MXPA02007519A - Composiciones farmaceuticas de toxina botulinica. - Google Patents
Composiciones farmaceuticas de toxina botulinica.Info
- Publication number
- MXPA02007519A MXPA02007519A MXPA02007519A MXPA02007519A MXPA02007519A MX PA02007519 A MXPA02007519 A MX PA02007519A MX PA02007519 A MXPA02007519 A MX PA02007519A MX PA02007519 A MXPA02007519 A MX PA02007519A MX PA02007519 A MXPA02007519 A MX PA02007519A
- Authority
- MX
- Mexico
- Prior art keywords
- pharmaceutical composition
- botulinum toxin
- polysaccharide
- composition according
- toxin
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 219
- 108030001720 Bontoxilysin Proteins 0.000 title claims abstract description 157
- 229940053031 botulinum toxin Drugs 0.000 title claims abstract description 140
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 109
- 239000005017 polysaccharide Substances 0.000 claims abstract description 109
- 150000004676 glycans Chemical class 0.000 claims abstract description 108
- 102000009027 Albumins Human genes 0.000 claims abstract description 77
- 108010088751 Albumins Proteins 0.000 claims abstract description 77
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims abstract description 71
- 150000001413 amino acids Chemical class 0.000 claims abstract description 61
- 229940050526 hydroxyethylstarch Drugs 0.000 claims abstract description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 24
- 241000282414 Homo sapiens Species 0.000 claims abstract description 18
- 239000011780 sodium chloride Substances 0.000 claims abstract description 17
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 92
- 108090000623 proteins and genes Proteins 0.000 claims description 92
- 108700012359 toxins Proteins 0.000 claims description 85
- 231100000765 toxin Toxicity 0.000 claims description 81
- 239000003053 toxin Substances 0.000 claims description 80
- 239000000203 mixture Substances 0.000 claims description 62
- 108010057266 Type A Botulinum Toxins Proteins 0.000 claims description 57
- 229940094657 botulinum toxin type a Drugs 0.000 claims description 53
- 238000009472 formulation Methods 0.000 claims description 45
- 239000002581 neurotoxin Substances 0.000 claims description 36
- 231100000618 neurotoxin Toxicity 0.000 claims description 36
- 101710138657 Neurotoxin Proteins 0.000 claims description 33
- 229920002472 Starch Polymers 0.000 claims description 25
- 235000019698 starch Nutrition 0.000 claims description 25
- 239000008107 starch Substances 0.000 claims description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 20
- 230000000087 stabilizing effect Effects 0.000 claims description 18
- 239000004472 Lysine Substances 0.000 claims description 17
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 17
- 230000036425 denaturation Effects 0.000 claims description 14
- 238000004925 denaturation Methods 0.000 claims description 14
- -1 hydroxybutyl Chemical group 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 238000003860 storage Methods 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 11
- 231100000419 toxicity Toxicity 0.000 claims description 11
- 230000001988 toxicity Effects 0.000 claims description 11
- 239000004475 Arginine Substances 0.000 claims description 10
- 108010055044 Tetanus Toxin Proteins 0.000 claims description 10
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 10
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 239000000178 monomer Substances 0.000 claims description 9
- 150000002016 disaccharides Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 229920000945 Amylopectin Polymers 0.000 claims description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
- 229940071643 prefilled syringe Drugs 0.000 claims description 3
- 230000001698 pyrogenic effect Effects 0.000 claims description 3
- 230000002776 aggregation Effects 0.000 claims description 2
- 238000004220 aggregation Methods 0.000 claims description 2
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 abstract description 11
- 239000008280 blood Substances 0.000 abstract description 11
- 235000018102 proteins Nutrition 0.000 description 91
- 235000001014 amino acid Nutrition 0.000 description 52
- 229940027278 hetastarch Drugs 0.000 description 29
- 239000004615 ingredient Substances 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000003381 stabilizer Substances 0.000 description 20
- 101710117542 Botulinum neurotoxin type A Proteins 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 229940089093 botox Drugs 0.000 description 15
- 239000008103 glucose Substances 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 235000000346 sugar Nutrition 0.000 description 12
- 150000001720 carbohydrates Chemical class 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 238000004108 freeze drying Methods 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 230000006641 stabilisation Effects 0.000 description 11
- 238000011105 stabilization Methods 0.000 description 11
- 241000193155 Clostridium botulinum Species 0.000 description 9
- 108010010803 Gelatin Proteins 0.000 description 9
- 108091006905 Human Serum Albumin Proteins 0.000 description 9
- 102000008100 Human Serum Albumin Human genes 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 239000008273 gelatin Substances 0.000 description 9
- 229920000159 gelatin Polymers 0.000 description 9
- 235000019322 gelatine Nutrition 0.000 description 9
- 235000011852 gelatine desserts Nutrition 0.000 description 9
- 102000029797 Prion Human genes 0.000 description 8
- 108091000054 Prion Proteins 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 235000014633 carbohydrates Nutrition 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 108010074523 rimabotulinumtoxinB Proteins 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 6
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 6
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 6
- 229940064366 hespan Drugs 0.000 description 6
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 239000007927 intramuscular injection Substances 0.000 description 6
- 238000010255 intramuscular injection Methods 0.000 description 6
- 239000012669 liquid formulation Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000002797 proteolythic effect Effects 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 5
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 5
- 101710176177 Protein A56 Proteins 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 5
- 231100000518 lethal Toxicity 0.000 description 5
- 230000001665 lethal effect Effects 0.000 description 5
- 229920001308 poly(aminoacid) Polymers 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 150000008163 sugars Chemical class 0.000 description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 206010033799 Paralysis Diseases 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 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 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
- 230000006870 function Effects 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000003508 Botulism Diseases 0.000 description 3
- 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 3
- 125000002353 D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-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
- 102000035195 Peptidases Human genes 0.000 description 3
- 108010039918 Polylysine Proteins 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000010836 blood and blood product Substances 0.000 description 3
- 229940125691 blood product Drugs 0.000 description 3
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 229920000656 polylysine Polymers 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 229960005480 sodium caprylate Drugs 0.000 description 3
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001112695 Clostridiales Species 0.000 description 2
- VPNYRYCIDCJBOM-UHFFFAOYSA-M Glycopyrronium bromide Chemical group [Br-].C1[N+](C)(C)CCC1OC(=O)C(O)(C=1C=CC=CC=1)C1CCCC1 VPNYRYCIDCJBOM-UHFFFAOYSA-M 0.000 description 2
- 241000282412 Homo Species 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
- 241000699670 Mus sp. Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 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
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical group OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 239000013583 drug formulation Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing 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
- 230000002163 immunogen Effects 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000003387 muscular Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000003186 pharmaceutical solution Substances 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
- 230000002035 prolonged effect Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 230000001148 spastic effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-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
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000000722 Akinetic Mutism Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108010086232 Cobra Neurotoxin Proteins Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 229920002527 Glycogen Polymers 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 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
- 201000000251 Locked-in syndrome Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 231100000757 Microbial toxin Toxicity 0.000 description 1
- 208000034819 Mobility Limitation Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- DZTHIGRZJZPRDV-LBPRGKRZSA-N N-acetyl-L-tryptophan Chemical compound C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 DZTHIGRZJZPRDV-LBPRGKRZSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 235000021314 Palmitic acid 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
- 108010010469 Qa-SNARE Proteins Proteins 0.000 description 1
- 108010005730 R-SNARE Proteins Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- 102000002215 Synaptobrevin Human genes 0.000 description 1
- 102000050389 Syntaxin Human genes 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
- 208000024780 Urticaria Diseases 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
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 229940079718 acetyltryptophanate Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000004469 amino acid formulation Substances 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 108010069022 botulinum toxin type D Proteins 0.000 description 1
- 108010069023 botulinum toxin type E Proteins 0.000 description 1
- 108010069038 botulinum toxin type F Proteins 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 238000012769 bulk production Methods 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 201000002866 cervical dystonia Diseases 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
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229920005565 cyclic polymer Polymers 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
- 230000002498 deadly effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 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
- 238000009826 distribution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000010544 human prion disease Diseases 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- KJLLKLRVCJAFRY-UHFFFAOYSA-N mebutizide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)NC(C(C)C(C)CC)NC2=C1 KJLLKLRVCJAFRY-UHFFFAOYSA-N 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 230000000813 microbial effect Effects 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
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 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
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 150000007523 nucleic acids Chemical group 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
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 244000052769 pathogen Species 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
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 235000004252 protein component Nutrition 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
- 230000007115 recruitment Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003019 respiratory muscle Anatomy 0.000 description 1
- 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 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 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
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 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
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000024033 toxin binding Effects 0.000 description 1
- 230000032258 transport Effects 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
- 210000002700 urine Anatomy 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
- 238000005303 weighing Methods 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000011686 zinc sulphate Substances 0.000 description 1
- 235000009529 zinc sulphate Nutrition 0.000 description 1
- BVGLZNQZEYAYBJ-QWZQWHGGSA-N α-cobratoxin Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)CC1=CC=C(O)C=C1 BVGLZNQZEYAYBJ-QWZQWHGGSA-N 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)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (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)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50014700A | 2000-02-08 | 2000-02-08 | |
| PCT/US2001/003641 WO2001058472A2 (en) | 2000-02-08 | 2001-02-05 | Botulinum toxin pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA02007519A true MXPA02007519A (es) | 2004-10-15 |
Family
ID=23988236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA02007519A MXPA02007519A (es) | 2000-02-08 | 2001-02-05 | Composiciones farmaceuticas de toxina botulinica. |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US20020064536A1 (OSRAM) |
| EP (4) | EP1253932B1 (OSRAM) |
| JP (7) | JP2003522154A (OSRAM) |
| KR (3) | KR100753765B1 (OSRAM) |
| CN (2) | CN1331532C (OSRAM) |
| AR (1) | AR027391A1 (OSRAM) |
| AT (2) | ATE519494T1 (OSRAM) |
| AU (2) | AU3331501A (OSRAM) |
| BR (1) | BR0108173A (OSRAM) |
| CA (3) | CA2494241C (OSRAM) |
| CY (1) | CY1108007T1 (OSRAM) |
| DE (2) | DE60110372T2 (OSRAM) |
| DK (3) | DK1514556T3 (OSRAM) |
| ES (3) | ES2275992T5 (OSRAM) |
| MX (1) | MXPA02007519A (OSRAM) |
| NZ (2) | NZ530779A (OSRAM) |
| PT (3) | PT1398038E (OSRAM) |
| TW (2) | TWI317283B (OSRAM) |
| WO (1) | WO2001058472A2 (OSRAM) |
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 |
| KR100753765B1 (ko) * | 2000-02-08 | 2007-08-31 | 알레간 인코포레이티드 | 보툴리눔 독소 약제학적 조성물 |
| US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
| US8632785B2 (en) * | 2000-02-08 | 2014-01-21 | Allergan, Inc. | Clostridial toxin pharmaceutical composition containing a gelatin fragment |
| 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 |
| JPWO2003082315A1 (ja) * | 2002-03-29 | 2005-07-28 | 財団法人化学及血清療法研究所 | 筋緊張亢進疾患治療剤 |
| 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 |
| AU2003300666A1 (en) * | 2002-12-20 | 2004-07-29 | Botulinum Toxin Research Associates, Inc. | Pharmaceutical botulinum toxin compositions |
| BRPI0408925A (pt) * | 2003-03-31 | 2006-04-04 | Alza Corp | veìculos de fase simples não-aquosos e formulações utilizando tais veìculos |
| 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 |
| 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 |
| US7354740B2 (en) | 2003-09-25 | 2008-04-08 | Allergan, Inc. | Animal product free system and process for purifying a botulinum toxin |
| US7160699B2 (en) | 2003-09-25 | 2007-01-09 | Allergan, Inc. | Media for clostridium bacterium and processes for obtaining a clostridial toxin |
| US20100266638A1 (en) | 2004-02-26 | 2010-10-21 | Allergan, Inc. | Headache treatment method |
| US20050191321A1 (en) | 2004-02-26 | 2005-09-01 | Allergan, Inc. | Methods for treating headache |
| US9078892B2 (en) * | 2004-02-26 | 2015-07-14 | Allergan, Inc. | Methods for treating pain and for treating a medication overuse disorder |
| 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 |
| EP3210620A1 (en) | 2004-08-04 | 2017-08-30 | Ipsen Biopharm Limited | Pharmaceutical composition containing botulinum neurotoxin a2 |
| ES2526913T3 (es) | 2004-08-04 | 2015-01-16 | Ipsen Biopharm Limited | Composición farmacéutica que contiene neurotoxina 2 botulínica |
| WO2006073410A1 (en) * | 2005-01-03 | 2006-07-13 | Botulinum Toxin Research Associates, Inc. | Compositions, methods and devices for preparing less painful botulinum toxin formulations |
| US7727537B2 (en) | 2005-02-14 | 2010-06-01 | Dpm Therapeutics Corp. | Stabilized compositions for topical administration and methods of making same |
| US7838011B2 (en) | 2005-02-14 | 2010-11-23 | Pankaj Modi | Stabilized protein compositions for topical administration and methods of making same |
| SG160357A1 (en) * | 2005-03-03 | 2010-04-29 | Revance Therapeutics Inc | Compositions and methods for topical application and transdermal delivery of botulinum toxins |
| 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 |
| US20090324647A1 (en) * | 2005-10-11 | 2009-12-31 | Borodic Gary E | 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 |
| PT2029740E (pt) | 2006-05-31 | 2012-07-06 | Genzyme Corp | Utilização de polissacáridos para promoção de actividade enzimática |
| 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. |
| CN101616682A (zh) * | 2006-12-29 | 2009-12-30 | 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 |
| US9107902B2 (en) * | 2007-06-13 | 2015-08-18 | Csl Behring Gmbh | Use of VWF stabilized FVIII preparations and of VWF preparations without FVIII for extravascular administration in the therapy and prophylactic treatment of bleeding disorders |
| BRPI0813948B8 (pt) * | 2007-07-10 | 2021-05-25 | Medy Tox Inc | composição líquida farmacêutica de toxina botulínica com estabilidade melhorada |
| 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 |
| 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 |
| 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 |
| 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 |
| WO2010016895A1 (en) * | 2008-08-05 | 2010-02-11 | Solstice Neurosciences, Inc. | Compositions of activated botulinum toxin type b |
| US20100034854A1 (en) * | 2008-08-05 | 2010-02-11 | Solstice Neurosciences, Inc. | Compositions of activated botulinum holotoxin type B (150 KD) |
| US20100112006A1 (en) * | 2008-11-03 | 2010-05-06 | Solstice Neurosciences, Inc. | Compositions of activated botulinum holotoxin type B (150 kD) |
| US20100112005A1 (en) * | 2008-11-03 | 2010-05-06 | Solstice Neurosciences, Inc. | Compositions of activated botulinum toxin type B |
| WO2010096134A1 (en) | 2008-12-04 | 2010-08-26 | Botulinum Toxin Research Associates, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
| KR20110106346A (ko) * | 2008-12-10 | 2011-09-28 | 알러간, 인코포레이티드 | 클로스트리디움 독소 약제학적 조성물 |
| HUE037595T2 (hu) | 2008-12-31 | 2018-09-28 | Revance Therapeutics Inc | Injektálható botulinum toxin készítmények |
| 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. |
| MX366344B (es) | 2009-06-25 | 2019-07-05 | Revance Therapeutics Inc | Formulaciones de toxina botulinica libres de albumina. |
| US8129139B2 (en) | 2009-07-13 | 2012-03-06 | Allergan, Inc. | Process for obtaining botulinum neurotoxin |
| EP2544658A2 (en) * | 2010-03-12 | 2013-01-16 | 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 |
| WO2012048854A2 (en) | 2010-10-12 | 2012-04-19 | Merz Pharma Gmbh & Co. Kgaa | Formulation suitable for stabilizing proteins, which is free of mammalian excipients |
| ES2636680T5 (es) * | 2011-03-31 | 2023-10-31 | Medy Tox Inc | Preparación liofilizada de toxina botulínica |
| 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 |
| RU2694820C9 (ru) * | 2014-12-23 | 2019-08-12 | Мерц Фарма Гмбх Унд Ко. Кгаа | Контейнер, предварительно заполненный ботулиновым токсином |
| MX385297B (es) * | 2015-02-03 | 2025-03-18 | Merz Pharma Gmbh & Co Kgaa | Recipiente precargado con toxina botulínica. |
| 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 |
| TWI777955B (zh) | 2016-05-27 | 2022-09-21 | 英商益普生生物製藥有限公司 | 神經毒素調配物 |
| WO2018038301A1 (en) | 2016-08-26 | 2018-03-01 | Hugel Inc. | Stabilized liquid formulation of botulinum toxin and preparation method thereof |
| WO2018038585A1 (ko) * | 2016-08-26 | 2018-03-01 | 주식회사 에이비바이오 | 보툴리눔 독소 및 안정화제를 포함하는 액상 제형 및 이의 제조방법 |
| HUE046449T2 (hu) | 2016-09-13 | 2020-03-30 | Allergan Inc | Stabilizált, nem fehérje eredetû, clostridiális toxin készítmények |
| EP3675900A4 (en) | 2017-08-28 | 2021-05-05 | Revance Therapeutics, Inc. | Transmucosal botulinum toxin compositions, kits, and methods for treating bladder disorders |
| KR20190038292A (ko) * | 2017-09-29 | 2019-04-08 | 한국프라임제약주식회사 | 효능 지속시간이 연장된 보툴리눔 독소 조성물 |
| CN111417420B (zh) * | 2017-11-17 | 2024-02-02 | 瑞典孤儿比奥维特鲁姆有限公司 | 带有离子交换材料的注射器组件 |
| 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 |
| CA3167217A1 (en) | 2020-01-13 | 2021-07-22 | Durect Corporation | Sustained release drug delivery systems with reduced impurities and related methods |
| KR102404217B1 (ko) * | 2020-04-08 | 2022-06-02 | (주)메디톡스 | 토출 속도 조절이 용이하고 안정한 보툴리눔 독소 사전충전된 주사기 제형 |
| BR112022020327A2 (pt) * | 2020-04-08 | 2022-12-13 | Medytox Inc | Formulação de seringa pré-carregada com toxina botulínica |
| 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 |
| EP4277702A1 (en) | 2021-01-12 | 2023-11-22 | Durect Corporation | Sustained release drug delivery systems and related methods |
| 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 |
| 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 |
| 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 |
| 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 |
| IT1249443B (it) * | 1990-08-30 | 1995-02-23 | Warner Lambert Co | Composizione comprendente un polimero idrofilo ed un differente materiale idrofilo. |
| 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 |
| AU2309692A (en) * | 1991-07-03 | 1993-02-11 | 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 |
| AU4646393A (en) * | 1992-06-23 | 1994-01-24 | Interactive Biologics Associates | 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 |
| JPH06192118A (ja) * | 1992-09-28 | 1994-07-12 | Wisconsin Alumni Res Found | ボツリヌス毒素を含む異常に過敏な筋運動障害の治療用薬剤組成物およびその製造方法 |
| 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 |
| PT701455E (pt) * | 1993-06-04 | 2001-09-27 | Biotime Inc | Solucao semelhante a plasma |
| 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 |
| DK0758900T3 (da) * | 1994-05-09 | 2002-07-29 | William J Binder | Botulinumtoksin til reduktion af migræne-hovedpinesmerter |
| US5670484A (en) * | 1994-05-09 | 1997-09-23 | Binder; William J. | Method for treatment of skin lesions associated with cutaneous cell-proliferative disorders |
| 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 |
| DE69531992T2 (de) * | 1994-08-04 | 2004-07-22 | Elan Drug Delivery Ltd., Ruddington | Feste verabreichungssysteme zur gesteuerten freisetzung von darin eingebauten molekülen sowie verfahren zu deren herstellung |
| AU2907695A (en) * | 1994-08-08 | 1996-03-07 | Wisconsin Alumni Research Foundation | Purification and pharmaceutical compositions containing type g botulinum neurotoxin |
| US5756468A (en) † | 1994-10-13 | 1998-05-26 | Wisconsin Alumni Research Foundation | Pharmaceutical compositions of botulinum toxin or botulinum neurotoxin and methods of preparation |
| US5512547A (en) * | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
| AU6034396A (en) * | 1995-06-06 | 1996-12-24 | L. Bruce Pearce | Improved compositions and methods for chemodenervation using neurotoxins |
| 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 |
| CA2242323C (en) * | 1996-03-13 | 2002-09-10 | Delta Biotechnology Limited | Fermentation control |
| 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 |
| DK0917879T3 (da) * | 1997-11-22 | 2002-11-04 | Roche Diagnostics Gmbh | Forbedret fremgangsmåde til stabilisering af proteiner |
| 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 |
| KR100753765B1 (ko) * | 2000-02-08 | 2007-08-31 | 알레간 인코포레이티드 | 보툴리눔 독소 약제학적 조성물 |
| 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 KR KR1020027010146A patent/KR100753765B1/ko not_active Expired - Lifetime
- 2001-02-05 JP JP2001557580A patent/JP2003522154A/ja active Pending
- 2001-02-05 PT PT03025104T patent/PT1398038E/pt unknown
- 2001-02-05 NZ NZ530779A patent/NZ530779A/en not_active IP Right Cessation
- 2001-02-05 CA CA2494241A patent/CA2494241C/en not_active Expired - Fee Related
- 2001-02-05 DE DE60110372T patent/DE60110372T2/de not_active Expired - Lifetime
- 2001-02-05 ES ES03025104T patent/ES2275992T5/es not_active Expired - Lifetime
- 2001-02-05 EP EP01905436A patent/EP1253932B1/en not_active Expired - Lifetime
- 2001-02-05 ES ES04029089T patent/ES2368061T3/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 WO PCT/US2001/003641 patent/WO2001058472A2/en not_active Ceased
- 2001-02-05 AU AU3331501A patent/AU3331501A/xx active Pending
- 2001-02-05 DE DE60125986T patent/DE60125986T3/de not_active Expired - Lifetime
- 2001-02-05 CN CNB2004100117577A patent/CN1331532C/zh not_active Expired - Fee Related
- 2001-02-05 PT PT04029089T patent/PT1514556E/pt unknown
- 2001-02-05 NZ NZ520201A patent/NZ520201A/en not_active IP Right Cessation
- 2001-02-05 AU AU2001233315A patent/AU2001233315B2/en not_active Ceased
- 2001-02-05 EP EP03025104A patent/EP1398038B2/en not_active Expired - Lifetime
- 2001-02-05 PT PT01905436T patent/PT1253932E/pt unknown
- 2001-02-05 CA CA002478621A patent/CA2478621C/en not_active Expired - Lifetime
- 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 DK DK01905436T patent/DK1253932T3/da active
- 2001-02-05 EP EP04029089A patent/EP1514556B1/en not_active Expired - Lifetime
- 2001-02-05 CA CA002400318A patent/CA2400318C/en not_active Expired - Fee Related
- 2001-02-05 AT AT01905436T patent/ATE293988T1/de active
- 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 DK03025104.5T patent/DK1398038T4/da active
- 2001-02-05 MX MXPA02007519A patent/MXPA02007519A/es active IP Right Grant
- 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 |
|---|---|---|
| CA2400318C (en) | Botulinum toxin pharmaceutical compositions | |
| AU2001233315A1 (en) | Botulinum toxin pharmaceutical compositions | |
| US7758873B2 (en) | Polysaccharide containing botulinum toxin pharmaceutical compositions and uses thereof | |
| US20060269575A1 (en) | Botulinum toxin pharmaceutical compositions formulated with recombinant albumin | |
| AU2005203171B2 (en) | Botulinum toxin pharmaceutical compositions | |
| AU2008201176B2 (en) | Botulinum toxin pharmaceutical compositions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |