DK2198007T3 - Farmaceutiske sammensætninger, som indeholder clostridium difficile-toksoiderne a og b - Google Patents
Farmaceutiske sammensætninger, som indeholder clostridium difficile-toksoiderne a og b Download PDFInfo
- Publication number
- DK2198007T3 DK2198007T3 DK08830210.4T DK08830210T DK2198007T3 DK 2198007 T3 DK2198007 T3 DK 2198007T3 DK 08830210 T DK08830210 T DK 08830210T DK 2198007 T3 DK2198007 T3 DK 2198007T3
- Authority
- DK
- Denmark
- Prior art keywords
- toxoid
- composition
- toxoids
- sodium
- sucrose
- Prior art date
Links
- 241000193163 Clostridioides difficile Species 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 239000000203 mixture Substances 0.000 claims abstract description 107
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 94
- 230000002776 aggregation Effects 0.000 claims abstract description 67
- 238000004220 aggregation Methods 0.000 claims abstract description 67
- 238000000034 method Methods 0.000 claims abstract description 29
- 239000003053 toxin Substances 0.000 claims abstract description 15
- 231100000765 toxin Toxicity 0.000 claims abstract description 15
- 108700012359 toxins Proteins 0.000 claims abstract description 15
- 239000002671 adjuvant Substances 0.000 claims description 57
- 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 claims description 36
- 229930006000 Sucrose Natural products 0.000 claims description 36
- 239000005720 sucrose Substances 0.000 claims description 36
- 239000000872 buffer Substances 0.000 claims description 29
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 27
- 239000001509 sodium citrate Substances 0.000 claims description 24
- 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 claims description 21
- 208000015181 infectious disease Diseases 0.000 claims description 19
- -1 aluminum compound Chemical class 0.000 claims description 16
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical group O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 12
- 239000001508 potassium citrate Substances 0.000 claims description 11
- 229960002635 potassium citrate Drugs 0.000 claims description 11
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 11
- 235000011082 potassium citrates Nutrition 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000012064 sodium phosphate buffer Substances 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- 239000008057 potassium phosphate buffer Substances 0.000 claims description 7
- 239000001488 sodium phosphate Substances 0.000 claims description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 6
- 229910052782 aluminium Inorganic materials 0.000 claims description 5
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- 239000006260 foam Substances 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical group [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000007979 citrate buffer Substances 0.000 claims 1
- 239000008363 phosphate buffer Substances 0.000 claims 1
- 230000007423 decrease Effects 0.000 abstract description 5
- 102000004169 proteins and genes Human genes 0.000 description 47
- 108090000623 proteins and genes Proteins 0.000 description 47
- 235000018102 proteins Nutrition 0.000 description 46
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 37
- 239000000600 sorbitol Substances 0.000 description 37
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 34
- 229920000053 polysorbate 80 Polymers 0.000 description 34
- 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 30
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 30
- 239000008121 dextrose Substances 0.000 description 30
- 238000002983 circular dichroism Methods 0.000 description 29
- 229960005486 vaccine Drugs 0.000 description 24
- 238000009472 formulation Methods 0.000 description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 20
- 230000010512 thermal transition Effects 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 230000036039 immunity Effects 0.000 description 14
- 238000005259 measurement Methods 0.000 description 14
- 235000002639 sodium chloride Nutrition 0.000 description 13
- 238000003860 storage Methods 0.000 description 13
- FWEOQOXTVHGIFQ-UHFFFAOYSA-M 8-anilinonaphthalene-1-sulfonate Chemical compound C=12C(S(=O)(=O)[O-])=CC=CC2=CC=CC=1NC1=CC=CC=C1 FWEOQOXTVHGIFQ-UHFFFAOYSA-M 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 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 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 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 11
- 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 11
- 238000000113 differential scanning calorimetry Methods 0.000 description 11
- 230000005847 immunogenicity Effects 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical group OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 230000003111 delayed effect Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 230000000087 stabilizing effect Effects 0.000 description 10
- 238000004108 freeze drying Methods 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 241000699800 Cricetinae Species 0.000 description 7
- 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 7
- 238000001035 drying Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000004611 spectroscopical analysis Methods 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 235000014633 carbohydrates Nutrition 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 239000003599 detergent Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000013019 agitation Methods 0.000 description 5
- 238000003795 desorption Methods 0.000 description 5
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 150000005846 sugar alcohols Polymers 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical group [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000000295 emission spectrum Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 102000015636 Oligopeptides Human genes 0.000 description 3
- 108010038807 Oligopeptides Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 238000001142 circular dichroism spectrum Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000001757 thermogravimetry curve Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 2
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 2
- 101710084578 Short neurotoxin 1 Proteins 0.000 description 2
- 101710182532 Toxin a Proteins 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 2
- 229940047712 aluminum hydroxyphosphate Drugs 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000012931 lyophilized formulation Substances 0.000 description 2
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 2
- 239000011654 magnesium acetate Substances 0.000 description 2
- 235000011285 magnesium acetate Nutrition 0.000 description 2
- 229940069446 magnesium acetate Drugs 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 235000011147 magnesium chloride Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001308 poly(aminoacid) Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000012460 protein solution Substances 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 1
- 241000272478 Aquila Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 238000012480 Far-UV circular dichroism spectroscopy Methods 0.000 description 1
- 235000018081 Hibiscus syriacus Nutrition 0.000 description 1
- 244000130592 Hibiscus syriacus Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000004696 Poly ether ether ketone Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710182223 Toxin B Proteins 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- PTTGRYBBCYZPSL-UHFFFAOYSA-H [Al+3].[Al+3].OOP([O-])([O-])=O.OOP([O-])([O-])=O.OOP([O-])([O-])=O Chemical compound [Al+3].[Al+3].OOP([O-])([O-])=O.OOP([O-])([O-])=O.OOP([O-])([O-])=O PTTGRYBBCYZPSL-UHFFFAOYSA-H 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000005311 autocorrelation function Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUPQTSLXMOCDHR-UHFFFAOYSA-N benzene-1,4-diol;bis(4-fluorophenyl)methanone Chemical compound OC1=CC=C(O)C=C1.C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 JUPQTSLXMOCDHR-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000009021 linear effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002530 polyetherether ketone Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 229940031572 toxoid vaccine Drugs 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
Claims (16)
1. Sammensætning, som omfatter et toksoid fra Clostridium difficile og farmaceutisk acceptable excipienser, der omfatter (a) en buffer valgt blandt en natrium- eller kaliumcitratbuffer og en natrium- eller kaliumphosphatbuffer; og (b) saccharose, hvor de farmaceutisk acceptable excipienser forøger den termiske stabilitet af toksoidet og/eller reducerer eller udsætter aggregering af toksoidet i forhold til en sammensætning, der er uden de farmaceutisk acceptable excipienser.
2. Sammensætning ifølge krav 1, som endvidere omfatter formaldehyd i en koncentration på 0,001 til 0,020%.
3. Sammensætning ifølge krav 1 eller 2, hvor: (a) de farmaceutisk acceptable excipienser reducerer eller udsætter aggregering af toksoidet med 50% eller mere i forhold til en sammensætning, der er uden de farmaceutisk acceptable excipienser; eller (b) de farmaceutisk acceptable excipienser forøger den termiske stabilitet af toksoidet med 0,5°C eller mere i forhold til en sammensætning, der er uden de farmaceutisk acceptable excipienser.
4. Sammensætning ifølge et hvilket som helst af kravene 1-3, hvor sammensætningen omfatter et toksoid af C. difficile-toksinerne A og B.
5. Sammensætning ifølge krav 4, hvor: (a) toksoiderne A og B er til stede i sammensætningen i et forhold på fra 5:1 (A:B) til 1:5 (A:B); eller (b) toksoiderne A og B er til stede i sammensætningen i et forhold på fra 3:1 til 3:2 eller 1:1 (A:B).
6. Sammensætning ifølge et hvilket som helst af kravene 1-5, hvor sammensætningen er en farmaceutisk sammensætning.
7. Sammensætning ifølge et hvilket som helst af kravene 1-6, som endvidere omfatter en adjuvans.
8. Sammensætning ifølge krav 7, hvor adjuvansen omfatter en aluminiumforbindelse, hvor aluminiumforbindelsen eventuelt er en aluminiumhydroxidforbindelse.
9. Sammensætning ifølge et hvilket som helst af kravene 1-8, hvor sammensætningen foreligger (a) på væskeform eller (b) på tør pulverform, lyofiliseret, frysetørret, spraytørret eller skumtørret.
10. Sammensætning ifølge et hvilket som helst af kravene 1-9, hvor (a) citratbufferen er natriumcitrat; eller (b) phosphatbufferen er natriumphosphat.
11. Sammensætning ifølge et hvilket som helst af kravene 1-9, hvor sammensætningen omfatter: (a) Clostridium difficile-toksoiderne A og B, 5-100 mM natrium- eller kaliumcitrat, 2-20% saccharose og ^ 0,020% formaldehyd, pH 5,5-8,5; (b) Clostridium difficile-toksoiderne A og B, 10-30 mM natrium- eller kaliumcitrat, 2-10% saccharose og ^ 0,020% formaldehyd, pH 6, 5-8,0; (c) Clostridium difficile-toksoiderne A og B, 20 mM natriumcitrat, 5% saccharose og 0,016% formaldehyd, pH 7,5; (d) Clostridium difficile-toksoiderne A og B, 5-100 mM natrium- eller kaliumphosphat, 2-20% saccharose og ^ 0,020% formaldehyd, pH 5,5-8,5; (e) Clostridium difficile-toksoiderne A og B, 10-30 mM natrium- eller kaliumphosphat, 2-10% saccharose og > 0,020% formaldehyd, pH 6,5-8,0; eller (f) Clostridium difficile-toksoiderne A og B, 20 mM kaliumphosphat, 5% saccharose og 0,016% formaldehyd, pH 7,5.
12. Sammensætning ifølge et hvilket som helst af kravene 1-9, hvor sammensætningen foreligger i lyofiliseret form og omfatter: (a) Clostridium difficile-toksoiderne A og B, 10-30 mM natrium- eller kaliumcitrat, 2-10% saccharose og t 0,020% formaldehyd, pH 6,5-8,0; eller (b) Clostridium difficile-toksoiderne A og B, 20 mM natriumcitrat, 5% saccharose og 0,016% formaldehyd, pH 7,5.
13. Fremgangsmåde til fremstilling af en sammensætning, som omfatter et toksoid fra Clostridium difficile og farmaceutisk acceptable excipienser, der omfatter (a) en buffer valgt blandt en natrium- eller kaliumcitratbuffer og en natrium- eller kaliumphosphatbuffer; og (b) saccharose, hvor de farmaceutisk acceptable excipienser forøger den termiske stabilitet af toksoidet og/eller reducerer eller udsætter aggregering af toksoidet i forhold til en sammensætning, der er uden de farmaceutisk acceptable excipienser, hvilken fremgangsmåde omfatter tilvejebringelse af et toksoid fra Clostridium difficile og blanding af toksoidet fra Clostridium difficile med de farmaceutisk acceptable excipienser.
14. Sammensætning ifølge et hvilket som helst af kravene 1-12 til anvendelse ved en fremgangsmåde til forebyggelse eller behandling af C. difficile-infektion eller -sygdom hos et individ.
15. Anvendelse af en kombination af (a) en buffer valgt blandt en natrium- eller kaliumcitratbuffer og en natrium- eller kaliumphosphatbuffer; og (b) saccharose, til at forøge den termiske stabilitet og/eller reducere eller udsætte aggregeringen af et toksoid fra Clostridium difficile in vitro.
16. Anvendelse ifølge krav 15, hvor komponenterne (a) og (b) tilvejebringes i en sammensætning, hvilken sammensætning er som defineret ifølge et hvilket som helst af kravene 1-12.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97249607P | 2007-09-14 | 2007-09-14 | |
| PCT/US2008/010767 WO2009035707A1 (en) | 2007-09-14 | 2008-09-15 | Pharmaceutical compositions containing clostridium difficile toxoids a and b |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2198007T3 true DK2198007T3 (da) | 2018-01-15 |
Family
ID=40452372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK08830210.4T DK2198007T3 (da) | 2007-09-14 | 2008-09-15 | Farmaceutiske sammensætninger, som indeholder clostridium difficile-toksoiderne a og b |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US9320790B2 (da) |
| EP (3) | EP2198007B1 (da) |
| JP (3) | JP5503543B2 (da) |
| KR (2) | KR20160005378A (da) |
| CN (2) | CN106039299A (da) |
| AU (1) | AU2008299885C1 (da) |
| BR (1) | BRPI0816790A8 (da) |
| CA (1) | CA2699435A1 (da) |
| CY (1) | CY1119979T1 (da) |
| DK (1) | DK2198007T3 (da) |
| ES (2) | ES2657485T3 (da) |
| HR (1) | HRP20180054T1 (da) |
| HU (1) | HUE037932T2 (da) |
| IL (1) | IL204366A (da) |
| MX (1) | MX2010002815A (da) |
| NO (1) | NO2198007T3 (da) |
| PL (1) | PL2198007T3 (da) |
| PT (1) | PT2198007T (da) |
| RU (1) | RU2550271C2 (da) |
| SI (1) | SI2198007T1 (da) |
| WO (1) | WO2009035707A1 (da) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2198007B1 (en) | 2007-09-14 | 2017-10-25 | Sanofi Pasteur Biologics, LLC | Pharmaceutical compositions containing clostridium difficile toxoids a and b |
| SMT201700124T1 (it) | 2010-09-03 | 2017-05-08 | Valneva Austria Gmbh | Polipeptide isolato delle proteine di tossina a e tossina b di c. difficile e relativi usi |
| GB201105981D0 (en) * | 2011-04-08 | 2011-05-18 | Glaxosmithkline Biolog Sa | Novel process |
| ES2969952T3 (es) | 2011-04-22 | 2024-05-23 | Wyeth Llc | Composiciones relacionadas con una toxina mutante de Clostridium difficile y sus procedimientos |
| KR101135486B1 (ko) * | 2011-05-25 | 2012-04-13 | 함종욱 | 보툴리눔 에이형 독소의 액상제품 |
| BR122016023101B1 (pt) | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| EP2917238A1 (en) | 2012-11-08 | 2015-09-16 | Eleven Biotherapeutics, Inc. | Il-6 antagonists and uses thereof |
| HRP20230359T1 (hr) | 2012-12-05 | 2023-06-09 | Glaxosmithkline Biologicals Sa | Imunogeni pripravak |
| US10137186B2 (en) | 2013-03-14 | 2018-11-27 | Takeda Vaccines, Inc. | Compositions and methods for live, attenuated alphavirus formulations |
| US20160030542A1 (en) * | 2013-03-15 | 2016-02-04 | Sanofi Pasteur, Inc. | Toxoid, Compositions and Related Methods |
| JP2016516721A (ja) | 2013-03-15 | 2016-06-09 | サノフィ パストゥール インコーポレイテッド | トキソイド、組成物および関連方法 |
| CN105611942A (zh) | 2013-06-14 | 2016-05-25 | 圣诺菲·帕斯图尔公司 | 针对艰难梭菌免疫的组合物和方法 |
| PT3010537T (pt) | 2013-06-17 | 2019-12-03 | De Staat Der Nederlanden Vert Door De Mini Van Vws Miniie Van Volksgezondheid Welzijn En Sport | Métodos para a prevenção da agregação de componentes virais |
| US9930893B2 (en) * | 2014-02-10 | 2018-04-03 | The Johns Hopkins University | Inhibitors of DXP synthase and methods of use thereof |
| US11142571B2 (en) | 2014-11-07 | 2021-10-12 | Sesen Bio, Inc. | IL-6 antibodies |
| US20180110849A1 (en) | 2015-05-15 | 2018-04-26 | Sanofi Pasteur, Inc. | Methods for immunizing against clostridium difficile |
| BE1023343B1 (nl) * | 2015-05-20 | 2017-02-09 | Mycartis Nv | Opslagbuffer |
| EP3419599A4 (en) | 2016-02-23 | 2019-09-11 | Sesen Bio, Inc. | IL-6 ANTAGONIST FORMULATIONS AND USE THEREOF |
| IL265109B2 (en) | 2016-09-13 | 2024-05-01 | Allergan Inc | Stabilized non-protein clostridial toxin compositions |
| US20210196568A1 (en) * | 2018-05-21 | 2021-07-01 | Chugai Seiyaku Kabushiki Kaisha | Lyophilized formulation sealed in glass container |
| WO2021255690A2 (en) * | 2020-06-19 | 2021-12-23 | Pfizer Inc. | Immunogenic compositions against clostridioides (clostridium) difficile and methods thereof |
| TW202438104A (zh) * | 2022-12-13 | 2024-10-01 | 美商輝瑞股份有限公司 | 誘發針對困難梭狀芽孢桿菌之免疫反應的免疫原性組成物和方法 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4879218A (en) * | 1982-09-13 | 1989-11-07 | Virginia Tech Intellectual Properties, Inc. | Antibody for C.difficile |
| US5736139A (en) * | 1989-10-31 | 1998-04-07 | Ochidian Pharmaceuticals, Inc. | Treatment of Clostridium difficile induced disease |
| JPH03193735A (ja) | 1989-12-22 | 1991-08-23 | Shionogi & Co Ltd | グリコペプチド系抗生物質の安定化組成物 |
| ATE156019T1 (de) * | 1991-10-16 | 1997-08-15 | Schering Corp | Lipophile zusammensetzungen von oligosaccharid- antibiotikasalzen |
| WO1994000481A1 (en) | 1992-06-23 | 1994-01-06 | Associated Synapse Biologics | Pharmaceutical composition containing botulinum b complex |
| US5562909A (en) | 1993-07-12 | 1996-10-08 | Massachusetts Institute Of Technology | Phosphazene polyelectrolytes as immunoadjuvants |
| US5902565A (en) * | 1993-12-24 | 1999-05-11 | Csl Limited | Spray dried vaccine preparation comprising aluminium adsorbed immunogens |
| US5512547A (en) | 1994-10-13 | 1996-04-30 | Wisconsin Alumni Research Foundation | Pharmaceutical composition of botulinum neurotoxin and method of preparation |
| JPH08333277A (ja) | 1995-06-05 | 1996-12-17 | Hoechst Japan Ltd | ヒト血液凝固第ｘｉｉｉ因子の安定化された水性液製剤 |
| EP0877623A1 (en) * | 1995-07-07 | 1998-11-18 | Oravax, Inc. | Intranasal vaccination against gastrointestinal disease |
| US5932223A (en) | 1996-09-26 | 1999-08-03 | Merck & Co., Inc. | Rotavirus vaccine formulations |
| PT892054E (pt) * | 1997-06-20 | 2007-02-28 | Intervet Int Bv | Vacina de clostridium perfringens |
| EP1568378B1 (en) | 1997-10-20 | 2016-03-16 | Sanofi Pasteur Biologics, LLC | Immunization against Clostridium difficile disease |
| US6969520B2 (en) * | 1997-10-20 | 2005-11-29 | Acambis Inc. | Active immunization against clostridium difficile disease |
| EP1024826B1 (en) | 1997-10-20 | 2005-03-16 | Acambis, Inc. | Passive immunization against clostridium difficile disease |
| US6013635A (en) * | 1998-05-28 | 2000-01-11 | Synsorb Biotech, Inc. | Treatment of C. difficile toxin B associated conditions |
| JP2000117967A (ja) * | 1998-10-16 | 2000-04-25 | Fuji Photo Film Co Ltd | インクジェット記録方法 |
| FR2791895B1 (fr) | 1999-03-23 | 2001-06-15 | Pasteur Merieux Serums Vacc | Utilisation de trehalose pour stabiliser un vaccin liquide |
| CN1227030C (zh) * | 1999-04-19 | 2005-11-16 | 史密丝克莱恩比彻姆生物有限公司 | 包含皂甙和免疫刺激寡核苷酸的佐剂组合物 |
| US6599715B1 (en) * | 1999-05-12 | 2003-07-29 | The Regents Of The University Of California | Real time viability detection of bacterial spores |
| US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
| EP3192528A1 (en) | 2002-02-14 | 2017-07-19 | Chugai Seiyaku Kabushiki Kaisha | Formulation of anti-il6r antibody-containing solutions comprising a sugar as a stabilizer |
| AU2003225057A1 (en) * | 2002-04-19 | 2003-11-03 | The Regents Of The University Of Michigan | Polymer compositions that stabilize and control the release of formaldehyde-treated vaccine antigens |
| US20040235139A1 (en) * | 2002-12-23 | 2004-11-25 | Demain Arnold L. | Clostridium difficile culture and toxin production methods |
| DE10333317A1 (de) * | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
| JP4671864B2 (ja) | 2003-10-09 | 2011-04-20 | 中外製薬株式会社 | タンパク質溶液の安定化方法 |
| KR100852824B1 (ko) | 2004-07-26 | 2008-08-18 | 메르츠 파마 게엠베하 운트 코. 카가아 | 보툴리눔 신경독소를 포함하는 치료 조성물 |
| EP1802349A1 (en) | 2004-10-13 | 2007-07-04 | Ilypsa, Inc. | Pharmaceutical compositions comprising a toxin-binding oligosaccharide and a polymeric particle |
| FR2881139A1 (fr) * | 2005-01-26 | 2006-07-28 | Agronomique Inst Nat Rech | Composition pour la lyophilisation de proteines |
| US8137677B2 (en) | 2005-10-06 | 2012-03-20 | Allergan, Inc. | Non-protein stabilized clostridial toxin pharmaceutical compositions |
| BRPI0613001B8 (pt) | 2005-10-06 | 2021-05-25 | Allergan Inc | composições farmacêuticas de toxina clostrídica estabilizada por uma não-proteína |
| 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 |
| CA2668834C (en) | 2006-11-07 | 2016-10-11 | Sanofi Pasteur Biologics Co. | Stabilization of vaccines by lyophilization |
| EP2198007B1 (en) | 2007-09-14 | 2017-10-25 | Sanofi Pasteur Biologics, LLC | Pharmaceutical compositions containing clostridium difficile toxoids a and b |
| US20110243991A1 (en) * | 2008-12-03 | 2011-10-06 | Boehringer Ingelheim Vetmedica Gmbh | Process for production of vaccines |
-
2008
- 2008-09-15 EP EP08830210.4A patent/EP2198007B1/en not_active Not-in-force
- 2008-09-15 CA CA2699435A patent/CA2699435A1/en not_active Abandoned
- 2008-09-15 WO PCT/US2008/010767 patent/WO2009035707A1/en not_active Ceased
- 2008-09-15 KR KR1020157036693A patent/KR20160005378A/ko not_active Abandoned
- 2008-09-15 ES ES08830210.4T patent/ES2657485T3/es active Active
- 2008-09-15 PT PT88302104T patent/PT2198007T/pt unknown
- 2008-09-15 PL PL08830210T patent/PL2198007T3/pl unknown
- 2008-09-15 CN CN201610227574.1A patent/CN106039299A/zh active Pending
- 2008-09-15 RU RU2010114730/10A patent/RU2550271C2/ru not_active IP Right Cessation
- 2008-09-15 EP EP16174817.3A patent/EP3124044B8/en active Active
- 2008-09-15 BR BRPI0816790A patent/BRPI0816790A8/pt not_active IP Right Cessation
- 2008-09-15 US US12/677,864 patent/US9320790B2/en active Active
- 2008-09-15 DK DK08830210.4T patent/DK2198007T3/da active
- 2008-09-15 CN CN200880116603.0A patent/CN101855336B/zh active Active
- 2008-09-15 HU HUE08830210A patent/HUE037932T2/hu unknown
- 2008-09-15 JP JP2010524889A patent/JP5503543B2/ja active Active
- 2008-09-15 HR HRP20180054TT patent/HRP20180054T1/hr unknown
- 2008-09-15 KR KR1020107007994A patent/KR101679812B1/ko not_active Expired - Fee Related
- 2008-09-15 NO NO08830210A patent/NO2198007T3/no unknown
- 2008-09-15 MX MX2010002815A patent/MX2010002815A/es unknown
- 2008-09-15 ES ES16174817T patent/ES3001561T3/es active Active
- 2008-09-15 SI SI200831906T patent/SI2198007T1/en unknown
- 2008-09-15 AU AU2008299885A patent/AU2008299885C1/en not_active Ceased
- 2008-09-15 EP EP24220340.4A patent/EP4537849A3/en active Pending
-
2010
- 2010-03-09 IL IL204366A patent/IL204366A/en active IP Right Grant
-
2013
- 2013-11-22 JP JP2013241821A patent/JP6258674B2/ja active Active
-
2016
- 2016-03-29 US US15/083,428 patent/US9687541B2/en active Active
- 2016-10-31 JP JP2016212540A patent/JP2017052773A/ja active Pending
-
2017
- 2017-06-26 US US15/632,480 patent/US10639362B2/en active Active
-
2018
- 2018-01-23 CY CY20181100084T patent/CY1119979T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008299885B2 (en) | Pharmaceutical compositions containing clostridium difficile toxoids A and B | |
| CA3097058A1 (en) | Additives for protein formulations to improve thermal stability | |
| HRP20010901A2 (en) | Compositions of a-beta peptide and processes for producing same | |
| AU2013228096A1 (en) | Methods and compositions for stabilizing dried biological materials | |
| Anamur et al. | Stability of collapse lyophilized influenza vaccine formulations | |
| US20230066762A1 (en) | Immunogenic composition | |
| AU2015201233B2 (en) | Pharmaceutical compositions containing clostridium difficile toxoids a and b | |
| HK1230484A1 (en) | Pharmaceutical compositions containing clostridium difficile toxoids a and b | |
| HK1147285A (en) | Pharmaceutical compositions containing clostridium difficile toxoids a and b | |
| WO2024100130A1 (en) | Thermostable vaccin formulations and process for preparing the same | |
| JP2011516461A (ja) | 液体配合物及び凍結乾燥した配合物 | |
| BE1022254B1 (fr) | Formulation de vaccin saccharidique | |
| JP2023526024A (ja) | Ｉｌ－２融合ポリペプチド組成物ならびにその作製及び使用方法 | |
| Panton | Surfactant selection in biopharmaceutical product development | |
| HK1206625B (en) | Neisseria meningitidis compositions and methods thereof |