KR20180085124A - Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction - Google Patents
Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction Download PDFInfo
- Publication number
- KR20180085124A KR20180085124A KR1020170008323A KR20170008323A KR20180085124A KR 20180085124 A KR20180085124 A KR 20180085124A KR 1020170008323 A KR1020170008323 A KR 1020170008323A KR 20170008323 A KR20170008323 A KR 20170008323A KR 20180085124 A KR20180085124 A KR 20180085124A
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- homoharringtonine
- allergic
- treatment
- allergies
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- HYFHYPWGAURHIV-UHFFFAOYSA-N homoharringtonine Natural products C1=C2CCN3CCCC43C=C(OC)C(OC(=O)C(O)(CCCC(C)(C)O)CC(=O)OC)C4C2=CC2=C1OCO2 HYFHYPWGAURHIV-UHFFFAOYSA-N 0.000 title abstract description 42
- 229960002230 omacetaxine mepesuccinate Drugs 0.000 title abstract description 39
- HYFHYPWGAURHIV-JFIAXGOJSA-N omacetaxine mepesuccinate Chemical compound C1=C2CCN3CCC[C@]43C=C(OC)[C@@H](OC(=O)[C@@](O)(CCCC(C)(C)O)CC(=O)OC)[C@H]4C2=CC2=C1OCO2 HYFHYPWGAURHIV-JFIAXGOJSA-N 0.000 title description 37
- 238000000605 extraction Methods 0.000 title 2
- 241000488899 Cephalotaxus Species 0.000 title 1
- 230000003266 anti-allergic effect Effects 0.000 title 1
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 42
- 239000000284 extract Substances 0.000 claims abstract description 41
- 230000007815 allergy Effects 0.000 claims abstract description 32
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 235000013376 functional food Nutrition 0.000 claims abstract description 7
- 230000036541 health Effects 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 12
- 240000008397 Ganoderma lucidum Species 0.000 claims description 9
- 235000001637 Ganoderma lucidum Nutrition 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 108010021724 tonin Proteins 0.000 claims description 4
- 235000013399 edible fruits Nutrition 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 229920001131 Pulp (paper) Polymers 0.000 claims 1
- 229920000297 Rayon Polymers 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 abstract description 24
- 206010003645 Atopy Diseases 0.000 abstract description 21
- 201000008937 atopic dermatitis Diseases 0.000 abstract description 21
- 206010012438 Dermatitis atopic Diseases 0.000 abstract description 18
- 230000000172 allergic effect Effects 0.000 abstract description 15
- 208000010668 atopic eczema Diseases 0.000 abstract description 14
- -1 homoharringtonine compound Chemical class 0.000 abstract description 6
- 208000017520 skin disease Diseases 0.000 abstract description 3
- 241000742992 Cephalotaxus koreana Species 0.000 abstract description 2
- 235000000777 Cephalotaxus harringtonia var koreana Nutrition 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 26
- 239000000427 antigen Substances 0.000 description 22
- 102000036639 antigens Human genes 0.000 description 22
- 108091007433 antigens Proteins 0.000 description 22
- 230000014509 gene expression Effects 0.000 description 20
- 102100021455 Histone deacetylase 3 Human genes 0.000 description 18
- 101000899282 Homo sapiens Histone deacetylase 3 Proteins 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 16
- 230000000638 stimulation Effects 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 101150045565 Socs1 gene Proteins 0.000 description 14
- 102000058018 Suppressor of Cytokine Signaling 1 Human genes 0.000 description 14
- 108700027336 Suppressor of Cytokine Signaling 1 Proteins 0.000 description 14
- 208000003455 anaphylaxis Diseases 0.000 description 14
- 230000006698 induction Effects 0.000 description 14
- 206010002198 Anaphylactic reaction Diseases 0.000 description 13
- 241000282472 Canis lupus familiaris Species 0.000 description 13
- 102000007478 beta-N-Acetylhexosaminidases Human genes 0.000 description 12
- 108010085377 beta-N-Acetylhexosaminidases Proteins 0.000 description 12
- 239000013566 allergen Substances 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 10
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 9
- 235000004727 Opuntia ficus indica Nutrition 0.000 description 9
- 240000009297 Opuntia ficus-indica Species 0.000 description 9
- 230000002052 anaphylactic effect Effects 0.000 description 9
- 230000036783 anaphylactic response Effects 0.000 description 9
- 238000010171 animal model Methods 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- LOTKRQAVGJMPNV-UHFFFAOYSA-N 1-fluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C([N+]([O-])=O)=C1 LOTKRQAVGJMPNV-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 238000001114 immunoprecipitation Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- 102000009438 IgE Receptors Human genes 0.000 description 6
- 108010073816 IgE Receptors Proteins 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000009169 immunotherapy Methods 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 208000030961 allergic reaction Diseases 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 108010042617 dinitrophenyl-human serum albumin conjugate Proteins 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 235000012649 Cephalotaxus drupacea Nutrition 0.000 description 4
- 244000077190 Cephalotaxus harringtonia Species 0.000 description 4
- 235000016381 Cephalotaxus harringtonia Nutrition 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 101150058160 Lyn gene Proteins 0.000 description 4
- 102000043136 MAP kinase family Human genes 0.000 description 4
- 108091054455 MAP kinase family Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 235000021110 pickles Nutrition 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010012434 Dermatitis allergic Diseases 0.000 description 3
- 241000222336 Ganoderma Species 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- 102000013968 STAT6 Transcription Factor Human genes 0.000 description 3
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229960004784 allergens Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000000428 dust Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 210000003630 histaminocyte Anatomy 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 235000012149 noodles Nutrition 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 2
- 208000016557 Acute basophilic leukemia Diseases 0.000 description 2
- 206010002199 Anaphylactic shock Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 108010047041 Complementarity Determining Regions 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 240000001307 Myosotis scorpioides Species 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 244000184734 Pyrus japonica Species 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 201000009961 allergic asthma Diseases 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 229940001468 citrate Drugs 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000003028 enzyme activity measurement method Methods 0.000 description 2
- 235000020710 ginseng extract Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 235000013622 meat product Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000024717 negative regulation of secretion Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 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 description 1
- SUUHZYLYARUNIA-YEWWUXTCSA-N (3s)-5-fluoro-3-[[(2s)-2-[[(2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]propanoyl]amino]-4-oxopentanoic acid Chemical compound OC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 SUUHZYLYARUNIA-YEWWUXTCSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000093727 Berzelia alopecuroides Species 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229940123169 Caspase inhibitor Drugs 0.000 description 1
- 241000488900 Cephalotaxaceae Species 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 241000218631 Coniferophyta Species 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000010787 Interleukin-4 Receptors Human genes 0.000 description 1
- 108010038486 Interleukin-4 Receptors Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000736199 Paeonia Species 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 235000011552 Rhamnus crocea Nutrition 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000029662 T-helper 1 type immune response Effects 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000121220 Tricholoma matsutake Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229940074608 allergen extract Drugs 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 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
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 230000002729 effect on secretion Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000024711 extrinsic asthma Diseases 0.000 description 1
- 235000019985 fermented beverage Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 108010077372 mast cell degranulating peptide Proteins 0.000 description 1
- QMBRLNFAEHGOLY-UHFFFAOYSA-N mcd peptide Chemical compound N1C(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)C(C)CC)CSSCC(C(=O)NCC(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(N)=O)NC(=O)C(C(C)CC)NC(=O)C(CCCCN)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C(C)CC)NC(=O)C(CC2N=CN=C2)NC(=O)C2CCCN2C(=O)C(CCCCN)NC(=O)C(C(C)CC)NC(=O)C(C(C)C)NC2=O)CSSCC1C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC2CC1C=NC=N1 QMBRLNFAEHGOLY-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Chemical class 0.000 description 1
- 239000002184 metal Chemical class 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
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 239000006272 natural pesticide Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
- A23L29/045—Organic compounds containing nitrogen as heteroatom
-
- 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
- A61K36/13—Coniferophyta (gymnosperms)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/304—Foods, ingredients or supplements having a functional effect on health having a modulation effect on allergy and risk of allergy
Abstract
Description
본 발명은 아토피와 같은 알러지 피부 질환을 개선하거나 치료하기 위한 조성물에 관한 것이다. 보다 상세하게는, 본 발명은 개비자나무의 추출물 또는 여기서 분리된 호모해링토닌 화합물을 함유하는 알러지 또는 아토피성 피부염의 예방, 개선 또는 치료용 약학 조성물, 건강 기능성 식품조성물 그리고 화장제 조성물에 에 대한 것이다.The present invention relates to a composition for improving or treating allergic skin diseases such as atopy. More particularly, the present invention relates to pharmaceutical compositions, health functional food compositions and cosmetic compositions for preventing, ameliorating or treating allergic or atopic dermatitis containing extracts of ganoderma var. will be.
아토피는 재발성 만성 피부질환이며, 경제 성장과 더불어 식생활 및 환경의 변화로 인하여 발병률이 증가하고 있는 질병이다. 한국에서도 최근 식생활의 서구화 또는 황사, 먼지, 꽃가루 등의 공기오염에 따른 알러지 또는 아토피성 피부염의 환자들이 급속히 증가하기 시작했다. Atopy is a recurrent chronic skin disease, and it is a disease that the incidence is increasing due to changes in diet and environment, along with economic growth. In Korea, recently, the westernization of dietary habits, or allergic or atopic dermatitis due to air pollution such as dust, dust, pollen, etc. have started to increase rapidly.
지난 30년간 유아 또는 소아의 아토피성 피부염 유병률은 2 내지 3배로 증가하였으며, 어른 성인에게서도 그 유병율의 증가세가 매우 뚜렷하게 나타나고 있다. 아토피의 병리학적 원인에 대해 확실하게 밝혀진 것은 없으며, 대개 유전적 요인과 면역 및 비면역학적 요소가 함께 관여하는 것으로 알려져 있다. The prevalence of atopic dermatitis in infants or children has increased by two to three times over the past 30 years, and the prevalence of the disease has also been increasing markedly in adult adults. None of the pathophysiological causes of atopy have been clearly identified, and it is generally known that genetic factors, immune and non-epidemiological factors are involved together.
종래의 알러지(allergy) 및 아토피성 피부염을 치료하는 방법에는 알러겐(allergen) 회피요법, 항 알러지 약물사용, 특정 알러겐에 대한 면역 치료 요법 등이 있다. 이중 가장 널리 사용되는 알러지 치료 약물로는 항히스타민 약품과 코르티코스테로이드(corticosteroid)계통의 약품이 있으나 균의 내성 문제 또는 표피의 성장억제 등과 같은 부작용을 유발할 가능성이 높다는 문제점이 있다. Conventional methods for treating allergy and atopic dermatitis include allergen avoidance therapy, use of anti-allergic drugs, and immunotherapy for specific allergens. Among the most widely used drugs for treating allergies are antihistamines and corticosteroid drugs, but there is a high possibility of causing side effects such as resistance to bacterial resistance or inhibition of growth of the epidermis.
따라서 새로운 개념의 알러지 및 아토피성 피부염 치료제 개발이 시급하며, 새로운 개념 에 따른 알러지 및 아토피성 피부염의 치료제 개발이 활발히 이루어지고 있다. Therefore, it is urgent to develop a new concept of allergy and atopic dermatitis treatment, and development of a therapeutic agent for allergic and atopic dermatitis according to a new concept is actively carried out.
특히 천연물 추출물 및 분리된 유효성분의 알러지 또는 아토피 치료 효과에 대한 많은 연구가 이루어지고 있는데, 대표적으로는 영지버섯, 백년초, 달맞이유, 알로에, 송이버섯, 팥꽃나무, 녹차, 인삼 등이 보고되고 있다. 그러나, 이들 천연물의 경우 그 알러지 또는 아토피 치료 효과가 미미하다는 단점이 있었다. In particular, many studies have been conducted on the effect of natural extracts and isolated active ingredients in the treatment of allergies or atopy. Typical examples thereof include Ganoderma lucidum, Paeonia spp., Aloe vera, Aloe, Pine mushroom, Green tea, . However, these natural products have a disadvantage in that the effect of treating allergies or atopy is minimal.
현재 개발 중이거나 또는 기존의 알러지 및 아토피성 피부염에 대한 치료방법은 다음과 같다. Methods for treatment of currently undergoing or existing allergies and atopic dermatitis are as follows.
(1) 특정 알러겐을 이용한 면역치료법(Specific allergen immunotherapy)(1) Specific allergen immunotherapy using specific allergens
전통적인 면역 요법으로서, 알러겐(allergen)을 장기간에 걸쳐 그 양을 서서히 증가시키면서 알러지 환자에 투입하는 방법인데, 상기 방법은 알러지성 비염의 치료에 효과를 보였고 알러지성 천식에도 효과가 있다. 이러한 면역요법 은 T 세포 반응을 Th2 유형에서 Th1으로 바꾸게 함으로써 알러지 환자의 증상을 완화시키게 하고 알러겐의 특이적 IgG 반응을 유도하는 치료방법이다. 그러나, 상기 면역 요법은 환자의 증상을 완화시킬 수는 있지만, 근본적인 치료방법이 되지는 못한다는 문제점이 있다. As a conventional immunotherapy, allergen is gradually added to an allergic patient for a prolonged period of time. This method is effective for the treatment of allergic rhinitis and is effective for allergic asthma. This immunotherapy is a therapeutic method that alleviates symptoms of allergic patients and induces allergen-specific IgG responses by changing the T cell response from Th2 type to Th1. However, although the above-mentioned immunotherapy can alleviate the symptoms of the patient, there is a problem that it can not be a fundamental treatment method.
(2) 사이토카인(Cytokine) 요법(2) Cytokine therapy
인터루킨 4(IL-4)는 IgE 항체 생성에 매우 중요한 역할을 하여, 알러지 치료의 표적 단백질로 인식되어 왔으며, 동물 모델에 따르면 IL4 수용체에 대한 항체는 각종의 알러지 질환을 억제하는 것으로 알려져 있다. Interleukin-4 (IL-4) plays a very important role in the production of IgE antibodies and has been recognized as a target protein for allergic therapy. According to animal models, antibodies to IL4 receptor are known to inhibit various allergic diseases.
이중, STAT6(signal transducer and activator of transcription 6: 전사 인자의 일종) 결손 쥐 실험결과에 따르면 IL-4에 의한 신호전달에 결함을 보이는데, 이러한 결과를 토대로 STAT6을 표적으로 한 치료제 개발이 시도되고 있다. Of these, STAT6 (signal transducer and activator of transcription 6) deficient mice show defects in signal transduction by IL-4. Based on these results, a therapeutic agent targeting STAT6 has been attempted .
이외에도 IL-5, IL-13, IL-9 등의 사이토카인(cytokine) 들을 표적으로 하는 치료제 개발이 시도되고 있다. In addition, the development of therapeutic agents targeting cytokines such as IL-5, IL-13 and IL-9 has been attempted.
(3) 펩티드 면역 치료(3) Peptide immunotherapy
이 방법은 알러지 유발원에 의해 유도되는 CD4 T세포 반응을 억제하는 펩티드 단편을 이용하는 방법이다. 알러겐 추출물(Allergen extracts)을 이용하는 경우 IgE에 의해 매개되는 과민성 쇼크반응을 야기할 수 있는 등 그 위험성이 크지만, 펩티드 단편을 이용할 경우 이러한 문제를 초래하지 아니한다는 장점이 알려져 있기 때문이다. This method uses a peptide fragment that inhibits CD4 T cell response induced by an allergen. When Allergen extracts are used, the risk of IgE-mediated hypersensitivity shock is high. However, it is known that the use of peptide fragments does not cause such problems.
실례로 고양이의 알러지 유발원, 단백질 Fel d에서 유래된 펩티드의 경우 Th2(T-helper 2) 사이토카인의 발현 수준을 감소시킴으로써 알러지 증상을 완화시킨다는 연구결과가 보고되고 있다. For example, research has shown that peptides derived from allergens and antigens of cats, Fel d, alleviate allergic symptoms by decreasing the expression level of Th2 (T-helper 2) cytokines.
그러나, 긴 펩티드들의 경우에는 부작용이 보고 되고 있기 때문에 최근에는 비교적 짧은 펩티드(16 or 17량체의 아미노산)을 이용하는 치료법이 활발히 개발되고 있다. However, in the case of long peptides, side effects have been reported, and recently, therapies using relatively short peptides (16 or 17 amino acids) have been actively developed.
그리고, 벌의 독소(venom)에 포함되어있는 펩티드(mast cell degranulating peptide)를 이용하여 IgE 항체가 랫의 호염기구 세포 주(RBL2H3)의 수용체에 결합하는 것을 방해함으로써 알러지를 치료하는 시도가 이루어지고 있다. Attempts have been made to treat allergies by inhibiting the binding of IgE antibodies to receptors in the rat basophil cell line (RBL2H3) using a peptide (mast cell degranulating peptide) contained in the bee venom have.
그리고, 안젤리카(Angelica Buku 등; Peptides 22, 1993-1998, 2001)나 애나(Anna Erdei, Immunology letters 92, 39-42, 2004,) 등은 보체(complement) 에서 유래된 펩티드들을 이용하여 항원에 의한 비반 세포의 활성화를 억제함으로써 상기 펩티드들(보체에서 유래된 펩티드들)이 알러지 치료제로서 가능성이 있음을 보여주었다. And, Anna Erdei, Immunology letters 92, 39-42, 2004, etc.) can be used to identify antigen-specific peptides using peptides derived from complement, such as angelica (Angelica Buku et al; Peptides 22, 1993-1998, 2001) By inhibiting the activation of mast cells, the peptides (peptides derived from the complement) showed potential as an allergy treatment.
이와타와(Iwata A)등은 자살을 억제하는 범용 케스페이즈(caspase) 억제제인 z-VAD-Fmk(N-benzyloxycarbonyl- Val-Ala-Asp-fluoromethylketone) 펩티드가 동물 실험모델에서 T 세포의 활성화를 억제함으로써 천식을 억제한다는 것을 밝혀냈다 (J. Immunol. 2003 170(6):3386-3391). Iwata A et al. Have shown that z-VAD-Fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) peptide, a universal caspase inhibitor that suppresses suicide, inhibits T cell activation in animal models Inhibiting asthma (J. Immunol. 2003 170 (6): 3386-3391).
(4) Vaccine (백신)(4) Vaccine (vaccine)
바이러스(Virus) 혹은 세균에 의한 감염은 흔히 대식세포를 활성화시키는 보조 T-셀의(Th1) 면역반응을 유발하여 알러지 반응을 억제하는 효과를 나타내는데, 이러한 점에 착안하여 Th1 반응을 유발하는 백신의 경우 알러지를 억제할 수 있는 효과를 나타내리라 예상된다. Viruses or bacterial infections often produce an effect of suppressing allergic responses by inducing (Th1) immune responses in auxiliary T cells that activate macrophages. Taking this into account, vaccines that induce Th1 responses It is expected that it will have an effect of inhibiting allergy.
이중, 결핵균의 경우 IFN-gamma, IL-12등 Th1반응을 유발하여 알러겐(allergen)에 대한 감수성을 저하시키는 역할을 할 수 있으며, 실례로 BCG 접종은 알러지 유발을 억제한다는 보고가 있다. In the case of Mycobacterium tuberculosis, the Th1 response such as IFN-gamma and IL-12 may be induced to lower the susceptibility to allergen. For example, it has been reported that the BCG vaccination inhibits allergy induction.
또한, DNA 백신이 Th1 반응을 유도한다는 여러 보고들이 있어 이를 이용한 알러지 치료제 개발이 이루어지고 있다. In addition, there are various reports that DNA vaccine induces Th1 response, and development of an allergic therapeutic agent using the vaccine has been made.
예를 들면, 베타-갈락토시데이즈 유전자가 Th1 반응을 유도한다는 보고가 있으며, 집 먼지 진드기 알러겐의 일종인 Der p5을 암호화하는 유전자의 경우 IgE 생성을 억제하고, 히스타민 분비를 억제한다는 연구결과가 있다. For example, it has been reported that the beta-galactosidase gene induces a Th1 response, and a gene encoding Der p5, a kind of house dust mite allergen, inhibits IgE production and inhibits histamine secretion .
그리고, 동물실험의 경우 CpG-ODN(CpG oligodeoxynucleotides)이 보조 T-림파구반응(Th1)을 유발한다는 보고가 있고, CpG-ODN 의 경우에는 자연살상세포:natural killer, 수지상 세포(Dendric cell)등을 자극하는데, 자극 받은 DC(수지상 세포)은 MHC class II, CD80, CD86 와 같은 상호자극 역할을 하는 물질 (costimulatory molecules)의 발현을 유도하고 IL-1, IL-6, IL-12, TNF-alpha 등과 같은 Th1 면역 반응을 매개하는 사이토카인 들의 발현을 증가시키는 효과를 나타내는 것으로 알려져 있다. In animal studies, CpG-ODN (CpG oligodeoxynucleotides) have been reported to induce Auxiliary T-lymphocyte reaction (Th1). In the case of CpG-ODN, natural killer, dendric cell Stimulated DCs (dendritic cells) induce the expression of costimulatory molecules such as MHC class II, CD80 and CD86 and induce the expression of IL-1, IL-6, IL-12, TNF-alpha And the like, which are known to increase the expression of cytokines that mediate the Th1 immune response.
이중, CpG-ODN이 실제로 인체 내에서 알러지 유발을 억제하는 지는 많은 연구결과를 요하나 현재 in vitro 실험 결과에 따르면 인간 림프구(human lymph℃ytes)는 CpG-ODN 에 대한 반응이 쥐와 유사함을 보이는 것으로 알려져 CpG-ODN은 알러지 치료제로 개발이 예상된다. Although many studies have shown that CpG-ODN actually inhibits allergenicity in humans, in vitro studies have shown that human lymphocyte responses to CpG-ODN are similar to those of rats It is known that CpG-ODN is expected to be developed as an allergy treatment.
(5) 항 IgE 항체 치료(5) Anti-IgE antibody treatment
가장 효과적인 알러지 치료는 IgE항체를 중화시키는 방법으로, IgE의 중화를 위해서는 수용체와 결합하는 IgE의 특정 부위에 대한 항체를 제조하는 것이 효과적인 방법이다. The most effective allergic therapy is a method of neutralizing IgE antibodies. For the neutralization of IgE, it is effective to prepare antibodies against specific sites of IgE binding to the receptor.
따라서, 과민성 쇼크(Anaphylactic shock)를 유발하지 아니하는 항(anti) IgE-항체들이 제조되었으며, 이러한 항체들은 IgE을 인지하나 히스타민(histamine) 분비를 초래하지 아니하므로 향후 매우 효과적인 알러지 치료제로 개발될 것으로 예상된다. Therefore, anti-IgE antibodies that do not cause anaphylactic shock have been produced. These antibodies recognize IgE but do not cause histamine secretion, and thus they will be developed as highly effective allergic agents in the future It is expected.
이중, 현재까지는 CDR(complementarity determining region) 이식 방법을 이용하여 수종의 알러지 치료용 인간화 항체가 만들어졌고, 이러한 항체들은 IgE 생성을 선택적으로 억제하여 치료하는 것으로 보고되고 있다. To date, a number of humanized antibodies have been developed for the treatment of allergies using CDR (complementarity determining region) transplantation methods, and these antibodies have been reported to selectively inhibit the production of IgE.
또한, 비만세포(mast cell)과 호염기구 세포(basophils)는 일반적으로 아토피성 피부염과 천식 등에 중요한 역할을 담당하여, 알러지(아토피성 피부염, 알러지성 비염 및 천식 등) 치료제 개발에 이상적인 표적 세포로 사용될 수 있다(Kobayashi et al., 2000; Williams et al., 2000; Matsuda et al., 1997; Pawankar et al., 1997). In addition, mast cells and basophils generally play an important role in atopic dermatitis and asthma, making them ideal target cells for the development of allergy (atopic dermatitis, allergic rhinitis and asthma) 2000; Matsuda et al., 1997; Pawankar et al., 1997).
보다 구체적으로는, 점막 비만 세포인 RBL2H3 세포주(rat basophilic leukemia)는 그 표면에 IgE 항체의 수용체(immunoglobulin receptor FcεRI)를 갖고 있는데, 이 수용체를 특정 항원으로 자극을 하여 수용체 간에 복합체를 이루면, 세포 내에서 탈과립(degranulation)과 베타 헥소스아미니데이즈(β-hexosaminidase), 류코트라이엔(leukotriene), 히스타민(histamine) 등의 매개물질 분비(mediator release), MAPK(mitogen activated protein kinase), 티로신 키나제(tyrosine kinase) 및 포스포리파제 C(phospholipase C)의 활성, ROS(활성 산소 종, Reactive oxygen species) 생성, 칼슘 유입(calcium influx) 및 사이토카인(cytokine) 생성 등의 다양한 반응이 일어난다(Reth et al., 1999; Cambier et al., 1995; Wange et al., 1996). More specifically, the RBL2H3 cell line (rat basophilic leukemia) has an IgE antibody receptor (immunoglobulin receptor FcεRI) on its surface. When the receptor is stimulated with a specific antigen to form a complex between the receptors, Mediator release such as degranulation and beta-hexosaminidase, leukotriene and histamine, mitogen-activated protein kinase (MAPK), tyrosine kinase tyrosine kinase, and phospholipase C, ROS (reactive oxygen species) generation, calcium influx and cytokine production (Reth et al , 1999; Cambier et al., 1995; Wange et al., 1996).
특히, RBL2H3 세포 내에 탈과립 반응은 과립 내에 포함된 베타 헥소스아미니데이즈(β-hexosaminidase)라는 효소가 분비되어 알러지 반응을 유도하고, 상기 유도 반응이 베타 헥소스아미니데이즈 효소의 분비를 급격히 증가시켜 과도한 알러지 반응이 일어나게 하는 것으로 알려져 있다. In particular, the deagglutination reaction in RBL2H3 cells secretes an enzyme called beta-hexosaminidase contained in the granules to induce an allergic reaction, and the induction reaction rapidly increases the secretion of beta-hexosaminidase enzyme Which is known to cause excessive allergic reactions.
그리고, 알러지 반응 시 칼슘(calcium) 이온의 유입이 증가되면, 타이로신키나제의 일종인 세린/타이로신 키나제(Syk)의 활성화가 일어나서 MAPK(mitogen activated protein kinase) 등의 키나제 활성이 연쇄적으로 일어나게 되고, 활성화된 키나제 등에 의해 알러지 반응이 유도되는 것으로 알려져 있다. When the calcium ion is increased in the allergic reaction, activation of serine / tyrosine kinase (Syk), which is a type of tyrosine kinase, occurs and thus kinase activities such as mitogen activated protein kinase (MAPK) It is known that allergic reactions are induced by activated kinases and the like.
한편, 개비자나무는 개비자나무과(Cephalotaxaceae)에 속하는 나무로 개비자나무(Cephalotaxus Koreana Nakai/Cephalotaxus harringtonia (knight) K.koch), 누개비자나무(Cephalotaxus harringtonia var. nana (Nakai) Rehder), 큰개비자나무(Cephalotaxus harringtonia (knight) K.koch), 참개비자나무(Cephalotaxus harringtonia var. fastigiata) 등이 있다. On the other hand, dog visa is a tree belonging to the family Cephalotaxaceae (Cephalotaxus Koreana Nakai / Cephalotaxus harringtonia (knight) K. koch), Cephalotaxus harringtonia var. Nana (Nakai) Rehder, Cephalotaxus harringtonia (knight) K. koch, and Cephalotaxus harringtonia var fastigiata.
개비자나무는, 한반도의 특산종으로 주로 중부지방 이남에 분포하며 중국, 일본 등의 동부아시아와 히말라야 등지에서도 자라는 것으로 알려져 있다. It is known to grow in eastern Asia and the Himalayas of China and Japan.
일반적으로 높이가 약 3미터에 이르며 수피는 암갈색을 띠고 세로로 갈라져 있는 상록침엽수이다. 한방에서는 개비자나무의 붉은색 열매를 토향비라 하여 구충제, 변비, 기침, 가래, 강장 등에 사용되어 왔다. It is usually about 3 meters high, and the bark is an evergreen conifer with a dark brown color and a vertical crack. In one room, red berries of dog visa trees have been used as insect repellent, constipation, cough, sputum, tincture and so on.
최근에는 개비자나무 잎과 줄기 등에서 추출한 알칼로이드 성분이 항균 및 암세포 증식 억제효과를 나타내는 것으로 알려져 있어 림프육종, 식도암, 폐암 등의 치료에도 사용되어 왔다. Recently, it has been known that alkaloid components extracted from leaves, stems and leaves of dogs have antibacterial and cancer cell proliferation inhibitory effect and have been used for treatment of lymphatic sarcoma, esophageal cancer and lung cancer.
또한 개비자나무의 살충, 항균 효과를 이용하여 친환경 농업에서 천연농약으로도 사용되기도 한다. It is also used as a natural pesticide in environmentally friendly agriculture by utilizing the insecticidal and antibacterial effect of dog visa trees.
그러나 이러한 개비자나무가 알러지 및 아토피 억제에 효과가 있다는 것은 전혀 이제까지 알려진 바가 없다. However, it is not known at all that these dogs are effective in suppressing allergies and atopy.
따라서, 본 발명은 개비자나무 추출물 또는 이에 함유된 호모해링토닌 화합물을 포함하는 알러지 또는 아토피 질환 예방 및 치료용 약학 조성물, 식품 또는 화장품에 관한 것이다. Accordingly, the present invention relates to a pharmaceutical composition, food or cosmetic product for preventing and treating allergic or atopic diseases, comprising an extract of ganoderma lucidum or a homoharringtonine compound contained therein.
먼저, 본 발명은 개비자나무 추출물 또는 추출물에 함유된 호모해링토닌 화합물을 이용하여 알러지 예방 및 치료용 의약 조성물 또는 건강기능성식품 조성물을 제공하고자 한다. First, the present invention provides a pharmaceutical composition or health functional food composition for prevention and treatment of allergy using homoharringtonine compound contained in ganoderma lucidum extract or extract.
본 발명에 따른 알러지용 의약 조성물 또는 건강보조식품은 식품의약안정청(KFDA)의 통상적인 약제학제 제제로의 제형화 기준 또는 건강보조식품의 제형 기준에 의거하여 제형화한다. The medicinal composition for allergies or the health supplement according to the present invention is formulated on the basis of a formulation standard of a conventional pharmaceutical preparation of KFDA or a formulation standard of a health supplement.
본 발명의 개비자나무 추출물 및 그 유효성분인 호모해링토닌 화합물은 그 자체를 사용하거나, 약제학적으로 허용이 가능한 산 부가염 또는 금속 복합체, 예를 들어 아연, 철 등과 같은 염의 형태로 사용할수 있다. The extract of Opuntia ficus-indica var. Japonica extract of the present invention and the homoharringtonine compound as an active ingredient thereof can be used in the form of a salt thereof, or in the form of pharmaceutically acceptable acid addition salts or metal complexes such as zinc and iron .
좀 더 구체적으로는 산부가염은 염화수소, 브롬화수소, 황산염, 인산염, 말레산염, 아세트염, 시트로산염, 벤조산 염, 숙신산염, 말린산염, 아스코로브산염, 타르탈산염을 사용하는 것이 바람직하다. More specifically, it is preferable to use hydrochloric acid, hydrogen bromide, sulfate, phosphate, maleate, acetate, citrate, benzoate, succinate, malate, ascorbate and tartrate as acid addition salts.
그리고, 본 발명의 개비자나무 추출물 및 그 유효성분인 호모해링토닌을 함유하는 조성물은 통상적인 방법으로, 투여방법, 투여형태 및 치료목적에 따라 상기 유효성분을 약제학적으로 허용 가능한 담체와 함께 혼합하여 희석하거나, 용기 형태의 담체 내에 봉입시키는 것이 바람직하다. The composition of the present invention containing the extract of Opuntia ficus-indica and the active ingredient homoharringtonine of the present invention can be prepared by mixing the active ingredient with a pharmaceutically acceptable carrier according to the administration method, dosage form and therapeutic purpose, It is preferable to dilute it or to enclose it in a container-shaped carrier.
상기 담체가 희석제로 사용되는 경우에는, 염수, 완충제, 덱스트로스, 물, 글리세롤, 링거액, 락토즈, 수크로즈, 칼슘 실리케이트, 메틸 셀룰로오즈 및 에탄올로 이루어진 군에서 선택된 적어도 1종 이상의 담체를 사용한 경구 투여와 비경구투여용으로 분말, 과립, 주사액, 시럽, 용액제, 정제, 좌약, 페사리(pessaries), 연고, 크림 또는 에어로졸 등과 같은 제형으로 제조한다. When the carrier is used as a diluent, oral administration using at least one carrier selected from the group consisting of saline, buffer, dextrose, water, glycerol, Ringer's solution, lactose, sucrose, calcium silicate, methyl cellulose and ethanol Granules, injections, syrups, solutions, tablets, suppositories, pessaries, ointments, creams or aerosols for parenteral administration.
다만, 본 발명의 담체가 상기의 담체만으로 한정되는 것은 아니다. 이때, 비경구 투여는 경구 이외에 직장, 정맥, 복막, 근육, 동맥, 경피, 비강, 흡입 등을 통한 유효성분의 투여를 의미한다. However, the carrier of the present invention is not limited to the above carrier. In this case, parenteral administration means administration of the active ingredient through rectal, intravenous, peritoneal, muscular, arterial, transdermal, nasal, inhalation, etc. in addition to orally.
그리고, 본 발명의 제형에 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함하여 포유동물에 투여된 후 활성성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 제형화할 수 있다. The formulation of the present invention can further be formulated so as to provide rapid, sustained or delayed release of the active ingredient after being administered to mammals, including a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifier, have.
그리고, 본 발명의 추출물이나 호모해링토닌 화합물의 투여량은 환자의 상태, 투여 경로 및 투여 형태에 따라 조절될 수 있어서 한정되지 아니하며, 증상에 따라 본 발명의 분야에서 통상의 지식을 가진 자라면 자명하게 다양한 범위 내에서 사용할 수 있다. 통상적으로는 본 발명에서는 실험적인 유효량으로 체중 1㎏ 당 0.1∼100㎎을 하루에 연속적 또는 간헐적으로 투여가 가능하다. The dose of the extract of the present invention or the homo-maring tolnin compound may be adjusted depending on the patient's condition, route of administration and dosage form, and is not limited to those of ordinary skill in the art, It can be used within a wide range. Generally, in the present invention, an experimentally effective amount of 0.1 to 100 mg / kg body weight can be administered continuously or intermittently daily.
또한, 본 발명의 개비자나무 추출물, 분획물 또는 분리된 화합물의 유효량을 기준으로, 본 발명은 개비자나무 추출물, 분획물 또는 분리된 화합물 그 자체 또는 식품학적으로 허용된 담체를 혼합한 조성물을 기본식이소재(其本食餌素材)로 포함하는 식품을 제공한다. In addition, the present invention relates to a composition comprising a ganoderma lucidum extract, a fraction or a separated compound itself or a composition comprising a pharmaceutically acceptable carrier, based on the effective amount of the ganoderma extract of the present invention, Provide the foods that are included in the material (the main food material).
본 발명의 식품은 식육가공품, 어육제품, 두부, 묵, 죽, 라면이나 국수 등의 면류, 간장, 된장, 고추장, 혼합장 등의 조미식품, 소스, 과자, 발효유 나 치즈 등의 유가공품, 김치나 장아찌 등의 절임식품, 과실, 채소, 두유, 발효음료 등의 음료수의 식품에 포함하여 사용할 수 있다. The food of the present invention can be applied to various foods such as meat products, meat products, tofu, mushrooms, porridge, noodles such as noodles and noodles, seasonings such as soy sauce, miso, Pickles such as pickles, pickles such as pickles, fruits, vegetables, soybean milk, and fermented beverages.
또한 식품학적으로 허용된 담체는 상술 한 약제학적으로 허용된 담체도 사용할 수 있다. The pharmaceutically acceptable carrier may also be the above-mentioned pharmaceutically acceptable carrier.
그리고, 본 발명은, 상기 개비자나무 추출물, 분획물 또는 분리된 유효성분 화합물의 유효량을 기준으로, 개비자나무 추출물, 분획물 또는 분리된 화합물 그 자체를 화장품학적으로 허용된 담체로 혼합한 조성물을 기능성 성분으로 포함하는 화장료 또는 화장품을 제공하고자 한다. The present invention also relates to a method for producing a composition comprising a composition obtained by mixing a ganoderma lucidum extract, a fraction or a separated compound itself with a cosmetically acceptable carrier, based on the effective amount of the ganoderma extract, fraction or isolated active ingredient compound, Cosmetics or cosmetics containing the above-mentioned ingredients.
본 발명의 화장료 또는 화장품은 화장수, 영양로션, 영양크림, 맛사지 크림, 팩 및 영양 에센스로 이루어진 군에서 선택된 형태로 제조되어 사용된다. The cosmetic or cosmetic of the present invention is prepared and used in a form selected from the group consisting of lotion, nutritional lotion, nutritional cream, massage cream, pack and nutritional essence.
본 발명의 화장품 제조방법과 담체는 당업계에 널리 알려진 모든 공지의 제조방법에 따른다.The cosmetic preparation method and carrier of the present invention are based on all known production methods well known in the art.
본 발명의 1차적인 목적은 개비자 나무 추출물에서 분리된 하기 화학식 (I)의 호모해링토닌 화합물을 함유하는 알레르기 치료용 약학 조성물을 제공하는 것이다. The primary object of the present invention is to provide a pharmaceutical composition for the treatment of allergies comprising a homoharring tolnine compound of the formula (I) isolated from an extract of Opuntia ficus-indica.
화학식 (I)(I)
본 발명의 또 다른 목적은 개비자나무 추출물 또는 이에 함유된 호모해링토닌을 유효성분으로 함유하는 알러지 및 아토피 예방, 개선용 건강 기능성 식품 조성물을 제공하는 것이다. It is still another object of the present invention to provide a health functional food composition for preventing and improving allergy and atopy which contains an extract of Opuntia ficus-indica or a homoharring tonnage contained therein as an active ingredient.
본 발명의 또 다른 목적은 개비자나무 추출물 또는 이에 함유된 호모해링토닌을 유효성분으로 함유하는 알러지 및 아토피 예방, 개선용 화장품 조성물을 제공하는 것이다.It is still another object of the present invention to provide a cosmetic composition for prevention and improvement of allergy and atopy comprising an extract of Opuntia ficus-indica or a homoharring tonin contained therein as an active ingredient.
이러한 본 발명의 목적들은 개비자 나무 추출물 또는 하기 화학식(I)을 갖는 호모해링토닌 화합물을 유효성분으로 함유하는 알러지 예방, 개선 또는 치료용 약학적 조성물을 제공함으로써 달성된다. These objects of the present invention are achieved by providing a pharmaceutical composition for preventing, ameliorating or treating allergy, which comprises as an active ingredient an extract of Opuntia ficus-indica or a homoharringtonine compound having the following formula (I).
화학식 (I)(I)
또한 본 발명의 또 다른 목적은 개비자나무 추출물 또는 호모해링토닌을 유효성분으로 함유하는 알러지 및 아로피 예방, 개선 효과를 나타내는 건강 기능성 식품 조성물을 제공함으로써 달성된다. Another object of the present invention is attained by providing a health functional food composition showing the effect of preventing or alleviating allergies and arthropods containing an extract of Aspergillus odorus or homoharringtonone as an active ingredient.
또한 본 발명의 또 다른 목적은 개비자나무 추출물 또는 이로부터 분리된 화합물인 호모해링토닌을 유효성분으로 함유하는 알러지 및 아토피 예방, 개선 또는 효과를 나타내는 화장품 조성물을 제공하는 것이다.It is still another object of the present invention to provide a cosmetic composition showing the prevention, improvement or effect of allergy and atopy comprising an extract of Ishizuka citri, or a compound isolated therefrom, as an active ingredient.
본 발명에 따른 상기 개비자나무 추출물 또는 이에 함유된 화합물인 호모해링토닌은 알러지의 주요지표 단백질들을 유의적으로 감소시키면서, 아토피 마우스 모델에서 아토피 억제 효과를 나타냄으로써, 알러지 예방, 개선, 치료에 유용하게 사용될 수 있다.The homozygous tree extract of the present invention or a compound contained therein, which is a compound of the present invention, is effective for prevention, improvement, and treatment of allergy by exhibiting an atopy inhibitory effect in an atopic mouse model while significantly reducing major index proteins of allergy Lt; / RTI >
도 1은 RBL2H3 세포 주에서 항원 자극에 의해 증가하는 HDAC3, SOCS1의 발현이 개비자나무 추출물에 의하여 감소됨을 나타낸다.
도 2는 항원 자극 시 알레르기 반응에 따른 FcεRI-HDAC3, FcεRI-SOCS1, FcεRI-Lyn의 결합이 개비자나무 추출물에 의하여 억제됨을 나타낸다.
도 3은 개비자나무로부터 유효성분인 호모해링토닌이 농도 의존적으로 항원 자극에 의하여 증가하는 HDAC3, SOCS1, TGaseII의 발현을 감소시킴을 나타낸다.
도 4는 호모해링토닌이 알레르기 반응의 지표 반응인 β-Hexosaminidase 활성을 농도 의존적으로 감소시킴을 나타낸다.
도 5는 호모해링토닌이 항원 자극에 의해 증가하는 HDAC3, SOCS1의 발현 및 FcεRI-Lyn, FcεRI-HDAC3, FcεRI-SOCS1의 결합을 억제함을 나타낸다.
도 6은 호모해링토닌이 β-Hexosaminidase 활성을 감소시킴을 나타낸다.
도 7은 BALB/c 동물모델인 수동성 피하 아나필락시스 유도에 따른 혈관투과성의 증가를 호모해링토닌이 감소시킴을 나타낸다.
도 8은 수동성 피하 아나필락시스 모델에서 호모해링토닌이 β-Hexosaminidase 활성 증가를 억제함을 나타낸다.
도 9는 폐 조직을 이용한 웨스턴 블록 결과로서, 호모해링토닌이 수동성 피하 아나필락시스에 의한 HDAC3, SOCS1, TGaseII 발현 감소 및 FcεRI-Lyn, FcεRI-HDAC3, FcεRI-SOCS1 결합을 억제함을 나타낸다.
도 10은 호모해링토닌이 BALB/c 동물모델인 수동적 전신성 아나필락시스 유도에 따른 직장 온도 감소를 억제함을 나타낸다.
도 11은 호모해링토닌이 수동적 전신성 아나필락시스 모델에서 β-Hexosaminidase 활성 증가를 억제함을 나타낸다.
도 12는 폐 조직을 이용한 웨스턴 결과로서, 호모해링토닌이 수동적 전신성 아나필락시스에 의한 HDAC3, SOCS1, TGaseII 발현 감소 및 FcεRI-Lyn, FcεRI-HDAC3, FcεRI-SOCS1 결합을 억제함을 나타낸다.
도 13은 BALB/c 는 호모해링토닌에 의해 동물모델인 아토피 모델에서 아토피가 유도된 마우스아토피 피부염이 감소됨을 나타낸다.
도 14는 아토피 모델에서 피부 조직을 이용한 웨스턴 결과로서, 호모해링토닌에 의해 HDAC3, SOCS1, TGaseII 발현이 감소됨을 나타낸다.
도 15는 피부 조직을 이용한 면역 침강 결과로 FcεRI-Lyn, FcεRI-HDAC3, FcεRI-SOCS1의 결합이 호모해링토닌에 의해 억제됨을 나타낸다.FIG. 1 shows that the expression of HDAC3, SOCS1, which is increased by antigen stimulation in RBL2H3 cell line, is reduced by the extract of Opuntia ficus-indica.
FIG. 2 shows that the binding of FcεRI-HDAC3, FcεRI-SOCS1, and FcεRI-Lyn by the allergic reaction during antigen stimulation is inhibited by the extract of Opuntia ficus-indica.
FIG. 3 shows that the homoharring tonnurin, which is an active ingredient, from dog visa trees decreases the expression of HDAC3, SOCS1, and TGaseII, which are increased by antigen stimulation in a concentration-dependent manner.
Fig. 4 shows that homoharringtonine decreases the β-hexosaminidase activity, which is an index response of the allergic reaction, in a concentration-dependent manner.
FIG. 5 shows that homoharringtonine inhibits the binding of FcεRI-Lyn, FcεRI-HDAC3, and FcεRI-SOCS1 to the expression of HDAC3, SOCS1, which is increased by antigen stimulation.
FIG. 6 shows that homoharring tolnine reduces β-Hexosaminidase activity.
Fig. 7 shows that the increase in vascular permeability due to the passive subcutaneous anaphylactic induction of the BALB / c animal model is reduced by the homoharring tonnage.
Figure 8 shows that homoharringtonine inhibits the increase of [beta] -hexosaminidase activity in the passive anaphylactic model.
FIG. 9 shows the result of Western bloc using lung tissue, showing that homoharringtonine inhibits the expression of HDAC3, SOCS1 and TGaseII by passive subcutaneous anaphylaxis and inhibits FcεRI-Lyn, FcεRI-HDAC3 and FcεRI-SOCS1 binding.
Figure 10 shows that homoharringtonine inhibits rectal temperature reduction following BALB / c animal model of passive systemic anaphylaxis induction.
Figure 11 shows that homoharringtonine inhibits the increase of [beta] -hexosaminidase activity in the passive systemic anaphylactic model.
Figure 12 shows that homoharringtonine inhibits the binding of FcεRI-Lyn, FcεRI-HDAC3, and FcεRI-SOCS1 to HDAC3, SOCS1, and TGaseII expression by passive systemic anaphylaxis.
Figure 13 shows that BALB / c is reduced by atorvastatin-induced mouse atopic dermatitis in an animal model atopic model by homoharringtonine.
FIG. 14 shows that the expression of HDAC3, SOCS1, and TGaseII is reduced by homoharringtonine as a Western result using skin tissue in an atopic model.
FIG. 15 shows that the binding of FcεRI-Lyn, FcεRI-HDAC3, and FcεRI-SOCS1 is inhibited by homo-binding tootin as a result of immunoprecipitation using skin tissue.
이하, 본 발명을 구체적인 실시예에 의해 보다 더 상세히 설명하고자 한다. Hereinafter, the present invention will be described in more detail by way of specific examples.
하지만, 본 발명의 제조방법은 바람직한 하나의 실시예일 뿐, 본 발명이 후술한 제조방법으로 국한되는 것은 아니며, 이러한 내용으로부터 약간 벗어나는 내용이라 하더라도 본 발명의 분야에서 통상의 지식을 가진 자라면 용이하게 알 수 있는 자명한 것이다. However, the manufacturing method of the present invention is only one preferred embodiment, and the present invention is not limited to the following manufacturing method. Even if the present invention is slightly deviated from the above description, It is self-evident.
실시예Example 1. 항원 자극에 의한 알레르기 관련 유전자 발현 및 베타 1. Allergy-related gene expression and beta by antigen stimulation 헥소스아미니데이Hekosamina Day 즈 분비 증가에 개비자나무 추출물이 미치는 영향 The effect of dog visa extract on growth
본 실시예에서는 개비자나무 추출물이 항원 자극 시 증가하는 알러지 표지 단백질 발현 및 효소의 분비 억제를 유발하는지 여부를 확인하고자, 종래 알려진 표준 시험에법에 따라 수행하였다. In this example, to determine whether or not the ganoderma lucidum extract induced allergic marker protein expression and inhibition of secretion of the enzyme upon stimulation with antigens, the test was conducted according to a known standard test.
DNP-특이적 IgE 항체 (100 ng/ml)로 감작된 RBL2H3 (rat basophilic leukemia) 세포에 개비자나무 추출물을 각 농도별로 2시간 전 처리 후 DNP-HSA (100 ng/ml)를 1시간 자극하였다. DNP-HSA (100 ng / ml) was stimulated for 1 hour with RB2H3 (rat basophilic leukemia) cells sensitized with DNP-specific IgE antibody (100 ng / ml) .
베타 헥소스아미니데이즈 활성을 측정한 결과 항원자극에 의해 증가한 베타 헥소스아미니데이즈 활성이 개비자나무 추출물에 의해 모두 감소됨을 확인하였다. As a result of measuring the activity of beta-hexosaminidase, it was confirmed that the activity of beta-hexosaminidase increased by the antigen stimulation was all reduced by the extract of dogs.
DNP-특이적 IgE 항체 (100 ng/ml)로 감작된 RBL2H3 세포에 개비자나무 추출물 (10μg/ml)을 2시간 전 처리 후 DNP-HSA (100 ng/ml)를 1시간 자극한 후 세포 용출물을 이용하여 웨스턴 블롯 및 면역침강법을 수행하였다. RBL2H3 cells sensitized with DNP-specific IgE antibody (100 ng / ml) were pretreated with DNP-HSA (100 ng / ml) for 2 hours, Western blot and immunoprecipitation were performed using water.
항원 자극에 의한 HDAC3, SOCS1, TGaseII 발현 증가 및 FcεRI과 Lyn, HDAC3, SOCS1의 결합은 개비자나무 추출물에 의해 억제됨을 알 수 있었다 (도 1과 2). The expression of HDAC3, SOCS1, and TGaseII by antigen stimulation and the combination of FcεRI and Lyn, HDAC3, and SOCS1 were inhibited by canine extract (FIGS. 1 and 2).
이상의 결과들로 볼 때 개비자나무 추출물은 in vitro 알러지 반응을 억제하는 것으로 확인할 수 있었다. From the above results, it was verified that the extract of cannabis extract inhibits the in vitro allergic response.
실시예2Example 2 . 개비자나무로부터 유효성분인 . The active ingredient from dog visa trees 호모해링토닌의Homo-haring tonin 분리 detach
개비자나무 추출물에 의한 알러지 반응에 주요 작용을 하는 유효성분을 분리하기 위하여 개비자나무의 잎을 건조시킨 후 분쇄한 뒤 약 10배(w/v)의 비율의 메탄올을 이용하여 유효성분을 추출하였다. In order to isolate the active ingredient which plays a major role in the allergic reaction by the dog visa extract, the leaves of the dog visa tree are dried and pulverized, and the active ingredient is extracted by using methanol at a ratio of about 10 times (w / v) Respectively.
이 메탄올 추출물에 용매로 클로로포름을 사용하여 상 분리를 유도하였고 클로로포름 층으로 이동된 추출물을 모아 감압상태에서 건조한 뒤 실리카겔 컬럼상에 로딩하고 클로로포름 및 메탄올 농도구배 하에 용출시켜 소분획물을 얻었고, 고순도의 유효성분을 얻기 위하여 이를 다시 HPLC 정제과정을 거쳐 고순도의 호모해링토닌을 얻을 수 있었다. The methanol extracts were subjected to phase separation using chloroform as a solvent. The extracts were transferred to a chloroform layer and dried under reduced pressure. The extracts were loaded onto a silica gel column and eluted under a gradient of chloroform and methanol to obtain small fractions. To obtain the components, high purity homoharring tonal was obtained through HPLC purification process.
실시예Example 3. 3. 호모해링토닌이Homo Haringtonin 항원 자극에 의한 알레르기 관련 유전자 발현 및 베타 Allergy-related gene expression and beta by antigen stimulation 헥소스아미니데이즈Hexa Minimal Days 분비 증가에 미치는 영향 Effect on secretion increase
호모해링토닌이 항원 자극 시 증가하는 알레르기 표지 단백질 발현 및 효소의 분비 억제를 유발하는지 확인하고자 종래의 방법에 따라 실험을 수행하였다. Experiments were conducted according to the conventional method in order to determine whether homoharringtonine induces allergic marker protein expression and inhibition of secretion of the enzyme upon antigen stimulation.
소혈청알부민 (BSA) 용액(2%)으로 6 well plate를 코팅(2시간 반응)한 후, 각 well당 2X105개의 RBL2H3 세포주를 분주하였다. 다음날 Anti DNP IgE 항체(100 ng/ml)로 RBL2H3 세포주를 감작시키고, 16시간 뒤 호모해링토닌(1μM)를 2시간 전 처리 한 후, 항원 (DNP-HSA, 100 ng/ml)을 1시간 처리하였다. A 6-well plate was coated with bovine serum albumin (BSA) solution (2%) (2 hours reaction), and 2X10 5 RBL2H3 cell lines were dispensed per well. The next day, RBL2H3 cell line was sensitized with anti-DNP IgE antibody (100 ng / ml), 16 hours later, homoharringtonine (1 μM) was pretreated for 2 hours, and the antigen (DNP-HSA, 100 ng / ml) Respectively.
반응 후 세포를 PBS 완충용액으로 1회 씻어준 후, lysis buffer(62.5 mM Tris-HCl, pH 6.8, 2 %(w/v)SDS, 10%(v/v)glycerol, 50 mM DTT, 0.01%(w/v) bromophenol blue, 10mM NaF, 1%(v/v)protease inhibitor cocktail, 1mM sodium orthovanadate)에 용해시켰다. 용해된 물질을 스크래퍼 (scraper)로 긁어 에펜도르프 튜브(eppendorf tube)에 넣고, 4℃ 13,000rpm 조건에서 15 분간 원심 분리하여 수득한 상등액을 같은 농도로 정량 후 5분 동안 끓이고 SDS-PAGE를 수행하였다. After the reaction, the cells were washed once with PBS buffer, and then lysed in a lysis buffer (62.5 mM Tris-HCl, pH 6.8, 2% (w / v) SDS, 10% (v / v) glycerol, (w / v) bromophenol blue, 10 mM NaF, 1% (v / v) protease inhibitor cocktail, and 1 mM sodium orthovanadate. The supernatant obtained by scraping the dissolved substance with a scraper into an eppendorf tube and centrifuging at 13,000 rpm for 15 minutes at 4 ° C was sampled at the same concentration and boiled for 5 minutes and subjected to SDS-PAGE .
Membrane에 1차 항체를 2시간 동안 반응시킨 다음 10분씩 3번 TBS-T로 씻어준 후, 2차 항체를 1:3000으로 하여 2시간 동안 반응시켰다. The primary antibody was reacted for 2 hours in the membrane, followed by washing with TBS-T 3 times for 10 minutes, and then the secondary antibody was reacted at 1: 3000 for 2 hours.
10분씩 3번 TBS-T로 씻어준 후, ECK (Enhanced chemiluminescence kit)를 사용하여 발색을 유도하였다. After washing with TBS-T 3 times for 10 minutes, color development was induced using ECK (Enhanced chemiluminescence kit).
항원 자극에 의해 증가하는 알레르기 반응 지표 단백질인 TGaseII, HDAC3, SOCS1의 발현이 호모해링토닌에 의하여 농도 의존적으로 감소함을 확인할 수 있었다 (도 3). It was confirmed that expression of TGaseII, HDAC3, and SOCS1, which are allergic response indicator proteins that are increased by antigen stimulation, is decreased in a concentration-dependent manner by homoharringtonine (FIG. 3).
항원 자극 시에, 증가하는 알레르기의 표지 효소인 베타 헥소스아미니데이즈 (β-hexosaminidase)의 분비 억제 현상을 호모해립톤이 유발하는지 여부를 확인하고자 하였다. The aim of the present study was to determine whether the secretion inhibition of β-hexosaminidase, the labeling enzyme of increasing allergen, was caused by homotypic lipolysis during antigen stimulation.
먼저, BSA 용액(2%)으로 96-well plate의 각 well을 코팅(2시간 반응)한 후, 각 well 당 2X104 개의 RBL2H3 세포주를 분주하였다. 다음날 Anti-DNP IgE 항체(100 ng/ml)로 RBL2H3 세포주를 16시간 감작 한 뒤 배지를 석션 하고, 호모해링토닌을 농도별로 2시간 전 처리한 뒤, 완충용액으로 1회 씻어준 후, Tyrode's 완충용액(119 mM NaCl, 4.74 mM KCl, 2.54 mM CaCl2, 1.19 mM MgSO4, 1.19 mM KH2PO4, 10 mM HEPES, 5mM glucose, 0.1% BSA, pH7.3) 100㎕를 넣어 주고 15 분간 배양하였다. First, each well of a 96-well plate was coated with BSA solution (2%) (2 hours reaction), and 2X10 4 RBL2H3 cell lines were dispensed per well. The following day, the RBL2H3 cell line was sensitized with Anti-DNP IgE antibody (100 ng / ml) for 16 hours, the medium was suctioned, the homoharring tonal was treated for 2 hours before concentration, washed once with buffer solution and then Tyrode's
배양 후, DNP-HSA (100 ng/ml)로 처리한 다음, 1 시간을 더 배양하였다. After culturing, the cells were treated with DNP-HSA (100 ng / ml) and then cultured for another hour.
그리고, 상등 액(80㎕)을 취해서 다른 96well plate에 넣고 동일한 부피의 기질 용액(0.2M citrate, 1mM 4-methylumberliferyl-N-acetyl-β-D-glucosamine, pH4.5)을 넣어 1시간 동안 반응을 수행하고, 1 시간 반응하는 동안 남은 세포에 lysis 완충용액(1% Triton X-100 in 1X PBS)을 처리하여, 스크래퍼(scraper)로 긁어 에펜도르프 튜브(eppendorf tube)에 넣고, 4℃ 12,000g 조건에서 5 분간 원심 분리하여 수득한 상등액을 새로운 96 well plate에 넣어 동일량 기질 용액과 반응하였다. The supernatant (80 μl) was taken and placed in another 96-well plate. The same volume of substrate solution (0.2 M citrate, 1 mM 4-methylumberliferyl-N-acetyl-β-D-glucosamine, pH 4.5) (1% Triton X-100 in 1X PBS), scraped with a scraper into an eppendorf tube, and incubated at 4 ° C for 12,000 g The supernatant obtained by centrifugation for 5 minutes under the condition was placed in a new 96 well plate and reacted with the same amount of substrate solution.
기질 반응을 중지시키기 위해 정지액 (sodium bicarbonate pH 10.0)100㎕를 넣어주고 5 분간 반응시킨 후, 흡광도를 405nm에서 측정하였다. 항원 자극에 의해 증가하는 베타 헥소스아미니데이즈의 활성이 호모해링토닌의 농도 의존적으로 감소되는 현상을 확인하였다 (도 4). To stop the substrate reaction, 100 μl of a stop solution (sodium bicarbonate pH 10.0) was added and reacted for 5 minutes, and the absorbance was measured at 405 nm. The activity of beta-hexosaminidase, which is increased by antigen stimulation, was found to be decreased in a concentration-dependent manner in homo-harringing tonin (FIG. 4).
다시 한 번, 호모해링토닌의 알레르기 반응 억제 효과를 확인하고자, 가장 효과가 좋은 농도인 1μM을 DNP-특이적 IgE 항체로 감작한 RBL2H3 세포주에 2시간 전처리 한 후, 항원으로 1시간 자극시킨 뒤 웨스턴 블롯 및 면역침강법을 수행하였다. Again, in order to confirm the inhibitory effect of homoharringtonine on allergic reactions, 1 μM of the most effective concentration was pretreated with DNP-specific IgE antibody-sensitized RBL2H3 cell line for 2 hours, stimulated with antigen for 1 hour, Blot and immunoprecipitation were performed.
면역침강법은 세포 용해물에 각각의 antibody (2μg)와 함께 1시간 동안 4℃에서 면역침강을 수행하였다. Protein A/G-agrose를 더하고 4℃, 2시간 동안 shaker에서 반응한 뒤, lysis buffer로 3번씩 washing하였다. bead 부분만 남기고 2X sample buffer를 넣고 끓인 후 SDS-PAGE 와 Western blot analyses를 수행하였다. Immunoprecipitation was performed by immersing the cell lysate with each antibody (2 μg) for 1 hour at 4 ° C. Protein A / G-agrose was added, reacted at 4 ° C for 2 hours in a shaker, and washed three times with lysis buffer. SDS-PAGE and Western blot analyzes were performed after boiling with 2X sample buffer.
항원에 의한 HDAC3와 SOCS1의 발현 증가는 호모해링토닌에 의하여 감소되고, 항원 자극에 의한 FcεRI과 Lyn, HDAC3의 결합이 억제됨을 확인할 수 있었고 (도 9), 호모해링토닌에 의한 베타 헥소스아미니데이즈 방출 역시 감소함을 확인하였다. The increase in expression of HDAC3 and SOCS1 by the antigen was reduced by homoharringtonine, and it was confirmed that the binding of FcεRI to Lyn and HDAC3 by antigen stimulation was inhibited (FIG. 9), and β-hexosaminidase Days emissions also decreased.
이상의 결과들에 의해서, 호모해링토닌은 in vitro 알레르기 반응을 억제할 수 있다는 사실이 확인되었다. These results confirmed that homoharringtonine can suppress allergic reactions in vitro.
실시예Example 4. 4. BALBBALB /C 동물모델에서 / C in animal models 호모해링토닌이Homo Haringtonin 수동성 피하 알레르기성 쇼크(anaphylaxis) 유발에 미치는 영향 Influence of passive subcutaneous allergic shock (anaphylaxis) induction
수동성 피하 아나필락시스 (passive cutaneous anaphylaxis)는 공지의 방법으로 유도되었다. Passive cutaneous anaphylaxis was induced by a known method.
구체적으로, BALB/c 마우스에 DNP-특이적 IgE 항체(0.5 μg/kg)를 마우스 귀에 피내 주사하였다. Specifically, BALB / c mice were injected with DNP-specific IgE antibody (0.5 μg / kg) in the mouse ear.
24시간 후에 호모해링토닌 (27μg/kg)을 정맥주사하고 2 시간 뒤 DNP-HSA (250μg/kg)을 2% Evans blue 용액이 포함된 PBS에 녹여 정맥주사하여 전술한 아나필락시스를 유도하였다. After 24 hours, homoharringtonine (27 μg / kg) was intravenously injected. Two hours later, DNP-HSA (250 μg / kg) was dissolved in PBS containing 2% Evans blue solution and injected intravenously to induce the above-described anaphylaxis.
항원 자극 30분 후에 마우스의 귀를 잘라서 포름아마이드 용액에 담가 에반스 용액을 용출하고 용출정도를 광학밀도 (optical density)를 측정함으로써 아나필락시스 정도를 측정하였다. After 30 minutes of antigen stimulation, the ear of the mouse was cut and the degree of anaphylaxis was measured by immersing it in a formal amide solution to elute the Evans solution and measuring the optical density of the elution.
또한 조직으로부터 용출물을 수득하여 웨스턴블롯, 면역침강, 효소 활성 측정을 수행하였다. 수동적 피하 아나필락시스를 유도한 결과 항원 자극에 의해 증가된 에반스 용액의 용출을 호모해링토닌이 억제함을 확인할 수 있었다 (도 7). Western blot, immunoprecipitation, and enzyme activity measurements were also performed by obtaining eluates from the tissues. As a result of induction of passive subcutaneous anaphylaxis, it was confirmed that homoharringtonine inhibited the elution of the Evans solution increased by the antigen stimulation (Fig. 7).
귀 조직을 이용한 효소 활성 측정 결과, 아나필락시스 유도는 베타 헥소스아미니데이즈 활성을 증가시키고, 이는 호모해링토닌에 의해 억제됨을 알 수 있었다 (도 8). As a result of measurement of enzyme activity using ear tissues, it was found that anaphylactic induction increased beta-hexosaminidase activity, which was inhibited by homoharring tonin (FIG. 8).
마우스의 귀 조직을 이용한 웨스턴 블롯 결과, 아나필락시스 유도에 의해 증가된 SOCS1, HDAC3, TGaseII의 발현이 호모해링토닌에 의해 감소됨을 확인하였다 (도 9 왼쪽). As a result of western blotting using mouse ear tissues, it was confirmed that the expression of SOCS1, HDAC3, and TGaseII increased by anaphylactic induction was reduced by homoharringtonine (Fig. 9, left).
또한 아나필락시스에 의해 유도되는 FcεRI과 Lyn, HDAC3의 결합이 호모해링토닌에 의해 억제되는 것을 알 수 있었다 (도 9 오른쪽). It was also found that the binding of FcεRI, Lyn, and HDAC3 induced by anaphylactic was inhibited by homoharringtonine (FIG. 9, right).
이상의 결과들로 볼 때 호모해링토닌은 수동성 피하 아나필락시스를 억제하는 효과를 가지는 것으로 확인되었다. These results suggest that homoharringtonine has the effect of inhibiting passive anaphylaxis.
실시예 5. 호모해링토닌이 동물모델에서 수동적 전신성 아나필락시스 유발에 미치는 영향Example 5. Effect of homoharringtonine on passive systemic anaphylactic induction in animal models
수동적 전신성 아나필락시스 (passive systemic anaphylaxis)는 공지된 방법에 따라 유도되었다. Passive systemic anaphylaxis was induced according to known methods.
구체적으로, BALB/C 마우스에 DNP-특이적 IgE 항체 (0.5 μg/kg)를 정맥주사 하여 감작하고 24시간 후에 호모해링토닌(27μg/kg)을 정맥주사 하고 2 시간 뒤 DNP-HSA (250μg/kg)을 정맥주사하여 아나필락시스를 유도하였다. Specifically, DNP-specific IgE antibody (0.5 μg / kg) was intravenously injected into BALB / C mice, and 24 hours later, homozygous haringtonin (27 μg / kg) was intravenously injected. After 2 hours, DNP- kg) intravenously to induce anaphylaxis.
10분 간격으로 2시간동안 직장 온도 (rectal temperature)를 digital gauge를 이용하여 측정하고 조직으로부터 용출물을 수득하여 웨스턴블롯, 면역침강, 효소 활성 측정을 수행하였다. The rectal temperature was measured using a digital gauge for 2 hours at intervals of 10 minutes, and Western blotting, immunoprecipitation, enzyme activity measurement was performed by obtaining eluates from the tissues.
공지의 방법에 따른 아나필락시스의 유도 시 나타나는 직장 온도의 강하를 호모해링토닌이 억제하는 것을 확인하였다 (도 10). It was confirmed that homoeolytic toinin inhibited the drop of the rectal temperature upon induction of anaphylaxis according to the known method (FIG. 10).
마우스의 폐 조직을 이용한 효소활성 측정 결과 아나필락시스 유도는 베타 헥소스아미니데이즈 활성을 증가시키고 호모해링토닌은 이의 증가를 억제하는 것을 확인하였다 (도 11). As a result of measurement of enzyme activity using lung tissue of mice, it was confirmed that anaphylactic induction increased beta-hexosaminidase activity and homoharringtonine suppressed its increase (Fig. 11).
마우스의 폐 조직을 이용한 웨스턴 블롯 결과 아나필락시스 유도에 의한 TGaseII, HDAC3, SOCS1의 발현 증가 및 FcεRI과 Lyn, HDAC3의 결합은 호모해링토닌에 의해 억제되는 것을 알 수 있었다 (도 12). Western blotting using mouse lung tissues revealed that the expression of TGaseII, HDAC3, and SOCS1 by anaphylactic induction was increased and the binding of FcεRI, Lyn, and HDAC3 was inhibited by homoharringtonine (FIG. 12).
이상의 결과들로 볼 때 호모해링토닌은 수동적 전신성 아나필락시스를 억제함을 알 수 있었다. These results suggest that homoharringtonine inhibits passive systemic anaphylaxis.
실시예 6. 호모해링토닌이 아토피 동물모델에서 아토피 유발에 미치는 효과Example 6: Effect of homoharringtonine on atopy induction in atopic animal model
본 실시예에서는 6주령의 BALB/c 마우스를 사용하여 호모해링토닌이 화학물질에 의한 아토피 유발 억제효과가 있는지의 여부를 조사하였다. In this example, 6-week-old BALB / c mice were used to investigate whether homoharringtonine has an effect of inhibiting atopic dermatitis induced by chemicals.
BALB/c 마우스에서 자연발생적인 아토피 피부염이 유도될 확률이 낮기 때문에, 다음과 같이 DNFB(2,4- dinitrofluorobenzene, DNFB)를 처리하여 접촉성 과민반응(contact hypersensitivity reaction)으로 아토피 피부염이 유도되도록 하였다. 아세톤/올리브유(1:3)에 0.15%의 DNFB를 혼합하고 150㎕를 6 주령의 BALB/c 마우스 등에 3일 간격으로 4번 발라준 후 아토피 피부염을 유도하였다. Because of the low probability that naturally occurring atopic dermatitis is induced in BALB / c mice, treatment with DNFB (2,4-dinitrofluorobenzene, DNFB) induces atopic dermatitis by contact hypersensitivity reaction . 0.15% of DNFB was mixed with acetone / olive oil (1: 3) and 150 μl was applied to BALB / c mice at 6 weeks of age for 4 times at intervals of 3 days, and then atopic dermatitis was induced.
이때, 호모해링토닌의 아토피 치료효과를 관찰하기 위해서 호모해링토닌(27μg/kg)을 꼬리 정맥주사로 3일 간격으로 4번 주입한 후 병변의 상태를 사진을 찍어서 관찰하였다. At this time, homoharringtonine (27 μg / kg) was injected four times at 3-day intervals by intravenous injection to observe the effect of homoharringtonine on atopy. The condition of the lesion was photographed and observed.
이러한 결과, 호모해링토닌을 아토피가 유도된 마우스에 주입하였을 때 아토피 피부염이 현저하게 없어짐을 확인할 수 있었다 (도 13). As a result, it was confirmed that atopic dermatitis was remarkably eliminated when homoharring tonin was injected into atopy-induced mice (Fig. 13).
마우스의 피부에서 웨스턴 블롯 및 면역침강법을 수행한 결과 DNFB에 의한 HDAC3, SOCS1, TGaseII 발현 증가 및 FcεRI과 Lyn, HDAC3, SOCS1의 결합은 호모해링토닌에 의해 억제됨을 알 수 있었다 (도 14). Western blot and immunoprecipitation of the mouse skin showed that HDAC3, SOCS1, and TGaseII expression by DNFB, and the binding of FcεRI and Lyn, HDAC3, and SOCS1 were inhibited by homoharringtonine (FIG. 14).
마우스의 피부조직을 이용한 면역조직화학염색법 결과 DNFB에 의한 피부 두께 및 HDAC3 증가, Toluidine blue 염색을 통한 비만세포의 조직 침투가 호모해링토닌에 의해 감소함을 알 수 있었다 (도 15). Immunohistochemical staining using mouse skin showed that the skin thickness and HDAC3 increase by DNFB, and tissue infiltration of mast cells through Toluidine blue staining were decreased by homo-marringtonine (Fig. 15).
이상의 결과들로 볼 때 호모해링토닌은 아토피 피부염 치료 효과가 있는 것으로 알 수 있었다. These results suggest that homoharringtonine is effective in the treatment of atopic dermatitis.
따라서, 본 발명의 개비자나무 추출물 및 이에 포함된 그 성분인 호모해링토닌은 알러지 및 아토피 피부염 예방 및 치료에 효과가 있음을 확인할 수 있었다. Therefore, it was confirmed that the extract of Opuntia ficus-indica var. Japonica extract of the present invention and its component homoharring tonnone are effective in the prevention and treatment of allergy and atopic dermatitis.
이상의 결과들을 통해, 본 발명의 개비자나무 추출물 및 그 유효성분인 호모해링토닌은 세포주 실험에서 각종 알러지 반응을 억제시켰고, 아토피 유발 동물 모델 실험에서도 개비자나무 추출물 및 그 유효성분인 호모해링토닌이 아나필락스 및 DNFB (2,4-dinitrofluorobenzene) 에 의한 아토피 유발을 억제하는 것으로 확인되었다. From the above results, it can be seen that the dog ginseng extract of the present invention and the active ingredient homoharringtonone inhibited various allergic reactions in the cell line experiment, and in the atopy-induced animal model experiment, the ginseng extract and the active ingredient homoharringtonine It was confirmed that it suppresses the atopy induction by anapyllactose and DNFB (2,4-dinitrofluorobenzene).
따라서, 개비자나무 추출물 및 그 유효성분인 호모해링토닌이 아토피를 포함한 알러지 질환의 예방 및 치료용 조성물로서 신규한 용도를 발명하였다.Therefore, the dog visa extract and the active ingredient Homoharringtonine have invented a novel use as a composition for the prevention and treatment of allergy diseases including atopy.
Claims (10)
화학식 (I)
A pharmaceutical composition for the treatment of allergies comprising a homoharringtone compound of the formula (I):
(I)
A pharmaceutical composition for the treatment of allergies comprising dog veta extract.
화학식 (I)
A pharmaceutical composition for the treatment of allergies, characterized in that the pharmaceutical composition according to claim 2 contains a homoharring tonon of the above formula (1).
(I)
2) 알코올을 용매로 사용하여 상기 개비자나무 분쇄물로부터 유효성분을 추출하는 단계; 그리고
3) 알코올에 용해된 상기 유효성분을 클로로포름으로 추출하는 단계를
포함하는, 개비자나무 추출물 제조 방법. 1) drying and crushing any one or a mixture thereof selected from the group consisting of leaves, stem, fruit and roots of a visas;
2) extracting the active ingredient from the ground viscose wood pulp using alcohol as a solvent; And
3) Extracting the active ingredient dissolved in alcohol with chloroform
≪ / RTI >
The method according to claim 8, wherein the ganoderma lucidum extract comprises homo-digesting toin of the above formula (1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170008323A KR20180085124A (en) | 2017-01-17 | 2017-01-17 | Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170008323A KR20180085124A (en) | 2017-01-17 | 2017-01-17 | Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180085124A true KR20180085124A (en) | 2018-07-26 |
Family
ID=63047967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020170008323A KR20180085124A (en) | 2017-01-17 | 2017-01-17 | Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR20180085124A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200072924A (en) | 2018-12-13 | 2020-06-23 | 영남대학교 산학협력단 | Composition for preventing or treating cell senescence associated diseases comprising homoharringtonine |
| WO2022080729A1 (en) * | 2020-10-16 | 2022-04-21 | 국립암센터 | Composition for preventing or treating lung cancer, comprising compound isolated from cephalotaxaceae extract as active ingredient |
| WO2022255583A1 (en) * | 2021-05-31 | 2022-12-08 | 영남대학교 산학협력단 | Composition containing homoharringtonine as active ingredient for preventing or treating muscle diseases |
| CN115778866A (en) * | 2022-12-29 | 2023-03-14 | 云南大学 | Application of Cephalotaxus fortunei extract in cosmetics or preparing medicines |
| KR20230058815A (en) | 2021-10-25 | 2023-05-03 | 영남대학교 산학협력단 | Pharmaceutical composition for treating or preventing progeria comprising homoharringtonine as an active ingredient |
-
2017
- 2017-01-17 KR KR1020170008323A patent/KR20180085124A/en unknown
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200072924A (en) | 2018-12-13 | 2020-06-23 | 영남대학교 산학협력단 | Composition for preventing or treating cell senescence associated diseases comprising homoharringtonine |
| WO2022080729A1 (en) * | 2020-10-16 | 2022-04-21 | 국립암센터 | Composition for preventing or treating lung cancer, comprising compound isolated from cephalotaxaceae extract as active ingredient |
| KR20220050607A (en) | 2020-10-16 | 2022-04-25 | 국립암센터 | A composition for preventing or treating lung cancer comprising the compound isolated from the extract of Cephalotaxus as an active ingredient |
| CN116710099A (en) * | 2020-10-16 | 2023-09-05 | 国立癌中心 | Composition for preventing or treating lung cancer comprising compound isolated from cephalotaxus fortunei extract as active ingredient |
| KR20240008391A (en) | 2020-10-16 | 2024-01-18 | 국립암센터 | A composition for preventing or treating lung cancer comprising the compound isolated from the extract of Cephalotaxus as an active ingredient |
| WO2022255583A1 (en) * | 2021-05-31 | 2022-12-08 | 영남대학교 산학협력단 | Composition containing homoharringtonine as active ingredient for preventing or treating muscle diseases |
| KR20230058815A (en) | 2021-10-25 | 2023-05-03 | 영남대학교 산학협력단 | Pharmaceutical composition for treating or preventing progeria comprising homoharringtonine as an active ingredient |
| CN115778866A (en) * | 2022-12-29 | 2023-03-14 | 云南大学 | Application of Cephalotaxus fortunei extract in cosmetics or preparing medicines |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20180085124A (en) | Anti-allergy Compositions Comprising Extraction of Cephalotaxus or Homoharringtonine Separated from the Extraction | |
| KR101458763B1 (en) | Pharmaceutical, cosmetic, and functional food compositions comprising smilacis chinae rhizoma of smilax china l. for allergic diseases | |
| RU2423139C2 (en) | COMPOSITION CONTAINING Actinidia AND METHODS OF THEIR APPLICATION | |
| US20100111927A1 (en) | Compositions Comprising Actinidia and Methods of Use Thereof | |
| CN102686230A (en) | Compound comprising extracts or fractions of chrysanthemum boreale makino having anti-inflammation activity | |
| KR101486147B1 (en) | Composition having ability to inhibit TSLP secretion and to improve allergic disease | |
| KR101367423B1 (en) | Pharmaceutical composition and cosmetic compostion for improving skin condition and preparation method thereof | |
| KR101934794B1 (en) | Composition for preventing, improving or treating atopic dermatitis comprising extract mixture of Diospyros lotus leaf and grape fruit stem as effective component | |
| TW201249454A (en) | Non-polysaccharide compound and usage thereof, and extraction method from Dendrobium genus plant | |
| KR101538743B1 (en) | Composition for Preventing, Improving or Treating of Ｔｈ1-mediated Immune Disease or Ｔｈ2-mediated Immune Disease Comprising Extracts from Saussurea lappa Clarke and Biota orientalis (L.) Endl. as an Active Ingredients | |
| KR20060092373A (en) | Herb medicinal compositions for prevention and alleviation of childern's atopic eczema or dermatitis | |
| KR102507470B1 (en) | Pharmaceutical composition for the prevention or treatment of allergic diseases containing Streptococcus pyogenes dead cells or SpeA protein | |
| KR102271471B1 (en) | Composition for preventing and treating allergy comprising asiatic tearthumb | |
| KR20090101600A (en) | Composition of matter having plant extracts to improve atopic dermatitis | |
| CN101291679A (en) | Compositions comprising actinidia and methods of use thereof | |
| KR20160022190A (en) | A composition for the treatment or prevention of asthma comprising erythronium japonicum | |
| KR20150095012A (en) | Composition for skin external application of treatment or prevention atopic dermatitis comprising cordycepin | |
| KR102209969B1 (en) | Composition comprising Fritillariae Thunbergii Bulbs extract for preventing or treating atopic dermatitis | |
| KR20110087149A (en) | Functional food composition and pharmaceutical composition for the prevention and alleviation of allergy symptoms | |
| KR102416215B1 (en) | Composition for preventing or treating atopic diseases comprising extract of spirodela polyrhiza and extract of olive leaf | |
| KR101575702B1 (en) | Pharmaceutical compositions containing extract of Phellinus baumii or fraction thereof of wound-healing or skin activation | |
| KR20190061370A (en) | A composition for treating dermatitis comprising aerial part of Gypsophila oldhamiana Miq. extract and fractions and use thereof | |
| KR101821118B1 (en) | Composition for Preventing or Treating Allergic Disease Comprising Gambogic Acid | |
| KR102206870B1 (en) | Combined Formulation for Prevention or Treatment of Atopic Dermatitis and Process for Thereof | |
| KR101987364B1 (en) | A composition for treating dermatitis comprising aerial part of Arachis hypogaea L. extract and fractions and use thereof |