CN117679521A - 用于防治面部神经微卡压综合征的药物组合物及其应用 - Google Patents
用于防治面部神经微卡压综合征的药物组合物及其应用 Download PDFInfo
- Publication number
- CN117679521A CN117679521A CN202311159255.8A CN202311159255A CN117679521A CN 117679521 A CN117679521 A CN 117679521A CN 202311159255 A CN202311159255 A CN 202311159255A CN 117679521 A CN117679521 A CN 117679521A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- pharmaceutical composition
- acupoint
- treatment
- combination
- 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.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 49
- 210000000256 facial nerve Anatomy 0.000 title claims abstract description 33
- 208000011580 syndromic disease Diseases 0.000 title claims abstract description 27
- 239000007924 injection Substances 0.000 claims abstract description 56
- 238000002347 injection Methods 0.000 claims abstract description 56
- 238000011282 treatment Methods 0.000 claims abstract description 55
- 230000008439 repair process Effects 0.000 claims abstract description 39
- 238000012549 training Methods 0.000 claims abstract description 32
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 33
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 33
- 229940053128 nerve growth factor Drugs 0.000 claims description 33
- 102000004169 proteins and genes Human genes 0.000 claims description 31
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 229960005321 mecobalamin Drugs 0.000 claims description 30
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 claims description 30
- 235000007672 methylcobalamin Nutrition 0.000 claims description 30
- 239000011585 methylcobalamin Substances 0.000 claims description 30
- ZIHHMGTYZOSFRC-UWWAPWIJSA-M cobamamide Chemical compound C1(/[C@](C)(CCC(=O)NC[C@H](C)OP(O)(=O)OC2[C@H]([C@H](O[C@@H]2CO)N2C3=CC(C)=C(C)C=C3N=C2)O)[C@@H](CC(N)=O)[C@]2(N1[Co+]C[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C3=NC=NC(N)=C3N=C1)O)[H])=C(C)\C([C@H](C/1(C)C)CCC(N)=O)=N\C\1=C/C([C@H]([C@@]\1(CC(N)=O)C)CCC(N)=O)=N/C/1=C(C)\C1=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]1CCC(N)=O ZIHHMGTYZOSFRC-UWWAPWIJSA-M 0.000 claims description 22
- 235000006279 cobamamide Nutrition 0.000 claims description 22
- 239000011789 cobamamide Substances 0.000 claims description 22
- 229960003957 dexamethasone Drugs 0.000 claims description 21
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 15
- 230000001537 neural effect Effects 0.000 claims description 13
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- HJXMNVQARNZTEE-UHFFFAOYSA-N Butylphthalide Chemical compound C1=CC=C2C(CCCC)OC(=O)C2=C1 HJXMNVQARNZTEE-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 150000002270 gangliosides Chemical class 0.000 claims description 10
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 10
- YWAFNFGRBBBSPD-OCMLZEEQSA-M sodium;[[(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound [Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 YWAFNFGRBBBSPD-OCMLZEEQSA-M 0.000 claims description 10
- 229930003451 Vitamin B1 Natural products 0.000 claims description 9
- 229960003495 thiamine Drugs 0.000 claims description 9
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 9
- 235000010374 vitamin B1 Nutrition 0.000 claims description 9
- 239000011691 vitamin B1 Substances 0.000 claims description 9
- 238000001356 surgical procedure Methods 0.000 claims description 8
- GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 claims description 5
- JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 claims description 5
- XSTJTOKYCAJVMJ-GVTSEVKNSA-N (z)-but-2-enedioic acid;(e)-1-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one Chemical compound OC(=O)\C=C/C(O)=O.COC1=C(OC)C(OC)=CC(\C=C\C(=O)N2CCN(CC(=O)N3CCCC3)CC2)=C1 XSTJTOKYCAJVMJ-GVTSEVKNSA-N 0.000 claims description 5
