JPWO2016157929A1 - インターフェロンαの経口投与による慢性難治性外耳炎治療効果 - Google Patents
インターフェロンαの経口投与による慢性難治性外耳炎治療効果 Download PDFInfo
- Publication number
- JPWO2016157929A1 JPWO2016157929A1 JP2017509313A JP2017509313A JPWO2016157929A1 JP WO2016157929 A1 JPWO2016157929 A1 JP WO2016157929A1 JP 2017509313 A JP2017509313 A JP 2017509313A JP 2017509313 A JP2017509313 A JP 2017509313A JP WO2016157929 A1 JPWO2016157929 A1 JP WO2016157929A1
- Authority
- JP
- Japan
- Prior art keywords
- ifnα
- composition
- present
- interferon
- otitis externa
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 206010033072 otitis externa Diseases 0.000 title claims abstract description 64
- 108010047761 Interferon-alpha Proteins 0.000 title claims abstract description 55
- 102000006992 Interferon-alpha Human genes 0.000 title claims abstract description 55
- 230000001684 chronic effect Effects 0.000 title claims abstract description 52
- 238000011282 treatment Methods 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 claims abstract description 91
- 235000013305 food Nutrition 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 230000002265 prevention Effects 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 52
- 230000037396 body weight Effects 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 8
- 229940112822 chewing gum Drugs 0.000 claims description 5
- 235000015218 chewing gum Nutrition 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 235000011837 pasties Nutrition 0.000 claims description 4
- 229940068682 chewable tablet Drugs 0.000 claims description 2
- 239000007910 chewable tablet Substances 0.000 claims description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 16
- 229940124597 therapeutic agent Drugs 0.000 abstract description 6
- 230000002829 reductive effect Effects 0.000 abstract description 5
- 230000002045 lasting effect Effects 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 description 64
- 241000196324 Embryophyta Species 0.000 description 55
- 125000003275 alpha amino acid group Chemical group 0.000 description 51
- 210000004027 cell Anatomy 0.000 description 51
- 102000004169 proteins and genes Human genes 0.000 description 39
- 235000018102 proteins Nutrition 0.000 description 32
- 238000012360 testing method Methods 0.000 description 31
- 241000282472 Canis lupus familiaris Species 0.000 description 27
- 230000014509 gene expression Effects 0.000 description 23
- 230000004071 biological effect Effects 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 210000000883 ear external Anatomy 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 235000016623 Fragaria vesca Nutrition 0.000 description 18
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 18
- 240000009088 Fragaria x ananassa Species 0.000 description 17
- 102000014150 Interferons Human genes 0.000 description 16
- 108010050904 Interferons Proteins 0.000 description 16
- 229940079322 interferon Drugs 0.000 description 16
- 239000013598 vector Substances 0.000 description 16
- 108010076504 Protein Sorting Signals Proteins 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 241000124008 Mammalia Species 0.000 description 13
- 235000013399 edible fruits Nutrition 0.000 description 13
- 210000004195 gingiva Anatomy 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- 241000282465 Canis Species 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 125000000539 amino acid group Chemical group 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 9
- 241000555676 Malassezia Species 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 206010050337 Cerumen impaction Diseases 0.000 description 7
- 230000000840 anti-viral effect Effects 0.000 description 7
- 210000002939 cerumen Anatomy 0.000 description 7
- 230000001055 chewing effect Effects 0.000 description 7
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 210000000214 mouth Anatomy 0.000 description 6
- 210000002200 mouth mucosa Anatomy 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 201000004624 Dermatitis Diseases 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 240000007594 Oryza sativa Species 0.000 description 5
- 241000711975 Vesicular stomatitis virus Species 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 229920000591 gum Polymers 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000003449 preventive effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 235000007164 Oryza sativa Nutrition 0.000 description 4
- 240000008042 Zea mays Species 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 230000000120 cytopathologic effect Effects 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 235000009566 rice Nutrition 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 241000589158 Agrobacterium Species 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 229920002907 Guar gum Polymers 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 3
- 206010020649 Hyperkeratosis Diseases 0.000 description 3
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 241000282335 Procyon Species 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000000665 guar gum Substances 0.000 description 3
- 235000010417 guar gum Nutrition 0.000 description 3
- 229960002154 guar gum Drugs 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 102000054765 polymorphisms of proteins Human genes 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 210000001938 protoplast Anatomy 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol 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]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282421 Canidae Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 244000307700 Fragaria vesca Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002581 Glucomannan Polymers 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
- 239000004471 Glycine Substances 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283203 Otariidae Species 0.000 description 2
- 208000005141 Otitis Diseases 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 2
- 241000283216 Phocidae Species 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 208000019258 ear infection Diseases 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 229940046240 glucomannan Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 235000009973 maize Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 230000007102 metabolic function Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 210000003254 palate Anatomy 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 241001455214 Acinonyx jubatus Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- 241000282455 Ailurus fulgens Species 0.000 description 1
- 241000320697 Aquabacterium Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000701489 Cauliflower mosaic virus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 241000283153 Cetacea Species 0.000 description 1
- 229920001412 Chicle Polymers 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241001125840 Coryphaenidae Species 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 241000283155 Delphinidae Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000282818 Giraffidae Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000282821 Hippopotamus Species 0.000 description 1
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 1
- 241000282313 Hyaenidae Species 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 241000209510 Liliopsida Species 0.000 description 1
- 241000428198 Lutrinae Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 241001299738 Malassezia pachydermatis Species 0.000 description 1
- 240000001794 Manilkara zapota Species 0.000 description 1
- 235000011339 Manilkara zapota Nutrition 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000992305 Newcastle disease virus B1 Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 208000025174 PANDAS Diseases 0.000 description 1
- 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 240000004718 Panda Species 0.000 description 1
- 235000016496 Panda oleosa Nutrition 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 241000282373 Panthera pardus Species 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229920002367 Polyisobutene Polymers 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 241000283080 Proboscidea <mammal> Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000283011 Rangifer Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006159 Sabouraud's agar Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 240000004584 Tamarindus indica Species 0.000 description 1
- 235000004298 Tamarindus indica Nutrition 0.000 description 1
- 241000283068 Tapiridae Species 0.000 description 1
- 241000723873 Tobacco mosaic virus Species 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 241000282458 Ursus sp. Species 0.000 description 1
- 240000001417 Vigna umbellata Species 0.000 description 1
- 235000011453 Vigna umbellata Nutrition 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 235000007244 Zea mays Nutrition 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 241000981595 Zoysia japonica Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 238000003277 amino acid sequence analysis Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000011681 asexual reproduction Effects 0.000 description 1
- 238000013465 asexual reproduction Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 210000005178 buccal mucosa Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000003235 crystal violet staining Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 235000021316 daily nutritional intake Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- 235000010985 glycerol esters of wood rosin Nutrition 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 108010006088 interferon alfa-n1 Proteins 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013384 milk substitute Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 235000012015 potatoes Nutrition 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012449 sabouraud dextrose agar Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000008786 sensory perception of smell Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000014639 sexual reproduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 235000021012 strawberries Nutrition 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 230000000152 swallowing effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
- A61K9/0058—Chewing gums
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Fodder In General (AREA)
- Confectionery (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
[1]インターフェロンαを有効成分として含む、慢性難治性外耳炎の予防および/または治療の経口投与用組成物。
[2]インターフェロンαと咀嚼性の担体を含む、上記[1]に記載の組成物。
[3]咀嚼性の担体が食品である、上記[2]に記載の組成物。
[4]咀嚼錠またはチューインガムである、上記[3]に記載の組成物。
[5]インターフェロンαとペースト状の担体を含む、上記[1]に記載の組成物。
[6]体重1kgあたり0.5〜25000LU/日のインターフェロンαが配合されている、上記[1]〜[5]に記載の組成物。
[7]インターフェロンαを経口投与することを含む、慢性難治性外耳炎を予防および/または治療するための方法。
[8]インターフェロンαと咀嚼性の担体またはペースト状の担体とを含む組成物を経口投与することを含む、上記[7]に記載の方法。
[9]体重1kgあたり0.5〜25000LU/日のインターフェロンαが経口投与される、上記[8]に記載の方法。
[10]インターフェロンαと薬学的に許容される担体とを含む、慢性難治性外耳炎を予防および/または治療するための医薬組成物。
[11]薬学的に許容される担体が咀嚼性の担体またはペースト状の担体である、上記[10]に記載の医薬組成物。
[12]体重1kgあたり0.5〜25000LU/日のインターフェロンαが配合されている、上記[11]に記載の医薬組成物。
[13]慢性難治性外耳炎の治療および/または予防のための経口用組成物の製造におけるインターフェロンαの使用。
CaIFN-a1:M28624 CaIFN-a2:M28625 CaIFN-a3:O97945
CaIFN-a4:AB102731 CaIFN-a5:AB125934 CaIFN-a6:AB125935
CaIFN-a7:AB125936 CaIFN-a8:AB125937
FeIFN-w:E02521 FeIFN-a1:AY117395 FeIFN-a2:AY117394
FeIFN-a3:AY117393 FeIFN-a5:AY117392 FeIFN-a6:AY117391
FeIFN-a7:AB094996 FeIFN-a8:AB094997 FeIFN-a9:AB094998
FeIFN-a10:AB094999 FeIFN-a11:AB095000 FeIFN-a12:AB095001
FeIFN-a13:AB095002 FeIFN-a14:AB095003
D00460、M13660、M13710、X01969、X01971、X01972、X01973、X01974
M10952、M10953、M10954、M10955、M11001、X93087、X93088、X93089
IFN-a1:X57191.1
HuIFN-a1:DQ185447 HuIFN-a2:NM000605 HuIFN-a3:E00176
HuIFN-a4:NM021068 HuIFN-a5:NM002169 HuIFN-a6:NM021002
HuIFN-a7:NM021057 HuIFN-a8:NM002170 HuIFN-a10:NM002171
HuIFN-a13:NM006900 HuIFN-a14:NM002172 HuIFN-a16:NM002173
HuIFN-a17:NM021268 HuIFN-a21:NM002175 HuIFN-a2a:AAS92248
HuIFN-a2b:AAP20099 HuIFN-a1b:AAL35223 HuIFN-a4b:CAA26701
HuIFN-aI’:AAA52725(=HuIFN-a17subtype)
HuIFN-aI1:CAA01748(=HuIFN-a17subtype)
HuIFN-a-j:CAA23792 HuIFN-aT:I79343 HuIFN-aO:I79344
HuIFN-aN:I58999 HuIFN-aB:0902162A
オーアイエフ(大塚製薬製、BALL-1)
スミフェロン(住友製薬製、NAMALWA)
Wellferon(Glaxo-Wellcome、α-n1)
Alferon(Purdue Frederick Co.、α-n3)
なお、上記の天然型IFNαの由来として併記した、BALL−1、NAMALWA、α−n1、およびα−n3は、いずれも各IFNαが由来する細胞株の名前である。天然型とは、遺伝子組み換えによらず、生体から樹立された細胞株が産生するIFNαを言う。天然型のIFNαは、例えば、由来として記載した上記の細胞株を培養することによって、その培養物から回収することができる。これらの細胞株の培養と、培養物からのIFNαの回収のための方法は公知である。
(a)前記天然のIFNαのアミノ酸配列を含むタンパク質;
(b)前記天然のIFNαのアミノ酸配列において、1もしくは複数のアミノ酸残基が、置換、欠失、付加、または挿入されたアミノ酸配列を含み、天然のIFNαと同等の生物学的活性を有するタンパク質;
(c)前記天然のIFNαをコードする塩基配列からなるDNAとストリンジェントな条件においてハイブリダイズするDNAによってコードされ、天然のIFNαと同等の生物学的活性を有するタンパク質;および
(d)前記天然のIFNαのアミノ酸配列と90%以上の同一性を有するアミノ酸配列を含み、天然のIFNαと同等の生物学的活性を有するタンパク質。
(1)中性疎水性側鎖(アラニン、トリプトファン、バリン、フェニルアラニン、プロリン、メチオニン、ロイシン);
(2)中性極性側鎖(アスパラギン、グリシン、グルタミン、システイン、セリン、チロシン、トレオニン);
(3)塩基性側鎖(アルギニン、ヒスチジン、リシン);
(4)酸性側鎖(アスパラギン酸、グルタミン酸);
(5)脂肪族側鎖(アラニン、イソロイシン、グリシン、バリン、ロイシン);
(6)脂肪族水酸基側鎖(セリン、トレオニン);
(7)アミン含有側鎖(アスパラギン、アルギニン、グルタミン、ヒスチジン、リシン);
(8)芳香族側鎖(チロシン、トリプトファン、フェニルアラニン);および
(9)硫黄含有側鎖(システイン、メチオニン)
原核細胞(例えば、大腸菌)
真核細胞(例えば、CHO細胞、COS細胞、酵母発現システム、および昆虫細胞)
カリフラワーモザイクウイルスの35Sプロモーター(Odell et al.1985 Nature 313:810);
イネのアクチンプロモーター(Zhang et al.1991 Plant Cell 3:1155);
トウモロコシのユビキチンプロモーター(Cornejo et al.1993 Plant Mol.Biol.23:567)
ジャガイモ:Visserらの方法(Theor.Appl.Genet 78:594(1989));チユーバーディスク法
インターフェロンαを含む食品組成物:
通常、哺乳動物の食品(food)あるいは飼料(feed)として摂取される成分にインターフェロンαを配合することによって、本発明の組成物とすることができる。飼料が特にペット動物に与えられる場合には、ペットフードと呼ばれる。ペットフードは、本発明における食料あるいは飼料に含まれる。なおペット動物とは、鑑賞や愛玩を目的として飼育されている非ヒト動物を言う。したがって、例えば、食肉、卵、毛、乳汁などの出荷や使役を目的として飼育されている動物は、通常家畜に含まれ、ペットとは区別される。ただし、警察犬や盲導犬などの、使役を目的として飼育される動物(使役動物;working animal)に対して、愛玩動物と同じ飼料が与えられる場合もある。飼育の目的が使役であっても、ペットと同じ動物種に対してペットと同じ飼料が与えられる場合には、当該飼料は本発明でいうペットフードに含まれる。
本発明におけるIFNαを含む組成物は、咀嚼性の担体と配合して、咀嚼性組成物とすることができる。すなわち本発明は、IFNαと咀嚼性の担体(chewable carrier)を含む組成物を提供する。本発明において、咀嚼性の担体とは、動物の口腔に投与したときに、咀嚼される成分を言う。咀嚼性の担体は、噛み砕かれる素材であることもできるし、咀嚼によって小さな破片に砕かれにくい素材であることもできる。具体的には、例えば、グルコース、シュクロース、マルトース、ソルビトール、キシリトール、トレハロース、でんぷん、ゼラチン、アルギン酸、アルギン酸塩、セルロース、エチルセルロース、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、グアガム(guar gum;ポリガラクトマンナン)、グルコマンナン、キサンタンガム、カーボポール等を示すことができる。
本発明におけるIFNαを含む組成物は、ペースト状の担体と配合して、ペースト状の組成物とすることもできる。すなわち、本発明は、IFNαとペースト状の担体(paste carrier)を含む組成物を提供する。本発明において、ペースト状の担体とは、半固形状(semi−solid consistency)を有する担体と言うこともできる。あるいはペースト状の担体には、ゲル状の担体が含まれる。
なお本明細書において引用された全ての先行技術文献は、参照として本明細書に組み入れられる。
CaIFNα4遺伝子は、紫外線で不活化したニューカッスル病ウイルスB1株により刺激したイヌ細胞(MDCK細胞)のmRNAを鋳型として作製したcDNAライブラリーから、PCR法によりクローニングした。なお、クローニングに使用したプライマーの配列は以下の通りである。
センスプライマー:5'-GCAGGATCCACGATGGCCCTGC-3'(配列番号3);および
アンチセンスプライマー:5'- GCTGAGCTCAAAGTTCATCCTTATGATGATGATGATGATGTTTCCTCCTCCTTACTCTT-3'(配列番号4)
塩基配列確認後のプラスミドを制限酵素BamHI・SacIにて同時消化し、CaIFNα−4−His−KDEL遺伝子(BamHI−SacI断片)を切り出した。植物発現用ベクターpBE2113−GUS(Plant Cell Physiol.1996,37,49−59)を同じく制限酵素BamHI・SacIにて同時消化し、CIAP処理を施した後、CaIFNα−4−His−KDEL遺伝子(BamHI−SacI断片)と混和してライゲース処理を行い、pBE2113−CaIFNα−4−His−KDELを作製した。
pBE2113−CaIFNα−4−His−KDELをアグロバクテリウム(Rhizobium radiobacter LBA4404)に導入し、カナマイシン(Km)耐性株を選抜し、イチゴの形質転換実験を行った。Km添加培地を用いてカルス誘導と再分化を行い、Km耐性個体を選抜した。Km耐性個体の葉から抽出したDNAを鋳型とし、Genomic PCR法にて、CaIFNα−4遺伝子の導入を確認した(図1)。
目的タンパク質の発現が確認された高発現系統のイチゴ培養苗を馴化し、水耕栽培し果実を採取した。
CaIFNαの生理活性評価の陽性対照および標準品として、再表2007−080942(特願2007−553936)に準じて、バキュロウイルス発現CaIFNα−4を調製した。採取したCaIFNα−4遺伝子組換えイチゴ果実をPBSで破砕して、果実破砕液を調製した。陰性対照として非組換えイチゴ果実破砕液を調製した。生理活性評価は、一般的なインターフェロンα生物活性測定法である豚水疱性口炎ウイルス(Vesicular Somatitis Virus,VSV)による細胞変性効果(Cytopathic Effect,CPE)抑制法にて実施した。感受性細胞としてイヌ由来A−72細胞を用いた。CaIFNα−4力価測定には、破砕液、陽性対照および陰性対照を維持培地で104倍〜128×104倍まで2段階希釈したものを試料として供試した。試験方法の詳細を以下に記載する。なお、本明細書にてインターフェロンαの抗ウイルス活性は単位「LU」で表すが、単位「LU」はインターフェロンαの活性を示す国際単位「IU」とは、抗ウイルス活性において同義である。
収穫したCaIFNα−4発現イチゴ果実を凍結乾燥し、破砕して凍結乾燥粉末を調製した。CaIFNα−4発現イチゴ凍結乾燥粉末と安定化剤であるマルトースとを混合し、試験薬を調製した。試験薬の力価試験を実施し、1.2×104LU/gであることを確認した。
上記実施例6で調製した試験薬を被験犬に供与し、マラセチア性外耳炎に対する炎症抑制効果を検証した。被験犬は6ヶ月齢のシバイヌを6頭用意し、以下の要領でマラセチア菌の実験感染を実施した。
試験薬をCaIFNα−4として2500LU相当量を計量(約0.2g)し、これに少量の水(100μl以下)を滴下して練り、ペースト状にした。ペースト状試験薬の全量を被験犬の歯肉に塗布した。
以上のことから、イヌインターフェロンαの歯肉塗布投与は、マラセチア菌に起因する難治性外耳炎に対して炎症抑制効果を示すことが明らかとなった。
投与試験は、実施例7に記載の方法に準じるが、有効成分であるCaIFNα−4の含有量を1/10にした試験薬を投与期間を変えて被験犬(シバ系雑種、2歳4ヶ月)に供与して、マラセチア性外耳炎に対する炎症抑制効果を検証した。検証に使用した被験犬は以下の通りである。
以上のことから、イヌインターフェロンαの歯肉塗布投与は、実施例7で採用した濃度を1/10にしたとしても、マラセチア菌に起因する難治性外耳炎に対して炎症抑制効果を示すことが明らかとなった。
Claims (13)
- インターフェロンαを有効成分として含む、慢性難治性外耳炎の予防および/または治療の経口投与用組成物。
- インターフェロンαと咀嚼性の担体を含む、請求項1に記載の組成物。
- 咀嚼性の担体が食品である、請求項2に記載の組成物。
- 咀嚼錠またはチューインガムである、請求項3に記載の組成物。
- インターフェロンαとペースト状の担体を含む、請求項1に記載の組成物。
- 体重1kgあたり0.5〜25000LU/日のインターフェロンαが配合されている、請求項1〜5のいずれか1項に記載の組成物。
- インターフェロンαを経口投与することを含む、慢性難治性外耳炎を予防および/または治療するための方法。
- インターフェロンαと咀嚼性の担体またはペースト状の担体とを含む組成物を経口投与することを含む、請求項7に記載の方法。
- 体重1kgあたり0.5〜25000LU/日のインターフェロンαが経口投与される、請求項7または8に記載の方法。
- インターフェロンαと薬学的に許容される担体とを含む、慢性難治性外耳炎を予防および/または治療するための医薬組成物。
- 薬学的に許容される担体が咀嚼性の担体またはペースト状の担体である、請求項10に記載の医薬組成物。
- 体重1kgあたり0.5〜25000LU/日のインターフェロンαが配合されている、請求項10または11に記載の医薬組成物。
- 慢性難治性外耳炎の治療および/または予防のための経口用組成物の製造におけるインターフェロンαの使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015073774 | 2015-03-31 | ||
JP2015073774 | 2015-03-31 | ||
PCT/JP2016/050727 WO2016157929A1 (ja) | 2015-03-31 | 2016-01-12 | インターフェロンαの経口投与による慢性難治性外耳炎治療効果 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2016157929A1 true JPWO2016157929A1 (ja) | 2018-01-25 |
JP6815649B2 JP6815649B2 (ja) | 2021-01-20 |
Family
ID=57006670
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017509313A Active JP6815649B2 (ja) | 2015-03-31 | 2016-01-12 | インターフェロンαの経口投与による慢性難治性外耳炎治療効果 |
Country Status (4)
Country | Link |
---|---|
US (1) | US10799448B2 (ja) |
EP (1) | EP3278812B1 (ja) |
JP (1) | JP6815649B2 (ja) |
WO (1) | WO2016157929A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108117595B (zh) * | 2018-02-28 | 2020-06-26 | 中国科学院微生物研究所 | 一种犬α干扰素的制备及其应用 |
CN108864292B (zh) * | 2018-06-27 | 2021-08-17 | 军事科学院军事医学研究院军事兽医研究所 | 一种干扰素重组融合蛋白及其应用 |
GB202011945D0 (en) * | 2020-07-31 | 2020-09-16 | Ilc Therapeutics Ltd | Compositions and methods relating to the treatment of diseases |
CN112695053B (zh) * | 2021-02-05 | 2022-03-29 | 华中农业大学 | 一种重组猫干扰素的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10273448A (ja) * | 1997-03-28 | 1998-10-13 | Mochida Pharmaceut Co Ltd | アトピー性疾患治療のための口腔内投与用治療薬 |
WO2007080942A1 (ja) * | 2006-01-12 | 2007-07-19 | The Kitasato Institute | インターフェロンαを含む口腔組成物 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BRPI0703127A2 (pt) * | 2007-08-22 | 2009-04-14 | Ouro Fino Participacoes E Empreendimentos Sa | composição para o tratamento de otites agudas ou crÈnicas causadas por fungos e/ou bactérias em animais de companhia |
-
2016
- 2016-01-12 WO PCT/JP2016/050727 patent/WO2016157929A1/ja active Application Filing
- 2016-01-12 EP EP16771815.4A patent/EP3278812B1/en active Active
- 2016-01-12 US US15/562,870 patent/US10799448B2/en active Active
- 2016-01-12 JP JP2017509313A patent/JP6815649B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10273448A (ja) * | 1997-03-28 | 1998-10-13 | Mochida Pharmaceut Co Ltd | アトピー性疾患治療のための口腔内投与用治療薬 |
WO2007080942A1 (ja) * | 2006-01-12 | 2007-07-19 | The Kitasato Institute | インターフェロンαを含む口腔組成物 |
Non-Patent Citations (6)
Title |
---|
"遺伝子組み換えイチゴで動物用医薬品を開発", NOSAI会報, JPN6016011132, February 2014 (2014-02-01), pages 1 - 2, ISSN: 0004282120 * |
加納 塁, 獣医臨床皮膚科, vol. 19, no. 3, JPN6016011127, 2013, pages 131 - 134, ISSN: 0004282117 * |
岩崎 利郎: "犬のアトピー性皮膚炎の治療と管理について", MPアグロ ジャーナル, JPN6016011128, July 2012 (2012-07-01), pages 4 - 9, ISSN: 0004282118 * |
新間 陽一他: "そうだ!「産総研」があった! 産総研ライフサイエンス分野のオープンイノベーションハブ", 日本薬理学雑誌, vol. 143, no. 6, JPN6016011134, 2014, pages 295 - 301, ISSN: 0004282121 * |
河口 祐一郎, 獣医臨床皮膚科, vol. 20, no. 3, JPN6016011125, 2014, pages 161 - 163, ISSN: 0004282116 * |
田林 紀子他: "遺伝子組換えイチゴを原薬とする動物薬の開発", 生物工学会誌, vol. 92, no. 10, JPN6016011131, 2014, pages 537 - 539, ISSN: 0004282119 * |
Also Published As
Publication number | Publication date |
---|---|
EP3278812A4 (en) | 2018-12-26 |
US20190029953A1 (en) | 2019-01-31 |
EP3278812A1 (en) | 2018-02-07 |
WO2016157929A1 (ja) | 2016-10-06 |
JP6815649B2 (ja) | 2021-01-20 |
EP3278812B1 (en) | 2022-11-09 |
US10799448B2 (en) | 2020-10-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9629900B2 (en) | Oral composition containing interferon-α | |
JP6815649B2 (ja) | インターフェロンαの経口投与による慢性難治性外耳炎治療効果 | |
JP2005533481A5 (ja) | ||
KR20160089466A (ko) | 대장균증용 백신 | |
Chen et al. | Molecular characterization and expression analysis of interleukin 15 (IL15) and interleukin-15 receptor subunit alpha (IL15Rα) in dojo loach (Misgurnus anguillicaudatus): their salient roles during bacterial, parasitic and fungal infection | |
Lei et al. | Molecular characterization and antibacterial immunity functional analysis of liver-expressed antimicrobial peptide 2 (LEAP-2) gene in golden pompano (Trachinotus ovatus) | |
ES2336861T3 (es) | Produccion de il-10 en biorreactor de planta de cultivo no alimenticia. | |
JP7249149B2 (ja) | バイオフィルムの堆積および産生を阻害するための組成物および方法 | |
JPS61111693A (ja) | λP▲Lの下つき▼プロモ−タ−とリボソ−ム結合部位の置換に便利なように工学処理した制限部位とを含有する発現ベクタ−、このベクタ−を含有するプラスミド、このプラスミドを含有する宿主、および関連方法 | |
KR102586836B1 (ko) | 클로스트리디움 퍼프린젠스에 대한 특이적인 사멸능을 가지는 신규한 박테리오파지 및 이를 포함하는 항균 조성물 | |
EP4053272A1 (en) | Novel serine protease variant | |
CN111620954B (zh) | 一种抗非洲猪瘟病毒的融合蛋白及其制备方法和应用 | |
JP2002017186A (ja) | トランスジェニック植物 | |
Gan et al. | Spatiotemporal expression of MYD88 gene in pigs from birth to adulthood | |
KR101919314B1 (ko) | 구제역 바이러스 백신 조성물 | |
JP7046173B2 (ja) | ブタg-csf変異体とその使用 | |
EP3750984A1 (en) | Transformed, salmo salar interferon gamma (ifng)-producing lactococcus lactis bacterium, food and composition comprising same, for immunostimulation in aquaculture species | |
CZ29275U1 (cs) | Protiprůjmová veterinární kompozice s obsahem laktoferinu |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170726 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170801 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181212 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20181212 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191217 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200217 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20200616 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200916 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20200916 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20201012 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20201013 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20201201 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201216 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6815649 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |