JP6420233B2 - 末梢神経損傷を処置するためのニューレグリンの使用 - Google Patents
末梢神経損傷を処置するためのニューレグリンの使用 Download PDFInfo
- Publication number
- JP6420233B2 JP6420233B2 JP2015503646A JP2015503646A JP6420233B2 JP 6420233 B2 JP6420233 B2 JP 6420233B2 JP 2015503646 A JP2015503646 A JP 2015503646A JP 2015503646 A JP2015503646 A JP 2015503646A JP 6420233 B2 JP6420233 B2 JP 6420233B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- weeks
- body weight
- neuregulin
- injury
- 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
- 102000014413 Neuregulin Human genes 0.000 title description 287
- 108050003475 Neuregulin Proteins 0.000 title description 287
- 208000010886 Peripheral nerve injury Diseases 0.000 title description 129
- 239000000203 mixture Substances 0.000 claims description 375
- 230000037396 body weight Effects 0.000 claims description 301
- 210000005036 nerve Anatomy 0.000 claims description 131
- 238000000034 method Methods 0.000 claims description 92
- 238000001356 surgical procedure Methods 0.000 claims description 66
- 208000028389 Nerve injury Diseases 0.000 claims description 53
- 230000008764 nerve damage Effects 0.000 claims description 52
- 210000003497 sciatic nerve Anatomy 0.000 claims description 51
- 210000001519 tissue Anatomy 0.000 claims description 38
- 206010028980 Neoplasm Diseases 0.000 claims description 35
- 208000016192 Demyelinating disease Diseases 0.000 claims description 19
- 206010012305 Demyelination Diseases 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 18
- 102000048238 Neuregulin-1 Human genes 0.000 claims description 16
- 108090000556 Neuregulin-1 Proteins 0.000 claims description 15
- 206010060862 Prostate cancer Diseases 0.000 claims description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
- 238000002271 resection Methods 0.000 claims description 7
- 238000012084 abdominal surgery Methods 0.000 claims description 6
- 238000010878 colorectal surgery Methods 0.000 claims description 6
- 208000004296 neuralgia Diseases 0.000 claims description 6
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 230000003187 abdominal effect Effects 0.000 claims description 5
- 206010039670 Sciatic nerve injury Diseases 0.000 claims description 4
- 230000006378 damage Effects 0.000 description 122
- 208000014674 injury Diseases 0.000 description 107
- 208000027418 Wounds and injury Diseases 0.000 description 105
- 238000011282 treatment Methods 0.000 description 81
- 210000000578 peripheral nerve Anatomy 0.000 description 71
- 238000010186 staining Methods 0.000 description 50
- 241001465754 Metazoa Species 0.000 description 46
- 201000001881 impotence Diseases 0.000 description 39
- 208000010228 Erectile Dysfunction Diseases 0.000 description 38
- 239000003981 vehicle Substances 0.000 description 38
- 108090000765 processed proteins & peptides Proteins 0.000 description 35
- 208000025962 Crush injury Diseases 0.000 description 30
- 241000700159 Rattus Species 0.000 description 29
- 230000001965 increasing effect Effects 0.000 description 27
- 210000001087 myotubule Anatomy 0.000 description 27
- 230000006870 function Effects 0.000 description 25
- 230000004220 muscle function Effects 0.000 description 24
- 210000003205 muscle Anatomy 0.000 description 23
- 108091006774 SLC18A3 Proteins 0.000 description 19
- 102000045965 Vesicular Acetylcholine Transport Proteins Human genes 0.000 description 19
- DVGHHMFBFOTGLM-UHFFFAOYSA-L fluorogold Chemical compound F[Au][Au]F DVGHHMFBFOTGLM-UHFFFAOYSA-L 0.000 description 18
- 206010016654 Fibrosis Diseases 0.000 description 16
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 16
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 16
- 230000003247 decreasing effect Effects 0.000 description 16
- 230000004064 dysfunction Effects 0.000 description 16
- 230000004761 fibrosis Effects 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 230000009986 erectile function Effects 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 210000002027 skeletal muscle Anatomy 0.000 description 14
- 230000009885 systemic effect Effects 0.000 description 14
- 230000000472 traumatic effect Effects 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 13
- 210000005226 corpus cavernosum Anatomy 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 230000001976 improved effect Effects 0.000 description 13
- 210000004116 schwann cell Anatomy 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 206010020751 Hypersensitivity Diseases 0.000 description 12
- 206010028289 Muscle atrophy Diseases 0.000 description 12
- 210000003050 axon Anatomy 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 230000020763 muscle atrophy Effects 0.000 description 12
- 201000000585 muscular atrophy Diseases 0.000 description 12
- 210000004126 nerve fiber Anatomy 0.000 description 12
- 201000001119 neuropathy Diseases 0.000 description 12
- 230000007823 neuropathy Effects 0.000 description 12
- 208000033808 peripheral neuropathy Diseases 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 11
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 11
- 208000026935 allergic disease Diseases 0.000 description 11
- 230000009610 hypersensitivity Effects 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 10
- 206010040030 Sensory loss Diseases 0.000 description 10
- 230000008033 biological extinction Effects 0.000 description 10
- 230000000670 limiting effect Effects 0.000 description 10
- 238000011084 recovery Methods 0.000 description 10
- 230000008929 regeneration Effects 0.000 description 10
- 238000011069 regeneration method Methods 0.000 description 10
- 208000004454 Hyperalgesia Diseases 0.000 description 9
- 208000002193 Pain Diseases 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 230000003376 axonal effect Effects 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 102100040896 Growth/differentiation factor 15 Human genes 0.000 description 8
- 101000893549 Homo sapiens Growth/differentiation factor 15 Proteins 0.000 description 8
- 101000653754 Rattus norvegicus Sphingosine 1-phosphate receptor 5 Proteins 0.000 description 8
- 239000000443 aerosol Substances 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 230000008482 dysregulation Effects 0.000 description 8
- 210000001640 nerve ending Anatomy 0.000 description 8
- 210000002569 neuron Anatomy 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 208000003098 Ganglion Cysts Diseases 0.000 description 7
- 208000005400 Synovial Cyst Diseases 0.000 description 7
- 210000003403 autonomic nervous system Anatomy 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000007906 compression Methods 0.000 description 7
- 230000006835 compression Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000006872 improvement Effects 0.000 description 7
- 230000030214 innervation Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000002889 sympathetic effect Effects 0.000 description 7
- 108010029485 Protein Isoforms Proteins 0.000 description 6
- 102000001708 Protein Isoforms Human genes 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- 108091005601 modified peptides Proteins 0.000 description 6
- 210000003899 penis Anatomy 0.000 description 6
- 238000004321 preservation Methods 0.000 description 6
- 238000011471 prostatectomy Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000001953 sensory effect Effects 0.000 description 6
- 230000037152 sensory function Effects 0.000 description 6
- 210000002460 smooth muscle Anatomy 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 5
- 102000012545 EGF-like domains Human genes 0.000 description 5
- 108050002150 EGF-like domains Proteins 0.000 description 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 208000016285 Movement disease Diseases 0.000 description 5
- 229930012538 Paclitaxel Natural products 0.000 description 5
- 206010053552 allodynia Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 210000005252 bulbus oculi Anatomy 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 230000035606 childbirth Effects 0.000 description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
- 229960004316 cisplatin Drugs 0.000 description 5
- 230000035601 cold sensitivity Effects 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000008991 intestinal motility Effects 0.000 description 5
- 238000007917 intracranial administration Methods 0.000 description 5
- 230000008338 local blood flow Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000023105 myelination Effects 0.000 description 5
- 229960001592 paclitaxel Drugs 0.000 description 5
- 230000001734 parasympathetic effect Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 230000002335 preservative effect Effects 0.000 description 5
- 230000000241 respiratory effect Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 230000035807 sensation Effects 0.000 description 5
- 235000019615 sensations Nutrition 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 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 5
- 230000008733 trauma Effects 0.000 description 5
- 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 206010052428 Wound Diseases 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000002146 bilateral effect Effects 0.000 description 4
- 210000005056 cell body Anatomy 0.000 description 4
- 210000004207 dermis Anatomy 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 210000003414 extremity Anatomy 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000018052 penile erection Effects 0.000 description 4
- 230000002980 postoperative effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000002307 prostate Anatomy 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 230000002567 autonomic effect Effects 0.000 description 3
- 231100000877 autonomic nervous system dysfunction Toxicity 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- -1 carrier Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 238000002716 delivery method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 230000007849 functional defect Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 208000036260 idiopathic disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000004112 neuroprotection Effects 0.000 description 3
- 230000000324 neuroprotective effect Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 238000011472 radical prostatectomy Methods 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 101150028074 2 gene Proteins 0.000 description 2
- 101150090724 3 gene Proteins 0.000 description 2
- 101150033839 4 gene Proteins 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 206010004954 Birth trauma Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 241001091538 Dimorphandra Group A Species 0.000 description 2
- 208000036119 Frailty Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 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
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 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 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 101150038921 NRG1 gene Proteins 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010010974 Proteolipids Proteins 0.000 description 2
- 102000016202 Proteolipids Human genes 0.000 description 2
- 206010040021 Sensory abnormalities Diseases 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 206010073696 Wallerian degeneration Diseases 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 210000003766 afferent neuron Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 210000000609 ganglia Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000009442 healing mechanism Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 230000003447 ipsilateral effect Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 210000001699 lower leg Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000007659 motor function Effects 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000003040 nociceptive effect Effects 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000007441 retrograde transport Effects 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 230000020341 sensory perception of pain Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 229950003937 tolonium Drugs 0.000 description 2
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000008734 wallerian degeneration Effects 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 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
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 1
- LHYQAEFVHIZFLR-UHFFFAOYSA-L 4-(4-diazonio-3-methoxyphenyl)-2-methoxybenzenediazonium;dichloride Chemical compound [Cl-].[Cl-].C1=C([N+]#N)C(OC)=CC(C=2C=C(OC)C([N+]#N)=CC=2)=C1 LHYQAEFVHIZFLR-UHFFFAOYSA-L 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000034656 Contusions Diseases 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000979249 Homo sapiens Neuromodulin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 206010048654 Muscle fibrosis Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 241000238367 Mya arenaria Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 206010029174 Nerve compression Diseases 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- 102100023206 Neuromodulin Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000006538 Nitric Oxide Synthase Type I Human genes 0.000 description 1
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000033712 Self injurious behaviour Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 101710192064 Sonic hedgehog protein A Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 210000003489 abdominal muscle Anatomy 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- DAPUDVOJPZKTSI-UHFFFAOYSA-L ammonium nickel sulfate Chemical compound [NH4+].[NH4+].[Ni+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DAPUDVOJPZKTSI-UHFFFAOYSA-L 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000003192 autonomic ganglia Anatomy 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 230000032846 axon ensheathment Effects 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000007348 cell dedifferentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000003292 diminished effect Effects 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
- 239000006185 dispersion Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 230000000374 effect on fibrosis Effects 0.000 description 1
- 238000010218 electron microscopic analysis Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000001856 erectile effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 210000003195 fascia Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 230000000893 fibroproliferative effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000002683 hand surgery Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 210000000194 hypogastric plexus Anatomy 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical group 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000003562 morphometric effect Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 231100001034 myelin sheath degeneration Toxicity 0.000 description 1
- 230000001114 myogenic effect Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 208000028412 nervous system injury Diseases 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000003018 neuroregenerative effect Effects 0.000 description 1
- 230000001928 neurorestorative effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000001002 parasympathetic nervous system Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000007832 reinnervation Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000036362 sensorimotor function Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 230000009960 sympathetic pathway Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000007483 tonsillectomy Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000009834 vaporization Methods 0.000 description 1
- 230000008016 vaporization Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1883—Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261618381P | 2012-03-30 | 2012-03-30 | |
| US61/618,381 | 2012-03-30 | ||
| US201261674060P | 2012-07-20 | 2012-07-20 | |
| US61/674,060 | 2012-07-20 | ||
| US201261693585P | 2012-08-27 | 2012-08-27 | |
| US201261693589P | 2012-08-27 | 2012-08-27 | |
| US61/693,589 | 2012-08-27 | ||
| US61/693,585 | 2012-08-27 | ||
| US201361785419P | 2013-03-14 | 2013-03-14 | |
| US61/785,419 | 2013-03-14 | ||
| PCT/US2013/034634 WO2013149163A1 (en) | 2012-03-30 | 2013-03-29 | Use of neuregulin to treat peripheral nerve injury |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017076415A Division JP2017149746A (ja) | 2012-03-30 | 2017-04-07 | 末梢神経損傷を処置するためのニューレグリンの使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015514096A JP2015514096A (ja) | 2015-05-18 |
| JP2015514096A5 JP2015514096A5 (enExample) | 2015-08-06 |
| JP6420233B2 true JP6420233B2 (ja) | 2018-11-07 |
Family
ID=48128617
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015503646A Expired - Fee Related JP6420233B2 (ja) | 2012-03-30 | 2013-03-29 | 末梢神経損傷を処置するためのニューレグリンの使用 |
| JP2017076415A Pending JP2017149746A (ja) | 2012-03-30 | 2017-04-07 | 末梢神経損傷を処置するためのニューレグリンの使用 |
| JP2019070976A Pending JP2019131582A (ja) | 2012-03-30 | 2019-04-03 | 末梢神経損傷を処置するためのニューレグリンの使用 |
| JP2021004728A Active JP7108724B2 (ja) | 2012-03-30 | 2021-01-15 | 末梢神経損傷を処置するためのニューレグリンの使用 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017076415A Pending JP2017149746A (ja) | 2012-03-30 | 2017-04-07 | 末梢神経損傷を処置するためのニューレグリンの使用 |
| JP2019070976A Pending JP2019131582A (ja) | 2012-03-30 | 2019-04-03 | 末梢神経損傷を処置するためのニューレグリンの使用 |
| JP2021004728A Active JP7108724B2 (ja) | 2012-03-30 | 2021-01-15 | 末梢神経損傷を処置するためのニューレグリンの使用 |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US20150094263A1 (enExample) |
| EP (3) | EP2830645B1 (enExample) |
| JP (4) | JP6420233B2 (enExample) |
| CN (2) | CN104321072A (enExample) |
| AU (4) | AU2013237896B2 (enExample) |
| BR (1) | BR112014024308B1 (enExample) |
| CA (1) | CA2869070A1 (enExample) |
| DK (2) | DK3278811T3 (enExample) |
| ES (2) | ES2647917T3 (enExample) |
| IL (3) | IL288785B2 (enExample) |
| MX (1) | MX354598B (enExample) |
| NZ (1) | NZ700546A (enExample) |
| PL (2) | PL3278811T3 (enExample) |
| PT (2) | PT2830645T (enExample) |
| WO (1) | WO2013149163A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3338791T3 (da) | 2008-07-17 | 2019-12-16 | Acorda Therapeutics Inc | Terapeutisk dosering af en neuregulin i behandling eller profylaxis af hjertesvigt |
| PL3235504T3 (pl) | 2009-10-14 | 2020-03-31 | Acorda Therapeutics, Inc. | Zastosowanie neureguliny do leczenia uszkodzenia nerwu obwodowego |
| ITUB20155471A1 (it) * | 2015-11-11 | 2017-05-11 | Univ Degli Studi Di Torino | Coniugato della neuregulina 1 per il trattamento delle lesioni dei nervi periferici |
| IL294038A (en) * | 2015-12-04 | 2022-08-01 | Univ Iowa Res Found | Device, systems and methods for prediction, screening and monitoring of encephalopathy / delirium |
| CA3082878C (en) | 2017-11-17 | 2024-02-20 | The Research Foundation for State University of New York | A method for treating damaged peripheral nerves using x-ray microbeam irradiation |
| CN110946991A (zh) * | 2018-09-27 | 2020-04-03 | 广州中医药大学(广州中医药研究院) | 神经调节蛋白1的应用 |
| CN114929099B (zh) * | 2019-08-01 | 2025-08-15 | 马克·埃文斯 | 用于在分娩期间和分娩之前降低人类胎儿神经损伤风险及鉴定神经损伤存在的方法和设备 |
| CN116116737B (zh) * | 2023-04-14 | 2023-06-30 | 新华手术器械有限公司 | 止血钳毛坯自动上料装置及使用方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US888A (en) | 1838-08-20 | perkins | ||
| US7037A (en) | 1850-01-22 | Grid-ikon slide-valve | ||
| US5716930A (en) | 1991-04-10 | 1998-02-10 | Ludwig Institute For Cancer Research | Glial growth factors |
| US5530109A (en) | 1991-04-10 | 1996-06-25 | Ludwig Institute For Cancer Research | DNA encoding glial mitogenic factors |
| US6087323A (en) * | 1992-04-03 | 2000-07-11 | Cambridge Neuroscience, Inc. | Use of neuregulins as modulators of cellular communication |
| US7037888B1 (en) | 1992-04-03 | 2006-05-02 | Acorda Therapeutics, Inc. | Methods for treating muscle diseases and disorders |
| EP1028735A4 (en) * | 1997-10-14 | 2003-08-06 | Cenes Pharmaceuticals Inc | THERAPEUTIC METHOD COMPRISING THE USE OF NEUREGULIN |
| CA2409996C (en) * | 2000-05-23 | 2016-03-01 | Cenes Pharmaceuticals, Inc. | Nrg-2 nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods |
| WO2009046453A2 (en) * | 2007-10-05 | 2009-04-09 | New England Medical Center (Nemc) | Use of neuregulin-1 in reducing brain damage |
| CN104645315A (zh) * | 2008-02-29 | 2015-05-27 | 阿索尔达治疗公司 | 达到所需胶质生长因子2血浆水平的方法 |
| DK3338791T3 (da) * | 2008-07-17 | 2019-12-16 | Acorda Therapeutics Inc | Terapeutisk dosering af en neuregulin i behandling eller profylaxis af hjertesvigt |
| KR101237927B1 (ko) * | 2009-05-07 | 2013-03-04 | (주)문엔제이 | 신경손상 및 신경질환 예방 또는 치료용 약학조성물 |
| PL3235504T3 (pl) * | 2009-10-14 | 2020-03-31 | Acorda Therapeutics, Inc. | Zastosowanie neureguliny do leczenia uszkodzenia nerwu obwodowego |
| CA2845198A1 (en) * | 2010-08-13 | 2012-02-16 | Georgetown University | Ggf2 and methods of use |
-
2013
- 2013-03-29 DK DK17187879.6T patent/DK3278811T3/da active
- 2013-03-29 AU AU2013237896A patent/AU2013237896B2/en not_active Ceased
- 2013-03-29 EP EP13716919.9A patent/EP2830645B1/en active Active
- 2013-03-29 JP JP2015503646A patent/JP6420233B2/ja not_active Expired - Fee Related
- 2013-03-29 IL IL288785A patent/IL288785B2/en unknown
- 2013-03-29 PL PL17187879T patent/PL3278811T3/pl unknown
- 2013-03-29 US US14/389,655 patent/US20150094263A1/en not_active Abandoned
- 2013-03-29 ES ES13716919.9T patent/ES2647917T3/es active Active
- 2013-03-29 CN CN201380026579.2A patent/CN104321072A/zh active Pending
- 2013-03-29 CN CN201610027758.3A patent/CN106511971A/zh active Pending
- 2013-03-29 PT PT137169199T patent/PT2830645T/pt unknown
- 2013-03-29 PT PT171878796T patent/PT3278811T/pt unknown
- 2013-03-29 CA CA2869070A patent/CA2869070A1/en active Pending
- 2013-03-29 PL PL13716919T patent/PL2830645T3/pl unknown
- 2013-03-29 WO PCT/US2013/034634 patent/WO2013149163A1/en not_active Ceased
- 2013-03-29 EP EP17187879.6A patent/EP3278811B1/en active Active
- 2013-03-29 ES ES17187879T patent/ES2857810T3/es active Active
- 2013-03-29 NZ NZ700546A patent/NZ700546A/en not_active IP Right Cessation
- 2013-03-29 BR BR112014024308-5A patent/BR112014024308B1/pt not_active IP Right Cessation
- 2013-03-29 DK DK13716919.9T patent/DK2830645T3/da active
- 2013-03-29 EP EP20211026.8A patent/EP3842059A1/en not_active Withdrawn
- 2013-03-29 MX MX2014011838A patent/MX354598B/es active IP Right Grant
-
2014
- 2014-09-29 IL IL234882A patent/IL234882B/en active IP Right Grant
-
2015
- 2015-12-22 US US14/978,287 patent/US20160346353A1/en not_active Abandoned
-
2017
- 2017-04-07 JP JP2017076415A patent/JP2017149746A/ja active Pending
-
2018
- 2018-01-24 AU AU2018200592A patent/AU2018200592A1/en not_active Abandoned
-
2019
- 2019-04-03 JP JP2019070976A patent/JP2019131582A/ja active Pending
- 2019-04-05 AU AU2019202401A patent/AU2019202401B2/en not_active Ceased
-
2020
- 2020-03-09 IL IL273186A patent/IL273186B/en unknown
- 2020-10-30 AU AU2020260539A patent/AU2020260539A1/en not_active Abandoned
-
2021
- 2021-01-15 JP JP2021004728A patent/JP7108724B2/ja active Active
-
2022
- 2022-03-28 US US17/705,840 patent/US20230117985A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7108724B2 (ja) | 末梢神経損傷を処置するためのニューレグリンの使用 | |
| JP2020015751A (ja) | 末梢神経損傷を処置するためのニューレグリンの使用 | |
| HK40055472A (en) | Ggf2 to treat surgical peripheral nerve injury or neuropathic pain therefrom | |
| HK1249038B (en) | Use of ggf2 to treat neuropathic pain upon peripheral nerve injury | |
| HK1206632B (en) | Neuregulin for use in treating peripheral nerve injury |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150311 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20150526 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150619 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150619 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160425 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160722 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20161207 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170407 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170517 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20170518 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20170526 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180502 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180607 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180706 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180806 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181011 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6420233 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |