EA033472B1 - Композиция для стабилизации гиалуронидазы и ее применение - Google Patents
Композиция для стабилизации гиалуронидазы и ее применение Download PDFInfo
- Publication number
- EA033472B1 EA033472B1 EA201501068A EA201501068A EA033472B1 EA 033472 B1 EA033472 B1 EA 033472B1 EA 201501068 A EA201501068 A EA 201501068A EA 201501068 A EA201501068 A EA 201501068A EA 033472 B1 EA033472 B1 EA 033472B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- insulin
- units
- composition
- lys
- compositions
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 498
- 108010003272 Hyaluronate lyase Proteins 0.000 title claims abstract description 88
- 229960002773 hyaluronidase Drugs 0.000 title claims abstract description 84
- 102000001974 Hyaluronidases Human genes 0.000 title claims abstract description 67
- 230000006641 stabilisation Effects 0.000 title 1
- 238000011105 stabilization Methods 0.000 title 1
- NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 claims abstract description 74
- 108010054155 lysyllysine Proteins 0.000 claims abstract description 74
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 650
- 102000004877 Insulin Human genes 0.000 claims description 370
- 108090001061 Insulin Proteins 0.000 claims description 370
- 229940125396 insulin Drugs 0.000 claims description 297
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 162
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 143
- 102100021102 Hyaluronidase PH-20 Human genes 0.000 claims description 136
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 claims description 131
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 125
- 239000003755 preservative agent Substances 0.000 claims description 124
- 101150055528 SPAM1 gene Proteins 0.000 claims description 121
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 117
- 229920001184 polypeptide Polymers 0.000 claims description 115
- 230000000694 effects Effects 0.000 claims description 112
- 235000002639 sodium chloride Nutrition 0.000 claims description 100
- 239000011780 sodium chloride Substances 0.000 claims description 81
- 150000001413 amino acids Chemical class 0.000 claims description 78
- 239000004026 insulin derivative Substances 0.000 claims description 70
- 230000002335 preservative effect Effects 0.000 claims description 55
- 239000004094 surface-active agent Substances 0.000 claims description 54
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 40
- 206010012601 diabetes mellitus Diseases 0.000 claims description 27
- 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 claims description 25
- 101100178973 Homo sapiens SPAM1 gene Proteins 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 25
- 239000008103 glucose Substances 0.000 claims description 25
- 229930182817 methionine Natural products 0.000 claims description 25
- 239000003381 stabilizer Substances 0.000 claims description 25
- 108010065920 Insulin Lispro Proteins 0.000 claims description 23
- 239000006172 buffering agent Substances 0.000 claims description 22
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 claims description 22
- 229960004717 insulin aspart Drugs 0.000 claims description 22
- VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 claims description 22
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 20
- 210000004369 blood Anatomy 0.000 claims description 20
- 239000008280 blood Substances 0.000 claims description 20
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 20
- 241000283690 Bos taurus Species 0.000 claims description 19
- 241001494479 Pecora Species 0.000 claims description 19
- 239000003963 antioxidant agent Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 19
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 18
- 239000008181 tonicity modifier Substances 0.000 claims description 18
- 108010073961 Insulin Aspart Proteins 0.000 claims description 17
- 230000003078 antioxidant effect Effects 0.000 claims description 17
- 235000011187 glycerol Nutrition 0.000 claims description 17
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 17
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 17
- 229940068977 polysorbate 20 Drugs 0.000 claims description 17
- 239000007983 Tris buffer Substances 0.000 claims description 16
- 244000005700 microbiome Species 0.000 claims description 16
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 claims description 13
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 13
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 13
- 229920000053 polysorbate 80 Polymers 0.000 claims description 13
- 229940068968 polysorbate 80 Drugs 0.000 claims description 13
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 12
- 230000007935 neutral effect Effects 0.000 claims description 12
- 230000000087 stabilizing effect Effects 0.000 claims description 12
- 229960002068 insulin lispro Drugs 0.000 claims description 11
- 230000002641 glycemic effect Effects 0.000 claims description 10
- 230000001965 increasing effect Effects 0.000 claims description 10
- 229920001993 poloxamer 188 Polymers 0.000 claims description 10
- 229940044519 poloxamer 188 Drugs 0.000 claims description 10
- 235000000346 sugar Nutrition 0.000 claims description 9
- 101001041117 Homo sapiens Hyaluronidase PH-20 Proteins 0.000 claims description 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 8
- 108010005991 Pork Regular Insulin Proteins 0.000 claims description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 208000004104 gestational diabetes Diseases 0.000 claims description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 8
- 229920005862 polyol Polymers 0.000 claims description 8
- 150000003077 polyols Chemical class 0.000 claims description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 8
- 150000003862 amino acid derivatives Chemical class 0.000 claims description 7
- 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 6
- 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 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 230000006870 function Effects 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 229920001451 polypropylene glycol Polymers 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
- 229950008882 polysorbate Drugs 0.000 claims description 5
- 239000001488 sodium phosphate Substances 0.000 claims description 5
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 5
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 5
- 229960005150 glycerol Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 4
- 229960000502 poloxamer Drugs 0.000 claims description 4
- 229960002920 sorbitol Drugs 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims description 3
- 238000012544 monitoring process Methods 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 description 221
- 108090000790 Enzymes Proteins 0.000 description 221
- 229940088598 enzyme Drugs 0.000 description 214
- 229920002674 hyaluronan Polymers 0.000 description 213
- 229940099552 hyaluronan Drugs 0.000 description 194
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 192
- 230000000593 degrading effect Effects 0.000 description 180
- 125000003275 alpha amino acid group Chemical group 0.000 description 87
- 235000001014 amino acid Nutrition 0.000 description 82
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 81
- 229940024606 amino acid Drugs 0.000 description 80
- -1 s Chemical class 0.000 description 72
- 108050009363 Hyaluronidases Proteins 0.000 description 63
- 108090000623 proteins and genes Proteins 0.000 description 49
- 235000018102 proteins Nutrition 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 34
- 239000000126 substance Substances 0.000 description 34
- 238000011081 inoculation Methods 0.000 description 29
- 150000007523 nucleic acids Chemical class 0.000 description 27
- 230000007423 decrease Effects 0.000 description 26
- 241000282414 Homo sapiens Species 0.000 description 25
- 102000039446 nucleic acids Human genes 0.000 description 25
- 108020004707 nucleic acids Proteins 0.000 description 25
- 125000000539 amino acid group Chemical group 0.000 description 23
- 235000006109 methionine Nutrition 0.000 description 22
- 229960004452 methionine Drugs 0.000 description 22
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- 229960003160 hyaluronic acid Drugs 0.000 description 19
- 238000001802 infusion Methods 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
- 235000006708 antioxidants Nutrition 0.000 description 17
- 239000000872 buffer Substances 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 230000000845 anti-microbial effect Effects 0.000 description 15
- 238000001514 detection method Methods 0.000 description 15
- 239000002773 nucleotide Substances 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 235000013824 polyphenols Nutrition 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 230000002255 enzymatic effect Effects 0.000 description 14
- 239000002243 precursor Substances 0.000 description 14
- 238000003860 storage Methods 0.000 description 14
- 230000001580 bacterial effect Effects 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- 239000012528 membrane Substances 0.000 description 12
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 241000894007 species Species 0.000 description 12
- 239000011701 zinc Substances 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 230000002538 fungal effect Effects 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 229940124597 therapeutic agent Drugs 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 229910052725 zinc Inorganic materials 0.000 description 10
- 108010076504 Protein Sorting Signals Proteins 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000004071 biological effect Effects 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 201000001421 hyperglycemia Diseases 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 101000585728 Homo sapiens Protein O-GlcNAcase Proteins 0.000 description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 230000002411 adverse Effects 0.000 description 7
- 239000004599 antimicrobial Substances 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 229960002885 histidine Drugs 0.000 description 7
- 102000046319 human OGA Human genes 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 150000002989 phenols Chemical class 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 108010023736 Chondroitinases and Chondroitin Lyases Proteins 0.000 description 6
- 102000011413 Chondroitinases and Chondroitin Lyases Human genes 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000001276 controlling effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 235000012054 meals Nutrition 0.000 description 6
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 6
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 6
- 229960002216 methylparaben Drugs 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- LXQFWEBCTJENGB-BZDVOYDHSA-N (2s)-6-amino-2-[[(2s)-2,6-diaminohexanoyl]amino]hexanoic acid;dihydrochloride Chemical class Cl.Cl.NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN LXQFWEBCTJENGB-BZDVOYDHSA-N 0.000 description 5
- 241000700199 Cavia porcellus Species 0.000 description 5
- 229920001287 Chondroitin sulfate Polymers 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 108010076181 Proinsulin Proteins 0.000 description 5
- 230000009102 absorption Effects 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 5
- 239000002068 microbial inoculum Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 108010066381 preproinsulin Proteins 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 4
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 4
- 229920002567 Chondroitin Polymers 0.000 description 4
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 4
- 108010090613 Human Regular Insulin Proteins 0.000 description 4
- 102000013266 Human Regular Insulin Human genes 0.000 description 4
- 108091006905 Human Serum Albumin Proteins 0.000 description 4
- 102000008100 Human Serum Albumin Human genes 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 241000282567 Macaca fascicularis Species 0.000 description 4
- 241000282560 Macaca mulatta Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000282577 Pan troglodytes Species 0.000 description 4
- 238000012300 Sequence Analysis Methods 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- RCHHVVGSTHAVPF-ZPHPLDECSA-N apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 4
- 229940112930 apidra Drugs 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000012707 chemical precursor Substances 0.000 description 4
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 229940101556 human hyaluronidase Drugs 0.000 description 4
- 229940103471 humulin Drugs 0.000 description 4
- 108010048296 hyaluronidase PH-20 Proteins 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 108700039926 insulin glulisine Proteins 0.000 description 4
- 229940127560 insulin pen Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 229960003646 lysine Drugs 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229940112879 novolog Drugs 0.000 description 4
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 4
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 4
- 230000004481 post-translational protein modification Effects 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 235000011008 sodium phosphates Nutrition 0.000 description 4
- 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 3
- WEDIKSVWBUKTRA-WTKGVUNUSA-N CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC WEDIKSVWBUKTRA-WTKGVUNUSA-N 0.000 description 3
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 3
- 108090000819 Chondroitin-sulfate-ABC endolyases Proteins 0.000 description 3
- 102000037716 Chondroitin-sulfate-ABC endolyases Human genes 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- 208000028399 Critical Illness Diseases 0.000 description 3
- 241000238424 Crustacea Species 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000545744 Hirudinea Species 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 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 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940107200 chondroitin sulfates Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000000368 destabilizing effect Effects 0.000 description 3
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 229960002449 glycine Drugs 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 229940038661 humalog Drugs 0.000 description 3
- 229940044700 hylenex Drugs 0.000 description 3
- 230000003345 hyperglycaemic effect Effects 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 229960002429 proline Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000002381 testicular Effects 0.000 description 3
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 3
- 229940033663 thimerosal Drugs 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 229940054953 vitrase Drugs 0.000 description 3
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 2
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 2
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 2
- HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 2
- WJLVQTJZDCGNJN-UHFFFAOYSA-N Chlorhexidine hydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 WJLVQTJZDCGNJN-UHFFFAOYSA-N 0.000 description 2
- 102000018963 Chondroitin Lyases Human genes 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 108010057186 Insulin Glargine Proteins 0.000 description 2
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical group 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
- 241000605114 Pedobacter heparinus Species 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 241000282405 Pongo abelii Species 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241000588767 Proteus vulgaris Species 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 239000004288 Sodium dehydroacetate Substances 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 241000256856 Vespidae Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003888 alpha glucosidase inhibitor Chemical class 0.000 description 2
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- 229960001599 aminoquinuride Drugs 0.000 description 2
- 229940042450 amphadase Drugs 0.000 description 2
- 235000021120 animal protein Nutrition 0.000 description 2
- 229940127003 anti-diabetic drug Drugs 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- 229960003872 benzethonium Drugs 0.000 description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 150000004283 biguanides Chemical class 0.000 description 2
- 229940076094 bovine hyaluronidase Drugs 0.000 description 2
- 229940067596 butylparaben Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000021523 carboxylation Effects 0.000 description 2
- 238000006473 carboxylation reaction Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 229960002798 cetrimide Drugs 0.000 description 2
- 229960003260 chlorhexidine Drugs 0.000 description 2
- 229960002242 chlorocresol Drugs 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 210000001771 cumulus cell Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 150000002016 disaccharides Chemical group 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 230000006126 farnesylation Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000004554 glutamine Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 229940014041 hyaluronate Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 229950004152 insulin human Drugs 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229950004994 meglitinide Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940100630 metacresol Drugs 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- HOUSDILKOJMENG-UHFFFAOYSA-N n,n'-bis(4-amino-2-methylquinolin-6-yl)urea Chemical compound N1=C(C)C=C(N)C2=CC(NC(=O)NC3=CC4=C(N)C=C(N=C4C=C3)C)=CC=C21 HOUSDILKOJMENG-UHFFFAOYSA-N 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 229940007042 proteus vulgaris Drugs 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 2
- 229940079839 sodium dehydroacetate Drugs 0.000 description 2
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 150000004044 tetrasaccharides Chemical class 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical group Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- IDOQDZANRZQBTP-UHFFFAOYSA-N 2-[2-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=CC=C1OCCO IDOQDZANRZQBTP-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- YVOOPGWEIRIUOX-UHFFFAOYSA-N 2-azanyl-3-sulfanyl-propanoic acid Chemical compound SCC(N)C(O)=O.SCC(N)C(O)=O YVOOPGWEIRIUOX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000607620 Aliivibrio fischeri Species 0.000 description 1
- 241000256837 Apidae Species 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000186073 Arthrobacter sp. Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000604931 Bdellovibrio bacteriovorus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 108030004675 Chondroitin AC lyases Proteins 0.000 description 1
- 108010026719 Chondroitin Lyases Proteins 0.000 description 1
- 108030006206 Chondroitin-sulfate-ABC exolyases Proteins 0.000 description 1
- 101710106625 Chondroitinase-AC Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 244000165918 Eucalyptus papuana Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000589565 Flavobacterium Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000962530 Homo sapiens Hyaluronidase-1 Proteins 0.000 description 1
- 101000962526 Homo sapiens Hyaluronidase-2 Proteins 0.000 description 1
- 101001041128 Homo sapiens Hyaluronidase-3 Proteins 0.000 description 1
- 101001041120 Homo sapiens Hyaluronidase-4 Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 229940122393 Hyaluronidase inhibitor Drugs 0.000 description 1
- 102100039283 Hyaluronidase-1 Human genes 0.000 description 1
- 102100039285 Hyaluronidase-2 Human genes 0.000 description 1
- 102100021081 Hyaluronidase-4 Human genes 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 229920001202 Inulin Polymers 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101100128278 Mus musculus Lins1 gene Proteins 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 108700031300 NovoSol Basal insulin Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000157908 Paenarthrobacter aurescens Species 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193985 Streptococcus agalactiae Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 241000194021 Streptococcus suis Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 101000993800 Sus scrofa Insulin Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229920004929 Triton X-114 Polymers 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 241000703751 Victivallis vadensis Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- ZWIJWDCFGVKPGY-RTRLPJTCSA-N [[(3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]amino] acetate Chemical group C(C)(=O)ON[C@H]1C(O)O[C@@H]([C@H]([C@@H]1O)O)CO ZWIJWDCFGVKPGY-RTRLPJTCSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- XYAUIVRRMJYYHR-UHFFFAOYSA-N acetic acid;propane-1,2,3-triol Chemical compound CC(O)=O.OCC(O)CO XYAUIVRRMJYYHR-UHFFFAOYSA-N 0.000 description 1
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- YAJCHEVQCOHZDC-QMMNLEPNSA-N actrapid Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@H](C)CC)[C@H](C)CC)[C@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C(N)=O)C1=CNC=N1 YAJCHEVQCOHZDC-QMMNLEPNSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3N=CN=C3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000667 effect on insulin Effects 0.000 description 1
- 230000009230 endogenous glucose production Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 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
- 230000002163 immunogen Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 229960002869 insulin glargine Drugs 0.000 description 1
- 230000006362 insulin response pathway Effects 0.000 description 1
- 229940029339 inulin Drugs 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000000415 mammalian chromosome Anatomy 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229910052755 nonmetal Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229940103453 novolin Drugs 0.000 description 1
- 235000006180 nutrition needs Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- RDYOACUIENLGER-UHFFFAOYSA-N phenol;propane-1,2,3-triol Chemical compound OCC(O)CO.OC1=CC=CC=C1 RDYOACUIENLGER-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- CKRORYDHXIRZCH-UHFFFAOYSA-N phosphoric acid;dihydrate Chemical compound O.O.OP(O)(O)=O CKRORYDHXIRZCH-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 229940055019 propionibacterium acne Drugs 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 229940124272 protein stabilizer Drugs 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161520962P | 2011-06-17 | 2011-06-17 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201501068A1 EA201501068A1 (ru) | 2016-07-29 |
| EA033472B1 true EA033472B1 (ru) | 2019-10-31 |
Family
ID=46513830
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201501068A EA033472B1 (ru) | 2011-06-17 | 2012-06-15 | Композиция для стабилизации гиалуронидазы и ее применение |
| EA201400031A EA201400031A1 (ru) | 2011-06-17 | 2012-06-15 | Стабильные составы на основе фермента, разрушающего хиалуронан |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201400031A EA201400031A1 (ru) | 2011-06-17 | 2012-06-15 | Стабильные составы на основе фермента, разрушающего хиалуронан |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP2720712B1 (cg-RX-API-DMAC7.html) |
| JP (3) | JP2014518216A (cg-RX-API-DMAC7.html) |
| KR (2) | KR101874401B1 (cg-RX-API-DMAC7.html) |
| CN (2) | CN105797140B (cg-RX-API-DMAC7.html) |
| AU (2) | AU2012271359B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR112013032396A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2839511C (cg-RX-API-DMAC7.html) |
| EA (2) | EA033472B1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2566549T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL229749A0 (cg-RX-API-DMAC7.html) |
| MX (1) | MX340172B (cg-RX-API-DMAC7.html) |
| NZ (2) | NZ717728A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2012174478A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9993529B2 (en) | 2011-06-17 | 2018-06-12 | Halozyme, Inc. | Stable formulations of a hyaluronan-degrading enzyme |
| SI3130347T1 (sl) | 2011-12-30 | 2020-02-28 | Halozyme, Inc. | Variante polipeptida PH20, formulacije in uporabe le-teh |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| CA2895875A1 (en) | 2012-12-21 | 2014-06-26 | Sanofi | Exendin-4 derivatives |
| TWI780236B (zh) * | 2013-02-04 | 2022-10-11 | 法商賽諾菲公司 | 胰島素類似物及/或胰島素衍生物之穩定化醫藥調配物 |
| SG10201913433SA (en) * | 2013-02-04 | 2020-03-30 | Sanofi Sa | Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives |
| AR098168A1 (es) * | 2013-10-25 | 2016-05-04 | Sanofi Sa | Formulación estable de insulina glulisina |
| EP3080150B1 (en) | 2013-12-13 | 2018-08-01 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| RU2016132342A (ru) | 2014-01-09 | 2018-02-14 | Санофи | Стабилизированные фармацевтические составы на основе инсулиновых аналогов и/или инсулиновых производных |
| JP6562902B2 (ja) * | 2014-03-28 | 2019-08-21 | テルモ株式会社 | 生体血管内血液置換用液体、生体血管内血液置換用液体製剤およびプレフィルドシリンジ |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| CN104095871A (zh) * | 2014-07-10 | 2014-10-15 | 青岛蔚蓝生物股份有限公司 | 一种含盐酸林可霉素与硫酸大观霉素的兽用注射液 |
| CA2958145C (en) * | 2014-07-16 | 2023-09-26 | New York University | Use of hyaluronidase for treatment of muscle stiffness |
| AR102869A1 (es) * | 2014-12-16 | 2017-03-29 | Lilly Co Eli | Composiciones de insulina de rápida acción |
| AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
| AR105284A1 (es) | 2015-07-10 | 2017-09-20 | Sanofi Sa | Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón |
| CN105018457A (zh) * | 2015-07-20 | 2015-11-04 | 宁波美成生物科技有限公司 | 虫荧光素酶稳定剂 |
| CN114835793A (zh) * | 2015-11-16 | 2022-08-02 | Ubi蛋白公司 | 用于延长蛋白质半衰期的方法 |
| KR102295786B1 (ko) | 2016-09-06 | 2021-09-01 | 신파 티엔리 파머슈티컬 컴퍼니 리미티드 (항저우) | 스킨케어 및/또는 상처치유 촉진에 있어서 복령 추출물 및 이의 활성 성분의 용도 |
| US10369190B2 (en) | 2016-09-13 | 2019-08-06 | Allergan, Inc. | Non-protein clostridial toxin compositions |
| CN108070532A (zh) * | 2016-11-16 | 2018-05-25 | 福建力多利生物科技有限公司 | 一种生产葡萄糖氧化酶的方法 |
| US11510967B2 (en) | 2017-09-08 | 2022-11-29 | Eli Lilly And Company | Pharmaceutical combinations comprising insulin and at least an agent selected from meloxicam, bromfenac sodium, acetylsalicylic acid, salicyclic acid and paracetamol |
| CN107918020B (zh) * | 2017-11-15 | 2019-01-01 | 浙江夸克生物科技有限公司 | 中性粒细胞明胶酶相关脂质运载蛋白测定试剂盒 |
| CN118853631A (zh) | 2018-07-25 | 2024-10-29 | 阿特根公司 | 新型透明质酸水解酶突变体和包含其的药物组合物 |
| EP3937904A1 (en) * | 2019-03-15 | 2022-01-19 | Eli Lilly and Company | Preserved formulations |
| CN110592056A (zh) * | 2019-09-19 | 2019-12-20 | 昆明理工大学 | 噬菌体裂解酶复合粉剂及其制备方法和应用 |
| CN110713983B (zh) * | 2019-11-04 | 2022-06-10 | 深圳市体内生物医药科技有限公司 | 一种表达透明质酸酶的免疫细胞及其应用 |
| CA3137324A1 (en) * | 2020-01-23 | 2021-07-29 | Alteogen, Inc. | Novel hyaluronidase variants with improved stability and pharmaceutical composition containing the same |
| BR112022019726A2 (pt) | 2020-08-07 | 2023-03-07 | Alteogen Inc | Método para produzir hialuronidase recombinante |
| JP2024501029A (ja) | 2020-12-28 | 2024-01-10 | ブリストル－マイヤーズ スクイブ カンパニー | Ｐｄ１／ｐｄ－ｌ１抗体の皮下投与 |
| EP4566674A3 (en) | 2020-12-28 | 2025-08-06 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| JP2024501721A (ja) * | 2020-12-30 | 2024-01-15 | 上海宝済薬業股▲ふん▼有限公司 | 組換えヒトヒアルロニダーゼ製剤およびその用途 |
| WO2023075506A1 (ko) * | 2021-10-29 | 2023-05-04 | (주)알테오젠 | 인간 히알루로니다제 ph20과 약물을 포함하는 약학 조성물 |
| CN115820766B (zh) * | 2021-12-28 | 2024-11-12 | 华熙生物科技股份有限公司 | 一种酶法制备软骨素寡聚糖的方法及软骨素寡聚糖组合物 |
| US20250332252A1 (en) | 2022-06-02 | 2025-10-30 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
| IL321554A (en) * | 2022-12-23 | 2025-08-01 | Hanmi Pharmaceutical Co Ltd | Formulations comprising immune stimulating il-2 analog conjugates |
| KR102554775B1 (ko) * | 2023-02-07 | 2023-07-12 | 한국코러스 주식회사 | 히알루로니다제의 안정화제 및 이를 포함하는 히알루로니다제 제형 |
| CN117243852A (zh) * | 2023-11-01 | 2023-12-19 | 华熙生物科技股份有限公司 | 一种皮肤外用组合物及其用途 |
| CN119074669B (zh) * | 2024-06-21 | 2025-04-18 | 邢珺月 | 一种靶向缓解化疗心脏毒性的纳米酶及其制备方法和应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009134380A2 (en) * | 2008-04-28 | 2009-11-05 | Halozyme, Inc. | Super fast-acting insulin compositions |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4002531A (en) | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| EP0162007A1 (de) * | 1984-04-18 | 1985-11-21 | Geriaco AG | Stabiles, lagerungsfähiges Insulinpräparat zur Behandlung von Akne vulgaris |
| EP0250119A3 (en) * | 1986-06-20 | 1990-04-18 | Vasocor | Atherosclerotic anti-idiotype antibody immunoassay and reagents |
| US5324844A (en) | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5122614A (en) | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| US6093563A (en) | 1994-07-08 | 2000-07-25 | Ibex Technologies R And D, Inc. | Chondroitin lyase enzymes |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5747027A (en) | 1995-04-07 | 1998-05-05 | The Regents Of The University Of California | BH55 hyaluronidase |
| US5672662A (en) | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| US6610292B2 (en) * | 1995-11-22 | 2003-08-26 | Ista Pharmaceuticals, Inc. | Use of hyaluronidase in the manufacture of an ophthalmic preparation for liquefying vitreous humor in the treatment of eye disorders |
| DE69826705T2 (de) | 1997-11-12 | 2006-02-23 | Alza Corp., Palo Alto | Verfahren zur dermalen verabreichung von polypeptiden |
| US6669663B1 (en) * | 1999-04-30 | 2003-12-30 | Medtronic, Inc. | Closed loop medicament pump |
| US6563022B2 (en) * | 1999-07-05 | 2003-05-13 | Toyo Boseki Kabushiki Kaisha | Cotton plants with improved cotton fiber characteristics and method for producing cotton fibers from these cotton plants |
| DK1259562T3 (da) | 1999-12-22 | 2006-04-18 | Nektar Therapeutics Al Corp | Sterisk hindrede derivater af vandoplöselige polymerer |
| MXPA02011481A (es) * | 2000-05-19 | 2003-06-06 | Alcon Inc | Derivados de disulfuro que son utiles para el tratamiento de enfermedades alergicas. |
| US6902548B1 (en) * | 2001-03-19 | 2005-06-07 | Ed Schuler | Use of Streptomyces hyalurolyticus enzyme in ophthalmic treatments |
| US20030125234A1 (en) * | 2001-12-11 | 2003-07-03 | Middaugh Charles Russell | Alteration of protein stability |
| EP2572733A1 (en) | 2003-02-26 | 2013-03-27 | Nektar Therapeutics | Polymer-factor VIII moiety conjugates |
| US7871607B2 (en) | 2003-03-05 | 2011-01-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases |
| EP1603541B2 (en) | 2003-03-05 | 2013-01-23 | Halozyme, Inc. | SOLUBLE HYALURONIDASE GLYCOPROTEIN (sHASEGP), PROCESS FOR PREPARING THE SAME, USES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEREOF |
| US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| WO2004094630A1 (en) * | 2003-04-23 | 2004-11-04 | Hexima Ltd | Insect chymotrypsin and inhibitors thereof |
| US7279457B2 (en) | 2004-03-12 | 2007-10-09 | Biodel, Inc. | Rapid acting drug delivery compositions |
| AU2005227757C1 (en) * | 2004-03-31 | 2009-08-13 | Hexima Ltd | Arabinogalactan protein compositions and methods for fostering somatic embryogenic competence |
| WO2005118799A1 (en) * | 2004-04-15 | 2005-12-15 | Ista Pharmaceuticals, Inc. | Ovine hyaluronidase |
| WO2007047242A2 (en) * | 2005-10-14 | 2007-04-26 | Soll David B | Ophthalmic surgical irrigating solutions containing hyaluronidase |
| US20100210506A1 (en) * | 2005-10-20 | 2010-08-19 | Mdrna, Inc. | Intranasal administration of rapid acting insulin |
| US20090325860A1 (en) * | 2006-08-04 | 2009-12-31 | Nastech Pharmaceutical Company Inc. | Compositions for intranasal delivery of human insulin and uses thereof |
| IL186598A0 (en) * | 2007-10-11 | 2008-11-03 | Mohammad Abdulrazik | Composition and method for the treatment or prevention of glaucoma and ocular hypertension |
| EP3760715B1 (en) | 2008-03-06 | 2021-08-04 | Halozyme, Inc. | Large-scale production of soluble hyaluronidase |
| TWI451876B (zh) * | 2008-06-13 | 2014-09-11 | Lilly Co Eli | 聚乙二醇化之離脯胰島素化合物 |
| EA022752B1 (ru) | 2008-12-09 | 2016-02-29 | Галозим, Инк. | Длинные растворимые полипептиды рн20 и их использование |
| TWI520745B (zh) * | 2009-07-06 | 2016-02-11 | 賽諾菲阿凡提斯德意志有限公司 | 含甲硫胺酸之胰島素製劑 |
| CN102655853B (zh) | 2009-09-17 | 2015-07-29 | 巴克斯特卫生保健有限公司 | 透明质酸酶和免疫球蛋白的稳定的复合制剂及其使用方法 |
| EP2720713A2 (en) * | 2011-06-17 | 2014-04-23 | Halozyme, Inc. | Continuous subcutaneous insulin infusion methods with a hyaluronan degrading enzyme |
| SI3130347T1 (sl) * | 2011-12-30 | 2020-02-28 | Halozyme, Inc. | Variante polipeptida PH20, formulacije in uporabe le-teh |
-
2012
- 2012-06-15 CN CN201610243096.3A patent/CN105797140B/zh active Active
- 2012-06-15 CN CN201280039713.8A patent/CN103974715A/zh active Pending
- 2012-06-15 JP JP2014516067A patent/JP2014518216A/ja active Pending
- 2012-06-15 EP EP12735366.2A patent/EP2720712B1/en active Active
- 2012-06-15 EA EA201501068A patent/EA033472B1/ru not_active IP Right Cessation
- 2012-06-15 MX MX2013014923A patent/MX340172B/es active IP Right Grant
- 2012-06-15 NZ NZ717728A patent/NZ717728A/en unknown
- 2012-06-15 KR KR1020177027130A patent/KR101874401B1/ko active Active
- 2012-06-15 EA EA201400031A patent/EA201400031A1/ru unknown
- 2012-06-15 KR KR1020147001375A patent/KR20140043438A/ko not_active Ceased
- 2012-06-15 CA CA2839511A patent/CA2839511C/en active Active
- 2012-06-15 ES ES12735366.2T patent/ES2566549T3/es active Active
- 2012-06-15 AU AU2012271359A patent/AU2012271359B2/en not_active Ceased
- 2012-06-15 WO PCT/US2012/042816 patent/WO2012174478A2/en not_active Ceased
- 2012-06-15 BR BR112013032396A patent/BR112013032396A2/pt not_active IP Right Cessation
- 2012-06-15 NZ NZ618331A patent/NZ618331A/en not_active IP Right Cessation
-
2013
- 2013-12-02 IL IL229749A patent/IL229749A0/en unknown
-
2016
- 2016-04-19 AU AU2016202472A patent/AU2016202472B2/en active Active
- 2016-10-12 JP JP2016200761A patent/JP6224802B2/ja active Active
-
2017
- 2017-06-06 JP JP2017111643A patent/JP2017197556A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009134380A2 (en) * | 2008-04-28 | 2009-11-05 | Halozyme, Inc. | Super fast-acting insulin compositions |
| US20090304665A1 (en) * | 2008-04-28 | 2009-12-10 | Frost Gregory I | Super fast-acting insulin compositions |
Non-Patent Citations (1)
| Title |
|---|
| HOMPESCH Marcus et al. Accelerated insulin Pharmacokinetics and Improved Postprandial Glycemic Control in Patients With Type 1 Diabetes After Coadministration of Prandial Insulines With Hyaluronidase. Diabetes Care, March 2011, Vol. 34(3): pp. 666-668 doi:10.2337/dc10-1892. Epub 2011 Jan 27 * |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ717728A (en) | 2016-04-29 |
| JP2017197556A (ja) | 2017-11-02 |
| EA201400031A1 (ru) | 2014-07-30 |
| NZ618331A (en) | 2016-04-29 |
| MX2013014923A (es) | 2014-02-11 |
| WO2012174478A9 (en) | 2013-05-30 |
| AU2012271359B2 (en) | 2016-05-19 |
| AU2016202472B2 (en) | 2017-02-02 |
| KR20170116173A (ko) | 2017-10-18 |
| BR112013032396A2 (pt) | 2016-11-22 |
| KR101874401B1 (ko) | 2018-07-04 |
| CN103974715A (zh) | 2014-08-06 |
| CN105797140B (zh) | 2020-08-11 |
| MX340172B (es) | 2016-06-28 |
| EP2720712A2 (en) | 2014-04-23 |
| JP2014518216A (ja) | 2014-07-28 |
| EP2720712B1 (en) | 2016-03-02 |
| ES2566549T3 (es) | 2016-04-13 |
| CA2839511C (en) | 2018-07-31 |
| JP2017036313A (ja) | 2017-02-16 |
| WO2012174478A2 (en) | 2012-12-20 |
| JP6224802B2 (ja) | 2017-11-01 |
| WO2012174478A3 (en) | 2013-04-11 |
| CA2839511A1 (en) | 2012-12-20 |
| KR20140043438A (ko) | 2014-04-09 |
| IL229749A0 (en) | 2014-01-30 |
| CN105797140A (zh) | 2016-07-27 |
| EA201501068A1 (ru) | 2016-07-29 |
| AU2012271359A1 (en) | 2014-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101874401B1 (ko) | 히알루로난 분해 효소의 안정한 제형 | |
| KR101676543B1 (ko) | 히알루로난 분해효소를 이용한 연속적인 피하 인슐린 주입 방법 | |
| KR101516534B1 (ko) | 초속효성 인슐린 조성물 | |
| US9993529B2 (en) | Stable formulations of a hyaluronan-degrading enzyme | |
| NZ618301B2 (en) | Continuous subcutaneous insulin infusion methods with a hyaluronan degrading enzyme |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG TJ TM |