JP5876930B2 - 炎症性腸疾患の予防および治療のための薬物の調製におけるサルモネラフラゲリン誘導体の使用 - Google Patents
炎症性腸疾患の予防および治療のための薬物の調製におけるサルモネラフラゲリン誘導体の使用 Download PDFInfo
- Publication number
- JP5876930B2 JP5876930B2 JP2014517394A JP2014517394A JP5876930B2 JP 5876930 B2 JP5876930 B2 JP 5876930B2 JP 2014517394 A JP2014517394 A JP 2014517394A JP 2014517394 A JP2014517394 A JP 2014517394A JP 5876930 B2 JP5876930 B2 JP 5876930B2
- Authority
- JP
- Japan
- Prior art keywords
- czlc331
- pharmaceutical composition
- protein
- treatment
- tat
- 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.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title claims description 53
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims description 34
- 108010040721 Flagellin Proteins 0.000 title claims description 24
- 241000607142 Salmonella Species 0.000 title claims description 23
- 230000002265 prevention Effects 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000003814 drug Substances 0.000 title description 28
- 229940079593 drug Drugs 0.000 title description 26
- 108090000623 proteins and genes Proteins 0.000 claims description 63
- 102000004169 proteins and genes Human genes 0.000 claims description 47
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 33
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 33
- 241000894006 Bacteria Species 0.000 claims description 20
- 239000013604 expression vector Substances 0.000 claims description 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 17
- 230000009465 prokaryotic expression Effects 0.000 claims description 17
- 230000014509 gene expression Effects 0.000 claims description 16
- 101710149951 Protein Tat Proteins 0.000 claims description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 108091026890 Coding region Proteins 0.000 claims description 10
- 230000026683 transduction Effects 0.000 claims description 9
- 238000010361 transduction Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- 241000588724 Escherichia coli Species 0.000 claims description 7
- 239000002662 enteric coated tablet Substances 0.000 claims description 7
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000003259 recombinant expression Methods 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 241000792859 Enema Species 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 239000007920 enema Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 230000002463 transducing effect Effects 0.000 claims description 4
- 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 claims description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 229940095399 enema Drugs 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 229940069328 povidone Drugs 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000008215 water for injection Substances 0.000 claims description 3
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 2
- 239000007888 film coating Substances 0.000 claims description 2
- 238000009501 film coating Methods 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 239000008297 liquid dosage form Substances 0.000 claims description 2
- -1 oral preparation Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 13
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims 2
- 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 claims 1
- 238000010367 cloning Methods 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 44
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 40
- 241000699670 Mus sp. Species 0.000 description 35
- 230000000694 effects Effects 0.000 description 20
- 210000001072 colon Anatomy 0.000 description 18
- 102000002689 Toll-like receptor Human genes 0.000 description 14
- 108020000411 Toll-like receptor Proteins 0.000 description 14
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 13
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 13
- 229960001940 sulfasalazine Drugs 0.000 description 13
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 13
- 230000000112 colonic effect Effects 0.000 description 11
- 210000004877 mucosa Anatomy 0.000 description 10
- 230000009471 action Effects 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 240000000220 Panda oleosa Species 0.000 description 7
- 235000016496 Panda oleosa Nutrition 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000008595 infiltration Effects 0.000 description 7
- 238000001764 infiltration Methods 0.000 description 7
- 208000032843 Hemorrhage Diseases 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 6
- 208000034158 bleeding Diseases 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 208000027744 congestion Diseases 0.000 description 6
- 210000002175 goblet cell Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 5
- 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 4
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 108010082126 Alanine transaminase Proteins 0.000 description 3
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 238000000246 agarose gel electrophoresis Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 230000002222 downregulating effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 208000035861 hematochezia Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 101710199886 Protein 0.5 Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000008234 Toll-like receptor 5 Human genes 0.000 description 2
- 108010060812 Toll-like receptor 5 Proteins 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 230000003471 anti-radiation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940121657 clinical drug Drugs 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000009429 distress Effects 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 229940079360 enema for constipation Drugs 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 208000004235 neutropenia Diseases 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000000718 radiation-protective agent Substances 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010079458 CBLB502 Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108700020359 Drosophila Tl Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- 241001131785 Escherichia coli HB101 Species 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 206010028140 Mucous stools Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 238000009004 PCR Kit Methods 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000027503 bloody stool Diseases 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000008951 colonic inflammation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000005261 decarburization Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229950009493 entolimod Drugs 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 230000003082 hepatotoxic effect Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000005026 intestinal epithelial barrier Anatomy 0.000 description 1
- 208000037817 intestinal injury Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000003621 irrigation water Substances 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000007863 pattern recognition receptors Human genes 0.000 description 1
- 108010089193 pattern recognition receptors Proteins 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000001950 radioprotection Effects 0.000 description 1
- 230000004223 radioprotective effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2893—Tablet coating processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/255—Salmonella (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110186065 | 2011-07-05 | ||
| CN201110186065.6 | 2011-07-05 | ||
| PCT/CN2012/000097 WO2013004069A1 (zh) | 2011-07-05 | 2012-01-19 | 沙门氏菌鞭毛蛋白衍生物在制备防治炎症性肠病药物中的应用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014522819A JP2014522819A (ja) | 2014-09-08 |
| JP2014522819A5 JP2014522819A5 (enExample) | 2015-03-05 |
| JP5876930B2 true JP5876930B2 (ja) | 2016-03-02 |
Family
ID=47436474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014517394A Expired - Fee Related JP5876930B2 (ja) | 2011-07-05 | 2012-01-19 | 炎症性腸疾患の予防および治療のための薬物の調製におけるサルモネラフラゲリン誘導体の使用 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9259453B2 (enExample) |
| EP (1) | EP2730287B1 (enExample) |
| JP (1) | JP5876930B2 (enExample) |
| KR (1) | KR101814558B1 (enExample) |
| CN (1) | CN102861317B (enExample) |
| AU (1) | AU2012278744B2 (enExample) |
| CA (1) | CA2840924A1 (enExample) |
| WO (1) | WO2013004069A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11273198B2 (en) | 2017-05-04 | 2022-03-15 | Second Genome, Inc. | Proteins for the treatment of epithelial barrier function disorders |
| US10402165B2 (en) | 2017-08-30 | 2019-09-03 | Gsi Technology Inc. | Concurrent multi-bit adder |
| CN108159397A (zh) * | 2018-02-28 | 2018-06-15 | 中南大学湘雅三医院 | 一种肠罗斯氏菌重组鞭毛蛋白在制备防治炎症性肠病药物中的应用 |
| CN108404113A (zh) * | 2018-05-16 | 2018-08-17 | 中国人民解放军军事科学院军事医学研究院 | 用于抗辐射损伤的口服辐抗肽药物组合物 |
| US20220218786A1 (en) * | 2019-03-28 | 2022-07-14 | The Catholic University Of Korea Industry-Academic Cooperation Foundation | Composition for preventing or treating graft-versus-host disease comprising tlr5 agonist derived from flagellin as effective component |
| CN110420317B (zh) * | 2019-07-25 | 2022-11-22 | 中国人民解放军军事科学院军事医学研究院 | Cblb502蛋白在防治创伤后应激障碍中的应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20050073865A (ko) * | 2004-01-12 | 2005-07-18 | 대한민국(전남대학교총장) | 비브리오 패혈증균 편모 구성인자 플라젤린을유효성분으로 함유하는 백신 보조제 |
| JP5285278B2 (ja) * | 2004-12-22 | 2013-09-11 | クリーブランド クリニック ファウンデイション | フラゲリン関連ポリペプチドおよびその使用 |
| AR052195A1 (es) * | 2005-01-19 | 2007-03-07 | Vaxinnate Corp | Composiciones de patrones moleculares asociados a patogenos en metodos de uso |
| CA2531261A1 (en) * | 2005-12-21 | 2007-06-21 | Institut Pasteur | Control of intestinal inflammatory syndromes with a preparation of killed or non infectious bacteria |
| JP2011519834A (ja) * | 2008-04-25 | 2011-07-14 | インスティチュート フォー システムズ バイオロジー | フラジェリンポリペプチドワクチン |
| CN101411872A (zh) * | 2008-11-25 | 2009-04-22 | 中国科学院武汉病毒研究所 | 预防龋齿的疫苗试剂盒及其使用方法 |
-
2012
- 2012-01-19 CN CN201210018080.4A patent/CN102861317B/zh not_active Expired - Fee Related
- 2012-01-19 KR KR1020147002932A patent/KR101814558B1/ko not_active Expired - Fee Related
- 2012-01-19 CA CA2840924A patent/CA2840924A1/en not_active Abandoned
- 2012-01-19 EP EP12807820.1A patent/EP2730287B1/en not_active Not-in-force
- 2012-01-19 US US14/131,050 patent/US9259453B2/en not_active Expired - Fee Related
- 2012-01-19 JP JP2014517394A patent/JP5876930B2/ja not_active Expired - Fee Related
- 2012-01-19 WO PCT/CN2012/000097 patent/WO2013004069A1/zh not_active Ceased
- 2012-01-19 AU AU2012278744A patent/AU2012278744B2/en not_active Ceased
-
2015
- 2015-11-13 US US14/940,648 patent/US9630999B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR20140054018A (ko) | 2014-05-08 |
| EP2730287B1 (en) | 2018-02-28 |
| JP2014522819A (ja) | 2014-09-08 |
| US9630999B2 (en) | 2017-04-25 |
| NZ619871A (en) | 2016-02-26 |
| US20140248348A1 (en) | 2014-09-04 |
| WO2013004069A1 (zh) | 2013-01-10 |
| CN102861317B (zh) | 2014-07-02 |
| EP2730287A4 (en) | 2015-03-18 |
| AU2012278744A1 (en) | 2014-02-20 |
| US20160060305A1 (en) | 2016-03-03 |
| KR101814558B1 (ko) | 2018-01-30 |
| EP2730287A1 (en) | 2014-05-14 |
| US9259453B2 (en) | 2016-02-16 |
| CN102861317A (zh) | 2013-01-09 |
| CA2840924A1 (en) | 2013-01-10 |
| AU2012278744B2 (en) | 2016-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9630999B2 (en) | Use of Salmonella flagellin derivative in preparation of drug for preventing and treating inflammatory bowel diseases | |
| WO2021023264A1 (zh) | 用于治疗非洲猪瘟的药物组合物及其用途 | |
| WO2015010615A1 (zh) | 一种重组trail蛋白及其制备方法和用途 | |
| JP6293882B2 (ja) | 遺伝的に安定な腫瘍溶解性ｒｎａウイルス、その製造方法およびその使用 | |
| CN112472698A (zh) | 溴酚-吡唑啉类化合物在治疗猪冠状病毒疾病中的应用 | |
| CN108586609B (zh) | 一种抗猪流行性腹泻病毒的单克隆抗体及应用 | |
| Xu et al. | Naringenin inhibits PRV replication by regulating the TLR4/NF-κB pathway mediated inflammatory response | |
| JP7544801B2 (ja) | シアノバクテリア抽出物、その調製方法と利用方法 | |
| EP2653477B1 (en) | Scorpion active peptides and preparation methods and applications thereof | |
| CN106543287A (zh) | 构象表位疫苗和应用 | |
| CN102295683B (zh) | 抗单纯疱疹病毒多肽及其应用 | |
| JP5031827B2 (ja) | 予防或いは肝損傷を治療するペプチッド | |
| NZ619871B2 (en) | Use of salmonella flagellin derivative in preparation of drug for preventing and treating inflammatory bowel diseases | |
| CN102108097A (zh) | 一种新型glp-1衍生物 | |
| CN102218139A (zh) | 一种治疗和/或预防病毒感染的药物 | |
| CN106674353B (zh) | 一种新的天花粉融合蛋白及其应用 | |
| CN102784157A (zh) | 纤细薯蓣皂苷的用途以及含有纤细薯蓣皂苷的药物组合物 | |
| CN103131719B (zh) | 具有免疫保护性的脑多头带绦虫烯醇酶TmENO重组蛋白 | |
| CN110420317B (zh) | Cblb502蛋白在防治创伤后应激障碍中的应用 | |
| RU2812805C1 (ru) | Способ ингибирования сигнального пути PD-1/PD-L1 в раковых клетках мочевого пузыря | |
| JP6841404B2 (ja) | ペプチド | |
| CN118561960B (zh) | 一种多肽片段及其制备方法和应用 | |
| CN101850113B (zh) | 一种预防猪生殖与呼吸综合征的疫苗 | |
| Prusty et al. | COVID-19 Pandemic: Epidemiology, diagnosis, and treatment knowledge | |
| WO2023225802A1 (zh) | 三叶因子2/干扰素α2融合蛋白及其防治病毒感染性疾病的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150116 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150116 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150828 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150908 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151202 |
|
| 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: 20160105 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160122 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5876930 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |