KR101618012B1 - Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts - Google Patents
Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts Download PDFInfo
- Publication number
- KR101618012B1 KR101618012B1 KR1020150122854A KR20150122854A KR101618012B1 KR 101618012 B1 KR101618012 B1 KR 101618012B1 KR 1020150122854 A KR1020150122854 A KR 1020150122854A KR 20150122854 A KR20150122854 A KR 20150122854A KR 101618012 B1 KR101618012 B1 KR 101618012B1
- Authority
- KR
- South Korea
- Prior art keywords
- composition
- present
- extract
- dry eye
- eye syndrome
- Prior art date
Links
- 239000000284 extract Substances 0.000 title claims abstract description 50
- 208000003556 Dry Eye Syndromes Diseases 0.000 title claims abstract description 44
- 206010013774 Dry eye Diseases 0.000 title claims abstract description 44
- 239000000203 mixture Substances 0.000 title claims abstract description 42
- 241000723437 Chamaecyparis Species 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 230000002265 prevention Effects 0.000 claims description 5
- 241000723436 Chamaecyparis obtusa Species 0.000 claims description 4
- 238000000194 supercritical-fluid extraction Methods 0.000 claims description 3
- 206010016766 flatulence Diseases 0.000 claims description 2
- 238000010367 cloning Methods 0.000 claims 2
- 235000013305 food Nutrition 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 12
- 102000004127 Cytokines Human genes 0.000 abstract description 11
- 108090000695 Cytokines Proteins 0.000 abstract description 11
- 206010061218 Inflammation Diseases 0.000 abstract description 11
- 230000004054 inflammatory process Effects 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 11
- 230000002757 inflammatory effect Effects 0.000 abstract description 8
- 230000006378 damage Effects 0.000 abstract description 7
- 210000002919 epithelial cell Anatomy 0.000 abstract description 7
- 230000008595 infiltration Effects 0.000 abstract description 7
- 238000001764 infiltration Methods 0.000 abstract description 7
- 210000002540 macrophage Anatomy 0.000 abstract description 7
- 230000004489 tear production Effects 0.000 abstract description 7
- 230000015556 catabolic process Effects 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 230000001934 delay Effects 0.000 abstract description 5
- 210000004561 lacrimal apparatus Anatomy 0.000 abstract description 2
- 231100001083 no cytotoxicity Toxicity 0.000 abstract description 2
- 238000012216 screening Methods 0.000 abstract 1
- 238000000605 extraction Methods 0.000 description 12
- 239000003889 eye drop Substances 0.000 description 11
- 229920000742 Cotton Polymers 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 235000011845 white flour Nutrition 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 230000005779 cell damage Effects 0.000 description 6
- 208000037887 cell injury Diseases 0.000 description 6
- 229940012356 eye drops Drugs 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000004087 cornea Anatomy 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 4
- -1 fluoroalkane Chemical compound 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 235000004347 Perilla Nutrition 0.000 description 3
- 244000124853 Perilla frutescens Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 210000003056 antler Anatomy 0.000 description 3
- 208000003464 asthenopia Diseases 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
- 230000037396 body weight Effects 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960004551 cotton seed extract Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 241000196324 Embryophyta Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 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 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 244000018795 Prunus mume Species 0.000 description 2
- 235000011158 Prunus mume Nutrition 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229920002359 Tetronic® Polymers 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000012459 cleaning agent Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 210000000795 conjunctiva Anatomy 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 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 2
- NDVASEGYNIMXJL-UHFFFAOYSA-N sabinene Chemical compound C=C1CCC2(C(C)C)C1C2 NDVASEGYNIMXJL-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 239000004034 viscosity adjusting agent Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- NDVASEGYNIMXJL-NXEZZACHSA-N (+)-sabinene Natural products C=C1CC[C@@]2(C(C)C)[C@@H]1C2 NDVASEGYNIMXJL-NXEZZACHSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- SQCZQTSHSZLZIQ-UHFFFAOYSA-N 1-chloropentane Chemical compound CCCCCCl SQCZQTSHSZLZIQ-UHFFFAOYSA-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
- FXNDIJDIPNCZQJ-UHFFFAOYSA-N 2,4,4-trimethylpent-1-ene Chemical group CC(=C)CC(C)(C)C FXNDIJDIPNCZQJ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-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
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 206010015958 Eye pain Diseases 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 241000219428 Fagaceae Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000007993 MOPS buffer Substances 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 244000252132 Pleurotus eryngii Species 0.000 description 1
- 235000001681 Pleurotus eryngii Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000204900 Talipariti tiliaceum Species 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 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
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- KQAZVFVOEIRWHN-UHFFFAOYSA-N alpha-thujene Natural products CC1=CCC2(C(C)C)C1C2 KQAZVFVOEIRWHN-UHFFFAOYSA-N 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 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
- 239000003855 balanced salt solution Substances 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
- 235000013361 beverage Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 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
- 235000008429 bread Nutrition 0.000 description 1
- 229960003655 bromfenac Drugs 0.000 description 1
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 235000019282 butylated hydroxyanisole 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
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 231100000478 corneal permeability Toxicity 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000004452 decreased vision Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical compound CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 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
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229920001987 poloxamine Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 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
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[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 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 229930006696 sabinene Natural products 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
- 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
- 229960004499 scopolamine hydrobromide Drugs 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000008362 succinate buffer Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
-
- A23L1/3002—
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The present invention relates to a method for screening The present invention relates to a composition for preventing or ameliorating dry eye syndrome comprising an extract of obtusa as an active ingredient. The composition of the present invention, which is an effective component of the present invention, accelerates tear production, delays tear film breakdown time, Has the effect of preventing or ameliorating dry eye syndrome by not only delaying damage of epithelial cells but also reducing the expression level of inflammatory cytokines in the ocular surface and lacrimal gland and inhibiting infiltration of macrophages by inflammatory reaction. In addition, the extract of the present invention has no cytotoxicity and side effects, and can be safely used in a pharmaceutical composition, a quasi-drug composition or a food composition.
Description
The present invention relates to a composition for preventing or ameliorating dry eye syndrome comprising an extract of a cotton wool extract as an active ingredient, and more particularly to a pharmaceutical, quasi-drug or food composition for preventing or improving dry eye syndrome, .
Recently, as the use of digital products such as televisions, computers and game machines, the increase of contact lenses, and the growth of the cultural industry, modern people's eyes are abused without rest, except when sleeping. .
Dry eye syndrome is a common disease occurring in 5.5 ~ 15% of adults worldwide. It causes not only mere tears but also eye irritation and tear layer instability due to inflammation of tears and ocular surface (cornea and conjunctiva) It is known as a disease that can damage the surface. Features of this disease include ocular pain, irregular corneal surface, corneal ulcer, and decreased vision. Corneal permeability changes in chronic eye dryness and dry keratitis are well known to cause inflammation, which is known to be induced by increased inflammation mediated cytokines.
Recent studies have shown that inflammation and apoptosis of the ocular surface play a very important role in the induction of dry eye syndrome. In addition, excessive use of televisions, game machines, development of computers, and excessive use of eyes due to excessive fatigue by the examinees cause easy eye fatigue, which is the biggest cause of dry eye syndrome. One of the biggest causes of eye fatigue is stress, and stress, which is always mentioned in all common sense, adds to the fatigue of our eyes. Therefore, materials that can prevent or ameliorate dry eye syndrome by reducing eye fatigue have been studied and developed. Recently, as misuse and abuse of drugs and side effects to chemicals have become serious problems, new substitute drugs derived from natural substances Is required.
On the other hand, Chamaecyparis The phytoncide contained in the obtusa , that is, the essential oil, is a directional substance that the tree blows to protect itself from the outside environment such as various insects and bacteria, and is excellent in the ability to remove odor and harmful substances in the air , Antimicrobial / insecticidal effect, stress relieving effect, and atopy / allergy prevention. However, little is known about its role in ocular diseases such as dry eye syndrome, and there has been no report on the results of applying the extract from the eye for the purpose of ophthalmic treatment.
Accordingly, the present inventors have conducted studies to develop new substances that prevent or ameliorate dry eye syndrome. The inventors of the present invention have found that the monoprotein extract promotes tear production in eye dry animal models, delays tear film breakdown time, and delays corneal epithelial cell damage In addition, the present inventors have found that dry eye syndrome can be effectively used for preventing or improving ocular surface and lacrimal gland by reducing inflammatory cytokines and inhibiting infiltration of macrophages by inflammatory reaction, thus completing the present invention.
It is an object of the present invention to provide a composition for preventing or ameliorating dry eye syndrome comprising an extract of Prunus mume as an active ingredient.
It is another object of the present invention to provide a pharmaceutical composition, a quasi-drug composition or a food composition for preventing or ameliorating dry eye syndrome comprising the composition.
The present invention provides a composition for the prevention or amelioration of dry eye syndrome comprising an extract of Prunus mume as an active ingredient.
In the present invention, the above-mentioned extract is preferably at least one selected from the group consisting of trunks, branches, leaves, fruits, bark and roots of temperate trees, preferably dried and powdered Next, extraction can be carried out by an extraction method known in the art, for example, a direct extraction method using an extraction solvent, a steam distillation method, a supercritical fluid extraction method, or a cold pressing method. In one specific embodiment of the present invention, supercritical fluid extraction was used.
In the case of extracting the textiles extract using an extraction solvent, the extraction solvent may be, for example, water, anhydrous or lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, n-propanol, iso- A polar solvent comprising normal-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol), acetic acid, dimethylformamide (DMFO) or dimethyl sulfoxide (DMSO); Or acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, Butene, 1-chloropentane, o -xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, chloroform, dichloromethane, - Non-polar solvents including dichloroethane, anniline, diethylamine, ether, carbon tetrachloride and THF may be used.
In addition to the above-mentioned extraction method using the above-mentioned extraction solvent, the above-mentioned antler extraction can also be obtained through a conventional purification process. For example, by separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographies (made for separation by size, charge, hydrophobicity or affinity), and the like, The extract can also be obtained through fractionation.
In the present invention, the flatulence extract may be any extract, fraction and purified product obtained in each step of extraction or purification (separation, fractionation), diluted solution thereof, concentrate or dried product thereof.
In the present invention, the extract of the above-mentioned method according to the present invention promotes tear production, delays tear film breakdown time, delays corneal epithelial cell damage, and inhibits inflammatory cytokines Decrease the expression level of cyne and inhibit macrophage infiltration by inflammatory reaction.
Therefore, the composition comprising the extract of the present invention as an active ingredient can be usefully used for preventing or improving dry eye syndrome.
Since the composition of the present invention is extracted from a natural plant material, which is extracted from a natural plant material, there is no adverse effect on the human body even when the composition is administered in an excessive amount. Therefore, the quantitative upper limit of the composition of the present invention can be selected by a person skilled in the art .
In a preferred embodiment of the present invention, the composition of the present invention may be contained in an amount of 0.01 to 10% by weight, preferably 0.05 to 5% by weight, based on the total weight of the whole composition.
As used herein, the term "comprising as an active ingredient" is meant to include an amount sufficient to achieve the efficacy or activity of the above-described "
The composition of the present invention may contain, as an active ingredient, an ingredient useful for prevention or improvement of dry eye syndrome such as an antioxidant, a steroid-based or nonsteroidal anti-inflammatory drug, and the like in addition to the above-
As the antioxidant, ascorbic acid and its ester, sodium bisulfite, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol, or a combination thereof may be used, but the present invention is not limited thereto.
Examples of the anti-inflammatory drug include, but are not limited to, dexamethasone, fluorometholone, prednisolone, bromfenac, diclofenac, prubiprofen, ketorolac, or a salt thereof.
As one specific use of the present invention, the composition of the present invention can be used as a pharmaceutical composition for preventing or improving dry eye syndrome.
When the composition of the present invention is used as a pharmaceutical composition, it may contain, as a useful ingredient, a buffer, a viscosity adjusting agent, a surfactant, a stabilizer, a chelating agent and a combination thereof commonly used in the preparation of a therapeutic agent for dry eye syndrome , Or a pharmaceutically acceptable carrier.
Examples of the buffer include MES (2- (N-morpholino) ethanesulfonic acid hemin sodium salt), HEPES (N- {hydroxyethyl} piperazine-N '- {2- ethanesulfonic acid} -Bis (2-hydroxyethyl) 2-aminoethanesulfonic acid), MOPS (3- {N-morpholino} propanesulfonic acid), BIS- ) Methane), citrate buffers, maleate buffers, succinate buffers, malate buffers, boric acid / sodium borate buffers, or combinations thereof may be used, but are not limited thereto.
As the viscosity adjusting agent, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, or a combination thereof may be used, It is not.
Examples of the surfactant include polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, ethylene glycol, propylene glycol, polysorbate such as Tween 80, Tween 60, Tween 20, poloxamer such as Pluronic F127, Pluronic F108 ), Poloxamines (e.g., Tetronic 1508, Tetronic 908), Brij, Myrj, long chain fatty alcohols having a carbon number of 12 or more (e.g., oleyl alcohol, stearyl alcohol, myristyl alcohol and docosohexanoyl Alcohol, etc.) or a combination thereof may be used, but is not limited thereto.
The pharmaceutically acceptable carriers are those conventionally used in the art to which the present invention belongs and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate , Microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, no. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc., in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably administered by parenteral administration, more preferably intravenous infusion, subcutaneous injection, muscle injection, intraperitoneal injection, percutaneous administration, mucosal administration, Administration, and more preferably, topical administration.
A suitable dosage of the pharmaceutical composition of the present invention may vary depending on such factors as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, route of administration, excretion rate, . The dosage of the pharmaceutical composition of the present invention is 0.01 to 80 mg / kg (body weight) on an adult basis, preferably 0.1 to 60 mg / kg (body weight). In addition, depending on the judgment of a doctor or a pharmacist, it may be administered once or several times a day at intervals of a certain time. In particular, in the case of topical administration, it is preferable that the preparation is not used once to several times per day in an amount of 0.001 to 3% (w / v, the same applies), preferably 0.01 to 1%.
The pharmaceutical composition of the present invention may be formulated into a unit dosage form by using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by those having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container.
According to a preferred embodiment of the present invention, the formulation of the pharmaceutical composition of the present invention may be formulated as a solution, suspension, syrup, emulsion, liposome, excipient, powder, granule, tablet, ointment, An eye drop, a contact lens cleaner or a contact lens lubricant, and may further comprise a dispersant or stabilizer.
As another specific application of the present invention, the composition of the present invention can be used as a quasi-drug composition for preventing or improving dry eye syndrome.
When the composition of the present invention is used as a quasi-drug composition, it may be suitably used in accordance with a conventional method such as using the above-described antler extract directly or in combination with other quasi-drugs or quasi-drugs.
The quasi-drug composition may be prepared and used in the form of a product selected from the group consisting of a sterilizing agent, a shower foam, an eye wash solution, a wet tissue, a hand wash, a humidifier cleaning agent, an ointment agent and a filter cleaning agent, .
As another specific use of the present invention, the composition of the present invention can be used as a food composition for preventing or improving dry eye syndrome.
When the composition of the present invention is used as a food composition, the above-described antler extract can be used as it is, or can be used together with other food or food ingredients. For example, it can be used with proteins, carbohydrates, fats, nutrients, seasonings and flavors. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Daisaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavors (saccharine, aspartame, etc.) can be used as flavorings.
There is no particular limitation on the kind of the food. Examples of the food to which the above-mentioned flat-nose extract can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, , Alcoholic beverages and vitamin complexes, and includes all health foods in a conventional sense.
When the food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice and the like may be further added in addition to the white flour extract of the present invention.
In addition, the food composition may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin , Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juices, beverages and vegetable drinks. These components may be used independently or in combination.
On the other hand, the extract of the present invention is extracted from a natural white flour, and is harmless to the human body. Since it has little toxicity and side effects, it can be safely used for a long period of use and can be safely applied to a pharmaceutical composition, quasi-drug composition or food composition Can be applied.
The present invention relates to a method for inhibiting corneal epithelial cell damage, comprising the steps of: (a) culturing an animal model of ocular dryness; (b) accelerating tear production, delaying tear film destruction time, And inhibit the infiltration of macrophages by inflammatory reactions, thereby preventing or ameliorating dry eye syndrome. In addition, the extract of the present invention has no cytotoxicity and side effects, and can be safely used in a pharmaceutical composition, a quasi-drug composition or a food composition.
FIG. 1 is a graph showing the effect of accelerated tear production on an eye-dry animal model (DED) of a cotton-on-white extract.
FIG. 2 is a graph showing the effect of inhibiting tear film destruction on the dry animal model (DED) of an opthalmic extract.
FIG. 3 is a graph showing the inhibitory effect on the corneal epithelial cell damage on the dry eye animal model (DED) of the extract of the white flour.
FIG. 4 is a graph showing the effect of inhibiting the secretion of inflammatory cytokines in an eye-dry animal model (DED) of an extract of a cotton bud.
FIG. 5 is a graph showing the effect of suppressing the macrophage infiltration on the dry animal model (DED) of the eyebrow extract.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
Example 1: Manufacture of cottonseed extract
The stems and leaves of the perilla seeds were dried and ground to a particle size of 0.2 mm to 2 mm to prepare white flour wood powder. The extraction solvent carbon dioxide was prepared by liquefaction by injecting into a cooler at -20 ° C.
Subsequently, the white flour is firstly extracted with supercritical carbon dioxide at a temperature of 40 to 50 ° C and a pressure of 100 to 200 bar, and then the primary supercritical extract of the perilla wood is heated at a temperature of 45 to 55 ° C and a temperature of 100 to 200 bar Secondary extraction was performed with supercritical carbon dioxide under pressure to extract an oil containing a large amount of functional ingredients such as sabinene and pinene from cottonwood.
Example 2: prevention or improvement of dry eye syndrome Experiment on effects
2-1. Materials and methods
Experimental dry eye (EDE) and experimental procedure
8-week-old C57BL / 6 mice were exposed to 0.5 mg / 0.2 ml scopolamine hydrobromide (Sigma-Aldrich, St. Louis, MO) three times a day Hour, 13: 30, and 18: 00) to induce dry eye. At this time, the experimental space was maintained at a temperature of 30% humidity and a temperature of 25 ° C.
During the experiment, animal behavior, food and water intake were not restricted. Mice were distributed into the following six groups: untreated (UT); EDE control group (eye drop group); Balanced salt solution (BSS, Alcon, Forth value, TX); 0.001% treated with cottonseed extract; 0.01% cotton wool extract-treated group; 0.1% cottonseed extract treatment group. At this time, the eye drops containing the white flour extract were prepared by diluting with BSS.
Then, the mice that induced dry eye syndrome were treated with eye drops or balanced salt containing 2 μl of the perilla extract four times a day.
Analysis of tear production
(Phenol-red impregnated cotton thread, Zone-quick, Oasis, Glendora, CA) was applied to the external conjunctival sac of the mouse for 20 seconds Lt; / RTI > The length of the cotton yarn turned red by tear was then measured using a microscope (SMZ 1500; Nikon, Melville, NY) and then the length was converted to volume.
Tear film breakdown time analysis
In order to examine the tear film break-up time, which is a factor determining the stability of tear film (tear film stability), the most important clinical factor for dry eye syndrome, a conjunctival sac of mouse treated with eye drop containing curd extract, , 1 μl of 1% Fluorescein was instilled, eyes were closed about 3 times, and the eyes were opened and gently spread. Then, a slit tear film was prepared through a slit lamp microscope equipped with a Cobalt blue filter The time (in seconds) until the first defect occurred was measured.
Corneal surface damage analysis
After induction of dry eye syndrome, 1 μl of 1% fluorescein (Fluorescein) was instilled into the conjunctival sac of the mouse treated with eye drops containing the white flour extract, and the eye was washed with saline and then the rat cornea was observed with a slit- The degree of damage (degree of fluorescent staining) was scored and evaluated. For this purpose, the cornea was divided into quarters, and each quadrant was evaluated to 0-4 points as follows (total 0-16 points).
Immunohistological analysis
After induction of dry eye syndrome, the eye tissues of the mice treated with the scutellum extract were fixed in 10% formalin, embedded in paraffin, and fixed on a slide glass with a thickness of 4 ㎛. The slide glass was then immersed in ethanol and blocked with BSA. The anti-CD11b antibody was then treated at room temperature for 3 hours. After washing with PBS, the FITC-conjugated anti-goto secondary antibody was treated and mounted on a mounting solution containing DAPI. The BX-40 apparatus equipped with eXcope, X3 digital camera (DIXI Optics, Korea) (Olympus, Japan).
Analysis of inflammation-mediated cytokine concentration
After the induction of dry eye syndrome, the conjunctiva of mice treated with eyebrowswax containing the extract of Fagaceae was collected through surgery, and the quantities of cytokines known to cause inflammation by Western blot analysis after protein separation were quantified.
Specifically, after inducing dry eye syndrome, conjunctival tissues of mice treated with eye drops containing the white flour extract were washed twice with PBS solution, followed by addition of lysis buffer (PRO-PREP protein extraction solution, Intron Biotechnology, Korea) Lt; 0 > C for 10 minutes. The cells were then centrifuged at 17,000 rpm, 4 ° C for 20 minutes, and the supernatant was recovered. Then 30 μg of each supernatant was mixed with SDS loading buffer (60 mM Tris, 25% glycerol, 2% SDS, 0.5% 2-mercaptoethanol, 0.1% bromophenol blue) Was loaded onto a polyacrylamide gel, electrophoresed and transferred to a nitrocellulose membrane (NCM). Then, the NCM was blocked with TBS (10 mM Tris, 100 mM NaCl, 0.1% tween 20) solution containing 5% unmodified milk powder at room temperature for 1 hour. TTBS solution for 10 minutes, followed by reaction with primary antibody (Prx2, Prx4, Prx5 diluted 1: 1000 dilution) for 2 hours, and then washed three times with TTBS solution. Then peroxidase (peroxidase) contains a secondary antibody (goat-anti mouse 1: 10,000 , goat-anti rabbit 1: 10,000) sikyeotgo reaction for 1 hour, the detection of the antibody Amersham ECL TM Western Blotting Detection Reagents ( GE Healthcare, UK) and confirmed by LAS (GE Healthcare, UK).
Statistical analysis
The results were expressed as standard error (± SEM). The statistical significance of the differences between the experimental groups was analyzed by one-way analysis of variance (ANOVA), Turkish post test, SPSS 17.0 software (SPSS Inc., Chicago, ). P values less than 0.05 were considered statistically significant.
2-2. Experiment result
Tear production and tear film breakdown analysis
After treatment of the eye drops containing the white flake extract, mice having dry eye syndrome were treated with the method described above to analyze the effects of restoring the tear secretion and blocking the tear film breakdown time. As a result, as shown in FIG. 1 and FIG. 2, the 0.1% cotton wool extract showed a decrease in the amount of tear secreted by dry eye syndrome, and inhibited the tear film destruction by dry eye syndrome.
Corneal epithelial cell damage analysis
The corneal epithelium cells were stained with fluorescein stain to measure the degree of corneal epithelial damage by the method described above after treating the eye drop containing the extract of the white flake with the mouse causing dry eye syndrome. As a result, as shown in FIG. 3, it was confirmed that the 0.1% cotton wool extract effectively inhibited corneal epithelial cell damage by dry eye syndrome.
Analysis of inflammatory mediated cytokine expression
The amount of inflammatory cytokine protein expression in the conjunctival tissues was measured in order to confirm that the conjunctival tissues could inhibit inflammatory cytokine increase after treatment with the eye drop containing the extract of Pleurotus eryngii. As a result, as shown in FIG. 4, it was confirmed that 0.001%, 0.01%, and 0.1% of the cotton wool extract effectively decreased the expression level of the inflammatory cytokine induced by dry eye syndrome.
Immunohistological analysis
After treatment of the eye drops containing the extract of the white flies, the mouse induced dry eye syndrome was examined to see if it could inhibit macrophage infiltration by inflammation in the cornea. As a result, as shown in FIG. 5, it was confirmed that the 0.1% cotton wool extract effectively inhibited macrophage infiltration induced by dry eye syndrome.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150122854A KR101618012B1 (en) | 2015-08-31 | 2015-08-31 | Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150122854A KR101618012B1 (en) | 2015-08-31 | 2015-08-31 | Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101618012B1 true KR101618012B1 (en) | 2016-05-04 |
Family
ID=56022225
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150122854A KR101618012B1 (en) | 2015-08-31 | 2015-08-31 | Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101618012B1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220046272A (en) * | 2020-10-07 | 2022-04-14 | 주식회사 휴메디솔 | Contact lens multifunctional solution based on biocompatible MPC polymer and its manufacturing method |
| WO2023101046A1 (en) * | 2021-12-01 | 2023-06-08 | 주식회사 휴메디솔 | Contact lens solution based on mpc and protease, and method for preparing same |
| WO2023101047A1 (en) * | 2021-12-01 | 2023-06-08 | 주식회사 휴메디솔 | Protease-based contact lens cleaning solution and method for preparing same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101211969B1 (en) | 2012-06-14 | 2012-12-12 | 주식회사 코씨드바이오팜 | Compositions for treating ophthalmoxerosis comprising extract of fish eye as active ingredients |
| KR101438744B1 (en) | 2012-08-02 | 2014-09-15 | 전남대학교산학협력단 | Compositions for Preventing or Treating of Dry Eyes or Inflammatory Eye Surface Diseases Comprising Adiponectin as Active Ingredient |
-
2015
- 2015-08-31 KR KR1020150122854A patent/KR101618012B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101211969B1 (en) | 2012-06-14 | 2012-12-12 | 주식회사 코씨드바이오팜 | Compositions for treating ophthalmoxerosis comprising extract of fish eye as active ingredients |
| KR101438744B1 (en) | 2012-08-02 | 2014-09-15 | 전남대학교산학협력단 | Compositions for Preventing or Treating of Dry Eyes or Inflammatory Eye Surface Diseases Comprising Adiponectin as Active Ingredient |
Non-Patent Citations (1)
| Title |
|---|
| Cornea. vol.29(5), pp.559-563* |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220046272A (en) * | 2020-10-07 | 2022-04-14 | 주식회사 휴메디솔 | Contact lens multifunctional solution based on biocompatible MPC polymer and its manufacturing method |
| KR102479119B1 (en) | 2020-10-07 | 2022-12-19 | 주식회사 휴메디솔 | Contact lens multifunctional solution based on biocompatible MPC polymer and its manufacturing method |
| WO2023101046A1 (en) * | 2021-12-01 | 2023-06-08 | 주식회사 휴메디솔 | Contact lens solution based on mpc and protease, and method for preparing same |
| WO2023101047A1 (en) * | 2021-12-01 | 2023-06-08 | 주식회사 휴메디솔 | Protease-based contact lens cleaning solution and method for preparing same |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101618012B1 (en) | Composition for preventing or improving dry eye syndrome comprising Chamaecyparis obtuse extracts | |
| KR101764786B1 (en) | Composition for treatment and prevention of dry eye syndrome comprising Polygonum Cuspidatum extract or fraction thereof | |
| JP2021517557A (en) | Composition for prevention or treatment of xerophthalmia containing Aoki extract | |
| US11191801B2 (en) | Pharmaceutical composition for preventing or treating diabetic complications and angioedema, containing natural mixture extract as active ingredient | |
| KR101797072B1 (en) | Composition for preventing, treating, or improving ocular fatigue, ocular inflammation, or dry eye syndrome comprising Camellia japonica extracts | |
| KR101762797B1 (en) | Compositions for preventing or treating dry eye syndrome comprising extract of maple leaves or fraction thereof | |
| KR101864729B1 (en) | Pharmaceutical composition for improving ocular fatigue and dry eye comprising Eurya japonica extracts | |
| US20220072077A1 (en) | Composition for preventing or treating skin diseases comprising bridalwreath spirea | |
| KR20180065933A (en) | Composition for preventing or treating of inflammatory eye disease comprising extract of maple leaf or fractions thereof | |
| KR20180136039A (en) | Composition for treatment and prevention of dry eye syndrome comprising Polygonum Cuspidatum extract or fraction thereof | |
| KR102056926B1 (en) | Composition for preventing, ameliorating or treating anterior eye disease comprising Adenophorae Radix extract as effective component | |
| KR102442039B1 (en) | Pharmaceutical composition for the prevention or treatment of eye diseases using Phaeodactylum tricornutum as an active ingredient | |
| KR20190076732A (en) | Composition for treatment and prevention of dry eye syndrome comprising mixed extract or fraction thereof | |
| KR20200022930A (en) | Use of Arctium lappa extract for eye health | |
| KR102481709B1 (en) | A composition for treating dry eye syndrome comprising a extract of Vaccinium Uliginosum as an active ingredient | |
| US20220362356A1 (en) | Composition For Preventing Or Treating Rheumatoid Arthritis, Comprising Snake Venom | |
| KR102340531B1 (en) | Composition for preventing or treating rheumatoid arthritis comprising venom derived from Agkistrodon piscivorous piscivorous | |
| KR101838142B1 (en) | Composition for prevention or treatment of corneal diseases comprising small black soybean extract | |
| KR20180019802A (en) | Pharmaceutical composition for prevention or treatment of retina disorder comprising palmate maple leaf extract | |
| KR102138860B1 (en) | Composition for lowering intraocular pressure regulating comprising extract of maple leaves | |
| KR101928026B1 (en) | Composition for treatment and prevention of dry eye syndrome comprising Aster koraiensis extract or fraction thereof | |
| KR102571939B1 (en) | A composition for improving dry eye syndrome comprising Tetraselmis chuii | |
| KR101860510B1 (en) | Composition for Improving Retinal Diseases Using an Extract of Lithospermum erythrorhizon | |
| KR101862546B1 (en) | Composition for Improving Retinal Diseases Using an Extract of Achillea sibirica | |
| KR102442038B1 (en) | Pharmaceutical composition for the prevention or treatment of eye diseases using Nannochloropsis sp. as an active ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20190429 Year of fee payment: 4 |