CA3032473A1 - Topical rapamycin therapy - Google Patents
Topical rapamycin therapy Download PDFInfo
- Publication number
- CA3032473A1 CA3032473A1 CA3032473A CA3032473A CA3032473A1 CA 3032473 A1 CA3032473 A1 CA 3032473A1 CA 3032473 A CA3032473 A CA 3032473A CA 3032473 A CA3032473 A CA 3032473A CA 3032473 A1 CA3032473 A1 CA 3032473A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- rapamycin
- weight
- patient
- glycol
- 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.)
- Abandoned
Links
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 123
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims abstract description 115
- 229960002930 sirolimus Drugs 0.000 title claims abstract description 115
- 230000000699 topical effect Effects 0.000 title abstract description 53
- 238000002560 therapeutic procedure Methods 0.000 title description 6
- 239000000203 mixture Substances 0.000 claims abstract description 118
- 238000011282 treatment Methods 0.000 claims abstract description 63
- 208000003120 Angiofibroma Diseases 0.000 claims abstract description 36
- 208000026911 Tuberous sclerosis complex Diseases 0.000 claims abstract description 33
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 28
- 230000001815 facial effect Effects 0.000 claims description 25
- 206010040882 skin lesion Diseases 0.000 claims description 23
- 231100000444 skin lesion Toxicity 0.000 claims description 23
- 230000003902 lesion Effects 0.000 claims description 21
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 229960004063 propylene glycol Drugs 0.000 claims description 13
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 12
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 12
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 12
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 12
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 12
- 239000006071 cream Substances 0.000 claims description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 208000009443 Vascular Malformations Diseases 0.000 claims description 11
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 9
- 239000000600 sorbitol Substances 0.000 claims description 9
- 208000031857 Campbell de Morgan spots Diseases 0.000 claims description 8
- 208000003019 Neurofibromatosis 1 Diseases 0.000 claims description 8
- 208000024834 Neurofibromatosis type 1 Diseases 0.000 claims description 8
- 206010037649 Pyogenic granuloma Diseases 0.000 claims description 8
- 208000014402 familial multiple discoid fibromas Diseases 0.000 claims description 8
- 201000011066 hemangioma Diseases 0.000 claims description 8
- 208000009056 telangiectasis Diseases 0.000 claims description 8
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 7
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 7
- 235000019271 petrolatum Nutrition 0.000 claims description 7
- 229940083037 simethicone Drugs 0.000 claims description 7
- 235000010199 sorbic acid Nutrition 0.000 claims description 7
- 239000004334 sorbic acid Substances 0.000 claims description 7
- 229940075582 sorbic acid Drugs 0.000 claims description 7
- 239000003871 white petrolatum Substances 0.000 claims description 7
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 6
- 229940081733 cetearyl alcohol Drugs 0.000 claims description 6
- 239000000975 dye Substances 0.000 claims description 6
- 239000003205 fragrance Substances 0.000 claims description 6
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 6
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
- 208000032541 Epidermal naevus Diseases 0.000 claims description 5
- 206010025219 Lymphangioma Diseases 0.000 claims description 5
- 239000002033 PVDF binder Substances 0.000 claims description 5
- 208000006787 Port-Wine Stain Diseases 0.000 claims description 5
- 241000588769 Proteus <enterobacteria> Species 0.000 claims description 5
- 206010039785 Sebaceous naevus Diseases 0.000 claims description 5
- 229940073669 ceteareth 20 Drugs 0.000 claims description 5
- 208000009197 gingival hypertrophy Diseases 0.000 claims description 5
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 5
- 206010030983 oral lichen planus Diseases 0.000 claims description 5
- 208000023112 overgrowth syndrome Diseases 0.000 claims description 5
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims 1
- 210000003491 skin Anatomy 0.000 abstract description 30
- 238000010521 absorption reaction Methods 0.000 abstract description 8
- 230000009885 systemic effect Effects 0.000 abstract description 7
- 210000004927 skin cell Anatomy 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 22
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 19
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 239000000902 placebo Substances 0.000 description 12
- 239000008186 active pharmaceutical agent Substances 0.000 description 10
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 101000795659 Homo sapiens Tuberin Proteins 0.000 description 7
- 230000002411 adverse Effects 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 101000795643 Homo sapiens Hamartin Proteins 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000008406 cosmetic ingredient Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 102100031561 Hamartin Human genes 0.000 description 5
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 5
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 5
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- -1 e.g. Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- 230000001594 aberrant effect Effects 0.000 description 4
- 230000036765 blood level Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 239000000049 pigment Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 229960001302 ridaforolimus Drugs 0.000 description 4
- 229960000235 temsirolimus Drugs 0.000 description 4
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 3
- 231100000321 erythema Toxicity 0.000 description 3
- 229960005167 everolimus Drugs 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 235000013980 iron oxide Nutrition 0.000 description 3
- 229940124302 mTOR inhibitor Drugs 0.000 description 3
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 229960001679 octinoxate Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000001243 protein synthesis Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- CXVGEDCSTKKODG-UHFFFAOYSA-N sulisobenzone Chemical compound C1=C(S(O)(=O)=O)C(OC)=CC(O)=C1C(=O)C1=CC=CC=C1 CXVGEDCSTKKODG-UHFFFAOYSA-N 0.000 description 3
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 3
- 239000004408 titanium dioxide Substances 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- YYSFXUWWPNHNAZ-PKJQJFMNSA-N umirolimus Chemical compound C1[C@@H](OC)[C@H](OCCOCC)CC[C@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 YYSFXUWWPNHNAZ-PKJQJFMNSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- MEZZCSHVIGVWFI-UHFFFAOYSA-N 2,2'-Dihydroxy-4-methoxybenzophenone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1O MEZZCSHVIGVWFI-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- GYLDXIAOMVERTK-UHFFFAOYSA-N 5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)N=C1C1=CC=C(OC(N)=N2)C2=C1 GYLDXIAOMVERTK-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 206010065869 Astrocytoma, low grade Diseases 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
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- FMRHJJZUHUTGKE-UHFFFAOYSA-N Ethylhexyl salicylate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1O FMRHJJZUHUTGKE-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- RFSMUFRPPYDYRD-CALCHBBNSA-N Ku-0063794 Chemical compound C1=C(CO)C(OC)=CC=C1C1=CC=C(C(=NC(=N2)N3C[C@@H](C)O[C@@H](C)C3)N3CCOCC3)C2=N1 RFSMUFRPPYDYRD-CALCHBBNSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000012868 Overgrowth Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- HEAHZSUCFKFERC-LRVMPXQBSA-N [(2e)-2-[[4-[(z)-[7,7-dimethyl-3-oxo-4-(sulfomethyl)-2-bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound CC1(C)C2CCC1(CS(O)(=O)=O)C(=O)\C2=C/C(C=C1)=CC=C1\C=C/1C(=O)C2(CS(O)(=O)=O)CCC\1C2(C)C HEAHZSUCFKFERC-LRVMPXQBSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 229960005193 avobenzone Drugs 0.000 description 2
- 210000000270 basal cell Anatomy 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- CMDKPGRTAQVGFQ-RMKNXTFCSA-N cinoxate Chemical compound CCOCCOC(=O)\C=C\C1=CC=C(OC)C=C1 CMDKPGRTAQVGFQ-RMKNXTFCSA-N 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229960003747 ecamsule Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229960000655 ensulizole Drugs 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 231100000021 irritant Toxicity 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- SOXAGEOHPCXXIO-DVOMOZLQSA-N menthyl anthranilate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)C1=CC=CC=C1N SOXAGEOHPCXXIO-DVOMOZLQSA-N 0.000 description 2
- 229960002248 meradimate Drugs 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229960003921 octisalate Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 2
- 229960001173 oxybenzone Drugs 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 229940099538 rapamune Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229950009216 sapanisertib Drugs 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 201000004059 subependymal giant cell astrocytoma Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960000368 sulisobenzone Drugs 0.000 description 2
- 230000000475 sunscreen effect Effects 0.000 description 2
- 239000000516 sunscreening agent Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 229950007775 umirolimus Drugs 0.000 description 2
- 230000006444 vascular growth Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000011787 zinc oxide Substances 0.000 description 2
- CGTADGCBEXYWNE-GTTQIJKGSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-GTTQIJKGSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- PDHSAQOQVUXZGQ-JKSUJKDBSA-N (2r,3s)-2-(3,4-dihydroxyphenyl)-3-methoxy-3,4-dihydro-2h-chromene-5,7-diol Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2OC)=CC=C(O)C(O)=C1 PDHSAQOQVUXZGQ-JKSUJKDBSA-N 0.000 description 1
- KBKGPMDADJLBEM-UHFFFAOYSA-N 1-(4-pentylphenyl)ethanone Chemical compound CCCCCC1=CC=C(C(C)=O)C=C1 KBKGPMDADJLBEM-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- TYYHDKOVFSVWON-UHFFFAOYSA-N 2-butyl-2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(CCCC)C(=O)C1=CC=CC=C1 TYYHDKOVFSVWON-UHFFFAOYSA-N 0.000 description 1
- VSXIZXFGQGKZQG-UHFFFAOYSA-N 2-cyano-3,3-diphenylprop-2-enoic acid Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)O)C1=CC=CC=C1 VSXIZXFGQGKZQG-UHFFFAOYSA-N 0.000 description 1
- 239000004808 2-ethylhexylester Substances 0.000 description 1
- WSSJONWNBBTCMG-UHFFFAOYSA-N 2-hydroxybenzoic acid (3,3,5-trimethylcyclohexyl) ester Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C1=CC=CC=C1O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
- ZHYGVVKSAGDVDY-QQQXYHJWSA-N 7-o-demethyl cypher Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](O)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 ZHYGVVKSAGDVDY-QQQXYHJWSA-N 0.000 description 1
- KVLFRAWTRWDEDF-IRXDYDNUSA-N AZD-8055 Chemical compound C1=C(CO)C(OC)=CC=C1C1=CC=C(C(=NC(=N2)N3[C@H](COCC3)C)N3[C@H](COCC3)C)C2=N1 KVLFRAWTRWDEDF-IRXDYDNUSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- NOQGZXFMHARMLW-UHFFFAOYSA-N Daminozide Chemical compound CN(C)NC(=O)CCC(O)=O NOQGZXFMHARMLW-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- LLQPHQFNMLZJMP-UHFFFAOYSA-N Fentrazamide Chemical compound N1=NN(C=2C(=CC=CC=2)Cl)C(=O)N1C(=O)N(CC)C1CCCCC1 LLQPHQFNMLZJMP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101710175981 Hamartin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- WYWZRNAHINYAEF-UHFFFAOYSA-N Padimate O Chemical compound CCCCC(CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-UHFFFAOYSA-N 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 208000012641 Pigmentation disease Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000002027 Tuberin Human genes 0.000 description 1
- 108050009309 Tuberin Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 125000004945 acylaminoalkyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- JROFGZPOBKIAEW-HAQNSBGRSA-N chembl3120215 Chemical compound N1C=2C(OC)=CC=CC=2C=C1C(=C1C(N)=NC=NN11)N=C1[C@H]1CC[C@H](C(O)=O)CC1 JROFGZPOBKIAEW-HAQNSBGRSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 238000002192 cholecystectomy Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 229960001063 cinoxate Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000002681 cryosurgery Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960004960 dioxybenzone Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- XJFGDLJQUJQUEI-UHFFFAOYSA-N dodecyl decanoate dodecyl octanoate Chemical compound CCCCCCCCCCCCOC(=O)CCCCCCC.CCCCCCCCCCCCOC(=O)CCCCCCCCC XJFGDLJQUJQUEI-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- HEAHZSUCFKFERC-UHFFFAOYSA-N ecamsule Chemical compound CC1(C)C2CCC1(CS(O)(=O)=O)C(=O)C2=CC(C=C1)=CC=C1C=C1C(=O)C2(CS(O)(=O)=O)CCC1C2(C)C HEAHZSUCFKFERC-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003168 generic drug Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 229960004881 homosalate Drugs 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000002647 laser therapy Methods 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- YBGZDTIWKVFICR-UHFFFAOYSA-N octinoxate Chemical compound CCCCC(CC)COC(=O)C=CC1=CC=C(OC)C=C1 YBGZDTIWKVFICR-UHFFFAOYSA-N 0.000 description 1
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical group C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 1
- 229960000601 octocrylene Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229950000516 padimate Drugs 0.000 description 1
- LXTZRIBXKVRLOA-UHFFFAOYSA-N padimate a Chemical compound CCCCCOC(=O)C1=CC=C(N(C)C)C=C1 LXTZRIBXKVRLOA-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920009537 polybutylene succinate adipate Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002884 skin cream Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 229940100411 torisel Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- UEVAMYPIMMOEFW-UHFFFAOYSA-N trolamine salicylate Chemical compound OCCN(CCO)CCO.OC(=O)C1=CC=CC=C1O UEVAMYPIMMOEFW-UHFFFAOYSA-N 0.000 description 1
- 229940030300 trolamine salicylate Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- SZCZSKMCTGEJKI-UHFFFAOYSA-N tuberin Natural products COC1=CC=C(C=CNC=O)C=C1 SZCZSKMCTGEJKI-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
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
- A61K31/33—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662372940P | 2016-08-10 | 2016-08-10 | |
| US62/372,940 | 2016-08-10 | ||
| PCT/US2017/046320 WO2018031789A1 (en) | 2016-08-10 | 2017-08-10 | Topical rapamycin therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3032473A1 true CA3032473A1 (en) | 2018-02-15 |
Family
ID=59684091
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3032473A Abandoned CA3032473A1 (en) | 2016-08-10 | 2017-08-10 | Topical rapamycin therapy |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20190167649A1 (enExample) |
| EP (1) | EP3496712A1 (enExample) |
| JP (1) | JP2019527711A (enExample) |
| KR (1) | KR20190039220A (enExample) |
| CN (1) | CN109689053A (enExample) |
| AU (1) | AU2017311491A1 (enExample) |
| BR (1) | BR112019002689A2 (enExample) |
| CA (1) | CA3032473A1 (enExample) |
| MX (1) | MX2019001670A (enExample) |
| RU (1) | RU2019106483A (enExample) |
| WO (1) | WO2018031789A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL302385B2 (en) | 2017-01-06 | 2024-06-01 | Palvella Therapeutics Inc | Non-aqueous preparations of mTOR inhibitors and methods of use |
| WO2019156999A1 (en) * | 2018-02-06 | 2019-08-15 | Georgetown University | TOPICAL mTOR INHIBITORS FOR CUTANEOUS PROLIFERATIVE AND VASCULAR CONDITIONS |
| JP2021530463A (ja) | 2018-07-02 | 2021-11-11 | パルヴェラ セラピューティクス、インク． | ｍＴＯＲ阻害剤の無水組成物および使用方法 |
| EP3829578A4 (en) * | 2018-08-30 | 2022-08-17 | Chemistryrx | COMPOSITIONS CONTAINING SIROLIMUS |
| CN109431997B (zh) * | 2018-12-20 | 2021-06-04 | 武汉科福新药有限责任公司 | 一种雷帕霉素局部注射制剂及其制备方法 |
| JP2022521006A (ja) | 2019-02-20 | 2022-04-04 | エイアイ・セラピューティクス・インコーポレーテッド | 局所ラパマイシン製剤ならびに顔面血管線維腫および他の皮膚疾患の治療におけるそれらの使用 |
| WO2020175131A1 (ja) * | 2019-02-27 | 2020-09-03 | 国立大学法人大阪大学 | 脈管異常治療用外用剤 |
| JP7755854B2 (ja) * | 2020-01-24 | 2025-10-17 | ノーベルファーマ株式会社 | ラパマイシン含有外用剤 |
| AU2020277132B1 (en) * | 2020-11-24 | 2021-11-04 | Aft Pharmaceuticals Limited | A Rapamycin Composition |
| AU2023203871B1 (en) * | 2023-06-20 | 2024-07-25 | Aft Pharmaceuticals Ltd | A Rapamycin Method of Treatment and Composition |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9606452D0 (en) | 1996-03-27 | 1996-06-05 | Sandoz Ltd | Organic compounds |
| EP0937082A2 (en) | 1996-07-12 | 1999-08-25 | Ariad Pharmaceuticals, Inc. | Materials and method for treating or preventing pathogenic fungal infection |
| GB9723669D0 (en) | 1997-11-07 | 1998-01-07 | Univ Aberdeen | Skin penetration enhancing components |
| AU2003259803B2 (en) | 2002-08-12 | 2007-08-02 | The Regents Of The University Of Michigan | Diagnosis and treatment of tuberous sclerosis |
| EP1853612A1 (en) | 2005-03-02 | 2007-11-14 | Wyeth | Purification of rapamycin |
| AU2007211613C1 (en) | 2006-02-02 | 2018-01-04 | Novartis Ag | Tuberous Sclerosis treatment |
| US20120022095A1 (en) | 2010-06-24 | 2012-01-26 | Teng Joyce M C | Topical rapamycin for treatment of facial angiofibromas in tuberous sclerosis |
| WO2012142145A1 (en) * | 2011-04-12 | 2012-10-18 | Dow Pharmaceutical Sciences | Methods of treating skin conditions exhibiting telangiectasia |
| CA2899206C (en) * | 2013-01-24 | 2019-07-09 | Transderm, Inc. | Compositions for transdermal delivery of mtor inhibitors |
| HUP1400075A2 (hu) * | 2014-02-14 | 2015-08-28 | Druggability Technologies Ip Holdco Jersey Ltd | Sirolimus és származékainak komplexei, elõállítása és gyógyszerészeti kompozíciói |
| KR20180081501A (ko) * | 2015-09-24 | 2018-07-16 | 드렉셀유니버시티 | 진피 장애를 치료하거나 예방하는 신규한 조성물 및 방법 |
| CN105663027B (zh) * | 2016-04-01 | 2018-12-18 | 中国人民解放军广州军区武汉总医院 | 西罗莫司外用制剂、其制备方法及用途 |
-
2017
- 2017-08-10 CA CA3032473A patent/CA3032473A1/en not_active Abandoned
- 2017-08-10 US US16/324,274 patent/US20190167649A1/en not_active Abandoned
- 2017-08-10 EP EP17755383.1A patent/EP3496712A1/en not_active Withdrawn
- 2017-08-10 WO PCT/US2017/046320 patent/WO2018031789A1/en not_active Ceased
- 2017-08-10 AU AU2017311491A patent/AU2017311491A1/en not_active Abandoned
- 2017-08-10 CN CN201780049324.6A patent/CN109689053A/zh active Pending
- 2017-08-10 KR KR1020197006896A patent/KR20190039220A/ko not_active Ceased
- 2017-08-10 JP JP2019506721A patent/JP2019527711A/ja active Pending
- 2017-08-10 RU RU2019106483A patent/RU2019106483A/ru unknown
- 2017-08-10 BR BR112019002689A patent/BR112019002689A2/pt not_active IP Right Cessation
- 2017-08-10 MX MX2019001670A patent/MX2019001670A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2019106483A (ru) | 2020-09-11 |
| WO2018031789A1 (en) | 2018-02-15 |
| US20190167649A1 (en) | 2019-06-06 |
| JP2019527711A (ja) | 2019-10-03 |
| MX2019001670A (es) | 2019-07-04 |
| CN109689053A (zh) | 2019-04-26 |
| BR112019002689A2 (pt) | 2019-05-14 |
| EP3496712A1 (en) | 2019-06-19 |
| RU2019106483A3 (enExample) | 2020-12-04 |
| AU2017311491A1 (en) | 2019-02-07 |
| KR20190039220A (ko) | 2019-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190167649A1 (en) | Topical rapamycin therapy | |
| US12268673B2 (en) | Anhydrous compositions of mTOR inhibitors and methods of use | |
| ES2627405T3 (es) | Composiciones que comprenden brimonidina para el tratamiento del eritema | |
| JP6438466B2 (ja) | イベルメクチンによる丘疹膿疱性の酒さの治療 | |
| KR20140004186A (ko) | 표면활성제 조성물 | |
| US20130102572A1 (en) | Methods of treating skin conditions exhibiting telangiectasia | |
| US20250114497A1 (en) | Skin composition | |
| Rodríguez-Navarro et al. | Comparison of neosaxitoxin versus bupivacaine via port infiltration for postoperative analgesia following laparoscopic cholecystectomy: a randomized, double-blind trial | |
| JP2019507758A (ja) | プリドピジンを使用する神経変性眼疾患の治療 | |
| KR20140012651A (ko) | 파라벤 조성물 | |
| JP2021530463A (ja) | ｍＴＯＲ阻害剤の無水組成物および使用方法 | |
| JP2006522059A (ja) | 皮膚疾患の処置にて使用するための免疫抑制剤を含んでなる医薬組成物 | |
| ES2351045T3 (es) | Utilización de una composición farmacéutica que comprende calcitriol y propionato de clobetazol para el tratamiento de la psoriasis. | |
| Stein et al. | Betamethasone valerate foam for treatment of nonscalp psoriasis | |
| TWI863995B (zh) | 皮膚型紅斑狼瘡之治療 | |
| JP6929860B2 (ja) | 手湿疹の治療 | |
| JP2017502053A (ja) | 炎症性皮膚状態を治療するためのアラントイン組成物 | |
| US7357938B2 (en) | Sulfacetamide formulations for treatment of rosacea | |
| US10772813B2 (en) | Compositions and methods of administering a colchicine based topical composition for the prevention of radiation fibrosis | |
| JP2024507266A (ja) | ヒドロゲル組成物、ならびに放射線によって引き起こされる皮膚損傷の予防および／または処置におけるその使用 | |
| JP2007262030A (ja) | 皮膚外用剤 | |
| US8501202B2 (en) | Sulfacetamide formulations for treatment of skin dermatoses | |
| Sigg et al. | A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium-and long-term efficacy and safety of topical rapamycin | |
| DeVillez | Clinical Comparison of the Safety and Efficacy of Brevoxyl® Gel and Benzamycin® Gel | |
| JP2007262031A (ja) | 知覚過敏型肌掻痒感改善剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20231107 |