KR101504730B1 - Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma - Google Patents
Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma Download PDFInfo
- Publication number
- KR101504730B1 KR101504730B1 KR20130147048A KR20130147048A KR101504730B1 KR 101504730 B1 KR101504730 B1 KR 101504730B1 KR 20130147048 A KR20130147048 A KR 20130147048A KR 20130147048 A KR20130147048 A KR 20130147048A KR 101504730 B1 KR101504730 B1 KR 101504730B1
- Authority
- KR
- South Korea
- Prior art keywords
- asthma
- composition
- bronchial asthma
- tnf
- extract
- Prior art date
Links
- 208000006673 asthma Diseases 0.000 title claims abstract description 66
- 241000405911 Rehmannia glutinosa Species 0.000 title claims abstract description 6
- YEFOAORQXAOVJQ-UHFFFAOYSA-N wuweizischun A Natural products C1C(C)C(C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-UHFFFAOYSA-N 0.000 title claims abstract description 6
- 208000030603 inherited susceptibility to asthma Diseases 0.000 title claims description 43
- 241001522129 Pinellia Species 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 64
- 239000000284 extract Substances 0.000 claims abstract description 42
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 9
- 230000036541 health Effects 0.000 claims description 6
- 241001522232 Pinellia ternata Species 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 235000013376 functional food Nutrition 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 241001400472 Omiza Species 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000002778 food additive Substances 0.000 claims 1
- 235000013373 food additive Nutrition 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 43
- 108010002616 Interleukin-5 Proteins 0.000 abstract description 41
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 abstract description 36
- 230000000694 effects Effects 0.000 abstract description 34
- 210000004072 lung Anatomy 0.000 abstract description 23
- 210000001519 tissue Anatomy 0.000 abstract description 22
- 210000004989 spleen cell Anatomy 0.000 abstract description 18
- 238000010172 mouse model Methods 0.000 abstract description 15
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 7
- 208000026935 allergic disease Diseases 0.000 abstract description 7
- 230000009610 hypersensitivity Effects 0.000 abstract description 4
- 231100001083 no cytotoxicity Toxicity 0.000 abstract description 4
- 230000006378 damage Effects 0.000 abstract description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 41
- 102000000743 Interleukin-5 Human genes 0.000 description 39
- YEFOAORQXAOVJQ-RZFZLAGVSA-N schisandrol a Chemical compound C1[C@H](C)[C@@](C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-RZFZLAGVSA-N 0.000 description 27
- 102000004127 Cytokines Human genes 0.000 description 26
- 108090000695 Cytokines Proteins 0.000 description 26
- 230000028327 secretion Effects 0.000 description 23
- 108010058846 Ovalbumin Proteins 0.000 description 22
- 229940092253 ovalbumin Drugs 0.000 description 22
- 239000000469 ethanolic extract Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 16
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 15
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 15
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 229940010454 licorice Drugs 0.000 description 15
- 238000005259 measurement Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 210000004988 splenocyte Anatomy 0.000 description 14
- 241000202807 Glycyrrhiza Species 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000002158 endotoxin Substances 0.000 description 11
- 229920006008 lipopolysaccharide Polymers 0.000 description 11
- 230000002757 inflammatory effect Effects 0.000 description 10
- 230000000172 allergic effect Effects 0.000 description 9
- 208000010668 atopic eczema Diseases 0.000 description 9
- 235000013361 beverage Nutrition 0.000 description 9
- 210000004207 dermis Anatomy 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 231100000263 cytotoxicity test Toxicity 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 230000002685 pulmonary effect Effects 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 5
- 230000010085 airway hyperresponsiveness Effects 0.000 description 5
- 210000004969 inflammatory cell Anatomy 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 230000036428 airway hyperreactivity Effects 0.000 description 4
- 229940037003 alum Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 208000037656 Respiratory Sounds Diseases 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 206010047924 Wheezing Diseases 0.000 description 3
- XAQHXGSHRMHVMU-UHFFFAOYSA-N [S].[S] Chemical compound [S].[S] XAQHXGSHRMHVMU-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000000621 bronchi Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 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 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010008469 Chest discomfort Diseases 0.000 description 2
- 206010011224 Cough Diseases 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
- 208000001840 Dandruff Diseases 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 244000303040 Glycyrrhiza glabra Species 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108090000176 Interleukin-13 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 208000005279 Status Asthmaticus Diseases 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 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 2
- 238000013329 compounding Methods 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 2
- 229960002329 methacholine Drugs 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- -1 olive oil Chemical compound 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 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
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 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
- 239000000080 wetting agent Substances 0.000 description 2
- 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
- UWYHEGBHZPUZEE-UHFFFAOYSA-N 2,3-dihydroxy-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C(O)=C1O UWYHEGBHZPUZEE-UHFFFAOYSA-N 0.000 description 1
- NBWRJAOOMGASJP-UHFFFAOYSA-N 2-(3,5-diphenyl-1h-tetrazol-1-ium-2-yl)-4,5-dimethyl-1,3-thiazole;bromide Chemical compound [Br-].S1C(C)=C(C)N=C1N1N(C=2C=CC=CC=2)N=C(C=2C=CC=CC=2)[NH2+]1 NBWRJAOOMGASJP-UHFFFAOYSA-N 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-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
- 208000000884 Airway Obstruction Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 241001480043 Arthrodermataceae Species 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 239000004606 Fillers/Extenders Substances 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
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000010786 Interleukin-5 Receptors Human genes 0.000 description 1
- 108010038484 Interleukin-5 Receptors Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 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
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 241000700159 Rattus Species 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
- 102000005886 STAT4 Transcription Factor Human genes 0.000 description 1
- 108010019992 STAT4 Transcription Factor Proteins 0.000 description 1
- 102000013968 STAT6 Transcription Factor Human genes 0.000 description 1
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 240000001949 Taraxacum officinale Species 0.000 description 1
- 235000005187 Taraxacum officinale ssp. officinale Nutrition 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution 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
- 229940127225 asthma medication Drugs 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000010083 bronchial hyperresponsiveness Effects 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 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
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 210000000991 chicken egg Anatomy 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000037304 dermatophytes Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 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
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 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
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 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
- 239000000945 filler Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol 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
- 235000013402 health food Nutrition 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229910052500 inorganic mineral 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
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 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
- 239000000401 methanolic extract Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000007896 negative regulation of T cell activation Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 229940124595 oriental medicine Drugs 0.000 description 1
- 210000001672 ovary Anatomy 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
- 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
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate 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
- 230000003449 preventive effect Effects 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
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 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
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 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
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 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
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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/80—Scrophulariaceae (Figwort family)
- A61K36/804—Rehmannia
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/79—Schisandraceae (Schisandra family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
- A61K36/8888—Pinellia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- 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
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
Description
본 발명은 숙지황(熟地黃, Rehmannia glutinosa), 반하(半夏, Pinellia ternata) 및 오미자(五味子, Schizandra chinensis) 혼합 추출물을 유효성분으로 함유하는 기관지 천식의 예방과 치료를 위한 조성물에 관한 것이다.The present invention relates to a composition for preventing and treating bronchial asthma containing, as an active ingredient, a mixed extract of Rehmannia glutinosa , Pinellia ternata, and Schizandra chinensis .
본 발명에 따른 조성물은 세포 독성이 없고, 비장세포의 TNF-α와 IL-5의 발현을 억제하며, 기관지 천식 마우스 모델에서 기도과민성을 억제하고, 폐조직의 손상을 개선하며, 기관지 천식 마우스 모델의 폐조직에서 TNF-α와 IL-5의 발현을 억제하는 효과를 보유하고 있다.
The composition according to the present invention is free from cytotoxicity and inhibits the expression of TNF-a and IL-5 in spleen cells, inhibits airway hyper-sensitivity in bronchial asthma mouse model, improves lung tissue damage, And TNF-a and IL-5 in lung tissues.
천식이란 폐 속에 있는 기관지가 예민해진 상태로, 때때로 기관지가 좁아져서 숨이 차고 가랑가랑하는 숨소리가 들리면서 기침을 심하게 하는 증상을 나타내는 병을 말하는데, 기관지의 알레르기 염증 반응 때문에 발생하는 알레르기 질환이다.Asthma is an allergic disease caused by allergic inflammation of the bronchial tree. It is a condition in which the bronchus in the lung is sensitive, sometimes the bronchus narrows, and breathing, cramp and breath sounds are heard.
기관지 천식의 대표적인 증상은 호흡곤란, 기침, 천명(쌕쌕거리는 거친 숨소리)이다. 이러한 증상이 반복적으로, 발작적으로 나타나지만 실제로 천식 환자는 전형적인 천식의 증상 외에 비전형적인 증상을 호소하는 경우도 많다. 즉, 호흡곤란이나 쌕쌕거리는 숨소리 등의 증상은 없고 단지 마른 기침만 반복적으로 나타나는 경우, 가슴이 답답하거나 흉부 압박감을 호소하는 경우 또는 목구멍에 가래가 결려있는 것 같은 증상만을 호소하는 경우도 있다. 일반적으로 감기에 걸린 후에 호흡곤란이 악화하거나, 달리기 같은 운동 후에 호흡곤란, 거친 숨소리 증상들이 많이 나타난다.
The most common symptoms of bronchial asthma are dyspnea, cough, and wheezing (wheezing). These symptoms repeatedly, seizure, but in fact, asthma patients in addition to the typical symptoms of asthma, often in the case of atypical symptoms. In other words, there are no symptoms such as breathing difficulties or wheezing, breathing, only repetitive dry cough, complaints of chest tightness, complaints of chest tightness, or complaints of sputum in the throat. Generally, after suffering from a cold, dyspnea deteriorates, or after exercise such as running, difficulty in breathing, and many symptoms of rough breathing.
때로는 심한 천식 발작으로 즉각적인 응급치료 및 입원 치료가 절대적으로 필요한 경우가 있는데, 이때 환자는 곧 죽을 것 같은 공포를 느끼며, 실제로 심한 천식 발작은 생명을 위협하기도 한다. 하지만 천식 약물을 적절하게 사용하고 환경 관리를 잘한다면 정상 건강인처럼 살아갈 수 있다.
Sometimes severe asthma attacks require immediate first aid and inpatient treatment, in which the patient feels fearful of death and, in fact, severe asthma attacks are life-threatening. However, if you use asthma medications properly and manage the environment well, you can live like a normal healthy person.
천식은 유전적 요인과 환경적 요인이 합쳐져서 생기는 대표적인 알레르기 질환이다. 즉, 부모로부터 물려받은 알레르기 체질과 주위의 천식유발 인자들이 상호작용을 일으켜 면역체계에 혼란이 생기면서 천식이 발생하게 된다. 알레르기란 정상에서 벗어난 과민반응을 의미하는 것으로, 정상인에게는 증상이 유발되지 않지만 알레르기 환자에게는 과민반응으로 여러 증상이 나타나게 되는 것을 말한다.
Asthma is a typical allergic disease caused by the combined genetic and environmental factors. In other words, allergic inheritance inherited from parents and surrounding asthma inducing factors interact with each other, resulting in confusion in the immune system, resulting in asthma. Allergy means a hypersensitive reaction that deviates from normal, which means that symptoms are not caused by normal people but by allergic patients, various symptoms are caused by hypersensitivity reaction.
이처럼 과도한 면역반응으로 인한 염증성 사이토카인의 분비는 기관지 염증에 의한 기도과민성과 점액 과분비를 동반한 가역적 기도 폐쇄를 유발하므로, 과도한 면역반응을 억제하는 것이 천식의 예방과 치료에 중요하다고 할 수 있다.
The secretion of inflammatory cytokines due to excessive immune responses leads to reversible airway obstruction accompanied by airway hyperresponsiveness and mucous hypersecretion due to bronchial inflammation. Therefore, inhibiting excessive immune responses is important for the prevention and treatment of asthma.
기관지 천식의 염증반응은 T 세포, B 세포, 호중구, 비만세포 및 호산구 등의 염증세포와 사이토카인, 케모카인과 같은 화학 매개체들에 의해 유발된다. 특히 천식의 기도염증에서는 T 세포 중 CD4+ type 2 helper T(Th2) 세포들이 생성하는 사이토카인인 IL-4, IL-5 및 IL-13이 알레르기성 기관지 천식의 기도 과민성과 호산성 염증반응에 중요한 매개역할을 수행하는 것으로 알려져 있다.
Inflammatory responses of bronchial asthma are caused by inflammatory cells such as T cells, B cells, neutrophils, mast cells and eosinophils, and chemical mediators such as cytokines and chemokines. In particular, IL-4, IL-5, and IL-13, which are cytokines produced by CD4 +
한편, 출원번호 제10-2011-0120552호 '기관지 천식의 예방과 치료를 위한 조성물'은 본 출원인(한국기초과학지원연구원)과 충북테크노파크가 공동 과제로 수행한 내용을 특허 출원한 것이다. Meanwhile, Application No. 10-2011-0120552 'Composition for prevention and treatment of bronchial asthma' is a patent application filed by the present applicant (Korea Basic Science Research Institute) and Chungbuk Techno Park as a joint project.
위 종래 기술은 한의학상 처방 중 하나인 금수육군전(金水六君煎)을 변형한 것으로, 숙지황, 반하, 진피, 감초, 길경 및 오미자의 메탄올 추출물을 유효성분으로 함유하는 기관지 천식의 예방과 치료를 위한 조성물에 관한 것이다.The above-mentioned conventional technology is a modification of Kangsu Army Gun (one of the prescription of oriental medicine), and it is a preventive and therapeutic treatment of bronchial asthma containing methanol extract of Sukjipphi, Baihe, Dandelion, Licorice, Gakyung and Omija as active ingredients ≪ / RTI >
위 종래 기술에 따른 조성물을 'OMC-2010'이라 명명하였으며, OMC-2010은 세포 독성이 없고, NO 생성을 억제하며, 기관지 조직의 치료, 기도저항의 억제, 염증성 물질의 억제, 항염증성 물질의 증가, T세포 활성화 억제, 폐조직 단백질 STAT4 및 STAT6의 억제 및 간독성이 없는 효과를 입증하여 특허 등록되었다.
The composition according to the prior art was named 'OMC-2010', and OMC-2010 has no cytotoxicity, inhibits NO production, inhibits the treatment of bronchial tissue, inhibits airway resistance, inhibits inflammatory substances, , Inhibition of T cell activation, inhibition of lung tissue proteins STAT4 and STAT6, and hepatotoxicity.
이후, 본 출원인은 상기 기술을 발전시키기 위해 아래와 같은 연구를 더 수행하였다.
Hereafter, the Applicant has further carried out the following research to develop the above technique.
우선, OMC-2010의 면역조절효과를 조사하기 위해, OMC-2010 열수 추출물과 에탄올 추출물을 마우스 비장세포에 처리하여 전염증성 사이토카인인 IL-1β, IL-6, TNF-α등을 조사하고, Th2 사이토카인인 IL-4, IL-5, IL-13의 발현을 관찰하였다.First, in order to investigate the immunomodulatory effect of OMC-2010, OMC-2010 hydrothermal extract and ethanol extract were treated with mouse splenocytes to investigate proinflammatory cytokines IL-1β, IL-6 and TNF-α, Th2 cytokines IL-4, IL-5 and IL-13 were observed.
그 결과, OMC-2010 에탄올 추출물은 TNF-α, IL-5 및 IL-1β의 발현을 유의하게 억제하였으며, OMC-2010 열수 추출물 역시 TNF-α와 IL-5의 발현을 유의하게 억제함을 알 수 있었다.As a result, the OMC-2010 ethanol extract significantly inhibited the expression of TNF-α, IL-5 and IL-1β, and the OMC-2010 hot water extract also significantly inhibited the expression of TNF-α and IL-5 I could.
이를 통하여, OMC-2010 추출물이 면역 질환 및 천식 등에 유효할 것으로 추정할 수 있었다.
The results suggest that OMC-2010 extract may be useful for immunological diseases and asthma.
위 결과를 토대로, 본 출원인은 OMC-2010 구성 약재 중 실제로 사이토카인 억제 역할을 하는 약재가 무엇인지 밝히기 위해 OMC-2010 구성 약재인 숙지황, 반하, 진피, 감초, 길경 및 오미자를 각각 열수 추출과 에탄올 추출한 다음, 비장세포에 처리하여 전염증성 사이토카인인 TNF-α와 Th2 사이토카인인 IL-5의 발현을 관찰하였다.Based on the above results, Applicant has found that the medicines of OMC-2010, which are actually cytokine inhibiting agents, are hydrolyzed and extracted with ethanol, ethanol, And then treated with splenocytes to observe the proinflammatory cytokines TNF-a and Th2 cytokine IL-5.
그 결과, 열수 추출물 중에서는 숙지황이, 에탄올 추출물 중에서는 숙지황, 반하, 오미자가 각각 TNF-α와 IL-5를 억제하는 것으로 나타났다.
As a result, it was found that Sulfur Sulfur was inhibited in hot water extract and Sulfur Sulfur, Vanha and Omija inhibited TNF-α and IL-5, respectively.
따라서 이후 연구에서는 실제로 사이토카인 억제 효과가 있는 숙지황, 반하 및 오미자의 에탄올 추출물을 이용하여 실험을 수행하였다.Therefore, in the following study, experiments were carried out using ethanol extracts of Sukjipu, Banha and Omija, which have cytokine inhibitory effect.
다음, 구성 약재들의 효과적인 배합 비율을 선정하고자, 숙지황, 반하, 오미자를 여러 비율로 섞은 후 혼합추출하여 TNF-α와 IL-5의 발현을 관찰하였으며, 알레르기성 기관지 천식 마우스 모델에서 유의한 효과가 있는지 확인하였다.
TNF-α and IL-5 expression were observed by mixing with various ratios of Sukjwanghwang, Banha and Omija in order to select the effective compounding ratio of the constituent drugs, and a significant effect was observed in the allergic bronchial asthma mouse model .
즉 본 발명은 이전의 발명을 더욱 발전시킨 것으로, 발명의 구성과 효능이 이전건에 비해 현저하게 진보한 것이라 할 수 있다.
That is, the present invention has further improved the previous invention, and the composition and the efficacy of the invention are remarkably improved as compared with the prior art.
본 발명의 목적은 천연물 소재의 효과적인 배합비율을 선정하고, 기관지 천식 마우스 모델에서 효능을 확인한 기관지 천식의 예방과 치료를 위한 조성물 및 건강기능식품을 제공함에 있다.
It is an object of the present invention to provide a composition and health functional food for prevention and treatment of bronchial asthma by selecting an effective blending ratio of a natural material and confirming its efficacy in a bronchial asthma mouse model.
본 발명은 숙지황(熟地黃, Rehmannia glutinosa), 반하(半夏, Pinellia ternata) 및 오미자(五味子, Schizandra chinensis) 혼합 추출물을 유효성분으로 함유하는 기관지 천식의 예방과 치료를 위한 조성물을 제공함으로써 기술적 과제를 해결하고자 한다.The present invention provides a composition for prevention and treatment of bronchial asthma containing, as an active ingredient, a mixed extract of Rehmannia glutinosa , Pinellia ternata, and Schizandra chinensis , .
또한 상기 숙지황, 반하 및 오미자의 중량 비율은 동일한 것을 특징으로 하는 기관지 천식의 예방과 치료를 위한 조성물을 제공함으로써, 기술적 과제를 해결하고자 한다.The present invention also provides a composition for preventing and treating bronchial asthma characterized in that the weight ratio of Sulfur Sulfur, Vanha and Omiza are the same.
또한 상기 혼합 추출을 위한 용매는 70% 에탄올인 것을 특징으로 하는 기관지 천식의 예방과 치료를 위한 조성물을 제공함으로써, 기술적 과제를 해결하고자 한다.
The present invention also provides a composition for preventing and treating bronchial asthma, wherein the solvent for the mixed extraction is 70% ethanol.
본 발명의 추출물 자체는 독성 및 부작용이 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다.
Since the extract of the present invention has little toxicity and side effects, it can be safely used even for long-term administration for the purpose of prevention.
본 발명의 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드, 록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트, 및 광물유를 들 수 있다.
The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be contained in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose , Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy, hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
경구 투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전부, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose)또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다.
Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as calcium carbonate, sucrose, ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used.
경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.
Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌 글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsion-freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용 될 수 있다.
As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물 형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 1일 0.0001g/kg 내지 10g/kg으로 투여하는 것이 바람직하다.The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, it is preferable to administer it at 0.0001 g / kg to 10 g / kg per day.
투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
The administration may be carried out once a day or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.
또한 본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.
In addition, the composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
본 발명은 상기의 제조방법으로 얻어진 추출물을 유효성분으로 함유하는 기관지 천식의 예방 및 개선용 건강기능식품을 제공한다.
The present invention provides a health functional food for prevention and improvement of bronchial asthma containing an extract obtained by the above production method as an active ingredient.
본 발명의 추출물을 포함하는 조성물은 기관지 천식의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.
The composition containing the extract of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of bronchial asthma. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used as powders, granules, tablets, capsules or beverages have.
본 발명의 추출물은 기관지 천식의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 상기 추출물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 1 내지 5 중량%로 가할 수 있으며 건강 음료 조성물은 100㎖를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다.
The extract of the present invention can be added to foods or beverages for the purpose of prevention and improvement of bronchial asthma. At this time, the amount of the extract in the food or beverage may generally be 1 to 5% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition may be added in an amount of 0.02 to 10 g, 1 g.
본 발명의 건강 음료 조성물은 지시된 비율의 필수 성분으로서 상기 추출물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient, such as ordinary beverages, in addition to containing the above-mentioned extract as an essential ingredient in the indicated ratio.
상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리통 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 일긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물들은 천연 과일 쥬스 및 채소 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above, the composition of the present invention can be applied to various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and aging agents (cheese, chocolate etc.), pectic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명에 따른 조성물은 비장세포에서 세포 독성을 보이지 않으며, 비장세포의 TNF-α와 IL-5의 발현은 유의하게 억제하는 효과를 보유하고 있다.The composition according to the present invention does not show cytotoxicity in spleen cells and has an effect of significantly suppressing the expression of TNF-a and IL-5 in spleen cells.
또한 본 발명에 따른 조성물은 기관지 천식 마우스 모델에서 기도과민성을 억제하고, 폐조직의 조직학적 손상을 유의하게 억제하며, 폐조직에서 TNF-α와 IL-5의 발현을 유의하게 억제하는 현저한 효과를 보유하고 있다.
In addition, the composition according to the present invention significantly inhibits airway hyperresponsiveness, inhibits the histological damage of lung tissue, and significantly inhibits expression of TNF-a and IL-5 in lung tissue in a bronchial asthma mouse model .
도 1은 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 열수 추출물과 에탄올 추출물의 세포 독성 실험결과를 나타낸 도면이다.
도 2는 실시예 1에 따른 열수 추출물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
도 3은 실시예 1에 따른 에탄올 추출물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
도 4는 실시예 1에 따른 열수 추출물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
도 5는 실시예 1에 따른 에탄올 추출물이 IL-5 분비에 미치는 영향을 나타낸 그래프이다.
도 6은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물의 세포 독성 실험결과를 나타낸 도면이다.
도 7은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
도 8은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물이 IL-5 분비에 미치는 영향을 나타낸 그래프이다.
도 9는 기관지 천식 모델을 유도하기 위해 OVA와 Alum을 주입하는 과정을 도시한 도면이다.
도 10은 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 기도과민성에 대한 효과를 나타낸 그래프이다.
도 11은 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 폐조직병리검사 결과를 나타낸 그래프이다.
도 12는 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 폐조직 사이토카인 측정 결과를 나타낸 그래프이다.FIG. 1 is a graph showing the results of cytotoxicity tests of hot water extracts and ethanol extracts of Sulfur (RG), Banha (PT), dermis (CUM), licorice (GU), Gilligan (PG) and omija (SC).
FIG. 2 is a graph showing the effect of the hot-water extract according to Example 1 on TNF-α secretion. FIG.
FIG. 3 is a graph showing the effect of the ethanol extract according to Example 1 on TNF-.alpha. Secretion. FIG.
4 is a graph showing the effect of the hot-water extract according to Example 1 on TNF-α secretion.
5 is a graph showing the effect of ethanol extract according to Example 1 on IL-5 secretion.
FIG. 6 is a graph showing the relationship between the A (RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition.
FIG. 7 is a graph showing the relationship between A (RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition on TNF-α secretion.
(RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition on IL-5 secretion.
FIG. 9 is a diagram illustrating a process of injecting OVA and Alum to induce a bronchial asthma model.
10 is a graph showing the effect of A (RG: PT: SC = 1: 1: 1) according to Example 2 on bronchial asthma mouse model induced by OVA on airway hyperresponsiveness.
11 is a graph showing the results of pulmonary histopathology of A (RG: PT: SC = 1: 1: 1) according to Example 2 in an OVA-induced bronchial asthma mouse model.
12 is a graph showing the results of measurement of lung tissue cytokines of A (RG: PT: SC = 1: 1: 1) according to Example 2 in a bronchial asthma mouse model induced by OVA.
본 명세서 및 청구범위에 사용된 용어나 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 안 되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다.
The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.
따라서 본 명세서에 기재된 실험예와 참고예는 본 발명의 가장 바람직한 일실시예에 불과한 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.
Therefore, the experimental examples and the reference examples described in the present specification are merely the most preferred embodiments of the present invention and are not intended to represent all of the technical ideas of the present invention. Therefore, various equivalents and variations Examples should be understood.
참고예Reference example 1. 실험 준비 1. Experimental preparation
여기에서, 실험예 1을 비롯한 이하 모든 실험예의 실험 준비는 아래의 실험 준비 과정과 동일하게 수행되었음을 밝혀둔다.
Here, it should be noted that the preparation of the experiment of all the following experimental examples including Experimental Example 1 was carried out in the same manner as the following experimental preparation procedure.
1-1. 실험동물1-1. Experimental animal
모든 실험은 원광대학교에서 정해놓은 동물 관리 규정에 따라 수행되었다. 본 실험에 사용한 C57BL/6 Mouse (체중 15-20 g, 6주령, female)는 (주)오리엔트 바이오(성남, 경기도, 대한민국)에서 구입하였다. 실험동물은 원광대학교 한의과대학 동물 사육실에서 일정한 온도(온도: 21±2℃, 습도:50~60%, 명암: 12시간 주기하에서 일반 고형사료((주)오리엔트 바이오, 성남)와 물을 충분히 공급하면서 환경 적응을 위해 일주일 동안 적응 시킨 후 실험하였다.
All experiments were carried out in accordance with the animal management regulations set by Wonkwang University. The C57BL / 6 mouse (body weight 15-20 g, 6 wk, female) used in this experiment was purchased from Orient Bio Co., Ltd. (Seongnam, Gyeonggi-do, Korea). Experimental animals were fed with general solid feed (Orient Bio, Seongnam) and water at a constant temperature (temperature: 21 ± 2 ℃, humidity: 50 ~ 60% And adapted for a week for environmental adaptation.
1-2. 마우스 1-2. mouse 비장세포Splenocyte (Mouse splenocyte) 준비(Mouse splenocyte) preparation
C57BL/6 마우스로부터 비장(spleen)을 분리하여 micro slide glass로 잘개 으깬 뒤, 0.4 ㎛ nylon cell strainer로 여과하였다. 1200 rpm에서 10분간 원심분리 한 후, 증류수를 이용하여 적혈구를 파괴하였다. 비장세포를 세척하여 RPMI-1640으로 부유한 후 세포수를 측정하였다.
The spleen was separated from the C57BL / 6 mouse, cut with a micro slide glass, and filtered through a 0.4 ㎛ nylon cell strainer. After centrifugation at 1200 rpm for 10 minutes, red blood cells were destroyed using distilled water. The spleen cells were washed, suspended in RPMI-1640, and the number of cells was measured.
1-3. 약재1-3. Medicinal
실험 약재인 숙지황(RG), 반하(PT), 진피(CUM), 감초(GU), 길경(PG) 및 오미자(SC)는 Omniherb(영천, 대한민국)에서 구입, 정선한 후 실험 약재로 사용하였다. 충북테크노파크 전통의약산업센터에서 확인한 후 약재를 사용하였으며, 일부는 -80℃에서 보관하였다.
Experimental medicines were purchased from Omniherb (Yeongcheon, Korea) and used as experimental medicines after they were purchased and selected from Rg, Hwang, PT, Dum, GU, . It was confirmed by Chungbuk Techno Park Traditional Medicine Industry Center and used medicinal materials. Some of them were stored at -80 ℃.
1-4. 시약 및 기기1-4. Reagents and devices
본 실험에 사용된 시약으로 LPS(Lipopolysaccharides), 난알부민(OVA, chicken egg ovalbumin, Grade V), Alum (aluminum hydroxide)은 Sigma(St. Louis, USA)에서 구입하여 사용하였다.Lipopolysaccharides (LPS), ovary albumin (OVA), and alum (aluminum hydroxide) were purchased from Sigma (St. Louis, USA) as reagents.
본 실험에서 사용된 기기는 clean bench, vortex mixer (Vision scientific Co. Korea), autoclave (Sanyo, Japan), micro-pipet (Gilson, France), homogenizer (OMNI, USA) 등을 사용하였다.
The instruments used in this study were a clean bench, a vortex mixer (Vision scientific Co. Korea), autoclave (Sanyo, Japan), a micro-pipette (Gilson, France) and a homogenizer (OMNI, USA).
실시예Example
1. OMC-2010 구성약재 각각의 추출물 제조 1. Preparation of each extract of OMC-2010 constitutive medicine
1-1. 1-1. 열수Heat number 추출물의 제조 Preparation of extract
숙지황(RG), 반하(PT), 진피(CUM), 감초(GU), 길경(PG) 및 오미자(SC) 10 g을 300 ml의 물에 약탕기(대웅, 한국)로 3시간 가열 추출하였다.10 g of Sukjunghwang (RG), Banha (PT), Dermatophyte (CUM), Licorice (GU), Gilyeong (PG) and Omija (SC) were extracted with 300 ml of water for 3 hours in a hot water bath (Dae Woong, Korea).
이 후 여과하여 동결 건조로 각각 건조 분말을 얻었으며, 실험을 위하여 4℃에 보관하였다. After that, they were filtered and lyophilized to obtain dry powders, respectively, which were stored at 4 ° C for experiments.
분말을 생리식염수에 녹여 stock solution을 제조하였으며, 제조된 stock solution은 -20℃에 보관하면서 분석방법에 적합하도록 희석하여 사용되었다.
The stock solution was prepared by dissolving the powder in physiological saline. The stock solution was diluted to be suitable for the analysis while being stored at -20 ° C.
1-2. 70% 에탄올 추출물의 제조1-2. Preparation of 70% ethanol extract
숙지황(RG), 반하(PT), 진피(CUM), 감초(GU), 길경(PG) 및 오미자(SC) 10 g에 300 ml의 70% 에탄올 용액을 가하여 37℃ 항온수조에서 24시간동안 추출하였다. 추출 후 에탄올층(상등액)을 회전감압농축기(EYELA, Rikakiki Co., Tokyo, Japan)로 농축한 후, 생리식염수에 녹여 stock solution을 제조하였다. 제조된 stock solution은 -20℃에 보관하면서 분석방법에 적합하도록 희석하여 사용되었다.
300 ml of 70% ethanol solution was added to 10 g of Sukjunghwang (RG), Banha (PT), dermis (CUM), licorice (GU) Respectively. After extraction, the ethanol layer (supernatant) was concentrated with a rotary evaporator (EYELA, Rikakiki Co., Tokyo, Japan) and dissolved in physiological saline to prepare a stock solution. The prepared stock solution was diluted to be suitable for the analytical method while being stored at -20 ° C.
실험예Experimental Example
1. One.
실시예Example
1 추출물의 세포 독성 실험 1 cytotoxicity test of extract
1-1. 실험시료 준비1-1. Preparation of test samples
실시예 1에 따른 열수 추출물 및 70% 에탄올 추출물을 각각 희석하여 0.1 ㎎/㎖, 0.5 ㎎/㎖, 1 ㎎/㎖의 농도로 실험시료를 준비하였다.The hot-water extract and the 70% ethanol extract according to Example 1 were respectively diluted to prepare test samples at concentrations of 0.1 mg / ml, 0.5 mg / ml and 1 mg / ml.
여기에서, 이하 실험예 2 내지 5의 실험시료 준비는 1-1.의 실험시료 준비와 동일한 과정으로 수행되었음을 밝혀둔다.
Hereinafter, the preparation of the test samples in Experimental Examples 2 to 5 was carried out in the same manner as the preparation of the test samples in 1-1.
1-2. 세포 독성 실험1-2. Cytotoxicity experiment
OMC-2010 구성약재인 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)가 마우스 비장 세포의 대사 및 독성에 영향을 미쳐서 사이토카인 조절에 관여할 수 있음을 배제하기 위하여, 비장 세포에서 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)를 48시간 동안 처리하여 세포 생존율을 관찰하였다.
(RG), pandemic (PT), dermis (CUM), licorice (GU), Gillian (PG) and omija (SC) affect the metabolism and toxicity of mouse splenocytes, (RG), inferior (PT), dermis (CUM), licorice (GU), gill kyung (PG) and omija (SC) were treated for 48 hours in the splenocytes to determine the cell survival rate Were observed.
Spleen cell의 생존율은 밀집세포의 미토콘드리아 탈수소 효소에 의해 자줏빛 formazan 생성물로 변하는 MTT환원을 바탕으로 MTT분석법으로 측정하였다. The survival rate of spleen cells was measured by MTT assay based on MTT reduction, which turned into a purple formazan product by the mitochondrial dehydrogenase of dense cells.
지수성장을 하는 세포들은 RPMI-1640 배지에서 동일한 밀도로 현탁하였고, 여러 가지 농도로 숙지황(RG), 반하(PT), 진피(CUM), 감초(GU), 길경(PG) 및 오미자(SC) 추출물을 처리하였다. Exponentially growing cells were suspended in RPMI-1640 medium at the same density. The cells were treated with various concentrations of Sergiyang (RG), Banha (PT), dermis (CUM), licorice (GU) The extract was treated.
48시간 동안 배양한 뒤 5 mg/ml의 농도로 배양하기 위해서 MTT용액을 첨가하고 다시 30분 동안 배양하였다. After culturing for 48 hours, MTT solution was added to cultivate at a concentration of 5 mg / ml and cultured again for 30 minutes.
MTT-formazan 생성물은 DMSO를 첨가함으로써 용해하였다. formazan의 양은 용해액을 96-well plate에 loading한 후, 540 nm에 흡수되는 양을 측정하여 결정하였다.
The MTT-formazan product was dissolved by the addition of DMSO. The amount of formazan was determined by loading the solution on a 96-well plate and measuring the absorbed amount at 540 nm.
1-3. 세포 독성 실험결과1-3. Cytotoxicity test results
도 1은 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 열수 추출물과 에탄올 추출물의 세포 독성 실험결과를 나타낸 도면이다.
FIG. 1 is a graph showing the results of cytotoxicity tests of hot water extracts and ethanol extracts of Sulfur (RG), Banha (PT), dermis (CUM), licorice (GU), Gilligan (PG) and omija (SC).
세포 독성 실험결과, OMC-2010 구성약재의 열수 추출물과 에탄올 추출물은 마우스 비장세포에서 세포 독성을 보이지 않았다
As a result of the cytotoxicity test, the hot-water extract and the ethanol extract of OMC-2010 constitutive drug did not show cytotoxicity in mouse splenocytes
실험예Experimental Example 2. 2. 실시예Example 1에 따른 1 열수Heat number 추출물의 TNF-α 분비 억제 실험 TNF-α secretion inhibition experiment of extract
2-1. 염증성 활성 물질 측정2-1. Measurement of inflammatory active substances
OMC-2010 구성약재 열수 추출물이 마우스 비장세포에서 LPS로 유도한 TNF-α 및 IL-5 발현에 미치는 영향을 조사하기 위해, 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC) 열수 추출물 또는 에탄올 추출물을 마우스 비장세포에 1시간 동안 전처리한 후, LPS (1 ㎍/ml)를 48시간 동안 처리하여 비장 세포의 활성화 및 사이토카인 분비를 촉진시켰다.
In order to investigate the effects of hydrothermal extract of OMC-2010 composition on TNF-α and IL-5 expression induced by LPS in mouse spleen cells, (1 ㎍ / ml) were treated for 48 hrs, and the activation of splenocytes and the secretion of cytokines were measured. Respectively.
Total RNA를 추출하기 위해, 세포에 TriZol 1 ㎖를 넣은 후 Chloroform 200 ㎕를 넣고 vortexing한 후 12,000 rpm, 4℃에서 15분 동안 원심분리한 후 상층액을 분리하여, -20℃에 보관된 isopropanol 500 ㎕를 넣은 뒤 상온에서 30분 동안 놓아두었다. 이를 12,000 rpm, 4℃에서 10분 동안 원심 분리하여 용액을 버리고 80% ethanol 1 ㎖을 넣은 후 7,500 rpm, 4℃에서 5분 동안 원심 분리하였다. ethanol을 버리고, DEPC treated water에 녹인 후 fluorometer를 이용하여 정량하였다. 동량의 mRNA를 cDNA로 합성하였다. cDNA를 가지고 Taqman 방식으로 염증성 활성 물질을 측정하였다. 각 primer와 probe는 Applied Bio systems (CA, USA)에서 구입하였다.
To extract total RNA, 1 ml of TriZol was added to the cells, 200 μl of Chloroform was added, vortexed, centrifuged at 12,000 rpm at 4 ° C for 15 minutes, and the supernatant was separated and stored in isopropanol 500 And then allowed to stand at room temperature for 30 minutes. The resulting solution was centrifuged at 12,000 rpm at 4 ° C for 10 minutes. The solution was discarded, and 1 ml of 80% ethanol was added thereto, followed by centrifugation at 7,500 rpm and 4 ° C for 5 minutes. Ethanol was discarded and dissolved in DEPC treated water and quantified using a fluorometer. The same amount of mRNA was synthesized with cDNA. The inflammatory active substance was measured by cDNA using Taqman method. Each primer and probe was purchased from Applied Bio systems (CA, USA).
여기에서, 이 후 실험예 3 내지 5의 염증성 활성 물질을 측정한 실험의 실험 방법은 위 방법과 동일한 과정으로 수행되었음을 밝혀둔다.
Hereinafter, it is revealed that the experimental method of the experiment in which the inflammatory active substances of Experimental Examples 3 to 5 were measured was performed in the same manner as the above method.
2-2. TNF-α 측정 결과2-2. Results of TNF-α measurement
도 2는 실시예 1에 따른 열수 추출물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
FIG. 2 is a graph showing the effect of the hot-water extract according to Example 1 on TNF-α secretion. FIG.
TNF-α는 전신성 염증과, 급성 반응을 조절하는 사이토카인이다. 주로 활성화된 대식세포에서 생성되며, 또한 CD4+ T cell이나 NK cell에서도 생성된다. TNF-α is a cytokine that regulates systemic inflammation and acute response. It is mainly produced by activated macrophages and also by CD4 + T cells or NK cells.
