JP4528443B2 - 環状プロサポシン由来のペプチドおよびその使用 - Google Patents
環状プロサポシン由来のペプチドおよびその使用 Download PDFInfo
- Publication number
- JP4528443B2 JP4528443B2 JP2000567569A JP2000567569A JP4528443B2 JP 4528443 B2 JP4528443 B2 JP 4528443B2 JP 2000567569 A JP2000567569 A JP 2000567569A JP 2000567569 A JP2000567569 A JP 2000567569A JP 4528443 B2 JP4528443 B2 JP 4528443B2
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- amino acid
- acid
- cyclic
- peptides
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 106
- 102000004196 processed proteins & peptides Human genes 0.000 title description 31
- 125000004122 cyclic group Chemical group 0.000 title description 18
- 102100036197 Prosaposin Human genes 0.000 title description 9
- 101710152403 Prosaposin Proteins 0.000 title description 9
- 150000001413 amino acids Chemical class 0.000 claims description 91
- 235000001014 amino acid Nutrition 0.000 claims description 89
- 229940024606 amino acid Drugs 0.000 claims description 86
- 230000002209 hydrophobic effect Effects 0.000 claims description 33
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 20
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 20
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 20
- 235000003704 aspartic acid Nutrition 0.000 claims description 20
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 20
- 235000013922 glutamic acid Nutrition 0.000 claims description 20
- 239000004220 glutamic acid Substances 0.000 claims description 20
- 102000001189 Cyclic Peptides Human genes 0.000 claims description 16
- 108010069514 Cyclic Peptides Proteins 0.000 claims description 16
- 230000014511 neuron projection development Effects 0.000 claims description 16
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 14
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 14
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 14
- 239000004472 Lysine Substances 0.000 claims description 14
- 235000018977 lysine Nutrition 0.000 claims description 14
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 13
- 239000004475 Arginine Substances 0.000 claims description 12
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 12
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 12
- 235000009697 arginine Nutrition 0.000 claims description 12
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 11
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 11
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 11
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 11
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 11
- 239000004473 Threonine Substances 0.000 claims description 11
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 11
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 11
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 11
- 229960000310 isoleucine Drugs 0.000 claims description 11
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 11
- 239000004474 valine Substances 0.000 claims description 11
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 10
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 10
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 10
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 10
- 235000009582 asparagine Nutrition 0.000 claims description 10
- 229960001230 asparagine Drugs 0.000 claims description 10
- 229930182817 methionine Natural products 0.000 claims description 10
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims description 10
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- 235000004279 alanine Nutrition 0.000 claims description 7
- 230000001737 promoting effect Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000016273 neuron death Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 102000017852 Saposin Human genes 0.000 description 21
- 108050007079 Saposin Proteins 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 19
- 208000016192 Demyelinating disease Diseases 0.000 description 17
- 208000004296 neuralgia Diseases 0.000 description 17
- 208000021722 neuropathic pain Diseases 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 230000023105 myelination Effects 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 206010012305 Demyelination Diseases 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 230000000508 neurotrophic effect Effects 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 206010012601 diabetes mellitus Diseases 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 10
- 108010025020 Nerve Growth Factor Proteins 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 102000007072 Nerve Growth Factors Human genes 0.000 description 7
- 230000008499 blood brain barrier function Effects 0.000 description 7
- 210000001218 blood-brain barrier Anatomy 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 230000001537 neural effect Effects 0.000 description 7
- 101800005149 Peptide B Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 238000007917 intracranial administration Methods 0.000 description 6
- 239000003900 neurotrophic factor Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 210000004116 schwann cell Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 108010091748 peptide A Proteins 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- -1 cyclic amino acid Chemical class 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 210000002161 motor neuron Anatomy 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 210000001428 peripheral nervous system Anatomy 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 230000000472 traumatic effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102100037597 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 208000004454 Hyperalgesia Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 210000005064 dopaminergic neuron Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 210000000578 peripheral nerve Anatomy 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000035807 sensation Effects 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 3
- 229960001052 streptozocin Drugs 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000008736 traumatic injury Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 101500007657 Crotalus durissus terrificus Crotoxin chain gamma Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 description 2
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000003210 demyelinating effect Effects 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000000609 ganglia Anatomy 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000003458 metachromatic effect Effects 0.000 description 2
- 210000003007 myelin sheath Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000002241 neurite Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 208000027232 peripheral nervous system disease Diseases 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000001044 sensory neuron Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 210000003523 substantia nigra Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001228 trophic effect Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- KSDDQEGWVBODMD-OULINLAESA-N (2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-sulfanylpropanoyl]amino]-4-carboxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-4-carboxybutanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CS)CC1=CC=CC=C1 KSDDQEGWVBODMD-OULINLAESA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 1
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 125000000030 D-alanine group Chemical group [H]N([H])[C@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 101500025567 Homo sapiens Saposin-C Proteins 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 108010010224 NK-lysin Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029174 Nerve compression Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000005890 Neuroma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000003837 chick embryo Anatomy 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 231100000722 genetic damage Toxicity 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 150000002614 leucines Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 230000007514 neuronal growth Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000020925 non fasting Nutrition 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000002856 peripheral neuron Anatomy 0.000 description 1
- 210000005223 peripheral sensory neuron Anatomy 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108010076038 prosaptide Proteins 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9835998P | 1998-08-28 | 1998-08-28 | |
| US60/098,359 | 1998-08-28 | ||
| PCT/US1999/019378 WO2000012553A1 (en) | 1998-08-28 | 1999-08-20 | Cyclic prosaposin-derived peptides and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010034833A Division JP2010150272A (ja) | 1998-08-28 | 2010-02-19 | 環状プロサポシン由来のペプチドおよびその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002523518A JP2002523518A (ja) | 2002-07-30 |
| JP2002523518A5 JP2002523518A5 (pl) | 2006-08-10 |
| JP4528443B2 true JP4528443B2 (ja) | 2010-08-18 |
Family
ID=22268937
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000567569A Expired - Fee Related JP4528443B2 (ja) | 1998-08-28 | 1999-08-20 | 環状プロサポシン由来のペプチドおよびその使用 |
| JP2010034833A Pending JP2010150272A (ja) | 1998-08-28 | 2010-02-19 | 環状プロサポシン由来のペプチドおよびその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010034833A Pending JP2010150272A (ja) | 1998-08-28 | 2010-02-19 | 環状プロサポシン由来のペプチドおよびその使用 |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1105420A1 (pl) |
| JP (2) | JP4528443B2 (pl) |
| KR (1) | KR20010079695A (pl) |
| CN (1) | CN1324367A (pl) |
| AU (1) | AU751034B2 (pl) |
| BR (1) | BR9913490A (pl) |
| CA (1) | CA2341810A1 (pl) |
| CZ (1) | CZ2001655A3 (pl) |
| HU (1) | HUP0103265A3 (pl) |
| IL (1) | IL141586A0 (pl) |
| PL (1) | PL204359B1 (pl) |
| WO (1) | WO2000012553A1 (pl) |
| ZA (1) | ZA200102489B (pl) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010150272A (ja) * | 1998-08-28 | 2010-07-08 | Myelos Corp | 環状プロサポシン由来のペプチドおよびその使用 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5571787A (en) | 1993-07-30 | 1996-11-05 | Myelos Corporation | Prosaposin as a neurotrophic factor |
| AUPQ084899A0 (en) * | 1999-06-08 | 1999-07-01 | University Of Melbourne, The | Neurotrophin agonists |
| IL137820A (en) * | 2000-08-10 | 2009-06-15 | S I S Shulov Inst For Science | Pharmaceutical composition for topical administration comprising an analgesic peptide |
| CN100366286C (zh) * | 2003-04-28 | 2008-02-06 | 常州南云科技有限公司 | Saposin C-DOPS:一种抗癌新药 |
| EP2020988B1 (en) | 2006-04-28 | 2017-08-16 | Children's Hospital Medical Center | Compositions comprising fusogenic proteins or polypeptides derived from prosaposin for application in transmembrane drug delivery systems |
| CN101541307A (zh) * | 2006-10-20 | 2009-09-23 | 儿童医院医疗中心 | 自发形成的椭圆体磷脂单层囊泡 |
| CN103275187B (zh) * | 2013-06-14 | 2014-10-29 | 四川合泰新光生物科技有限公司 | 一种镇痛肽fi及其基因和应用 |
| JP7066412B2 (ja) | 2015-04-23 | 2022-05-13 | ザ プロクター アンド ギャンブル カンパニー | 界面活性剤可溶性抗ふけ剤の送達 |
| ES2893974T3 (es) | 2016-03-03 | 2022-02-10 | Procter & Gamble | Composición anticaspa en aerosol |
| WO2018075850A1 (en) | 2016-10-21 | 2018-04-26 | The Procter & Gamble Company | Dosage of foam for delivering consumer desired dosage volume and surfactant amount in an optimal formulation space |
| CN109843383A (zh) | 2016-10-21 | 2019-06-04 | 宝洁公司 | 用于在最佳制剂空间中递送消费者期望的剂量体积、表面活性剂量和头皮健康剂量的泡沫剂型 |
| US11129783B2 (en) | 2016-10-21 | 2021-09-28 | The Procter And Gamble Plaza | Stable compact shampoo products with low viscosity and viscosity reducing agent |
| EP3528894A1 (en) | 2016-10-21 | 2019-08-28 | The Procter and Gamble Company | Concentrated shampoo dosage of foam for providing hair care benefits |
| WO2018075846A1 (en) | 2016-10-21 | 2018-04-26 | The Procter & Gamble Company | Concentrated shampoo dosage of foam designating hair conditioning benefits |
| US20180110690A1 (en) | 2016-10-21 | 2018-04-26 | The Procter & Gamble Company | Concentrated Shampoo Dosage of Foam for Providing Hair Care Benefits |
| EP3528774A1 (en) | 2016-10-21 | 2019-08-28 | The Procter and Gamble Company | Concentrated shampoo dosage of foam designating hair volume benefits |
| US11224567B2 (en) | 2017-06-06 | 2022-01-18 | The Procter And Gamble Company | Hair compositions comprising a cationic polymer/silicone mixture providing improved in-use wet feel |
| US11141370B2 (en) | 2017-06-06 | 2021-10-12 | The Procter And Gamble Company | Hair compositions comprising a cationic polymer mixture and providing improved in-use wet feel |
| US11679073B2 (en) | 2017-06-06 | 2023-06-20 | The Procter & Gamble Company | Hair compositions providing improved in-use wet feel |
| MX388495B (es) | 2017-10-10 | 2025-03-20 | Procter & Gamble | Composición de champú compacto que contiene surfactantes libres de sulfato. |
| WO2019074988A1 (en) | 2017-10-10 | 2019-04-18 | The Procter & Gamble Company | METHOD OF TREATING HAIR OR SKIN WITH PERSONAL FOAM COMPOSITION IN THE FORM OF FOAM |
| EP3694483B1 (en) | 2017-10-10 | 2022-09-07 | The Procter & Gamble Company | Sulfate free clear personal cleansing composition comprising low inorganic salt |
| JP2020536876A (ja) | 2017-10-10 | 2020-12-17 | ザ プロクター アンド ギャンブル カンパニーＴｈｅ Ｐｒｏｃｔｅｒ ＆ Ｇａｍｂｌｅ Ｃｏｍｐａｎｙ | アミノ酸系アニオン性界面活性剤及びカチオン性ポリマーを含むコンパクトシャンプー組成物 |
| US10912732B2 (en) | 2017-12-20 | 2021-02-09 | The Procter And Gamble Company | Clear shampoo composition containing silicone polymers |
| MX2020014144A (es) | 2018-06-29 | 2021-03-25 | Procter & Gamble | Composicion anticaspa en aerosol con bajo contenido de surfactante. |
| US12226505B2 (en) | 2018-10-25 | 2025-02-18 | The Procter & Gamble Company | Compositions having enhanced deposition of surfactant-soluble anti-dandruff agents |
| JP7410298B2 (ja) | 2019-12-06 | 2024-01-09 | ザ プロクター アンド ギャンブル カンパニー | 頭皮活性物質の付着を強化する硫酸塩を含まない組成物 |
| CN115151310B (zh) | 2020-02-27 | 2024-12-20 | 宝洁公司 | 功效和美观性增强的含硫去头皮屑组合物 |
| MX2023005560A (es) | 2020-11-23 | 2023-05-29 | Procter & Gamble | Composiciones para el cuidado personal libres de surfactantes sulfatados. |
| US11819474B2 (en) | 2020-12-04 | 2023-11-21 | The Procter & Gamble Company | Hair care compositions comprising malodor reduction materials |
| US11771635B2 (en) | 2021-05-14 | 2023-10-03 | The Procter & Gamble Company | Shampoo composition |
| US11986543B2 (en) | 2021-06-01 | 2024-05-21 | The Procter & Gamble Company | Rinse-off compositions with a surfactant system that is substantially free of sulfate-based surfactants |
| CN118265516A (zh) | 2021-12-09 | 2024-06-28 | 宝洁公司 | 含有效防腐的不含硫酸盐个人清洁组合物 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL106106A0 (en) * | 1993-06-22 | 1993-10-20 | Interpharm Lab Ltd | Library of polymeric molecules and its preparation |
| US6271196B1 (en) * | 1996-03-05 | 2001-08-07 | Regents Of The University Of Ca | Methods of alleviating neuropathic pain using prosaposin-derived peptides |
| PL204359B1 (pl) * | 1998-08-28 | 2010-01-29 | Myelos Corp | Cykliczne peptydy, zawierająca je kompozycja farmaceutyczna i ich zastosowania |
-
1999
- 1999-08-20 PL PL346346A patent/PL204359B1/pl not_active IP Right Cessation
- 1999-08-20 EP EP99943903A patent/EP1105420A1/en not_active Withdrawn
- 1999-08-20 CN CN99812627A patent/CN1324367A/zh active Pending
- 1999-08-20 WO PCT/US1999/019378 patent/WO2000012553A1/en not_active Ceased
- 1999-08-20 CZ CZ2001655A patent/CZ2001655A3/cs unknown
- 1999-08-20 CA CA002341810A patent/CA2341810A1/en not_active Abandoned
- 1999-08-20 KR KR1020017002478A patent/KR20010079695A/ko not_active Withdrawn
- 1999-08-20 JP JP2000567569A patent/JP4528443B2/ja not_active Expired - Fee Related
- 1999-08-20 AU AU56905/99A patent/AU751034B2/en not_active Ceased
- 1999-08-20 IL IL14158699A patent/IL141586A0/xx not_active IP Right Cessation
- 1999-08-20 BR BR9913490-0A patent/BR9913490A/pt not_active IP Right Cessation
- 1999-08-20 HU HU0103265A patent/HUP0103265A3/hu unknown
-
2001
- 2001-03-27 ZA ZA200102489A patent/ZA200102489B/en unknown
-
2010
- 2010-02-19 JP JP2010034833A patent/JP2010150272A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010150272A (ja) * | 1998-08-28 | 2010-07-08 | Myelos Corp | 環状プロサポシン由来のペプチドおよびその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| PL204359B1 (pl) | 2010-01-29 |
| ZA200102489B (en) | 2002-06-04 |
| CA2341810A1 (en) | 2000-03-09 |
| WO2000012553A1 (en) | 2000-03-09 |
| BR9913490A (pt) | 2001-09-25 |
| IL141586A0 (en) | 2002-03-10 |
| AU751034B2 (en) | 2002-08-08 |
| KR20010079695A (ko) | 2001-08-22 |
| HUP0103265A3 (en) | 2002-09-30 |
| HUP0103265A2 (hu) | 2002-02-28 |
| CZ2001655A3 (cs) | 2001-11-14 |
| PL346346A1 (en) | 2002-02-11 |
| JP2010150272A (ja) | 2010-07-08 |
| EP1105420A1 (en) | 2001-06-13 |
| CN1324367A (zh) | 2001-11-28 |
| JP2002523518A (ja) | 2002-07-30 |
| AU5690599A (en) | 2000-03-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU751034B2 (en) | Cyclic prosaposin-derived peptides and uses thereof | |
| DE69736712T2 (de) | Verfahren zur milderung von neuropatischen schmerz mit prosaposin verwandten peptiden | |
| JPH09503999A (ja) | 治療剤としてのプロサポシンおよびサイトカイン由来ペプチド | |
| US6849602B1 (en) | Compositions for alleviating neuropathic pain with prosaposin receptor agonists | |
| AU751161B2 (en) | Retro-inverso neurotrophic and analgesic peptides | |
| WO1998039357A1 (en) | Method of alleviating neuropathic pain | |
| WO1998042746A9 (en) | Synthetic saposin c-derived neurotrophic peptides | |
| EP0971956A2 (en) | Synthetic saposin c-derived neurotrophic peptides | |
| MXPA01001966A (en) | Cyclic prosaposin-derived peptides and uses thereof | |
| AU2002300005B2 (en) | Method of alleviating neuropathic pain | |
| AU4267297A (en) | Method of alleviating neuropathic pain | |
| US20020128193A1 (en) | Retro-inverso prosaposin-derived peptides and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060614 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060614 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070117 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20080919 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080919 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090702 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091023 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100219 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100304 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100520 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100607 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130611 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |