ES2755029T3 - Liofilización por encima de la temperatura de colapso - Google Patents
Liofilización por encima de la temperatura de colapso Download PDFInfo
- Publication number
- ES2755029T3 ES2755029T3 ES09791186T ES09791186T ES2755029T3 ES 2755029 T3 ES2755029 T3 ES 2755029T3 ES 09791186 T ES09791186 T ES 09791186T ES 09791186 T ES09791186 T ES 09791186T ES 2755029 T3 ES2755029 T3 ES 2755029T3
- Authority
- ES
- Spain
- Prior art keywords
- temperature
- collapse
- lyophilized
- pharmaceutical substance
- product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000004108 freeze drying Methods 0.000 title description 88
- 238000000034 method Methods 0.000 claims abstract description 56
- 238000001035 drying Methods 0.000 claims abstract description 45
- 239000003814 drug Substances 0.000 claims abstract description 38
- 150000004676 glycans Chemical class 0.000 claims abstract description 32
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 32
- 239000005017 polysaccharide Substances 0.000 claims abstract description 32
- 239000012669 liquid formulation Substances 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims abstract description 25
- 238000009472 formulation Methods 0.000 claims abstract description 19
- 229930006000 Sucrose Natural products 0.000 claims abstract description 13
- 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 abstract description 13
- 239000005720 sucrose Substances 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000007710 freezing Methods 0.000 claims abstract description 10
- 230000008014 freezing Effects 0.000 claims abstract description 10
- 230000008018 melting Effects 0.000 claims abstract description 9
- 238000002844 melting Methods 0.000 claims abstract description 9
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims abstract description 6
- 230000005496 eutectics Effects 0.000 claims abstract description 6
- 238000000859 sublimation Methods 0.000 claims abstract description 6
- 230000008022 sublimation Effects 0.000 claims abstract description 6
- 206010013023 diphtheria Diseases 0.000 claims abstract description 3
- 229940124733 pneumococcal vaccine Drugs 0.000 claims abstract description 3
- 239000013543 active substance Substances 0.000 claims abstract 2
- 239000000463 material Substances 0.000 claims description 51
- 230000009477 glass transition Effects 0.000 claims description 25
- 239000003381 stabilizer Substances 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 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 claims description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 5
- 239000004471 Glycine Substances 0.000 claims description 5
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims description 5
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 229940050526 hydroxyethylstarch Drugs 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 239000004475 Arginine Substances 0.000 claims description 4
- 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 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 4
- 229920002307 Dextran Polymers 0.000 claims description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 4
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 4
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 description 78
- 108090000623 proteins and genes Proteins 0.000 description 48
- 102000004169 proteins and genes Human genes 0.000 description 48
- 229960005486 vaccine Drugs 0.000 description 23
- 239000000126 substance Substances 0.000 description 19
- 108010078791 Carrier Proteins Proteins 0.000 description 11
- 150000001720 carbohydrates Chemical class 0.000 description 11
- 230000021615 conjugation Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 102000014914 Carrier Proteins Human genes 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 241000287828 Gallus gallus Species 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000005251 capillar electrophoresis Methods 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 229940031348 multivalent vaccine Drugs 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 108091023037 Aptamer Proteins 0.000 description 3
- 108010060123 Conjugate Vaccines Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000005277 cation exchange chromatography Methods 0.000 description 3
- 229940031670 conjugate vaccine Drugs 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 238000000569 multi-angle light scattering Methods 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 241000251730 Chondrichthyes Species 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 101710101803 DNA-binding protein J Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 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
- 230000002238 attenuated effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000012777 commercial manufacturing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000004848 nephelometry Methods 0.000 description 2
- 239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 108010040473 pneumococcal surface protein A Proteins 0.000 description 2
- -1 pneumolysis Proteins 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229940031626 subunit vaccine Drugs 0.000 description 2
- 229940031572 toxoid vaccine Drugs 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 101001051090 Bacillus anthracis Lethal factor Proteins 0.000 description 1
- 101000585552 Bacillus anthracis Protective antigen Proteins 0.000 description 1
- 108010071023 Bacterial Outer Membrane Proteins Proteins 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 108091006146 Channels Proteins 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
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000588698 Erwinia Species 0.000 description 1
- 101710082714 Exotoxin A Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 102000017033 Porins Human genes 0.000 description 1
- 108010013381 Porins Proteins 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 229940123573 Protein synthesis inhibitor Drugs 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 229940123752 RNA synthesis inhibitor Drugs 0.000 description 1
- 102000010912 Transferrin-Binding Proteins Human genes 0.000 description 1
- 108010062476 Transferrin-Binding Proteins Proteins 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000001384 anti-glaucoma Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000001262 anti-secretory effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 239000013628 high molecular weight specie Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 238000001565 modulated differential scanning calorimetry Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 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
- 238000011020 pilot scale process Methods 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000000007 protein synthesis inhibitor Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000013336 robust study Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000646 scanning calorimetry Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
Classifications
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8642608P | 2008-08-05 | 2008-08-05 | |
| PCT/US2009/052852 WO2010017296A1 (en) | 2008-08-05 | 2009-08-05 | Lyophilization above collapse |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2755029T3 true ES2755029T3 (es) | 2020-04-21 |
Family
ID=41401614
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09791186T Active ES2755029T3 (es) | 2008-08-05 | 2009-08-05 | Liofilización por encima de la temperatura de colapso |
| ES19181153T Active ES2968301T3 (es) | 2008-08-05 | 2009-08-05 | Liofilización por encima del colapso |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES19181153T Active ES2968301T3 (es) | 2008-08-05 | 2009-08-05 | Liofilización por encima del colapso |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9884019B2 (enExample) |
| EP (2) | EP2323629B1 (enExample) |
| JP (1) | JP5785077B2 (enExample) |
| CA (1) | CA2729972C (enExample) |
| ES (2) | ES2755029T3 (enExample) |
| WO (1) | WO2010017296A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090061033A (ko) * | 2006-10-03 | 2009-06-15 | 와이어쓰 | 동결건조 방법 및 장치 |
| AU2007234612B2 (en) | 2006-12-14 | 2013-06-27 | Johnson & Johnson Regenerative Therapeutics, Llc | Protein stabilization formulations |
| US7678764B2 (en) | 2007-06-29 | 2010-03-16 | Johnson & Johnson Regenerative Therapeutics, Llc | Protein formulations for use at elevated temperatures |
| CN101801405A (zh) | 2007-08-07 | 2010-08-11 | 先进科技及再生医学有限责任公司 | 包含于酸性水溶液中的gdf-5的蛋白质配方 |
| US7947649B2 (en) * | 2008-04-14 | 2011-05-24 | Advanced Technologies And Regenerative Medicine, Llc | Liquid buffered GDF-5 formulations |
| CA2729972C (en) | 2008-08-05 | 2018-11-20 | Wyeth Llc | Lyophilization above collapse |
| WO2014140361A1 (en) | 2013-03-15 | 2014-09-18 | Takeda Gmbh | Formulation of an antibody and use thereof |
| TWI745671B (zh) | 2013-03-15 | 2021-11-11 | 美商百歐維拉提夫治療公司 | 因子ix多肽調配物 |
| EA038573B1 (ru) * | 2014-03-24 | 2021-09-16 | Биовератив Терапьютикс Инк. | Лиофилизированный состав, содержащий фактор ix, для предупреждения приступов кровотечения |
| AR103173A1 (es) | 2014-12-22 | 2017-04-19 | Novarits Ag | Productos farmacéuticos y composiciones líquidas estables de anticuerpos il-17 |
| EP3323410A1 (en) * | 2016-11-22 | 2018-05-23 | RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.p.a. | Pharmaceutical parenteral formulation containing carglumic acid |
| CN107543373B (zh) * | 2017-09-06 | 2019-04-26 | 华派生物工程集团有限公司 | 一种活疫苗的冷冻干燥方法 |
| IL318714A (en) | 2018-05-10 | 2025-03-01 | Regeneron Pharma | Formulations that include high concentrations of VEGF receptor fusion protein |
| CN109369821B (zh) * | 2018-11-28 | 2021-12-14 | 四川恒通动保生物科技有限公司 | 一种黄芪多糖的高效提取制备方法 |
| JP7266108B2 (ja) | 2019-02-18 | 2023-04-27 | イーライ リリー アンド カンパニー | 治療用抗体製剤 |
| CA3168873A1 (en) | 2020-02-04 | 2021-08-12 | Regeneron Pharmaceuticals, Inc. | Target residual moisture content for lyophilized drug product |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5298261A (en) * | 1992-04-20 | 1994-03-29 | Oregon Freeze Dry, Inc. | Rapidly distintegrating tablet |
| BR9507909A (pt) * | 1994-06-03 | 1997-08-12 | Procter & Gamble | Formas de dosagem de rápida dissolução |
| RU2111426C1 (ru) | 1995-11-03 | 1998-05-20 | Государственный научный центр вирусологии и биотехнологии "Вектор" | Способ лиофильной сушки биопрепарата |
| HUP0102812A3 (en) | 1998-03-03 | 2002-01-28 | Lilly Co Eli | Pharmaceutical compositions containing the phospholipase inhibitor sodium {[3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1h-indol-4-yl]oxy}acetate and process for pruducing them |
| DK2130554T3 (da) * | 1999-02-22 | 2012-12-03 | Univ Connecticut | Albuminfrie faktor VIII-præparater |
| GB9908014D0 (en) * | 1999-04-08 | 1999-06-02 | Scherer Corp R P | Pharmaceutical compositions |
| GB0404586D0 (en) * | 2004-03-01 | 2004-04-07 | Britannia Pharmaceuticals Ltd | Improvements in or relating to organic materials |
| PL1750760T3 (pl) * | 2004-06-02 | 2018-02-28 | Universal Stabilization Technologies, Inc. | Konserwacja za pomocą parowania |
| ES2349472T3 (es) * | 2004-08-12 | 2011-01-03 | Schering Corporation | Formulación estable de interferón pegilado. |
| WO2006029467A1 (en) | 2004-09-16 | 2006-03-23 | Btf Pty Ltd | Rapid freeze drying process |
| WO2006081320A2 (en) | 2005-01-27 | 2006-08-03 | Human Genome Sciences, Inc. | Pharmaceutical formulation |
| JP5405122B2 (ja) * | 2005-12-21 | 2014-02-05 | ワイス・エルエルシー | 低粘度のタンパク質製剤およびその用途 |
| CA2726837A1 (en) | 2008-06-26 | 2009-12-30 | Wyeth Llc | Lyophilization cycle robustness strategy |
| CA2729972C (en) | 2008-08-05 | 2018-11-20 | Wyeth Llc | Lyophilization above collapse |
-
2009
- 2009-08-05 CA CA2729972A patent/CA2729972C/en active Active
- 2009-08-05 US US12/536,321 patent/US9884019B2/en active Active
- 2009-08-05 ES ES09791186T patent/ES2755029T3/es active Active
- 2009-08-05 EP EP09791186.1A patent/EP2323629B1/en active Active
- 2009-08-05 ES ES19181153T patent/ES2968301T3/es active Active
- 2009-08-05 JP JP2011522218A patent/JP5785077B2/ja active Active
- 2009-08-05 EP EP19181153.8A patent/EP3572073B1/en not_active Revoked
- 2009-08-05 WO PCT/US2009/052852 patent/WO2010017296A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US9884019B2 (en) | 2018-02-06 |
| WO2010017296A1 (en) | 2010-02-11 |
| EP2323629A1 (en) | 2011-05-25 |
| JP5785077B2 (ja) | 2015-09-24 |
| EP3572073B1 (en) | 2023-12-20 |
| EP2323629B1 (en) | 2019-10-09 |
| ES2968301T3 (es) | 2024-05-08 |
| JP2011530524A (ja) | 2011-12-22 |
| US20100041870A1 (en) | 2010-02-18 |
| CA2729972C (en) | 2018-11-20 |
| CA2729972A1 (en) | 2010-02-11 |
| EP3572073C0 (en) | 2023-12-20 |
| EP3572073A1 (en) | 2019-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2755029T3 (es) | Liofilización por encima de la temperatura de colapso | |
| ES2434840T3 (es) | Formulación de proteína liofilizada isotónica estable | |
| US11241498B2 (en) | Room temperature stable lyophilized protein | |
| CN101855336B (zh) | 含艰难梭菌类毒素a和b的药物组合物 | |
| DK2701720T3 (en) | Lyophilized preparation with cytotoxic dipeptides | |
| ES2242453T3 (es) | Vectores peptidicos de sustancias a traves de la barrera hematoencefalica. | |
| ES2897659T3 (es) | Formulaciones de vacunas térmicamente estables, procesos y microagujas que incluyen las formulaciones de vacunas | |
| CN101039660B (zh) | 稳定的聚乙二醇化干扰素制剂 | |
| JP7264986B2 (ja) | 抗Her2抗体薬物コンジュゲートの製剤 | |
| JP2013100329A (ja) | 薬学的製剤 | |
| ES2775698T3 (es) | Procedimiento de producción de gránulos liofilizados que comprenden el factor VIII | |
| JP2012121894A (ja) | Il−1アンタゴニスト製剤 | |
| AU2017349163B2 (en) | ExPEC glycoconjugate vaccine formulations | |
| TW200306205A (en) | Lyophilised preparation comprising antibodies against the EGF receptor | |
| PT1771208E (pt) | Utilização de derivados de tioflavina radiorotulados em imagiologia amiloide para avaliar terapias anti-amiloide | |
| SG183561A1 (en) | Stable aqueous mia/cd-rap formulations | |
| KR20210078514A (ko) | 항-rsv 항체의 제제 및 그의 사용 방법 | |
| JP2022512294A (ja) | 抗体製剤 | |
| Hawe et al. | Physico-chemical lyophilization behavior of mannitol, human serum albumin formulations | |
| ES2974424T3 (es) | Formulaciones | |
| ES2922481T3 (es) | Formulación farmacéutica liofilizada y su uso | |
| ES2427140T3 (es) | Preparación farmacéutica liofilizada galénica, estable, de polipéptidos recombinantes que fijan los carbohidratos | |
| ES2749474T3 (es) | Agente farmacéutico estable y liofilizado que contiene nocatiacina | |
| CN110121340B (zh) | 聚乙二醇化精氨酸脱亚氨酶的调配物 | |
| JP2010519220A (ja) | マンニトール誘導性のタンパク質凝集を抑制するためのスクロースの使用 |