TNF-α의 주요한 역할은 면역세포의 조절이다. TNF-α는 세포자살(apopotosis)을 유도하며, 추가적인 IL-1beta, IL-6의 분비를 촉진시킨다. 실제로 TNF-α의 분비를 억제하였을 때, 대장염, 천식 등을 억제했다는 보고가 다수 있다. 그렇기 때문에 TNF-α의 억제는 큰 의미를 가질 수 있다.
The primary role of TNF-a is the regulation of immune cells. TNF-α induces apoptosis and promotes the secretion of additional IL-1beta and IL-6. In fact, when TNF-α secretion was suppressed, there were many reports of suppression of colitis and asthma. Therefore, inhibition of TNF-α may have a significant effect.
숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 열수 추출물이 마우스 비장세포에서 LPS로 유도한 TNF-α의 발현에 미치는 영향을 살펴본 결과, 숙지황 열수 추출물은 TNF-α 발현을 유의하게 억제하였으나 반하, 진피, 감초, 길경 및 오미자는 억제하지 못하였다.
The effect of hydrothermal extracts of RG, PT, DGC, GU, Gyeonggi (PG) and omija (SC) on the expression of TNF-α induced by LPS in mouse spleen cells As a result, the hydrolyzate of Sukjanghwang significantly inhibited the expression of TNF-α, but did not inhibit dandruff, licorice, licorice and omija.
실험예Experimental Example
3. 3.
실시예Example
1에 따른 에탄올 추출물의 TNF-α 분비 억제 실험 1 inhibition of TNF-α secretion by ethanol extracts
3-1. TNF-α 측정 결과3-1. Results of TNF-α measurement
도 3은 실시예 1에 따른 에탄올 추출물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
FIG. 3 is a graph showing the effect of the ethanol extract according to Example 1 on TNF-.alpha. Secretion. FIG.
숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 에탄올 추출물이 마우스 비장세포에서 LPS로 유도한 TNF-α의 발현에 미치는 영향을 살펴본 결과, 숙지황, 반하 및 오미자 에탄올 추출물은 TNF-α 발현을 유의하게 억제하였으나 진피, 감초 및 길경은 억제하지 못하였다.
The effect of ethanol extracts of RG, PT, CUM, guanine, PG, and SC on TNF-α expression induced by LPS in mouse spleen cells As a result, the extracts of Sukjwanghwang, Banha and Omija significantly inhibited TNF-α expression but did not inhibit dermis, licorice, and gill kyung.
실험예Experimental Example
4. 4.
실시예Example
1에 따른 1
열수Heat number
추출물의 IL-5 분비 억제 실험 IL-5 secretion inhibition experiment of extract
4-1. IL-5 측정 결과4-1. Results of IL-5 measurement
도 4는 실시예 1에 따른 열수 추출물이 IL-5 분비에 미치는 영향을 나타낸 그래프이다.
4 is a graph showing the effect of the hot-water extract according to Example 1 on IL-5 secretion.
IL-5는 Th2 사이토카인으로, 주로 IL-5 수용체와 결합하여 B세포의 성장에 관여하고, 면역글로불린(immunoglobulin)의 생성에 기여한다. 또한 호산구(eosinophil)의 활성에 아주 중요한 매개체로서, 천식 반응에 관련하여 아주 중요한 사이토카인이다. 임상적으로도 IL-5는 알러지성 천식의 발견 지표로 사용되어 왔고, 호산구의 활성과 큰 유사성을 가지는 것으로 보여 많이 사용되고 있다
IL-5 is a Th2 cytokine, mainly involved in the growth of B cells by binding to the IL-5 receptor, and contributes to the production of immunoglobulins. It is also a very important mediator of eosinophil activity and is a very important cytokine in relation to the asthmatic response. Clinically, IL-5 has been used as an index for the detection of allergic asthma, and it has been widely used because it has a great similarity with the activity of eosinophils
숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 열수 추출물이 마우스 비장세포에서 LPS로 유도한 IL-5의 발현에 미치는 영향을 살펴본 결과, 숙지황 열수 추출물은 IL-5 발현을 유의하게 억제하였으나 반하, 진피, 감초, 길경 및 오미자는 억제하지 못하였다.
The effect of hydrothermal extracts of RG, PT, CUM, GU, Gyeonggi (PG) and omija (SC) on the expression of IL-5 induced by LPS in mouse spleen cells As a result, the hydrolyzate of Sukkiwang hydrothermal extract significantly inhibited IL-5 expression, but did not inhibit dandruff, licorice, licorice and omija.
실험예Experimental Example
5. 5.
실시예Example
1에 따른 에탄올 추출물의 IL-5 분비 억제 실험 1 inhibition of IL-5 secretion by ethanol extracts
5-1. IL-5 측정 결과5-1. Results of IL-5 measurement
도 5는 실시예 1에 따른 에탄올 추출물이 IL-5 분비에 미치는 영향을 나타낸 그래프이다.
5 is a graph showing the effect of ethanol extract according to Example 1 on IL-5 secretion.
숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 에탄올 추출물이 마우스 비장세포에서 LPS로 유도한 IL-5의 발현에 미치는 영향을 살펴본 결과, 숙지황, 반하 및 오미자 에탄올 추출물은 IL-5 발현을 유의하게 억제하였으나 진피, 감초 및 길경은 억제하지 못하였다.
The effect of ethanol extracts of RG, PT, CUM, guanine, PG, and SC on LPS-induced IL-5 expression in mouse spleen cells As a result, the extracts of Sukjwanghwang, Banha and Omija significantly inhibited IL-5 expression but did not inhibit dermis, licorice, and gill kyung.
실험예 1 내지 5를 정리해보면, 실시예 1에 따른 숙지황 (RG), 반하 (PT), 진피 (CUM), 감초 (GU), 길경 (PG) 및 오미자 (SC)의 열수 추출물과 에탄올 추출물 은 세포 독성이 나타나지 않았으며, 숙지황의 열수 추출물과 숙지황, 반하, 오미자의 에탄올 추출물이 TNF-α와 IL-5를 유의하게 억제하는 것으로 나타났다. The results of Experimental Examples 1 to 5 are summarized in Table 1 below. The hot water extract and ethanol extract of Sukjunggwang (RG), Banha (PT), dermis (CUM), licorice (GU), Gil Kyung (PG) There was no cytotoxicity. The ethanol extracts of Sukjwanghwang, Banha and Omija significantly inhibited TNF-α and IL-5.
이를 통하여 OMC-2010 열수 추출물에서는 숙지황이, OMC-2010 에탄올 추출물에서는 숙지황, 반하 및 오미자가 주로 작용하는 것으로 추측할 수 있다.
Therefore, it can be inferred that Sukjwanghwang in OMC-2010 hot water extract and Sukjihwang, Banha and Omija in OMC-2010 ethanol extract act mainly.
본 출원인은 효과가 좋은 것으로 나타난 숙지황, 반하 및 오미자 에탄올 추출물의 배합비율을 다르게 하여 실험함으로써, 면역세포 조절 능력에 유효한 효과를 보이는 조성 비율을 선정하고, 알레르기성 기관지 천식 마우스 모델에서의 효과를 알아보기 위해 다음의 실시예 2 및 실험예 6 내지 11을 수행하였다.
The Applicant has determined the composition ratio showing effective effects on the immune cell control ability by examining the blending ratios of the Sukjwanghwang, Banha and Omija ethanol extracts, which are shown to be effective, to differentiate the effects of the allergic bronchial asthma mouse model The following Example 2 and Experimental Examples 6 to 11 were carried out for the purpose of illustration.
실시예Example
2. 숙지황, However,
반하Inferiority
및 오미자의 추출 및 배합비율 조성 And extracting and mixing ratio of omija
숙지황, 반하, 오미자를 (A) 1:1:1; (B) 2:1:1; (C) 1:2:1; (D) 1:1:2 비율로 섞은 처방을 각각 A, B, C, D로 분류하였으며, 각 처방에 50배의 70% 에탄올 용액을 가하여 37℃ 항온 수조에서 24시간 동안 추출하였다. (A) 1: 1: 1; (B) 2: 1: 1; (C) 1: 2: 1; (D) 1: 1: 2 ratios were classified as A, B, C, and D, respectively, and 50% of 70% ethanol solution was added to each prescription and extracted for 24 hours in a constant temperature water bath at 37 ℃.
추출 후 에탄올층(상등액)을 회전감압농축기(EYELA, RikakikiCo., Tokyo, Japan)로 농축한 후, 생리식염수 녹여 stock solution을 제조하였다. 제조된 stock solution은 －20℃에 보관하면서 분석방법에 적합하도록 희석하여 사용하였다.
After extraction, the ethanol layer (supernatant) was concentrated with a rotary evaporator (EYELA, RikakikiCo., Tokyo, Japan) and physiological saline was dissolved to prepare a stock solution. The prepared stock solution was diluted to be suitable for the analytical method while being stored at -20 ° C.
실험예Experimental Example
6. 6.
실시예Example
2에 따른 배합비율별 조성물의 세포 독성 실험 Cytotoxicity test of composition according to compounding ratio according to 2
6-1. 실험시료 준비6-1. Preparation of test samples
실시예 2에 따른 A, B, C, D의 조성물을 각각 희석하여 0.1 ㎎/㎖, 0.5 ㎎/㎖, 1 ㎎/㎖의 농도로 실험시료를 준비하였다.The compositions of A, B, C and D according to Example 2 were each diluted to prepare test samples at concentrations of 0.1 mg / ml, 0.5 mg / ml and 1 mg / ml.
여기에서, 이하 실험예 7 내지 8의 실험시료 준비는 6-1.의 실험시료 준비와 동일한 과정으로 수행되었음을 밝혀둔다.
Hereinafter, the preparation of the test samples of Experimental Examples 7 to 8 was carried out in the same manner as the preparation of the test samples of 6-1.
6-2. 세포 독성 실험6-2. Cytotoxicity experiment
숙지황, 반하, 오미자 배합비율별 조성물인 A (1:1:1), B (2:1:1), C (1:2:1), D (1:1:2)가 마우스 비장 세포의 대사 및 독성에 영향을 미쳐서 사이토카인 조절에 관여할 수 있음을 배제하기 위하여, 비장 세포에서 A, B, C, D를 48시간 동안 처리하여 세포 생존율을 관찰하였다.
(1: 1: 1), B (2: 1: 1), C (1: 2: 1) and D (1: 1: 2) To obviate the possibility of involvement in cytokine regulation by affecting metabolism and toxicity, cell viability was examined by treatment of splenocytes with A, B, C, D for 48 hours.
Spleen cell의 생존율은 밀집세포의 미토콘드리아 탈수소 효소에 의해 자줏빛 formazan 생성물로 변하는 MTT환원을 바탕으로 3-(4,5-dimethylthiazol-2-yl)-2,, 5-diphenyl-2H-tetrazolium bromide (MTT)용액을 이용하여 측정했다. The survival rate of Spleen cells was determined by MTT reduction, which is converted to a purple formazan product by the mitochondrial dehydrogenase of dense cells. 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide ) Solution.
간단히 설명하면 지수성장을 하는 세포들은 RPMI-1640 배지에서 동일한 밀도로 현탁하였고, 여러 가지 농도로 A, B, C, D를 처리하였다. Briefly, exponentially growing cells were suspended in RPMI-1640 medium at the same density and treated with A, B, C, D at various concentrations.
A, B, C, D를 처리하여 48시간 동안 배양한 뒤 5 mg/ml의 농도로 배양하기 위해서 MTT용액을 첨가하고 다시 30분 동안 배양하였다. A, B, C, and D were cultured for 48 hours, MTT solution was added for cultivation at a concentration of 5 mg / ml, and the cells were cultured again for 30 minutes.
MTT-formazan 생성물은 DMSO를 첨가함으로써 용해했다. formazan의 양은 용해액을 96-well plate에 loading한 후, 540 nm에 흡수되는 양을 측정함으로써 결정하였다.
The MTT-formazan product was dissolved by the addition of DMSO. The amount of formazan was determined by loading the solution on a 96-well plate and measuring the absorbed amount at 540 nm.
6-3. 세포 독성 실험결과6-3. Cytotoxicity test results
도 6은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물의 세포 독성 실험결과를 나타낸 도면이다.
FIG. 6 is a graph showing the relationship between the A (RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition.
세포 독성 실험결과, 실시예 2에 따른 A, B, C, D 조성물은 마우스 비장세포에서 세포 독성을 보이지 않았다
As a result of the cytotoxicity test, the compositions A, B, C and D according to Example 2 showed no cytotoxicity in mouse splenocytes
실험예Experimental Example 7. 7. 실시예Example 2에 따른 배합비율별 조성물의 TNF-α 분비 억제 실험 2, inhibition of TNF-α secretion by the composition ratio
7-1. 염증성 활성 물질 측정7-1. Measurement of inflammatory active substances
숙지황, 반하, 오미자 배합비율별 조성물인 A, B, C, D가 마우스 비장세포에서 LPS로 유도한 전염증성 사이토카인 발현에 미치는 영향을 조사하기 위해, A, B, C, D를 마우스 비장세포에 1시간 동안 전처리한 후, LPS (1 μg/ml)를 48시간 동안 처리하여 비장 세포의 활성화 및 사이토카인 분비를 촉진시켜 TNF-α의 발현정도를 확인하였다.
In order to investigate the effect of A, B, C, and D on the expression of proinflammatory cytokines induced by LPS in mouse spleen cells, A, B, C, (1 μg / ml) for 48 hours to stimulate splenocyte activation and secretion of cytokines, thereby confirming the expression level of TNF-α.
Total RNA는 TRI-zol (invitrogen, USA) 시약을 이용하여 추출하였다. 먼저 배양한 세포에 A, B, C, D를 전 처리하고 LPS로 자극한 후 48시간 배양한 세포를 PBS로 2회 씻은 다음 PBS 1 ml씩 가해 세포를 포집하였다. 포집된 세포를 원심분리하여 상층액은 버리고 침전물에 TRI-zol 용액을 1 ml 가하여 세포를 용해시킨 후 100 ul의 chloroform 용액을 넣어 고르게 잘 섞어준 뒤 15,000 rpm, 4℃에서 20분간 원심 분리하여 맨 위의 상층액을 취하였다. 그 후 -20℃에 보관된 2-propanol과 1:1로 희석하여 잘 섞어준 뒤 15,000 rpm, 4℃에서 10분간 원심 분리하여 상층액은 버리고 남은 침전물에 80% ethanol 500 ul를 넣어 15,000 rpm, 4℃에서 5분간 원심 분리하여 침전물을 건조시켰다. 그리고 침전물에 DEPC treated water를 15 ul씩 넣어 RNA를 용해시키고 fluorometer를 이용하여 정량한 뒤 동량의 mRNA를 cDNA로 합성하여 실험에 사용하였다. Total RNA was extracted using TRI-zol (Invitrogen, USA) reagent. The cultured cells were pretreated with A, B, C, and D, stimulated with LPS, and incubated for 48 hours. The cells were washed twice with PBS, and 1 ml of PBS was added to collect the cells. The collected cells were centrifuged, and the supernatant was discarded. 1 ml of the TRI-zol solution was added to the precipitate to dissolve the cells. 100 μl of chloroform solution was added thereto, and the mixture was homogeneously mixed. The mixture was centrifuged at 15,000 rpm at 4 ° C for 20 minutes The supernatant above was taken. The mixture was centrifuged at 15,000 rpm for 10 minutes at 4 ° C. The supernatant was discarded and the supernatant was discarded. 500 μl of 80% ethanol was added at 15,000 rpm, The precipitate was dried by centrifugation at 4 DEG C for 5 minutes. Then, 15 μl of DEPC treated water was added to the precipitate to dissolve the RNA, and the RNA was quantified using a fluorometer, and the same amount of mRNA was synthesized and used in the experiment.
합성된 cDNA를 가지고 Taqman 방식으로 염증성 활성 물질을 측정하였다. 각 primer는 Applied Bio systems (CA, USA)에서 구입하였다. TNF-alpha는 Mm00443258_m1 #4331182를 사용하였으며, IL-5는 Mm00439646_m1 #4331182를 사용하여 StepOne Software v2.2.2 Applied Bio systems (CA, USA)로 분석하였다.The synthesized cDNA was used to measure the inflammatory active substance by Taqman method. Each primer was purchased from Applied Bio systems (CA, USA). TNF-alpha was analyzed using Mm00443258_m1 # 4331182 and IL-5 was analyzed with StepOne Software v2.2.2 Applied Bio systems (CA, USA) using Mm00439646_m1 # 4331182.
또한 기관지 천식을 유도한 후 적출한 폐조직은 TRI-zol 시약을 200 ul 넣고 homogenizer를 이용하여 조직이 용해될 때까지 분쇄한 다음 TRI-zol 시약의 total volume이 1 ml이 될 수 있도록 800 ul의 시약을 더 첨가한 후 splenocyte RNA 추출방법과 동일한 방법으로 mRNA를 추출하였다.
After the induction of bronchial asthma, 200 μl of TRI-zol reagent was added to the extracted lung tissue, and the mixture was homogenized until the tissue was dissolved. Then, 800 μl of TRI-zol reagent After adding more reagents, mRNA was extracted by the same method as splenocyte RNA extraction method.
여기에서, 이 후 실험예 8 및 11의 염증성 활성 물질을 측정한 실험의 실험 방법은 위 방법과 동일한 과정으로 수행되었음을 밝혀둔다.
Hereinafter, it is revealed that the experimental method of the experiment in which the inflammatory active substances of Experimental Examples 8 and 11 were measured was the same as the above method.
7-2. TNF-α 측정 결과7-2. Results of TNF-α measurement
도 7은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물이 TNF-α 분비에 미치는 영향을 나타낸 그래프이다.
FIG. 7 is a graph showing the relationship between A (RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition on TNF-α secretion.
숙지황 (RG), 반하 (PT) 및 오미자 (SC)의 배합비율별 조성물이 마우스 비장세포에서 LPS로 유도한 TNF-α의 발현에 미치는 영향을 살펴본 결과, A (RG:PT:SC=1:1:1)는 TNF-α 발현을 유의하게 억제하였으나 B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2)는 TNF-α 발현을 억제하지 못하였다.
A (RG: PT: SC = 1: 1) was used to examine the effects of the composition of RG, PT, and SC on the expression of TNF-α induced by LPS in mouse spleen cells. (RG: PT: SC = 2: 1: 1), C (RG: PT: SC = 1: 2: 1) and D (RG: PT: SC = 1: 1: 2) did not inhibit TNF-α expression.
실험예Experimental Example
8. 8.
실시예Example
2에 따른 배합비율별 조성물의 IL-5 분비 억제 실험 2, inhibition of IL-5 secretion by the composition ratio
8-1. IL-5 측정 결과8-1. Results of IL-5 measurement
도 8은 실시예 2에 따른 A (RG:PT:SC=1:1:1), B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2) 조성물이 IL-5 분비에 미치는 영향을 나타낸 그래프이다.
(RG: PT: SC = 1: 1: 1), B (RG: PT: SC = 2: 1) and D (RG: PT: SC = 1: 1: 2) composition on IL-5 secretion.
숙지황 (RG), 반하 (PT) 및 오미자 (SC)의 배합비율별 조성물이 마우스 비장세포에서 LPS로 유도한 TNF-α의 발현에 미치는 영향을 살펴본 결과, A (RG:PT:SC=1:1:1)는 IL-5 발현을 유의하게 억제하였으나 B (RG:PT:SC=2:1:1), C (RG:PT:SC=1:2:1), D (RG:PT:SC=1:1:2)는 IL-5 발현을 억제하지 못하였다.
A (RG: PT: SC = 1: 1) was used to examine the effects of the composition of RG, PT, and SC on the expression of TNF-α induced by LPS in mouse spleen cells. (RG: PT: SC = 2: 1: 1), C (RG: PT: SC = 1: 2: SC = 1: 1: 2) did not inhibit IL-5 expression.
실험예Experimental Example
9. OVA로 유도한 기관지 천식에서 기도과민성 측정 9. Measurement of airway hyperresponsiveness in OVA-induced bronchial asthma
9-1. 기관지 천식 마우스 모델 제작9-1. Model of bronchial asthma mouse
도 9는 기관지 천식 모델을 유도하기 위해 OVA와 Alum을 주입하는 과정을 도시한 도면이다.
FIG. 9 is a diagram illustrating a process of injecting OVA and Alum to induce a bronchial asthma model.
비장세포에서 TNF-α와 IL-5의 생성을 유의성 있게 억제할 수 있었던 숙지황, 반하, 오미자 1:1:1 배합비율 A 조성물의 기관지 천식모델에서의 효과를 확인하기 위하여, 100 ㎍의 OVA(chicken egg ovalbumin, Grade V)와 1 ㎎ Alum (aluminum hydroxide)을 PBS (phosphate buffered saline, pH 7.4) 0.2 ㎖에 혼합하여 복강내로 주사하였다. In order to confirm the effect of A composition 1: 1: 1 mixture of A, B, and C, which was able to significantly inhibit the production of TNF-α and IL-5 in spleen cells, a 100 μg OVA chicken egg ovalbumin, Grade V) and 1 ㎎ Alum (aluminum hydroxide) were mixed in 0.2 ml of PBS (phosphate buffered saline, pH 7.4) and injected intraperitoneally.
1차 전신 감작 후 15일째에 동일한 방법으로 2차 감작을 통해 면역 boosting을 유도한 후, 숙지황, 반하, 오미자 1:1:1 배합비율 조성물을 생리식염수로 농도별로 희석하여 18일부터 24일까지 일주일간 경구 투여하였다. 또한 5% OVA in PBS를 22, 23, 24일에 3일 연속 30분간 분무하여 알레르기성 기관지 천식을 유도하였다. 마지막 OVA을 분무한 뒤, 24시간 후에 마우스를 분석하였다.
On the 15th day after the first systemic sensitization, the immune boosting was induced by the second sensitization in the same manner, and the composition of the mixture of Sukjihwang, Haengja, and Omija at a ratio of 1: 1: 1 was diluted with physiological saline Orally for one week. In addition, 5% OVA in PBS was sprayed on
여기에서, 실험예 10 내지 11에 사용된 기관지 천식 마우스 모델의 제작 방법 역시 위 방법과 동일하게 진행되었음을 밝혀둔다.
Here, it is noted that the method of manufacturing the bronchial asthma mouse model used in Experimental Examples 10 to 11 was also carried out in the same manner as above.
9-2. 기도과민성(Airway hyper-reactivity; AHR) 측정9-2. Airway hyper-reactivity (AHR) measurement
천식환자는 기도가 예민하여 자극을 받으면 쉽게 기도 안쪽이 붓고, 객담이 생기며 기관지를 둘러싼 근육이 수축하여 기도가 좁아지게 된다. 이러한 기도과민성 여부는 기도 저항을 측정하여 판단할 수 있다.
Patients with asthma are sensitive to the airway, and if they are stimulated, the inside of the airway becomes swollen, the sputum develops, the muscles surrounding the bronchus contract, and the airway narrows. Such a hypersensitivity can be judged by measuring airway resistance.
마우스 비장세포에서 TNF-α와 IL-5의 발현에 유의성 있는 효과를 보인 A (1:1:1)를 기관지 천식 모델 적용하여 알레르기성 과민반응에 의해 나타나는 기도과민성의 변화를 확인하기 위하여 정상군 (Normal)과 천식유발군 (ovalbumin, OVA) 및 실험군 (A 0.05, 0.1, 0.5 g/kg 처리군)에 methacholine을 농도별로 노출시켜 그에 대한 기도저항값 (Penh)을 조사하였다.
A (1: 1: 1), which showed significant effects on the expression of TNF-α and IL-5 in mouse spleen cells, was examined by bronchial asthma model to determine the changes of AHR caused by allergic hypersensitivity (Penh) was measured by exposing methacholine to normal (normal), ovalbumin (OVA) and experimental group (A 0.05, 0.1, 0.5 g / kg).
실험방법은 마지막 OVA 분무 24시간 후, methacholine (Sigma, USA)을 PBS로 희석하여 2.5 mg/ml, 10 mg/ml, 20 mg/ml, 및 50 mg/ml의 농도로 각각 5분간 분무하여 노출시킨 후 동물용 체적 변동 측정기를 사용하여 Penh (enhanced pause) 값을 5초 간격으로 3분간 측정하여 평균을 대표값으로 취하였다.
After 24 hours of the last OVA spraying, methacholine (Sigma, USA) was diluted with PBS and sprayed for 5 minutes at concentrations of 2.5 mg / ml, 10 mg / ml, 20 mg / And the mean value was taken as the representative value by measuring the enhanced pause (Penh) value at intervals of 5 seconds using an animal volumetric analyzer for 3 minutes.
9-3. 기도과민성 측정 결과9-3. Results of AHR
도 10은 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 기도과민성에 대한 효과를 나타낸 그래프이다.
10 is a graph showing the effect of A (RG: PT: SC = 1: 1: 1) according to Example 2 on bronchial asthma mouse model induced by OVA on airway hyperresponsiveness.
실험결과, 숙지황, 반하 및 오미자 1:1:1 배합 조성물을 처리한 실험군의 Penh 값은 0.05 g/kg, 0.1 g/kg 농도에서 농도 의존적으로 감소하여 유의한 효과를 확인할 수 있었으나, 0.5 g/kg 농도에서는 Penh 값이 다시 증가하였다.
As a result, the Penh values of 0.05, 0.1, and 0.1 g / kg of the test group treated with the composition of 1: 1: kg, the Penh value increased again.
실험예Experimental Example
10. OVA로 유도한 기관지 천식에서 10. OVA-induced bronchial asthma
폐조직병리검사Lung histopathology
10-1. 10-1. 폐조직병리검사Lung histopathology
기관지 천식 유발 마우스의 폐조직에 A 조성물이 미치는 효과를 확인하기 위하여 OVA 마지막 분무 24시간 후에 폐조직을 H&E 염색해 관찰하였다.To determine the effect of the A composition on the lung tissue of bronchial asthma-induced mice, H & E staining of the lung tissue was observed 24 hours after the last spray of OVA.
마우스에서 폐조직을 떼어내어 10% 포르말린에 고정시키고, 파라핀으로 embedding 한 후 4 ㎛ 두께로 조직을 잘라 슬라이드에 붙인 뒤 Hematoxylin/eosin (H&E) 염색하여 ×200 배율로 관찰하였다.
The lung tissue was removed from the mouse, fixed in 10% formalin, and embedded in paraffin. The tissue was cut to a thickness of 4 쨉 m and stained with hematoxylin / eosin (H & E) staining.
10-2. 10-2. 폐조직병리검사Lung histopathology 결과 result
도 11은 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 폐조직병리검사 결과를 나타낸 그래프이다.
11 is a graph showing the results of pulmonary histopathology of A (RG: PT: SC = 1: 1: 1) according to Example 2 in an OVA-induced bronchial asthma mouse model.
폐조직병리검사 결과, 정상군에서는 기도벽이 얇고 선명하며, 염증세포의 침윤이 보이지 않으나, 천식유발군에서는 기도벽의 두께가 두꺼워져 있고 염증세포의 침착이 현저하게 증가한 것을 확인할 수 있었다.
Pulmonary histopathological examination revealed that the airway wall was thin and clear, and no infiltration of inflammatory cells was observed in the normal group. However, in the asthma - induced group, the thickening of airway wall and the deposition of inflammatory cells were markedly increased.
실험군 A 조성물 0.05 g/kg군에서는 기도의 협착과 기도벽의 두께가 천식유발군에 비해 감소하였는데, A 조성물 0.1 g/kg군에서는 천식유발군에 비해 기도벽이 얇아지고, 손상된 폐포의 형태도 정상수준으로 돌아왔으며 염증성세포의 침윤 또한 정상군의 수준으로 감소한 것을 확인할 수 있었다. In the 0.05 g / kg A group, airway stenosis and airway wall thickness were decreased compared to the asthmatic group. In the A composition 0.1 g / kg group, the airway wall became thinner and the shape of the damaged alveoli Normal level, and infiltration of inflammatory cells also decreased to the level of normal group.
하지만 실험군 A 조성물 0.5 g/kg군의 결과 기도벽 두께 증가와 폐조직 내의 염증 수준이 A 조성물 0.1 g/ kg 농도에 비해 증가하는 것으로 확인되었다.
However, as a result of the 0.5 g / kg group of the experimental group A, it was confirmed that the airway wall thickness increase and the inflammation level in the lung tissue were increased compared with the 0.1 g / kg concentration of the A composition.
실험예Experimental Example
11. OVA로 유도한 기관지 천식에서 11. In asthma induced by OVA
폐조직의Pulmonary
사이토카인 측정 Cytokine measurement
11-1. 11-1. 폐조직의Pulmonary 사이토카인 측정 Cytokine measurement
비장세포의 활성화로 인하여 발현된 사이토카인을 유의하게 억제할 수 있었던 숙지황, 반하, 오미자가 1:1:1의 배합비율로 포함된 A 조성물이 기관지 천식에서의 사이토카인 억제효과를 나타내는지 확인하기 위하여 기관지 천식 유발 마우스의 폐조직에서 사이토카인의 농도를 조사하였다. Confirmation that the A composition, which contains 1: 1: 1 mixture of Sukjwanghwang, Banha, and Omija, which was able to inhibit the cytokine expressed by the activation of splenocytes, showed a cytokine inhibitory effect in bronchial asthma The concentrations of cytokines in lung tissues of bronchial asthma induced mice were examined.
이때 사이토카인은 면역작용에 관여하는 염증성 세포들로 인하여 발현된 전염증성 사이토카인 TNF-α와 Th2 타입의 사이토카인인 IL-5의 농도를 조사하였다. 항원을 인지한 면역세포 및 T 림프구는 림프절에서 활성화하여 염증조직으로 이동하게 된다. 알레르기성 항원인 OVA에 특이적으로 작용한 면역세포들은 다수가 염증부위인 폐조직으로 이동하여 염증작용 및 Th-2 반응을 통하여 사이토카인을 생산하기 때문에 폐조직 내에서 발현되는 사이토카인양을 조사하였다
At this time, cytokines were examined for IL-5, a proinflammatory cytokine TNF-α and Th2-type cytokine, which are expressed by inflammatory cells involved in immune function. Immune cells and T lymphocytes that recognize the antigen are activated in the lymph nodes and migrate to the inflamed tissue. Immune cells specifically acting on OVA, an allergic antigen, migrate to the lung tissue, which is an inflammatory site, and produce cytokines through inflammatory action and Th-2 response. Therefore, cytokine expression in lung tissue is examined And
11-2. 11-2. 폐조직의Pulmonary 사이토카인 측정 결과 Cytokine measurement result
도 12는 OVA로 유도된 기관지 천식 마우스 모델에서 실시예 2에 따른 A (RG:PT:SC=1:1:1)의 폐조직 사이토카인 측정 결과를 나타낸 그래프이다.
12 is a graph showing the results of measurement of lung tissue cytokines of A (RG: PT: SC = 1: 1: 1) according to Example 2 in a bronchial asthma mouse model induced by OVA.
폐조직의 mRNA 레벨에서 사이토카인 변화 정도를 확인한 결과, 천식유발군에서 TNF-α와 IL-5 모두 정상군에 비하여 확연하게 증가하는 것을 확인할 수 있었으며, 실험군인 A 조성물 0.1 g/kg에서 TNF-α와 IL-5의 발현이 유의하게 억제되었다. 하지만 실험군 A 조성물 0.5 g/kg 농도에서는 유의한 억제효과가 나타나지 않았다.
As a result of confirming the degree of cytokine change in the lung tissue mRNA level, TNF-α and IL-5 in the asthmatic induction group were significantly increased compared to the normal group, and TNF- α and IL-5 were significantly inhibited. However, no significant inhibitory effect was observed at the concentration of 0.5 g / kg of the experimental group A composition.
실험예 6 내지 11을 정리하여 살펴보면, 숙지황, 반하 및 오미자 배합비율별 에탄올 추출물은 비장세포에서 세포 독성을 보이지 않았으며, 숙지황, 반하 및 오미자 1:1:1 비율 조성물이 비장세포의 TNF-α와 IL-5의 발현은 유의하게 억제하였다. Experimental Examples 6 to 11 are summarized as follows. Ethanol extracts of Sukjwanghwang, Banha, and Omija did not show cytotoxicity in spleen cells. The composition of 1: 1: 1 ratio of Sukjwang, And IL-5, respectively.
또한 숙지황, 반하 및 오미자 1:1:1 비율인 조성물의 농도 0.1 g/kg에서 기관지 천식 마우스 모델의 기도과민성을 억제하고, 폐조직의 조직학적 손상을 유의하게 억제하였으며, 폐조직에서 TNF-α와 IL-5의 발현을 유의하게 억제하였다.
In addition, inhibition of bronchial asthma mouse model of bronchial asthma was suppressed and histological damage of lung tissue was significantly inhibited at a concentration of 0.1 g / kg of composition of 1: 1: 1 ratio, And IL-5, respectively.
Claims (6)
A composition for preventing, ameliorating or treating asthma comprising as an active ingredient a mixed extract of Rehmannia glutinosa , Semihu , Pinellia ternata, and Schizandra chinensis .
상기 숙지황, 반하 및 오미자의 중량 비율은 동일한 것을 특징으로 하는 기관지 천식의 예방, 개선 또는 치료를 위한 조성물.
The method according to claim 1,
The composition for preventing, ameliorating or treating asthma of bronchial asthma characterized in that the weight percentages of Sulfur, Sulfur, and Omiza are the same.
상기 혼합 추출을 위한 용매는 70% 에탄올인 것을 특징으로 하는 기관지 천식의 예방, 개선 또는 치료를 위한 조성물.
The method according to claim 1,
The composition for preventing, ameliorating or treating asthma according to claim 1, wherein the solvent for the mixed extraction is 70% ethanol.
상기 혼합 추출물의 1일 투여량은 0.05 g/kg 내지 0.5 g/kg인 것을 특징으로 하는 기관지 천식의 예방, 개선 또는 치료를 위한 조성물.
The method according to claim 1,
Wherein the daily dose of the mixed extract is 0.05 g / kg to 0.5 g / kg.
A health functional food for preventing or ameliorating bronchial asthma containing as an active ingredient a mixed extract of Sukjipu (熟地黄, Rehmannia glutinosa ), Banha ( Pinatsia pinellia ternata) and Schizandra chinensis .
식품학적으로 허용 가능한 식품첨가제를 더 포함하는 것을 특징으로 하는 기관지 천식의 예방 또는 개선을 위한 건강기능식품.
The method of claim 5,
A health functional food for prevention or improvement of bronchial asthma characterized by further comprising a food-acceptable food additive.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20130147048A KR101504730B1 (en) | 2013-11-29 | 2013-11-29 | Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20130147048A KR101504730B1 (en) | 2013-11-29 | 2013-11-29 | Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101504730B1 true KR101504730B1 (en) | 2015-03-20 |
Family
ID=53028209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR20130147048A KR101504730B1 (en) | 2013-11-29 | 2013-11-29 | Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101504730B1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060061855A (en) * | 2004-08-30 | 2006-06-08 | 퓨리메드 주식회사 | Herb composition for asthma maintenance therapy and manufacturing method thereof |
| KR20130055059A (en) * | 2011-11-18 | 2013-05-28 | 재단법인충북테크노파크 | A pharmaceutical for treating or preventing asthma |
-
2013
- 2013-11-29 KR KR20130147048A patent/KR101504730B1/en active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060061855A (en) * | 2004-08-30 | 2006-06-08 | 퓨리메드 주식회사 | Herb composition for asthma maintenance therapy and manufacturing method thereof |
| KR20130055059A (en) * | 2011-11-18 | 2013-05-28 | 재단법인충북테크노파크 | A pharmaceutical for treating or preventing asthma |
Non-Patent Citations (1)
| Title |
|---|
| 정승연 등, 대한한방내과학회지, 2006년, 제27권, 제2호, pp. 521-532 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Huang et al. | The immunopharmaceutical effects and mechanisms of herb medicine | |
| Alamgir et al. | Recent advances on the ethnomedicinal plants as immunomodulatory agents | |
| AU2006218875B2 (en) | Compositions comprising Actinidia and methods of use thereof | |
| US8518462B2 (en) | Compound comprising extracts or fractions of chrysanthemum boreale makino having anti-inflammation activity | |
| US20100111927A1 (en) | Compositions Comprising Actinidia and Methods of Use Thereof | |
| KR101458763B1 (en) | Pharmaceutical, cosmetic, and functional food compositions comprising smilacis chinae rhizoma of smilax china l. for allergic diseases | |
| RU2671501C1 (en) | Composition containing extract or fraction from justicia plant | |
| KR101495117B1 (en) | A Composition comprising the extract of Cudrania tricuspidata trunk as an active ingredient for preventing and treating atopic diseases | |
| Bethapudi et al. | Bioactive turmerosaccharides from curcuma longa extract (NR-INF-02): potential ameliorating effect on osteoarthritis pain | |
| Rahim et al. | Anti-allergic rhinitis effects of medicinal plants and their bioactive metabolites via suppression of the immune system: a mechanistic review | |
| KR20190051150A (en) | Antiallergic composition comprising Allomyrina dichotoma larva extract | |
| US20080175888A1 (en) | Combination Therapy Comprising Actinidia and Steroids and Uses Thereof | |
| Girish et al. | Influence of Tinospora cordifolia on wound healing in albino rats | |
| KR20140040183A (en) | Pharmaceutical, cosmetic, and functional food compositions comprising smilacis chinae rhizoma of smilax china l. for allergic diseases | |
| Sá-Nunes et al. | Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang®) | |
| KR101504730B1 (en) | Pharmaceutical composition comprising rehmannia glutinosa, pinellia tenata and schizandra chinensis for preventing, improving or treating bronchial asthma | |
| Zhang et al. | Daphnetin contributes to allergen-induced Th2 cytokine expression and type 2-immune responses in atopic dermatitis and asthma | |
| KR20150078613A (en) | Anti-allergy composition comprising the extracts of aloeswood and concentratedunderground water as an active ingredient | |
| Ali et al. | Immunogenetic disorders: Treatment with phytomedicines | |
| KR101361626B1 (en) | Pharmaceutical, cosmetic, and functional food compositions comprising smilacis chinae rhizoma of smilax china l. for allergic diseases | |
| EP3019183B1 (en) | Reuptake inhibitors | |
| KR101739425B1 (en) | Composition for preventing or improving inflammatory disorders comprising fraction of Oenanthe javanica ethanol extract as effective component | |
| KR100825869B1 (en) | Extract of Angelica archangelica Having Anti-Asthma Activity | |
| US20220211792A1 (en) | Composition containing natural extracts for enhancement of innate immunity or antiviral use against influenza virus or corona virus | |
| KR20230149568A (en) | Composition for preventing, improving or treating allergic respiratory disease comprising Alpinia officinarum extract as effective component |