JP2011500661A - 血管腫の治療用の薬剤を製造するためのβ遮断薬の使用 - Google Patents
血管腫の治療用の薬剤を製造するためのβ遮断薬の使用 Download PDFInfo
- Publication number
- JP2011500661A JP2011500661A JP2010529467A JP2010529467A JP2011500661A JP 2011500661 A JP2011500661 A JP 2011500661A JP 2010529467 A JP2010529467 A JP 2010529467A JP 2010529467 A JP2010529467 A JP 2010529467A JP 2011500661 A JP2011500661 A JP 2011500661A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- use according
- blockers
- beta
- blocker
- 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.)
- Granted
Links
- 239000002876 beta blocker Substances 0.000 title claims abstract description 59
- 229940097320 beta blocking agent Drugs 0.000 title claims abstract description 56
- 239000003814 drug Substances 0.000 title claims abstract description 50
- 201000011066 hemangioma Diseases 0.000 title claims abstract description 38
- 238000011282 treatment Methods 0.000 title claims abstract description 33
- 229940079593 drug Drugs 0.000 title claims description 36
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims abstract description 84
- 229960003712 propranolol Drugs 0.000 claims abstract description 41
- 208000001969 capillary hemangioma Diseases 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 239000006188 syrup Substances 0.000 claims description 7
- 235000020357 syrup Nutrition 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 5
- CEMAWMOMDPGJMB-UHFFFAOYSA-N (+-)-Oxprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OCC=C CEMAWMOMDPGJMB-UHFFFAOYSA-N 0.000 claims description 4
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 claims description 4
- 229960002122 acebutolol Drugs 0.000 claims description 4
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 claims description 4
- 229960004324 betaxolol Drugs 0.000 claims description 4
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 claims description 4
- 229960001222 carteolol Drugs 0.000 claims description 4
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 claims description 4
- 229960004195 carvedilol Drugs 0.000 claims description 4
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 claims description 4
- 239000006071 cream Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 229960001632 labetalol Drugs 0.000 claims description 4
- 239000006210 lotion Substances 0.000 claims description 4
- 229960004570 oxprenolol Drugs 0.000 claims description 4
- 229960002035 penbutolol Drugs 0.000 claims description 4
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 claims description 4
- 229960002508 pindolol Drugs 0.000 claims description 4
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- -1 ceriprolol Chemical compound 0.000 claims description 3
- 239000012669 liquid formulation Substances 0.000 claims description 3
- 239000006186 oral dosage form Substances 0.000 claims description 3
- 229940042126 oral powder Drugs 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 230000001975 sympathomimetic effect Effects 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- NXWGWUVGUSFQJC-GFCCVEGCSA-N (2r)-1-[(2-methyl-1h-indol-4-yl)oxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NC[C@@H](O)COC1=CC=CC2=C1C=C(C)N2 NXWGWUVGUSFQJC-GFCCVEGCSA-N 0.000 claims description 2
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims description 2
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 claims description 2
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 claims description 2
- FBMYKMYQHCBIGU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N FBMYKMYQHCBIGU-UHFFFAOYSA-N 0.000 claims description 2
- 229960002213 alprenolol Drugs 0.000 claims description 2
- PAZJSJFMUHDSTF-UHFFFAOYSA-N alprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1CC=C PAZJSJFMUHDSTF-UHFFFAOYSA-N 0.000 claims description 2
- 229960002274 atenolol Drugs 0.000 claims description 2
- 229960002781 bisoprolol Drugs 0.000 claims description 2
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 claims description 2
- 229950005341 bucindolol Drugs 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 229960003745 esmolol Drugs 0.000 claims description 2
- AQNDDEOPVVGCPG-UHFFFAOYSA-N esmolol Chemical compound COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 AQNDDEOPVVGCPG-UHFFFAOYSA-N 0.000 claims description 2
- 239000006260 foam Substances 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 claims description 2
- 229960000831 levobunolol Drugs 0.000 claims description 2
- 229950008578 medroxalol Drugs 0.000 claims description 2
- MPQWSYJGFLADEW-UHFFFAOYSA-N medroxalol Chemical compound C=1C=C2OCOC2=CC=1CCC(C)NCC(O)C1=CC=C(O)C(C(N)=O)=C1 MPQWSYJGFLADEW-UHFFFAOYSA-N 0.000 claims description 2
- 229960003134 mepindolol Drugs 0.000 claims description 2
- 229960002704 metipranolol Drugs 0.000 claims description 2
- BLWNYSZZZWQCKO-UHFFFAOYSA-N metipranolol hydrochloride Chemical compound [Cl-].CC(C)[NH2+]CC(O)COC1=CC(C)=C(OC(C)=O)C(C)=C1C BLWNYSZZZWQCKO-UHFFFAOYSA-N 0.000 claims description 2
- 229960002237 metoprolol Drugs 0.000 claims description 2
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims description 2
- 229960004255 nadolol Drugs 0.000 claims description 2
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 claims description 2
- 229960000619 nebivolol Drugs 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 229940098462 oral drops Drugs 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims description 2
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 claims description 2
- 229960000203 propafenone Drugs 0.000 claims description 2
- 229960002370 sotalol Drugs 0.000 claims description 2
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 229960004605 timolol Drugs 0.000 claims description 2
- 208000009660 capillary infantile hemangioma Diseases 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 abstract description 6
- 102000014150 Interferons Human genes 0.000 abstract description 5
- 108010050904 Interferons Proteins 0.000 abstract description 5
- 229960001334 corticosteroids Drugs 0.000 abstract description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 abstract description 4
- 229960004528 vincristine Drugs 0.000 abstract description 4
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 229940047124 interferons Drugs 0.000 abstract 1
- 210000002889 endothelial cell Anatomy 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000009885 systemic effect Effects 0.000 description 9
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 8
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 8
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 8
- 229960005205 prednisolone Drugs 0.000 description 8
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 8
- 230000037396 body weight Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 150000003431 steroids Chemical class 0.000 description 7
- 230000000747 cardiac effect Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000002062 proliferating effect Effects 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 239000002870 angiogenesis inducing agent Substances 0.000 description 5
- 230000001772 anti-angiogenic effect Effects 0.000 description 5
- 210000000744 eyelid Anatomy 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 4
- 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 4
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 4
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 3
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 3
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 3
- 229960002537 betamethasone Drugs 0.000 description 3
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 3
- 210000001043 capillary endothelial cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 208000019622 heart disease Diseases 0.000 description 3
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 3
- 230000001969 hypertrophic effect Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 210000003681 parotid gland Anatomy 0.000 description 3
- 230000035752 proliferative phase Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- AQHHHDLHHXJYJD-AWEZNQCLSA-N (2s)-1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol Chemical compound C1=CC=C2C(OC[C@@H](O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-AWEZNQCLSA-N 0.000 description 2
- AQHHHDLHHXJYJD-CQSZACIVSA-N (R)-(+)-propranolol Chemical compound C1=CC=C2C(OC[C@H](O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-CQSZACIVSA-N 0.000 description 2
- 206010049021 Axillary mass Diseases 0.000 description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100029855 Caspase-3 Human genes 0.000 description 2
- 102000004091 Caspase-8 Human genes 0.000 description 2
- 108090000538 Caspase-8 Proteins 0.000 description 2
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 208000002125 Hemangioendothelioma Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 206010047571 Visual impairment Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 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 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 230000004528 endothelial cell apoptotic process Effects 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000012151 immunohistochemical method Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 2
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 2
- 230000000366 juvenile effect Effects 0.000 description 2
- 208000004731 long QT syndrome Diseases 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000003087 receptor blocking agent Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010055031 vascular neoplasm Diseases 0.000 description 2
- 208000029257 vision disease Diseases 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 241000766026 Coregonus nasus Species 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102100022183 E3 ubiquitin-protein ligase MIB1 Human genes 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000035211 Heart Murmurs Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000973503 Homo sapiens E3 ubiquitin-protein ligase MIB1 Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 101000945496 Homo sapiens Proliferation marker protein Ki-67 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000002177 Hypoxia-inducible factor-1 alpha Human genes 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 102100026849 Lymphatic vessel endothelial hyaluronic acid receptor 1 Human genes 0.000 description 1
- 101710178181 Lymphatic vessel endothelial hyaluronic acid receptor 1 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028747 Nasal necrosis Diseases 0.000 description 1
- 206010028780 Nasal ulcer Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 102100034836 Proliferation marker protein Ki-67 Human genes 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 206010062119 Sympathomimetic effect Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 208000003637 Tufted angioma Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010071989 Vascular endothelial growth factor overexpression Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- MXKCYTKUIDTFLY-ZNNSSXPHSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)-D-Galp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](NC(C)=O)[C@H](O[C@H]3[C@H]([C@@H](CO)OC(O)[C@@H]3O)O)O[C@@H]2CO)O[C@H]2[C@H]([C@H](O)[C@H](O)[C@H](C)O2)O)O[C@H](CO)[C@H](O)[C@@H]1O MXKCYTKUIDTFLY-ZNNSSXPHSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 208000009887 angiolipoma Diseases 0.000 description 1
- 230000002927 anti-mitotic effect Effects 0.000 description 1
- 230000005744 arteriovenous malformation Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate 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)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- STDBAQMTJLUMFW-UHFFFAOYSA-N butobarbital Chemical compound CCCCC1(CC)C(=O)NC(=O)NC1=O STDBAQMTJLUMFW-UHFFFAOYSA-N 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate 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)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009552 doppler ultrasonography Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000003038 endothelium Anatomy 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
- 210000002615 epidermis Anatomy 0.000 description 1
- 208000027836 epithelioid hemangioma Diseases 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 201000005923 hemangioma of subcutaneous tissue Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 201000009379 histiocytoid hemangioma Diseases 0.000 description 1
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000008185 minitablet Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 229940124624 oral corticosteroid Drugs 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229960004604 propranolol hydrochloride Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000037152 sensory function Effects 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 229940125794 sodium channel blocker Drugs 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 201000009483 spindle cell hemangioma Diseases 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 201000011531 vascular cancer Diseases 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
Images
Classifications
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
-
- 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
- A61K31/18—Sulfonamides
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- 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
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Otolaryngology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
Abstract
Description
さらに、本発明の使用による血管腫の治療方法も開示される。
以下の本文では、括弧でくくられた太字の参照番号は引用した文献および出版物に付された参照番号であり、前記文献および出版物は明細書の「実施例」部分の後の参照文献リストにも列挙されている。
さらに、治療を受けるほとんどの患者が乳児(infant)または小さな小児であるため、既知化合物に対する患者の忍容性が最も重要なものとなる。
≪β遮断薬≫とは、本明細書中では、β−受容体遮断剤、βアドレナリン作動性受容体遮断剤、β遮断剤、β−遮断剤もしくはβ−アドレナリン作動性受容体遮断剤、または任意の種類(β−1、β−2、β−3またはその他)のβ−アドレナリン作動性受容体に、天然または人工のアゴニストが結合するのを阻害する化学物質を示すその他任意の名称をも指す。
本発明によれば、該薬剤はまた、他の血管腫瘍、例えば、血管腫(すなわち類上皮血管腫、類洞血管腫、紡錘細胞血管腫)、房状血管腫(tufted angioma)、血管内皮腫(すなわちカポジ様血管内皮腫)、フォンヒッペル−リンダウ症候群における血管腫、ブルタヴィーユ病における線維血管腫および血管脂肪腫、化膿性肉芽腫、血管肉腫、例えばカポジ肉腫、増殖性の動静脈奇形、腫瘍に関連した血管増殖を含んでなる群から選択された血管腫瘍を治療するための薬剤であってもよい。参照文献:M.Wassef and coll.,“Vascular tumours and malformations, classification, pathology and imaging.”Ann Chir Plast Esth 2006;51:263−281[20]は、上記の活発な増殖腫瘍の解剖病理学的な分類を開示している。
本発明によれば、薬剤は、液体製剤、発泡性経口剤形、経口用散剤、多粒子系(multiparticule system)、口腔内崩壊性剤形を含んでなる群から選択された経口投与用薬剤であってよい。
本発明によれば、薬剤は、直腸内投与用の薬剤、例えば坐薬または硬ゼラチンカプセルであってよい。
当業者には、本明細書中で使用される用語「形態」が、薬剤を実際に利用するための該薬剤の薬剤製剤を指すことが明白に理解される。例えば、薬剤は、注射可能な形態(例えばAvlocardyl(登録商標)5mg/mlとして)、シロップ剤(例えばEfferalgan(登録商標)3%として)、経口懸濁液(例えばEfferalgan(登録商標)3%として)、ペレット剤(例えばDafalgan(登録商標)1gとして)、散剤(例えばDoliprane(登録商標)100mgとして)、顆粒剤(例えばZoltum(登録商標)10mgとして)、噴霧剤、経皮パッチ剤(例えばCordipatch(登録商標)5mg/24時間として)または局所用の形態(クリーム剤、ローション剤、洗眼剤)(例えばそれぞれDermovalクリーム(登録商標)、Betneval(登録商標)ローション、およびChibroxine(登録商標)洗眼剤として)を含んでなる群から選択された形態であってよい。
薬学的に許容可能な担体は、被投与者に応じて、ヒトまたは動物へのβ遮断薬の投与のために使用される任意の既知の薬学的担体であってよい。例えば、この担体は、例えばモノメトキシポリエチレングリコール(例えばViraferonpeg(登録商標)に含まれるもの)またはリポソーム(例えばAmbizome(登録商標)に含まれるもの)を含んでなる群から選択可能である。
血管腫およびβ−遮断薬、ならびに使用可能な製剤形態は上記に定義された通りである。
血管腫に関して本発明者らが行ったさらなる探索は、アドレナリン作動性β2受容体が血管腫の内皮細胞の表面に存在することを示している(下記の実施例を参照)。このことは、本発明で得られた結果を裏付け、生理病理学的説明を提供し、かつ本発明の枠組の中でのβ−遮断薬の作用機構を追認する。このことはまた、β−遮断薬としてのプロプラノロールの有効性と活性との間の関係をも裏付ける。
本明細書中以下に開示される実験結果において、病変の触知可能な軟化を伴う強烈な赤色から紫色への色の変化が、IHに罹患した乳幼児において観察された。この結果は、内皮細胞の増殖停止の原因である血管腫の慢性的低酸素状態を引き起こしたと考えることもできる。
この点で、該治療の標的が内皮細胞自体であるか、または間質細胞もしくは肥満細胞のような他の細胞であるかは明らかではない。IHの退縮について説明するために恐らく必要であろう第3の機構は、β遮断によって引き起こされた初期の内皮細胞アポトーシスである。
男児が鼻錐体にIHを発症した。2か月齢において、鼻腔の仕切り部分および鼻橋のネクローシスに伴う呼吸困難のため全身投与のステロイドが導入された。3mg/kg(体重)/日(mg/kg/日)のプレドニゾロンで1か月の治療後、血管腫は安定化したが鼻腔のネクローシスは進行した。この乳児がプレドニゾロン錠の服用を次第に拒絶するようになったので、本発明者らは等用量のベタメタゾンを滴剤として(0.5mg/kg/日)導入した。4か月齢では、血管腫は増殖を停止し、鼻内の潰瘍が治癒した。
2例目の乳児は30週で生まれた三つ児の一人の男児であり、出生時より右上腕全体ならびに右側の前頭頂部および上眼瞼部にプラーク状のIHを示した。
この投薬計画にもかかわらずIHは拡大し続け、2か月齢では眼瞼を開くことが不可能となり、添付の図1に示されるように巨大な腫瘍によって顔の右側が変形した。さらに、腋窩ひだは、臨床的計測で直径5cmの腫瘍IHコンポーネントによって占められた。
プレドニゾロンの用量を3mg/kg/日に減量し、本発明によるプロプラノロール2mg/kg/日を用いた治療を開始した。
7日後、添付の図2の写真に示されるように、血管腫の皮下コンポーネントの大きさの劇的な縮小により自発的に目を開くことが可能となった。耳下腺および腋窩の腫瘤の大きさはかなり縮小された。
6か月齢では、目の開きは十分であり、重大な視力障害はみられず、耳下腺および腋窩の皮下の血管腫コンポーネントは触知できず、IHは顔および腕の両方においてかなり弱まった。
女児は右眼周囲のIHを発症し、該IHは最初に第3週齢において見られ、内眼角に局在した。2か月齢では、IHの皮下コンポーネントは眼窩内に及び、上眼瞼の開きを制限した。
両親からインフォームド・コンセントを得た後、この女児はプロプラノロール2mg/kg/日での治療を受けた。12時間で病変部の平坦化がみられ、続いて段階的に改善された。
7か月齢では、IHは平坦で色が薄くなっており、超音波検査法では皮下コンポーネントを識別することができなかった。
血管腫に罹患した別の7人の小児もプロプラノロールの治療を受け、同様の結果が得られた。治療の失敗は本発明においては観察されていない。この種の結果は、例えばコルチコステロイド療法またはインターフェロンを用いた先行技術においては達成されていない。
本発明者らは、年少の小児において心臓病の適応に一般に使用される、良好な忍容性の非選択性β−遮断薬であるプロプラノロールが、Leaute−Labreze C,Dumas de la Roque E,Hubiche T,Boralevi F,Thambo JB.“Propranolol for severe hemangiomas of infancy.”New Engl J Med 2008,358;24:2650−51[16]において報告されるように、IHの増殖相を制御することができることを偶然に見出した。性比の歪みについての可能な説明、および内皮細胞によるHIF−2α経路の活性化とその後のVEGF過剰発現は、皮膚の毛細血管腫の病原論に関与する(Giatromanolaki et al,The HIF−2alpha/VEGF pathway activation in cutaneous capillary haemangiomas.Pathology 2005:149−51[17])。驚くべきことに、心臓肥大の治療用のβ遮断薬の研究から、シュー(Shyu)らは、カルジベジオール(cardivedilol)がHIF−1αおよびVEGFのタンパク質およびmRNAの両方をベースライン値へと戻すことを明らかにした(Shyu et al.,Cardiovedilol prevents cardiac hypertrophy and overexpression of hypoxia−inducible factor−1 alpha and vascular endothelial growth factor in pressure−overloaded rat heart.J Biomed Sci.2005;12:409−420[18])。IHにおけるin vivoおよびin vitroでのβ−アドレナリン作動性受容体下流の血管新生カスケード、およびHI表現型に影響を及ぼす潜在的な遺伝的決定要因を調査する、さらなる探索が行われる。
皮膚生検をパラフィンに包埋し、切断して5μm切片とし、一般的な形態学的評価のためにヘマトキシリン・エオシン染色した。α2−アドレナリン作動性受容体の存在およびHIF1−αの発現レベルを視覚化するために、切片を、それぞれウサギ抗ヒトα2−アドレナリン作動性受容体モノクローナル抗体1:100(PA1−20659、米国ゴールデン所在のABR)またはマウス抗ヒトHIF1−αモノクローナル抗体1:1000(ab8366、英国ケンブリッジ所在のabcam)とともに4℃で一晩インキュベートした。二次システムとして、本発明者らは、α2−アドレナリン作動性受容体についてはウサギ、およびHIF1−αについてはマウスに対して、染色感度を増強するEnvision(登録商標)ホースラディッシュペルオキシダーゼシステム(K4002、K4000、フランス国トラップ所在のDako)を使用した。切片をアミノエチルカルバミド(K3461、フランス国トラップ所在のDako)に曝露し、ヘマトキシリンで対比染色した。
Claims (19)
- 血管腫の治療用の薬剤を製造するためのβ遮断薬の使用。
- β遮断薬は、非選択性β遮断薬、β1−選択性β遮断薬、α1/β−アドレナリン作動性アンタゴニストの混合物、β2−選択性β遮断薬、および2以上のβ−遮断薬の混合物を含んでなる群から選択される、請求項1に記載の使用。
- β遮断薬は非選択性β遮断薬である、請求項1に記載の使用。
- 非選択性β遮断薬は、アルプレノロール、ブシンドロール、カルテオロール、カルベジロール、ラベタロール、レボブノロール、メドロキサロール、メピンドロール、メチプラノロール、ナドロール、オクスプレノロール、ペンブトロール、ピンドロール、プロパフェノン、プロプラノロール、ソタロール、チモロール、これらの薬学的に許容可能な塩およびこれらの混合物を含んでなる群から選択される、請求項3に記載の使用。
- β遮断薬はβ1−選択性β遮断薬である、請求項1または2に記載の使用。
- β1−選択性β遮断薬は、アセブトロール、アテノロール、ベタキソロール、ビソプロロール、セリプロロール、エスモロール、メトプロロール、ネビボロールを含んでなる群から例えば選択される、請求項5に記載の使用。
- β遮断薬は内因性交感神経刺激作用を有する、請求項1に記載の使用。
- β遮断薬は、アセブトロール、ベタキソロール、カルテオロール、カルベジロール、ラベタロール、オクスプレノロール、ペンブトロール、ピンドロール、プロプラノロールを含んでなる群から選択される、請求項7に記載の使用。
- 前記β遮断薬はプロプラノロールまたはその薬学的に許容可能な塩である、請求項1に記載の使用。
- 薬剤は毛細血管腫及び乳幼児の毛細血管腫のうちの少なくともいずれか一方を治療するための薬剤である、請求項1〜9のいずれか1項に記載の使用。
- 薬剤はシロップ剤または注射液である、請求項1〜10のいずれか1項に記載の使用。
- 薬剤は、液体製剤、発泡性経口剤形、経口用散剤、多粒子系、口腔内崩壊性剤形を含んでなる群から選択された経口投与用薬剤である、請求項1〜10のいずれか1項に記載の使用。
- 経口投与用薬剤は、溶液、シロップ剤、懸濁剤、乳剤および経口用滴剤を含んでなる群から選択された液体製剤である、請求項12に記載の使用。
- 薬剤は口腔内および舌下経路用の薬剤である、請求項1〜10のいずれか1項に記載の使用。
- 薬剤は局所経皮投与用の薬剤である、請求項1〜10のいずれか1項に記載の使用。
- 局所投与用の薬剤は、軟膏剤、クリーム剤、ゲル剤、ローション剤、パッチ剤、泡沫剤を含んでなる群から選択される、請求項15に記載の使用。
- 薬剤は鼻腔投与用の薬剤である、請求項1〜10のいずれか1項に記載の使用。
- 薬剤は直腸内投与用の薬剤である、請求項1〜10のいずれか1項に記載の使用。
- 薬剤は非経口投与用の薬剤である、請求項1〜10のいずれか1項に記載の使用。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07291273A EP2050441A1 (en) | 2007-10-19 | 2007-10-19 | Use of beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
EP07291273.6 | 2007-10-19 | ||
US98950707P | 2007-11-21 | 2007-11-21 | |
US60/989,507 | 2007-11-21 | ||
PCT/IB2008/002746 WO2009050567A2 (en) | 2007-10-19 | 2008-10-16 | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011500661A true JP2011500661A (ja) | 2011-01-06 |
JP5552700B2 JP5552700B2 (ja) | 2014-07-16 |
Family
ID=39156667
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010529467A Active JP5552700B2 (ja) | 2007-10-19 | 2008-10-16 | 血管腫の治療用の薬剤を製造するためのβ遮断薬の使用 |
Country Status (31)
Country | Link |
---|---|
US (2) | US8338489B2 (ja) |
EP (3) | EP2050441A1 (ja) |
JP (1) | JP5552700B2 (ja) |
KR (2) | KR20150110827A (ja) |
CN (2) | CN102006864B (ja) |
AR (1) | AR068927A1 (ja) |
AT (1) | ATE512661T1 (ja) |
AU (1) | AU2008313405B2 (ja) |
BR (1) | BRPI0816536A2 (ja) |
CA (1) | CA2701953C (ja) |
CL (1) | CL2008003083A1 (ja) |
CO (1) | CO6270209A2 (ja) |
CY (1) | CY1112604T1 (ja) |
DE (1) | DE08838691T1 (ja) |
DK (2) | DK2233135T3 (ja) |
ES (2) | ES2390534T3 (ja) |
HK (1) | HK1148940A1 (ja) |
HR (2) | HRP20110659T1 (ja) |
IL (1) | IL205129A (ja) |
MA (1) | MA31843B1 (ja) |
MX (1) | MX2010004295A (ja) |
MY (1) | MY156750A (ja) |
NZ (1) | NZ584307A (ja) |
PA (1) | PA8799401A1 (ja) |
PL (2) | PL2233135T3 (ja) |
PT (2) | PT2233135E (ja) |
RU (1) | RU2471500C2 (ja) |
SI (2) | SI2233135T1 (ja) |
TN (1) | TN2010000170A1 (ja) |
TW (1) | TWI531365B (ja) |
WO (1) | WO2009050567A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022071481A1 (ja) * | 2020-09-30 | 2022-04-07 | 日産化学株式会社 | 水溶性のβブロッカー及びレシチンを含む複合体 |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8987262B2 (en) | 2007-10-19 | 2015-03-24 | Universite de Bordeaux | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
EP2050441A1 (en) | 2007-10-19 | 2009-04-22 | Université Victor Segalen Bordeaux 2 | Use of beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
WO2010118340A1 (en) | 2009-04-09 | 2010-10-14 | University Of Medicine And Dentistry Of New Jersey | Treatment of cutaneous hemangioma |
EP2246044A1 (en) | 2009-04-21 | 2010-11-03 | Pierre Fabre Dermo-Cosmétique | Paediatric solutions comprising a beta-blocker |
US20140170112A1 (en) * | 2011-03-12 | 2014-06-19 | Vicus Therapeutics, Llc | Compositions for ameliorating systemic inflammation and methods for making and using them |
CN102579412A (zh) * | 2012-02-16 | 2012-07-18 | 山东省立医院 | 一种治疗婴幼儿血管瘤的外用药物及其制备方法 |
CN103536607A (zh) * | 2012-07-10 | 2014-01-29 | 邵金辉 | 土霉素,普罗帕酮和安乃近的抗肿瘤作用 |
CN103054793B (zh) * | 2013-01-05 | 2015-01-21 | 广州军区广州总医院 | 一种用于治疗婴幼儿血管瘤的盐酸普萘洛尔乳膏及其制备方法 |
WO2014150899A1 (en) * | 2013-03-15 | 2014-09-25 | Chapin Matthew J | Topical ophthalmic formulations for treating migraine |
CN104274390B (zh) * | 2014-09-04 | 2017-06-13 | 郑家伟 | 一种噻吗洛尔长效透皮制剂及其在血管瘤中的应用 |
RU2584082C1 (ru) * | 2015-01-21 | 2016-05-20 | Ильдар Наилевич Нурмеев | Способ лечения гемангиом |
CN105434337B (zh) * | 2015-04-03 | 2019-08-16 | 武汉科福新药有限责任公司 | 盐酸普萘洛尔亚微乳凝胶及其制备方法和用途 |
CN105106105A (zh) * | 2015-08-14 | 2015-12-02 | 天津市聚星康华医药科技有限公司 | 噻吗洛尔外用制剂治疗婴幼儿血管瘤的应用及其制备方法 |
US20170360829A1 (en) * | 2016-01-27 | 2017-12-21 | Gillies Mcindoe Research Institute | Treatment of vascular anomalies |
RU2617516C1 (ru) * | 2016-03-24 | 2017-04-25 | Государственное бюджетное учреждение здравоохранения города Москвы Научно-исследовательский институт неотложной детской хирургии и травматологии Департамента здравоохранения города Москвы | Способ лечения младенческих гемангиом |
CN106474061B (zh) * | 2016-12-08 | 2019-01-22 | 黑龙江童医生儿童生物制药有限公司 | 一种盐酸普萘洛尔口服乳剂及其制备方法 |
CN108261411B (zh) * | 2016-12-30 | 2021-04-30 | 武汉科福新药有限责任公司 | 用于婴幼儿血管瘤治疗的口腔膜剂及其制备方法 |
CA3072389A1 (en) * | 2017-08-07 | 2019-02-14 | Consejo Superior De Investigaciones Cientificas | Selective beta2-adrenergic receptor antagonist for treating von hippel-lindau |
CN108299279B (zh) * | 2018-02-09 | 2021-03-23 | 北京梅尔森医药技术开发有限公司 | 取代芳基胺醇化合物及其制备方法和用途 |
CN110314154A (zh) * | 2018-03-28 | 2019-10-11 | 武汉恒信源药业有限公司 | 左旋普萘洛尔在制备治疗血管病变药物中的应用 |
US20210346319A1 (en) * | 2018-10-04 | 2021-11-11 | Emory University | Pharmaceutical Compositions of R-(+)-Propranolol in Enantiomeric Excess and Therapeutic Uses Related Thereto |
RU2701213C1 (ru) * | 2018-12-27 | 2019-09-25 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет имени Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) | Способ лечения инфантильных гемангиом |
US11154518B2 (en) * | 2018-12-28 | 2021-10-26 | Chang Gung Memorial Hospital, Linkou | Methods and apparatus for treating a wound |
US20220218716A1 (en) * | 2019-05-24 | 2022-07-14 | Pediatric Derm Developement Llc | Treatment of infantile hemangioma |
CN111773226A (zh) * | 2019-06-26 | 2020-10-16 | 首都医科大学附属北京儿童医院 | 噻吗洛尔或其盐在制备预防和/或治疗丛状血管瘤的药物中的用途 |
US20230090708A1 (en) * | 2020-01-29 | 2023-03-23 | Massey Ventures Limited | Methods and compositions for the treatment of hemangioma |
US20230248671A1 (en) * | 2020-07-10 | 2023-08-10 | Chang Gung Memorial Hospital, Linkou | Use of beta-1 adrenergic receptor antagonist for preparing compositions for reducing epithelial cell damage induced by epidermal growth factor receptor inhibitors and inhibiting cancer cells |
CN113274348A (zh) * | 2021-06-11 | 2021-08-20 | 四川大学华西医院 | 用于治疗婴幼儿血管瘤的阿替洛尔凝胶、制备方法及应用 |
PL244294B1 (pl) * | 2022-09-20 | 2024-01-03 | Univ Medyczny W Lodzi | Kompozycja farmaceutyczna do stosowania miejscowego oraz jej zastosowanie w leczeniu naczyniaków krwionośnych u dzieci |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002504086A (ja) * | 1996-05-01 | 2002-02-05 | イーライ・リリー・アンド・カンパニー | Vegf関連疾患の治療的処置 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL301580A (ja) * | 1962-12-11 | |||
US3466325A (en) * | 1965-04-30 | 1969-09-09 | Haessle Ab | 1-(ortho-alkenyl phenoxy) - 2-hydroxy-3-isopropylaminopropanes and the salts thereof |
GB1253709A (en) | 1968-05-22 | 1971-11-17 | Frosst & Co Charles E | Thiadiazole derivatives |
US3657237A (en) * | 1968-05-22 | 1972-04-18 | Frosst & Co Charles E | Process for making 1 2 5-thiadiazoles in the sinister configuration |
US3655663A (en) * | 1969-04-21 | 1972-04-11 | Burton K Wasson | 4-(3-secondary amino-2-hydroxy-proxy) 1 2 5-thiadiazoles |
SE354851B (ja) * | 1970-02-18 | 1973-03-26 | Haessle Ab | |
AT334385B (de) * | 1973-12-20 | 1976-01-10 | Chemie Linz Ag | Verfahren zur herstellung von neuen phenoxypropylaminderivaten und deren salzen |
FR2330383A1 (fr) * | 1975-11-06 | 1977-06-03 | Synthelabo | Nouveaux ethers de phenols substitues, leurs sels, leur preparation et les medicaments qui les renferment |
US5116867A (en) * | 1989-06-30 | 1992-05-26 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | D-propranolol as a selective adenosine antagonist |
US5182102A (en) * | 1991-07-12 | 1993-01-26 | Alcon Laboratories, Inc. | Anti-glaucoma compositions |
DK1155689T3 (da) * | 1993-07-19 | 2006-11-20 | Angiotech Pharm Inc | Antiangiogene stents og fremgangsmåder til fremstilling heraf |
US6232299B1 (en) * | 1996-05-01 | 2001-05-15 | Eli Lilly And Company | Use of protein kinase C inhibitors to enhance the clinical efficacy of oncolytic agents and radiation therapy |
GB9616672D0 (en) * | 1996-08-08 | 1996-09-25 | Scherer Ltd R P | Pharmaceutical compositions |
EP1389201A1 (de) * | 2001-05-08 | 2004-02-18 | Schering Aktiengesellschaft | N-oxidanthranylamid-derivate und deren verwendung als arzneimittel |
US20050244458A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular neuropathies |
EP1781331A1 (en) * | 2004-08-09 | 2007-05-09 | Université Catholique de Louvain | Use of agonists and antagonists of beta-adrenoceptors for treating arterial diseases |
TW200716141A (en) * | 2005-05-05 | 2007-05-01 | Combinatorx Inc | Compositions and methods for treatment for neoplasms |
US8987262B2 (en) | 2007-10-19 | 2015-03-24 | Universite de Bordeaux | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
EP2050441A1 (en) | 2007-10-19 | 2009-04-22 | Université Victor Segalen Bordeaux 2 | Use of beta blocker for the manufacture of a medicament for the treatment of hemangiomas |
-
2007
- 2007-10-19 EP EP07291273A patent/EP2050441A1/en not_active Withdrawn
-
2008
- 2008-10-14 TW TW097139397A patent/TWI531365B/zh active
- 2008-10-16 WO PCT/IB2008/002746 patent/WO2009050567A2/en active Application Filing
- 2008-10-16 MY MYPI2010001459A patent/MY156750A/en unknown
- 2008-10-16 EP EP09015563.1A patent/EP2233135B8/en active Active
- 2008-10-16 AU AU2008313405A patent/AU2008313405B2/en active Active
- 2008-10-16 SI SI200830749T patent/SI2233135T1/sl unknown
- 2008-10-16 PL PL09015563T patent/PL2233135T3/pl unknown
- 2008-10-16 EP EP08838691A patent/EP2187878B1/en active Active
- 2008-10-16 PT PT09015563T patent/PT2233135E/pt unknown
- 2008-10-16 DE DE08838691T patent/DE08838691T1/de active Pending
- 2008-10-16 CN CN2008801118925A patent/CN102006864B/zh active Active
- 2008-10-16 AT AT08838691T patent/ATE512661T1/de active
- 2008-10-16 SI SI200830362T patent/SI2187878T1/sl unknown
- 2008-10-16 CN CN2012104556417A patent/CN103169971A/zh active Pending
- 2008-10-16 DK DK09015563.1T patent/DK2233135T3/da active
- 2008-10-16 US US12/599,266 patent/US8338489B2/en active Active
- 2008-10-16 PT PT08838691T patent/PT2187878E/pt unknown
- 2008-10-16 BR BRPI0816536A patent/BRPI0816536A2/pt not_active Application Discontinuation
- 2008-10-16 KR KR1020157025385A patent/KR20150110827A/ko not_active Application Discontinuation
- 2008-10-16 ES ES09015563T patent/ES2390534T3/es active Active
- 2008-10-16 RU RU2010112816/15A patent/RU2471500C2/ru active
- 2008-10-16 CA CA2701953A patent/CA2701953C/en active Active
- 2008-10-16 NZ NZ584307A patent/NZ584307A/en unknown
- 2008-10-16 PL PL08838691T patent/PL2187878T3/pl unknown
- 2008-10-16 JP JP2010529467A patent/JP5552700B2/ja active Active
- 2008-10-16 MX MX2010004295A patent/MX2010004295A/es active IP Right Grant
- 2008-10-16 KR KR1020107010904A patent/KR101562627B1/ko active IP Right Grant
- 2008-10-16 PA PA20088799401A patent/PA8799401A1/es unknown
- 2008-10-16 DK DK08838691.7T patent/DK2187878T3/da active
- 2008-10-16 ES ES08838691T patent/ES2368299T3/es active Active
- 2008-10-17 AR ARP080104555A patent/AR068927A1/es not_active Application Discontinuation
- 2008-10-17 CL CL2008003083A patent/CL2008003083A1/es unknown
-
2010
- 2010-04-08 CO CO10040510A patent/CO6270209A2/es not_active Application Discontinuation
- 2010-04-15 IL IL205129A patent/IL205129A/en active IP Right Grant
- 2010-04-16 TN TN2010000170A patent/TN2010000170A1/fr unknown
- 2010-05-10 MA MA32829A patent/MA31843B1/fr unknown
- 2010-07-19 HK HK11103063.3A patent/HK1148940A1/xx unknown
-
2011
- 2011-09-07 CY CY20111100858T patent/CY1112604T1/el unknown
- 2011-09-13 HR HR20110659T patent/HRP20110659T1/hr unknown
-
2012
- 2012-09-27 HR HRP20120765AT patent/HRP20120765T1/hr unknown
- 2012-11-16 US US13/678,902 patent/US9173858B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002504086A (ja) * | 1996-05-01 | 2002-02-05 | イーライ・リリー・アンド・カンパニー | Vegf関連疾患の治療的処置 |
Non-Patent Citations (2)
Title |
---|
JPN6013019123; Clinical Cancer Research vol.9, 2003, p.4514-4521 * |
JPN6013019125; Journal of Pediatric Surgery vol.28, no.10, 1993, p.1253-1257 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022071481A1 (ja) * | 2020-09-30 | 2022-04-07 | 日産化学株式会社 | 水溶性のβブロッカー及びレシチンを含む複合体 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5552700B2 (ja) | 血管腫の治療用の薬剤を製造するためのβ遮断薬の使用 | |
US8987262B2 (en) | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas | |
US10898495B2 (en) | Treatment of demyelinating diseases | |
Chen et al. | Blocking GluN2B subunits reverses the enhanced seizure susceptibility after prolonged febrile seizures with a wide therapeutic time-window | |
US20220323428A1 (en) | Byl719 (alpelisib) for use in the treatment of pik3ca-related overgrowth spectrum (pros-cloves syndrome) | |
US7192941B2 (en) | Estradiol metabolites for the treatment of pulmonary hypertension | |
US20130302337A1 (en) | Methods and compositions for treating alzheimer's disease | |
AU2014201660B2 (en) | Use of a beta blocker for the manufacture of a medicament for the treatment of hemangiomas | |
US11351229B2 (en) | Combination therapies for treating infantile spasms and other treatment resistant epilepsies | |
SA08290744B1 (ar) | إستعمال محصر للبيتا لصناعة دواء لمعالجة ورم وعائى | |
JP2024508498A (ja) | 睡眠時無呼吸の治療における使用のためのレボキセチン及びムスカリン受容体拮抗薬(mra)の組み合わせ |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110921 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20120123 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130423 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130719 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130726 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130823 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131029 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140129 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140408 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20140509 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140508 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140509 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5552700 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S201 | Request for registration of exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R314201 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R153 | Grant of patent term extension |
Free format text: JAPANESE INTERMEDIATE CODE: R153 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S211 | Written request for registration of transfer of exclusive licence |
Free format text: JAPANESE INTERMEDIATE CODE: R314211 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |