CN115025082A - 齿阿米素在制备黑色素生成诱导剂中的应用 - Google Patents
齿阿米素在制备黑色素生成诱导剂中的应用 Download PDFInfo
- Publication number
- CN115025082A CN115025082A CN202210689711.9A CN202210689711A CN115025082A CN 115025082 A CN115025082 A CN 115025082A CN 202210689711 A CN202210689711 A CN 202210689711A CN 115025082 A CN115025082 A CN 115025082A
- Authority
- CN
- China
- Prior art keywords
- melanin
- amicin
- cells
- dental
- odontamicin
- 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
- 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 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000000411 inducer Substances 0.000 title claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 28
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 claims description 30
- 208000017520 skin disease Diseases 0.000 claims description 20
- 206010048768 Dermatosis Diseases 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 11
- 208000012641 Pigmentation disease Diseases 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 7
- -1 bacteriostats Substances 0.000 claims description 5
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 230000000475 sunscreen effect Effects 0.000 claims description 3
- 239000000516 sunscreening agent Substances 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 2
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000375 suspending agent Substances 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims 1
- 239000000872 buffer Substances 0.000 claims 1
- 239000007884 disintegrant Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 52
- 210000004027 cell Anatomy 0.000 abstract description 41
- 230000008099 melanin synthesis Effects 0.000 abstract description 36
- 210000002780 melanosome Anatomy 0.000 abstract description 31
- 108090000623 proteins and genes Proteins 0.000 abstract description 15
- 239000000049 pigment Substances 0.000 abstract description 14
- 210000003491 skin Anatomy 0.000 abstract description 12
- 102000004169 proteins and genes Human genes 0.000 abstract description 11
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000001939 inductive effect Effects 0.000 abstract description 4
- 230000026731 phosphorylation Effects 0.000 abstract description 4
- 238000006366 phosphorylation reaction Methods 0.000 abstract description 4
- 102000014914 Carrier Proteins Human genes 0.000 abstract description 3
- 108091008324 binding proteins Proteins 0.000 abstract description 3
- 238000004166 bioassay Methods 0.000 abstract description 3
- 230000004936 stimulating effect Effects 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 230000001419 dependent effect Effects 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 230000037361 pathway Effects 0.000 abstract description 2
- 102000003425 Tyrosinase Human genes 0.000 description 22
- 108060008724 Tyrosinase Proteins 0.000 description 22
- 201000001441 melanoma Diseases 0.000 description 19
- 230000014509 gene expression Effects 0.000 description 18
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 13
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 13
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 12
- 210000002752 melanocyte Anatomy 0.000 description 12
- 229940043437 protein kinase A inhibitor Drugs 0.000 description 11
- 239000012656 protein kinase A inhibitor Substances 0.000 description 10
- 108010065251 protein kinase modulator Proteins 0.000 description 10
- 108010050345 Microphthalmia-Associated Transcription Factor Proteins 0.000 description 9
- 102000013760 Microphthalmia-Associated Transcription Factor Human genes 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000036564 melanin content Effects 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 description 7
- 102100022430 Melanocyte protein PMEL Human genes 0.000 description 7
- 102000006581 rab27 GTP-Binding Proteins Human genes 0.000 description 7
- 108010033990 rab27 GTP-Binding Proteins Proteins 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 6
- 102100026158 Melanophilin Human genes 0.000 description 5
- 101710158003 Melanophilin Proteins 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000019612 pigmentation Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 4
- 101150006914 TRP1 gene Proteins 0.000 description 4
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 4
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 4
- 229960004705 kojic acid Drugs 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 229910052709 silver Inorganic materials 0.000 description 4
- 239000004332 silver Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 3
- AHMIDUVKSGCHAU-UHFFFAOYSA-N Dopaquinone Natural products OC(=O)C(N)CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 101000583031 Homo sapiens Unconventional myosin-Va Proteins 0.000 description 3
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 3
- AHMIDUVKSGCHAU-LURJTMIESA-N L-dopaquinone Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-LURJTMIESA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 102100030409 Unconventional myosin-Va Human genes 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000003061 melanogenesis Effects 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000003367 Hypopigmentation Diseases 0.000 description 2
- 101710093778 L-dopachrome tautomerase Proteins 0.000 description 2
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 2
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 2
- 101710173693 Short transient receptor potential channel 1 Proteins 0.000 description 2
- 101710173694 Short transient receptor potential channel 2 Proteins 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 210000003780 hair follicle Anatomy 0.000 description 2
- 230000003425 hypopigmentation Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000003711 photoprotective effect Effects 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- NZVQLVGOZRELTG-UHFFFAOYSA-N visnagin Chemical compound O1C(C)=CC(=O)C2=C1C=C1OC=CC1=C2OC NZVQLVGOZRELTG-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000905376 Actaea dahurica Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010001557 Albinism Diseases 0.000 description 1
- 244000153158 Ammi visnaga Species 0.000 description 1
- 235000010585 Ammi visnaga Nutrition 0.000 description 1
- 241000208173 Apiaceae Species 0.000 description 1
- 101100076252 Caenorhabditis elegans mdh-2 gene Proteins 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 241000256113 Culicidae Species 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- 102000010638 Kinesin Human genes 0.000 description 1
- 108010063296 Kinesin Proteins 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 1
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 241000218201 Ranunculaceae Species 0.000 description 1
- 206010038419 Renal colic Diseases 0.000 description 1
- 206010040825 Skin depigmentation Diseases 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 206010062225 Urinary tract pain Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 108010051081 dopachrome isomerase Proteins 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003101 melanogenic effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000000933 neural crest Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 230000037370 skin discoloration Effects 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 108010014402 tyrosinase-related protein-1 Proteins 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/10—Preparations for permanently dyeing the hair
-
- 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
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Birds (AREA)
- Toxicology (AREA)
- Cosmetics (AREA)
Abstract
本发明属于医药技术领域,提供了齿阿米素在制备黑色素生成诱导剂中的应用,本发明对黑色素生成相关蛋白进行了多种生物学测定,确认了齿阿米素在刺激黑色素合成和黑素体转运中的作用,齿阿米素可以通过诱导PKA依赖性途径进行cAMP反应组件结合蛋白(CREB)的磷酸化来刺激黑色素的合成、黑素体的运输以及细胞中树突结构的形成,并增加细胞内cAMP的水平,可以将齿阿米素用作治疗色素性皮肤的药物的活性成分,并且齿阿米素是天然产物,药物的副作用小。
Description
技术领域
本发明涉及医药技术领域,更具体地,涉及齿阿米素在制备黑色素生成诱导剂中的应用。
背景技术
人类皮肤颜色的最大主要决定因素是黑色素细胞产生的黑色素的数量,黑色素细胞来源于神经嵴,并在胚胎发育过程中迁移到色素产生部位。黑色素通常存在于皮肤、眼睛、毛囊和大脑的黑质中,在皮肤中,黑色素细胞位于表皮和毛囊上皮的基底层。黑色素颗粒均匀分布在皮肤细胞中,以吸收来自太阳的紫外线并至少部分保护皮肤以免受有害射线、活性氧和致癌因子的伤害。
黑色素的形成过程是一系列复杂的生理生化过程,其中包括黑色素细胞的迁移与分化,黑素体的形成与成熟,黑色素的生成、运输以及代谢。任何影响这种复杂反应的因素都有可能导致皮肤色素疾病,并且已知黑色素的生成涉及数百种不同的基因。
黑色素的合成发生在黑色素细胞中,在黑色素细胞内部,酪氨酸是黑色素合成的重要底物,通过激活酪氨酸酶产生黑色素。酪氨酸酶是一种铜酶,它可以直接利用分子氧使得酪氨酸反应生成多巴,多巴进一步转化为多巴醌,然后形成许多中间产物,最后形成吲哚醌,聚合形成黑色素,更常见的产物是真黑素呈棕色,在半胱氨酸存在的情况下,可以形成褐黑素,呈红色或黄色。
色素沉着的表皮黑色素细胞和黑色素瘤细胞的形态学特征表明,成熟的、完全色素沉着的黑素体(III期和IV期)由非色素沉着的前体(I期和II期)发育而来,这里统称为前黑素体。黑色素的合成和储存发生在称为黑素体的独特溶酶体相关的细胞器中,这些细胞器通过复杂的调节机制控制黑色素的产生。维持黑素体腔内离子环境和pH值对于主要的黑素生成酶的正常功能至关重要。黑素细胞特异性糖蛋白(Pmel17)在前黑素体的管腔中富集,含有黑色素的成熟黑素体被三联蛋白复合物的肌动蛋白丝捕获,成熟黑素体由三个亚基组成,包括Rab27a、Melanophilin(Mlph)和Myosin Va(Myo5a)。经典的形态学研究表明,黑素体的成熟过程有四个不同的阶段,涉及多种酶和结构蛋白。Pmel17在黑色素中间体的聚合或稳定化过程中发挥作用,以及保护黑色素细胞免受有毒黑色素中间体的侵害。黑素体通过结合微管蛋白和驱动蛋白而受到控制,并沿着微管从核周区域向黑色素细胞树突尖端定向移动,再转移到角质形成细胞,从而在皮肤实现色素沉着和光保护。
色素性皮肤病广泛存在,可以涉及许多皮肤部位,也就是弥漫性的;或者可以仅聚集在某些皮肤部位,也就是局灶性的。色素异常包括色素减弱、色素脱失(头发灰白,白癜风等)和色素沉着过度(老年斑,黄褐斑,痤疮病变等),色素缺乏时,色素减少,脱色时,色素完全消退,皮肤呈白色。黑色素的合成与一些皮肤病,如白化病和白癜风等密切相关,这类疾病的特征是是皮肤变色或脱色,受影响的皮肤斑块变白,皮肤上的毛发也可能会变白,可能是由于表皮中的黑色素减少、黑色素细胞功能衰竭或减少所致,色素性皮肤病一直困扰着人们的生活,因此亟需开发一种色素性皮肤病的治疗药物。
发明内容
本发明旨在至少解决上述现有技术中存在的技术问题之一。为此,本发明提出齿阿米素在制备黑色素生成诱导剂中的应用,本发明发现齿阿米素具有刺激黑色素生成的生物活性,能够刺激酪氨酸酶活性以及黑素体的合成和转运。
本发明的第一方面提供齿阿米素在制备黑色素生成诱导剂中的应用。
齿阿米素(Visnagin),是一种呋喃色酮衍生物,又名阿密茴素、甲氧呋豆素等,齿阿米素的分子结构如下式(Ⅰ)所示。齿阿米素为伞形科植物阿米芹(Ammi visngaa L)和毛茛科植物兴安升麻[Cimicifuga dahurica(Turz.)Maxim.]等中草药植物的根茎提取物,这些植物通常分布于欧洲、埃及和土耳其等中东国家以及摩洛哥等北非国家。
齿阿米素很久以前就被用于传统医学,如欧洲民间通常用齿阿米素医治尿泌系统疾患,在现代医学中经常用作治疗支气管哮喘、解痉药和治疗冠状循环疾病,如狭心症、冠状血栓症等多种疾病,并也用作抗氧化剂,抗菌剂,杀蚊子幼虫等。齿阿米素还可治疗低血压、心绞痛、抗痉挛、抗凝血、扩张血管,具有神经保护和抗炎等药理活性。齿阿米素已在中东地区用于缓解肾绞痛和尿路疼痛,通过与线粒体苹果酸脱氢酶(MDH2)结合来降低阿霉素对心脏的毒性。在动物研究中,齿阿米素可作为血管扩张剂,并通过抑制钙流入细胞来降低血压,此外,还通过延长晶体成核的诱导时间来防止肾结石的形成。但是齿阿米素在调节黑色素合成、黑素体转运中的药理作用、治疗色素性皮肤病的具体应用尚未有描述。在本发明中,研究了齿阿米素对黑色素合成、黑素体转运和黑素细胞中相关蛋白的影响,证实了齿阿米素具有诱导黑色素合成的活性,可应用于制备治疗色素性皮肤病的药物中。
本发明的第二方面提供齿阿米素在制备治疗色素性皮肤病药物中的应用。
优选地,所述色素性皮肤病为色素沉着障碍皮肤病。
本发明的第三方面提供一种治疗色素性皮肤病的药物,包括上述齿阿米素。
优选地,所述药物还包括药学上可接受的辅料。
优选地,所述药学上可接受的辅料包括溶剂、填充剂、润滑剂、崩解剂、缓冲剂、助溶剂、抗氧剂、抑菌剂、乳化剂、粘合剂或助悬剂中的一种或几种。
优选地,所述药物的剂型为软膏剂或凝胶剂。
优选地,所述药物的剂型为软膏剂时,所述辅料为脂溶性辅料。脂溶性辅料能有助于更好地经皮吸收。
优选地,所述脂溶性辅料为甘油和凡士林。
优选地,所述药物的剂型为凝胶剂,所述辅料为卡波姆。
本发明第四方面提供一种治疗色素性皮肤病的药物的制备方法
本发明保护上述治疗色素性皮肤病的药物的制备方法,包括如下步骤:将各原料组分混合搅拌,即得。
本发明第五方面提供一种乌发产品,包括上述齿阿米素。
本发明第六方面提供一种防晒产品,包括上述齿阿米素。
相对于现有技术,本发明的有益效果如下:
(1)本发明研究了齿阿米素对黑色素合成、黑素体转运和黑素细胞中相关蛋白的影响进行了多种生物学测定,包括黑色素含量测定、酪氨酸酶活性检测、cAMP活性检测、荧光素酶活性分析、蛋白质免疫印迹分析和Fontana-Masson染色技术等,结果证明了齿阿米素在刺激黑色素合成和黑素体转运中的作用,通过多种生物学测定证实,齿阿米素可以通过诱导PKA依赖性途径进行环磷酸腺苷(cAMP)反应组件结合蛋白(CREB)的磷酸化以刺激黑色素的合成、黑素体转运以及细胞中树突结构的形成,并提高细胞内cAMP的水平;
(2)本发明表明齿阿米素具有诱导黑色素合成的活性,可以利用齿阿米素作为治疗色素性皮肤的药物的活性成分,并且齿阿米素是天然产物,药物的副作用小。
附图说明
图1为齿阿米素对B16F10黑色素瘤细胞活力、细胞毒性、黑色素含量和酪氨酸酶活性的影响;
图2为齿阿米素对B16F10黑色素瘤细胞黑色素含量和酪氨酸酶活性的影响;
图3为齿阿米素在黑色素减退条件下对B16F10黑色素瘤细胞黑色素含量和酪氨酸酶活性的影响;
图4为不同浓度的齿阿米素对黑素体合成和黑素体迁移的影响;
图5为齿阿米素对黑素体运输控制相关的蛋白的调控作用;
图6为不同浓度的齿阿米素对MITF活性的影响;
图7为不同浓度的齿阿米素对黑色素生成相关基因表达的影响;
图8为不同浓度的齿阿米素对黑色素生成相关基因表达的影响;
图9为齿阿米素对B16F10黑色素瘤细胞cAMP/CREB信号通路的影响;
图10为PKA抑制剂H89对B16F10黑色素瘤细胞活力的影响;
图11为PKA抑制剂H89对B16F10黑色素瘤细胞的颜色的影响;
图12为PKA抑制剂H89对齿阿米素介导的酪氨酸酶活性的影响;
图13为PKA抑制剂H89对齿阿米素介导的B16F10黑色素瘤细胞黑色素含量的影响;
图14为PKA抑制剂H89对树突状结构的产生和黑素体的运输的影响;
图15为PKA抑制剂H89对齿阿米素诱导的磷酸化CREB表达的影响;
图16为齿阿米素激活的cAMP/CREB信号通路对于细胞中的黑色素合成的必要性。
具体实施方式
为了让本领域技术人员更加清楚明白本发明所述技术方案,现列举以下实施例进行说明。需要指出的是,以下实施例对本发明要求的保护范围不构成限制作用。
以下实施例中所用的原料、试剂或装置如无特殊说明,均可从常规商业途径得到,或者可以通过现有已知方法得到。
实施例1
通过使用噻唑蓝(MTT)测定法和乳酸脱氢酶(LDH)检测法来探究齿阿米素对B16F10黑素瘤细胞的细胞毒性作用。实验中,所有Control组为不作任何药物处理的空白对照组。如图1所示,图1A为不同浓度的齿阿米素对B16F10黑色素瘤细胞的细胞活力影响;图1B为不同齿阿米素对B16F10黑色素瘤细胞的细胞毒性影响,结果显示,以50μM、100μM和150μM的齿阿米素处理48h后,B16F10黑素瘤细胞中没有明显的细胞毒性。
实施例2
选择50μM、100μM和150μM三种浓度的齿阿米素来探究不同浓度的齿阿米素对细胞中黑色素含量的影响,酪氨酸酶在将酪氨酸氧化为多巴醌(多巴醌是黑色素合成的底物)中起着重要作用,因此,本发明还评估了齿阿米素对细胞中酪氨酸酶活性的影响。如图2所示,图2A为不同浓度的齿阿米素对细胞中黑色素含量的影响,图2B为不同浓度的齿阿米素对细胞中黑色素含量的影响,结果显示,添加了毛喉素(FSK,黑色素生成诱导剂)的阳性对照组细胞中的黑色素含量增加,同时齿阿米素处理后细胞内黑色素含量以剂量依赖的方式增加。如图2C所示,图2C为不同浓度的齿阿米素对细胞中酪氨酸酶活性的影响,图中结果显示,在齿阿米素处理后,酪氨酸酶活性以剂量依赖性方式显着增加,表明齿阿米素具有刺激细胞中黑色素生成的活性。
实施例3
曲酸是一种被广泛采用的黑色素生成抑制剂,本发明利用曲酸减少黑色素的合成并模拟色素减退的情况,并研究齿阿米素在黑色素减退条件下对黑色素合成的作用。如图3所示,图3A为齿阿米素在黑色素减退条件下对黑色素合成的影响,图3B为齿阿米素在黑色素减退条件下对酪氨酸酶活性的影响,在曲酸的存在下,黑色素含量水平显着降低,但是添加齿阿米素之后,黑色素的含量均较对照组(Control)高,表明齿阿米素有助于恢复色素沉着,并增加色素含量已经减少的细胞中的酪氨酸酶活性,证实了齿阿米素在黑色素减退条件下的促进黑色素合成的潜在作用。
实施例4
黑色素是银亲和性物质,能够结合银离子并将其还原成金属银,利用黑色素的该特性来进行可视化处理,具体为:在利用齿阿米素对B16F10黑素瘤细胞细胞进行处理后,利用Fontana-Masson染色技术对B16F10黑素瘤细胞染色。如图4所示,其中图4(1)为对照组,图4(2)为利用50μM的齿阿米素处理的细胞情况,图4(3)为利用100μM的齿阿米素处理的细胞情况,图4(4)为利用150μM的齿阿米素处理的细胞情况,结果显示随着齿阿米素的浓度增加,观察到细胞树枝状尖端处伸长,树枝状晶体增加,黑色素的生成增加,黑色素更多地聚集在尖端树突处,说明齿阿米素能够刺激黑素体合成,并刺激了黑素体的迁移。
实施例5
为了进一步阐明齿阿米素对黑素体运输的调控,研究了几种与黑素体运输控制相关的关键蛋白。PMEL17是参与黑素体形成的膜蛋白;转运相关蛋白Rab27a和Myosin VA是基于肌动蛋白的黑素体转运的关键调节剂。如图5所示,图5A为齿阿米素对PMEL17、Tubulin的调控作用,图5B为齿阿米素对Myosin VA、Melanophilin、Rab27a的调控作用,蛋白免疫印迹结果证实齿阿米素增加了PMEL17、转运相关蛋白Rab27a、Melanophilin和Myosin VA的表达,这表明在齿阿米素处理后,黑素体及其转运相关蛋白的数量增加。
实施例6
在B16F10黑色素瘤细胞中酪氨酸酶、酪氨酸酶相关蛋白1(TRP-1)和酪氨酸酶相关蛋白2(TRP-2)参与了黑色素生成的酶促级联反应,而MITF是主要转录因子,它控制以上的几种酶的表达。为了探索齿阿米素诱导黑色素生成过程中的潜在作用机制,进行了荧光素酶测定以验证齿阿米素是否能够激活MITF-荧光素酶的基因的表达。用双荧光素酶活性实验检测启动子水平,结果如图6所示,齿阿米素以剂量依赖的方式显着地诱导提高MITF转录活性。用QPCR实验检测mRNA的表达水平,用蛋白免疫印迹方法检测蛋白表达水平,结果分别如图7和图8所示,结果表明,在齿阿米素处理24小时后,促进了黑色素生成相关基因(包括MITF、酪氨酸酶(Tyrosinase)、Trp-1、Trp-2)的表达。因此,以上结果证明了齿阿米素可以显着地增强MITF的表达,并伴随在黑色素生成过程中的关键蛋白表达的上调。
实施例7
在证明齿阿米素能够诱导MITF、酪氨酸酶、TRP-1和TRP-2的蛋白表达后,本发明还进一步研究了齿阿米素促进黑素生成的分子机制。如图9所示,图9A为使用高剂量(150μM)齿阿米素对环磷酸腺苷反应组件结合蛋白(CREB)的磷酸化过程的影响,结果显示,采用高浓度(150μM)齿阿米素对B16F10黑素瘤细胞进行处理,在齿阿米素处理后15分钟至30分钟内,齿阿米素引起了CREB的快速磷酸化。此外,图9B为不同浓度的齿阿米素对细胞内环腺苷酸(cAMP)活性水平的影响,在齿阿米素处理30分钟后,细胞内环腺苷酸(cAMP)活性水平也得到提高。
实施例8
为了进一步研究cAMP/CREB信号途径在B16F10细胞中由齿阿米素诱导黑色素合成的过程,采用了PKA抑制剂H89进行相关测试。测试前,先采用5μM H89处理B16F10黑素瘤细胞48小时,如图10所示,在细胞中未显示出明显的细胞毒性作用,因此该浓度用于所有后续测试。首先,B16F10黑素瘤细胞用H89(5μM)预处理30分钟,然后再暴露在指定浓度的齿阿米素中48小时。通过观察图11中B16F10中的颜色变化以及图13中黑色素水平的定量可知,H89有效地减少了齿阿米素处理过的细胞中的黑色素含量。由图12可知,H89还抑制了齿阿米素介导的酪氨酸酶活性,这是黑色素生成过程中的关键步骤。此外,由图14(1)-(4)可知,PKA抑制剂抑制了树突状结构的产生和黑素体的运输,因此以上结果表明了PKA信号转导途径对于齿阿米素诱导的黑色素生成过程中起到关键作用。
实施例9
为了确定齿阿米素激活的cAMP/CREB信号通路对于细胞中的黑色素合成是否必不可少,因此在添加齿阿米素之前,先将B16F10黑素瘤细胞与5μM H89一起孵育30分钟,然后通过蛋白质免疫印迹方法分析磷酸化CREB(p-CREB)和总CREB的水平。由图15可知,结果显示,当H89存在时,齿阿米素诱导的磷酸化CREB表达显着下调,而总CREB的表达没有变化,表明H89抑制了齿阿米素诱导的cAMP/CREB信号通路。由图16可知,图16A为PKA抑制剂H89对MITF、酪氨酸酶、Trp-1、Trp-2、Rab27a表达的影响,图16B为PKA抑制剂H89对MyosinVA、Melanophilin、Pmel17、Rab27a表达的影响,加入PKA抑制剂H89时,MITF、酪氨酸酶、Trp-1、Trp-2、Rab27a、Melanophilin、MyosinVA和Pmel17蛋白表达水平均被抑制。综上所述,本发明的研究结果表明,H89减少了齿阿米素诱导的各种影响黑色素合成的刺激作用。
本发明证明了齿阿米素在调节黑色素细胞中黑色素合成的作用;证实了齿阿米素诱导黑色素生成,增加了黑色素的含量以及酪氨酸酶活性;在含有曲酸的条件下,能够有效恢复色素水平、荧光素酶活性、MITF、酪氨酸酶、Trp-1和Trp-2等调节黑色素合成的关键蛋白的表达水平,齿阿米素诱导黑素体转运,这对于色素沉着起着重要作用。
齿阿米素可促进黑色素的合成,可用于治疗非遗传性色素性皮肤病,帮助色素沉着障碍患者恢复色素沉着,而且齿阿米素作为天然成分,还可以减少药物的副作用,另外,还可以将齿阿米素用作光保护的组分用于防晒产品的制备中,不会对皮肤造成损伤,或用作乌发产品的主要活性组分,如洗发水、护发素以及染发剂等。
应用例
一种治疗色素性皮肤病的药物,包括齿阿米素,为凝胶剂型。
上述治疗色素性皮肤病的药物的制备方法,包括如下步骤:
按重量百分比制备为重量分数为1%的齿阿米素预先溶解在40mL的2-丙醇中,然后用水和丙二醇将溶液补足至100mL(水:2-丙醇:丙二醇=2:2:1),然后将纤维素的羟基衍生物(Natrosol,1g)、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯(重量分数分别为0.08%和0.02%)一起添加,搅拌至完全水合(约24小时),即制得治疗色素性皮肤病的药物。
Claims (10)
1.齿阿米素在制备黑色素生成诱导剂中的应用。
2.齿阿米素在制备治疗色素性皮肤病药物中的应用。
3.根据权利要求2所述的应用,其特征在于,所述色素性皮肤病为色素沉着障碍皮肤病。
4.一种治疗色素性皮肤病的药物,其特征在于,包括所述齿阿米素。
5.根据权利要求4所述的药物,其特征在于,所述药物还包括药学上可接受的辅料。
6.根据权利要求5所述的药物,其特征在于,所述药学上可接受的辅料包括溶剂、填充剂、润滑剂、崩解剂、缓冲剂、助溶剂、抗氧剂、抑菌剂、乳化剂、粘合剂或助悬剂中的一种或几种。
7.根据权利要求4所述的药物,其特征在于,所述药物的剂型为软膏剂或凝胶剂。
8.权利要求4-7任一项所述药物的制备方法,其特征在于,包括如下步骤:将各原料组分混合搅拌,即得。
9.一种乌发产品,其特征在于,包括所述齿阿米素。
10.一种防晒产品,其特征在于,包括所述齿阿米素。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210689711.9A CN115025082A (zh) | 2022-06-17 | 2022-06-17 | 齿阿米素在制备黑色素生成诱导剂中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210689711.9A CN115025082A (zh) | 2022-06-17 | 2022-06-17 | 齿阿米素在制备黑色素生成诱导剂中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115025082A true CN115025082A (zh) | 2022-09-09 |
Family
ID=83124766
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210689711.9A Pending CN115025082A (zh) | 2022-06-17 | 2022-06-17 | 齿阿米素在制备黑色素生成诱导剂中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115025082A (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2574660A1 (fr) * | 1984-12-18 | 1986-06-20 | Oreal | Composition cosmetique accelerant le bronzage a base de furochromones |
-
2022
- 2022-06-17 CN CN202210689711.9A patent/CN115025082A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2574660A1 (fr) * | 1984-12-18 | 1986-06-20 | Oreal | Composition cosmetique accelerant le bronzage a base de furochromones |
Non-Patent Citations (2)
Title |
---|
JUDITH S. KINLEY ET AL.: "Quantitative Assessment of Epidermal Melanogenesis in C3H/Tif hr/hr Mice Treated with Topical Furocoumarins and UVA Radiation", 《JOURNAL OF INVESTIGATIVE DERMATOLOGY》, vol. 103, no. 1, pages 103 - 103 * |
洪巧瑜等: "外来植物药阿米芹的中药药性探讨", 《中华中医药杂志》, vol. 37, no. 4, pages 2284 - 2288 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2503454C1 (ru) | Ингибитор гепараназной активности | |
Park et al. | Aromatic-turmerone inhibits α-MSH and IBMX-induced melanogenesis by inactivating CREB and MITF signaling pathways | |
Hu et al. | The melanogenic effects and underlying mechanism of paeoniflorin in human melanocytes and vitiligo mice | |
CN109069473A (zh) | 用于亮肤和减少色素沉着过度的组合物和方法 | |
US10695428B2 (en) | Use of a photosensitive agent capable of producing reactive oxygen species in the production of a drug for the photodynamic therapy of a disease related to stem cells, in vitro use, and pharmaceutical composition | |
CN107260612B (zh) | 祛除黄褐斑组合物、应用、复合制剂及制备方法 | |
KR101900065B1 (ko) | 프로텍틴 dx를 유효성분으로 포함하는 피부 노화 예방 또는 치료용 조성물 및 그의 용도 | |
CN115025082A (zh) | 齿阿米素在制备黑色素生成诱导剂中的应用 | |
Cho et al. | Photochemical reaction to increase melanogenesis using Buddleja officinalis and blue light-emitting diode irradiation in B16F10 | |
EP1249237B1 (en) | Topical cosmetic and pharmaceutical composition comprising specific alkoxylated diester of fumaric acid | |
US7763263B2 (en) | Skin external agents and drugs | |
US20060153782A1 (en) | Skin photoageing and actinic damage treatment | |
EP2772255B1 (en) | Composition comprising syringaresinol for improving the skin | |
KR101208013B1 (ko) | 참바늘버섯 균사체 추출물을 함유하는 피부 외용제 조성물 | |
EP3218507B1 (en) | Methods and compositions for enhancing skin pigmentation | |
CN111643717B (zh) | 用于色素性皮肤病的医用敷料及其制备方法 | |
WO2004045573A1 (en) | Composition for skin whitening containing n-acetylophytosphingosine | |
KR101769545B1 (ko) | 다프닌을 포함하는 상처 치료용 조성물 및 그의 용도 | |
KR101301012B1 (ko) | 마테 발효물을 함유하는 피부 외용제 조성물 | |
Hong et al. | Antimelanogenic chemicals with in vivo efficacy against skin pigmentation in guinea pigs | |
JPH05509291A (ja) | フェニルアミン系脱色素、抗黒色腫剤 | |
TWI605832B (zh) | Plant extract composition for desalinating skin and reducing melanin, pharmaceuticals and uses thereof | |
KR102626704B1 (ko) | 장미꽃잎 추출물을 유효성분으로 포함하는 발모 촉진용 조성물 | |
KR101056656B1 (ko) | 신경 전달 물질 분비 억제를 통한 피부 미백 화장료 조성물 | |
CN118178243A (zh) | 包含半甘草异黄酮作为有效成分的皮肤美白用组合物及其应用 |
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 |