 %Allantoin 0.1 wt%
에탄올 6.0 중량 %Ethanol 6.0 wt%
PEG 12 노닐페닐에테르 0.3 중량 %PEG 12 nonylphenyl ether 0.3% by weight
폴리솔베이트60 0.3 중량 %Polysorbate60 0.3 wt%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 팩에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a pack in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
제조예Production Example 6. 젤 6. Gel
이오논 0.5 중량 %Ionone 0.5 wt%
에틸렌디아민초산나트륨 0.05 중량 %0.05% by weight of ethylenediamine sodium acetate
글리세린 5.0 중량 %Glycerin 5.0 wt%
카르복시비닐폴리머 0.3 중량 %Carboxy vinyl polymer 0.3 wt%
에탄올 5.0 중량 %Ethanol 5.0 wt%
PEG 60 경화피마자유 0.5 중량 %PEG 60 Cured Castor Oil 0.5% by weight
트리에탄올아민 0.3 중량 %0.3% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 젤에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a gel in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
상기 배합비는 비교적 화장료 조성물에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그외의 색채 화장품을 포함하는 다양한 용도의 화장품에 적용될 수 있는 것이고, 그 효능에 따라 인체에 얇게 도포하여 바를 수 있는 약제 즉, 연고로 제조에 이용될 수 있으며 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The compounding ratio is a relatively suitable composition for the cosmetic composition in a preferred embodiment, but can be applied to cosmetics of various uses, including other color cosmetics, according to the efficacy that can be applied to a thin coating on the human body, that is, It can be used for manufacturing as ointment, and the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
하기에 본 발명의 추출물을 함유하는 가축 사료 조성물의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of preparing a livestock feed composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.
제조예Production Example 7. 사료 첨가제의 제조 7. Preparation of Feed Additives
이오논 0.1~10%Ionone 0.1 ~ 10%
제3 인산칼슘 1~20%Tricalcium phosphate 1-20%
비타민 E 0.01~0.1%Vitamin E 0.01 ~ 0.1%
효소 분말 1~10%
유산균 0.1~10%Lactobacillus 0.1-10%
포도당 20~90%Glucose 20-90%
제조예Production Example 8. 사료의 제조 8. Preparation of feed
상기 제조예 7의 사료첨가제를 유효성분으로 하여 하기와 같은 조성으로 사료를 제조하였다.The feed additive of Preparation Example 7 was used as an active ingredient to prepare a feed having the following composition.
제조예 7의 사료 첨가제 0.1~10%Feed additive 0.1 ~ 10% of Preparation Example 7
밀기울 40~49.9%Bran 40-49.9%
마일로 21.20%Milo 21.20%
대두박 20.00%Soybean meal 20.00%
어분 3.00%Fish Meal 3.00%
당밀 4.00%Molasses 4.00%
미네랄 1.53%Mineral 1.53%
비타민 0.27%0.27% vitamin
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.
Claims (14)
An antistress composition comprising ionone or a salt thereof as an active ingredient.
상기 이오논은 부신피질 자극 호르몬 방출인자(corticotropin releasing factor, CRF)의 활성을 저해하는 것을 특징으로 하는 항스트레스용 조성물.
The method of claim 1,
The ionone is antistress composition, characterized in that to inhibit the activity of corticotropin releasing factor (CRF).
상기 이오논은 혈중 코르티코스테론(corticosterone) 농도를 감소시키는 것을 특징으로 하는 항스트레스용 조성물.
The method of claim 1,
The ionone is antistress composition, characterized in that to reduce the concentration of corticosterone (corticosterone) in the blood.
상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함하는 것을 특징으로 하는 항스트레스용 조성물.
The method of claim 1,
The composition is an antistress composition, characterized in that it further comprises jasmon (jasmone) or a salt thereof as an active ingredient.
Functional food composition for antistress comprising ionone or a salt thereof as an active ingredient.
A composition for the prevention or improvement of depression or anxiety disorder comprising ionone or salt thereof as an active ingredient.
상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함하는 것을 특징으로 하는 우울증 또는 불안장애의 예방 또는 개선용 조성물.
The method of claim 6,
The composition is a composition for the prevention or improvement of depression or anxiety disorders, characterized in that it further comprises as an active ingredient (jasmone) or salts thereof.
Functional food composition for the prevention or improvement of depression or anxiety disorder containing ionone (ionone) or salts thereof as an active ingredient.
Pharmaceutical composition for the prevention or treatment of depression or anxiety disorder comprising ionone (ionone) or salts thereof as an active ingredient.
상기 조성물은 자스몬(jasmone) 또는 이의 염을 유효성분으로 더 포함하는 것을 특징으로 하는 우울증 또는 불안장애의 예방 또는 치료용 약학적 조성물.
The method of claim 9,
The composition is a pharmaceutical composition for preventing or treating depression or anxiety disorder, characterized in that it further comprises as an active ingredient (jasmone) or a salt thereof.
Cosmetic composition for the prevention or improvement of depression or anxiety disorder containing ionone (ionone) or salts thereof as an active ingredient.
Perfume composition for the prevention or improvement of depression or anxiety disorder containing ionone (ionone) or salts thereof as an active ingredient.
An antistress cosmetic composition comprising ionone or a salt thereof as an active ingredient.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020180025864A KR102037719B1 (en) | 2018-03-05 | 2018-03-05 | Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients |
PCT/KR2019/002326 WO2019172566A1 (en) | 2018-03-05 | 2019-02-26 | Anti-stress agent, anti-depressant or anti-anxiety agent composition containing ionone as active ingredient |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020180025864A KR102037719B1 (en) | 2018-03-05 | 2018-03-05 | Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20190105392A KR20190105392A (en) | 2019-09-17 |
KR102037719B1 true KR102037719B1 (en) | 2019-10-29 |
Family
ID=67846763
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020180025864A KR102037719B1 (en) | 2018-03-05 | 2018-03-05 | Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients |
Country Status (2)
Country | Link |
---|---|
KR (1) | KR102037719B1 (en) |
WO (1) | WO2019172566A1 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102090209B1 (en) * | 2019-11-07 | 2020-03-18 | 연세대학교 산학협력단 | A Composition for Preventing or Treating Stress-related Disorders Comprising Methyl Benzoate as an Active Ingredient |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006097759A1 (en) * | 2005-03-18 | 2006-09-21 | Quest International Services B.V. | Perfume compositions |
US20070042056A1 (en) * | 2003-05-30 | 2007-02-22 | Hitoshi Aoshima | Anti-stress agent |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006036722A (en) * | 2004-07-29 | 2006-02-09 | Lion Corp | Sleeping inducing agent |
US20070207220A1 (en) * | 2006-03-01 | 2007-09-06 | Kathryn Luedtke | Method for improving sleep behaviors |
-
2018
- 2018-03-05 KR KR1020180025864A patent/KR102037719B1/en active IP Right Grant
-
2019
- 2019-02-26 WO PCT/KR2019/002326 patent/WO2019172566A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070042056A1 (en) * | 2003-05-30 | 2007-02-22 | Hitoshi Aoshima | Anti-stress agent |
WO2006097759A1 (en) * | 2005-03-18 | 2006-09-21 | Quest International Services B.V. | Perfume compositions |
Also Published As
Publication number | Publication date |
---|---|
KR20190105392A (en) | 2019-09-17 |
WO2019172566A1 (en) | 2019-09-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10960040B2 (en) | Composition for preventing and treating muscle diseases or improving muscular function, containing platycodon grandiflorum extract | |
US10576057B2 (en) | Methods for treating muscle wasting and degeneration diseases | |
KR101937321B1 (en) | Composition having anti-stress, anti-depressant or anxiolytic effect comprising at least one compound selected from the group consisting of undecanal, dodecanal, and pharmaceutically acceptable salts thereof as active ingredient | |
TW201116286A (en) | Ceramide production enhancer and moisturizing agent | |
EP1629837A1 (en) | Antistress agent | |
KR101809379B1 (en) | Composition comprising Diosmin or as active ingredients for Preventing or treating muscle disease | |
KR102037719B1 (en) | Composition for anti-stress agents, antidepressants or anxiolytics including Ionone as active ingredients | |
KR20210047594A (en) | Compositions for reinforcing skin barrier and improving atopic dermatitis using hydrangenol or phyllodulcin as an active ingredient | |
KR102076937B1 (en) | Composition including ocimene or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
KR102076936B1 (en) | Composition including thiazole or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
KR102081029B1 (en) | Composition including suberic acid or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
WO2013161821A1 (en) | Cgrp responsiveness promoter | |
KR102076939B1 (en) | Composition including ethyl vanilin or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
EP3925603A1 (en) | Composition for allergy prevention, atopic dermatitis alleviation or skin regeneration, containing, as active ingredient, undecane or undecanal | |
KR102089903B1 (en) | Composition including camphor or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
KR20190009093A (en) | Composition comprising citrale or as active ingredients for muscle strengthening, development, differentiation, regeneration or inhibiting muscle atrophy | |
KR102160868B1 (en) | Composition including nonane as active ingredients for anti-allergy, improvement of atopic dermatitis, or skin regeneration | |
KR102147591B1 (en) | Composition including guaiyl acetate as active ingredients for anti-allergy, improvement of atopic dermatitis, or skin regeneration | |
KR101997336B1 (en) | Composition comprising ethyl vanillin or as active ingredients for muscle strengthening, development, differentiation, regeneration or inhibiting muscle atrophy | |
KR101997334B1 (en) | Composition comprising furaneol or as active ingredients for muscle strengthening, development, differentiation, regeneration or inhibiting muscle atrophy | |
KR101830395B1 (en) | Composition comprising squalene for enhancement of muscle function and prevention of muscle damage | |
KR102544229B1 (en) | Composition for antistress comprising natural substance extract mixture and uses thereof | |
KR20200080892A (en) | Composition comprising piperonal as active ingredients for muscle strengthening, development, differentiation, regeneration or inhibiting muscle atrophy | |
KR102076938B1 (en) | Composition including carvone or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis | |
JP7371851B2 (en) | Composition containing oleanane-type triterpene that prevents or improves physical fatigue and feeling of fatigue |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |