JPH10506791A - 治療用送達系としての微生物 - Google Patents
治療用送達系としての微生物Info
- Publication number
- JPH10506791A JPH10506791A JP8512318A JP51231896A JPH10506791A JP H10506791 A JPH10506791 A JP H10506791A JP 8512318 A JP8512318 A JP 8512318A JP 51231896 A JP51231896 A JP 51231896A JP H10506791 A JPH10506791 A JP H10506791A
- Authority
- JP
- Japan
- Prior art keywords
- protein
- lactobacillus
- bacillus
- bacillus subtilis
- administration
- 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.)
- Pending
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 29
- 244000005700 microbiome Species 0.000 title claims description 66
- 238000012384 transportation and delivery Methods 0.000 title abstract description 12
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 142
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 97
- 241000894006 Bacteria Species 0.000 claims abstract description 69
- 239000000203 mixture Substances 0.000 claims abstract description 24
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 71
- 244000063299 Bacillus subtilis Species 0.000 claims description 66
- 241000588724 Escherichia coli Species 0.000 claims description 30
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 28
- 241000186660 Lactobacillus Species 0.000 claims description 24
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 22
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 22
- 229940039696 lactobacillus Drugs 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 10
- 102000003814 Interleukin-10 Human genes 0.000 claims description 6
- 108090000174 Interleukin-10 Proteins 0.000 claims description 6
- 229960000160 recombinant therapeutic protein Drugs 0.000 claims description 6
- 102000004127 Cytokines Human genes 0.000 claims description 5
- 108090000695 Cytokines Proteins 0.000 claims description 5
- 108010050904 Interferons Proteins 0.000 claims description 5
- 102000014150 Interferons Human genes 0.000 claims description 5
- 239000002753 trypsin inhibitor Substances 0.000 claims description 5
- 108010051696 Growth Hormone Proteins 0.000 claims description 4
- 102000018997 Growth Hormone Human genes 0.000 claims description 4
- 108010047761 Interferon-alpha Proteins 0.000 claims description 4
- 102000006992 Interferon-alpha Human genes 0.000 claims description 4
- 239000000122 growth hormone Substances 0.000 claims description 4
- 229940079322 interferon Drugs 0.000 claims description 4
- 241000894007 species Species 0.000 claims description 4
- 229960005486 vaccine Drugs 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 241000607142 Salmonella Species 0.000 claims description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 claims description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 claims description 2
- 239000000430 cytokine receptor antagonist Substances 0.000 claims description 2
- 230000002163 immunogen Effects 0.000 claims description 2
- 239000008196 pharmacological composition Substances 0.000 claims description 2
- 102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 claims 1
- 108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 45
- 238000000034 method Methods 0.000 abstract description 24
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 111
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 104
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 100
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 100
- 235000018102 proteins Nutrition 0.000 description 88
- 241000283973 Oryctolagus cuniculus Species 0.000 description 33
- 150000001413 amino acids Chemical group 0.000 description 31
- 230000014509 gene expression Effects 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 27
- 239000013612 plasmid Substances 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 20
- 230000028070 sporulation Effects 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 18
- 239000006228 supernatant Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 102000000589 Interleukin-1 Human genes 0.000 description 16
- 108010002352 Interleukin-1 Proteins 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 15
- 244000057717 Streptococcus lactis Species 0.000 description 12
- 235000014897 Streptococcus lactis Nutrition 0.000 description 12
- 238000010367 cloning Methods 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 230000006698 induction Effects 0.000 description 11
- 230000001939 inductive effect Effects 0.000 description 11
- 230000035772 mutation Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- 108090000193 Interleukin-1 beta Proteins 0.000 description 8
- 102000003777 Interleukin-1 beta Human genes 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 241000186000 Bifidobacterium Species 0.000 description 7
- 108020004705 Codon Proteins 0.000 description 7
- 241000588722 Escherichia Species 0.000 description 7
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 210000004877 mucosa Anatomy 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 210000004215 spore Anatomy 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 210000001072 colon Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 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 6
- 210000004347 intestinal mucosa Anatomy 0.000 description 6
- 210000000936 intestine Anatomy 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 230000014621 translational initiation Effects 0.000 description 6
- 208000013016 Hypoglycemia Diseases 0.000 description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 5
- 241000193996 Streptococcus pyogenes Species 0.000 description 5
- 230000036760 body temperature Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000002218 hypoglycaemic effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 210000002429 large intestine Anatomy 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 210000000813 small intestine Anatomy 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 241000186146 Brevibacterium Species 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- -1 IL- 12 Proteins 0.000 description 4
- 241000194019 Streptococcus mutans Species 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 241000282465 Canis Species 0.000 description 3
- 241000193403 Clostridium Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 3
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 3
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 244000199866 Lactobacillus casei Species 0.000 description 3
- 235000013958 Lactobacillus casei Nutrition 0.000 description 3
- 241000186684 Lactobacillus pentosus Species 0.000 description 3
- 241000186610 Lactobacillus sp. Species 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 241000194026 Streptococcus gordonii Species 0.000 description 3
- 210000000683 abdominal cavity Anatomy 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 210000004921 distal colon Anatomy 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 230000002262 irrigation Effects 0.000 description 3
- 238000003973 irrigation Methods 0.000 description 3
- 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 3
- 229940017800 lactobacillus casei Drugs 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 102220201851 rs143406017 Human genes 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 230000002865 vaccinogenic effect Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 210000004885 white matter Anatomy 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
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- WIIZWVCIJKGZOK-IUCAKERBSA-N 2,2-dichloro-n-[(1s,2s)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide Chemical compound ClC(Cl)C(=O)N[C@@H](CO)[C@@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-IUCAKERBSA-N 0.000 description 2
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 2
- 208000031295 Animal disease Diseases 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000193738 Bacillus anthracis Species 0.000 description 2
- 241000186012 Bifidobacterium breve Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 241000186226 Corynebacterium glutamicum Species 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241000588914 Enterobacter Species 0.000 description 2
- 241000588697 Enterobacter cloacae Species 0.000 description 2
- 241000194032 Enterococcus faecalis Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108020005350 Initiator Codon Proteins 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000004195 Isomerases Human genes 0.000 description 2
- 108090000769 Isomerases Proteins 0.000 description 2
- 241000588915 Klebsiella aerogenes Species 0.000 description 2
- 241001138401 Kluyveromyces lactis Species 0.000 description 2
- 241000235058 Komagataella pastoris Species 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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-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
- 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
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 2
- 241001561398 Lactobacillus jensenii Species 0.000 description 2
- 241000186604 Lactobacillus reuteri Species 0.000 description 2
- 241000186783 Lactobacillus vaginalis Species 0.000 description 2
- 241000194036 Lactococcus Species 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
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- 241000320412 Ogataea angusta Species 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 241000186429 Propionibacterium Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000191963 Staphylococcus epidermidis Species 0.000 description 2
- 241000191973 Staphylococcus xylosus Species 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000002253 acid Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 2
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 2
- 108090000637 alpha-Amylases Proteins 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000004534 cecum Anatomy 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940092559 enterobacter aerogenes Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000003767 ileocecal valve Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 210000003127 knee Anatomy 0.000 description 2
- 238000002350 laparotomy Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000004994 reproductive system Anatomy 0.000 description 2
- 229940081969 saccharomyces cerevisiae Drugs 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000001228 trophic effect Effects 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
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-M (S)-lactate Chemical compound C[C@H](O)C([O-])=O JVTAAEKCZFNVCJ-REOHCLBHSA-M 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 241000186018 Bifidobacterium adolescentis Species 0.000 description 1
- 241000186014 Bifidobacterium angulatum Species 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000186011 Bifidobacterium catenulatum Species 0.000 description 1
- 241001608472 Bifidobacterium longum Species 0.000 description 1
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 101150104494 CAV1 gene Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 101150047856 Cav2 gene Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 101100096502 Danio rerio spring gene Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 208000000655 Distemper Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000701832 Enterobacteria phage T3 Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 241001058146 Erium Species 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 208000004729 Feline Leukemia Diseases 0.000 description 1
- 241000714201 Feline calicivirus Species 0.000 description 1
- 241000714165 Feline leukemia virus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 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
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 102000012428 Hematopoietic Cell Growth Factors Human genes 0.000 description 1
- 108010022580 Hematopoietic Cell Growth Factors Proteins 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 241000341655 Human papillomavirus type 16 Species 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 241000024378 Ilybius subtilis Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014429 Insulin-like growth factor Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 229940118432 Interleukin receptor antagonist Drugs 0.000 description 1
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 238000008575 Iron Assay Methods 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- 235000014663 Kluyveromyces fragilis Nutrition 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 240000001046 Lactobacillus acidophilus Species 0.000 description 1
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 1
- 241000186713 Lactobacillus amylovorus Species 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 1
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 1
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 1
- 241000218492 Lactobacillus crispatus Species 0.000 description 1
- 241001134659 Lactobacillus curvatus Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 241000186606 Lactobacillus gasseri Species 0.000 description 1
- 240000002605 Lactobacillus helveticus Species 0.000 description 1
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 1
- 241000186685 Lactobacillus hilgardii Species 0.000 description 1
- 241000186605 Lactobacillus paracasei Species 0.000 description 1
- 240000006024 Lactobacillus plantarum Species 0.000 description 1
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 1
- 241000186612 Lactobacillus sakei Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 101100096504 Mus musculus Spring1 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- 101100426090 Rattus norvegicus Trim9 gene Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010051497 Rhinotracheitis Diseases 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 244000253911 Saccharomyces fragilis Species 0.000 description 1
- 235000018368 Saccharomyces fragilis Nutrition 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000297434 Stenotarsus subtilis Species 0.000 description 1
- 108700011201 Streptococcus IgG Fc-binding Proteins 0.000 description 1
- 241000194024 Streptococcus salivarius Species 0.000 description 1
- 241000194020 Streptococcus thermophilus Species 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 206010044302 Tracheitis Diseases 0.000 description 1
- 206010044314 Tracheobronchitis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 101100096505 Xenopus laevis spring1 gene Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 230000008952 bacterial invasion Effects 0.000 description 1
- 210000004666 bacterial spore Anatomy 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 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 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
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 229940004120 bifidobacterium infantis Drugs 0.000 description 1
- 229940009291 bifidobacterium longum Drugs 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 208000014058 canine distemper Diseases 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 208000010717 cat disease Diseases 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 229940073579 ethanolamine hydrochloride Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000005098 feline infectious peritonitis Diseases 0.000 description 1
- 238000012262 fermentative production Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000035784 germination Effects 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000012482 interaction analysis Methods 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229940113601 irrigation solution Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940031154 kluyveromyces marxianus Drugs 0.000 description 1
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 1
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 229940054346 lactobacillus helveticus Drugs 0.000 description 1
- 229940072205 lactobacillus plantarum Drugs 0.000 description 1
- 229940001882 lactobacillus reuteri Drugs 0.000 description 1
- 229940035901 lactobacillus sp Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 231100000350 mutagenesis Toxicity 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
- 239000013642 negative control Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000004763 spore germination Effects 0.000 description 1
- 239000007362 sporulation medium Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940031008 streptococcus mutans Drugs 0.000 description 1
- 229940076156 streptococcus pyogenes Drugs 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 108010042582 tosylarginine methyl ester hydrolase Proteins 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000009105 vegetative growth Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/746—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/75—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Bacillus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT94A002025 | 1994-10-05 | ||
| ITMI942025A IT1270123B (it) | 1994-10-05 | 1994-10-05 | Composizioni farmaceutiche contenenti microorganismi ingegnerizzati e loro uso per terapia |
| PCT/EP1995/003921 WO1996011277A1 (en) | 1994-10-05 | 1995-10-04 | Microorganisms as therapeutic delivery systems |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10506791A true JPH10506791A (ja) | 1998-07-07 |
Family
ID=11369649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8512318A Pending JPH10506791A (ja) | 1994-10-05 | 1995-10-04 | 治療用送達系としての微生物 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0784689A1 (it) |
| JP (1) | JPH10506791A (it) |
| AU (1) | AU3745395A (it) |
| CA (1) | CA2201721A1 (it) |
| IT (1) | IT1270123B (it) |
| WO (1) | WO1996011277A1 (it) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002528392A (ja) * | 1998-10-20 | 2002-09-03 | フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー | 大腸炎処置のためのサイトカイン産生性ラクトコッカス株の使用 |
| JP2003504025A (ja) * | 1999-07-05 | 2003-02-04 | フラームス・インテルウニフェルシタイル・インスティチュート・フォール・ビオテヒノロヒー | トレフォイルペプチドの送達 |
| WO2006028214A1 (ja) | 2004-09-10 | 2006-03-16 | Asahi Glass Company, Limited | 経口投与ワクチン |
| JP2008067708A (ja) * | 1995-10-20 | 2008-03-27 | Actogenix Nv | 生物学的に活性のあるポリペプチドのデリバリー |
| JP2013517256A (ja) * | 2010-01-14 | 2013-05-16 | インセルム（インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル） | 炎症性腸疾患（ｉｂｄ）及び過敏性腸症候群（ｉｂｓ）の予防及び治療のための組換体プロバイオティック細菌 |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6190657B1 (en) | 1995-06-07 | 2001-02-20 | Yale University | Vectors for the diagnosis and treatment of solid tumors including melanoma |
| US6080849A (en) * | 1997-09-10 | 2000-06-27 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
| AU749695B2 (en) | 1997-09-10 | 2002-07-04 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
| FR2791998B1 (fr) * | 1999-04-07 | 2001-06-08 | Agronomique Inst Nat Rech | Lactocoques modifies exprimant une catalase et leurs utilisations |
| US6962696B1 (en) | 1999-10-04 | 2005-11-08 | Vion Pharmaceuticals Inc. | Compositions and methods for tumor-targeted delivery of effector molecules |
| ATE381351T1 (de) * | 2000-07-27 | 2008-01-15 | Univ Pennsylvania | Anwendung des herpes simplex virus glykoproteins- d zur unterdrückung von immunantworten |
| CA2342040C (en) | 2000-09-21 | 2012-07-10 | Kyowa Hakko Kogyo Co., Ltd. | Anaerobic bacterium as a drug for cancer gene therapy |
| US7780961B2 (en) | 2001-05-03 | 2010-08-24 | Actogenix N.V. | Self-containing Lactococcus strain |
| WO2003063786A2 (en) * | 2002-01-31 | 2003-08-07 | Symbigene, Inc. | Methods and composition for delivering nucleic acids and/or proteins to the respiratory system |
| WO2004007695A2 (en) * | 2002-03-08 | 2004-01-22 | Osel, Inc. | Lactobacilli expressing biologically active polypeptides and uses thereof |
| EP1513545B1 (en) * | 2002-06-19 | 2008-03-19 | Actogenix N.V. | Methods and means to promote gut absorption |
| EP1590443A4 (en) * | 2003-01-29 | 2009-01-07 | Osel Inc | SURFACE EXPRESSION OF BIOLOGICALLY ACTIVE PROTEINS IN BACTERIA |
| EP1786445B1 (en) | 2004-08-25 | 2011-06-08 | The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services | Live microbial microbicides |
| US7456011B2 (en) | 2005-01-12 | 2008-11-25 | Osel, Inc. | Modified cyanovirin-n polypeptide |
| EP1957100B1 (en) | 2005-11-29 | 2016-07-13 | Intrexon Actobiotics NV | Induction of mucosal tolerance to antigens |
| BRPI0711119A2 (pt) * | 2006-05-02 | 2011-08-30 | Actogenix Nv | administração microbiana de peptìdeos intestinais associados à obesidade |
| AU2008204442B2 (en) | 2007-01-12 | 2013-03-14 | Intrexon Actobiotics Nv | Lactococcus promoters and uses thereof |
| EP2125010B1 (en) | 2007-01-25 | 2014-06-04 | Actogenix N.V. | Treatment of immune disease by mucosal delivery of antigens using genetically modified lactobacillus |
| JP2012504116A (ja) | 2008-09-29 | 2012-02-16 | アクトジェニックス・エヌブイ | 粘膜での微生物のコロニー形成の低減 |
| DK2424972T3 (da) | 2009-04-30 | 2013-10-14 | Actogenix Nv | Kryobeskyttende midler til frysetørring af mælkesyrebakterier |
| EP3192873A1 (en) | 2009-09-29 | 2017-07-19 | Intrexon Actobiotics NV | Lactobacillus and streptococcus promoters and uses thereof |
| US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
| FR2960001A1 (fr) * | 2010-05-12 | 2011-11-18 | Univ Rennes | Vecteur recombinant pour la production et la secretion de sequences d'acides amines d'interet par les bacteries propioniques et ses applications |
| US9476056B2 (en) | 2010-05-12 | 2016-10-25 | Universite De Rennes 1 | Recombinant vector for producing and secreting peptide or protein of interest by propionibacteria and applications thereof |
| AU2011268146A1 (en) | 2010-06-17 | 2013-01-10 | Actogenix Nv | Compositions and methods for treating inflammatory conditions |
| CN101921725B (zh) * | 2010-07-27 | 2013-06-05 | 浙江大学 | 一种口服免疫阻断鸡生长抑素作用的转化子及其应用 |
| ES2676707T3 (es) | 2011-09-23 | 2018-07-24 | Intrexon Actobiotics Nv | Bacterias gram positivas modificadas y usos de las mismas |
| HUE038336T2 (hu) | 2011-09-23 | 2018-10-29 | Intrexon Actobiotics Nv | Módosított gram-pozitív baktériumok és alkalmazásaik |
| AU2013299605A1 (en) | 2012-08-07 | 2015-03-26 | TopGeniX, Inc. | Topical composition comprising transformed bacteria expressing a compound of interest |
| US10064797B2 (en) | 2014-06-17 | 2018-09-04 | TopGeniX, Inc. | Topical formulations for UV protection |
| US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
| HRP20240085T1 (hr) | 2019-03-04 | 2024-03-29 | Aurealis Therapeutics AG | Prokariotski ekspresijski sustav indukciran kloridom |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1321962C (en) * | 1985-03-20 | 1993-09-07 | Aizo Matsushiro | Dental caries preventive preparations and method for preparing said preparations |
-
1994
- 1994-10-05 IT ITMI942025A patent/IT1270123B/it active IP Right Grant
-
1995
- 1995-10-04 EP EP95935431A patent/EP0784689A1/en not_active Withdrawn
- 1995-10-04 CA CA002201721A patent/CA2201721A1/en not_active Abandoned
- 1995-10-04 JP JP8512318A patent/JPH10506791A/ja active Pending
- 1995-10-04 WO PCT/EP1995/003921 patent/WO1996011277A1/en not_active Application Discontinuation
- 1995-10-04 AU AU37453/95A patent/AU3745395A/en not_active Abandoned
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008067708A (ja) * | 1995-10-20 | 2008-03-27 | Actogenix Nv | 生物学的に活性のあるポリペプチドのデリバリー |
| JP2002528392A (ja) * | 1998-10-20 | 2002-09-03 | フラームス・インテルウニフェルシタイル・インステイチュート・フォール・ビオテヒノロヒー・ヴェーゼットウェー | 大腸炎処置のためのサイトカイン産生性ラクトコッカス株の使用 |
| JP2010222364A (ja) * | 1998-10-20 | 2010-10-07 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | 大腸炎処置のためのサイトカイン産生性ラクトコッカス株の使用 |
| JP2003504025A (ja) * | 1999-07-05 | 2003-02-04 | フラームス・インテルウニフェルシタイル・インスティチュート・フォール・ビオテヒノロヒー | トレフォイルペプチドの送達 |
| JP4644401B2 (ja) * | 1999-07-05 | 2011-03-02 | アクトジェニックス・エヌブイ | トレフォイルペプチドの送達 |
| WO2006028214A1 (ja) | 2004-09-10 | 2006-03-16 | Asahi Glass Company, Limited | 経口投与ワクチン |
| US8282936B2 (en) | 2004-09-10 | 2012-10-09 | Asahi Glass Company, Ltd. | Human papillomavirus vaccine for oral administration |
| JP2013517256A (ja) * | 2010-01-14 | 2013-05-16 | インセルム（インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル） | 炎症性腸疾患（ｉｂｄ）及び過敏性腸症候群（ｉｂｓ）の予防及び治療のための組換体プロバイオティック細菌 |
Also Published As
| Publication number | Publication date |
|---|---|
| ITMI942025A1 (it) | 1996-04-05 |
| AU3745395A (en) | 1996-05-02 |
| IT1270123B (it) | 1997-04-28 |
| EP0784689A1 (en) | 1997-07-23 |
| WO1996011277A1 (en) | 1996-04-18 |
| CA2201721A1 (en) | 1996-04-18 |
| ITMI942025A0 (it) | 1994-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH10506791A (ja) | 治療用送達系としての微生物 | |
| ES2351349T3 (es) | Liberación de péptidos trébol. | |
| EP2344626B1 (en) | Reduced colonization of microbes at the mucosa | |
| EP3124614B1 (en) | Lactococcus promoters and uses thereof | |
| US20040106564A1 (en) | Use of slpi for treating chronic inflammatory intestinal diseases | |
| US5922583A (en) | Methods for production of recombinant plasmids | |
| JP2007503845A (ja) | 細菌における生物学的に活性なタンパク質の表面発現 | |
| US20120183503A1 (en) | Lactobacillus and streptococcus promoters and uses thereof | |
| AU704594B2 (en) | Production of recombinant peptides as natural hydrophobic peptide analogues | |
| Wells et al. | Progress in the development of mucosal vaccines based on Lactococcus lactis | |
| JP2001526533A (ja) | λ様プロモーターを有する遺伝子の誘導性発現のための調節系 | |
| AU2003249855B2 (en) | Cell wall mutants for delivery of biologically active compounds | |
| JP3288373B2 (ja) | 安定および生体活性改変ソマトトロピン類 | |
| MXPA06000264A (es) | Expresion recombinante de cisteina proteasa de streptococcus pyogenes y composiciones inmunogenicas de las mismas. | |
| AU2002357406B2 (en) | Defective entities and uses therefor | |
| WO2009020577A2 (en) | Innovative formulation for oral insulin delivery | |
| NZ533920A (en) | Defective entities and uses therefor |