DE69929189T2 - Ein Komplex aus Alpha-Fetoprotein (AFP) und einem polyungesättigten Fettsäurederivat zur Behandlung von Immunschwäche - Google Patents
Ein Komplex aus Alpha-Fetoprotein (AFP) und einem polyungesättigten Fettsäurederivat zur Behandlung von Immunschwäche Download PDFInfo
- Publication number
- DE69929189T2 DE69929189T2 DE69929189T DE69929189T DE69929189T2 DE 69929189 T2 DE69929189 T2 DE 69929189T2 DE 69929189 T DE69929189 T DE 69929189T DE 69929189 T DE69929189 T DE 69929189T DE 69929189 T2 DE69929189 T2 DE 69929189T2
- Authority
- DE
- Germany
- Prior art keywords
- afp
- aap
- reversible equilibrium
- complex according
- complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102000013529 alpha-Fetoproteins Human genes 0.000 title claims abstract description 143
- 108010026331 alpha-Fetoproteins Proteins 0.000 title claims abstract description 143
- 230000007812 deficiency Effects 0.000 title claims abstract description 5
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 title claims description 3
- 239000003814 drug Substances 0.000 claims abstract description 7
- 238000011275 oncology therapy Methods 0.000 claims abstract description 3
- 229940124597 therapeutic agent Drugs 0.000 claims abstract 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- 230000002441 reversible effect Effects 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 101000848653 Homo sapiens Tripartite motif-containing protein 26 Proteins 0.000 claims description 9
- 102000046101 human AFP Human genes 0.000 claims description 9
- 206010061598 Immunodeficiency Diseases 0.000 claims description 6
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 6
- 230000007813 immunodeficiency Effects 0.000 claims description 6
- 238000004113 cell culture Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 239000003022 immunostimulating agent Substances 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 208000004235 neutropenia Diseases 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 229940102223 injectable solution Drugs 0.000 claims 1
- 210000003954 umbilical cord Anatomy 0.000 claims 1
- -1 N-arachidonoyl aminoethyl phosphate Chemical compound 0.000 abstract description 7
- 229910019142 PO4 Inorganic materials 0.000 abstract description 5
- 239000010452 phosphate Substances 0.000 abstract description 5
- 230000003308 immunostimulating effect Effects 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 27
- 102000004169 proteins and genes Human genes 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 21
- 241001494479 Pecora Species 0.000 description 18
- 210000003743 erythrocyte Anatomy 0.000 description 18
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 230000028996 humoral immune response Effects 0.000 description 16
- 239000003446 ligand Substances 0.000 description 15
- 210000000952 spleen Anatomy 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 235000021342 arachidonic acid Nutrition 0.000 description 12
- 229940114079 arachidonic acid Drugs 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 229920002684 Sepharose Polymers 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 9
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 239000000693 micelle Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 238000002523 gelfiltration Methods 0.000 description 6
- 210000004989 spleen cell Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 101100012848 Rattus norvegicus Afp gene Proteins 0.000 description 5
- 239000012506 Sephacryl® Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 5
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 4
- 230000001605 fetal effect Effects 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 101150065749 Churc1 gene Proteins 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102100038239 Protein Churchill Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 241000220317 Rosa Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229930003827 cannabinoid Natural products 0.000 description 3
- 239000003557 cannabinoid Substances 0.000 description 3
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000004700 fetal blood Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- RVXUOAXLVOPXJP-UHFFFAOYSA-N 2-cyanoethyl phosphate;pyridin-1-ium Chemical compound C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.[O-]P([O-])(=O)OCCC#N RVXUOAXLVOPXJP-UHFFFAOYSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- WXAXNYYAYJKARR-UHFFFAOYSA-N benzene;2-(1,4-dioxan-2-yl)acetic acid Chemical compound C1=CC=CC=C1.OC(=O)CC1COCCO1 WXAXNYYAYJKARR-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- DVSZKTAMJJTWFG-UHFFFAOYSA-N docosa-2,4,6,8,10,12-hexaenoic acid Chemical class CCCCCCCCCC=CC=CC=CC=CC=CC=CC(O)=O DVSZKTAMJJTWFG-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- YZXBAPSDXZZRGB-UHFFFAOYSA-N icosa-5,8,11,14-tetraenoic acid Chemical compound CCCCCC=CCC=CCC=CCC=CCCCC(O)=O YZXBAPSDXZZRGB-UHFFFAOYSA-N 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000004957 immunoregulator effect Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108010030416 proteoliposomes Proteins 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- YZXBAPSDXZZRGB-CRJVGOJRSA-N (5z,8z,11z,14z)-5,6,8,9,11,12,14,15-octatritioicosa-5,8,11,14-tetraenoic acid Chemical compound CCCCCC(/[3H])=C(/[3H])C\C([3H])=C(\[3H])C\C([3H])=C(\[3H])C\C([3H])=C(\[3H])CCCC(O)=O YZXBAPSDXZZRGB-CRJVGOJRSA-N 0.000 description 1
- SCCCIUGOOQLDGW-UHFFFAOYSA-N 1,1-dicyclohexylurea Chemical compound C1CCCCC1N(C(=O)N)C1CCCCC1 SCCCIUGOOQLDGW-UHFFFAOYSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 1
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- XXGMIHXASFDFSM-UHFFFAOYSA-N Delta9-tetrahydrocannabinol Natural products CCCCCc1cc2OC(C)(C)C3CCC(=CC3c2c(O)c1O)C XXGMIHXASFDFSM-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases 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
- 206010041660 Splenomegaly Diseases 0.000 description 1
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- VVRQWXWJELSAJI-DOFZRALJSA-N [2-aminoethoxy(hydroxy)phosphoryl] (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OP(O)(=O)OCCN VVRQWXWJELSAJI-DOFZRALJSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940114078 arachidonate Drugs 0.000 description 1
- 125000002886 arachidonoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940090949 docosahexaenoic acid Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000007973 glycine-HCl buffer Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000002366 lipolytic effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 235000020978 long-chain polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000002487 multivesicular body Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000009703 regulation of cell differentiation Effects 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005055 short column chromatography Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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)
- Immunology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Marine Sciences & Fisheries (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9802162 | 1998-06-17 | ||
| SE9802162A SE9802162D0 (sv) | 1998-06-17 | 1998-06-17 | Immunostimulating composition |
| PCT/EP1999/004201 WO1999065936A2 (en) | 1998-06-17 | 1999-06-17 | Composition for the treatement of immune deficiencies and methods for its preparation and use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69929189D1 DE69929189D1 (de) | 2006-02-02 |
| DE69929189T2 true DE69929189T2 (de) | 2006-08-31 |
Family
ID=20411743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69929189T Expired - Lifetime DE69929189T2 (de) | 1998-06-17 | 1999-06-17 | Ein Komplex aus Alpha-Fetoprotein (AFP) und einem polyungesättigten Fettsäurederivat zur Behandlung von Immunschwäche |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6599507B2 (enExample) |
| EP (1) | EP1085909B1 (enExample) |
| JP (1) | JP4392991B2 (enExample) |
| AT (1) | ATE314094T1 (enExample) |
| AU (1) | AU748838B2 (enExample) |
| BR (1) | BR9911294B1 (enExample) |
| CA (1) | CA2335079C (enExample) |
| DE (1) | DE69929189T2 (enExample) |
| SE (1) | SE9802162D0 (enExample) |
| WO (1) | WO1999065936A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9802162D0 (sv) | 1998-06-17 | 1998-06-17 | Nomet Management Services Bv | Immunostimulating composition |
| SE9900941D0 (sv) * | 1998-12-23 | 1999-03-16 | Nomet Management Serv Bv | Novel retinoic acid derivatives and their use |
| ATE243701T1 (de) * | 1999-03-16 | 2003-07-15 | Ardenia Investments Ltd | Polyungesättigte fettsäurederivate und deren verwendung in der krebsbehandlung |
| WO2002004467A1 (en) * | 2000-07-12 | 2002-01-17 | Ardenia Investments Ltd. | Novel cytotoxic compounds and their use |
| US20070111936A1 (en) * | 2005-11-15 | 2007-05-17 | Vladimir Pak | Complex of alpha-fetoprotein and inducers of apoptosis for the treatment of cancer |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6096863A (en) * | 1996-08-23 | 2000-08-01 | Regents Of The University Of Minnesota | Self-assembling amphiphiles for construction of peptide secondary structures |
| SE9802162D0 (sv) | 1998-06-17 | 1998-06-17 | Nomet Management Services Bv | Immunostimulating composition |
-
1998
- 1998-06-17 SE SE9802162A patent/SE9802162D0/xx unknown
-
1999
- 1999-06-17 WO PCT/EP1999/004201 patent/WO1999065936A2/en not_active Ceased
- 1999-06-17 AU AU47734/99A patent/AU748838B2/en not_active Ceased
- 1999-06-17 JP JP2000554761A patent/JP4392991B2/ja not_active Expired - Fee Related
- 1999-06-17 AT AT99931090T patent/ATE314094T1/de not_active IP Right Cessation
- 1999-06-17 DE DE69929189T patent/DE69929189T2/de not_active Expired - Lifetime
- 1999-06-17 CA CA002335079A patent/CA2335079C/en not_active Expired - Fee Related
- 1999-06-17 EP EP99931090A patent/EP1085909B1/en not_active Expired - Lifetime
- 1999-06-17 BR BRPI9911294-9A patent/BR9911294B1/pt not_active IP Right Cessation
-
2000
- 2000-12-15 US US09/738,704 patent/US6599507B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1085909A2 (en) | 2001-03-28 |
| EP1085909B1 (en) | 2005-12-28 |
| US6599507B2 (en) | 2003-07-29 |
| WO1999065936A3 (en) | 2000-02-10 |
| BR9911294B1 (pt) | 2012-01-10 |
| HK1035866A1 (en) | 2001-12-14 |
| BR9911294A (pt) | 2002-01-02 |
| AU748838B2 (en) | 2002-06-13 |
| SE9802162D0 (sv) | 1998-06-17 |
| JP2004500315A (ja) | 2004-01-08 |
| CA2335079A1 (en) | 1999-12-23 |
| WO1999065936A2 (en) | 1999-12-23 |
| JP4392991B2 (ja) | 2010-01-06 |
| AU4773499A (en) | 2000-01-05 |
| CA2335079C (en) | 2008-01-08 |
| DE69929189D1 (de) | 2006-02-02 |
| ATE314094T1 (de) | 2006-01-15 |
| US20010034324A1 (en) | 2001-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kumar et al. | Angiogenesis factor from human myocardial infarcts | |
| DE69732225T2 (de) | Verfahren zur Verkapselung von biologisch aktiven Stoffen in Erythrocyten und Gerät dafür | |
| DE69126430T2 (de) | Ligand für das neu-gen-produkt | |
| DE69231062T3 (de) | Morphogen-induzierte Modulation von entzündlichen Antworten | |
| DE3027105A1 (de) | Verfahren zur herstellung eines die proliferation und differenzierung menschlicher granulopoetischer stammzellen stimulierenden faktors | |
| DD209634A5 (de) | Verfahren zur herstellung neuer glykoproteine und deren verwendung in therapeutischen mitteln gegen tumore | |
| DE9390311U1 (de) | Neue Makrophagen mit Eignung als Wirkstoffe von pharmazeutischen Zusammensetzungen | |
| DE3448144C2 (enExample) | ||
| DE69432313T2 (de) | Neuartiges sythetisches Peptil, diese enthaltende Zusammensetzung und Arznei-Zusammensetzung und Arznei gegen das Atemnotsyndrom | |
| DE2635065C2 (de) | Verfahren zur halbkontinuierlichen Behandlung von Gesamtblut zur Herstellung von biologisch aktiven hämatopoetischen Chalonextrakten | |
| DE69117029T2 (de) | Verfahren zur herstellung eines durch einbau einer lipophilen wirksubstanz modifizierten lipoproteins | |
| EP0145005B1 (de) | Lungen-Surfactant, Verfahren zu seiner Herstellung und seine pharmazeutische Verwendung | |
| DE69929189T2 (de) | Ein Komplex aus Alpha-Fetoprotein (AFP) und einem polyungesättigten Fettsäurederivat zur Behandlung von Immunschwäche | |
| DE3109335A1 (de) | Die neue, physiologisch wirksame substanz ebelacton und verfahren zur herstellung derselben | |
| EP0358130A2 (de) | Mittel mit immunsuppressiver Wirkung | |
| DE69228061T2 (de) | Sulfatierte glykolipide, die eine galaktose-3-0-sulfate-gruppierung enthalten, und spezifische fänger für diese für die verwendung in der prophylaxe oder therapie der prädiabetis, diabetis und/oder damit zusammenhängender komplikationen in einem individuum | |
| DE68912582T2 (de) | Anti-hiv-mittel. | |
| AT395017B (de) | Verfahren zur herstellung eines neuen lymphokins (lk 2) sowie verwendung von lk 2 zur herstellung eines pharmazeutischen praeparates | |
| DE69532557T2 (de) | Zubereitung enthaltend Glykane übereinstimmend mit Transferrin Glykaner als aktives Prinzip für die Induktion der Immuntoleranz gegen Antigene | |
| DE60024969T2 (de) | 2-methyl-3-butenyl-1-pyrophosphorsäuresalze und mittel zur behandlung von lymphozyten | |
| DE69909137T2 (de) | Polyungesättigte Fettsäurederivate und deren Verwendung in der Krebsbehandlung | |
| DE3880758T2 (de) | Von monozyten abstammendes gefaesswirksames protein und dessen analogen, verfahren zu seiner gewinnung und ihre verwendungen fuer therapeutische zwecke und zur antikoerperherstellung. | |
| DE69434256T2 (de) | Immunglobulin-Infusion bei der Xenotransplantation | |
| DE3633797C2 (de) | Verfahren zur Gewinnung von biologisch aktiven Eiweissen (Peptiden) aus menschlichem und tierischem Blut (bzw. anderen Körperflüssigkeiten) | |
| WO1989006538A1 (fr) | Procede de preparation d'une substance therapeutiquement active en particulier pour la cicatrisation et en geriatrie et composition therapeutique contenant une telle substance |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8327 | Change in the person/name/address of the patent owner |
Owner name: ARDENIA INVESTMENTS LTD., LONDON, GB |
|
| 8364 | No opposition during term of opposition |