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims description 5
- 108010087806 Carnosine Proteins 0.000 claims description 5
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 5
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims description 5
- XJXROGWVRIJYMO-SJDLZYGOSA-N Nervonic acid Natural products O=C(O)[C@@H](/C=C/CCCCCCCC)CCCCCCCCCCCC XJXROGWVRIJYMO-SJDLZYGOSA-N 0.000 claims description 5
- 101500013104 Pelophylax ridibundus Secretoneurin Proteins 0.000 claims description 5
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 claims description 5
- 229930003779 Vitamin B12 Natural products 0.000 claims description 5
- 229930003268 Vitamin C Natural products 0.000 claims description 5
- 229930003427 Vitamin E Natural products 0.000 claims description 5
- ZXNRTKGTQJPIJK-UHFFFAOYSA-N aniracetam Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)CCC1 ZXNRTKGTQJPIJK-UHFFFAOYSA-N 0.000 claims description 5
- 229960000793 aniracetam Drugs 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 5
- 229950005197 butylphthalide Drugs 0.000 claims description 5
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 claims description 5
- 229940044199 carnosine Drugs 0.000 claims description 5
- 229930183167 cerebroside Natural products 0.000 claims description 5
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 claims description 5
- 229960004201 cinepazide Drugs 0.000 claims description 5
- GWHCXVQVJPWHRF-UHFFFAOYSA-N cis-tetracosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-UHFFFAOYSA-N 0.000 claims description 5
- 229960001284 citicoline Drugs 0.000 claims description 5
- 229960004774 citicoline sodium Drugs 0.000 claims description 5
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 5
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 claims description 5
- 229950009041 edaravone Drugs 0.000 claims description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 5
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 claims description 5
- 229960001227 oxiracetam Drugs 0.000 claims description 5
- 229960004526 piracetam Drugs 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 5
- 235000019156 vitamin B Nutrition 0.000 claims description 5
- 239000011720 vitamin B Substances 0.000 claims description 5
- 235000019163 vitamin B12 Nutrition 0.000 claims description 5
- 239000011715 vitamin B12 Substances 0.000 claims description 5
- 235000019158 vitamin B6 Nutrition 0.000 claims description 5
- 239000011726 vitamin B6 Substances 0.000 claims description 5
- 235000019154 vitamin C Nutrition 0.000 claims description 5
- 239000011718 vitamin C Substances 0.000 claims description 5
- 235000019165 vitamin E Nutrition 0.000 claims description 5
- 239000011709 vitamin E Substances 0.000 claims description 5
- 229940046009 vitamin E Drugs 0.000 claims description 5
- 229940011671 vitamin b6 Drugs 0.000 claims description 5
- 241001529936 Murinae Species 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 101100404655 Rattus norvegicus Ngf gene Proteins 0.000 claims description 2
- 229940046001 vitamin b complex Drugs 0.000 claims 2
- 238000011285 therapeutic regimen Methods 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 14
- 230000009471 action Effects 0.000 abstract description 7
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 230000002195 synergetic effect Effects 0.000 abstract description 2
- 102000006386 Myelin Proteins Human genes 0.000 abstract 1
- 108010083674 Myelin Proteins Proteins 0.000 abstract 1
- 210000003050 axon Anatomy 0.000 abstract 1
- 210000005012 myelin Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 30
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 26
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 26
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 14
- 230000002980 postoperative effect Effects 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 10
- 230000002354 daily effect Effects 0.000 description 10
- 239000001963 growth medium Substances 0.000 description 10
- 208000004929 Facial Paralysis Diseases 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 8
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 8
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- -1 compound amino acid Chemical class 0.000 description 8
- 229940126864 fibroblast growth factor Drugs 0.000 description 8
- 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 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- 238000012258 culturing Methods 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000011269 treatment regimen Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000013592 cell lysate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012879 subculture medium Substances 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 102000004338 Transferrin Human genes 0.000 description 4
- 108090000901 Transferrin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 238000007664 blowing Methods 0.000 description 4
- 238000012937 correction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000012581 transferrin Substances 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 4
- 229930003270 Vitamin B Natural products 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000001815 facial effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000009210 therapy by ultrasound Methods 0.000 description 3
- 238000004383 yellowing Methods 0.000 description 3
- VTBHBNXGFPTBJL-UHFFFAOYSA-N 4-tert-butyl-1-sulfanylidene-2,6,7-trioxa-1$l^{5}-phosphabicyclo[2.2.2]octane Chemical compound C1OP2(=S)OCC1(C(C)(C)C)CO2 VTBHBNXGFPTBJL-UHFFFAOYSA-N 0.000 description 2
- 125000002124 5'-adenosyl group Chemical group N1=CN=C2N(C=NC2=C1N)[C@H]1[C@H](O)[C@H](O)[C@H](O1)C* 0.000 description 2
- 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 2
- 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 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012148 non-surgical treatment Methods 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000003954 umbilical cord Anatomy 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000059069 Atalantia monophylla Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- 206010016322 Feeling abnormal Diseases 0.000 description 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001529739 Prunella <angiosperm> Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 206010074054 Trigeminal neuritis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000014337 facial nerve disease Diseases 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000008113 selfheal Nutrition 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
- A61H39/00—Devices for locating or stimulating specific reflex points of the body for physical therapy, e.g. acupuncture
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- 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
- A63—SPORTS; GAMES; AMUSEMENTS
- A63B—APPARATUS FOR PHYSICAL TRAINING, GYMNASTICS, SWIMMING, CLIMBING, OR FENCING; BALL GAMES; TRAINING EQUIPMENT
- A63B23/00—Exercising apparatus specially adapted for particular parts of the body
- A63B23/025—Exercising apparatus specially adapted for particular parts of the body for the head or the neck
- A63B23/03—Exercising apparatus specially adapted for particular parts of the body for the head or the neck for face muscles
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Neurology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Botany (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Alternative & Traditional Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rehabilitation Therapy (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
Abstract
本发明涉及用于防治面部神经微卡压综合征的药物组合物及其治疗面部神经微卡压综合征中的应用,所述应用包括小针刀治疗、射频手术、穴位注射药物组合物、康复训练的联合使用,可实现协同增效,药物组合物起效快、持续作用时间延长、营养神经、促进髓鞘及轴突修复,达到较好的治疗效果。
Description
技术领域
本发明属于生物医药技术领域,具体涉及用于防治面部神经微卡压综合征的药物组合物及其应用。
背景技术
面部神经微卡压综合征是面部感觉和或运动神经末梢受到各种原因发生轻微卡压,进而出现的一侧面部不适、主观感觉异常或僵滞,部分伴有局限性微小肌肉运动异常或运动不协调,属于面瘫后遗症或慢性三叉神经炎或损害后遗症的一种。目前的治疗措施分为非手术治疗与手术治疗。非手术治疗采用局部制动,注射皮质类固醇和服用NSAID减轻卡压病变的炎性反应,或使用营养神经修复类药物修复受损的神经纤维和神经细胞。但面部神经微卡压综合征为缓慢进行性疾病很少自愈,后期多伴有心理疾患,迄今临床尚没有能够有效的药物和治疗方案。
专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)公开了有关具有修复功效的神经修复蛋白提取物及神经修复蛋白组合物的技术内容,前述申请及内容作为本申请必不可少的技术参考和组成部分。
发明内容
本发明的目的在于提供一种药物组合物用于制备防治面部神经微卡压综合征的药物中的应用。
本发明的优选技术方案中,所述应用包括小针刀治疗、射频手术、用于防治面部神经微卡压综合征的药物组合物、康复训练的联合使用。
本发明的优选技术方案中,所述小针刀治疗方案为,3天1次,3次一个疗程,1-2周后重复1个疗程,共持续2-3个疗程。
本发明的优选技术方案中,所述防治面部神经微卡压综合征的药物组合物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg、100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松2mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,组合物中,单次穴位注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg,地塞米松3mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物临配临用。
本发明的优选技术方案中,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。
本发明的优选技术方案中,单次穴位注射用的药物组合物每天穴位注射一次,7天为疗程。
本发明的优选技术方案中,每次穴位注射治疗2-6个疗程,优选为4-5个疗程。
本发明的优选技术方案中,所述用于防治面部神经微卡压综合征的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。
本发明的优选技术方案中,所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下,基于长时程温控高电压变频脉冲射频800秒-1400秒。
本发明的优选技术方案中,所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下,基于长时程温控高电压变频脉冲射频960秒-1200秒。
本发明的优选技术方案中,所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号:国作登字-2022-I-10250228和著作权登记号:国作登字-2022-F-10250229)。
本发明的优选技术方案中,所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。
本发明的优选技术方案中,第一套康复操训练包括,一是照镜子;二是慢闭眼,闭眼5秒后,睁开眼保持5秒,同时控制不出现口角连带上提动作,纠偏纠正连带运动;每天训练第一套康复操三组,每组训练30遍。
本发明的优选技术方案中,第二套康复操训练包括,一是照镜子;二是睁眼,尽量保持静默神经分支;三是口周噘嘴、呲牙和鼓腮;每天训练第一套康复操三组,每组训练10遍。
本发明的优选技术方案中,所述防治面部神经微卡压综合征的治疗方案为,脉冲射频手术、小针刀治疗、术后穴位注射给药以及术中和术后康复操训练。
本发明的优选技术方案中,所述面神经麻痹选自面肌痉挛、面瘫/连带运动、三叉神经痛、舌咽神经痛、面神经炎、周围性面瘫、眼肌痉挛修复中的任一种或其组合。
本发明的目的在于提供一种用于防治面部神经微卡压综合征的药物组合物,选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg、100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松2mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,组合物中,单次穴位注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg,地塞米松3mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物临配临用。
本发明的优选技术方案中,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。
本发明的优选技术方案中,单次穴位注射用的药物组合物每天穴位注射一次,7天为疗程。
本发明的优选技术方案中,每次穴位注射治疗2-6个疗程,优选为4-5个疗程。
本发明的优选技术方案中,所述用于防治面部神经微卡压综合征的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。
本发明的优选技术方案中,所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下,基于长时程温控高电压变频脉冲射频800秒-1400秒。
本发明的优选技术方案中,所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下,基于长时程温控高电压变频脉冲射频960秒-1200秒。
本发明的优选技术方案中,所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号:国作登字-2022-I-10250228和著作权登记号:国作登字-2022-F-10250229)。
本发明的优选技术方案中,所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。
本发明的优选技术方案中,第一套康复操训练包括,一是照镜子;二是慢闭眼,闭眼5秒后,睁开眼保持5秒,同时控制不出现口角连带上提动作,纠偏纠正连带运动;每天训练第一套康复操三组,每组训练30遍。
本发明的优选技术方案中,第二套康复操训练包括,一是照镜子;二是睁眼,尽量保持静默神经分支;三是口周噘嘴、呲牙和鼓腮;每天训练第一套康复操三组,每组训练10遍。
本发明的另一目的在于提供一种防治面部神经微卡压综合征的治疗方案,所述治疗方案包括用于防治面部神经微卡压综合征的药物组合物任选地与射频手术、小针刀治疗、康复训练操的任一种或其组合联合使用。
本发明的优选技术方案中,所述小针刀治疗方案为,3天1次,3次一个疗程,1-2周后重复1个疗程,共持续2-3个疗程。
本发明的优选技术方案中,所述防治面部神经微卡压综合征的药物组合物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg的组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物为鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg、100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,单次穴位注射用的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松2mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,组合物中,单次穴位注射的药物组合物由鼠神经生长因子90ug、甲钴胺1.0mg、腺苷钴胺0.5mg,地塞米松5mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,单次穴位注射的药物组合物由鼠神经生长因子60ug、甲钴胺0.8mg、腺苷钴胺0.5mg,地塞米松3mg和盐酸利多卡因1ml组成,其中,盐酸利多卡因的浓度选自0.8%、1%、1.5%、2%的任一种。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
本发明的优选技术方案中,所述单次穴位注射用的药物组合物临配临用。
本发明的优选技术方案中,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。
本发明的优选技术方案中,单次穴位注射用的药物组合物每天穴位注射一次,7天为疗程。
本发明的优选技术方案中,每次穴位注射治疗2-6个疗程,优选为4-5个疗程。
本发明的优选技术方案中,所述用于防治面部神经微卡压综合征的药物组合物任选地与射频手术、康复训练操的任一种或其组合联合使用。
本发明的优选技术方案中,所述射频手术在41℃-42℃、90V-140V、2Hz-6Hz条件下,基于长时程温控高电压变频脉冲射频800秒-1400秒。
本发明的优选技术方案中,所述射频手术在41℃-42℃、100V-120V、3Hz-5Hz条件下,基于长时程温控高电压变频脉冲射频960秒-1200秒。
本发明的优选技术方案中,所述康复训练操为发明人独创的面瘫康复训练操(著作权登记号:国作登字-2022-I-10250228和著作权登记号:国作登字-2022-F-10250229)。
本发明的优选技术方案中,所述的康复操训练选自第一套康复操训练、第二套康复操训练的任一种或其组合。
本发明的优选技术方案中,第一套康复操训练包括,一是照镜子;二是慢闭眼,闭眼5秒后,睁开眼保持5秒,同时控制不出现口角连带上提动作,纠偏纠正连带运动;每天训练第一套康复操三组,每组训练30遍。
本发明的优选技术方案中,第二套康复操训练包括,一是照镜子;二是睁眼,尽量保持静默神经分支;三是口周噘嘴、呲牙和鼓腮;每天训练第一套康复操三组,每组训练10遍。
为了清楚地表述本发明,本发明所述的具有修复功效的神经修复细胞蛋白提取物或神经修复细胞蛋白组合物参照专利申请(CN2023100429139、PCT/CN2023/073566、CN2023100429143、PCT/CN2023/073582)制得。
本发明的优选技术方案中,所述具有神经修复功效的神经修复细胞蛋白提取物的制备方法,包括如下步骤:
S-1:将密度为5.0×106个/mL-5.0×107个/mL的间充质传代干细胞置于含有DMEM/F12 40-50%、RPMI1640 40-50%、牛血清蛋白(BSA)0.1-2%、表皮细胞生长因子(EGF)1-15ug/mL、成纤维细胞生长因子(FGF)1-15ug/mL、胰岛素转铁蛋白1-15ug/mL、复方氨基酸(18AA)0.01-0.1%和2-10μmol/L应激物的培养基中,再将其置于37.0℃±0.5℃、5%±1.0%CO2条件下培养2h-6h后,分离,洗涤,收集细胞,其中,所述的应激物选自化合物1-16的任一种或其组合;
S-2:将收集细胞按照密度为5.0×106个/mL-5.0×107个/mL分散于溶剂中,再将其置于2℃-8℃条件下超声处理,制得细胞裂解液,其中,所述溶剂选自选自生理盐水、5%葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合;
S-3:将步骤S-2制得的细胞裂解液分离后,所得的分离液依次经0.45um、0.22um滤膜过滤,即得。
本发明的优选技术方案中,步骤S-1的培养基中含有DMEM/F12 42-45%、RPMI164042-45%、牛血清蛋白(BSA)0.5-1.5%、表皮细胞生长因子(EGF)5-10ug/mL、成纤维细胞生长因子(FGF)5-10ug/mL、胰岛素转铁蛋白5-10ug/mL、复方氨基酸(18AA)0.02-0.05%和3-8μmol/L的应激物。
本发明的优选技术方案中,步骤S-1的培养基中含有DMEM/F12 45%、RPMI164045%、牛血清蛋白(BSA)0.5%、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL,胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05%和4-6μmol/L的应激物。
本发明的优选技术方案中,步骤S-1的间充质传代干细胞密度为8.0×106-2.0×107个/mL,优选为8.0×106-1.0×107个/mL。
本发明的优选技术方案中,步骤S-1的间充质传代干细胞在培养基中培养3h-5h,优选为3.5h-4.5h。
本发明的优选技术方案中,步骤S-1中洗涤细胞的溶剂选自生理盐水、5%葡萄糖溶液、磷酸盐缓冲液(PBS)、TBPS缓冲液、TBST缓冲液、Tris缓冲液的任一种或其组合,细胞洗涤次数为2-5次,优选为3-4次。
本发明的优选技术方案中,步骤S-1所述的分离选自离心、过滤的任一种或其组合,其中,所述离心条件为1000-2000rpm*3-15min,优选为1200rpm-1500rpm*5-10min。
本发明的优选技术方案中,步骤S-2的超声条件为:在2℃-8℃、25kHZ、360W条件下工作3s再间隙1s,超声处理1-5min。
本发明的优选技术方案中,步骤S-3所述分离选自2000-8000rpm*10-30min离心、多级离心、多级过滤的任一种或其组合,优选为3000-7000rpm*15-25min。
本发明的优选技术方案中,步骤S-3的多级离心依次为3000-4000rpm*3-5min、5000-6000rpm*3-5min和7000rpm*5-8min。
本发明的优选技术方案中,所述多级过滤的滤膜孔径选自80um、50um、30um、10um、5um的任一种。
本发明的优选技术方案中,将步骤S-3制得的细胞蛋白提取物冻存,优选冻存于-40℃至-20℃。
本发明的优选技术方案中,将步骤S-3制得的细胞蛋白提取物采用核酸酶或全能核酸酶的任一种酶解后再分离纯化。
本发明的优选技术方案中,所述间充质传代干细胞的培养或原代间充质干细胞的培养采用本领域的培养方法。
本发明的优选技术方案中,所述间充质传代干细胞的培养包括下述步骤:将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到传代培养基中,再将其置于37.0℃±0.5℃、5%±1.0%CO2条件下培养10-15天,每隔2-3天,观察传代培养基变黄后,半量更换传代培养基,其中,所述传代培养基含有10%FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基。
本发明的优选技术方案中,所述原代间充质干细胞的培养包括下述步骤:
1)将脐带清洗消毒后,组织解剖,取华通胶层组织,将其切成3mm3的小块,离心,清洗,收集组织块,将其置于含10%胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基中,再将其置于37.0℃±0.5℃、5%±1.0%CO2条件下培养,每间隔2-3天半量更换培养基,培养至组织块爬出细胞;
2)振摇,收集低层细胞用PBS清洗后,加入0.25%的胰蛋白酶消化2min-3min,加入等体积的胰蛋白酶终止液停止消化,吸管轻轻吹打,1200-1500rpm*5-8min离心后,收集细胞,即得。
除非另有说明,本发明涉及液体与液体之间的百分比时,所述的百分比为体积/体积百分比;本发明涉及液体与固体之间的百分比时,所述百分比为体积/重量百分比;本发明涉及固体与液体之间的百分比时,所述百分比为重量/体积百分比;其余为重量/重量百分比。
除非另有说明,本发明采用如下方法进行评价:
1.取穴:按照由国家技术监督局发布的中华人民共和国国家标准《腧穴名称与定位》(GB/T 12345-2006)的穴位以定位。
2.面瘫运动功能评价量表
3.面瘫生活质量评价量表
与现有技术相比,本发明具有下述有益效果:
1、本发明科学筛选神经修复药物,配置成用于治疗面部神经微卡压综合征的药物组合物,各组分协同增效,药物组合物起效快、持续作用时间延长、治疗效果好,能降低单一药物使用时带来的副作用。同时配合采用射频治疗、小针刀治疗,加快了症状改善和面神经的恢复。
2、本发明操作简便、可节约药物使用量,显著降低生产成本,适合于大规模工业化生产等优点。
具体实施方式
下面结合具体实施例对本发明的详细内容做进一步解释和描述,但并不以此限制本发明的保护范围。
实施例1具有修复功效的神经修复细胞蛋白提取物的制备
1、原代间充质干细胞的培养
原代间充质干细胞的培养包括下述步骤:
1)将脐带清洗消毒后,组织解剖,取华通胶层组织,将其切成3mm3的小块,离心,清洗,收集组织块,将其置于培养瓶中,加入含10%胎牛血清FBS、100ug/ml青霉素、100ug/ml链霉素的DMEM/F12培养基,再将其置于37℃、5%CO2条件下培养,促进其贴壁,每间隔2-3天,观察培养基变黄后,半量更换培养基,培养10-12天,至组织块边上可见细胞爬出;
2)轻轻摇晃,使组织块掉落,分别收集组织块和低层细胞,其中,将收集的组织块再贴壁培养;
3)将收集的低层细胞用PBS清洗后,加入适量0.25%胰蛋白酶消化2min-3min,加入等体积的胰蛋白酶终止液停止消化,吸管轻轻吹打瓶底,1500rpm*5min离心后,收集细胞,即得。
2、原代间充质干细胞的传代培养(间充质传代干细胞的培养)
原代间充质干细胞的传代培养(间充质传代干细胞的培养):将原代间充质干细胞按照初始密度为5.0×105-5.0×106个/ml加入到含有10%FBS、100U/ml青霉素和100ug/ml链霉素的DMEM/F12培养基中,再将其置于37.0℃±0.5℃、5%±1.0%CO2条件下培养10-15天,每间隔2-3天,观察培养基变黄后,半量更换培养基。
3、化合物1-16的制备参照文献1(New limonophyllines A-C from the stem ofAtalantia monophylla and cytotoxicity against cholangiocarcinoma and HepG2cell lines,Arch.Pharm.Res.(2018)41:431–437)。
具有神经修复功效的神经修复细胞蛋白提取物的制备方法,包括如下步骤:
(1)将间充质传代细胞按照密度为8.0×106个/mL加入到含有DMEM/F1245%、RPMI1640 45%、牛血清蛋白(BSA)0.5%、表皮细胞生长因子(EGF)10ug/mL、成纤维细胞生长因子(FGF)10ug/mL、胰岛素转铁蛋白10ug/mL、复方氨基酸(18AA)0.05%和5μmol/L的化合物16的培养基中,再将其置于37℃、5%CO2条件下培养4h后,将其置于1200rpm*5min离心,用PBS洗涤3次后,收集细胞;
(2)将步骤(1)收集的细胞按照密度为1.0×107个/mL分散于生理盐水中,在2-8℃、25kHz、360W条件下超声3s、间隙1s,超声2min,制得细胞裂解液;
(3)将步骤(2)制得的细胞裂解液置于7000rpm*20min离心,将所得的离心液依次经0.45um、0.22um滤膜过滤,即得细胞蛋白提取物;
(4)在步骤(3)制得的细胞蛋白提取物加入所需量的甘露醇,搅拌,混合均匀后,冻干,所得冻干制剂中含有5%的甘露醇(m/m)。
试验例1本发明药物组合物用于面部神经微卡压综合征的治疗效果研究
选取面部神经微卡压综合征患者30名,分为1组(10名)、2组(10名)、3组(10名)。患者入组标准:符合面部神经微卡压综合征诊断标准,患者发病超过6个月;年龄20-70岁;H-B分级在II级以上;知情同意接受本试验;依从性好。禁忌症:面神经完全断裂或缺失者;穿刺部位感染或皮肤损伤者;累及面神经的局部肿瘤或其他占位性病变者;凝血功能障碍者,可能增加出血或血肿的风险;心脏起搏器植入者,可能干扰起搏器的正常工作;孕妇或哺乳期妇女者,可能影响胎儿或婴儿的健康;对电极针或局部麻醉药过敏者,可能引起过敏反应或其他不良反应;精神障碍或无法配合康复或矫正训练治疗者。
1组的治疗方案(每个疗程7天,治疗4个疗程):单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、维生素B1 200mg组成,临配临用,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射,每天穴位注射1次。
2组的治疗方案(每个疗程7天,治疗4个疗程)包括脉冲射频手术、小针刀治疗、术后穴位注射给药以及术中和术后康复操训练。
1、脉冲射频手术:采用射频控温热凝器(型号R-2000B M1,购自北琪医疗),基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ),在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒;手术中,配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动;
2、小针刀治疗,3天1次,3次一个疗程,1周后重复1个疗程,共持续3个疗程。
3、术后穴位注射给药方案:
单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成,临配临用,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射,每天穴位注射1次。
4、术后康复操训练:
第一套康复操:一是照镜子;二是慢闭眼,闭眼5秒后,睁开眼保持5秒,同时控制不出现口角连带上提动作,纠偏纠正连带运动。每天训练三组,每组训练30遍;第二套康复操:一是照镜子;二是睁眼,尽量保持静默神经分支;三是口周噘嘴、呲牙和鼓腮。每天训练三组,每组训练10遍。
3组的治疗方案(每个疗程7天,治疗4个疗程)包括脉冲射频手术、小针刀治疗、术后穴位注射给药以及术中和术后康复操训练。
1、脉冲射频手术:采用射频控温热凝器(型号R-2000B M1,购自北琪医疗),基于长时程温控高电压变频脉冲射频技术对病变部位进行神经激活修复调控微纠偏手术(脉冲宽度20ms、静息期480ms、最大电压值100V、脉冲频率2HZ),在41-42℃、90-140V、2-5Hz条件下脉冲射频1200秒;手术中,配合2组睁大眼保持、重复龇牙和重复鼓气的面部运动;
2、小针刀治疗,3天1次,3次一个疗程,1周后重复1个疗程,共持续3个疗程。
3、术后穴位注射给药方案:
(1)单次穴位注射的药物组合物由鼠神经生长因子30ug、甲钴胺0.5mg、腺苷钴胺0.5mg、地塞米松5mg和盐酸利多卡因1ml组成,临配临用,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射,每天穴位注射1次。
(2)单次穴位注射实施例1制得的神经修复细胞蛋白提取物冻干制剂130ug,用2ml生理盐水溶解,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴、对侧太阳穴、地仓穴,双手合谷穴进行穴位注射,每天穴位注射1次。
4、术后康复操训练:
第一套康复操:一是照镜子;二是慢闭眼,闭眼5秒后,睁开眼保持5秒,同时控制不出现口角连带上提动作,纠偏纠正连带运动。每天训练三组,每组训练30遍;第二套康复操:一是照镜子;二是睁眼,尽量保持静默神经分支;三是口周噘嘴、呲牙和鼓腮。每天训练三组,每组训练10遍。
疗效评定:满意度调查表和临床评分House-Brakmann面神经功能分级疗效评价表。
1组:重复治疗4-6个疗程,超过50%的患者面部神经微卡压症状改善。
2组:有效率为70%,显效率50%,患者术后满意度80%。无发热、过敏、症状加重等后遗症。6个月内重复治疗2~3次,疗效累积。患者遵照医嘱,注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响,基本无复发,生活质量显著提高。
3组:患者面部神经微卡压症状明显改善。有效率为100%,显效率90%,患者术后满意度100%。全部受试患者均无副作用和不良事件。患者遵照医嘱,注意减少甚至避免熬夜、疲劳、外部感染、受凉等因素的影响,基本无复发,生活质量显著提高。
以上对本发明具体实施方式的描述并不限制本发明,本领域技术人员可以根据本发明作出各种改变或变形,只要不脱离本发明的精神,均应属于本发明权利要求保护的范围。
Claims (10)
1.一种药物组合物用于制备防治面部神经微卡压综合征的药物中的应用,所述药物组合物选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。
2.如权利要求1所述的应用,所述应用包括小针刀治疗、射频手术、用于防治面部神经微卡压综合征的药物组合物、康复训练的联合使用。
3.如权利要求1-2任一项所述的应用,所述小针刀治疗方案为,3天1次,3次一个疗程,1-2周后重复1个疗程,共持续2-3个疗程。
4.如权利要求1-3任一项所述的应用,单次穴位注射用的药物组合物含有鼠神经生长因子30-90ug、甲钴胺0.5-1.0mg、腺苷钴胺0.1-0.5mg,地塞米松2-5mg的任一种或其组合。
5.如权利要求1-4任一项所述的应用,所述单次穴位注射用的药物组合物任选地含有100-300mg具有修复功效的神经修复细胞蛋白提取物和/或神经修复蛋白组合物的任一种或其组合。
6.如权利要求1-5任一项所述的应用,选取患侧面部的阳白穴、太阳穴、四白穴、迎香穴、巨髎穴、地仓穴和颊车穴进行穴位注射。
7.如权利要求1-6任一项所述的应用,单次穴位注射用的药物组合物每天穴位注射一次,7天为疗程。
8.如权利要求1-7任一项所述的应用,每次穴位注射治疗2-6个疗程,优选为4-5个疗程。
9.如权利要求1-8任一项所述的防治面部神经微卡压综合征的药物组合物,选自鼠神经生长因子、单唾液酸神经节苷脂(GM1)、脑苷肌肽、甲钴胺、腺苷钴胺、复合维生素B、丁苯酞、马来酸桂哌齐特、依达拉奉、依达拉奉右莰醇、胞磷胆碱、胞磷胆碱钠、神经节苷脂、奥拉西坦、吡拉西坦、茴拉西坦、神经生长因子、胞二磷胆碱、神经妥乐平、谷维素、维生素B1、维生素B6、维生素B12、维生素C、维生素E、复方脑肽节苷脂、脑蛋白、神经酸的任一种或其组合。
10.一种防治面部神经微卡压综合征的治疗方案,所述治疗方案包括如权利要求1-8任一项所述的防治面部神经微卡压综合征的药物组合物任选地与射频手术、小针刀治疗、康复训练操的任一种或其组合联合使用。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2022111013476 | 2022-09-09 | ||
CN2022111016934 | 2022-09-09 | ||
CN202211101347 | 2022-09-09 | ||
CN202211101693 | 2022-09-09 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117679521A true CN117679521A (zh) | 2024-03-12 |
Family
ID=90127306
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311159241.6A Pending CN117679520A (zh) | 2022-09-09 | 2023-09-09 | 用于防治后遗症期面神经麻痹的药物组合物及其应用 |
CN202311159251.XA Pending CN117679649A (zh) | 2022-09-09 | 2023-09-09 | 射频装置在治疗面瘫连带运动中的应用 |
CN202311159255.8A Pending CN117679521A (zh) | 2022-09-09 | 2023-09-09 | 用于防治面部神经微卡压综合征的药物组合物及其应用 |
CN202311159233.1A Pending CN117679518A (zh) | 2022-09-09 | 2023-09-09 | 用于防治恢复期面神经麻痹的药物组合物及其应用 |
CN202311159266.6A Pending CN117679522A (zh) | 2022-09-09 | 2023-09-09 | 用于防治神经系统病变的药物组合物及其应用 |
CN202311159238.4A Pending CN117679519A (zh) | 2022-09-09 | 2023-09-09 | 用于防治急性期面神经麻痹的药物组合物及其应用 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311159241.6A Pending CN117679520A (zh) | 2022-09-09 | 2023-09-09 | 用于防治后遗症期面神经麻痹的药物组合物及其应用 |
CN202311159251.XA Pending CN117679649A (zh) | 2022-09-09 | 2023-09-09 | 射频装置在治疗面瘫连带运动中的应用 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311159233.1A Pending CN117679518A (zh) | 2022-09-09 | 2023-09-09 | 用于防治恢复期面神经麻痹的药物组合物及其应用 |
CN202311159266.6A Pending CN117679522A (zh) | 2022-09-09 | 2023-09-09 | 用于防治神经系统病变的药物组合物及其应用 |
CN202311159238.4A Pending CN117679519A (zh) | 2022-09-09 | 2023-09-09 | 用于防治急性期面神经麻痹的药物组合物及其应用 |
Country Status (2)
Country | Link |
---|---|
CN (6) | CN117679520A (zh) |
WO (6) | WO2024051848A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN118045071B (zh) * | 2024-04-15 | 2024-06-07 | 苏州沪云新药研发股份有限公司 | 一种治疗缺血性脑卒中疾病的联合用药物及其应用 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1036973C (zh) * | 1993-10-14 | 1998-01-14 | 宋定邦 | 一种神经镇痛注射液 |
CN102631667B (zh) * | 2012-04-19 | 2013-10-02 | 赵廷宝 | 促神经再生注射剂及其制备方法 |
CN202682577U (zh) * | 2012-06-28 | 2013-01-23 | 四川旭康医疗电器有限公司 | 家用多功能综合治疗仪 |
CN102988403A (zh) * | 2012-12-06 | 2013-03-27 | 祁建春 | 用于治疗急性期面瘫的注射药物组合 |
US20140296948A1 (en) * | 2013-03-27 | 2014-10-02 | Hitops Gmbh | New therapy of cancer with pulsed radio frequency |
CN103638250B (zh) * | 2013-12-23 | 2015-08-12 | 李宣东 | 一种治疗面神经麻痹的中药制剂及其制备方法 |
US20150209390A1 (en) * | 2014-01-27 | 2015-07-30 | Snu R&Db Foundation | Method and pharmaceutical composition comprising adipose stem cell extract for treating or preventing neurologic disease |
CN204233210U (zh) * | 2014-11-15 | 2015-04-01 | 周国明 | 全频段复合式微创射频疼痛治疗仪 |
CN104587448A (zh) * | 2015-01-28 | 2015-05-06 | 赵廷宝 | 一种鞘内注射促神经再生注射剂的方法 |
CN104771602A (zh) * | 2015-04-17 | 2015-07-15 | 刘振亮 | 一种用于治疗面神经麻痹症的药物及其制备方法 |
CN106265678B (zh) * | 2016-07-18 | 2019-06-04 | 陕西省中医医院 | 一种用于治疗面瘫的膏药及其制备方法 |
CN108743366A (zh) * | 2018-02-28 | 2018-11-06 | 上海衡晟医院投资管理有限公司 | 生物水针激活听神经的方法 |
CN209075855U (zh) * | 2018-09-27 | 2019-07-09 | 金泽 | 面瘫疾患口腔内扩张及穴位刺激电子脉冲治疗仪 |
CN111419866A (zh) * | 2020-03-02 | 2020-07-17 | 南通大学 | miR-29a-3p在制备治疗周围神经损伤药物中的应用 |
US11806545B2 (en) * | 2020-10-23 | 2023-11-07 | Nextep BV | Therapy of eye conditions with pulsed radio frequency |
CN113082043A (zh) * | 2021-04-20 | 2021-07-09 | 王化兰 | 一种中医穴位注射治疗面神经麻痹的药物 |
-
2023
- 2023-09-09 CN CN202311159241.6A patent/CN117679520A/zh active Pending
- 2023-09-09 CN CN202311159251.XA patent/CN117679649A/zh active Pending
- 2023-09-09 CN CN202311159255.8A patent/CN117679521A/zh active Pending
- 2023-09-09 WO PCT/CN2023/117900 patent/WO2024051848A1/zh unknown
- 2023-09-09 WO PCT/CN2023/117896 patent/WO2024051844A1/zh unknown
- 2023-09-09 WO PCT/CN2023/117897 patent/WO2024051845A1/zh unknown
- 2023-09-09 WO PCT/CN2023/117898 patent/WO2024051846A1/zh unknown
- 2023-09-09 WO PCT/CN2023/117899 patent/WO2024051847A1/zh unknown
- 2023-09-09 CN CN202311159233.1A patent/CN117679518A/zh active Pending
- 2023-09-09 WO PCT/CN2023/117894 patent/WO2024051843A1/zh unknown
- 2023-09-09 CN CN202311159266.6A patent/CN117679522A/zh active Pending
- 2023-09-09 CN CN202311159238.4A patent/CN117679519A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
CN117679518A (zh) | 2024-03-12 |
WO2024051848A1 (zh) | 2024-03-14 |
CN117679520A (zh) | 2024-03-12 |
WO2024051847A1 (zh) | 2024-03-14 |
WO2024051846A1 (zh) | 2024-03-14 |
WO2024051843A1 (zh) | 2024-03-14 |
WO2024051844A1 (zh) | 2024-03-14 |
CN117679519A (zh) | 2024-03-12 |
CN117679649A (zh) | 2024-03-12 |
WO2024051845A1 (zh) | 2024-03-14 |
CN117679522A (zh) | 2024-03-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1599221B1 (en) | Treatment of sinusitis related chronic facial pain and headache with botulinum toxin | |
CN117679521A (zh) | 用于防治面部神经微卡压综合征的药物组合物及其应用 | |
EP1852500A1 (en) | Stem cells derived from bone marrow for tissue regeneration | |
RU2012117563A (ru) | Режим дозирования модулятора рецептора s1p | |
JP2023521064A (ja) | 疼痛調節因子を含む幹細胞由来エクソソーム及びその用途 | |
Liu et al. | Olfactory ensheathing cells and neuropathic pain | |
TWI794335B (zh) | 片仔癀及其製劑在治療腦中風後遺症的用途 | |
RU2410076C1 (ru) | Способ лечения моторно-вегетативных нарушений | |
RU2310424C1 (ru) | Способ повышения эффективности лечения атрофий зрительного нерва у детей | |
Nurwati et al. | Acupuncture improves diplopia and ptosis after subdural hematoma surgery: a case report | |
CN106039290A (zh) | 一种促红细胞生长素在重症颈椎病颈髓损伤中的探究与应用 | |
RU2286160C1 (ru) | Способ лечения травматических повреждений спинного мозга | |
RU2345740C1 (ru) | Способ лечения дистрофических заболеваний глаз грязелечебным средством "реликт-05" | |
RU2428994C1 (ru) | Лейкотромбоцитарная масса и препарат на ее основе | |
EP0981353B1 (en) | Facilitation of repair of neural injury with cm101/gbs toxin | |
UA140522U (uk) | Спосіб лікування діабетичної полінейропатії | |
RU2259836C1 (ru) | Биотрансплантат и способ лечения паркинсонизма | |
RU2192817C2 (ru) | Способ лечения частичной атрофии зрительного нерва | |
Mirakhori et al. | Evaluation of Amyloid Plaques in the Nervous System of Alzheimer's Patients with Reference to Non-Pharmacological Treatments in Patients | |
RU2124875C1 (ru) | Способ лечения больных с частичной атрофией зрительных нервов | |
RU2452436C1 (ru) | Способ лечения атрофии зрительного нерва сосудистого генеза | |
Isroilovich et al. | Effects of Cerebral Ischemic Strokes on the Facial Nerve | |
Rahlin | Neurological and Neuromuscular Systems Medical and Surgical Management of Alterations in Body Structures and Functions | |
Fairhurst | Neurological and Neuromuscular Systems | |
Doknic et al. | MON-LB56 Metabolic Profile in 107 Patients With Childhood Onset Growth Hormone Deficiency (CO-GHD) at the Time of Transition From Pediatric to Adulthood Endocrine Care |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication |