SA515370208B1 - طريقة لإنتاج سُم بوتيولينيوم - Google Patents
طريقة لإنتاج سُم بوتيولينيوم Download PDFInfo
- Publication number
- SA515370208B1 SA515370208B1 SA515370208A SA515370208A SA515370208B1 SA 515370208 B1 SA515370208 B1 SA 515370208B1 SA 515370208 A SA515370208 A SA 515370208A SA 515370208 A SA515370208 A SA 515370208A SA 515370208 B1 SA515370208 B1 SA 515370208B1
- Authority
- SA
- Saudi Arabia
- Prior art keywords
- botulinum toxin
- ber
- botulinum
- toxin
- precipitate
- Prior art date
Links
- 108030001720 Bontoxilysin Proteins 0.000 title claims abstract description 154
- 229940053031 botulinum toxin Drugs 0.000 title claims abstract description 145
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 67
- 238000005571 anion exchange chromatography Methods 0.000 claims abstract description 32
- 239000002244 precipitate Substances 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 16
- 101710163270 Nuclease Proteins 0.000 claims abstract description 11
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims abstract description 7
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 31
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 22
- 239000007853 buffer solution Substances 0.000 claims description 20
- 108010057266 Type A Botulinum Toxins Proteins 0.000 claims description 18
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 16
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 16
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 16
- 238000001556 precipitation Methods 0.000 claims description 14
- 238000004587 chromatography analysis Methods 0.000 claims description 13
- 238000000605 extraction Methods 0.000 claims description 12
- 239000001488 sodium phosphate Substances 0.000 claims description 10
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 9
- 238000003916 acid precipitation Methods 0.000 claims description 8
- 239000000284 extract Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- 102000006382 Ribonucleases Human genes 0.000 claims description 3
- 108010083644 Ribonucleases Proteins 0.000 claims description 3
- 239000012064 sodium phosphate buffer Substances 0.000 claims description 3
- 102000016911 Deoxyribonucleases Human genes 0.000 claims description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 claims description 2
- 229940122426 Nuclease inhibitor Drugs 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 claims description 2
- RNIHAPSVIGPAFF-UHFFFAOYSA-N Acrylamide-acrylic acid resin Chemical compound NC(=O)C=C.OC(=O)C=C RNIHAPSVIGPAFF-UHFFFAOYSA-N 0.000 claims 1
- 241001093575 Alma Species 0.000 claims 1
- 101100422780 Caenorhabditis elegans sur-5 gene Proteins 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 claims 1
- 241000549435 Pria Species 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 239000003223 protective agent Substances 0.000 claims 1
- -1 sodium phosphate anion Chemical class 0.000 claims 1
- 239000000872 buffer Substances 0.000 abstract description 6
- 108700012359 toxins Proteins 0.000 description 43
- 210000003205 muscle Anatomy 0.000 description 38
- 239000003053 toxin Substances 0.000 description 36
- 231100000765 toxin Toxicity 0.000 description 36
- 229940089093 botox Drugs 0.000 description 30
- 102000004169 proteins and genes Human genes 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 101710117542 Botulinum neurotoxin type A Proteins 0.000 description 16
- 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 15
- 229960004716 idoxuridine Drugs 0.000 description 15
- 238000000746 purification Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 239000012535 impurity Substances 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 230000008569 process Effects 0.000 description 12
- 238000004062 sedimentation Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 108010048262 DWP450 Proteins 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000003456 ion exchange resin Substances 0.000 description 9
- 229920003303 ion-exchange polymer Polymers 0.000 description 9
- 239000002609 medium Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000001769 paralizing effect Effects 0.000 description 7
- 238000011218 seed culture Methods 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 239000002581 neurotoxin Substances 0.000 description 6
- 231100000618 neurotoxin Toxicity 0.000 description 6
- 239000002435 venom Substances 0.000 description 6
- 231100000611 venom Toxicity 0.000 description 6
- 210000001048 venom Anatomy 0.000 description 6
- 101710154606 Hemagglutinin Proteins 0.000 description 5
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 101710138657 Neurotoxin Proteins 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
- 206010040954 Skin wrinkling Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000000185 hemagglutinin Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 208000018360 neuromuscular disease Diseases 0.000 description 5
- 231100000062 no-observed-adverse-effect level Toxicity 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 102100028188 Cystatin-F Human genes 0.000 description 4
- 101710169749 Cystatin-F Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 4
- 238000005349 anion exchange Methods 0.000 description 4
- 206010008129 cerebral palsy Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 231100000614 poison Toxicity 0.000 description 4
- 239000002574 poison Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000037303 wrinkles Effects 0.000 description 4
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000014094 Dystonic disease Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010019468 Hemiplegia Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 231100000654 protein toxin Toxicity 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 230000001839 systemic circulation Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 241000193403 Clostridium Species 0.000 description 2
- 208000000289 Esophageal Achalasia Diseases 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- 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 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 206010030136 Oesophageal achalasia Diseases 0.000 description 2
- 108010010469 Qa-SNARE Proteins Proteins 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 206010040744 Sinus headache Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 102000050389 Syntaxin Human genes 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 201000000621 achalasia Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940094657 botulinum toxin type a Drugs 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000013622 capto Q Substances 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 201000008417 spastic hemiplegia Diseases 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 210000002435 tendon Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- 241000270728 Alligator Species 0.000 description 1
- 206010002153 Anal fissure Diseases 0.000 description 1
- 240000000662 Anethum graveolens Species 0.000 description 1
- 206010059237 Auriculotemporal syndrome Diseases 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 206010064888 Cervicogenic headache Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000193155 Clostridium botulinum Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100028953 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 208000004041 Gustatory Sweating Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 101710141525 Neurotoxin 3 Proteins 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 206010034650 Peritoneal adhesions Diseases 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 206010036313 Post-traumatic headache Diseases 0.000 description 1
- 108010005730 R-SNARE Proteins Proteins 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 206010040925 Skin striae Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 206010067672 Spasmodic dysphonia Diseases 0.000 description 1
- 206010041415 Spastic paralysis Diseases 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- 208000031439 Striae Distensae Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000002215 Synaptobrevin Human genes 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- 208000024799 Thyroid disease Diseases 0.000 description 1
- 206010044074 Torticollis Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 101710099833 Venom protein Proteins 0.000 description 1
- 208000013142 Writer cramp Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 108010079650 abobotulinumtoxinA Proteins 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000036617 axillary hyperhidrosis Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 1
- JOCZJWVCEYOBNH-VPUKBDNTSA-N brevin Chemical compound O1C(C)C(O)C(OC)CC1OC1C(OC)CC(OC2C(CC(OC2C)OC2CC3=CCC4(O)C5(O)CCC(O)([C@@]5(C)C(O)C(OC(=O)C=5C=CC=CC=5)C4[C@@]3(C)CC2)C(C)=O)OC)OC1C JOCZJWVCEYOBNH-VPUKBDNTSA-N 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 201000002866 cervical dystonia Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012297 crystallization seed Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 201000003892 detrusor sphincter dyssynergia Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940098753 dysport Drugs 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 201000002904 focal dystonia Diseases 0.000 description 1
- 201000002865 focal hand dystonia Diseases 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 210000000527 greater trochanter Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000001660 hyperkinetic effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003715 interstitial flow Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229960004184 ketamine hydrochloride Drugs 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 230000037392 palmar hyperhidrosis Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000036563 plantar hyperhidrosis Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 201000007094 prostatitis Diseases 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 201000002849 spasmodic dystonia Diseases 0.000 description 1
- 201000007770 spastic cerebral palsy Diseases 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/18—Ion-exchange chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/30—Extraction; Separation; Purification by precipitation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24069—Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Analytical Chemistry (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020130092024A KR101339349B1 (ko) | 2013-08-02 | 2013-08-02 | 보툴리눔 독소의 제조방법 |
| PCT/KR2014/004003 WO2015016462A1 (en) | 2013-08-02 | 2014-05-07 | Method for production of botulinum toxin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SA515370208B1 true SA515370208B1 (ar) | 2017-07-08 |
Family
ID=49987856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SA515370208A SA515370208B1 (ar) | 2013-08-02 | 2015-11-29 | طريقة لإنتاج سُم بوتيولينيوم |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US9512418B2 (en:Method) |
| EP (1) | EP2920199B1 (en:Method) |
| JP (2) | JP6307150B2 (en:Method) |
| KR (1) | KR101339349B1 (en:Method) |
| CN (1) | CN105392795B (en:Method) |
| AR (1) | AR096541A1 (en:Method) |
| AU (1) | AU2014297167B2 (en:Method) |
| BR (1) | BR112015029973B1 (en:Method) |
| CA (1) | CA2912553C (en:Method) |
| CY (1) | CY1120410T1 (en:Method) |
| DK (1) | DK2920199T3 (en:Method) |
| ES (1) | ES2665288T3 (en:Method) |
| HR (1) | HRP20180679T1 (en:Method) |
| HU (1) | HUE036840T2 (en:Method) |
| LT (1) | LT2920199T (en:Method) |
| MX (1) | MX362821B (en:Method) |
| NO (1) | NO2920199T3 (en:Method) |
| PH (1) | PH12015501855A1 (en:Method) |
| PL (1) | PL2920199T3 (en:Method) |
| PT (1) | PT2920199T (en:Method) |
| RU (1) | RU2627159C2 (en:Method) |
| SA (1) | SA515370208B1 (en:Method) |
| SG (1) | SG11201509486VA (en:Method) |
| SI (1) | SI2920199T1 (en:Method) |
| WO (1) | WO2015016462A1 (en:Method) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8129139B2 (en) | 2009-07-13 | 2012-03-06 | Allergan, Inc. | Process for obtaining botulinum neurotoxin |
| KR101339349B1 (ko) * | 2013-08-02 | 2013-12-09 | 주식회사 대웅 | 보툴리눔 독소의 제조방법 |
| KR101723167B1 (ko) | 2015-04-28 | 2017-04-05 | 주식회사 대웅 | 보툴리눔 독소의 제조를 위한 배지 조성물 |
| KR101729251B1 (ko) | 2015-04-28 | 2017-04-21 | 주식회사 대웅 | 보툴리눔 독소의 제조를 위한 배지 조성물 |
| KR101723168B1 (ko) | 2015-04-28 | 2017-04-05 | 주식회사 대웅 | 보툴리눔 독소의 제조를 위한 배지 조성물 |
| KR101853463B1 (ko) * | 2015-09-09 | 2018-06-20 | 휴젤(주) | 보툴리눔 독소의 정제 방법 |
| KR101775682B1 (ko) | 2015-11-30 | 2017-09-06 | 주식회사 대웅 | 보툴리눔 독소의 제조방법 |
| CN109641941B (zh) * | 2016-05-16 | 2023-06-16 | 哈佛大学校长及研究员协会 | 用于纯化和激活肉毒杆菌神经毒素的方法 |
| KR102463881B1 (ko) | 2016-10-04 | 2022-11-07 | (주)메디톡스 | 보툴리눔 독소 함유 용액으로부터 보툴리눔 독소를 분리하는 방법 |
| KR101744900B1 (ko) | 2017-01-20 | 2017-06-08 | 주식회사 대웅 | 보툴리눔 독소를 포함하는 안정한 액상 조성물 |
| CN109646673A (zh) * | 2017-10-12 | 2019-04-19 | 秀杰股份公司 | 肉毒杆菌毒素的微结构制剂技术 |
| CA3124535A1 (en) | 2018-12-21 | 2020-06-25 | The Research Foundation For Microbial Diseases Of Osaka University | Botulinum toxin producing method |
| KR102516204B1 (ko) * | 2019-04-15 | 2023-03-30 | (주)제테마 | 보툴리눔 독소의 정제방법 |
| KR102516203B1 (ko) * | 2019-04-15 | 2023-03-30 | (주)제테마 | 보툴리눔 독소의 제조방법 |
| TWI854077B (zh) * | 2019-12-20 | 2024-09-01 | 瑞士商葛德瑪控股公司 | 生產肉毒桿菌毒素的方法 |
| TW202136286A (zh) * | 2019-12-20 | 2021-10-01 | 瑞士商葛德瑪控股公司 | 純化肉毒桿菌毒素的方法 |
| KR102724651B1 (ko) * | 2021-07-08 | 2024-11-01 | 주식회사 파마리서치바이오 | 비-독소 단백질이 제거된 클로스트리디움 보툴리눔 신경독소 단백질의 정제방법 |
| TWI852454B (zh) * | 2022-04-01 | 2024-08-11 | 大陸商重慶譽顏製藥有限公司 | 一種肉毒毒素蛋白組合物、製備方法及其應用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20030060150A (ko) * | 2002-01-07 | 2003-07-16 | (주)메디톡스 | 클로스트리디움 보툴리눔 ａ형 독소를 정제하는 방법 |
| RU2206337C1 (ru) * | 2002-10-29 | 2003-06-20 | Общество с ограниченной ответственностью "Токсины и сопутствующие продукты" | Лекарственный препарат для лечения мышечных дистоний и способ его получения |
| US7452697B2 (en) * | 2003-09-25 | 2008-11-18 | Allergan, Inc. | Chromatographic method and system for purifying a botulinum toxin |
| US7879341B2 (en) * | 2004-07-26 | 2011-02-01 | Merz Pharma Gmbh & Co. Kgaa | Therapeutic composition with a botulinum neurotoxin |
| AU2005327458B2 (en) * | 2005-03-03 | 2011-12-15 | Allergan, Inc. | Animal product free system and process for purifying a botulinum toxin |
| KR101025617B1 (ko) * | 2008-02-25 | 2011-03-30 | 메덱스젠 주식회사 | 클로스트리디움 보툴리눔으로부터 보툴리눔 독소를정제하는 방법 |
| US8129139B2 (en) * | 2009-07-13 | 2012-03-06 | Allergan, Inc. | Process for obtaining botulinum neurotoxin |
| HRP20181869T1 (hr) * | 2009-10-21 | 2019-01-11 | Revance Therapeutics, Inc. | Metode i sustavi za pročišćavanje nekompleksiranog botulinskog neurotoksina |
| KR101434558B1 (ko) * | 2011-07-21 | 2014-08-27 | (주)메디톡스 | 식물 유래 성분 함유 배지 및 가요성 폐쇄 용기를 이용하여 클로스트리디움 보툴리눔 독소를 생산하는 방법 |
| KR101339349B1 (ko) * | 2013-08-02 | 2013-12-09 | 주식회사 대웅 | 보툴리눔 독소의 제조방법 |
-
2013
- 2013-08-02 KR KR1020130092024A patent/KR101339349B1/ko active Active
-
2014
- 2014-05-07 US US14/654,819 patent/US9512418B2/en active Active
- 2014-05-07 PT PT148329667T patent/PT2920199T/pt unknown
- 2014-05-07 JP JP2016506267A patent/JP6307150B2/ja active Active
- 2014-05-07 HU HUE14832966A patent/HUE036840T2/hu unknown
- 2014-05-07 EP EP14832966.7A patent/EP2920199B1/en active Active
- 2014-05-07 MX MX2015016481A patent/MX362821B/es active IP Right Grant
- 2014-05-07 BR BR112015029973-3A patent/BR112015029973B1/pt active IP Right Grant
- 2014-05-07 RU RU2015151186A patent/RU2627159C2/ru active
- 2014-05-07 HR HRP20180679TT patent/HRP20180679T1/hr unknown
- 2014-05-07 PL PL14832966T patent/PL2920199T3/pl unknown
- 2014-05-07 ES ES14832966.7T patent/ES2665288T3/es active Active
- 2014-05-07 CA CA2912553A patent/CA2912553C/en active Active
- 2014-05-07 NO NO14832966A patent/NO2920199T3/no unknown
- 2014-05-07 CN CN201480012202.6A patent/CN105392795B/zh active Active
- 2014-05-07 SI SI201430702T patent/SI2920199T1/en unknown
- 2014-05-07 WO PCT/KR2014/004003 patent/WO2015016462A1/en not_active Ceased
- 2014-05-07 DK DK14832966.7T patent/DK2920199T3/en active
- 2014-05-07 LT LTEP14832966.7T patent/LT2920199T/lt unknown
- 2014-05-07 AU AU2014297167A patent/AU2014297167B2/en active Active
- 2014-05-07 SG SG11201509486VA patent/SG11201509486VA/en unknown
- 2014-06-06 AR ARP140102204A patent/AR096541A1/es active IP Right Grant
-
2015
- 2015-08-24 PH PH12015501855A patent/PH12015501855A1/en unknown
- 2015-11-29 SA SA515370208A patent/SA515370208B1/ar unknown
-
2017
- 2017-03-06 JP JP2017041239A patent/JP2017141237A/ja active Pending
-
2018
- 2018-04-26 CY CY20181100439T patent/CY1120410T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SA515370208B1 (ar) | طريقة لإنتاج سُم بوتيولينيوم | |
| DE60110372T2 (de) | Pharmazeutische zusammensetzungen mit botulinumtoxin | |
| EP2337790B1 (en) | Clostridial neurotoxins with altered persistency | |
| US20140308266A1 (en) | Modified neurotoxins with poly-glycine and uses thereof | |
| KR101025617B1 (ko) | 클로스트리디움 보툴리눔으로부터 보툴리눔 독소를정제하는 방법 | |
| EP2349312B1 (de) | N-terminal modifizierte tetrapeptidderivate mit c-terminalem argininmimetikum | |
| KR101853463B1 (ko) | 보툴리눔 독소의 정제 방법 | |
| US11957740B2 (en) | Complex of botulinum neurotoxin E and its binding protein as a formulation with enhanced potency | |
| KR20170082591A (ko) | Sirt6 활성화제 및 dna 복구 효소를 포함하는 조성물 | |
| JP2012500257A (ja) | エンテロコッカス・フェカリスｓｌ−５由来バクテリオシンの新規な用途 | |
| HK1215715B (zh) | 生产肉毒杆菌毒素的方法 | |
| EP0564801A1 (de) | Analyse des "host cell shut-offs" | |
| CN118215734A (zh) | 肉毒毒素制剂的干燥方法 | |
| US20240207303A1 (en) | mNA-based Delivery of Botulinum Toxin | |
| KR20050074806A (ko) | 결정형 보툴리늄 독소의 제조방법 | |
| US20130085267A1 (en) | Stabilization of Therapeutic Agents to Facilitate Administration | |
| JP2023543866A (ja) | 安定性が改善された組み換えボツリヌス毒素軽鎖タンパク質組成物 | |
| CN117982377A (zh) | 抗皱紧致组合物及其在化妆品中的应用 | |
| KR20250064438A (ko) | 대마줄기 추출 엑소좀 및 세포 투과성 펩타이드를 포함하는 화장료 조성물 |