JP5546453B2 - 脂肪肝疾患の治療におけるインターロイキン−２２の使用 - Google Patents
脂肪肝疾患の治療におけるインターロイキン−２２の使用 Download PDFInfo
- Publication number
- JP5546453B2 JP5546453B2 JP2010520208A JP2010520208A JP5546453B2 JP 5546453 B2 JP5546453 B2 JP 5546453B2 JP 2010520208 A JP2010520208 A JP 2010520208A JP 2010520208 A JP2010520208 A JP 2010520208A JP 5546453 B2 JP5546453 B2 JP 5546453B2
- Authority
- JP
- Japan
- Prior art keywords
- fatty liver
- cells
- composition
- liver
- treatment
- 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.)
- Active
Links
- 108010074109 interleukin-22 Proteins 0.000 title claims description 116
- 102100030703 Interleukin-22 Human genes 0.000 title claims description 111
- 208000010706 fatty liver disease Diseases 0.000 title claims description 59
- 238000011282 treatment Methods 0.000 title description 27
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 29
- 231100000240 steatosis hepatitis Toxicity 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 25
- 208000004930 Fatty Liver Diseases 0.000 claims description 24
- 101001010626 Homo sapiens Interleukin-22 Proteins 0.000 claims description 17
- 235000009200 high fat diet Nutrition 0.000 claims description 14
- 210000002966 serum Anatomy 0.000 claims description 14
- 102000003929 Transaminases Human genes 0.000 claims description 11
- 108090000340 Transaminases Proteins 0.000 claims description 11
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 208000026594 alcoholic fatty liver disease Diseases 0.000 claims description 6
- 230000007863 steatosis Effects 0.000 claims description 5
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 claims 1
- 206010016262 Fatty liver alcoholic Diseases 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 claims 1
- 108091033319 polynucleotide Proteins 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 210000004185 liver Anatomy 0.000 description 30
- 238000000034 method Methods 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 27
- 241000699670 Mus sp. Species 0.000 description 22
- 230000000694 effects Effects 0.000 description 19
- 241001529936 Murinae Species 0.000 description 18
- 241000700159 Rattus Species 0.000 description 18
- 230000014509 gene expression Effects 0.000 description 16
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 13
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000003623 enhancer Substances 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- 238000010367 cloning Methods 0.000 description 7
- 210000003494 hepatocyte Anatomy 0.000 description 7
- 230000008021 deposition Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000003053 toxin Substances 0.000 description 6
- 108010082126 Alanine transaminase Proteins 0.000 description 5
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 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 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 235000021588 free fatty acids Nutrition 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 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 4
- 108010027445 interleukin-22 receptor Proteins 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 210000001236 prokaryotic cell Anatomy 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- 108010062580 Concanavalin A Proteins 0.000 description 3
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 206010022489 Insulin Resistance Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 241000235070 Saccharomyces Species 0.000 description 3
- 108091023045 Untranslated Region Proteins 0.000 description 3
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 108020001096 dihydrofolate reductase Proteins 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 210000003000 inclusion body Anatomy 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102000005731 Glucose-6-phosphate isomerase Human genes 0.000 description 2
- 108010070600 Glucose-6-phosphate isomerase Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- -1 Hansenula Chemical compound 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108010002335 Interleukin-9 Proteins 0.000 description 2
- 244000285963 Kluyveromyces fragilis Species 0.000 description 2
- 241001138401 Kluyveromyces lactis Species 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 2
- 241000235648 Pichia Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 239000007799 cork Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000012215 gene cloning Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 238000007489 histopathology method Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 235000021590 normal diet Nutrition 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000607 toxicokinetics Toxicity 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical group 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 101150108727 trpl gene Proteins 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- WNQJZQMIEZWFIN-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(2-chlorobenzoyl)piperazine Chemical compound ClC1=CC=CC=C1C(=O)N1CCN(S(=O)(=O)C=2C=CC=CC=2)CC1 WNQJZQMIEZWFIN-UHFFFAOYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000011690 Adiponectin Human genes 0.000 description 1
- 108010076365 Adiponectin Proteins 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 101710187573 Alcohol dehydrogenase 2 Proteins 0.000 description 1
- 101710133776 Alcohol dehydrogenase class-3 Proteins 0.000 description 1
- 241000948470 Amanita phalloides Species 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000193755 Bacillus cereus Species 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 241000701922 Bovine parvovirus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 244000191482 Cantharellus cibarius Species 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 208000034599 Dysbetalipoproteinemia Diseases 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 241000672609 Escherichia coli BL21 Species 0.000 description 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 1
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010053070 Glutathione Disulfide Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241001149669 Hanseniaspora Species 0.000 description 1
- 102000014702 Haptoglobin Human genes 0.000 description 1
- 108050005077 Haptoglobin Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-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
- 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
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241000481961 Lachancea thermotolerans Species 0.000 description 1
- 241000235651 Lachancea waltii 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
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 241001503562 Lepiota Species 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 206010049287 Lipodystrophy acquired Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 208000007944 Nodular Nonsuppurative Panniculitis Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- 108020005115 Pyruvate Kinase Proteins 0.000 description 1
- 102000013009 Pyruvate Kinase Human genes 0.000 description 1
- 102000004879 Racemases and epimerases Human genes 0.000 description 1
- 108090001066 Racemases and epimerases Proteins 0.000 description 1
- 201000007981 Reye syndrome Diseases 0.000 description 1
- 241000223252 Rhodotorula Species 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 241000607142 Salmonella Species 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
- 241000311088 Schwanniomyces Species 0.000 description 1
- 241001123650 Schwanniomyces occidentalis Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 241001149964 Tolypocladium Species 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 1
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010060751 Type III hyperlipidaemia Diseases 0.000 description 1
- 244000000188 Vaccinium ovalifolium Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 208000026736 Weber-Christian disease Diseases 0.000 description 1
- 208000026589 Wolman disease Diseases 0.000 description 1
- 241000235013 Yarrowia Species 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000005652 acute fatty liver of pregnancy Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 125000000539 amino acid 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
- 230000003321 amplification Effects 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 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
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000006132 lipodystrophy Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000020888 liquid diet Nutrition 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003818 metabolic dysfunction Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003348 petrochemical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920002714 polyornithine Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 231100000272 reduced body weight Toxicity 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710044592.7 | 2007-08-06 | ||
| CN2007100445927A CN101361968B (zh) | 2007-08-06 | 2007-08-06 | 白介素-22在治疗脂肪肝中的应用 |
| PCT/US2008/071859 WO2009020844A1 (en) | 2007-08-06 | 2008-08-01 | Use of interleukin-22 in the treatment of fatty liver disease |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010535786A JP2010535786A (ja) | 2010-11-25 |
| JP2010535786A5 JP2010535786A5 (enExample) | 2011-09-15 |
| JP5546453B2 true JP5546453B2 (ja) | 2014-07-09 |
Family
ID=40341656
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010520208A Active JP5546453B2 (ja) | 2007-08-06 | 2008-08-01 | 脂肪肝疾患の治療におけるインターロイキン−２２の使用 |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US20110262385A1 (enExample) |
| EP (1) | EP2185202B1 (enExample) |
| JP (1) | JP5546453B2 (enExample) |
| CN (1) | CN101361968B (enExample) |
| AU (1) | AU2008284116B2 (enExample) |
| CA (1) | CA2695734C (enExample) |
| WO (1) | WO2009020844A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101361968B (zh) | 2007-08-06 | 2011-08-03 | 健能隆医药技术（上海）有限公司 | 白介素-22在治疗脂肪肝中的应用 |
| CN102260343A (zh) | 2010-05-25 | 2011-11-30 | 健能隆医药技术（上海）有限公司 | 重组人g-csf二聚体在治疗神经损伤疾病中的用途 |
| CN102380091A (zh) | 2010-08-31 | 2012-03-21 | 健能隆医药技术（上海）有限公司 | 白介素-22在治疗病毒性肝炎中的应用 |
| EP2616045B1 (en) | 2010-09-15 | 2017-10-25 | Randall J. Mrsny | Systems and methods of delivery of bioactive agents using bacterial toxin-derived transport sequences |
| US11246915B2 (en) | 2010-09-15 | 2022-02-15 | Applied Molecular Transport Inc. | Cholix toxin-derived fusion molecules for oral delivery of biologically active cargo |
| WO2013013613A1 (zh) | 2011-07-25 | 2013-01-31 | 健能隆医药技术（上海）有限公司 | G-csf二聚体在制备治疗神经退行性疾病药物中的应用 |
| CN103182072B (zh) | 2011-12-27 | 2017-05-03 | 健能隆医药技术（上海）有限公司 | 白介素‑22在治疗和预防神经损伤疾病或神经退行性疾病中的用途 |
| RS57393B1 (sr) | 2013-03-15 | 2018-09-28 | Hoffmann La Roche | Il-22 polipeptiidi i il-22 fuzioni proteini i metode za njihovu upotrebu |
| CN104623637A (zh) | 2013-11-07 | 2015-05-20 | 健能隆医药技术（上海）有限公司 | Il-22二聚体在制备静脉注射药物中的应用 |
| SI3139965T1 (sl) | 2014-05-07 | 2022-01-31 | Applied Molecular Transport Inc. | Fuzijske molekule, izpeljane iz toksina cholix, za peroralno dostavljanje biološko aktivnega tovora |
| EP3149049B1 (en) * | 2014-05-27 | 2022-10-26 | The University Of Queensland | Il-22 for use in treating metabolic disorders |
| WO2016144862A1 (en) | 2015-03-09 | 2016-09-15 | Intekrin Therapeutics, Inc. | Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy |
| WO2017181143A1 (en) | 2016-04-15 | 2017-10-19 | Generon (Shanghai) Corporation, Ltd. | Use of il-22 in treating necrotizing enterocolitis |
| CN110996951A (zh) | 2017-04-03 | 2020-04-10 | 科赫罗斯生物科学股份有限公司 | 治疗进行性核上性麻痹的PPARγ激动剂 |
| IL282986B2 (en) | 2018-11-07 | 2024-01-01 | Applied Molecular Transport Inc | Colics-derivative carriers for oral administration of heterologous cargo |
| PL3650037T3 (pl) | 2018-11-07 | 2022-06-06 | Applied Molecular Transport Inc. | Konstrukty dostarczające do transcytozy i powiązane z nimi sposoby |
| CA3150859A1 (en) | 2019-08-16 | 2021-02-25 | Applied Molecular Transport Inc. | Compositions, formulations, and interleukin production and purification |
| JPWO2022050230A1 (enExample) * | 2020-09-03 | 2022-03-10 |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4657760A (en) | 1979-03-20 | 1987-04-14 | Ortho Pharmaceutical Corporation | Methods and compositions using monoclonal antibody to human T cells |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| ZA811368B (en) | 1980-03-24 | 1982-04-28 | Genentech Inc | Bacterial polypedtide expression employing tryptophan promoter-operator |
| NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4943529A (en) | 1982-05-19 | 1990-07-24 | Gist-Brocades Nv | Kluyveromyces as a host strain |
| US4713339A (en) | 1983-01-19 | 1987-12-15 | Genentech, Inc. | Polycistronic expression vector construction |
| AU2353384A (en) | 1983-01-19 | 1984-07-26 | Genentech Inc. | Amplification in eukaryotic host cells |
| AU3145184A (en) | 1983-08-16 | 1985-02-21 | Zymogenetics Inc. | High expression of foreign genes in schizosaccharomyces pombe |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4879231A (en) | 1984-10-30 | 1989-11-07 | Phillips Petroleum Company | Transformation of yeasts of the genus pichia |
| US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| DE3675588D1 (de) | 1985-06-19 | 1990-12-20 | Ajinomoto Kk | Haemoglobin, das an ein poly(alkenylenoxid) gebunden ist. |
| US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| WO1987005330A1 (en) | 1986-03-07 | 1987-09-11 | Michel Louis Eugene Bergh | Method for enhancing glycoprotein stability |
| US4849227A (en) | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
| GB8610600D0 (en) | 1986-04-30 | 1986-06-04 | Novo Industri As | Transformation of trichoderma |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US5010182A (en) | 1987-07-28 | 1991-04-23 | Chiron Corporation | DNA constructs containing a Kluyveromyces alpha factor leader sequence for directing secretion of heterologous polypeptides |
| AU633248B2 (en) | 1987-12-21 | 1993-01-28 | University Of Toledo, The | Agrobacterium mediated transformation of germinating plant seeds |
| AU4005289A (en) | 1988-08-25 | 1990-03-01 | Smithkline Beecham Corporation | Recombinant saccharomyces |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| DE394538T1 (de) | 1989-04-28 | 1991-04-11 | Rhein Biotech Ges. Fuer Biotechnologische Prozesse Und Produkte Mbh, 4000 Duesseldorf | Hefezellen der schwanniomyces-gattung. |
| EP0402226A1 (en) | 1989-06-06 | 1990-12-12 | Institut National De La Recherche Agronomique | Transformation vectors for yeast yarrowia |
| FR2649120B1 (fr) | 1989-06-30 | 1994-01-28 | Cayla | Nouvelle souche et ses mutants de champignons filamenteux, procede de production de proteines recombinantes a l'aide de ladite souche et souches et proteines obtenues selon ce procede |
| US5225212A (en) | 1989-10-20 | 1993-07-06 | Liposome Technology, Inc. | Microreservoir liposome composition and method |
| DE69329295T2 (de) | 1992-12-02 | 2001-03-15 | Alkermes Controlled Therapeutics, Inc. | Wachstumhormon enthaltende mikrosphaeren mit kontrollierter freisetzung |
| US5951974A (en) | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| AU1684195A (en) | 1994-02-22 | 1995-09-04 | Georgia Tech Research Corporation | Reduction of friction during wire drawing |
| PT779806E (pt) | 1994-09-09 | 2001-02-28 | Takeda Chemical Industries Ltd | Preparacao de libertacao sustentada contendo um sal metalico de um peptido |
| JPH11506740A (ja) | 1995-06-07 | 1999-06-15 | アルカームズ コントロールド セラピューティックス，インコーポレイテッド | ヒト成長ホルモンの徐放性組成物 |
| ZA965368B (en) | 1995-07-14 | 1997-01-14 | Novo Nordisk As | A pharmaceutical formulation |
| US6551799B2 (en) * | 1999-12-07 | 2003-04-22 | Genentech, Inc. | Interleukin-22 polypeptides, nucleic acids encoding the same and methods for the treatment of pancreatic disorders |
| US20010023070A1 (en) | 1998-05-29 | 2001-09-20 | Reinhard Ebner | Interleukins-21 and 22 |
| AU4208799A (en) | 1998-05-29 | 1999-12-13 | Human Genome Sciences, Inc. | Interleukins-21 and 22 |
| US6274710B1 (en) | 1998-10-26 | 2001-08-14 | Ludwig Institute For Cancer Research | Antibodies which specifically bind T Cell inducible factors (TIFs) |
| AU760224B2 (en) | 1998-10-26 | 2003-05-08 | Wyeth | Isolated nucleic acid molecules which encode T cell inducible factors (TIFs), the proteins encoded, and uses thereof |
| US7307161B1 (en) | 1999-04-28 | 2007-12-11 | Genetics Institute, Llc | Human Gil-19/AE289 polynucleotides |
| US7226591B2 (en) | 2000-05-22 | 2007-06-05 | Genentech, Inc. | Interleukin-22 polypeptides, nucleic acids encoding the same and methods for the treatment of pancreatic disorders |
| CN1163263C (zh) | 2000-01-07 | 2004-08-25 | 华中理工大学 | 一种多肽类药物口腔喷雾剂 |
| GB0024442D0 (en) | 2000-10-05 | 2000-11-22 | Isis Innovation | Genetic factors affecting the outcome of viral infections |
| CN1335182A (zh) | 2001-08-08 | 2002-02-13 | 华中科技大学 | 胰岛素口腔喷剂及其制备工艺 |
| US6797493B2 (en) | 2001-10-01 | 2004-09-28 | Lee-Hwei K. Sun | Fc fusion proteins of human granulocyte colony-stimulating factor with increased biological activities |
| JP2005519986A (ja) | 2001-11-06 | 2005-07-07 | イーライ・リリー・アンド・カンパニー | 造血障害を治療するためのｉｌ−１９、ｉｌ−２２およびｉｌ−２４の使用 |
| EP1463752A4 (en) | 2001-12-21 | 2005-07-13 | Human Genome Sciences Inc | ALBUMIN FUSION PROTEINS |
| CN1176137C (zh) | 2002-01-15 | 2004-11-17 | 泛亚生物技术有限公司 | 多臂树杈型功能化聚乙二醇制备方法及它在药物中的应用 |
| US7597876B2 (en) | 2007-01-11 | 2009-10-06 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| US20030235561A1 (en) | 2002-06-25 | 2003-12-25 | Cell Based Delivery Inc. | Vascularized organized tissues and uses thereof |
| US20050148029A1 (en) | 2003-09-29 | 2005-07-07 | Biosite, Inc. | Methods and compositions for determining treatment regimens in systemic inflammatory response syndromes |
| DK1748789T3 (da) | 2003-11-05 | 2012-01-23 | Inst Rech Developpement Ird | IL-22 til forebyggelse af infektionssygdomme |
| JP5103022B2 (ja) | 2004-02-13 | 2012-12-19 | ノッド ファーマシューティカルズ， インコーポレイテッド | リン酸カルシウムナノ粒子のコア、生体分子および胆汁酸を含む粒子、ならびにそれらの製造方法および治療用途 |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| CN100515491C (zh) * | 2005-01-04 | 2009-07-22 | 健能隆医药技术（上海）有限公司 | 白介素-22的医药用途 |
| PE20061391A1 (es) | 2005-02-14 | 2007-01-09 | Wyeth Corp | Anticuerpos para interleucina-17f y otros antagonistas de la senalizacion de il-17f |
| WO2007047796A2 (en) * | 2005-10-17 | 2007-04-26 | Institute For Systems Biology | Tissue-and serum-derived glycoproteins and methods of their use |
| UA95613C2 (ru) * | 2005-11-09 | 2011-08-25 | Уеллстат Терепьютикс Корпорейшн | Соединения для лечения расстройсв метаболизма |
| WO2007115230A2 (en) | 2006-03-30 | 2007-10-11 | University Of Medicine And Dentistry Of New Jersey | A strategy for homo- or hetero-dimerization of various proteins in solutions and in cells |
| US8211649B2 (en) | 2006-03-31 | 2012-07-03 | Human Genome Sciences, Inc. | Methods of diagnosing and prognosing hodgkin's lymphoma |
| US20080031882A1 (en) | 2006-06-19 | 2008-02-07 | Liang Spencer C | Methods of modulating IL-22 and IL-17 |
| WO2008085229A2 (en) | 2006-11-15 | 2008-07-17 | Arteriocyte Inc. | Cell-based therapies for treating liver disease |
| CN101361968B (zh) | 2007-08-06 | 2011-08-03 | 健能隆医药技术（上海）有限公司 | 白介素-22在治疗脂肪肝中的应用 |
| WO2009041734A1 (ja) | 2007-09-26 | 2009-04-02 | Kyowa Hakko Kirin Co., Ltd. | ヒトトロンボポエチン受容体に対するアゴニスト抗体 |
| CN101168049A (zh) * | 2007-10-23 | 2008-04-30 | 中国人民解放军军事医学科学院基础医学研究所 | 白介素-22在制备治疗肝病药物中的应用及其制备方法 |
| CN101225110B (zh) | 2007-10-23 | 2010-10-20 | 中国人民解放军军事医学科学院基础医学研究所 | 人白细胞介素-22突变体及其构建方法和应用 |
| CN108815508A (zh) | 2007-11-07 | 2018-11-16 | 健泰科生物技术公司 | 用于治疗微生物病症的组合物和方法 |
| EP2385841B1 (en) | 2009-01-12 | 2016-11-16 | Generon (Shanghai) Corporation | Prevention and/or treatment of multiple organ dysfunction syndrome with interleukin-22 |
| WO2011087986A1 (en) | 2010-01-13 | 2011-07-21 | Amgen Inc. | Il-22-fc and hepcidin activity |
| CN102380091A (zh) | 2010-08-31 | 2012-03-21 | 健能隆医药技术（上海）有限公司 | 白介素-22在治疗病毒性肝炎中的应用 |
| CN103182072B (zh) | 2011-12-27 | 2017-05-03 | 健能隆医药技术（上海）有限公司 | 白介素‑22在治疗和预防神经损伤疾病或神经退行性疾病中的用途 |
| RS57393B1 (sr) | 2013-03-15 | 2018-09-28 | Hoffmann La Roche | Il-22 polipeptiidi i il-22 fuzioni proteini i metode za njihovu upotrebu |
| CN104623639A (zh) | 2013-11-07 | 2015-05-20 | 健能隆医药技术（上海）有限公司 | 白介素22二聚体在制备治疗胰腺炎药物中的应用 |
| CN104623637A (zh) | 2013-11-07 | 2015-05-20 | 健能隆医药技术（上海）有限公司 | Il-22二聚体在制备静脉注射药物中的应用 |
| US20160287670A1 (en) | 2013-11-07 | 2016-10-06 | Memorial Sloan-Kettering Cancer Center | Methods of use for il-22 in the treatment of gastrointestinal graft vs. host disease |
| WO2017181143A1 (en) | 2016-04-15 | 2017-10-19 | Generon (Shanghai) Corporation, Ltd. | Use of il-22 in treating necrotizing enterocolitis |
-
2007
- 2007-08-06 CN CN2007100445927A patent/CN101361968B/zh active Active
-
2008
- 2008-08-01 US US12/672,274 patent/US20110262385A1/en not_active Abandoned
- 2008-08-01 JP JP2010520208A patent/JP5546453B2/ja active Active
- 2008-08-01 CA CA2695734A patent/CA2695734C/en active Active
- 2008-08-01 EP EP20080797018 patent/EP2185202B1/en active Active
- 2008-08-01 WO PCT/US2008/071859 patent/WO2009020844A1/en not_active Ceased
- 2008-08-01 AU AU2008284116A patent/AU2008284116B2/en active Active
-
2014
- 2014-09-11 US US14/483,175 patent/US20140377222A1/en not_active Abandoned
-
2017
- 2017-09-01 US US15/694,670 patent/US10786551B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CA2695734A1 (en) | 2009-02-12 |
| CN101361968B (zh) | 2011-08-03 |
| CN101361968A (zh) | 2009-02-11 |
| US10786551B2 (en) | 2020-09-29 |
| US20180028614A1 (en) | 2018-02-01 |
| AU2008284116B2 (en) | 2014-01-09 |
| US20140377222A1 (en) | 2014-12-25 |
| US20110262385A1 (en) | 2011-10-27 |
| JP2010535786A (ja) | 2010-11-25 |
| EP2185202A4 (en) | 2013-11-06 |
| EP2185202A1 (en) | 2010-05-19 |
| EP2185202B1 (en) | 2015-05-06 |
| CA2695734C (en) | 2017-02-14 |
| WO2009020844A1 (en) | 2009-02-12 |
| AU2008284116A1 (en) | 2009-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5546453B2 (ja) | 脂肪肝疾患の治療におけるインターロイキン−２２の使用 | |
| TWI705071B (zh) | 經修飾之fgf-21多肽及其用途 | |
| JP6325585B2 (ja) | インターロイキン−２２のウイルス性肝炎の治療における応用 | |
| US7718604B2 (en) | Use of IL-22 for the treatment of conditions of metabolic disorders | |
| TWI835773B (zh) | 組合物及使用方法 | |
| JP2022532332A (ja) | 代謝性疾患を治療するための融合タンパク質 | |
| JP6825181B2 (ja) | 膵炎を治療するための薬剤の製造におけるｉｌ−２２二量体の使用 | |
| CN110087666B (zh) | 用于治疗糖尿病、高血压和高胆固醇血症的组合物和方法 | |
| TWI359030B (en) | Treatment of cellular proliferative disorders | |
| WO2019201333A1 (zh) | Glp-1衍生物及其治疗用途 | |
| CN101219208B (zh) | 白介素-22的医药用途 | |
| TW202029979A (zh) | Glp-2融合多肽及用於治療及預防胃腸病症之用途 | |
| JPH03127741A (ja) | 悪性腫瘍治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110801 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110801 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130521 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130521 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130905 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140106 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140107 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140128 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140128 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140226 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140319 |
|
| 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: 20140501 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140513 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5546453 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |