TWI317283B - Pharmaceutical composition comprising botulinum toxin and recombinant human serum albumin - Google Patents
Pharmaceutical composition comprising botulinum toxin and recombinant human serum albumin Download PDFInfo
- Publication number
- TWI317283B TWI317283B TW095148526A TW95148526A TWI317283B TW I317283 B TWI317283 B TW I317283B TW 095148526 A TW095148526 A TW 095148526A TW 95148526 A TW95148526 A TW 95148526A TW I317283 B TWI317283 B TW I317283B
- Authority
- TW
- Taiwan
- Prior art keywords
- botulinum toxin
- pharmaceutical composition
- toxin
- protein
- albumin
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 154
- 108030001720 Bontoxilysin Proteins 0.000 title claims description 147
- 229940053031 botulinum toxin Drugs 0.000 title claims description 137
- 108091006905 Human Serum Albumin Proteins 0.000 title claims description 13
- 102000008100 Human Serum Albumin Human genes 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 claims description 66
- 108010057266 Type A Botulinum Toxins Proteins 0.000 claims description 48
- 229940094657 botulinum toxin type a Drugs 0.000 claims description 48
- 239000003085 diluting agent Substances 0.000 claims description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229940071643 prefilled syringe Drugs 0.000 claims 1
- 108700012359 toxins Proteins 0.000 description 80
- 235000018102 proteins Nutrition 0.000 description 74
- 102000004169 proteins and genes Human genes 0.000 description 74
- 108090000623 proteins and genes Proteins 0.000 description 74
- 229920001282 polysaccharide Polymers 0.000 description 73
- 239000005017 polysaccharide Substances 0.000 description 73
- 150000004676 glycans Chemical class 0.000 description 72
- 231100000765 toxin Toxicity 0.000 description 69
- 239000003053 toxin Substances 0.000 description 67
- 102000009027 Albumins Human genes 0.000 description 64
- 108010088751 Albumins Proteins 0.000 description 64
- 235000001014 amino acid Nutrition 0.000 description 51
- 150000001413 amino acids Chemical group 0.000 description 50
- 229920002472 Starch Polymers 0.000 description 39
- 238000009472 formulation Methods 0.000 description 39
- 239000008107 starch Substances 0.000 description 38
- 235000019698 starch Nutrition 0.000 description 38
- 239000002581 neurotoxin Substances 0.000 description 34
- 231100000618 neurotoxin Toxicity 0.000 description 34
- 239000004480 active ingredient Substances 0.000 description 31
- 101710138657 Neurotoxin Proteins 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 24
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 24
- 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 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 18
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 18
- 239000008103 glucose Substances 0.000 description 17
- 229940050526 hydroxyethylstarch Drugs 0.000 description 17
- 239000003381 stabilizer Substances 0.000 description 16
- 235000000346 sugar Nutrition 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 101710117542 Botulinum neurotoxin type A Proteins 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 229940089093 botox Drugs 0.000 description 13
- 239000004471 Glycine Substances 0.000 description 12
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 11
- 239000004472 Lysine Substances 0.000 description 11
- -1 polysaccharides Chemical class 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 108010010803 Gelatin Proteins 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000004925 denaturation Methods 0.000 description 10
- 230000036425 denaturation Effects 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000008273 gelatin Substances 0.000 description 10
- 229920000159 gelatin Polymers 0.000 description 10
- 235000019322 gelatine Nutrition 0.000 description 10
- 235000011852 gelatine desserts Nutrition 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 241000193155 Clostridium botulinum Species 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 230000008901 benefit Effects 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000000178 monomer Substances 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003755 preservative agent Substances 0.000 description 7
- 150000008163 sugars Chemical class 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 102000029797 Prion Human genes 0.000 description 6
- 108091000054 Prion Proteins 0.000 description 6
- 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 6
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000007927 intramuscular injection Substances 0.000 description 6
- 238000010255 intramuscular injection Methods 0.000 description 6
- 230000002335 preservative effect Effects 0.000 description 6
- 230000000087 stabilizing effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 150000002016 disaccharides Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 239000012669 liquid formulation Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 208000003508 Botulism Diseases 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 241000193403 Clostridium Species 0.000 description 4
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 101710154606 Hemagglutinin Proteins 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 4
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 4
- 101710176177 Protein A56 Proteins 0.000 description 4
- 102000007562 Serum Albumin Human genes 0.000 description 4
- 108010071390 Serum Albumin Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 108010055044 Tetanus Toxin Proteins 0.000 description 4
- 235000021120 animal protein Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 231100001102 clostridial toxin Toxicity 0.000 description 4
- 125000001033 ether group Chemical group 0.000 description 4
- 229940064366 hespan Drugs 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000012678 infectious agent Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 235000013372 meat Nutrition 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229920000945 Amylopectin Polymers 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 3
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 108010039918 Polylysine Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229940027278 hetastarch Drugs 0.000 description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 239000002574 poison Substances 0.000 description 3
- 229920001308 poly(aminoacid) Polymers 0.000 description 3
- 229920000656 polylysine Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 108010074523 rimabotulinumtoxinB Proteins 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 239000004606 Fillers/Extenders Substances 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 238000003916 acid precipitation Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000010836 blood and blood product Substances 0.000 description 2
- 229940125691 blood product Drugs 0.000 description 2
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001914 calming effect Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 229960004203 carnitine Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical group OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 208000013403 hyperactivity Diseases 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- ULXUXOJWHHYKQL-UHFFFAOYSA-M sodium 4-acetyloxy-4-oxobutanoate Chemical compound [Na+].CC(=O)OC(=O)CCC([O-])=O ULXUXOJWHHYKQL-UHFFFAOYSA-M 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- YKABXFFXSJHQRB-RGMNGODLSA-N (2s)-2-acetamido-4-methylsulfanylbutanoic acid;sodium Chemical group [Na].CSCC[C@@H](C(O)=O)NC(C)=O YKABXFFXSJHQRB-RGMNGODLSA-N 0.000 description 1
- BTUDTSGOEFVJTD-WCCKRBBISA-N (2s)-2-amino-4-methylsulfanylbutanoic acid;sodium Chemical compound [Na].CSCC[C@H](N)C(O)=O BTUDTSGOEFVJTD-WCCKRBBISA-N 0.000 description 1
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 1
- CKFRJFUTYHQHCA-UHFFFAOYSA-N 2-phosphanylethanol Chemical compound OCCP CKFRJFUTYHQHCA-UHFFFAOYSA-N 0.000 description 1
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 description 1
- 101800000263 Acidic protein Proteins 0.000 description 1
- 101001023095 Anemonia sulcata Delta-actitoxin-Avd1a Proteins 0.000 description 1
- 101000641989 Araneus ventricosus Kunitz-type U1-aranetoxin-Av1a Proteins 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241001674044 Blattodea Species 0.000 description 1
- CWINKGJYRNIHLM-UHFFFAOYSA-N CC(=O)NNCCC1=CNC2=CC=CC=C21 Chemical compound CC(=O)NNCCC1=CNC2=CC=CC=C21 CWINKGJYRNIHLM-UHFFFAOYSA-N 0.000 description 1
- 101001028691 Carybdea rastonii Toxin CrTX-A Proteins 0.000 description 1
- 101000685083 Centruroides infamatus Beta-toxin Cii1 Proteins 0.000 description 1
- 101000685085 Centruroides noxius Toxin Cn1 Proteins 0.000 description 1
- 101001028688 Chironex fleckeri Toxin CfTX-1 Proteins 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 101000644407 Cyriopagopus schmidti U6-theraphotoxin-Hs1a Proteins 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
- 125000002353 D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- AQZGPSLYZOOYQP-UHFFFAOYSA-N Diisoamyl ether Chemical compound CC(C)CCOCCC(C)C AQZGPSLYZOOYQP-UHFFFAOYSA-N 0.000 description 1
- 206010013554 Diverticulum Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 208000004929 Facial Paralysis Diseases 0.000 description 1
- 101000941893 Felis catus Leucine-rich repeat and calponin homology domain-containing protein 1 Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 101000679608 Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) Cysteine rich necrotrophic effector Tox1 Proteins 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 241001520913 Phyllostachys edulis Species 0.000 description 1
- 235000003570 Phyllostachys pubescens Nutrition 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 208000032561 Rare neurodegenerative disease Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000004874 Synaptophysin Human genes 0.000 description 1
- 108090001076 Synaptophysin Proteins 0.000 description 1
- 206010044074 Torticollis Diseases 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
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 101710102828 Vesicle-associated protein Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 108010069022 botulinum toxin type D Proteins 0.000 description 1
- 108010069023 botulinum toxin type E Proteins 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 201000002866 cervical dystonia Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229920005565 cyclic polymer Polymers 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000002309 gasification Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 108091006034 isomerized proteins Proteins 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002772 monosaccharides Chemical group 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 208000016334 muscle symptom Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000000720 neurosecretory effect Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 229940124272 protein stabilizer Drugs 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000002683 reaction inhibitor Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000003019 respiratory muscle Anatomy 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000002795 scorpion venom Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- ATCJTYORYKLVIA-SRXJVYAUSA-N vamp regimen Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.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.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(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C(C45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 ATCJTYORYKLVIA-SRXJVYAUSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Physical Education & Sports Medicine (AREA)
- Inorganic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50014700A | 2000-02-08 | 2000-02-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200711657A TW200711657A (en) | 2007-04-01 |
| TWI317283B true TWI317283B (en) | 2009-11-21 |
Family
ID=23988236
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW095148526A TWI317283B (en) | 2000-02-08 | 2001-02-06 | Pharmaceutical composition comprising botulinum toxin and recombinant human serum albumin |
| TW090102480A TWI282739B (en) | 2000-02-08 | 2001-02-06 | Pharmaceutical compositions of stabilized botulinum toxin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW090102480A TWI282739B (en) | 2000-02-08 | 2001-02-06 | Pharmaceutical compositions of stabilized botulinum toxin |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US20020064536A1 (enExample) |
| EP (4) | EP1586329A1 (enExample) |
| JP (7) | JP2003522154A (enExample) |
| KR (3) | KR100753765B1 (enExample) |
| CN (2) | CN1258379C (enExample) |
| AR (1) | AR027391A1 (enExample) |
| AT (2) | ATE293988T1 (enExample) |
| AU (2) | AU3331501A (enExample) |
| BR (1) | BR0108173A (enExample) |
| CA (3) | CA2494241C (enExample) |
| CY (1) | CY1108007T1 (enExample) |
| DE (2) | DE60125986T3 (enExample) |
| DK (3) | DK1253932T3 (enExample) |
| ES (3) | ES2275992T5 (enExample) |
| MX (1) | MXPA02007519A (enExample) |
| NZ (2) | NZ530779A (enExample) |
| PT (3) | PT1253932E (enExample) |
| TW (2) | TWI317283B (enExample) |
| WO (1) | WO2001058472A2 (enExample) |
Families Citing this family (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW574036B (en) * | 1998-09-11 | 2004-02-01 | Elan Pharm Inc | Stable liquid compositions of botulinum toxin |
| US8632785B2 (en) * | 2000-02-08 | 2014-01-21 | Allergan, Inc. | Clostridial toxin pharmaceutical composition containing a gelatin fragment |
| CA2494241C (en) * | 2000-02-08 | 2011-06-14 | Allergan, Inc. | Botulinum toxin pharmaceutical compositions |
| US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
| DE10035156A1 (de) * | 2000-07-19 | 2002-02-07 | Biotecon Ges Fuer Biotechnologische Entwicklung & Consulting Mbh | Proteinkomplex als Vehikel für oral verfügbare Protein-Arzneimittel |
| US6423319B1 (en) * | 2000-10-04 | 2002-07-23 | Allergan Sales, Inc. | Methods for treating muscle injuries |
| DE10149030A1 (de) * | 2001-10-05 | 2003-04-10 | Viscum Ag | Stabile galenische gefriergetrocknete Arzneimittelzubereitung von rViscumin |
| US7140371B2 (en) * | 2002-03-14 | 2006-11-28 | Allergan, Inc. | Surface topography method for determining effects of a botulinum toxin upon a muscle and for comparing botulinum toxins |
| EP1491205A4 (en) * | 2002-03-29 | 2007-04-25 | Chemo Sero Therapeut Res Inst | MEANS FOR THE TREATMENT OF HYPERMYOTONIA |
| US7691394B2 (en) | 2002-05-28 | 2010-04-06 | Botulinum Toxin Research Associates, Inc. | High-potency botulinum toxin formulations |
| US7459164B2 (en) | 2002-05-28 | 2008-12-02 | Botulinum Toxin Research Associates, Inc. | Composition for therapeutic and cosmetic botulinum toxin |
| US7238357B2 (en) * | 2002-11-05 | 2007-07-03 | Allergan, Inc. | Methods for treating ulcers and gastroesophageal reflux disease |
| MXPA05006690A (es) * | 2002-12-20 | 2006-02-17 | Botulinum Toxin Res Ass Inc | Composiciones farmaceuticas de toxina botulinica mejoradas. |
| US20050008661A1 (en) * | 2003-03-31 | 2005-01-13 | Fereira Pamela J. | Non-aqueous single phase vehicles and formulations utilizing such vehicles |
| US7220422B2 (en) * | 2003-05-20 | 2007-05-22 | Allergan, Inc. | Methods and compositions for treating eye disorders |
| FR2855177B1 (fr) * | 2003-05-23 | 2005-07-08 | Raymond Robert | Composition contenant des acides nucleiques lyophilises en presence de collagene et de disaccharides |
| US7160699B2 (en) | 2003-09-25 | 2007-01-09 | Allergan, Inc. | Media for clostridium bacterium and processes for obtaining a clostridial toxin |
| US7148041B2 (en) * | 2003-09-25 | 2006-12-12 | Allergan, Inc. | Animal product free media and processes for obtaining a botulinum toxin |
| US7452697B2 (en) | 2003-09-25 | 2008-11-18 | Allergan, Inc. | Chromatographic method and system for purifying a botulinum toxin |
| US20100266638A1 (en) | 2004-02-26 | 2010-10-21 | Allergan, Inc. | Headache treatment method |
| US9078892B2 (en) * | 2004-02-26 | 2015-07-14 | Allergan, Inc. | Methods for treating pain and for treating a medication overuse disorder |
| US20050191321A1 (en) | 2004-02-26 | 2005-09-01 | Allergan, Inc. | Methods for treating headache |
| US7691381B2 (en) | 2004-04-15 | 2010-04-06 | Allergan, Inc. | Stabilized biodegradable neurotoxin implants |
| RU2255761C1 (ru) * | 2004-07-01 | 2005-07-10 | Общество с ограниченной ответственностью "Токсины и сопутствующие продукты" | Препарат для лечения мышечных дистоний из токсина культуры clostridium botulinum и способ его получения |
| GB2416122A (en) † | 2004-07-12 | 2006-01-18 | Ipsen Ltd | Botulinum neurotoxin composition |
| BRPI0513850A (pt) | 2004-07-26 | 2008-05-20 | Merz Pharma Gmbh & Co Kgaa | composição terapêutica com uma neurotoxina botulìnica |
| EP2813239B1 (en) * | 2004-08-04 | 2017-03-22 | Ipsen Biopharm Limited | Pharmaceutical composition containing botulinum neurotoxin A2 |
| US20080102090A1 (en) * | 2004-08-04 | 2008-05-01 | Naveed Panjwani | Pharmaceutical Compositon Containing Botulinum Neurotoxin A2 |
| WO2006073410A1 (en) * | 2005-01-03 | 2006-07-13 | Botulinum Toxin Research Associates, Inc. | Compositions, methods and devices for preparing less painful botulinum toxin formulations |
| US7838011B2 (en) | 2005-02-14 | 2010-11-23 | Pankaj Modi | Stabilized protein compositions for topical administration and methods of making same |
| US7727537B2 (en) | 2005-02-14 | 2010-06-01 | Dpm Therapeutics Corp. | Stabilized compositions for topical administration and methods of making same |
| BRPI0608249A2 (pt) * | 2005-03-03 | 2009-12-08 | Revance Therapeutics Inc | formulação, método para aplicação tópica e kit para distribuição transdérmica de toxina botulìnica |
| CN1930186A (zh) * | 2005-03-03 | 2007-03-14 | 阿勒根公司 | 为获得梭菌毒素的梭菌细菌培养基及方法 |
| US8926991B2 (en) * | 2005-06-14 | 2015-01-06 | Botulinum Toxin Research Associates, Inc. | Botulinum toxin and the treatment of primary disorders of mood and affect |
| US20230390368A1 (en) * | 2005-06-27 | 2023-12-07 | Revance Therapeutics, Inc. | Methods of Treating Cervical Dystonia in a Subject Having Underlying Condition(s) |
| US20070027105A1 (en) | 2005-07-26 | 2007-02-01 | Alza Corporation | Peroxide removal from drug delivery vehicle |
| US8323666B2 (en) * | 2005-08-01 | 2012-12-04 | Allergan, Inc. | Botulinum toxin compositions |
| FR2889936B1 (fr) | 2005-09-01 | 2007-12-21 | Sod Conseils Rech Applic | Methode pour quantifier une neurotoxine cholinergique dans un echantillon |
| US7744904B1 (en) | 2005-09-26 | 2010-06-29 | B.B. Scientific L.L.C. | Stabilization of Clostridium botulinum neurotoxin complex |
| AU2013202329B2 (en) * | 2005-10-06 | 2016-04-14 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
| US8168206B1 (en) * | 2005-10-06 | 2012-05-01 | Allergan, Inc. | Animal protein-free pharmaceutical compositions |
| US8137677B2 (en) * | 2005-10-06 | 2012-03-20 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
| WO2007044809A2 (en) * | 2005-10-11 | 2007-04-19 | Botulinum Toxin Research Associates, Inc. | Albumin-free botulinum toxin based pharmaceutical compositions containing a hyaluronidase and methods of use |
| CN100384993C (zh) * | 2005-11-02 | 2008-04-30 | 浙江大学 | 提高地衣芽孢杆菌zjuel31410弹性蛋白酶稳定性的方法 |
| FR2896693B1 (fr) * | 2006-01-27 | 2008-03-14 | Sod Conseils Rech Applic | Composition comprenant plusieurs toxines botuliques |
| DE102006019447A1 (de) * | 2006-04-24 | 2007-10-25 | Dressler, Dirk, Dr. | Markierung von Botulinum Toxin |
| US9175283B2 (en) | 2006-05-31 | 2015-11-03 | Genzyme Corporation | Use polysaccharides for promotion of enzymatic activity |
| FR2902341B1 (fr) | 2006-06-16 | 2011-02-25 | Scras | Utilisation therapeutique simultanee, separee ou etalee dans le temps d'au moins une neurotoxine botulique, et d'au moins un derive opiace |
| FR2907680B1 (fr) | 2006-10-27 | 2012-12-28 | Scras | Utilisation therapeutique d'au moins une neurotoxine botulique dans le traitement de la douleur induite par au moins un agent anti-cancereux |
| FR2910327B1 (fr) | 2006-12-22 | 2013-04-26 | Scras | Utilisation d'au moins une neurotoxine botulique pour traiter la douleur induite par les traitements therapeutiques du virus du sida. |
| CN102988995A (zh) * | 2006-12-29 | 2013-03-27 | 雷文斯治疗公司 | 用源自hiv-tat的多肽片段稳定的肉毒杆菌毒素的组合物及其局部施用和透皮递送的方法 |
| GB0705245D0 (en) | 2007-03-19 | 2007-04-25 | Stabilitech Ltd | Stable biological products |
| JP2010529155A (ja) * | 2007-06-13 | 2010-08-26 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 出血性疾患の治療及び予防的処置における血管外投与のためのｖｗｆ安定化ｆｖｉｉｉ製剤及びｆｖｉｉｉなしのｖｗｆ製剤の使用 |
| CA2690773C (en) * | 2007-07-10 | 2013-09-17 | Medy-Tox, Inc. | Pharmaceutical liquid composition of botulinum toxin with improved stability |
| US7473429B1 (en) * | 2007-07-27 | 2009-01-06 | Renfroe J Ben | Method for treatment of laminitis in animals |
| JP2009132686A (ja) * | 2007-10-26 | 2009-06-18 | Okayama Univ | ボツリヌス毒素由来のポリペプチド及びボツリヌス毒素の検出方法 |
| EP2072039A1 (en) | 2007-12-21 | 2009-06-24 | Merz Pharma GmbH & Co.KGaA | Use of a neurotoxic component of Clostridium botulinum toxin complex to reduce or prevent side effects |
| EP2072057A1 (en) | 2007-12-21 | 2009-06-24 | Merz Pharma GmbH & Co.KGaA | Early administration of Botulinum toxin in the treatment of cerebrovascular event and spinal cord injury |
| US9107815B2 (en) | 2008-02-22 | 2015-08-18 | Allergan, Inc. | Sustained release poloxamer containing pharmaceutical compositions |
| FR2930447B1 (fr) | 2008-04-25 | 2010-07-30 | Sod Conseils Rech Applic | Utilisation therapeutique d'au moins une neurotoxine botulique dans le traitement de la douleur dans le cas de la neuropathie diabetique |
| US20100034854A1 (en) * | 2008-08-05 | 2010-02-11 | Solstice Neurosciences, Inc. | Compositions of activated botulinum holotoxin type B (150 KD) |
| WO2010016895A1 (en) * | 2008-08-05 | 2010-02-11 | Solstice Neurosciences, Inc. | Compositions of activated botulinum toxin type b |
| WO2010051039A1 (en) * | 2008-11-03 | 2010-05-06 | Solstice Neurosciences, Inc. | Compositions of activated botulinum toxin type b |
| WO2010051038A1 (en) * | 2008-11-03 | 2010-05-06 | Solstice Neurosciences, Inc. | Compositions of activated botulinum holotoxin type b (150 kd) |
| WO2010096134A1 (en) | 2008-12-04 | 2010-08-26 | Botulinum Toxin Research Associates, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
| KR20160103551A (ko) * | 2008-12-10 | 2016-09-01 | 알러간, 인코포레이티드 | 클로스트리디움 독소 약제학적 조성물 |
| HRP20180739T1 (hr) | 2008-12-31 | 2018-06-29 | Revance Therapeutics, Inc. | Injekcijske formulacije botulinskog toksina |
| US20100184685A1 (en) * | 2009-01-19 | 2010-07-22 | Zavala Jr Gerardo | Systems and methods for treating post- operative, acute, and chronic pain using an intra-muscular catheter administrated combination of a local anesthetic and a neurotoxin protein |
| EP2248518B1 (en) | 2009-04-17 | 2013-01-16 | Merz Pharma GmbH & Co. KGaA | Formulation for stabilizing proteins, peptides or mixtures thereof. |
| CA2766521C (en) | 2009-06-25 | 2020-07-21 | Revance Therapeutics, Inc. | Albumin-free botulinum toxin formulations |
| US8129139B2 (en) | 2009-07-13 | 2012-03-06 | Allergan, Inc. | Process for obtaining botulinum neurotoxin |
| WO2011112996A2 (en) * | 2010-03-12 | 2011-09-15 | Surmodics, Inc. | Injectable drug delivery system |
| JP5769379B2 (ja) * | 2010-03-17 | 2015-08-26 | グンゼ株式会社 | Ｄａｎｃｅタンパク質溶液 |
| CN103140205A (zh) * | 2010-10-06 | 2013-06-05 | 阿勒根公司 | 用于肉毒杆菌毒素的储藏和后续处理的系统 |
| EP2627318B1 (en) | 2010-10-12 | 2017-08-16 | Merz Pharma GmbH & Co. KGaA | Formulation suitable for stabilizing proteins, which is free of mammalian excipients |
| BR112013025256B1 (pt) * | 2011-03-31 | 2022-01-18 | Medy-Tox Inc | Preparação liofilizada farmacêutica |
| KR101135486B1 (ko) | 2011-05-25 | 2012-04-13 | 함종욱 | 보툴리눔 에이형 독소의 액상제품 |
| US9393291B2 (en) | 2012-04-12 | 2016-07-19 | Botulinum Toxin Research Associates, Inc. | Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds |
| US11484580B2 (en) | 2014-07-18 | 2022-11-01 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
| US9901627B2 (en) | 2014-07-18 | 2018-02-27 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
| CN104189891B (zh) * | 2014-08-15 | 2016-03-30 | 北京四环生物制药有限公司 | 一种不含人血清蛋白的重组人促红素制剂 |
| JP6798993B2 (ja) | 2014-12-23 | 2020-12-09 | メルツ ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディト ゲゼルシャフト アウフ アクティーン | ボツリヌス毒素プレフィルド容器 |
| WO2016124213A1 (en) * | 2015-02-03 | 2016-08-11 | Merz Pharma Gmbh & Co. Kgaa | Botulinum toxin prefilled container |
| SG10202004337WA (en) | 2015-10-29 | 2020-06-29 | Revance Therapeutics Inc | Injectable botulinum toxin formulations and methods of use thereof having long duration of therapeutic or cosmetic effect |
| WO2017188618A1 (en) * | 2016-04-26 | 2017-11-02 | Korea Prime Pharm Co., Ltd. | A novel composition comprising botulinum toxin |
| EP4026532B1 (en) * | 2016-05-27 | 2025-11-26 | Ipsen Biopharm Limited | Liquid neurotoxin formulation stabilized with tryptophan or tyrosine |
| WO2018038585A1 (ko) * | 2016-08-26 | 2018-03-01 | 주식회사 에이비바이오 | 보툴리눔 독소 및 안정화제를 포함하는 액상 제형 및 이의 제조방법 |
| WO2018038301A1 (en) * | 2016-08-26 | 2018-03-01 | Hugel Inc. | Stabilized liquid formulation of botulinum toxin and preparation method thereof |
| HUE046449T2 (hu) | 2016-09-13 | 2020-03-30 | Allergan Inc | Stabilizált, nem fehérje eredetû, clostridiális toxin készítmények |
| WO2019046311A1 (en) | 2017-08-28 | 2019-03-07 | Revance Therapeutics, Inc. | TRANSMUCOSAL COMPOSITIONS OF BOTULINUM TOXIN, KITS AND METHODS FOR TREATING BLADDER DISORDERS |
| KR20190038292A (ko) * | 2017-09-29 | 2019-04-08 | 한국프라임제약주식회사 | 효능 지속시간이 연장된 보툴리눔 독소 조성물 |
| KR102657046B1 (ko) * | 2017-11-17 | 2024-04-15 | 스위디쉬 오르펀 바이오비트럼 에이비 (피유비엘) | 이온 교환 물질을 갖춘 주사기 조립체 |
| KR102063475B1 (ko) * | 2018-02-22 | 2020-01-09 | 주식회사 에이비바이오 | 보툴리눔 독소, 안정화제, 및 국소마취제를 포함하는 액상 제형 및 이의 제조방법 |
| WO2020111852A1 (ko) | 2018-11-30 | 2020-06-04 | 주식회사 휴온스글로벌 | 보툴리눔 독소의 안정화 액상 조성물 |
| KR102259423B1 (ko) * | 2018-11-30 | 2021-06-02 | 주식회사 휴온스바이오파마 | 보툴리눔 독소의 안정화 액상 조성물 |
| KR20220140711A (ko) | 2020-01-13 | 2022-10-18 | 듀렉트 코퍼레이션 | 불순물이 감소된 지속 방출 약물 전달 시스템 및 관련 방법 |
| KR102404217B1 (ko) * | 2020-04-08 | 2022-06-02 | (주)메디톡스 | 토출 속도 조절이 용이하고 안정한 보툴리눔 독소 사전충전된 주사기 제형 |
| WO2021206360A1 (ko) * | 2020-04-08 | 2021-10-14 | (주)메디톡스 | 토출 속도 조절이 용이하고 안정한 보툴리눔 독소 사전충전된 주사기 제형 |
| CN111675754A (zh) * | 2020-05-19 | 2020-09-18 | 四川一埃科技有限公司 | 一种肉毒毒素蛋白晶体结构及晶体制备方法和解析方法 |
| KR20230145053A (ko) | 2021-01-12 | 2023-10-17 | 듀렉트 코퍼레이션 | 지속 방출 약물 전달 시스템 및 관련 방법 |
| KR20250003215A (ko) | 2023-06-30 | 2025-01-07 | 주식회사 휴온스바이오파마 | 폴리솔베이트 20 및 세린을 포함하는 보툴리눔 독소의 안정화 액상 조성물 |
| WO2025059665A1 (en) | 2023-09-15 | 2025-03-20 | Revance Therapeutics, Inc. | Serial treatment with botulinum toxin for cervical dystonia |
| WO2025064729A1 (en) | 2023-09-19 | 2025-03-27 | Revance Therapeutics, Inc. | Treatment with botulinum toxin in patients in need of a rapid onset cosmetic effect and smoother skin appearance |
| CN118697853B (zh) * | 2024-06-27 | 2025-05-02 | 河北封章生物科技有限公司 | 一种稳定性提高的肉毒素制剂 |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5625041A (en) * | 1990-09-12 | 1997-04-29 | Delta Biotechnology Limited | Purification of proteins |
| US3269912A (en) * | 1963-04-08 | 1966-08-30 | Boehringer & Soehne Gmbh | Aluminum oxide depot vaccines |
| US3758382A (en) * | 1968-07-26 | 1973-09-11 | Us Navy | Ve agent process of freezing blood using a hydroxyalkyl starch as cryoprotecti |
| GB1514720A (en) * | 1974-10-07 | 1978-06-21 | Secr Defence | Preparation of hydroxyethyl starch |
| DE2457047C3 (de) * | 1974-12-03 | 1979-10-31 | Behringwerke Ag, 3550 Marburg | Verfahren zur Herstellung eines Derivates der leichten Kette des Tetanustoxins, dessen Verwendung zur Tetanusprophylaxe |
| NZ199722A (en) * | 1981-02-25 | 1985-12-13 | Genentech Inc | Dna transfer vector for expression of exogenous polypeptide in yeast;transformed yeast strain |
| US4391801A (en) * | 1981-10-29 | 1983-07-05 | Cutter Laboratories, Inc. | Plasma protein fraction substantially free of acetate ions |
| US4457916A (en) * | 1982-08-31 | 1984-07-03 | Asahi Kasei Kogyo Kabushiki Kaisha | Method for stabilizing Tumor Necrosis Factor and a stable aqueous solution or powder containing the same |
| JPS5959625A (ja) * | 1982-09-28 | 1984-04-05 | Dainippon Pharmaceut Co Ltd | ガン壊死因子を安定化する方法 |
| HU188847B (en) * | 1983-02-22 | 1986-05-28 | Human Oltoanyagtermeloe Es Kutato Intezet,Hu | Process for producing liophylized combined vaccines |
| JPS59163313A (ja) * | 1983-03-09 | 1984-09-14 | Teijin Ltd | 経鼻投与用ペプチドホルモン類組成物 |
| EP0150067A3 (en) * | 1984-01-23 | 1986-12-30 | Takeda Chemical Industries, Ltd. | Stable composition of gamma-interferon |
| JPS61161222A (ja) * | 1985-01-09 | 1986-07-21 | Takeda Chem Ind Ltd | γ型インタ−フエロンフラグメントの組成物 |
| JPS60258125A (ja) * | 1984-06-06 | 1985-12-20 | Hayashibara Biochem Lab Inc | 蛋白性生理活性物質を含有する水溶性乾燥物 |
| US4597966A (en) * | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
| JPS61194034A (ja) * | 1985-02-25 | 1986-08-28 | Teijin Ltd | 経鼻投与用粉末状組成物 |
| US4962091A (en) * | 1986-05-23 | 1990-10-09 | Syntex (U.S.A.) Inc. | Controlled release of macromolecular polypeptides |
| DE3621828A1 (de) * | 1986-06-28 | 1988-01-14 | Biotest Pharma Gmbh | Stabilisierung eines fuer therapeutische zwecke, insbesondere beim menschen, bestimmten interleukin-2-praeparates sowie dieses praeparat enthaltende stabilisierte waessrige loesung oder feststoff |
| JPH0696536B2 (ja) * | 1988-02-26 | 1994-11-30 | 佐藤製薬株式会社 | 制酸剤含有内用懸濁液 |
| JP2849632B2 (ja) * | 1988-04-08 | 1999-01-20 | 社団法人北里研究所 | ワクチン製剤 |
| FR2630115B1 (fr) * | 1988-04-14 | 1994-10-28 | Merieux Inst | Procede de stabilisation des solutions d'albumine humaine et solution obtenue |
| FR2649991B2 (fr) † | 1988-08-05 | 1994-03-04 | Rhone Poulenc Sante | Utilisation de derives stables du plasmide pkd1 pour l'expression et la secretion de proteines heterologues dans les levures du genre kluyveromyces |
| US5997856A (en) * | 1988-10-05 | 1999-12-07 | Chiron Corporation | Method and compositions for solubilization and stabilization of polypeptides, especially proteins |
| US5919665A (en) * | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
| US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| WO1991012718A1 (en) * | 1990-03-01 | 1991-09-05 | Agouron Pharmaceuticals, Inc. | Enhanced cryopreservation with thermal hysteresis peptide |
| US5401243A (en) * | 1990-08-21 | 1995-03-28 | Associated Synapse Biologics | Controlled administration of chemodenervating pharmaceuticals |
| JPH055065A (ja) * | 1990-08-30 | 1993-01-14 | Warner Lambert Co | 親水性ポリマー及びそれとは異なる親水性物質を含有する新規組成物 |
| US5695956A (en) * | 1990-11-26 | 1997-12-09 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Clostridium perfingens type a enterotoxin toxoid and methods of preparation and use as a vaccine and therapeutic agent |
| JP2916947B2 (ja) * | 1990-11-28 | 1999-07-05 | 興和株式会社 | Ｃｐｂ―ｉの安定化方法及び製剤組成物 |
| US5704297A (en) * | 1991-02-06 | 1998-01-06 | The Dupont Merck Pharmaceutical Company | Dry powder composition of hydroxyethyl starch suitable for reconstitution |
| CA2110899C (en) * | 1991-06-21 | 2006-08-08 | Jacob G. Michael | Orally administrable therapeutic proteins and method of making |
| WO1993000807A1 (en) * | 1991-07-03 | 1993-01-21 | Cryolife, Inc. | Method for stabilization of biomaterials |
| JPH0672891A (ja) * | 1992-08-31 | 1994-03-15 | Green Cross Corp:The | ヒト血清アルブミン含有製剤 |
| CA2138020C (en) * | 1992-06-23 | 1999-02-16 | Eric A. Johnson | Pharmaceutical composition containing botulinum b complex |
| US5445817A (en) * | 1992-08-21 | 1995-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Pertussis toxin used as a carrier protein with non-charged saccharides in conjugate vaccines |
| US5728553A (en) * | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| EP0593176A3 (en) * | 1992-09-28 | 1995-03-01 | Wisconsin Alumni Res Found | Pharmaceutical compositions containing botulinum toxin and method of manufacture. |
| US5466672A (en) * | 1992-12-04 | 1995-11-14 | Ophidian Pharmaceuticals, Inc. | Therapeutic use of clostridium difficile toxin A |
| JP3007785B2 (ja) * | 1993-03-16 | 2000-02-07 | 旭化成工業株式会社 | トロンボモジュリン組成物およびその変性防止方法 |
| US5562907A (en) * | 1993-05-14 | 1996-10-08 | Arnon; Stephen S. | Method to prevent side-effects and insensitivity to the therapeutic uses of toxins |
| CN1102851C (zh) * | 1993-06-04 | 2003-03-12 | 生物时间公司 | 类血浆溶液 |
| US5437291A (en) * | 1993-08-26 | 1995-08-01 | Univ Johns Hopkins | Method for treating gastrointestinal muscle disorders and other smooth muscle dysfunction |
| JP3533687B2 (ja) * | 1993-12-17 | 2004-05-31 | 三菱ウェルファーマ株式会社 | ヒト血清アルブミンの脱色方法 |
| JP3684584B2 (ja) * | 1993-12-17 | 2005-08-17 | 三菱ウェルファーマ株式会社 | ヒト血清アルブミンの脱色方法 |
| US5766605A (en) * | 1994-04-15 | 1998-06-16 | Mount Sinai School Of Medicine Of The City University Of New York | Treatment of autonomic nerve dysfunction with botulinum toxin |
| US5670484A (en) * | 1994-05-09 | 1997-09-23 | Binder; William J. | Method for treatment of skin lesions associated with cutaneous cell-proliferative disorders |
| DE69526340T2 (de) * | 1994-05-09 | 2002-11-14 | William J. Binder | Botulinumtoxin ZUR REDUKTION VON Migraine -KOPFSCHMERZEN |
| JPH07308199A (ja) † | 1994-05-18 | 1995-11-28 | Green Cross Corp:The | ヒト血清アルブミンの製造方法 |
| FI970867A7 (fi) * | 1994-08-04 | 1997-04-08 | Quadrant Drug Delivery Ltd | Kiinteät, annostelusysteemit hallittua vapautumista varten, joihin sys teemeihin molekyylit on sisällytetty ja menetelmät niiden valmistamise ksi |
| WO1996005222A1 (en) * | 1994-08-08 | 1996-02-22 | Wisconsin Alumni Research Foundation | Purification and pharmaceutical compositions containing type g botulinum neurotoxin |
| US5512547A (en) * | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
| US5756468A (en) * | 1994-10-13 | 1998-05-26 | Wisconsin Alumni Research Foundation | Pharmaceutical compositions of botulinum toxin or botulinum neurotoxin and methods of preparation |
| DE69627963T2 (de) * | 1995-06-06 | 2004-03-04 | Pearce, L. Bruce, Cambridge | Verbesserte zusammensetzungen und verfahren zur chemodenervation mit neurotoxinen |
| US5919463A (en) * | 1995-07-07 | 1999-07-06 | Oravax, Inc. | Clostridium difficle toxins as mucosal adjuvants |
| JP3098401B2 (ja) * | 1995-07-12 | 2000-10-16 | 株式会社エルティーティー研究所 | 経鼻投与用製剤 |
| DE19538687A1 (de) * | 1995-10-17 | 1997-04-24 | Boehringer Mannheim Gmbh | Stabile pharmazeutische Darreichungsformen enthaltend Parathormon |
| US5837265A (en) * | 1996-03-08 | 1998-11-17 | The Regents Of The University Of California | Chemically-modified clostridiatoxin with improved properties |
| ATE241695T1 (de) * | 1996-03-13 | 2003-06-15 | Delta Biotechnology Ltd | Gärungs-steuerungssysteme |
| US5721215A (en) * | 1996-03-20 | 1998-02-24 | Allergan | Injectable therapy for control of muscle spasms and pain related to muscle spasms |
| US5908825A (en) * | 1997-01-09 | 1999-06-01 | University Of Maryland At Baltimore | Dosage composition for nasal delivery and method of use of the same |
| JPH10245400A (ja) * | 1997-02-28 | 1998-09-14 | Eiken Chem Co Ltd | トランスフェリンレセプターの安定化方法 |
| JPH10251161A (ja) * | 1997-03-11 | 1998-09-22 | Green Cross Corp:The | 浮腫治療効果増強剤 |
| US6210683B1 (en) * | 1997-09-05 | 2001-04-03 | Merck & Co., Inc. | Stabilizers containing recombinant human serum albumin for live virus vaccines |
| US6051239A (en) * | 1997-10-20 | 2000-04-18 | Thomas Jefferson University | Compositions and methods for systemic delivery of oral vaccines and therapeutic agents |
| ES2179414T3 (es) * | 1997-11-22 | 2003-01-16 | Roche Diagnostics Gmbh | Procedimiento mejorado de estabilizacion de proteinas. |
| US6346519B1 (en) * | 1998-09-09 | 2002-02-12 | Advanced Medical Instruments | Method and composition for treating arthritis |
| TW574036B (en) * | 1998-09-11 | 2004-02-01 | Elan Pharm Inc | Stable liquid compositions of botulinum toxin |
| US6358917B1 (en) * | 1999-08-24 | 2002-03-19 | Jean D. A. Carruthers | Cosmetic use of botulinum toxin for treatment of downturned mouth |
| US6113915A (en) * | 1999-10-12 | 2000-09-05 | Allergan Sales, Inc. | Methods for treating pain |
| US6139845A (en) * | 1999-12-07 | 2000-10-31 | Allergan Sales, Inc. | Method for treating cancer with a neurotoxin |
| US6337075B1 (en) * | 2000-01-11 | 2002-01-08 | Allergan Sales, Inc. | Methods for treating diabetes |
| CA2494241C (en) * | 2000-02-08 | 2011-06-14 | Allergan, Inc. | Botulinum toxin pharmaceutical compositions |
| JP2003009897A (ja) * | 2001-07-03 | 2003-01-14 | Keiji Oguma | ボツリヌス毒素の分離・精製法 |
| MXPA01011542A (es) * | 2001-11-13 | 2003-05-22 | Alcon Inc | Regeneracion del cartilago articular da°ado por la osteoartritis de grado i y ii, mediante la aplicacion intra-articular de una mezcla de hialuronato de sodio y de condroitin sulfato en un vehiculo de gel. |
-
2001
- 2001-02-05 CA CA2494241A patent/CA2494241C/en not_active Expired - Fee Related
- 2001-02-05 CN CNB018046592A patent/CN1258379C/zh not_active Expired - Fee Related
- 2001-02-05 EP EP05006664A patent/EP1586329A1/en not_active Ceased
- 2001-02-05 DK DK01905436T patent/DK1253932T3/da active
- 2001-02-05 PT PT01905436T patent/PT1253932E/pt unknown
- 2001-02-05 AT AT01905436T patent/ATE293988T1/de active
- 2001-02-05 PT PT04029089T patent/PT1514556E/pt unknown
- 2001-02-05 EP EP03025104A patent/EP1398038B2/en not_active Expired - Lifetime
- 2001-02-05 NZ NZ530779A patent/NZ530779A/en not_active IP Right Cessation
- 2001-02-05 CA CA002400318A patent/CA2400318C/en not_active Expired - Fee Related
- 2001-02-05 DE DE60125986T patent/DE60125986T3/de not_active Expired - Lifetime
- 2001-02-05 JP JP2001557580A patent/JP2003522154A/ja active Pending
- 2001-02-05 DK DK04029089.2T patent/DK1514556T3/da active
- 2001-02-05 BR BR0108173-0A patent/BR0108173A/pt not_active IP Right Cessation
- 2001-02-05 KR KR1020027010146A patent/KR100753765B1/ko not_active Expired - Lifetime
- 2001-02-05 WO PCT/US2001/003641 patent/WO2001058472A2/en not_active Ceased
- 2001-02-05 DE DE60110372T patent/DE60110372T2/de not_active Expired - Lifetime
- 2001-02-05 MX MXPA02007519A patent/MXPA02007519A/es active IP Right Grant
- 2001-02-05 DK DK03025104.5T patent/DK1398038T4/da active
- 2001-02-05 EP EP04029089A patent/EP1514556B1/en not_active Expired - Lifetime
- 2001-02-05 NZ NZ520201A patent/NZ520201A/en not_active IP Right Cessation
- 2001-02-05 EP EP01905436A patent/EP1253932B1/en not_active Expired - Lifetime
- 2001-02-05 AU AU3331501A patent/AU3331501A/xx active Pending
- 2001-02-05 PT PT03025104T patent/PT1398038E/pt unknown
- 2001-02-05 CA CA002478621A patent/CA2478621C/en not_active Expired - Lifetime
- 2001-02-05 ES ES03025104T patent/ES2275992T5/es not_active Expired - Lifetime
- 2001-02-05 AT AT04029089T patent/ATE519494T1/de active
- 2001-02-05 ES ES01905436T patent/ES2237551T3/es not_active Expired - Lifetime
- 2001-02-05 CN CNB2004100117577A patent/CN1331532C/zh not_active Expired - Fee Related
- 2001-02-05 ES ES04029089T patent/ES2368061T3/es not_active Expired - Lifetime
- 2001-02-05 AU AU2001233315A patent/AU2001233315B2/en not_active Ceased
- 2001-02-06 TW TW095148526A patent/TWI317283B/zh not_active IP Right Cessation
- 2001-02-06 TW TW090102480A patent/TWI282739B/zh not_active IP Right Cessation
- 2001-02-08 AR ARP010100574A patent/AR027391A1/es not_active Application Discontinuation
-
2002
- 2002-01-14 US US10/047,058 patent/US20020064536A1/en not_active Abandoned
-
2004
- 2004-03-23 JP JP2004084590A patent/JP4118830B2/ja not_active Expired - Lifetime
-
2005
- 2005-03-18 JP JP2005079801A patent/JP2005179375A/ja active Pending
- 2005-07-05 JP JP2005196335A patent/JP2005336201A/ja not_active Withdrawn
-
2006
- 2006-03-14 KR KR1020060023656A patent/KR100665469B1/ko not_active Expired - Fee Related
- 2006-07-04 KR KR1020060062380A patent/KR100799400B1/ko not_active Expired - Fee Related
-
2007
- 2007-03-26 CY CY20071100420T patent/CY1108007T1/el unknown
- 2007-08-15 JP JP2007211802A patent/JP5080902B2/ja not_active Expired - Lifetime
-
2008
- 2008-04-25 US US12/109,486 patent/US20080213315A1/en not_active Abandoned
-
2011
- 2011-07-22 JP JP2011160451A patent/JP2011251988A/ja active Pending
- 2011-10-25 JP JP2011233808A patent/JP2012031194A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI317283B (en) | Pharmaceutical composition comprising botulinum toxin and recombinant human serum albumin | |
| KR100852821B1 (ko) | 보툴리눔 신경독소를 포함하는 치료 조성물 | |
| AU2001233315A1 (en) | Botulinum toxin pharmaceutical compositions | |
| AU2005203171B2 (en) | Botulinum toxin pharmaceutical compositions | |
| AU2008201176B2 (en) | Botulinum toxin pharmaceutical compositions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Expiration of patent term of an invention patent |