CN116367815A - 用于皮内使用的紫外吸收纳米颗粒和微颗粒 - Google Patents
用于皮内使用的紫外吸收纳米颗粒和微颗粒 Download PDFInfo
- Publication number
- CN116367815A CN116367815A CN202180070899.2A CN202180070899A CN116367815A CN 116367815 A CN116367815 A CN 116367815A CN 202180070899 A CN202180070899 A CN 202180070899A CN 116367815 A CN116367815 A CN 116367815A
- Authority
- CN
- China
- Prior art keywords
- ultraviolet light
- light absorbing
- skin
- particles
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 85
- 239000011859 microparticle Substances 0.000 title claims abstract description 60
- 239000002245 particle Substances 0.000 claims abstract description 154
- 210000003491 skin Anatomy 0.000 claims abstract description 108
- 239000006096 absorbing agent Substances 0.000 claims abstract description 72
- 239000000976 ink Substances 0.000 claims abstract description 67
- 238000000034 method Methods 0.000 claims abstract description 56
- 210000004207 dermis Anatomy 0.000 claims abstract description 30
- 239000000203 mixture Substances 0.000 claims description 70
- 238000009472 formulation Methods 0.000 claims description 44
- 229920000642 polymer Polymers 0.000 claims description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 37
- 239000000049 pigment Substances 0.000 claims description 33
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 32
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims description 28
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 28
- -1 [ [4- (2-ethylhexyloxy-oxomethyl) phenyl ]]Amino Chemical group 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 claims description 18
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 18
- 239000000377 silicon dioxide Substances 0.000 claims description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
- 239000004611 light stabiliser Substances 0.000 claims description 15
- 239000002202 Polyethylene glycol Substances 0.000 claims description 14
- 238000002513 implantation Methods 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 239000006185 dispersion Substances 0.000 claims description 13
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 13
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 12
- 235000011187 glycerol Nutrition 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 11
- NJCDRURWJZAMBM-UHFFFAOYSA-N 6-phenyl-1h-1,3,5-triazin-2-one Chemical compound OC1=NC=NC(C=2C=CC=CC=2)=N1 NJCDRURWJZAMBM-UHFFFAOYSA-N 0.000 claims description 10
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 claims description 10
- 239000003963 antioxidant agent Substances 0.000 claims description 10
- 235000006708 antioxidants Nutrition 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- 239000002562 thickening agent Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000011787 zinc oxide Substances 0.000 claims description 9
- HJIAMFHSAAEUKR-UHFFFAOYSA-N (2-hydroxyphenyl)-phenylmethanone Chemical class OC1=CC=CC=C1C(=O)C1=CC=CC=C1 HJIAMFHSAAEUKR-UHFFFAOYSA-N 0.000 claims description 8
- 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 claims description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000011258 core-shell material Substances 0.000 claims description 8
- 230000002500 effect on skin Effects 0.000 claims description 8
- 239000008103 glucose Substances 0.000 claims description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 239000011159 matrix material Substances 0.000 claims description 7
- 230000000149 penetrating effect Effects 0.000 claims description 7
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 7
- 235000013824 polyphenols Nutrition 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- ONTODYXHFBKCDK-UHFFFAOYSA-N 2-(2,4-dimethylphenyl)-1,3,5-triazine Chemical compound CC1=CC(C)=CC=C1C1=NC=NC=N1 ONTODYXHFBKCDK-UHFFFAOYSA-N 0.000 claims description 6
- QVOSVVYNFXPYDR-UHFFFAOYSA-N 2h-oxazin-3-ol Chemical compound OC1=CC=CON1 QVOSVVYNFXPYDR-UHFFFAOYSA-N 0.000 claims description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 235000021466 carotenoid Nutrition 0.000 claims description 6
- 150000001747 carotenoids Chemical class 0.000 claims description 6
- 229920001577 copolymer Polymers 0.000 claims description 6
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 239000004408 titanium dioxide Substances 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 229940088594 vitamin Drugs 0.000 claims description 6
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 5
- KBKGPMDADJLBEM-UHFFFAOYSA-N 1-(4-pentylphenyl)ethanone Chemical compound CCCCCC1=CC=C(C(C)=O)C=C1 KBKGPMDADJLBEM-UHFFFAOYSA-N 0.000 claims description 5
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-Tetramethylpiperidine Substances CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 claims description 5
- FJGQBLRYBUAASW-UHFFFAOYSA-N 2-(benzotriazol-2-yl)phenol Chemical class OC1=CC=CC=C1N1N=C2C=CC=CC2=N1 FJGQBLRYBUAASW-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- 239000005792 Geraniol Substances 0.000 claims description 5
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 5
- 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 claims description 5
- 229960005193 avobenzone Drugs 0.000 claims description 5
- 239000012964 benzotriazole Substances 0.000 claims description 5
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 5
- 229940113087 geraniol Drugs 0.000 claims description 5
- 229960004881 homosalate Drugs 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 claims description 5
- 229960002137 melagatran Drugs 0.000 claims description 5
- 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 claims description 5
- 229960000601 octocrylene Drugs 0.000 claims description 5
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 claims description 5
- 229960001173 oxybenzone Drugs 0.000 claims description 5
- 229920000058 polyacrylate Polymers 0.000 claims description 5
- 229920000151 polyglycol Polymers 0.000 claims description 5
- 239000010695 polyglycol Substances 0.000 claims description 5
- 229940031439 squalene Drugs 0.000 claims description 5
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 claims description 5
- 150000003626 triacylglycerols Chemical class 0.000 claims description 5
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 5
- 239000008158 vegetable oil Substances 0.000 claims description 5
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000005913 Maltodextrin Substances 0.000 claims description 4
- 229920002774 Maltodextrin Polymers 0.000 claims description 4
- 229920000877 Melamine resin Polymers 0.000 claims description 4
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical group COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
- 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 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 229930182830 galactose Natural products 0.000 claims description 4
- 150000002500 ions Chemical class 0.000 claims description 4
- 229940035034 maltodextrin Drugs 0.000 claims description 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 4
- 238000001782 photodegradation Methods 0.000 claims description 4
- 230000019612 pigmentation Effects 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229920000136 polysorbate Polymers 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000013008 thixotropic agent Substances 0.000 claims description 4
- 229920001285 xanthan gum Polymers 0.000 claims description 4
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 3
- 229920001661 Chitosan Polymers 0.000 claims description 3
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 claims description 3
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 claims description 3
- 206010040860 Skin haemorrhages Diseases 0.000 claims description 3
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 3
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 3
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 3
- 229940035674 anesthetics Drugs 0.000 claims description 3
- 239000003212 astringent agent Substances 0.000 claims description 3
- 230000001580 bacterial effect Effects 0.000 claims description 3
- 235000013734 beta-carotene Nutrition 0.000 claims description 3
- 239000011648 beta-carotene Substances 0.000 claims description 3
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 3
- 229960002747 betacarotene Drugs 0.000 claims description 3
- 229920000249 biocompatible polymer Polymers 0.000 claims description 3
- 229940114081 cinnamate Drugs 0.000 claims description 3
- 238000011109 contamination Methods 0.000 claims description 3
- 235000012754 curcumin Nutrition 0.000 claims description 3
- 239000004148 curcumin Substances 0.000 claims description 3
- 229940109262 curcumin Drugs 0.000 claims description 3
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 3
- 229930003935 flavonoid Natural products 0.000 claims description 3
- 235000017173 flavonoids Nutrition 0.000 claims description 3
- 150000002215 flavonoids Chemical class 0.000 claims description 3
- IVJISJACKSSFGE-UHFFFAOYSA-N formaldehyde;1,3,5-triazine-2,4,6-triamine Chemical compound O=C.NC1=NC(N)=NC(N)=N1 IVJISJACKSSFGE-UHFFFAOYSA-N 0.000 claims description 3
- 239000003193 general anesthetic agent Substances 0.000 claims description 3
- 235000002780 gingerol Nutrition 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- 150000005165 hydroxybenzoic acids Chemical class 0.000 claims description 3
- 150000002443 hydroxylamines Chemical class 0.000 claims description 3
- 235000012661 lycopene Nutrition 0.000 claims description 3
- 239000001751 lycopene Substances 0.000 claims description 3
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 claims description 3
- 229960004999 lycopene Drugs 0.000 claims description 3
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 3
- 239000003094 microcapsule Substances 0.000 claims description 3
- 239000002088 nanocapsule Substances 0.000 claims description 3
- 239000003921 oil Substances 0.000 claims description 3
- 235000019198 oils Nutrition 0.000 claims description 3
- 150000002989 phenols Chemical class 0.000 claims description 3
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 claims description 3
- 229920000570 polyether Polymers 0.000 claims description 3
- 239000004626 polylactic acid Substances 0.000 claims description 3
- 239000001648 tannin Substances 0.000 claims description 3
- 235000018553 tannin Nutrition 0.000 claims description 3
- 229920001864 tannin Polymers 0.000 claims description 3
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 3
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 claims description 3
- 235000019155 vitamin A Nutrition 0.000 claims description 3
- 239000011719 vitamin A Substances 0.000 claims description 3
- 229940045997 vitamin a Drugs 0.000 claims description 3
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 3
- QVLWFVJQTLYTCW-UHFFFAOYSA-N 2-(2,4-dibutoxyphenyl)-1,3,5-triazine Chemical compound C(CCC)OC1=C(C=CC(=C1)OCCCC)C1=NC=NC=N1 QVLWFVJQTLYTCW-UHFFFAOYSA-N 0.000 claims description 2
- LEVFXWNQQSSNAC-UHFFFAOYSA-N 2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-hexoxyphenol Chemical compound OC1=CC(OCCCCCC)=CC=C1C1=NC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=N1 LEVFXWNQQSSNAC-UHFFFAOYSA-N 0.000 claims description 2
- UUINYPIVWRZHAG-UHFFFAOYSA-N 2-(4,6-diphenyl-1,3,5-triazin-2-yl)-5-methoxyphenol Chemical compound OC1=CC(OC)=CC=C1C1=NC(C=2C=CC=CC=2)=NC(C=2C=CC=CC=2)=N1 UUINYPIVWRZHAG-UHFFFAOYSA-N 0.000 claims description 2
- OLFNXLXEGXRUOI-UHFFFAOYSA-N 2-(benzotriazol-2-yl)-4,6-bis(2-phenylpropan-2-yl)phenol Chemical compound C=1C(N2N=C3C=CC=CC3=N2)=C(O)C(C(C)(C)C=2C=CC=CC=2)=CC=1C(C)(C)C1=CC=CC=C1 OLFNXLXEGXRUOI-UHFFFAOYSA-N 0.000 claims description 2
- ZSSVCEUEVMALRD-UHFFFAOYSA-N 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol Chemical compound OC1=CC(OCCCCCCCC)=CC=C1C1=NC(C=2C(=CC(C)=CC=2)C)=NC(C=2C(=CC(C)=CC=2)C)=N1 ZSSVCEUEVMALRD-UHFFFAOYSA-N 0.000 claims description 2
- JGUMTYWKIBJSTN-UHFFFAOYSA-N 2-ethylhexyl 4-[[4,6-bis[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 JGUMTYWKIBJSTN-UHFFFAOYSA-N 0.000 claims description 2
- UADWUILHKRXHMM-UHFFFAOYSA-N 2-ethylhexyl benzoate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1 UADWUILHKRXHMM-UHFFFAOYSA-N 0.000 claims description 2
- 229940106004 2-ethylhexyl benzoate Drugs 0.000 claims description 2
- GQOSQTPZCDSDJT-UHFFFAOYSA-N 6-[2,6-bis(2,4-dimethylphenyl)-1h-1,3,5-triazin-4-ylidene]-3-(6-methylheptoxy)cyclohexa-2,4-dien-1-one Chemical compound C1=CC(OCCCCCC(C)C)=CC(=O)C1=C1N=C(C=2C(=CC(C)=CC=2)C)NC(C=2C(=CC(C)=CC=2)C)=N1 GQOSQTPZCDSDJT-UHFFFAOYSA-N 0.000 claims description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 2
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- 229930003268 Vitamin C Natural products 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 150000005415 aminobenzoic acids Chemical class 0.000 claims description 2
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 2
- 150000003936 benzamides Chemical class 0.000 claims description 2
- UADWUILHKRXHMM-ZDUSSCGKSA-N benzoflex 181 Natural products CCCC[C@H](CC)COC(=O)C1=CC=CC=C1 UADWUILHKRXHMM-ZDUSSCGKSA-N 0.000 claims description 2
- OCWYEMOEOGEQAN-UHFFFAOYSA-N bumetrizole Chemical compound CC(C)(C)C1=CC(C)=CC(N2N=C3C=C(Cl)C=CC3=N2)=C1O OCWYEMOEOGEQAN-UHFFFAOYSA-N 0.000 claims description 2
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 229930005346 hydroxycinnamic acid Natural products 0.000 claims description 2
- DEDGUGJNLNLJSR-UHFFFAOYSA-N hydroxycinnamic acid group Chemical class OC(C(=O)O)=CC1=CC=CC=C1 DEDGUGJNLNLJSR-UHFFFAOYSA-N 0.000 claims description 2
- 235000010359 hydroxycinnamic acids Nutrition 0.000 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 229920001451 polypropylene glycol Polymers 0.000 claims description 2
- PNXMTCDJUBJHQJ-UHFFFAOYSA-N propyl prop-2-enoate Chemical compound CCCOC(=O)C=C PNXMTCDJUBJHQJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000019154 vitamin C Nutrition 0.000 claims description 2
- 239000011718 vitamin C Substances 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 229910052956 cinnabar Inorganic materials 0.000 claims 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims 2
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 229950008882 polysorbate Drugs 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 29
- 208000000453 Skin Neoplasms Diseases 0.000 abstract description 15
- 201000000849 skin cancer Diseases 0.000 abstract description 13
- 230000007774 longterm Effects 0.000 abstract description 11
- 239000007787 solid Substances 0.000 abstract description 10
- 230000004224 protection Effects 0.000 abstract description 6
- 230000037072 sun protection Effects 0.000 abstract description 5
- 206010051246 Photodermatosis Diseases 0.000 abstract description 3
- 230000008845 photoaging Effects 0.000 abstract description 3
- 239000011358 absorbing material Substances 0.000 abstract description 2
- 239000011343 solid material Substances 0.000 abstract description 2
- 238000001429 visible spectrum Methods 0.000 abstract description 2
- 230000005855 radiation Effects 0.000 description 24
- 230000000475 sunscreen effect Effects 0.000 description 24
- 239000000516 sunscreening agent Substances 0.000 description 24
- 239000003814 drug Substances 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 17
- 229940079593 drug Drugs 0.000 description 14
- 206010034972 Photosensitivity reaction Diseases 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 230000007246 mechanism Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 238000011160 research Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000012552 review Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000008901 benefit Effects 0.000 description 8
- 239000002537 cosmetic Substances 0.000 description 8
- 238000012377 drug delivery Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 208000007578 phototoxic dermatitis Diseases 0.000 description 7
- 231100000018 phototoxicity Toxicity 0.000 description 7
- 238000012667 polymer degradation Methods 0.000 description 7
- 238000006116 polymerization reaction Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000009759 skin aging Effects 0.000 description 7
- 238000009826 distribution Methods 0.000 description 6
- 210000002615 epidermis Anatomy 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000001694 spray drying Methods 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000006750 UV protection Effects 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 206010037844 rash Diseases 0.000 description 5
- 208000017520 skin disease Diseases 0.000 description 5
- 230000006641 stabilisation Effects 0.000 description 5
- 238000011105 stabilization Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 206010042496 Sunburn Diseases 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 201000001981 dermatomyositis Diseases 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 229920001971 elastomer Polymers 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000009931 harmful effect Effects 0.000 description 4
- 239000010954 inorganic particle Substances 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000012782 phase change material Substances 0.000 description 4
- 239000002530 phenolic antioxidant Substances 0.000 description 4
- 230000008832 photodamage Effects 0.000 description 4
- 230000036211 photosensitivity Effects 0.000 description 4
- 208000017983 photosensitivity disease Diseases 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000005060 rubber Substances 0.000 description 4
- 210000004761 scalp Anatomy 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000027 toxicology Toxicity 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- 208000037147 Hypercalcaemia Diseases 0.000 description 3
- 208000003351 Melanosis Diseases 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 206010047642 Vitiligo Diseases 0.000 description 3
- 238000012382 advanced drug delivery Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 238000003491 array Methods 0.000 description 3
- 239000006229 carbon black Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 231100000321 erythema Toxicity 0.000 description 3
- 210000003722 extracellular fluid Anatomy 0.000 description 3
- 230000000148 hypercalcaemia Effects 0.000 description 3
- 208000030915 hypercalcemia disease Diseases 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 210000002510 keratinocyte Anatomy 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229910044991 metal oxide Inorganic materials 0.000 description 3
- 150000004706 metal oxides Chemical class 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000002539 nanocarrier Substances 0.000 description 3
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000000886 photobiology Effects 0.000 description 3
- 230000001699 photocatalysis Effects 0.000 description 3
- 231100000760 phototoxic Toxicity 0.000 description 3
- 229940068965 polysorbates Drugs 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 229920002379 silicone rubber Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- YUXBNNVWBUTOQZ-UHFFFAOYSA-N 4-phenyltriazine Chemical class C1=CC=CC=C1C1=CC=NN=N1 YUXBNNVWBUTOQZ-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 241001340526 Chrysoclista linneella Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010014970 Ephelides Diseases 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 229910010413 TiO 2 Inorganic materials 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 239000012965 benzophenone Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical compound [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 238000004146 energy storage Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 238000005562 fading Methods 0.000 description 2
- 235000002864 food coloring agent Nutrition 0.000 description 2
- 235000012041 food component Nutrition 0.000 description 2
- 239000005417 food ingredient Substances 0.000 description 2
- 238000012395 formulation development Methods 0.000 description 2
- 238000012637 gene transfection Methods 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 210000004209 hair Anatomy 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000007709 nanocrystallization Methods 0.000 description 2
- 239000006070 nanosuspension Substances 0.000 description 2
- 229920003052 natural elastomer Polymers 0.000 description 2
- 229920001194 natural rubber Polymers 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 238000010525 oxidative degradation reaction Methods 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000007146 photocatalysis Methods 0.000 description 2
- 230000003711 photoprotective effect Effects 0.000 description 2
- 230000002165 photosensitisation Effects 0.000 description 2
- 239000003504 photosensitizing agent Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000098 polyolefin Polymers 0.000 description 2
- 229920003225 polyurethane elastomer Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000003244 pro-oxidative effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000002278 reconstructive surgery Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- 208000008557 Actinic prurigo Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 235000005749 Anthriscus sylvestris Nutrition 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010072578 Chronic actinic dermatitis Diseases 0.000 description 1
- 229920001076 Cutan Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 231100000750 In vitro toxicology Toxicity 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 241000700562 Myxoma virus Species 0.000 description 1
- 231100000261 OECD 432 In Vitro 3T3 NRU Phototoxicity Test Toxicity 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 206010036087 Polymorphic light eruption Diseases 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 206010037145 Pseudoporphyria Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 208000012658 Skin autoimmune disease Diseases 0.000 description 1
- 206010040851 Skin fragility Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 239000004904 UV filter Substances 0.000 description 1
- 230000037338 UVA radiation Effects 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 238000004468 VIS-NIR spectroscopy Methods 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000004883 areola Anatomy 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000037365 barrier function of the epidermis Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 150000001565 benzotriazoles Chemical class 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000746 body region Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- CMDKPGRTAQVGFQ-RMKNXTFCSA-N cinoxate Chemical compound CCOCCOC(=O)\C=C\C1=CC=C(OC)C=C1 CMDKPGRTAQVGFQ-RMKNXTFCSA-N 0.000 description 1
- 229960001063 cinoxate Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000012084 conversion product Substances 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 238000002316 cosmetic surgery Methods 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000002639 dermal melanocyte Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 238000007720 emulsion polymerization reaction Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 208000002440 photoallergic dermatitis Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 230000000176 photostabilization Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000205 poly(isobutyl methacrylate) Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- BOQSSGDQNWEFSX-UHFFFAOYSA-N propan-2-yl 2-methylprop-2-enoate Chemical compound CC(C)OC(=O)C(C)=C BOQSSGDQNWEFSX-UHFFFAOYSA-N 0.000 description 1
- 230000001823 pruritic effect Effects 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 206010041307 solar urticaria Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 230000008791 toxic response Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 239000006097 ultraviolet radiation absorber Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/85—Polyesters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
- A61Q1/02—Preparations containing skin colorants, e.g. pigments
- A61Q1/025—Semi-permanent tattoos, stencils, e.g. "permanent make-up"
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0204—Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0245—Specific shapes or structures not provided for by any of the groups of A61K8/0241
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0279—Porous; Hollow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0283—Matrix particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/11—Encapsulated compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/29—Titanium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/31—Hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4966—Triazines or their condensed derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4993—Derivatives containing from 2 to 10 oxyalkylene groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8129—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers or esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers, e.g. polyvinylmethylether
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8147—Homopolymers or copolymers of acids; Metal or ammonium salts thereof, e.g. crotonic acid, (meth)acrylic acid; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8141—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides or nitriles thereof; Compositions of derivatives of such polymers
- A61K8/8152—Homopolymers or copolymers of esters, e.g. (meth)acrylic acid esters; Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/26—Optical properties
- A61K2800/262—Transparent; Translucent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/413—Nanosized, i.e. having sizes below 100 nm
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/42—Colour properties
- A61K2800/43—Pigments; Dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/65—Characterized by the composition of the particulate/core
- A61K2800/651—The particulate/core comprising inorganic material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/65—Characterized by the composition of the particulate/core
- A61K2800/654—The particulate/core comprising macromolecular material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Mathematical Physics (AREA)
- Emergency Medicine (AREA)
- Geometry (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
- Radiation-Therapy Devices (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
Abstract
披露了生物相容性UV吸收纳米颗粒或微颗粒,这些颗粒可以使用例如用于用纹身墨水制作纹身的技术等技术嵌入皮肤中。使用生物相容性UV吸收纳米颗粒或微颗粒的“纹身”为皮肤提供永久或半永久的防晒伤、光老化和皮肤癌保护,在可见光谱中保持清晰,或与使用者的特定肤色密切匹配。这些颗粒可以是嵌入固体材料或涂覆于固体材料的固体的均匀UV吸收剂、微囊化的UV吸收剂、或UV吸收材料。以隐形(不改变皮肤的颜色)材料提供长期的防晒保护并可嵌入皮肤(真皮层)。
Description
相关申请的交叉引用
本申请要求于2020年8月28日提交的美国临时申请号63/071,782的权益。
技术领域
本发明涉及生物相容性UV吸收微颗粒的组合物及其生产方法。
背景技术
紫外(UV)辐射是皮肤癌(黑色素瘤和非黑色素瘤)的主要风险因素,皮肤癌是美国和世界上其他主要浅肤色人群中最常见的恶性肿瘤(比所有其他癌症的总和更常见)。[Diepgen,T.L.;Mahler,V.The epidemiology of skin cancer[皮肤癌的流行病学].Br.J.Derm.[英国皮肤病学杂志]2002,146,1-6.]大部分穿过地球大气层的UV射线是UVA(320-400nm波长),而少量UVB射线(280-320nm波长)也到达地球表面。随着时间的推移,暴露于UVA和UVB会导致皮肤损伤累积,增加皮肤癌风险并加快老化速率。[Taylor,C.R.;Stern,R.S.;Leyden,J.J.;Gilchrest,B.A.Photoaging/Photodamage andPhotoprotection[光老化/光损伤和光保护].J.Am.Acad.Dermatol[美国皮肤病学会杂志].1990,22,1-15.]UVB是晒伤的主要原因,也是黑色素瘤(最不常见但最致命的皮肤癌之一)的主要风险因素,而穿透力更强的UVA射线与皮肤老化有关,并增加了最常见的角质形成细胞癌的风险。[Albert,M.R.;Weinstock,M.A.Keratinocyte Carcinoma[角质形成细胞癌].CA Cancer J.Clin.[临床医师癌症杂志]2003,53,292-302.]
对于在阳光下不受衣服保护的皮肤区域,推荐的UV防护策略是使用防晒系数(SPF)为15或更高的广谱局部防晒霜。[Koh,H.K.;Geller,A.C.;Miller,D.R.;Grossbart,T.A.;Lew,R.A.Prevention and Early Detection Strategies for Melanoma and SkinCancer:Current Status[黑色素瘤和皮肤癌的预防和早期检测策略:当前状态].Arch.Dermatol.[皮肤病学文献]1996,132,436-443.]SPF等级仅适用于UVB光;认为SPF N防晒霜可将入射的UVB辐照度降低到1/N的分数。遗憾的是,美国食品药品监督管理局(U.S.Food and Drug Administration,FDA)批准的用于非处方药防晒霜的十六种不同成分提供的UVA辐射防护不等,且FDA最近提出的规定表明,在大多数情况下,没有足够的数据证明其安全性。[美国食品药品监督管理局.Sunscreen Drug Products for Over-the-Counter Human Use:Proposed Rule[非处方人用防晒药品:拟议规定].Federal Register[联邦公报]2019,84,6204-6275.]最近发现,FDA批准的有机防晒霜成分可以进入血流中,且超过了FDA设定的0.5ng/mL浓度阈值,使得放弃非临床毒理学研究。[Matta,M.K.等人,Effect of Sunscreen Application Under Maximal Use Conditions on PlasmaConcentration of Sunscreen Active Ingredients:A Randomized Clinical Trial[最大使用条件下涂抹防晒霜对防晒霜活性成分血浆浓度的影响:随机临床试验].JAMA[美国医学会杂志]2019,21,2082-2091.]此外,防晒霜轻薄隐形、舒适,使得人们很难评估自己的防晒霜覆盖情况,也很难清楚何时再次涂抹,而且会恰当使用防晒霜的美国成年人比例<30%。[Holman,D.M.等人,Patterns of Sunscreen Use on the Face and Other ExposedSkin Among US Adults[美国成年人在面部和其他暴露皮肤上使用防晒霜的模式].J.Am.Acad.Dermatol[美国皮肤病学会杂志].2015,73,83-92.E1.]正确涂抹在皮肤上的风险、困难和不便,以及防晒霜的低使用率,促使人们为暴露在外的皮肤创新新的UV防护策略。
发明内容
本发明提供了生物相容性UV吸收纳米颗粒或微颗粒,这些颗粒可以使用例如用于用纹身墨水制作纹身的技术等技术嵌入皮肤中。使用生物相容性UV吸收纳米颗粒或微颗粒的“纹身”可以为皮肤提供永久或半永久的防晒伤、光老化和皮肤癌保护,在可见光谱中保持清晰,或可以与使用者的特定肤色密切匹配。这些颗粒可以例如是嵌入固体材料的固体的均匀UV吸收剂、微囊化的UV吸收剂、或UV吸收材料。以隐形(不会明显改变皮肤的颜色)材料提供长期的防晒保护并可嵌入皮肤(真皮层)。
示例性生物相容性UV吸收微颗粒是聚(甲基丙烯酸甲酯)(PMMA)与可商购的UV吸收剂(例如,防晒霜)的组合。可以用作UV吸收剂和光稳定剂的材料的一些实例包括2-羟基二苯甲酮、羟基苯基-s-三嗪、2-(2-羟基苯基)苯并三唑、苯酰胺、氨基苯甲酸、阿伏苯宗(Avobenzone)、西诺沙酯(Cinoxate)、二羟苯宗(Dioxybenzone)、胡莫柳酯(Homosalate)、美拉地酯(Meradimate)、奥克立林(Octocrylene)、桂皮酸盐、辛水杨酯、羟苯甲酮、帕蒂玛特O(Padimate O)、恩索利唑(Ensulizole)、舒利苯酮(Sulisobenzone)、二氧化钛、三乙醇胺水杨酸盐、氧化锌(包括前述化合物的衍生物)。UV吸收剂可以与例如以下聚合物材料组合:PMMA、聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、聚(二甲基硅氧烷)(PDMS)、聚乙二醇(PEG)、三聚氰胺甲醛、甲基丙烯酰胺壳聚糖等。
在第一方面,本发明提供了紫外(UV)光吸收颗粒,该颗粒包含聚(甲基丙烯酸甲酯)(PMMA)与UV吸收剂的组合。在有利的实施例中,UV吸收剂是可商购的UV吸收剂。在第一方面的特别有利的实施例中,可商购的UV吸收剂是2-羟基二苯甲酮、羟基苯基-s-三嗪、和2-(2-羟基苯基)苯并三唑、苯酰胺、氨基苯甲酸、阿伏苯宗、西诺沙酯、二羟苯宗、胡莫柳酯、美拉地酯、奥克立林、桂皮酸盐、辛水杨酯、羟苯甲酮、帕蒂玛特O、恩索利唑、舒利苯酮、二氧化钛、三乙醇胺水杨酸盐、氧化锌或其衍生物和/或组合。在某些实施例中,根据第一方面所述的紫外光吸收颗粒是核壳颗粒或纳米胶囊/微胶囊,其具有在包含PMMA的壳或胶囊中包含UV吸收剂的核。在另外的实施例中,根据第一方面所述的紫外光吸收颗粒可以是在PMMA基质中随机分散的UV吸收剂。
在第二方面,本发明提供了第二紫外光吸收颗粒。根据第二方面所述的紫外光吸收颗粒可以包括生物相容性聚合物与可商购的UV吸收剂的组合。在第二方面的某些实施例中,UV吸收剂可以是属于羟基苯基-s-三嗪家族的UV吸收剂。一种这样的羟基苯基-s-三嗪是贝莫曲嗪醇(bemotrizinol)。在仍另外的实施例中,UV吸收剂可以是2-(4,6-二苯基-1,3,5-三嗪-2-基)-5-[(己基)氧基]-苯酚、4-[[4,6-双[[4-(2-乙基己氧基-氧代甲基)苯基]氨基]-1,3,5-三嗪-2-基]氨基]苯甲酸2-乙基己基酯(乙基己基三嗪酮)、2-(2-羟基-4-甲氧基苯基)-4,6-二苯基-1,3,5-三嗪、2-(4,6-双-(2,4-二甲基苯基)-1,3,5-三嗪-2-基)-5-(辛基氧基)-苯酚、2-[4-[2-羟基-3-十三烷基氧丙基]氧基]-2-羟基苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪以及2-[4-[2-羟基-3-十二烷基氧丙基]氧基]-2-羟基苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪(400)、2-[2-羟基-4-[3-(2-乙基己基-1-氧基)-2-羟基丙基氧基]苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪(/>405)、6-[2,6-双(2,4-二甲基苯基)-1H-1,3,5-三嗪-4-亚基]-3-(6-甲基庚氧基)环已-2,4-二烯-1-酮、2,4-双(2-羟基-4-丁基氧基苯基)-6-(2,4-双-丁基氧基苯基-1,3,5-三嗪(460)、异辛基2-[4-[4,6-双[(1,1’-二苯基)-4-基]-1,3,5-三嗪-2-基]-3-羟基苯氧基]丙酸酯(/>479)、2-(2’-羟基-5-甲基苯基)-5-苯并三唑、2-(2H-苯并三唑-2-基)-4-(1,1,3,3-四甲基丁基)苯酚、2-(2’-羟基-3’-叔丁基-5’-甲基苯基)-5-氯苯并三唑、2-(2-羟基-3,5-二(1,1-二甲基-苄基)-2-苯并三唑、α-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙基]-ω-羟基聚(氧代-1,2-乙二基)、α-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙基]-ω-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙氧基]聚(氧基-1,2-乙二基)、2-(2H-苯并三唑-2-基)-4,6-双(1-甲基-1-苯基乙基)苯酚(/>900)、2-(2H-苯并三唑-2-基)-6-(1-甲基-1-苯基乙基)-4-(1,1,3,3-四甲基丁基)苯酚(/>928)、及其组合。
可以将光稳定剂添加至根据第二方面所述的紫外光吸收颗粒以抑制UV吸收剂的光降解,从而增加UV吸收剂的使用寿命。一种这样的光稳定剂可以是受阻胺。有用的受阻胺包括2,2,6,6-四甲基哌啶、2,2,6,6-四甲基哌啶的烷基化或羟胺类似物、或含有任何这些官能团的聚合物。
在第二方面的有利的实施例中,紫外光吸收颗粒适合注射至皮肤的真皮层中。颗粒可以呈如下的形式:(A)聚合物颗粒、(B)分子聚集体、(C)无机纳米颗粒或微颗粒、(D)表面包覆的纳米颗粒或微颗粒、(E)核壳纳米颗粒或微颗粒、或(F)介孔纳米颗粒或微颗粒。
在第二方面的进一步有利的实施例中,提供了紫外光吸收颗粒与可纹身生物传感器的组合,该生物传感器对辐射、离子浓度、pH或葡萄糖水平敏感,或对本领域技术人员明显可知的其他可测量分析物或生物分子敏感。
在根据第二方面所述的某些实施例中,紫外光吸收颗粒是聚(甲基丙烯酸甲酯)(PMMA)、聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、聚(二甲基硅氧烷)(PDMS)、聚乙二醇(PEG)、三聚氰胺甲醛、甲基丙烯酰胺壳聚糖。
适合在紫外光吸收颗粒中应用的可商购的UV吸收剂包括羟基二苯甲酮、羟基苯基-s-三嗪、和2-(2-羟基苯基)苯并三唑、苯酰胺、氨基苯甲酸、阿伏苯宗、西诺沙酯、二羟苯宗、胡莫柳酯、美拉地酯、奥克立林、桂皮酸盐、辛水杨酯、羟苯甲酮、帕蒂玛特O、恩索利唑、舒利苯酮、二氧化钛、三乙醇胺水杨酸盐、和氧化锌及其衍生物和/或组合。
根据第二方面所述的紫外光吸收颗粒可以包括抗氧化剂。有用的抗氧化剂的实例包括多酚、维生素、类胡萝卜素、受阻酚、亚磷酸盐、黑色素或其组合。关于多酚,多酚可以是类黄酮、羟基肉桂酸和羟基苯甲酸、单宁、姜黄素(cucurmin)、姜酚、及其组合。有用的维生素的实例包括维生素A、C、E或其组合。有用的类胡萝卜素的实例包括β-胡萝卜素、番茄红素或其组合。
在有利的实施例中,根据第二方面所述的紫外光吸收颗粒可以悬浮于生物相容性溶剂中,例如水、醇(例如,乙醇、异丙醇、甘油、低聚乙二醇和聚乙二醇)、油类(例如,植物油/甘油三酯、香叶醇、角鲨烯等)或其组合。适合的生物相容性溶剂的实例包括水、乙醇、异丙醇、甘油、低聚乙二醇和聚乙二醇、植物油/甘油三酯、香叶醇、角鲨烯及其组合。
根据第二方面所述的紫外光吸收颗粒可以包括例如以下的添加剂:(i)防止细菌污染的抗菌剂(例如醇)、(ii)稳定分散体并调整表面张力的生物相容性表面活性剂(例如,聚山梨醇酯)、(iii)增加黏度并降低色素沉着速率的增稠剂(例如黄原胶、聚丙烯酸酯、聚二醇)、(iv)促进剪切稀化的触变剂(例如二氧化硅)、(v)帮助防止墨水干燥并帮助它们粘合至针的防腐剂/粘合剂(例如聚醚、聚乙烯吡咯烷酮)、(vi)最大限度减少植入后皮肤出血的收敛剂、(vii)最大限度减少墨水植入期间疼痛的麻醉剂、及其组合。防腐剂可以是醇,例如乙醇、异丙醇、甘油、和聚(乙二醇)。有用的生物相容性表面活性剂的实例包括聚山梨醇酯、TWEEN-20、TWEEN-80和聚(乙烯醇)。有用的增稠剂的实例包括黄原胶、聚丙烯酸酯(例如聚(丙烯酸)以及聚(丙烯酸)和其他丙烯酸酯(包括丙烯酸甲酯、甲基丙烯酸甲酯、丙烯酸乙酯、丙烯酸丙酯、丙烯酸丁酯等)的共聚物)、聚二醇(例如聚(乙二醇)和聚(丙二醇))或其组合。
根据第二方面所述的紫外光吸收颗粒可以包括<1.0%(v/v)比率的稳定悬浮液的TWEEN-80表面活性剂、以及以10%-30%比率添加的聚乙二醇(分子量1000)或甘油,因而该聚乙二醇或甘油可以用作抗菌剂、增稠剂、或粘合剂。
在有利的实施例中,根据第二方面所述的紫外光吸收颗粒是在微颗粒至纳米颗粒尺寸范围内。
在第三方面,本发明提供了适合注射至皮肤的真皮层或皮内层的透明或几乎透明的纳米颗粒和/或微颗粒(这些纳米颗粒或微颗粒在UVA和UVB范围内可以具有高吸收性)与生物相容性溶剂的组合的配制品。根据第三方面所述的配制品可以包括适用于真皮植入的墨水或色素。
在第四方面,本发明提供了将紫外光吸收颗粒植入至受试者皮肤的方法。该方法可以包括以下步骤:(1)提供包含根据前四个方面所述的颗粒或配制品中任一种的组合物;(2)用具有所提供的组合物的微针接触皮肤;以及(3)用该微针穿透所接触的皮肤。在有利的实施例中,微针是可溶微针。可溶微针可以包括适合的载体(例如聚乙烯吡咯烷酮或聚乙烯醇及其液体预聚合物,或羧甲基纤维素、海藻糖、麦芽糖糊精、半乳糖、葡萄糖和丝的水溶液)。
在第五方面,本发明提供了将紫外光吸收颗粒植入至受试者皮肤的第二个方法。该方法可以包括以下步骤:(1)提供包含根据前四个方面所述的颗粒或配制品中任一种的组合物;(2)用无针纹身机接触皮肤,该无针纹身机配置为递送所提供的组合物与纹身墨水的组合;以及(3)以足够高的速度用该组合物与纹身墨水液滴的组合穿透所接触的皮肤以透入真皮。足够高的速度可以是超过40m/s的速度。
在第六方面,本发明提供了将紫外光吸收颗粒植入至受试者皮肤的第三个方法。该方法可以包括以下步骤:(1)提供包含根据前四个方面所述的颗粒或配制品中任一种的组合物;(2)用(电动)纹身机或永久化妆机(旋转式或线圈式)接触皮肤,该机器配置为递送所提供的组合物与纹身墨水的组合;以及(3)在足以透入真皮的条件下用该组合物与纹身墨水液滴的组合穿透所接触的皮肤。
在有利的实施例中,根据前述方面中任一项所述的紫外光吸收颗粒将包括可纹身UV传感器。此类可纹身UV传感器的实例披露于Butterfield,J.L.,Keyser,S.P.,Dikshit,K.V.,Kwon,H.,Koster,M.I.,和Bruns,C.J.(2020).Solar Freckles:Long-TermPhotochromic Tattoos for Intradermal Ultraviolet Radiometry[日光性雀斑:用于皮内紫外线辐射测量的长期光致变色纹身].ACS Nano[ACS纳米期刊],14(10),13619-13628。
在第七方面,本发明提供了用于将生物相容性UV吸收纳米颗粒或微颗粒(例如在前述方面中披露的颗粒)嵌入受试者皮肤中的试剂盒。此试剂盒在一个或多个小瓶、注射器、泡罩包装、或其他适合的容器中可以含有生物相容性UV吸收纳米颗粒或微颗粒。纳米颗粒或微颗粒可以在生物相容性溶剂中悬浮。悬浮颗粒可以以适用于递送至皮肤或受试者的浓度提供,或悬浮颗粒可以以浓缩形式提供,连同将颗粒与适合的稀释剂混合的说明书。另外,颗粒可以以干燥形式(例如脱水)提供,连同生物相容性稀释剂以及颗粒的悬浮液的说明书。试剂盒的实施例可以进一步包括一个或多个针以促进生物相容性UV吸收纳米颗粒或微颗粒的递送。在某些实施例中,针是微针。微针可以是可溶微针。可溶微针可以包括适合的载体(例如聚乙烯吡咯烷酮或聚乙烯醇及其液体预聚合物,或羧甲基纤维素、海藻糖、麦芽糖糊精、半乳糖、葡萄糖和丝稀释剂的水溶液)以及微针的使用说明书。
如先前所讨论的,试剂盒可以含有在一个或多个小瓶或其他适合的容器中的生物相容性UV吸收纳米颗粒或微颗粒。试剂盒可以进一步包括在相同容器中或在单独容器中的适用于真皮植入的墨水或色素。当单独提供时,试剂盒可以包括将颗粒与墨水或色素混合的说明书。试剂盒可以包括多种墨水或色素以使使用者能够进行递送物定制,以匹配接受真皮植入的受试者的肤色或期望的纹身。
试剂盒可以进一步包括在相同容器中或在单独容器中的对辐射、离子浓度、pH或葡萄糖水平敏感的可纹身生物传感器,连同生物传感器与生物相容性UV吸收纳米颗粒或微颗粒的组合的真皮植入说明书,及其混合(在一个或多个试剂盒中单独提供时)。
在另外的实施例中,生物相容性UV吸收纳米颗粒或微颗粒可以在适用于在无针注射系统中负载并且随后递送的小瓶或药筒中提供。
附图说明
为了更全面理解本发明,应参考以下结合附图的详细说明,其中:
图1中图示提供了不同紫外线吸收微颗粒配制品的图形表示。(A)聚合物颗粒、(B)分子聚集体、(C)无机纳米颗粒或微颗粒、(D)表面包覆的纳米颗粒或微颗粒、(E)核壳纳米颗粒或微颗粒、(F)介孔纳米颗粒或微颗粒。
图2中的一组图((A)中两张图以及(C)中一张图)以及图像(B)显示了紫外线吸收纳米颗粒的表征数据。(A)根据实例程序制备的PMMA纳米颗粒、以及通过在炉中在450℃下加热三聚氰胺制备的石墨相氮化碳纳米颗粒(g-C3N4)的尺寸分布数据。(B)根据实例程序制备的PMMA纳米颗粒的SEM显微图。(C)石墨相氮化碳制成的紫外线吸收纳米颗粒的稀释悬浮液的归一化UV可见光吸收光谱。
图3中两张图像(标记为A和B)显示了紫外线吸收纳米颗粒纹身墨水。(A)紫外线吸收微颗粒纹身墨水(配制品A)的小瓶照片,由于散射而呈现浑浊的白色。(B)相同纹身墨水的UV照片(波长灵敏度360-380nm)显示它在UVA范围内是“黑色”或高度吸收的。
图4中的一组图像对纹有以下几种物质的离体猪皮肤样品的可见光(上)和UV(下)照片进行了比较:炭黑纹身墨水、PDMS纳米颗粒纹身墨水以及基于实例程序中描述的掺杂贝莫曲嗪醇的PMMA纳米颗粒的紫外线吸收纳米颗粒纹身墨水。虽然纹身肉眼几乎不可见,就像PDMS一样,但由于植入的紫外线吸收纳米颗粒的UV吸收(像炭黑一样),它在UVA范围内呈深色。
具体实施方式
纹身是使用颜色添加剂(大多数时候从色素制造业借用)形式的皮内纳米颗粒(通常直径为20-900nm)形成的。[W.,等人,Lasers Surg.Med.[激光在外科与内科中的应用]2000,26,13-21;Hogsberg,T.,等人,Br.J.Dermatol.[英国皮肤病学杂志]2011,165,1210-1218;Rubio,L.,等人,Anal.Chim.Acta[分析化学学报]2019,1079,59-72;Hansen,P.,等人,Danish Environmental Protection Agency[丹麦环保署].2006.]纹身色素通常通过用携带包含这些色素的分散体的纹身墨水的针或针阵列在皮肤上反复纹刺而插入真皮中,尽管可替代的无针注射策略在美国专利2012/0179134A1中教导且在进一步开发当中。[Oyarte Gálvez,L.等人,High speed imaging of solid needle and liquidmicro-jet injections[固体针和液体微喷射注射的高速成像].J.Appl.Phys.[应用物理学杂志]2019,125,144504-13;Cu,K.;Bansal,R.;Mitragotri,S.;Rivas,D.F.DeliveryStrategies for Skin:Comparison of Nanoliter Jets,Needles and TopicalSolutions[皮肤的递送策略:纳升喷射、针和局部溶液的比较].Ann.Biomed.Eng.[生物医学工程纪事]2019,2028-2039.]如果不进行干预,纹身会在皮肤上留下永久性印记,因为色素会历经由真皮噬黑色素细胞捕获和释放的重复循环,在真皮中的迁移很少。[Baranska,A.等人,Unveiling Skin Macrophage Dynamics Explains Both Tattoo Persistenceand Strenuous Removal[揭示性皮肤巨噬细胞动力学解释纹身持久性和不易去除性].J.Exp.Med.[实验医学杂志]2018,215,1115-1133.]纹身褪色是由这些免疫细胞通过引流到淋巴结清除色素引起的,这一过程可能会因激光纹身去除治疗和太阳光下UV暴露相关的色素光降解而加速。[Engel,E.等人,JDDG[德国皮肤病学会杂志]2007,5,583-589;Engel,E.等人,Exp.Dermatol.[实验皮肤病学]2009,19,54-60;Gonzalez,C.D.等人,Photodermatology,Photoimmunology&Photomedicine[光皮肤病学、光免疫学和光医学]2020,36,73-74;Gonzalez,C.D.等人,J.Clin.Aesthet.Dermatol.[临床与美容皮肤病学杂志]2020,13,22-23.]
尽管纹身最常用于身体装饰,但已经开发出了纹身的少数生物医学应用。生物医学纹身已被用于解剖活检部位的术前划分,以及医学美容应用,如重建手术、脱发修复和耐药性白癜风。[Vassileva,S.和Hristakieva,E.,Medical Applications of Tattooing[纹身的医学应用].Clin.Dermatol.[皮肤病学临床]2007,25,367-374;Jalgaonkar,A.等人,Preoperative biopsy tract identification using india ink skin tattoo inturnous surgery[在肿瘤手术中使用印度墨水皮肤纹身进行术前活检道鉴别].Orthopaedic Proceedings[整形外科期刊]2012,94-B:增刊_XXXVII,321;Becker,H.TheUse of Intradermal Tattoo to Enhance the Final Result of Nipple-AreolaReconstruction[皮内纹身在改善乳头乳晕重建的最终结果中的使用].Plast.Reconstr.Surg.[整形与重建外科]1986,77,673;Rassman,W.R.等人,ScalpMicropigmentation:A Concealer for Hair and Scalp Deformities[头皮微色素着色:头发和头皮畸形的遮瑕膏].J.Clin.Aesth.Dermatol.[临床与美容皮肤病学杂志]2015,8,35-42;Tanioka,M.等人,Camouflage for patients with vitiligo vulgaris improvedtheir quality of life[寻常性白癜风患者的色彩伪装改善患者生活质量].J.Cosmet.Dermatol.[美容皮肤病学杂志]2010,9,72-75.]这些应用通常依赖于常规纹身色素给皮肤着色,尽管已经设计了一些活检前纹身色素展现出荧光[Chuang,G.S.;Gilchrest,B.A.Dermatol.Surg.[皮肤外科]2012,38,479.]以及可编程的皮内保留时间。[Choi,J.等人,Cross-Linked Fluorescent Supramolecular Nanoparticles as FiniteTattoo Pigments with Controllable Intradermal Retention Times[交联荧光超分子纳米颗粒作为具有可控皮内保留时间的有限的纹身色素].ACS Nano[ACS纳米期刊]2017,11,153-162]最近,在离体皮肤模型中探索了对离子浓度、pH和葡萄糖水平敏感的可纹身生物传感器的概念,并在小鼠体内证明了对高钙血症敏感的色素沉着的基于合成生物学的细胞纹身。[Vega,K.等人,Proceedings of the 2017ACM International Symposium onWearable Computers[2017年ACM可穿戴计算机国际研讨会论文集]2017,138-145;Yetisen,A.K.等人,Angew.Chem.Int.Ed.Engl.[应用化学国际英语版]2019,58,10506-10513;Jiang,N.等人,Fluorescent Dermal Tattoo Biosensors for ElectrolyteAnalysis[用于电解质分析的荧光真皮纹身生物传感器].Sens.Actuators BChem.[传感器和执行器B卷:化学]2020,320,128378;Tastanova,A.等人,Synthetic Biology-BasedCellular Biomedical Tattoo for Detection of Hypercalcemia Associated withCancer[用于检测癌症相关高钙血症的基于合成生物学的细胞生物医学纹身].Sci.Transl.Med.[科学转化医学]2018,10,eaap8562.]
本发明提供了皮肤的永久或半永久UV保护。在第一方面,本技术利用透明或几乎透明的纳米颗粒和/或微颗粒的配制品,该配制品在UVA和UVB范围内具有高吸收性(参见以下实例1)。在另外的方面,本发明提供了利用如在第一方面中所述的、可植入真皮的这些颗粒的分散体的墨水(参见以下实例2)。在仍另外的方面,本发明提供了将墨水植入真皮的技术,包括常规纹身、永久化妆、穿线和微针贴剂(参见以下实例3)。
实例1-材料和方法
本发明提供了可见透明或无色UV吸收颗粒的配制品(参见例如,图1)。平均颗粒直径将有利地在大约20nm至10微米的范围内,以便(i)促进通过纹身或其他方式植入真皮并且(ii)半永久或永久地保留于真皮中。当粒径小于该尺寸范围的下限(即小于约20nm)时,颗粒更容易被免疫系统清除。另一方面,颗粒过大(例如,超过约10微米)可能导致过度的肉芽肿或瘢痕疙瘩反应。颗粒可以含有“功能元素”,在图1中描绘为较暗的球体。这些功能元素最低限度可包含UV吸收剂。“UV吸收剂”是指任何符合以下两个标准的化合物:(i)该化合物在280-400nm的紫外线波长范围内吸收大量的光,以及(ii)该化合物在大约400-800nm的可见光波长范围内按比例吸收最小量的光(例如,在UV范围内≤10%的吸光度)。可以用分光光度计测量光吸光度。“实质性”吸光度可以是在特定波长下大于1L/(g·cm)的吸收系数。
除UV吸收剂之外,配制品还可以包含以下功能元素的任何组合:
UV吸收剂。可以包括另外的UV吸收剂以调整UV范围内颗粒的光谱分布或提高配制品的光稳定性。因此,通过非限制性实例,可以通过改变280-400nm波长范围内UV吸收特征的形状和强度来调整给定配制品的光谱分布。
各种类别的UV吸收剂都可以且适当地用于UV吸收颗粒中。有机UV吸收剂可以包括FDA批准的非处方防晒药物[参见例如,美国食品药品监督管理局.Sunscreen DrugProducts for Over-the-Counter Human Use:Proposed Rule[非处方人用防晒药品:拟议规定].Federal Register[联邦公报]2019,84,6204-6275]、用于涂层的工业添加剂(例如二苯甲酮、苯并三唑、和苯基三嗪)[如在美国专利号US 2006/0153783中教导的]、[参见例如,Keck,J.等人,J.Phys.Chem.[物理化学杂志]1996,100,14468-14475;Schaller,C.等人,J.Coat.Technol.Res.[涂覆技术与研究杂志]2007,5,25-31.]或在它们的重复单元中掺入这些部分的聚合物。[Huang,Z.等人,Sci.Reports[科学报告]2016,6:25508.]无机/矿物质UV吸收剂包括TiO2[Allen,N.S.等人,Polym.Degrad.Stabil.[聚合物降解与稳定性]2002,78,467-478.]、ZnO[Becheri,A.等人,J.Nanopart.Res.[纳米颗粒研究杂志]2007,10,679-689.]、掺杂的SiO2[He,Q.等人,J.Phys.Chem.Solids[固体物理与化学杂志]2004,65,395-402]、CeO2[Goubin,F.等人,Chem.Mater.[材料化学]2004,16,662-669.]等,其可以是结晶、多晶、或无定形的。UV吸收剂还可以包括有机/无机组合,[Mahltig,B.等人,ThinSolid Films[固体薄膜]2005,485,108-114],包括层状双氢氧化物。[Feng,Y.等人,Polym.Degrad.Stabil.[聚合物降解与稳定性]2006,91,789-794;Li,D.等人,J.SolidState Chem[固态化学杂志]2006,179,3114-3120;Cao,T.等人,RSC Advances[皇家化学学会进展]2013,3,6282-6285.]
光稳定剂。在小分子和聚合物有机UV吸收剂的情况下,混合可抑制光降解的光稳定剂通常是有益的,可以增加UV吸收剂和颗粒中其他材料的使用寿命。[Muasher,M.;Sain,M.The efficacy of photostabilizers on the color change of wood filled plasticcomposites[光稳定剂对木填充塑料复合材料颜色变化的影响].Polym.Degrad.Stabil.[聚合物降解与稳定性]2006,91,1156-1165;Andrady,A.L.等人,Effects of increasedsolar ultraviolet radiation on materials[增加的太阳紫外线辐射对材料的影响].J.Photochem.Photobiol.B[光化学与光生物学杂志B]1998,46,96-103.]受阻胺,特别是来自2,2,6,6-四甲基哌啶及其烷基化或羟胺类似物的那些,是一类有利的光稳定剂。这些光稳定剂在UVA和UVB照射下清除有机材料中产生的不期望的自由基,并随后再生(Denisov循环[Hodgson,J.L.;Coote,M.L.Clarifying the mechanism of the Denisov cycle:Howdo hindered amine light stabilizers protect polymer coatings from photo-oxidative degradation?[阐明Denisov循环的机制:受阻胺光稳定剂如何保护聚合物涂层免受光氧化降解?]Macromolecules[大分子]2010,43,4573-4583]),赋予他们持久的光稳定功能。[Klemchuk,P.P.;Gande,M.E.Stabilization mechanisms of hindered amines[受阻胺的稳定机制].Polym.Degrad.Stabil.[聚合物降解与稳定性]1988,22,241-274.]
抗氧化剂。抗氧化剂,例如受阻酚[参见例如,Klemchuk,P.P.;Horng,P.L.Transformation products of hindered phenolic antioxidants and colourdevelopment in polyolefins[聚烯烃中受阻酚类抗氧化剂的转化产物及显色].Polym.Degrad.Stabil.[聚合物降解与稳定性]1991,34,333-346]或亚磷酸盐[参见例如,J.Polym.Degrad.Stabil.[聚合物降解与稳定性]1993,41,177-184;Habicher,W.D.,等人,Macromol.Symp.[大分子研讨会专刊]1997,115,93-125.],也可以作为功能元素添加。这些功能元素通过牺牲性地防止聚合物中发生不必要的氧化反应(即,它们使烷基过氧基和氢过氧化物失活),在许多聚合物材料中提供了协同稳定效应。[J.Chemical and photochemical behaviour of phenolic antioxidants inpolymer stabilization:Astate of the art report,part II.[酚类抗氧化剂在聚合物稳定中的化学和光化学行为:领域现状报告,第二部分]Polym.Degrad.Stabil.[聚合物降解与稳定性]1993,39,103-115;/>J.;/>S.Photostabilization ofcoatings[涂层的光稳定性].Mechanisms and performance[机制和性能].Prog.Polym.Sci.[聚合物科学进展]2000,25,1261-1335.]许多适合的抗氧化剂也可以来自天然来源,包括多酚(例如类黄酮、羟基肉桂酸和羟基苯甲酸、单宁、姜黄素、姜酚)、维生素(例如维生素A、C、E)和类胡萝卜素(例如β-胡萝卜素、番茄红素)。[Dintcheva,N.T.;D’Anna,F.Anti-/pro-oxidant behavior of naturally occurring molecules inpolymers and biopolymers:a brief review[聚合物和生物聚合物中天然存在的分子的抗氧化/促氧化行为:简要综述].ACS Sustainable Chem.Eng.[ACS可持续化学与工程]2019,7,12656-12670.]虽然许多这些天然存在的化合物在可见光区不透明,但它们可适合少量使用,以便它们对颗粒的着色最小或呈肤色。由于天然黑色素也表现出抗氧化和抗炎作用[ElObeid,A.S.等人,Pharmacological Properties of Melanin and its Functionin Health[黑色素的药理特性及其健康功能].Basic Clin.Pharmacol.Toxicol.[基础临床药理毒理学]2017,120,515-522.],这些元素可以使颗粒具有类似天然黑色素的另外的健康益处。
着色剂。由于散射可能导致无色纳米颗粒或微颗粒呈现白色,因此可以将配制品与染料或色素形式的着色剂混合,以便使配制品的颜色与受试者/患者的肤色相匹配。在纳米颗粒或微颗粒的合成过程中,可以将生物相容性染料或色素与聚合物载体、UV吸收剂和任何其他成分混合,以使其外观呈现肤色的颜色。示例性生物相容性色素是黑色素。
优选地,颗粒将几乎没有毒性、免疫原性或致畸性。颗粒还将在20℃-40℃的温度范围(代表皮内条件)内的水性介质中表现出高的化学、物理和光稳定性。表现出这些特征的颗粒应在皮肤中维持其长期功能和生物相容性。功能元素也可以不溶于(或通过化学或包封策略而不溶,参见下文)水性介质,以防止它们分裂到组织间液中。除了可见光吸收外,优选应将颗粒的散射、反射和折射最小化,以将它们在皮肤中的可见性最小化。由于颗粒直径在100-200nm附近的散射最高[Dawson,P.L.;Acton,J.C.Impact of proteins on foodcolor[蛋白质对食物颜色的影响].Proteins in Food Processing,Second Ed.[食品加工中的蛋白质,第二版].2018,Elsevier Ltd.[爱思唯尔有限公司]页码599-638.],一些优选的粒径是在可见光或更高的尺寸范围(400nm及以上)。为了最大限度减少将导致颗粒呈白色(米氏散射(Mie scattering))的过多的反射和折射,可见光范围内颗粒的折射率可以与真皮的折射率紧密匹配(1.36-1.41[Ding,H.;等人.Refractive indices of human skintissues at eight wavelengths and estimated dispersion relations between300and 1600nm[人体皮肤组织在八个波长的折射率和在300和1600nm的估计分散关系].Physics in Medicine and Biology[医学和生物学中的物理学]2006,51,1479-1489])。通过使用染料或色素添加剂将过度散射的颗粒配制品的颜色与使用者的肤色相匹配,可以使这些颗粒配制品在皮肤中“不可见”。
配制品A,聚合物颗粒。功能元素可以通过多种策略整合到适当尺寸(约20-10,000nm)的聚合物或共聚物颗粒中,这些策略可大致分为分散方法和聚合方法。[Rao,J.P.;Geckeler,K.E.Polymer nanoparticles:Preparation techniques and size-controlparameters[聚合物纳米颗粒:制备技术和尺寸控制参数].Prog.Polym.Sci.[聚合物科学进展]2011,36,887-913.]分散方法涉及通过喷雾剂或乳剂中的溶剂蒸发,或通过溶剂交换、盐、透析或超临界流体的沉淀,将预先形成的聚合物从均匀溶液转化为纳米颗粒或微颗粒。在这些过程中,将功能元素溶于聚合物相中可将这些元素(非共价地)掺入到所得纳米颗粒或微颗粒的聚合物基质中。聚合物颗粒合成的聚合方法通常依赖于乳剂,其中通常在水溶液中分散的预聚合物树脂(单体)的纳米液滴或微液滴在聚合开始时直接聚合成颗粒。在这种情况下,功能元素可以溶解到乳剂的单体相中以在聚合时将它们掺入到聚合物基质中。日本专利JP 6129146中教导了可应用于水性分散体的UV吸收纳米颗粒的聚合方法。在分散和聚合两种方法中,功能元素也可以在聚合物合成期间作为单体被直接掺入聚合物结构的主链、侧链或交联中。在大多数情况下,功能元素可以用反应性官能团修饰以共价结合到聚合物或共聚物上。例如,将基于二苯甲酮、苯并三唑、或苯基三嗪的UV吸收剂用一个或多个丙烯酸或乙烯基官能团官能化,使其能够通过催化或自由基聚合进行聚合或共聚合。可替代地,功能元素可以偶联到预先合成的聚合物[Huang,Z.等人,Sci.Reports[科学报告]2016,6:25508],这些掺入功能元素的共价附接方法比混合方法更昂贵,但它们降低了任何功能元素从颗粒中浸出的风险。
该配制品中有利的聚合物基质包括聚(二甲基硅氧烷)(PDMS)和其他硅橡胶、或聚(甲基丙烯酸甲酯)(PMMA)和其他甲基丙烯酸酯化合物(例如,聚(甲基丙烯酸甲酯)、聚(甲基丙烯酸异丙酯)、聚(甲基丙烯酸异丁酯))。这些聚合物基质特别适合作为UV吸收颗粒应用,因为(i)它们的生物相容性已得到证实,(ii)它们小于1.5的折射率接近真皮的折射率,(iii)它们表现出高的长期稳定性,以及(iv)它们的生产相对方便和便宜。[Rahimi,A.;Mashak,A.Review on rubbers in medicine:natural,silicone and polyurethanerubbers[医用橡胶综述:天然橡胶、硅橡胶和聚氨酯橡胶].Plastics,Rubber andComposites[塑料、橡胶与复合材料]2013,42,223-230;Frazer,R.Q.等人,PMMA:AnEssential Material in Medicine and Dentistry[PMMA:医学和牙科的基本材料].Journal of Long-Term Effects of Medical Implants[医疗植入物的长期影响期刊]2005,15,629-639.]
配制品B,分子聚集体。当在生物温度下形成固体的小分子或寡聚物功能元素在水性介质中有足够的不溶性并具有足够的尺寸用于真皮植入时,它们可以直接作为聚集颗粒使用。使水溶性差的化合物成为小微粒的工艺被称为纳米化[Kesisoglou,F.等人,Nanosizing—Oral formulation development and biopharmaceutical evaluation[纳米化-口服配制品开发和生物制药评估].Adv.Drug Deliv.Rev.[先进药物递送评论]2007,59,631-644]或微粉化。[Rasenack,N.和Müller,B.W.Micron-Size Drug Particles:Common and Novel Micronization Techniques[微米尺寸药物颗粒:常见和新型微粉化技术].Pharm.Dev.Technol.[药物开发与技术]2004,9,1-13]分子聚集体可以通过以下制备为纳米颗粒或微颗粒:(i)由溶剂沉淀为非溶剂(理想地是水)[Rabinow,B.E.Nanosuspensions in drug delivery[药物递送中的纳米悬浮液].Nat.Rev.DrugDiscov.[自然综述:药物发现]2004,3,785-796],(ii)喷雾干燥工艺[Vehring,R.Pharmaceutical Particle Engineering via Spray Drying[经由喷雾干燥的制药颗粒工程].Pharm.Res.[药物研究]2007,25,999-1022],(iii)超临界流体技术[Martin,A.和Cocero,M.J.Micronization processes with supercritical fluids:Fundamentals andmechanisms[超临界流体微粉化工艺:基本原理和机制].Adv.Drug Deliv.Rev.[先进药物递送评论]2008,60,339-350]或(iv)研磨。[Merisko-Liversidge,E.等人,Nanosizing:aformulation approach for poorly-water-soluble compounds[纳米化:水溶性差化合物的配制方法].Eur.J.Pharm.Sci.[欧洲药物科学杂志]2003,18,113—120.]这些方法可用于生成纳米颗粒或微颗粒UV吸收剂或包含有机分子的功能元素的混合物。这种形式的示例性材料是微粉化的羟基苯基-s-三嗪。另一种示例性材料是石墨相氮化碳。
配制品C。无机颗粒。各种半导体金属氧化物可用作UV吸收剂。[Fajzulin,I.等人,Nanoparticulate inorganic UV absorbers:a review[纳米颗粒无机UV吸收剂:综述].J.Coat.Technol.Res.[涂覆技术与研究杂志]2015,12,617-632]与有机材料相比,这些材料不会光降解。TiO2和ZnO是非处方防晒霜中最常见的UV吸收剂,它们也常因自身美白效果被用作纹身墨水的颜色添加剂。这些材料的UV吸收率随颗粒尺寸的减小而增大,并在直径50nm以下的散射中占主导地位。[Egerton,T.A.和Tooley,I.R.UV absorption andscattering properties of inorganic-based sunscreens[基于无机的防晒霜的UV吸收和散射特性].Int.J.Cosmet.Sci.[国际美容科学杂志]2011,34,117-122]因此,这些材料可以以小(<50nm)粒径用作皮内UV吸收剂。然而,它们在可见光波长的高度散射和反射特性[Cole,C.等人,Metal oxide sunscreens protect skin by absorption,not byreflection or scattering[金属氧化物防晒霜通过吸收而不是反射或散射来保护皮肤].Photoderm.Photoimmunol.Photomed.[光皮肤病学、光免疫学和光医学]2015,32,5-10.]—由于其高折射率(对于TiO2是2.6,对于ZnO是1.9)—可能导致皮肤变白。当使用无机颗粒作为UV吸收剂时,可以通过使用另外的纹身色素颜色添加剂以匹配肤色来解决这个问题。然而,TiO2和ZnO还表现出光催化活性[Egambaram,O.P.;Kesavan Pillai,S.;Ray,S.S.Materials Science Challenges in Skin UV Protection:AReview[皮肤UV防护的材料科学挑战:综述].Photochem.Photobiol.[光化学与光生物学]2020,36,1345—1264],产生有害的活性氧类。虽然这使它们在皮肤表面具有杀菌作用,但可能会导致皮内组织和DNA损伤。也可以采用可替代的无机UV吸收剂(例如CeO2、Fe2O3),它们可能面临类似的问题,因为UV吸收率来自半导体带隙,而当半导体吸收的能量大于其带隙时,就会发生光催化。如果无机颗粒要用作UV吸收剂,它们可以与表面涂层一起使用(例如以下配制品D和E中所描述的那些)以防止光催化。
配制品D,表面包覆的颗粒。可以通过化学或物理方式在纳米颗粒或微颗粒的表面吸收单层或多层的UV吸收剂和其他功能元素。功能元素与颗粒的共价附接使UV吸收剂附着于颗粒表面。例如,表面包覆的颗粒可以使用二氧化硅颗粒作为底物。二氧化硅是合适的材料,因为(i)它已用作纹身墨水中的触变剂[Piccinini,P.等人,Safety of tattoos andpermanent make-up:Final report[纹身和永久化妆的安全性:最终报告].EuropeanCommission Joint Research Centre Science for Policy Report[欧盟委员会联合研究中心科学政策报告]2016,1-118]并且它可以是生物相容的,(ii)它很容易通过硅烷化而功能化[Voort,Der,P.V.;Vansant,E.F.Silylation of the Silica Surface AReview[二氧化硅表面硅烷化:综述].J.Liq.Chromatogr.R T.[液相色谱及相关技术杂志]2006,19,2723-2752.]其中具有多种烷氧基硅烷和卤代硅烷。将需要修饰功能元素以显示这些硅烷官能团以共价附接至SiO2。也可以配制聚合物颗粒用于表面修饰,只要它们显示可偶联至功能元素的反应性官能团。然而,由于该配制品中功能元素的低质量和体积比,预计其效果不如以下所示的配制品E和F。
配制品E。核壳颗粒。核壳颗粒包括核流体/聚合物壳、核流体/无机壳、核聚合物或凝胶/聚合物壳以及核聚合物或凝胶/无机壳的配制品。该配制品中方便的无机壳是二氧化硅,因为它使无机颗粒更具生物相容性。[Gerion,D.等人,Synthesis and properties ofbiocompatible water-soluble silica-coated CdSe/ZnS semiconductor quantum dots[生物相容性水溶性二氧化硅涂覆的CdSe/ZnS半导体量子点的合成和特性].J.Phys.Chem.B[物理化学杂志B]2001,105,8861-8871.]核或壳聚合物可以构成如配制品A中所讨论的相同聚合物,其中优选PDMS和PMMA,因为它们具有透明度和生物相容性。核壳颗粒也被称为纳米胶囊或微胶囊,尤其当它们含有流体核时,并且它们可以通过以下来生产:各种乳剂聚合技术[Jamekhorshid,A.等人,Areview of microencapsulation methodsof phase change materials(PCMs)as a thermal energy storage(TES)medium[相变材料(PCM)作为热能储存(TES)介质的微包封方法综述].Renew.Sust.Energy Rev.[可再生和可持续能源评论]2014,31,531-542]以及微流体反应器方法[Wang,J.-T.等人,Fabrication of Advanced Particles and Particle-Based Materials Assisted byDroplet-Based Microfluidics[液滴微流控辅助的先进颗粒和基于颗粒的材料的制作].Small[Small杂志]2011,7,1728-1754.]以及喷雾干燥。[Gharsallaoui,A.等人,Applications of spray-drying in microencapsulation of food ingredients:Anoverview[喷雾干燥在食品成分微包封中的应用:概述].Food Research International[国际食品研究]2007,40,1107-1121.]
配制品F。介孔二氧化硅纳米颗粒。介孔二氧化硅纳米颗粒(MSNP)作为药物递送应用的纳米载体得到了高度发展。[Slowing,I.I,等人,Mesoporous silica nanoparticlesas controlled release drug delivery and gene transfection carriers[介孔二氧化硅纳米颗粒作为控释药物递送和基因转染载体].Adv.Drug Deliv.Rev.[先进药物递送评论]2008,60,1278-1288.]它们在许多环境中的广泛使用和生物相容性也使它们成为UV吸收剂和吸收性微颗粒的其它功能元素的有吸引力的载体。[Asefa,T.;Tao,Z.Biocompatibility of mesoporous silica nanoparticles[介孔二氧化硅纳米颗粒的生物相容性].Chem.Res.Toxicol.[毒物学化学研究]2012,25,2265-2284;Tam,D.等人,Mesoporous silica nanoparticle nanocarriers:biofunctionality andbiocompatibility[介孔二氧化硅纳米颗粒纳米载体:生物功能性和生物相容性].Acc.Chem.Res.[化学研究述评]2013,46,792-801]然而,与药物递送相比,如果要释放颗粒的内容物,则功能元素必须永久包含在紫外线吸收性微颗粒中。因此,有利的方法是使用烷氧基硅烷和卤代硅烷将功能元素共价附接至SiO2表面。[Voort,Der,P.V.等人,J.Liq.Chromatogr.R.T.[液相色谱及相关技术杂志]2006,19,2723-2752]然而,也可以将功能元素包含在孔中,只要表面的孔开口被充分堵塞以消除质量输运(负载物释放)。与二氧化硅纳米颗粒(配制品D)相比,MSNP的优势在于其更高的表面积(每克可超过1000平方米),允许更高密度的功能元素被吸收到每个颗粒的表面(最终导致更强的UV吸收墨水和纹身)。
制备纳米颗粒或微颗粒的实例程序:配制品A的紫外线吸收纳米颗粒包含PMMA基质掺杂UV吸收剂贝莫曲嗪醇(由巴斯夫公司(BASF)作为S销售)。将100mg的PMMA(35,000Da)和25mg贝莫曲嗪醇溶解在4ml的二氯甲烷中。将该有机溶液添加至聚乙烯醇(PVA)的水溶液中,浓度为1%m/v。用手将混合物摇匀形成乳剂,然后用喇叭超声波仪(必能信公司(Branson))在室温下对该乳剂进行超声处理10分钟。将乳剂转移到带有搅拌棒的烧杯中,在室温下以-1000rpm的速度搅拌,使有机溶剂蒸发。6小时后,将悬浮液转移到离心管中。在离心的几个循环中漂洗颗粒,倒出上清液,并且重新注入纯化水。使用Nanotrac FLEX粒径分析仪(Microtrak公司)通过动态光散射估计颗粒的尺寸分布(图2A),通过扫描电子显微镜观察颗粒形状(图2B),使用Cary 5000UV可见NIR分光光度计(安捷伦公司(Agilent))收集其吸收数据(图2C)。
实例2-紫外线吸收纳米颗粒或微颗粒墨水
紫外线吸收纳米颗粒(例如上文实例1中所述的那些)可以在溶剂中分散以制备墨水。墨水配制品可以针对皮内递送方法进行定制,例如以下所述的方法,其可以包括各种纹身/永久化妆方法和微针或针贴剂。
纹身和永久化妆墨水。为了产生适用于真皮植入的液体墨水,将紫外线吸收颗粒悬浮在含有或不含添加剂的流体中。示例性流体是水,但也可以使用其他生物相容性溶剂,例如醇(例如,乙醇、异丙醇、甘油、低聚乙二醇和聚乙二醇)或油类(例如,植物油/甘油三酯、香叶醇、角鲨烯等)。用于这些墨水的适当的添加剂包括(i)防止细菌污染的抗菌剂(例如醇)、(ii)稳定分散体并调整表面张力的生物相容性表面活性剂(例如,聚山梨醇酯)、(iii)增加黏度并降低色素沉着速率的增稠剂(例如黄原胶、聚丙烯酸酯、聚二醇)[Petersen,H.;Roth,K.To Tattoo or Not to Tattoo[纹身还是不纹身]?Chem.UnsererZeit[当今化学]2016,50,44-66]、(iv)促进剪切稀化的触变剂[Piccinini,P等人,Safetyof tattoos and permanent make-up:Final report[纹身和永久化妆的安全性:最终报告].European Commission Joint Research Centre Science for Policy Report[欧盟委员会联合研究中心科学政策报告]2016,1-118.](例如二氧化硅)、(v)帮助防止墨水干燥并帮助它们粘合至针的防腐剂/粘合剂(例如聚醚、聚乙烯吡咯烷酮、PVA)、(vi)最大限度减少植入后皮肤出血的收敛剂、和/或(vii)最大限度减少墨水植入期间疼痛的麻醉剂。所得墨水可以用γ辐射或其他方式消毒,如高压釜、加热、UV辐射、X射线辐射,或在包装和储存之前用环氧乙烷处理。紫外线吸收微颗粒可以在合成后作为湿浆料或干浆料储存。
制备紫外线吸收纳米颗粒墨水的实例程序。通过将湿浆料以25%的质量比悬浮在反渗透纯化水中,制备了配制品A的紫外线吸收微颗粒的纹身墨水。用手剧烈振荡闪烁瓶中的悬浮液30秒。墨水通过照片和UV照片来表征(图3)。墨水在小时时间尺度上保持良好分散。虽然在该实例中没有使用,但有利的配制品包括以10%-30%的比率添加的甘油或聚(乙二醇)作为防腐剂、增稠剂和粘合剂。这些添加剂可以提高紫外线吸收纳米颗粒或微颗粒墨水的稳定性和可转移性。
微针纹身墨水。一种新兴的技术是微针贴剂,该技术应被证明适合于将诸如紫外线吸收微颗粒墨水的材料输送到真皮中,微针贴剂是一种具有穿透表皮的微结构突起的多种可能配置的装置,其典型地以经皮药物输送和疫苗应用为目标。[Prausnitz,M.R.Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin[用于疫苗接种和药物递送到皮肤的工程微针贴剂].Annual Rev.Chem.Biomol.Eng.[化学与生物分子工程年鉴]2017,8,177-200]美国专利号6,565,532B1教导了用于标记皮肤以及用于进行半永久皮下化妆的微针设备。虽然这些装置还没有出现在市场上,但有可能将其用于UV吸收纳米颗粒或微颗粒的皮内植入。这些微针贴剂的墨水配制品将由含有聚合物、预聚合物或微针递送方法基质的分子前体的流体中UV吸收纳米颗粒或微颗粒的悬浮液组成。例如,配制品将采用可溶微针阵列,因为与其他微针贴剂配制品相比,这种微针贴剂配制品优化用于递送相对大量的材料。[Bediz,B.等人,Dissolvable Microneedle Arraysfor Intradermal Delivery of Biologies:Fabrication and Application[皮内生物递送的可溶微针阵列:制作和应用].Pharm.Res.[药物研究]2013,31,117—135]用于可溶微针阵列的载体基质有利地是一种无毒材料,其强度足以穿透表皮,但具有足够的水溶性,以迅速在真皮的组织间液中溶解,从而释放其内容物。微针不可见紫外线吸收纳米颗粒或微颗粒墨水的合适载体的实例包括聚乙烯吡咯烷酮或聚乙烯醇及其液体预聚合物,或羧甲基纤维素、海藻糖、麦芽糖糊精、半乳糖、葡萄糖和丝的水溶液,其分别在固化或干燥后在微针模具内凝固。
针宽和深度尺寸<1mm的微针对于在真皮中永久植入材料来说可能太小,因为它的平均厚度约为2mm,并且可达厚度至高为4mm,[Oltulu,P.等人,Measurement ofepidermis,dermis,and total skin thicknesses from six different body regionswith a new ethical histometric technique[用新的伦理组织测量技术测量六个不同身体区域的表皮、真皮和总皮肤厚度].Turk.J.Plast.Surg.[土耳其整形外科杂志]2018,26,56-61.]并且纹身机最深可透入皮肤4mm。[Petersen,H.;Roth,K.To Tattoo or Not toTattoo[纹身还是不纹身]?Chem.Unserer Zeit[当今化学]2016,50,44-66.]更大尺寸的可溶针(例如>1mm)可以用相似的方法制备,使用具有更大尺寸特征的母版和模具,并且可更适用于本发明中提出的应用。
实例3-紫外线吸收微颗粒纹身的植入方法
紫外线吸收纳米颗粒或微颗粒“纹身”可以通过多种方法植入,这些方法通常涉及在不可见紫外线吸收纳米颗粒或微颗粒分散体中浸入的针或针阵列(参见上文实例2)。墨水涂覆的针可以重复刺穿皮肤以突破表皮屏障,并将墨水材料递送至真皮。将一个或多个针插入皮肤可以根据一些古老的土著纹身传统来用手进行,这些传统包括轻敲(玻里尼西亚达道(tatau,Polynesia))、刮擦(日本手雕(tebori))、用针和线的穿线/缝合(北美)、以及划开后用墨水擦揉(欧洲)。[Krutak,L.;Deter-Wolf,A.(编辑).Ancient Ink:TheArchaeology of Tattooing[古代墨水:纹身考古]2017.Seattle;London:University ofWashington Press[西雅图、伦敦:华盛顿大学出版社].]有利的方法是将针阵列附接到现代电动纹身或永久化妆机上,与手工驱动的方法相比,该电动机器可以提高效率并且最大限度减少疼痛。已经描述了无针纹身机,它以足够高的速度将纹身墨水液滴注入皮肤,穿透到真皮[Garitano,G.;Garitano,L.Needleless permanent makeup and tattoo device[无针永久化妆和纹身装置].美国专利6,689,095B1.(2004年2月10日).]。在与标准纹身墨水兼容的程度上,这些机器也可用于本申请。
可替代地,墨水可以在PDMS模具中被配制成可溶微针或针贴剂,如Bediz等人所述[Bediz,B.;Korkmaz,E.;Khilwani,R.;Donahue,C.;Erdos,G.;Falo,L.D.,Jr;Ozdoganlar,O.B.Dissolvable Microneedle Arrays for Intradermal Delivery of Biologies:Fabrication and Application[皮内生物递送的可溶微针阵列:制作和应用].Pharm.Res.[药物研究]2013,31,117-135],可以使用贴剂,它只需插入皮肤一次即可保留足够的时间,以允许UV吸收颗粒在真皮的组织间液中释放。
植入紫外线吸收微颗粒墨水的实例程序。使用离体猪皮肤模型,用配备有钢9RS纹身针阵列的旋转纹身机(Dragonhawk)将不可见紫外线吸收纳米颗粒纹身植入,该针阵列浸入大约25wt%的基于PMMA的不可见紫外线吸收纳米颗粒的水性分散液中(在上文实例1和2中所述),其中驱动功率为7V,作用面积为1平方厘米,直到获得外观均匀的“隐形”UV吸收设计的纹身。在纹身前后用异丙醇清洁皮肤样品。图4显示了这种不可见紫外线吸收颗粒纹身在可见光和UVA范围内的照片,并与UV吸收炭黑和UV透明PDMS纳米颗粒进行了比较,验证了基于UV吸收贝莫曲嗪醇/PMMA纳米颗粒的纹身在皮肤中吸收UV。
实例4-紫外线吸收纳米颗粒或微颗粒纹身的应用
创新的用途和益处。紫外线吸收纳米颗粒或微颗粒纹身可以用于降低个体患有UV诱发的皮肤癌的风险,防止和管理其他UV相关的皮肤障碍和并发症的症状,减少与UV暴露相关的皮肤损伤和老化,帮助维护和保护色素纹身和纹身皮肤,调节皮内UV辐射计和UV剂量计的灵敏度,或在皮肤上产生只有用UV相机才能检测到的不可见标记,如下所述。
降低皮肤癌风险。通过吸收UV光(否则会反向散射并被基因和组织吸收),紫外线吸收纳米颗粒或微颗粒纹身将减少使UV辐射成为皮肤癌的主要危险因素的UV辐射的有害影响。黑色素纹身在小鼠中表现出显著的抗光致癌作用,可能是由于UV吸收机制。[Lerche,C.M.等人,Black tattoos protect against UVR-induced skin cancer in mice[黑色纹身防止UVR诱发的小鼠皮肤癌].Photoderm.Photoimmunol.Photomed.[光皮肤病学、光免疫学和光医学]2015,31,261-268.]本发明的紫外线吸收纳米颗粒或微颗粒纹身技术提供类似或更优的防UV诱发皮肤癌的保护,同时不会显著改变皮肤颜色。
其他UV相关的皮肤并发症的症状管理。许多其他皮肤疾病和自身免疫性疾病也与UV暴露有关。
炎症/“晒伤”:UVB照射通过触发一系列细胞因子、血管活性和神经活性介质在皮肤炎症反应中协同产生,从而引起“晒伤”(红斑)。如果UVB剂量超过一定阈值,取决于黑色素密度和其他遗传因素,角质形成细胞会凋亡和死亡。[Clydesdale,G.J.等人,Ultraviolet light induced injury:Immunological and inflammatory effects[紫外光诱发的损伤:免疫和炎症作用].Immunol._Cell.Biol.[免疫学和细胞生物学]2001,79,547-568;Matsumura,Y.;Ananthaswamy,H.N.Toxic effects of ultraviolet radiationon the skin[紫外线辐射对皮肤的毒性作用].Toxicol.Appl.Pharmacol.[毒理学和应用药理学]2004,195,298-308.]
光性皮肤病:最常见的光性皮肤病是多形性日光疹,通常表现为UV暴露区域的丘疹。[Kang,S.等人,Fitzpatrick’s Dermatology,9e.[费氏皮肤病学第9版]McGraw-HillEducation[麦格劳希尔教育公司],2019.]光化性痒疹、慢性光化性皮炎和夏令痤疮是UV诱发的流行性或结节性发疹的不常见的形式。光化性皮炎症状与湿疹相似,但是由UV暴露引起的。感染HIV的患者患有这些光敏性的风险增加。日光性荨麻疹是一种罕见的病症,在暴露于UV的皮肤上形成荨麻疹或风团。种痘样水疱病是另一种罕见的病症,其涉及皮疹成熟为水疱发疹,并导致暴露在阳光下的皮肤(尤其是面部和手部)留下疤痕。
光毒性和光过敏:急性光毒性发生在与适当的光毒剂和足够UV光接触的数小时内,产生刺痛或灼烧感,随后可能伴有红斑和水肿、发痒(瘙痒)、以及在严重病例中的囊泡或大疱。[Kang,S.等人,Fitzpatrick’s Dermatology,9e.[费氏皮肤病学第9版]McGraw-Hill Education[麦格劳希尔教育公司],2019.]假性卟啉症发生于严重病例,并涉及水疱和皮肤脆性(skin fragility)。植物光皮炎也是由接触植物中发现的光毒性化合物后的UV暴露引起的。光过敏可能导致瘙痒湿疹样发疹,通常与接触性皮炎难以区分。
Favre-Racouchot综合征:粉刺是在患有这种综合征的患者的阳光损伤的皮肤(尤其在眼周)中发生的填充物质的毛囊和皮脂腺的增宽开口。[Paganelli,A.等人,Favre-Racouchot disease:systematic review and possible therapeutic strategies[Favre-Racouchot疾病:系统综述和可能的治疗策略].J.Eur.Acad.Dermatol.Venereol.[欧洲皮肤病学和性病学会杂志]2018,33,32-41.]
皮肌炎:患有自身免疫性疾病肌炎的女性应非常谨慎地对待UV暴露,因为UV暴露会增加她们发展为皮肌炎的可能性,[Love,L.A.;Weinberg,C.R.;McConnaughey,D.R.;Oddis,C.V.;Medsger,T.A.,Jr.;Reveille,J.D.;Arnett,F.C.;Targoff,I.N.;Miller,F.W.Ultraviolet radiation intensity predicts the relative distribution ofdermatomyositis and anti-Mi-2autoantibodies in women[紫外线辐射强度预测女性皮肌炎和抗Mi-2自身抗体的相对分布].Arthritis Rheum.[关节炎与风湿病]-美国2009,60,2499-2504.]一种自身免疫性疾病,会导致面部、眼睑、关节、胸部和背部出现皮疹和肿块。
红斑狼疮:高达93%患有自身免疫性疾病红斑狼疮的患者会出现UV光敏性,导致红斑、炎症病变和严重皮肤炎症等症状。[Wolf,S.J.等人,Human and Murine Evidencefor Mechanisms Driving Autoimmune Photosensitivity[驱动自身免疫光敏性机制的人类和鼠证据].Front.Immunol.[免疫学前沿]2018,9,699-12.]
上文病症的症状可以通过皮内UV吸收颗粒减轻、延迟或预防,因为它减少了皮肤组成结构在阳光下经历的有效UV暴露剂量。
减少皮肤老化:UV暴露对光损伤和光敏引起的皮肤老化(包括张力和弹性的丧失,以及沟纹、皱纹和病变的增加)的加速作用是熟知的和理解的。[Rittié,L.;Fisher,G.J.UV-light-induced signal cascades and skin aging[UV光诱发的信号级联和皮肤老化].Ageing Research Reviews[老化研究评论]2002,1,705-720;Svobodova,A.等人,Ultraviolet light induced alteration to the skin[紫外光诱发的皮肤改变].Biomed.Pap.Med.Fac.Univ.Palacky Olomouc Czech Repub.[捷克斯洛伐克奥洛穆茨帕拉茨基大学医学院生物医学论文]2006,150,25-38;Farage,M.A.等人,Intrinsic and extrinsicfactors in skin ageing:a review[皮肤老化的内在和外在因素:综述].Int.J.Cosmet.Sci.[国际美容科学杂志]2008,30,87-95.]紫外线吸收颗粒将通过高效吸收和耗散UV光的能量,防止UV光反向散射到表皮等其他组织层,从而降低由存在UV光的真皮内发生的光损伤和光敏事件引起的老化概率,并在较小程度上降低表皮等其他组织层的老化概率。
纹身色素和纹身皮肤的保持:UV暴露加速纹身褪色[Gonzalez,C.D.;Rundle,C.W.;Pona,A.;Walkosz,B.J.;Dellavalle,R.P.(2020).Ultraviolet radiation maycause premature fading of colored tattoos[紫外线辐射可能导致彩色纹身过早褪色].Photodermatology,Photoimmunology&Photomedicine[光皮肤病学、光免疫学和光医学],36,73-74],如本文所教导的紫外线吸收颗粒可以作为纹身墨水的添加剂,或者植入在现有纹身之上,或者在进行色素纹身前应用于皮肤的一个区域。以此类方式应用使得紫外线吸收颗粒在皮肤中充当光稳定色素防腐剂。这种紫外线吸收颗粒的应用会产生彩色纹身,随着时间的推移,这些纹身褪色的速度会降低。
此外,纹身偶尔会导致光性皮肤病、光皮炎和光毒性。[Anderson,R.R.SheddingSome Light on Tattoos?[给纹身一些启示?]Photochem.Photobiol.[光化学与光生物学]2004,80,155-3;Kazandjieva,J.;Tsankov,N.Tattoos:dermatological complications[纹身:皮肤并发症].Clin.Dermatol.[皮肤病学临床]2007,25,375-382;Khunger,N.等人,Complications of tattoos and tattoo removal:stop and think before you ink[纹身和去除纹身的并发症:纹身前需三思].J.Cutan.Aesthet.Surg.[皮肤与美容外科杂志]2015,8,30-36;Vangipuram,R.和Mask-Bull,L.Histopathologic Reaction Patterns inDecorative Tattoos[装饰性纹身的组织病理学反应模式].J.Pigment.Disord.[色素性障碍杂志]2016,3,1000232;Kim,S.Y.等人,Evaluation of phototoxicity of tattoopigments using the3T3 neutral red uptake phototoxicity test and a 3D humanreconstructed skin model[使用3T3中性红摄取光毒性试验和3D人体重建皮肤模型评估纹身色素的光毒性].Toxicology in Vitro[体外毒理学]2020,65,104813.]纹身中的许多色素在辐照时会产生有害的单线态氧。[Regensburger,J.等人,Tattoo inks containpolycyclic aromatic hydrocarbons that additionally generate deleterioussinglet oxygen[纹身墨水含有另外产生有害的单线态氧的多环芳烃]Exp.Dermatol.[实验皮肤病学]2009,19,e275-e281;T.等人,Black tattoo inks inducereactive oxygen species production correlating with aggregation of pigmentnanoparticles and product brand but not with the polycyclic aromatichydrocarbon content[黑色纹身墨水诱发活性氧类的产生与色素纳米颗粒的聚集和产品品牌相关,但与多环芳烃含量无关].Exp.Dermatol.[实验皮肤病学]2013,22,464-469.]如本文所教导的紫外线吸收颗粒将通过吸收UV光来降低这些情况下的光毒性,否则UV光会被纹身色素吸收并导致这些光毒性作用。
调整皮内辐射计和剂量计的灵敏度:UV光致变色纹身色素可以用作长期皮内UV辐射计和剂量计。[Butterfield,J.L.;Keyser,S.P.;Dikshit,K.V.;Kwon,H.;Koster,M.I.;Bruns,C.J.Long-Term Photochromic Tattoos for Intradermal UltravioletRadiometry[日光性雀斑:用于皮内紫外线辐射测量的长期光致变色纹身].Acs Nano[ACS纳米期刊]2020,14,13619—13628.]这些色素和紫外线吸收颗粒的混合物将以浓度依赖性的方式减少到达光致变色色素的有效UV辐照度,从而允许微调这些新兴皮内传感器的灵敏度。
仅可通过UV相机探测的不可见纹身:由于UV吸收颗粒在皮肤中肉眼不可见,但UV相机可见,因此本文所教导的UV吸收颗粒可用于在皮肤上产生只有用UV相机才可检测到的隐形标记。纹身墨水的这一应用可用于在皮肤中写入隐藏或编码信息,以实现身份验证的目的,如组织成员身份验证、身体艺术身份验证、医疗记录身份验证或既往经历身份验证。
定义
涉及本发明的化合物的术语“施用”及其变形(例如,“施用(administering)”化合物,“施用”重组黏液瘤病毒)意指将化合物引入需要治疗的受试者的系统中,例如经由注射引入受试者皮肤的真皮层中。当本发明的化合物与一种或多种其它活性剂组合提供时,“施用”及其变形各自被理解为包括化合物和其它药剂的同时和顺序引入。
如本文所用,术语“组合物”旨在涵盖包含指定量的指定成分的产品,以及任何直接或间接由指定量的指定成分的组合产生的产品。
“药学上可接受的”组分是适用于人类和/或动物且没有过度的不良副作用(例如毒性、刺激性和过敏反应)、与合理的益处/风险比相称的组分。
“安全有效量”是指以本发明的方式使用时,足以产生所需的治疗反应而没有过度的不良副作用(例如毒性、刺激性和过敏反应)、与合理的益处/风险比相称的组分的量。
当紫外光吸收颗粒的尺寸范围在20nm至10μm内,且化学和光化学稳定(抗降解),无过度的不良副作用(例如毒性、刺激性和过敏反应)、与合理的益处/风险比相称时,该颗粒“适合注射到皮肤的真皮层”。
如在整个申请中所用,术语“一个/种(a/an)”意指“至少一个/种”、“至少第一个/种”、“一个/种或多个/种”或“多个/种”所提及的组分或步骤,除非上下文另有明确规定。例如,术语“细胞(a cell)”包括多个细胞,包括其混合物。
术语“和/或”在本文任何地方使用时包括“和”、“或”和“由所述术语连接的要素的全部或任何其他组合”的含义。
如本文所用,术语“约”或“大约”意指在给定值或范围的20%内、优选在10%内、并且更优选在5%内。
如本文所用,术语“包含/包括”旨在意指产品、组合物和方法包括所提及的组分或步骤,但不排除其它。“基本上由……组成”用于定义产品、组合物和方法时,应意指排除具有任何本质意义的其他组分或步骤。因此,基本上由所述组分组成的组合物不会排除痕量污染物和药学上可接受的载体。“由……组成”应意指排除超过痕量元素的其他组分或步骤。
“UV吸收剂”或紫外光吸收剂是用于将紫外光(即波长短于光谱紫色端的电磁辐射,波长在4-400纳米范围内,包括光谱的UV-A、UV-B和/或UV-C范围内的光)耗散到较低能态的材料。
波长在320与400nm之间的紫外线A(UVA)紫外线辐射占抵达地球表面的这种辐射的99%以上。紫外线A增强了紫外线B辐射的有害影响,并且还导致了一些光敏性反应;它在治疗上用于治疗各种皮肤障碍。
波长在290与320nm之间的紫外线B(UVB)紫外线辐射占抵达地球表面的紫外线辐射的小于1%。紫外线B会导致晒伤和一系列细胞内的破坏性光化学变化,包括DNA损伤,会导致皮肤过早老化,癌前变化和恶性变化以及各种光敏性反应;它也在治疗上用于治疗皮肤障碍。
紫外线C(UVC)紫外线辐射的波长在200与290nm之间。
“可商购的”意指可通过第三方供应商以适当的形式、质量和数量购买成分、组分或其他投入(例如,UV吸收剂),以可行且经济的方式用于实现基本功能(例如,在采用UV吸收剂的系统中,其中UV吸收剂用于耗散与UV光相关的能量)。
“光稳定剂(photostabilizer/photo-stabilizer)”是有助于防止UV吸收剂或UV过滤剂因暴露于UV辐射而失去有效性的化合物。一些光稳定剂有助于通过静电和范德瓦尔斯(van der Waals)相互作用在结构和几何上稳定UV吸收剂分子,使得它们不易参与化学反应。另一种类型的光稳定剂通过更快地耗散UV的能量来保护UV吸收剂过滤剂,从而减少或甚至消除化学反应的可能性。这一过程被称为能量转移,并且当UV吸收剂和光稳定剂分子交换电子时就会发生。通过这种方式,UV吸收剂可以不受干扰地发挥功能,通过吸收有害射线来保护皮肤,而光稳定剂则发挥处理所得能量的功能。
生物相容性是描述材料与活组织相容性质的术语。生物相容性材料(例如,生物相容性聚合物、生物相容性UV吸收剂、生物相容性溶剂等)不会对活组织或活系统产生毒性或免疫反应,例如当暴露于身体或体液时,无毒、无伤害性或生理反应性,并且不会引起严重的免疫排斥。
生物传感器是通过响应于分析物或分析物族的发现或存在而生成信号来测量生物系统内的生物或化学反应的化合物或装置。生成的信号通常与反应中分析物的浓度成比例。
抗氧化剂是通过特异性淬灭自由基或螯合氧化还原金属来抑制或延迟生物相关分子的氧化的化合物或物质。自由基是在生物氧化反应期间产生的。
进一步提供了用于实践本发明的方法的试剂盒。“试剂盒”意指任何包含至少一种试剂(例如本发明的pH缓冲剂)的制品(例如,包装或容器)。试剂盒可以作为用于执行本发明的方法的单元被促销、分发或出售。另外,试剂盒可以含有描述试剂盒及其使用方法的包装说明书。任何或所有试剂盒试剂都可以在保护其免受外部环境影响的容器中提供,例如在密封容器或小袋中。
上文所述的优势以及从上述描述中显而易见的优势是有效实现的。由于在不脱离本发明的范围的情况下,可以对上述说明做出某些改变,所以意图是上述描述中所含或附图中所示的所有事项应被解释为说明性的,而不是限制性的。
本申请中引用的所有参考文献在与本文一致的程度上均通过引用以其全文并入本文。
可见上文所述的优势以及从上述描述中显而易见的优势是有效实现的,并且由于在不脱离本发明的范围的情况下,可以对上述说明做出某些改变,所以意图是上述描述中所含或附图中所示的所有事项应被解释为说明性的,而不是限制性的。
还应理解的是,以下权利要求书旨在覆盖本文所述的本发明的所有总体性的和特定的特征,以及本发明范围的所有陈述,由于语言表达的问题,也可以说是落入其中。以上是本发明的描述。
Claims (42)
1.一种紫外光吸收颗粒,其包含生物相容性聚合物与可商购的UV吸收剂的组合。
2.根据权利要求1所述的紫外光吸收颗粒,其中该UV吸收剂是可商购的UV吸收剂。
3.根据权利要求1所述的紫外光吸收颗粒,其中该UV吸收剂是属于羟基苯基-s-三嗪家族的UV吸收剂。
4.根据权利要求3所述的紫外光吸收颗粒,其中该羟基苯基-s-三嗪是贝莫曲嗪醇。
5.根据权利要求1所述的紫外光吸收颗粒,其中该UV吸收剂选自由以下组成的组:2-(4,6-二苯基-1,3,5-三嗪-2-基)-5-[(己基)氧基]-苯酚、4-[[4,6-双[[4-(2-乙基己氧基-氧代甲基)苯基]氨基]-1,3,5-三嗪-2-基]氨基]苯甲酸2-乙基己基酯(乙基己基三嗪酮)、2-(2-羟基-4-甲氧基苯基)-4,6-二苯基-1,3,5-三嗪、2-(4,6-双-(2,4-二甲基苯基)-1,3,5-三嗪-2-基)-5-(辛基氧基)-苯酚、2-[4-[2-羟基-3-十三烷基氧丙基]氧基]-2-羟基苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪以及2-[4-[2-羟基-3-十二烷基氧丙基]氧基]-2-羟基苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪(400)、2-[2-羟基-4-[3-(2-乙基己基-1-氧基)-2-羟基丙基氧基]苯基]-4,6-双(2,4-二甲基苯基)-1,3,5-三嗪(405)、6-[2,6-双(2,4-二甲基苯基)-1H-1,3,5-三嗪-4-亚基]-3-(6-甲基庚氧基)环已-2,4-二烯-1-酮、2,4-双(2-羟基-4-丁基氧基苯基)-6-(2,4-双-丁基氧基苯基-1,3,5-三嗪(/>460)、异辛基2-[4-[4,6-双[(1,1’-二苯基)-4-基]-1,3,5-三嗪-2-基]-3-羟基苯氧基]丙酸酯(/>479)、2-(2’-羟基-5-甲基苯基)-5-苯并三唑、2-(2H-苯并三唑-2-基)-4-(1,1,3,3-四甲基丁基)苯酚、2-(2’-羟基-3’-叔丁基-5’-甲基苯基)-5-氯苯并三唑、2-(2-羟基-3.5-二(1,1-二甲基-苄基)-2-苯并三唑、α-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙基]-ω-羟基聚(氧代-1,2-乙二基)、α-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙基]-ω-[3-[3-(2H-苯并三唑-2-基)-5-(1,1-二甲基乙基)-4-羟基苯基]-1-氧代丙氧基]聚(氧基-1,2-乙二基)、2-(2H-苯并三唑-2-基)-4,6-双(1-甲基-1-苯基乙基)苯酚(/>900)、2-(2H-苯并三唑-2-基)-6-(1-甲基-1-苯基乙基)-4-(1,1,3,3-四甲基丁基)苯酚(928)、及其组合。
6.根据权利要求1所述的紫外光吸收颗粒,其进一步包含光稳定剂,该光稳定剂抑制该UV吸收剂的光降解,从而增加该UV吸收剂的使用寿命。
7.根据权利要求6所述的紫外光吸收颗粒,其中该光稳定剂是受阻胺。
8.根据权利要求7所述的紫外光吸收颗粒,其中该受阻胺是2,2,6,6-四甲基哌啶、2,2,6,6-四甲基哌啶的烷基化或羟胺类似物、或含有任何这些官能团的聚合物。
9.根据权利要求1所述的紫外光吸收颗粒,其中该紫外光吸收颗粒适合注射至皮肤的真皮层并且该颗粒呈如下形式:(A)聚合物颗粒、(B)分子聚集体、(C)无机纳米颗粒或微颗粒、(D)表面包覆的纳米颗粒或微颗粒、(E)核壳纳米颗粒或微颗粒、或(F)介孔纳米颗粒或微颗粒。
10.根据权利要求1所述的紫外光吸收颗粒,其与对离子浓度、pH、或葡萄糖水平敏感的可纹身生物传感器组合。
11.根据权利要求1所述的紫外光吸收颗粒,其中该聚合物是选自由以下组成的组的聚合物:聚(甲基丙烯酸甲酯)(PMMA)、聚乳酸(PLA)、聚乳酸-羟基乙酸共聚物(PLGA)、聚(二甲基硅氧烷)(PDMS)、聚乙二醇(PEG)、三聚氰胺甲醛、甲基丙烯酰胺壳聚糖。
12.根据权利要求1所述的紫外光吸收颗粒,其中该可商购的UV吸收剂是选自由以下组成的组的UV吸收剂:羟基二苯甲酮、羟基苯基-s-三嗪、和2-(2-羟基苯基)苯并三唑、苯酰胺、氨基苯甲酸、阿伏苯宗、西诺沙酯、二羟苯宗、胡莫柳酯、美拉地酯、奥克立林、桂皮酸盐、辛水杨酯、羟苯甲酮、帕蒂玛特O、恩索利唑、舒利苯酮、二氧化钛、三乙醇胺水杨酸盐、和氧化锌及其衍生物和/或组合。
13.根据权利要求1所述的紫外光吸收颗粒,其进一步包含抗氧化剂。
14.根据权利要求13所述的紫外光吸收颗粒,其中该抗氧化剂选自由以下组成的组:多酚、维生素、类胡萝卜素、受阻酚、亚磷酸盐、黑色素或其组合。
15.根据权利要求14所述的紫外光吸收颗粒,其中该多酚是选自由以下组成的组的多酚:类黄酮、羟基肉桂酸和羟基苯甲酸、单宁、姜黄素、姜酚、及其组合。
16.根据权利要求14所述的紫外光吸收颗粒,其中该维生素是选自由以下组成的组的维生素:维生素A、C、E、或其组合。
17.根据权利要求14所述的紫外光吸收颗粒,其中该类胡萝卜素是选自由以下组成的组的类胡萝卜素:β-胡萝卜素、番茄红素、或其组合。
18.根据权利要求1所述的紫外光吸收颗粒,其中该颗粒悬浮于选自由以下组成的组的生物相容性溶剂:水、醇(例如,乙醇、异丙醇、甘油、低聚乙二醇和聚乙二醇)、油类(例如,植物油/甘油三酯、香叶醇、角鲨烯等)、或其组合。
19.根据权利要求18所述的紫外光吸收颗粒,其中该生物相容性溶剂是水、乙醇、异丙醇、甘油、低聚乙二醇和聚乙二醇、植物油/甘油三酯、香叶醇、角鲨烯及其组合。
20.根据权利要求1所述的紫外光吸收颗粒,其进一步包含选自由以下组成的组的添加剂:(i)防止细菌污染的抗菌剂、(ii)稳定分散体并调整表面张力的生物相容性表面活性剂、(iii)增加黏度并降低色素沉着速率的增稠剂、(iv)促进剪切稀化的触变剂(例如二氧化硅)、(v)帮助防止墨水干燥并帮助它们粘合至针的防腐剂/粘合剂(例如聚醚、聚乙烯吡咯烷酮)、(vi)最大限度减少植入后皮肤出血的收敛剂、(vii)最大限度减少墨水植入期间疼痛的麻醉剂、及其组合。
21.根据权利要求20所述的紫外光吸收颗粒,其中该抗菌剂是醇。
22.根据权利要求21所述的紫外光吸收颗粒,其中该醇选自由以下组成的组:乙醇、异丙醇、甘油和聚乙二醇)。
23.根据权利要求20所述的紫外光吸收颗粒,其中该生物相容性表面活性剂是聚山梨醇酯、TWEEN-20、TWEEN-80或聚(乙烯醇)。
24.根据权利要求20所述的紫外光吸收颗粒,其中该增稠剂是黄原胶、聚丙烯酸酯、聚二醇或其组合。
25.根据权利要求24所述的紫外光吸收颗粒,其中该聚丙烯酸酯选自由以下组成的组:聚(丙烯酸)以及聚(丙烯酸)的共聚物。
26.根据权利要求24所述的紫外光吸收颗粒,其中该聚二醇选自由以下组成的组:聚(乙二醇)和聚丙二醇)。
27.根据权利要求20所述的紫外光吸收颗粒,其中该增稠剂是丙烯酸甲酯、甲基丙烯酸甲酯、丙烯酸乙酯、丙烯酸丙酯、丙烯酸丁酯或其组合。
28.根据权利要求1所述的紫外光吸收颗粒,其进一步包含<1.0%(v/v)比率的稳定悬浮液的TWEEN-80表面活性剂、以及以10%-30%比率添加的聚乙二醇(分子量1000)或甘油,因而该聚乙二醇或甘油可以用作抗菌剂、增稠剂、或粘合剂。
29.根据权利要求1所述的紫外光吸收颗粒,其中该颗粒在微颗粒至纳米颗粒尺寸范围内。
30.一种紫外(UV)光吸收颗粒,其包含聚(甲基丙烯酸甲酯)(PMMA)与UV吸收剂的组合。
31.根据权利要求30所述的紫外光吸收颗粒,其中该UV吸收剂是可商购的UV吸收剂。
32.根据权利要求31所述的紫外光吸收颗粒,其中该可商购的UV吸收剂选自由以下组成的组:2-羟基二苯甲酮、羟基苯基-s-三嗪、和2-(2-羟基苯基)苯并三唑、苯酰胺、氨基苯甲酸、阿伏苯宗、西诺沙酯、二羟苯宗、胡莫柳酯、美拉地酯、奥克立林、桂皮酸盐、辛水杨酯、羟苯甲酮、帕蒂玛特O、恩索利唑、舒利苯酮、二氧化钛、三乙醇胺水杨酸盐、氧化锌及其衍生物和/或组合。
33.根据权利要求30所述的紫外光吸收颗粒,其中该紫外(UV)光吸收颗粒是核壳颗粒或纳米胶囊/微胶囊,其具有在包含PMMA的壳或胶囊中包含UV吸收剂的核。
34.根据权利要求30所述的紫外光吸收颗粒,其中该UV吸收剂随机分散在PMMA基质中。
35.一种适合注射至皮肤的真皮层或皮内层的透明或几乎透明的纳米颗粒和/或微颗粒与生物相容性溶剂组合的配制品,其中这些纳米颗粒或微颗粒在UVA和UVB范围内具有高吸收性。
36.根据权利要求35所述的配制品,其进一步包含适于真皮植入的墨水或色素。
37.一种将紫外光吸收颗粒植入受试者皮肤的方法,该方法包括以下步骤:
提供包含根据权利要求1至36所述的颗粒或配制品中的任一个的组合物;
用具有所提供的组合物的微针接触皮肤;以及用该微针穿透所接触的皮肤。
38.根据权利要求37所述的植入紫外光吸收颗粒的方法,其中该微针是可溶微针。
39.根据权利要求38所述的植入紫外光吸收颗粒的方法,其中该可溶微针包含适合的选自由以下组成的组的载体:聚乙烯吡咯烷酮或聚乙烯醇及其液体预聚合物,或羧甲基纤维素、海藻糖、麦芽糖糊精、半乳糖、葡萄糖和丝的水溶液。
40.一种植入紫外光吸收颗粒的方法,该方法包括以下步骤:
提供包含根据权利要求1至36所述的颗粒或配制品中的任一个的组合物;
用无针纹身机接触皮肤,该无针纹身机配置为递送所提供的组合物与纹身墨水的组合;以及
以足够高的速度用该组合物与纹身墨水液滴的组合穿透所接触的皮肤以透入真皮。
41.一种植入紫外光吸收颗粒的方法,该方法包括以下步骤:
提供包含根据权利要求1至36所述的颗粒或配制品中的任一个的组合物;
用(电动)纹身机(旋转式或线圈式)接触皮肤,该纹身机配置为递送所提供的组合物与纹身墨水的组合;以及在足以透入真皮的条件下用该组合物与纹身墨水液滴的组合穿透所接触的皮肤。
42.根据权利要求1-36中任一项所述的紫外光吸收颗粒,其与可纹身UV传感器组合。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063071782P | 2020-08-28 | 2020-08-28 | |
US63/071,782 | 2020-08-28 | ||
PCT/US2021/047941 WO2022047151A1 (en) | 2020-08-28 | 2021-08-27 | Ultraviolet-absorptive nanoparticles and microparticles for intradermal use |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116367815A true CN116367815A (zh) | 2023-06-30 |
Family
ID=80352380
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202180070899.2A Pending CN116367815A (zh) | 2020-08-28 | 2021-08-27 | 用于皮内使用的紫外吸收纳米颗粒和微颗粒 |
Country Status (13)
Country | Link |
---|---|
US (1) | US20230320973A1 (zh) |
EP (1) | EP4203895A1 (zh) |
JP (1) | JP2023539190A (zh) |
KR (1) | KR20230058441A (zh) |
CN (1) | CN116367815A (zh) |
AU (1) | AU2021333800A1 (zh) |
BR (1) | BR112023003401A2 (zh) |
CA (1) | CA3192648A1 (zh) |
CO (1) | CO2023003363A2 (zh) |
IL (1) | IL300673A (zh) |
MX (1) | MX2023002275A (zh) |
PE (1) | PE20231033A1 (zh) |
WO (1) | WO2022047151A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114453001B (zh) * | 2022-03-10 | 2023-06-06 | 江苏理工学院 | 芳环和氰基共掺杂的氮化碳纳米片及其制备方法和应用 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4478853A (en) * | 1982-05-17 | 1984-10-23 | S. C. Johnson & Son, Inc. | Skin conditioning composition |
US5990233A (en) * | 1996-08-16 | 1999-11-23 | National Starch And Chemical Investment Holding Corporation | Rheology modifiers for use in aqueous compositions |
US5985444A (en) * | 1998-04-03 | 1999-11-16 | 3M Innovative Properties Company | Amide functional ultraviolet light absorbers for fluoropolymers |
US6352764B1 (en) * | 1999-08-09 | 2002-03-05 | 3M Innovative Properties Company | Multi-layer articles including UV-absorbing polymeric compositions |
EP1378231A1 (en) * | 2002-06-17 | 2004-01-07 | Ciba Specialty Chemicals Holding Inc. | Formulation of UV absorbers by incorporation in solid lipid nanoparticles |
WO2005120440A1 (de) * | 2004-06-08 | 2005-12-22 | Merck Patent Gmbh | Partikel, funktionalisiert mit organischen verbindungen |
BRPI0821546A2 (pt) * | 2007-12-21 | 2015-11-03 | Basf Se | composição, película plástica agrícola ou película de acondicionamento, processo para produzir um óxido metálico nanoparticulado, óxido metálico nanoparticulado, e, uso de um óxido metálico nanoparticulado |
WO2011009077A2 (en) * | 2009-07-16 | 2011-01-20 | Trustees Of Boston University | Labeled skin lesion biopsy punch and uses thereof |
JP5291729B2 (ja) * | 2011-02-07 | 2013-09-18 | 株式会社 資生堂 | 日焼け止め化粧料 |
FR2993176B1 (fr) * | 2012-07-13 | 2014-06-27 | Oreal | Composition cosmetique contenant des particules composites filtrantes de taille moyenne superieure a 0,1 micron et des particules de filtre inorganique et une phase aqueuse |
EP3056194B1 (en) * | 2013-10-09 | 2020-08-19 | Shiseido Company, Ltd. | Low-stringiness thickener and cosmetic material admixed with said thickener |
US10195294B2 (en) * | 2015-05-22 | 2019-02-05 | Logicink Corporation | Programmable bacterial tattoo |
-
2021
- 2021-08-27 BR BR112023003401A patent/BR112023003401A2/pt unknown
- 2021-08-27 MX MX2023002275A patent/MX2023002275A/es unknown
- 2021-08-27 PE PE2023000532A patent/PE20231033A1/es unknown
- 2021-08-27 KR KR1020237009939A patent/KR20230058441A/ko unknown
- 2021-08-27 US US18/042,509 patent/US20230320973A1/en active Pending
- 2021-08-27 WO PCT/US2021/047941 patent/WO2022047151A1/en unknown
- 2021-08-27 EP EP21862818.8A patent/EP4203895A1/en active Pending
- 2021-08-27 AU AU2021333800A patent/AU2021333800A1/en active Pending
- 2021-08-27 CN CN202180070899.2A patent/CN116367815A/zh active Pending
- 2021-08-27 IL IL300673A patent/IL300673A/en unknown
- 2021-08-27 JP JP2023513084A patent/JP2023539190A/ja active Pending
- 2021-08-27 CA CA3192648A patent/CA3192648A1/en active Pending
-
2023
- 2023-03-17 CO CONC2023/0003363A patent/CO2023003363A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
IL300673A (en) | 2023-04-01 |
EP4203895A1 (en) | 2023-07-05 |
MX2023002275A (es) | 2023-05-16 |
KR20230058441A (ko) | 2023-05-03 |
JP2023539190A (ja) | 2023-09-13 |
AU2021333800A1 (en) | 2023-03-23 |
PE20231033A1 (es) | 2023-07-10 |
WO2022047151A1 (en) | 2022-03-03 |
CO2023003363A2 (es) | 2023-04-17 |
CA3192648A1 (en) | 2022-03-03 |
US20230320973A1 (en) | 2023-10-12 |
BR112023003401A2 (pt) | 2023-05-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Jose et al. | Role of solid lipid nanoparticles as photoprotective agents in cosmetics | |
US20050172852A1 (en) | Variable appearance tissue markings | |
KR101715542B1 (ko) | 근적외선 (nir) 발광 물질을 함유하는 기재 | |
Damiani et al. | Nanocarriers and microcarriers for enhancing the UV protection of sunscreens: an overview | |
US20140161851A1 (en) | Cosmetic Compositions With Near Infra-Red (NIR) Light - Emitting Material And Methods Therefor | |
ES2757776T3 (es) | Sistema de nanopartículas que comprende aceite y filtro de UV | |
KR20150092311A (ko) | 근적외선 (nir) 발광 물질을 함유하는 화장품 조성물 및 그를 위한 방법 | |
CN106038347A (zh) | 防晒剂组合物 | |
BHATTACHARJEE et al. | A comparison of Natural and Synthetic Sunscreen Agents: A Review. | |
KR20150092312A (ko) | 근적외선 (nir) 발광 물질을 함유하는 화장품 조성물 및 그를 위한 방법 | |
Grumezescu | Nanobiomaterials in Galenic formulations and cosmetics: Applications of nanobiomaterials | |
US20230320973A1 (en) | Ultraviolet-absorptive nanoparticles and microparticles for intradermal use | |
US20130177616A1 (en) | Nanostructured sun protection agent and process | |
Rajasekar et al. | Recent developments in sunscreens based on chromophore compounds and nanoparticles | |
Wawrzynczak et al. | Nanosunscreens: From nanoencapsulated to nanosized cosmetic active forms | |
KR102269990B1 (ko) | 자외선 차단용 복합구조체 및 이의 제조방법 | |
US20240173241A1 (en) | Multistable Photochromic Pigments For Intradermal Use | |
Yadav et al. | Sunscreens | |
KR20130109653A (ko) | 자외선 차단용 조성물 및 그의 용도 | |
EP4066900A1 (en) | Ink for temporary tattoos and process for producing it | |
Zhang et al. | Thermosensitive ZnO-PMMA/PEG microgels: A smart sunscreen with adapting SPF to ambient temperature fluctuations | |
Sristi et al. | 11 Nanoparticles mediated drug-delivery system | |
Hewitt | New and emerging sunscreen technologies | |
CN117297989A (zh) | 一种ros响应型负载光甘草啶介孔二氧化硅包覆二氧化钛美白的纳米粒的制备方法与应用 | |
Sheikh et al. | Nanoparticles mediated drug-delivery system in cosmetics |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40096639 Country of ref document: HK |