JP7403152B2 - 生分解可能な抗菌性スキャフォールドとしての一酸化窒素放出性ポリアミノグリコシドおよびそれに関する方法背景 - Google Patents
生分解可能な抗菌性スキャフォールドとしての一酸化窒素放出性ポリアミノグリコシドおよびそれに関する方法背景 Download PDFInfo
- Publication number
- JP7403152B2 JP7403152B2 JP2019553558A JP2019553558A JP7403152B2 JP 7403152 B2 JP7403152 B2 JP 7403152B2 JP 2019553558 A JP2019553558 A JP 2019553558A JP 2019553558 A JP2019553558 A JP 2019553558A JP 7403152 B2 JP7403152 B2 JP 7403152B2
- Authority
- JP
- Japan
- Prior art keywords
- hyperbranched
- nitric oxide
- aminoglycoside
- polyaminoglycoside
- hyperbranched polyaminoglycoside
- 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.)
- Active
Links
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title claims description 508
- 238000000034 method Methods 0.000 title claims description 57
- 230000000845 anti-microbial effect Effects 0.000 title description 15
- 229940126575 aminoglycoside Drugs 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 72
- 239000002840 nitric oxide donor Substances 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 28
- 230000001580 bacterial effect Effects 0.000 claims description 24
- 229920000570 polyether Polymers 0.000 claims description 24
- 230000000379 polymerizing effect Effects 0.000 claims description 20
- QJSFZHSTNBFQKU-UHFFFAOYSA-N imino(dioxido)azanium Chemical compound [O-][N+]([O-])=N QJSFZHSTNBFQKU-UHFFFAOYSA-N 0.000 claims description 18
- 230000000813 microbial effect Effects 0.000 claims description 18
- 241000194019 Streptococcus mutans Species 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 241000606749 Aggregatibacter actinomycetemcomitans Species 0.000 claims description 14
- 230000018537 nitric oxide storage Effects 0.000 claims description 14
- 241000605862 Porphyromonas gingivalis Species 0.000 claims description 13
- 230000009467 reduction Effects 0.000 claims description 12
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 11
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 239000003431 cross linking reagent Substances 0.000 claims description 5
- 238000011109 contamination Methods 0.000 claims description 4
- 230000003068 static effect Effects 0.000 claims description 4
- 231100000747 viability assay Toxicity 0.000 claims description 4
- 238000003026 viability measurement method Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 6
- 241000185992 Rhizobium viscosum Species 0.000 claims 1
- -1 R 9 Chemical compound 0.000 description 37
- 125000004432 carbon atom Chemical group C* 0.000 description 37
- 125000004429 atom Chemical group 0.000 description 34
- 241000894006 Bacteria Species 0.000 description 29
- 239000003795 chemical substances by application Substances 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 26
- 125000005842 heteroatom Chemical group 0.000 description 26
- 230000000844 anti-bacterial effect Effects 0.000 description 25
- 125000003118 aryl group Chemical group 0.000 description 24
- 125000001072 heteroaryl group Chemical group 0.000 description 23
- 125000000623 heterocyclic group Chemical group 0.000 description 23
- 229960000318 kanamycin Drugs 0.000 description 23
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 23
- 229930182823 kanamycin A Natural products 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 23
- 229930027917 kanamycin Natural products 0.000 description 22
- 229930182566 Gentamicin Natural products 0.000 description 21
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 21
- 229960002518 gentamicin Drugs 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 150000003335 secondary amines Chemical class 0.000 description 20
- 229930193140 Neomycin Natural products 0.000 description 19
- 244000005700 microbiome Species 0.000 description 19
- 229960004927 neomycin Drugs 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
- 201000010099 disease Diseases 0.000 description 17
- 125000002947 alkylene group Chemical group 0.000 description 16
- 230000006378 damage Effects 0.000 description 14
- 244000052769 pathogen Species 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 10
- 241000186044 Actinomyces viscosus Species 0.000 description 10
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 10
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical group C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 8
- 101150065749 Churc1 gene Proteins 0.000 description 8
- 102100038239 Protein Churchill Human genes 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 description 8
- 210000002950 fibroblast Anatomy 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- 210000000214 mouth Anatomy 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 210000000170 cell membrane Anatomy 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 208000002925 dental caries Diseases 0.000 description 7
- 125000004386 diacrylate group Chemical group 0.000 description 7
- 229920000587 hyperbranched polymer Polymers 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 238000006116 polymerization reaction Methods 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 230000001988 toxicity Effects 0.000 description 7
- 231100000419 toxicity Toxicity 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- PTSUYDXEEKDBQU-UHFFFAOYSA-N (6'-acetyloxy-5,6-diamino-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC(N)=C(N)C=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 PTSUYDXEEKDBQU-UHFFFAOYSA-N 0.000 description 6
- KUDUQBURMYMBIJ-UHFFFAOYSA-N 2-prop-2-enoyloxyethyl prop-2-enoate Chemical compound C=CC(=O)OCCOC(=O)C=C KUDUQBURMYMBIJ-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 241000233866 Fungi Species 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- UOZODPSAJZTQNH-LSWIJEOBSA-N paromomycin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO UOZODPSAJZTQNH-LSWIJEOBSA-N 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 229960005322 streptomycin Drugs 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- 241000192125 Firmicutes Species 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 239000000370 acceptor Substances 0.000 description 5
- 229960004821 amikacin Drugs 0.000 description 5
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229960000707 tobramycin Drugs 0.000 description 5
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CIDUJQMULVCIBT-MQDUPKMGSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4-amino-3-[[(2s,3r)-3-amino-6-(aminomethyl)-3,4-dihydro-2h-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](NC)[C@@](C)(O)CO1)O)NCC)[C@H]1OC(CN)=CC[C@H]1N CIDUJQMULVCIBT-MQDUPKMGSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- URWAJWIAIPFPJE-UHFFFAOYSA-N Rickamicin Natural products O1CC(O)(C)C(NC)C(O)C1OC1C(O)C(OC2C(CC=C(CN)O2)N)C(N)CC1N URWAJWIAIPFPJE-UHFFFAOYSA-N 0.000 description 4
- 229930192786 Sisomicin Natural products 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- HVVWZTWDBSEWIH-UHFFFAOYSA-N [2-(hydroxymethyl)-3-prop-2-enoyloxy-2-(prop-2-enoyloxymethyl)propyl] prop-2-enoate Chemical compound C=CC(=O)OCC(CO)(COC(=O)C=C)COC(=O)C=C HVVWZTWDBSEWIH-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000004599 antimicrobial Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 229960003807 dibekacin Drugs 0.000 description 4
- JJCQSGDBDPYCEO-XVZSLQNASA-N dibekacin Chemical compound O1[C@H](CN)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N JJCQSGDBDPYCEO-XVZSLQNASA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 4
- 229960000808 netilmicin Drugs 0.000 description 4
- 125000003367 polycyclic group Chemical group 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000009257 reactivity Effects 0.000 description 4
- 229960005456 sisomicin Drugs 0.000 description 4
- URWAJWIAIPFPJE-YFMIWBNJSA-N sisomycin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC=C(CN)O2)N)[C@@H](N)C[C@H]1N URWAJWIAIPFPJE-YFMIWBNJSA-N 0.000 description 4
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 3
- YWBOOOFNXVMNKI-UVYFCSKFSA-N (2r,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(1r,2r,3s,4r,6s)-4,6-diamino-2-[(2s,3r,4s,5r)-4-[(2r,3r,4r,5s,6s)-3-amino-6-(aminomethyl)-4,5-dihydroxyoxan-2-yl]oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol;sulfuric acid Chemical compound O.OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)[C@@H]1O YWBOOOFNXVMNKI-UVYFCSKFSA-N 0.000 description 3
- MUMXDRRTIYLYMY-YJKCNMNRSA-N (Z)-[dodecyl-[6-(dodecylazaniumyl)hexyl]amino]-oxido-oxidoiminoazanium Chemical compound CCCCCCCCCCCC[NH2+]CCCCCCN(CCCCCCCCCCCC)[N+](\[O-])=N\[O-] MUMXDRRTIYLYMY-YJKCNMNRSA-N 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- UOZODPSAJZTQNH-UHFFFAOYSA-N Paromomycin II Natural products NC1C(O)C(O)C(CN)OC1OC1C(O)C(OC2C(C(N)CC(N)C2O)OC2C(C(O)C(O)C(CO)O2)N)OC1CO UOZODPSAJZTQNH-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000001013 cariogenic effect Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000002086 nanomaterial Substances 0.000 description 3
- 150000004005 nitrosamines Chemical class 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 230000003239 periodontal effect Effects 0.000 description 3
- 229920000768 polyamine Polymers 0.000 description 3
- 239000012985 polymerization agent Substances 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- IHJPMPZEXZSDLU-UHFFFAOYSA-N 1-prop-2-enoyloxypropyl prop-2-enoate Chemical compound C=CC(=O)OC(CC)OC(=O)C=C IHJPMPZEXZSDLU-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- INQDDHNZXOAFFD-UHFFFAOYSA-N 2-[2-(2-prop-2-enoyloxyethoxy)ethoxy]ethyl prop-2-enoate Chemical compound C=CC(=O)OCCOCCOCCOC(=O)C=C INQDDHNZXOAFFD-UHFFFAOYSA-N 0.000 description 2
- HCLJOFJIQIJXHS-UHFFFAOYSA-N 2-[2-[2-(2-prop-2-enoyloxyethoxy)ethoxy]ethoxy]ethyl prop-2-enoate Chemical compound C=CC(=O)OCCOCCOCCOCCOC(=O)C=C HCLJOFJIQIJXHS-UHFFFAOYSA-N 0.000 description 2
- NCNNNERURUGJAB-UHFFFAOYSA-N 3-[2,2-bis(3-prop-2-enoyloxypropoxymethyl)butoxy]propyl prop-2-enoate Chemical compound C=CC(=O)OCCCOCC(CC)(COCCCOC(=O)C=C)COCCCOC(=O)C=C NCNNNERURUGJAB-UHFFFAOYSA-N 0.000 description 2
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 2
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
- JHWGFJBTMHEZME-UHFFFAOYSA-N 4-prop-2-enoyloxybutyl prop-2-enoate Chemical compound C=CC(=O)OCCCCOC(=O)C=C JHWGFJBTMHEZME-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229920002444 Exopolysaccharide Polymers 0.000 description 2
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical group COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 239000012901 Milli-Q water Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000000412 dendrimer Substances 0.000 description 2
- 229920000736 dendritic polymer Polymers 0.000 description 2
- 239000004053 dental implant Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- LZDSILRDTDCIQT-UHFFFAOYSA-N dinitrogen trioxide Chemical compound [O-][N+](=O)N=O LZDSILRDTDCIQT-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 229960003704 framycetin Drugs 0.000 description 2
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 description 2
- 150000002402 hexoses Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- PGBHMTALBVVCIT-VZXHOKRSSA-N neomycin C Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VZXHOKRSSA-N 0.000 description 2
- 230000009935 nitrosation Effects 0.000 description 2
- 238000007034 nitrosation reaction Methods 0.000 description 2
- 229960001914 paromomycin Drugs 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 201000001245 periodontitis Diseases 0.000 description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000003334 potential effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- YXMISKNUHHOXFT-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) prop-2-enoate Chemical compound C=CC(=O)ON1C(=O)CCC1=O YXMISKNUHHOXFT-UHFFFAOYSA-N 0.000 description 1
- FQYPKQOQUNFBDP-QMMMGPOBSA-N (2s)-6-amino-2-(2-methylprop-2-enoylamino)hexanoic acid Chemical compound CC(=C)C(=O)N[C@H](C(O)=O)CCCCN FQYPKQOQUNFBDP-QMMMGPOBSA-N 0.000 description 1
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- NNNLYDWXTKOQQX-UHFFFAOYSA-N 1,1-di(prop-2-enoyloxy)propyl prop-2-enoate Chemical compound C=CC(=O)OC(CC)(OC(=O)C=C)OC(=O)C=C NNNLYDWXTKOQQX-UHFFFAOYSA-N 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- LKLLNYWECKEQIB-UHFFFAOYSA-N 1,3,5-triazinane Chemical compound C1NCNCN1 LKLLNYWECKEQIB-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- IVJFXSLMUSQZMC-UHFFFAOYSA-N 1,3-dithiole Chemical compound C1SC=CS1 IVJFXSLMUSQZMC-UHFFFAOYSA-N 0.000 description 1
- QVFHFKPGBODJJB-UHFFFAOYSA-N 1,3-oxathiane Chemical compound C1COCSC1 QVFHFKPGBODJJB-UHFFFAOYSA-N 0.000 description 1
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JBYHSSAVUBIJMK-UHFFFAOYSA-N 1,4-oxathiane Chemical compound C1CSCCO1 JBYHSSAVUBIJMK-UHFFFAOYSA-N 0.000 description 1
- CPRVXMQHLPTWLY-UHFFFAOYSA-N 1,4-oxathiine Chemical compound O1C=CSC=C1 CPRVXMQHLPTWLY-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- CUCJJMLDIUSNPU-UHFFFAOYSA-N 1-oxidopiperidin-1-ium Chemical compound [O-][NH+]1CCCCC1 CUCJJMLDIUSNPU-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- DEGZUQBZHACZKW-UHFFFAOYSA-N 2-(methylamino)ethyl 2-methylprop-2-enoate Chemical compound CNCCOC(=O)C(C)=C DEGZUQBZHACZKW-UHFFFAOYSA-N 0.000 description 1
- ULEVTQHCVWIDPC-UHFFFAOYSA-N 2-(methylamino)ethyl prop-2-enoate Chemical compound CNCCOC(=O)C=C ULEVTQHCVWIDPC-UHFFFAOYSA-N 0.000 description 1
- BEWCNXNIQCLWHP-UHFFFAOYSA-N 2-(tert-butylamino)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCNC(C)(C)C BEWCNXNIQCLWHP-UHFFFAOYSA-N 0.000 description 1
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- NXBXJOWBDCQIHF-UHFFFAOYSA-N 2-[hydroxy-[2-(2-methylprop-2-enoyloxy)ethoxy]phosphoryl]oxyethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOP(O)(=O)OCCOC(=O)C(C)=C NXBXJOWBDCQIHF-UHFFFAOYSA-N 0.000 description 1
- XSHISXQEKIKSGC-UHFFFAOYSA-N 2-aminoethyl 2-methylprop-2-enoate;hydron;chloride Chemical compound Cl.CC(=C)C(=O)OCCN XSHISXQEKIKSGC-UHFFFAOYSA-N 0.000 description 1
- QPEJAHMNOVMSOZ-UHFFFAOYSA-N 2-azaspiro[3.3]heptane Chemical group C1CCC21CNC2 QPEJAHMNOVMSOZ-UHFFFAOYSA-N 0.000 description 1
- PSNDWZOXFDKLLH-UHFFFAOYSA-N 2-azaspiro[3.4]octane Chemical compound C1NCC11CCCC1 PSNDWZOXFDKLLH-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 1
- HPJALMWOZYIZGE-UHFFFAOYSA-N 2-oxa-6-azaspiro[3.3]heptane Chemical compound C1NCC11COC1 HPJALMWOZYIZGE-UHFFFAOYSA-N 0.000 description 1
- SUSDYISRJSLTST-UHFFFAOYSA-N 2-oxaspiro[3.3]heptane Chemical compound C1CCC21COC2 SUSDYISRJSLTST-UHFFFAOYSA-N 0.000 description 1
- NTMUDPWGPGZGQW-UHFFFAOYSA-N 2-oxaspiro[3.4]octane Chemical compound C1OCC11CCCC1 NTMUDPWGPGZGQW-UHFFFAOYSA-N 0.000 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- REEBWSYYNPPSKV-UHFFFAOYSA-N 3-[(4-formylphenoxy)methyl]thiophene-2-carbonitrile Chemical compound C1=CC(C=O)=CC=C1OCC1=C(C#N)SC=C1 REEBWSYYNPPSKV-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 description 1
- JANUDBLANRHSLI-UHFFFAOYSA-N 5-butyl-1,3,4-oxadiazol-2-amine Chemical compound CCCCC1=NN=C(N)O1 JANUDBLANRHSLI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
- 241000589875 Campylobacter jejuni Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 208000018035 Dental disease Diseases 0.000 description 1
- ASXBYYWOLISCLQ-UHFFFAOYSA-N Dihydrostreptomycin Natural products O1C(CO)C(O)C(O)C(NC)C1OC1C(CO)(O)C(C)OC1OC1C(N=C(N)N)C(O)C(N=C(N)N)C(O)C1O ASXBYYWOLISCLQ-UHFFFAOYSA-N 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000025157 Oral disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000014151 Stomatognathic disease Diseases 0.000 description 1
- 241001505901 Streptococcus sp. 'group A' Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000008312 Tooth Loss Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- DAKWPKUUDNSNPN-UHFFFAOYSA-N Trimethylolpropane triacrylate Chemical compound C=CC(=O)OCC(CC)(COC(=O)C=C)COC(=O)C=C DAKWPKUUDNSNPN-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- VEBCLRKUSAGCDF-UHFFFAOYSA-N ac1mi23b Chemical compound C1C2C3C(COC(=O)C=C)CCC3C1C(COC(=O)C=C)C2 VEBCLRKUSAGCDF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229960002222 dihydrostreptomycin Drugs 0.000 description 1
- ASXBYYWOLISCLQ-HZYVHMACSA-N dihydrostreptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O ASXBYYWOLISCLQ-HZYVHMACSA-N 0.000 description 1
- SNQXJPARXFUULZ-UHFFFAOYSA-N dioxolane Chemical compound C1COOC1 SNQXJPARXFUULZ-UHFFFAOYSA-N 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 150000002244 furazanes Chemical class 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000008810 intracellular oxidative stress Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
- 238000000569 multi-angle light scattering Methods 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- OKPYIWASQZGASP-UHFFFAOYSA-N n-(2-hydroxypropyl)-2-methylprop-2-enamide Chemical compound CC(O)CNC(=O)C(C)=C OKPYIWASQZGASP-UHFFFAOYSA-N 0.000 description 1
- XHIRWEVPYCTARV-UHFFFAOYSA-N n-(3-aminopropyl)-2-methylprop-2-enamide;hydrochloride Chemical compound Cl.CC(=C)C(=O)NCCCN XHIRWEVPYCTARV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- RQAKESSLMFZVMC-UHFFFAOYSA-N n-ethenylacetamide Chemical compound CC(=O)NC=C RQAKESSLMFZVMC-UHFFFAOYSA-N 0.000 description 1
- ZIWDVJPPVMGJGR-UHFFFAOYSA-N n-ethyl-2-methylprop-2-enamide Chemical compound CCNC(=O)C(C)=C ZIWDVJPPVMGJGR-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CHDKQNHKDMEASZ-UHFFFAOYSA-N n-prop-2-enoylprop-2-enamide Chemical compound C=CC(=O)NC(=O)C=C CHDKQNHKDMEASZ-UHFFFAOYSA-N 0.000 description 1
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 description 1
- 125000001326 naphthylalkyl group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical compound ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 1
- 125000005593 norbornanyl group Chemical group 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 1
- 229940041024 other aminoglycosides in atc Drugs 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-M peroxynitrite Chemical compound [O-]ON=O CMFNMSMUKZHDEY-UHFFFAOYSA-M 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical compound O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000004537 potential cytotoxicity Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- LBJQKYPPYSCCBH-UHFFFAOYSA-N spiro[3.3]heptane Chemical group C1CCC21CCC2 LBJQKYPPYSCCBH-UHFFFAOYSA-N 0.000 description 1
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- AWRLEXQNWFAMJM-UHFFFAOYSA-N tert-butyl 2-amino-4-(2-methylprop-2-enoylamino)butanoate Chemical compound CC(=C)C(=O)NCCC(N)C(=O)OC(C)(C)C AWRLEXQNWFAMJM-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- ICRHORQIUXBEPA-UHFFFAOYSA-N thionitrous acid Chemical compound SN=O ICRHORQIUXBEPA-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000010388 wound contraction Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
- A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/595—Polyamides, e.g. nylon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/224—Cyclohexane rings substituted by at least two nitrogen atoms with only one saccharide radical directly attached to the cyclohexyl radical, e.g. destomycin, fortimicin, neamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/228—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to adjacent ring-carbon atoms of the cyclohexane rings
- C07H15/232—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to adjacent ring-carbon atoms of the cyclohexane rings with at least three saccharide radicals in the molecule, e.g. lividomycin, neomycin, paromomycin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/76—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Actinomyces; for Streptomyces
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Pest Control & Pesticides (AREA)
- Epidemiology (AREA)
- Dentistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Environmental Sciences (AREA)
- Dermatology (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Description
この特許出願は、2018年3月28日に出願された米国仮特許出願第62/447,564号の優先権の利益を主張し、これは全ての目的でその全体が参照により本明細書に組み込まれる。
本発明は、国立衛生研究所によって授与された助成金番号DE025207の下で政府支援を受けてなされた。政府は、本発明においてある特定の権利を有する。
1つ以上の連結単位の連結単位は、第1のアミノグリコシド単位と第2のアミノグリコシド単位との間に共有結合架橋を形成する。いくつかの実施形態では、超分岐ポリアミノグリコシドのアミノグリコシド単位は、カナマイシンに由来する。いくつかの実施形態では、ストレプトマイシン、トブラマイシン、ゲンタマイシン、および/またはネオマイシンを、アミノグリコシド単位の一方または両方として使用することもできる。
式中、R1、R2、R3、R4、R5、R6、R9、およびR10のそれぞれは、独立して、-Hから選択されるか、または1つ以上の連結単位への共有結合を表し、1つ以上の連結単位の連結単位は、以下の構造で表され、
「-N-アミノグリコシド」は、式IIの構造を表す。
式中、R1、R2、R3、R4、R5、R6、R7、R8、R9、およびR10のそれぞれは、独立して、-Hから選択されるか、または1つ以上の連結単位への共有結合を表し、1つ以上の連結単位の連結単位は、以下の構造で表され、
少なくとも1つの連結単位は、第1のアミノグリコシド単位と第2のアミノグリコシド単位との間に共有結合架橋を形成し、超分岐ポリアミノグリコシドの少なくとも1つのアミノグリコシド単位は、ゲンタマイシンに由来する。
「-N-アミノグリコシド」は、式IIIの構造を表す。
「-N-アミノグリコシド」は、式IIIの構造を表す。
式中、R11、R12、R13、R14、R15、R16、R17、R18、R19、R20、R21、およびR22のそれぞれは、独立して、-Hから選択されるか、または1つ以上の連結単位への共有結合を表し、1つ以上の連結単位の連結単位は、以下の構造で表され、
少なくとも1つの連結単位は、第1のアミノグリコシド単位と第2のアミノグリコシド単位との間に共有結合架橋を形成し、超分岐ポリアミノグリコシドの少なくとも1つのアミノグリコシド単位は、ネオマイシンに由来する。
「-N-アミノグリコシド」は、式IVの構造を表す。
「-N-アミノグリコシド」は、式IVの構造を表す。
式中、変数は、本明細書の他の場所で記載される通りである。
式中、
式中、
アミノグリコシドは、抗菌薬として使用することができるポリアミンである。本明細書に記載されるいくつかの実施形態は、抗菌薬としての使用のためのポリアミノグリコシドに関する。いくつかの実施形態では、本明細書に開示されるポリアミノグリコシドは、一酸化窒素(NO)結合部分で官能化され、NO生成/放出のプラットフォームとして使用することができる。いくつかの実施形態では、ポリアミノグリコシドは、超分岐である。本明細書に開示される特定の実施形態は、殺菌および/または抗菌活性を有する超分岐ポリアミノグリコシドに関する。いくつかの実施形態では、超分岐ポリアミノグリコシドは、NO結合部分を含む。いくつかの実施形態では、超分岐ポリアミノグリコシドは、一酸化窒素(NO)ガスまたはいくつかの他のNO供与体と反応させて、NO供与性超分岐ポリアミノグリコシドを生成することができる。いくつかの実施形態では、超分岐ポリアミノグリコシドは、生分解性および/または生体適合性である。超分岐ポリアミノグリコシドが本明細書における例示的な構造として使用されるが、いくつかの実施形態によれば、直鎖ポリアミノグリコシド(例えば、非超分岐)も使用されることが理解されるべきである。
一酸化窒素(NO)は、主に微生物DNAおよび/または膜構造に対する酸化およびニトロソ化損傷を引き起こし得る反応性NO副産物(例えば、ペルオキシ亜硝酸および三酸化二窒素)の形成によって、細菌およびバイオフィルムの両方を根絶することができる広域スペクトルの抗菌薬である。有利なことに、NOがその抗菌効果を発揮する広範なメカニズムは、細菌が耐性を発達させるリスクを低減する。したがって、NO放出物質は、細菌感染と戦うための良好な標的であり得る。NO放出物質の抗菌有効性は、NOペイロードおよび関連する放出動態の両方に依存し得る。
G1およびG2は、独立して、置換または非置換ヘキソースまたはペントースである。いくつかの実施形態において、例えば、式Iの構造は、カナマイシンA、トブラマイシン、ジベカシン、ゲンタマイシン、シソマイシン、および/またはネチルマイシンのうちの1つ以上の中央ヘキソースであり、G1およびG2は、それらのアミノグリコシドの置換または非置換の隣接した6員糖環である。
式中、R5、R6、R7、R8、R9、およびR10は、独立して、-H、任意に置換されたC1~C6アルキル、1~6個の繰り返し単位を有する任意に置換された(C1~C6アルキル(複数可)で)ポリアミノ、1~6個の繰り返し単位を有する任意に置換された(C1~C6アルキル(複数可)で)ポリエーテルからなる群から選択されるか、または連結単位を介した超分岐ポリアミノグリコシドの別の原子への共有結合であり、
Xa、Xb、およびXcは、独立して、-H、-OH、およびC1~C6アルキルから選択される。
式中、R1、R2、R3、R4、R5、R6、R9、およびR10は、本明細書の他の場所で定義される通りである。いくつかの実施形態において、式IIは、出発物質としてカナマイシンを使用して調製することができ、および/または式IIは、カナマイシン含有超分岐ポリアミノグリコシドを具体化する。
式中、R23、R24、R25、R26、R27、R28、R29、およびR30は、独立して、-H、任意に置換されたC1~C6アルキル、1~6個の繰り返し単位を有する任意に置換された(C1~C6アルキル(複数可)で)ポリアミノ、1~6個の繰り返し単位を有する任意に置換された(C1~C6アルキル(複数可)で)ポリエーテルからなる群から選択されるか、または連結単位を介した超分岐ポリアミノグリコシドの別の原子への共有結合である。いくつかの実施形態において、式VIは、出発物質としてストレプトマイシンを使用して調製することができ、および/または式VIは、ストレプトマイシン含有超分岐ポリアミノグリコシドを具体化する。
式中、
W1、W2、またはW3は、独立して、本明細書の他の場所で開示されるように、アミノグリコシドまたはエンドキャッピング基から選択される。
1.1 物質および方法
細胞培養のための硫酸カンマイシン(KA)、三硫酸ネオマイシン塩水和物(NE)、硫酸ゲンタマイシン塩(GE)、N,N’-メチレンビス(アクリルアミド)(ビス-MBA)、エチレンジアミン(EDA)、モノ-エタノールアミン(MEA)、ヨウ化プロピジウム、3-(4,5-ジメチルチアゾール-2-イル)-5-(3-カルボキシメトキシフェニル)-2-(4-スルホフェニル)-2H-テトラゾリウム内部塩(MTS)、およびリン酸緩衝食塩水(PBS)は、Sigma-Aldrich(St.Loius、MO)から購入した。4,5-ジアミノフルオレセインジアセテート(DAF-2DA)は、Calbiochem(San Diego、CA)から購入した。CDC嫌気性生物5%ヒツジ血液アガー、ブレインハートインフュージョン(BHI)ブロスおよびアガー、ならびにGasPak(商標)EZキャンピーコンテナーシステムサシェは、Becton,Dickinson,and Company(Franklin Lakes、NJ)から購入した。Wilkins-Chalgren(W-C)ブロスは、Acumeida Neogen Corporation(Lansing、MI)から購入した。ヒト歯肉線維芽細胞株およびFibroLife線維芽細胞無血清培地は、Lifeline Cell Technology LLC(Frederick、MD)から購入した。純粋な一酸化窒素ガス、アルゴン、窒素、および一酸化窒素キャリブレーション(窒素中25.87ppm)は、Airgas(Durham、NC)から購入した。一般的な実験室の塩および溶媒は、Fisher Scientific(Pittsburgh、PA)から購入した。Millipore Milli-Q UV Gradient A10システム(Bethlehem、PA)を使用して、18.2MΩcmの最終抵抗率および≦10ppbの総有機物含有量まで水を精製した。プロトン核磁気共鳴(1H NMR)スペクトルは、400MHz Bruker装置で記録した。炭素核磁気共鳴(13C NMR)は、600MHz Bruker装置で行った。定量的13C NMRには、逆ゲーテッド1Hデカップリング法が10秒の保持時間で使用された。サイズ排除クロマトグラフィーは、光散乱(SEC-LS)と合わせて、分子量および多分散性を決定した。溶離液(PBS、0.01%アジド、pH7.4)は、Waters2414屈折率検出器(Waters Chromatography、Milford、MA)に接続されたminiDawn TREOS多角度光散乱検出器(Wyatt Technology、Santa Barbara、CA)に通した。
超分岐ポリアミノグリコシド(HPA)は、N,N’-メチレンビスアクリルアミド(MBA)と様々な天然アミノグリコシド(すなわち、カナマイシン、ネオマイシン、およびゲンタマイシン)との間のマイケル付加反応によって合成した。スキーム1に示されるように、MBAとアミノグリコシドとのモル比は、最初に3:2で制御し、アミノグリコシド末端HPA(すなわち、それぞれHPKA、HPNE、およびHPGE)を生成した。スキャフォールドの外部官能基は、末端基がNO供与体分解および細菌スキャフォールド会合挙動の動態を変更し得るため、一酸化窒素(NO)放出特性および殺菌活性に大きな影響を与えることが以前に報告されている。
アミノグリコシドをエンドキャッピングする潜在的な効果を評価するために、アミノグリコシドで終端していない超分岐ポリアミノグリコシドを、例として超分岐ポリカナマイシンを使用して調製した(スキーム2)。MBAとカナマイシンとの供給モル比を5:2に増加し、ビニル基末端HPKA*中間体を生成した。次に、エチレンジアミン(EDA)またはモノエタノールアミン(MEA)をエンドキャッピング試薬として使用してHPKA*と反応させ、EDA(HPKA-EDA)またはMEA(HPKA-MEA)で終端したHPKAを生成した。
HPAの分子量および多分散性指数(PDI)は、サイズ排除クロマトグラフィー-光散乱(SEC-LS)特徴分析によって決定し、データを表1にまとめた。
N-ジアゼニウムジオレートNO供与体修飾ポリサッカリドの合成.
NO放出用途のための高分子スキャフォールド(例えば、シリカ、ポリアミドアミンデンドリマー、キトサン)は、多くの場合、NO供与体の付加のための反応性部位を作成するための追加の修飾ステップを必要とする。超分岐ポリアミノグリコシドは、N-ジアゼニウムジオレートNO供与体(または他のNO供与体)で直接官能化することができる第2級アミンを提供する線状単位の存在から恩恵を受ける。
N-ジアゼニウムジオレートNO供与体の形成の成功は、非NO放出性スキャフォールドには不在である約250nmでのピークの出現によって示されるように、UV-vis分光法によって確認した(図6)。1H NMRおよびSEC-LS特徴分析(図示せず)は、NOと反応した後のスキャフォールドの完全性を確認した。
化学発光一酸化窒素分析計を使用して、PBS(pH7.4、37℃)中のスキャフォールドのNO放出特性を評価した。正確に計量した質量(約1mg)を有するNO放出性超分岐ポリアミノグリコシドを、脱酸素化した10mMのリン酸緩衝生理食塩水(PBS、30mL、pH7.4)に37℃で添加した。窒素をこの溶液に70mL min-1の流量で通気して、遊離したNOをSievers化学発光一酸化窒素アナライザー(Boulder、CO)に運搬した。200mL min-1での装置の収集速度に合わせるために、追加の窒素流をフラスコに供給した。観察されたNOレベルが10ppb mg-1スキャフォールド未満に減少するまで、リアルタイムNO放出プロファイルを記録した。総NO貯蔵量は、添加されたスキャフォールドの質量に対して、μmolNOmg-1スキャフォールドとして正規化した。
以下は、HPAの例となる実施形態を使用して行われた試験について説明する。対照およびNO放出性HPAの抗菌活性を、様々な歯科疾患を引き起こす細菌種(すなわち、P.gingivalis、A.actinomycetemcomitans、A.viscosus、およびS.mutans)に対して評価した。具体的には、P.gingivalisおよびA.actinomycetemcomitansは、グラム陰性クラスに属し、一般に歯周病に関する。S.mutansおよびA.viscosusは、グラム陽性種であり、虫歯の重要な病因物質とみなされている。本開示において選択される広範囲の口腔細菌種は、経口治療薬の態様において得られる結論の潜在的な普遍性を保証した。
浮遊細菌種(すなわち、P.gingivalis、A.actinomycetemcomitans、S.mutans、およびA.viscosus)をまず、15%グリセロールPBS中で-80℃で貯蔵した。殺菌アッセイを行うために、凍結ストックをBHIブロス(P.ginigvalisにはW-C嫌気性ブロス)において37℃で一晩増殖させ、光学密度(OD 600nm)により決定される108コロニー形成単位毎ミリリットル(CFU mL-1)まで増殖させた。P.ginigvalisは、嫌気的に培養した。A.actinomycetemcomitansおよびA.viscosusは、微好気性環境において培養した。S.mutansは、好気的に培養した。次に、細菌を、1%BHI(P.ginigvalisにはW-C嫌気性ブロス)が補足されたPBSにおいて106CFU/mLまで希釈し、様々なNO放出性物質およびそれぞれの対照物質に37℃で2時間曝露した。
殺菌アッセイは、栄養素が補足された条件下(すなわち、1%ブロス補足PBS、pH7.4、37℃)で行った。スキャフォールド抗菌有効性を定量化するために、最小殺菌濃度(MBC、mg mL-1)、細菌生存率の3log低減を使用した。浮遊細菌に対する物質の抗菌能力を定量化するために、最小殺菌濃度(例えば、2時間後に生存率の3log低減を達成するために必要な物質の最小濃度)を決定した。
この観察された殺菌作用の違いのメカニズムを解明するために、共焦点蛍光顕微鏡を使用して、それぞれDAF-2DAおよびPI蛍光プローブを使用して、細胞内NOおよび細胞膜損傷を視覚化した(図8Aおよび8B)。S.mutansをHPKA/NOに曝露した後、最初に細胞内NO蓄積(30分)、続いて細胞膜損傷の出現および蓄積NOの枯渇(60分から開始)が観察された。しかしながら、S.mutansの同じ濃度でのHPKA-MEA/NOへの曝露後、細胞膜損傷の少ない細胞内NOの出現のみが観察された。共焦点蛍光データは、HPKA/NOの改善された殺菌作用が、カナマイシン末端基とNOとの間の相乗効果によるより効率的な細胞膜損傷の結果であることを示した。
哺乳動物細胞に対する毒性は、新しく開発された抗菌薬を評価する際の重要な因子である。経口治療薬についてのこれらの超分岐ポリアミノグリコシドの可能性を評価するために、口腔物質の評価に使用される一般的な細胞株であるヒト歯肉線維芽細胞(HGF-1)に対する細胞毒性を、様々な濃度で試験した。HGF-1の生存率を、2時間の曝露時間後にMTSアッセイによって監視した。
細胞生存率%=[(Abs490-Absブランク)・/(Absコントロール-Absブランク)]×100%(式1)
本明細書では、広範囲にわたるNO貯蔵および放出動態が可能なNO放出性超分岐ポリアミノグリコシドを調製するための合成プロトコルが提供された。総NO貯蔵および関連するNO放出動態は、アミノグリコシドモノマーと特定の外部官能基との同一性に大きく依存した。NO放出性超分岐ポリアミノグリコシドの抗菌作用は、一般的な口腔内病原体に対して調査された。より効率的な細胞損傷をもたらしたアミノグリコシド末端基とNO放出能力との組み合わせは、スキャフォールドの改善された殺菌能力に寄与した。いくつかの実施形態において、アミノグリコシド末端基とNOとの組み合わせは、より大きな細菌膜損傷および殺菌作用を提供することがわかった。
Claims (15)
- (i)1つ以上のアミノグリコシド単位と1つ以上の架橋剤とを重合して超分岐ポリアミノグリコシドを形成する工程、
(ii)前記超分岐ポリアミノグリコシドを1つ以上の末端単位と反応させてエンドキャッピングした超分岐ポリアミノグリコシドを形成し、前記1つ以上の末端単位が、独立して以下からなる群から選択される工程、および
前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、式IIの構造を含む少なくとも1つのアミノグリコシド単位を有し、
それぞれの連結単位が、以下の構造を有し、
あるいは、
(i)1つ以上のアミノグリコシド単位と1つ以上の架橋剤とを重合して超分岐ポリアミノグリコシドを形成する工程、および
前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、式IIの構造を含む少なくとも1つのアミノグリコシド単位を有し、
それぞれの連結単位が、以下の構造を有し、
- 前記超分岐ポリアミノグリコシドまたはエンドキャッピングした超分岐ポリアミノグリコシドが、以下の構造を有する1つ以上の樹状単位を含み、
- 前記超分岐ポリアミノグリコシドまたはエンドキャッピングした超分岐ポリアミノグリコシドが、以下の構造を有する1つ以上の線状単位を含み、
- 前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、4kDa以下の数平均分子量を有する、請求項1に記載の組成物。
- 前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、7kDa以下の重量平均分子量を有する、請求項1に記載の組成物。
- 前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシド1mg当たりNO 0.4μmol以上のNO貯蔵能力を有する、請求項1に記載の組成物。
- 前記一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドが、2時間にわたって静的条件下で行われる細菌生存率アッセイにおいて、2mg/mL以下の濃度でP.aeruginosa、S.aureus、P.gingivalis、A.actinomycetemcomitans、A.viscosus、および/またはS.mutansのうちの1つ以上に対して99%以上の細菌低減を提供する、請求項1に記載の組成物。
- (i)1つ以上のアミノグリコシド単位と1つ以上の架橋剤とを重合して超分岐ポリアミノグリコシドを形成する工程、
(ii)前記超分岐ポリアミノグリコシドを1つ以上の末端単位と反応させてエンドキャッピングした超分岐ポリアミノグリコシドを形成し、前記1つ以上の末端単位が、-NH-((CH 2 ) a X 1 ) b -(CH 2 ) c Hの式を有し、式中、X 1 が、OまたはNHであり、a、b、およびcが、独立して、0~10の整数である工程、および
(iii)前記超分岐ポリアミノグリコシドまたはエンドキャッピングした超分岐ポリアミノグリコシド上の1つ以上の第2級アミンを修飾して、1つ以上のNO供与体を形成し、それにより一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドを形成する工程によって製造される、一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドを含み、
前記1つ以上の1つ以上のアミノグリコシド単位が、式Iの構造を含み、
式中、Xa、Xb、およびXcが、独立して、H、-OH、およびC1~C6アルキルからなる群から選択され、
式中、R1、R2、R3、R4、R5、R6、R7、R8、R9、およびR10のうちの少なくとも1つが、以下からなる群から選択される1つ以上の連結単位への共有結合であり、
式中、W1、W2、またはW3が、存在する場合、アミノグリコシド単位または末端単位のいずれかであり、
式中、Ra、Rb、およびRcが、独立して、C 1~C6アルキル、1~6個の繰り返し単位を有するポリアミノ、および1~6個の繰り返し単位を有するポリエーテルからなる群から選択され、前記繰り返し単位がC 1 ~C 6 アルキル(複数可)が介在する基を含む、一酸化窒素を対象に送達するための組成物、
あるいは、
(i)1つ以上のアミノグリコシド単位と1つ以上の架橋剤とを重合して超分岐ポリアミノグリコシドを形成する工程、および
(iii)前記超分岐ポリアミノグリコシドまたはエンドキャッピングした超分岐ポリアミノグリコシド上の1つ以上の第2級アミンを修飾して、1つ以上のNO供与体を形成し、それにより一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドを形成する工程によって製造される、一酸化窒素供与性の超分岐ポリアミノグリコシドまたは一酸化窒素供与性のエンドキャッピングした超分岐ポリアミノグリコシドを含み、
前記1つ以上の1つ以上のアミノグリコシド単位が、式Iの構造を含み、
式中、X a 、X b 、およびX c が、独立して、H、-OH、およびC 1 ~C 6 アルキルからなる群から選択され、
式中、R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、およびR 10 のうちの少なくとも1つが、以下からなる群から選択される1つ以上の連結単位への共有結合であり、
式中、W 1 、W 2 、またはW 3 が、存在する場合、アミノグリコシド単位または末端単位のいずれかであり、
式中、R a 、R b 、およびR c が、独立して、C 1 ~C 6 アルキル、1~6個の繰り返し単位を有するポリアミノ、および1~6個の繰り返し単位を有するポリエーテルからなる群から選択され、前記繰り返し単位がC 1 ~C 6 アルキル(複数可)が介在する基を含む、一酸化窒素を対象に送達するための組成物。 - 前記1つ以上のNO供与体が、独立して、以下からなる群から選択され、
- 前記1つ以上のNO供与体が、
式中、
- 前記1つ以上のアミノグリコシド単位の少なくとも1つが、式IIまたは式IIIのアミノグリコシド単位を含む、請求項8に記載の組成物。
- 微生物汚染減少用である、請求項1~11のいずれか一項に記載の組成物。
- 請求項1~11のいずれか一項に記載の組成物と、
薬学的に許容される担体と、を含む、薬学的配合物。 - 有効量の前記超分岐ポリアミノグリコシドまたは前記エンドキャッピングした超分岐ポリアミノグリコシドを含む、請求項1~11のいずれか一項に記載の組成物、または請求項13に記載の薬学的配合物。
- 微生物感染を治療または予防するための医薬品の調製における請求項1~11のいずれか一項に記載の組成物、または請求項13に記載の薬学的配合物の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762477564P | 2017-03-28 | 2017-03-28 | |
US62/477,564 | 2017-03-28 | ||
PCT/IB2018/052144 WO2018178902A1 (en) | 2017-03-28 | 2018-03-28 | Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020515688A JP2020515688A (ja) | 2020-05-28 |
JP2020515688A5 JP2020515688A5 (ja) | 2021-05-06 |
JP7403152B2 true JP7403152B2 (ja) | 2023-12-22 |
Family
ID=63677204
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019553558A Active JP7403152B2 (ja) | 2017-03-28 | 2018-03-28 | 生分解可能な抗菌性スキャフォールドとしての一酸化窒素放出性ポリアミノグリコシドおよびそれに関する方法背景 |
Country Status (7)
Country | Link |
---|---|
US (1) | US11723914B2 (ja) |
EP (1) | EP3600338A4 (ja) |
JP (1) | JP7403152B2 (ja) |
CN (1) | CN110461338A (ja) |
AU (1) | AU2018247167B2 (ja) |
CA (1) | CA3055474A1 (ja) |
WO (1) | WO2018178902A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3523367A4 (en) | 2016-10-07 | 2020-06-03 | The University Of North Carolina At Chapel Hill | HYPERRAMIFIED POLYESTERS MEDIATED BY S-NITROSOTHIOL |
AU2018205823A1 (en) | 2017-01-03 | 2019-07-18 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing alginates as biodegradable antibacterial scaffolds and methods pertaining thereto |
WO2018178902A1 (en) | 2017-03-28 | 2018-10-04 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto |
US20200332061A1 (en) * | 2017-11-15 | 2020-10-22 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing hyperbranched compounds as antibacterial scaffolds and methods pertaining thereto |
EP3762039A4 (en) | 2018-03-06 | 2021-12-22 | The University of North Carolina at Chapel Hill | NITRIC OXIDE RELEASING CYCLODEXTRINS AS BIODEGRADABLE ANTIBACTERIAL SCAFFOLDS AND RELATED PROCESSES |
JP2022516461A (ja) * | 2018-12-28 | 2022-02-28 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 一酸化窒素放出抗菌性ポリマーおよびそれから製造された足場、ならびにそれに関する方法 |
CN115232318B (zh) * | 2022-08-24 | 2023-12-26 | 宁波锋成先进能源材料研究院有限公司 | 一种非离子高分子表面活性剂及其制备方法和应用 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050085413A1 (en) | 2001-11-09 | 2005-04-21 | Betty Jin | Dimeric pharmaceutical compounds and their use |
WO2010037179A1 (en) | 2008-10-03 | 2010-04-08 | Glycan Biosciences Pty Ltd | Anionic conjugates of glycosylated bacterial metabolite |
JP2010168390A (ja) | 1997-07-03 | 2010-08-05 | Usa Government | 新規な一酸化窒素放出アミジンおよびエナミン誘導ジアゼニウムジオレート、組成物およびそれらの用途、ならびにその製造方法 |
JP2011509267A (ja) | 2008-01-10 | 2011-03-24 | ニコックス エス エイ | 神経因性疼痛を癒すためのアセトアミノフェンのニトロオキシ誘導体と抗痙攣剤とを含む組成物 |
JP2012512700A (ja) | 2008-12-19 | 2012-06-07 | メドトロニック ヴァスキュラー インコーポレイテッド | 一酸化窒素放出医療装置を作製するための乾質ジアゼニウムジオレート化方法 |
WO2013029009A1 (en) | 2011-08-24 | 2013-02-28 | Novan, Inc. | Tunable nitric oxide-releasing macromolecules having multiple nitric oxide donor structures |
JP2015524877A (ja) | 2012-08-17 | 2015-08-27 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 水溶性一酸化窒素放出ポリグルコサミンおよびそれらの使用 |
Family Cites Families (85)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4169079A (en) | 1977-10-24 | 1979-09-25 | Iwao Tabushi | Polystyrene based polymers containing cyclodextrin derivatives, metal complexes of the same, and process for the production of the same |
US5574027A (en) | 1989-11-22 | 1996-11-12 | Bernstein; Lawrence R. | Pharmaceutical compositions of gallium complexes of 3-hydroxy-4-pyrones |
US5234933A (en) | 1991-10-31 | 1993-08-10 | Board Of Governors Of Wayne State University And Vanderbilt University | Cyclic hydroxamic acids |
DE4210332C1 (ja) | 1992-03-30 | 1993-07-15 | Gruenenthal Gmbh, 5100 Aachen, De | |
US5814666A (en) | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
US5238832A (en) | 1992-06-08 | 1993-08-24 | Board Of Governors Of Wayne State University | Aryl aliphatic acids |
US5910316A (en) | 1992-08-24 | 1999-06-08 | The United States Of America, As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents to treat impotency |
US5525357A (en) | 1992-08-24 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
US5650447A (en) | 1992-08-24 | 1997-07-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Nitric oxide-releasing polymers to treat restenosis and related disorders |
US5691423A (en) | 1992-08-24 | 1997-11-25 | The United States Of America As Represented By The Department Of Health And Human Services | Polysaccharide-bound nitric oxide-nucleophile adducts |
US5632981A (en) | 1992-08-24 | 1997-05-27 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
US5405919A (en) | 1992-08-24 | 1995-04-11 | The United States Of America As Represented By The Secretary Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions and methods of treating biological disorders |
US6200558B1 (en) | 1993-09-14 | 2001-03-13 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
US5840759A (en) | 1993-10-08 | 1998-11-24 | The United States Of America As Represented By The Department Of Health And Human Services | Use of nitric oxide releasing compounds to protect noncancerous cells from chemotherapeutic agents |
AU685178B2 (en) | 1993-10-08 | 1998-01-15 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Use of nitric oxide-releasing compounds as hypoxic cell radiation sensitizers |
ATE192922T1 (de) | 1993-11-02 | 2000-06-15 | Us Health | Verwendung von stickstoffoxid freisetzenden verbindungen zur herstellung eines arzneimittels zum schutz gegen die ischämischen reperfusionsschäden |
CA2205564C (en) | 1994-11-22 | 2006-07-11 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Pharmaceutical compositions comprising nitric oxide-releasing biopolymers |
US5714511A (en) | 1995-07-31 | 1998-02-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Selective prevention of organ injury in sepsis and shock using selection release of nitric oxide in vulnerable organs |
US6232434B1 (en) | 1996-08-02 | 2001-05-15 | Duke University Medical Center | Polymers for delivering nitric oxide in vivo |
US5770645A (en) | 1996-08-02 | 1998-06-23 | Duke University Medical Center | Polymers for delivering nitric oxide in vivo |
US20030093143A1 (en) | 1999-03-01 | 2003-05-15 | Yiju Zhao | Medical device having surface depressions containing nitric oxide releasing compound |
JP4285775B2 (ja) | 1996-09-27 | 2009-06-24 | アメリカ合衆国 | O▲上2▼―アリール化またはo▲上2▼―グリコシル化1―置換ジアゼン―1―イウム―1,2―ジオレート類およびo▲上2▼―置換1―[(2―カルボキシラト)ピロリジン―1―イル]ジアゼン―1―イウム―1,2―ジオレート類 |
US6610660B1 (en) | 1996-09-27 | 2003-08-26 | The United States Of America As Represented By The Department Of Health And Human Services | O2-arylated or O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-[(2-carboxylato) pyrrolidin-1-yl] diazen-1-ium-1,2-diolates |
NO305033B1 (no) | 1997-05-09 | 1999-03-22 | Algipharma As | Fremgangsmate for fremstilling av uronsyreblokker fra alginat |
US6180082B1 (en) | 1997-11-24 | 2001-01-30 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Method to enhance tissue accumulation of radiolabeled compounds |
US6207855B1 (en) | 1998-06-23 | 2001-03-27 | Duke University Medical Center | Stable no-delivering compounds |
US6261594B1 (en) | 1998-11-25 | 2001-07-17 | The University Of Akron | Chitosan-based nitric oxide donor compositions |
CN1223378C (zh) | 2000-05-02 | 2005-10-19 | 施万制药 | 含有糖肽抗生素和环糊精的药物组合物 |
JP2002179647A (ja) | 2000-12-11 | 2002-06-26 | Kikkoman Corp | ニコチアナミン又はニコチアナミン含有物の製造法 |
AU2003226603A1 (en) | 2002-04-19 | 2003-11-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Beta-agonist compounds comprising nitric oxide donor groups and reactive oxygen species scavenger groups and their use in the treatment of respiratory disorders |
US20040038947A1 (en) | 2002-06-14 | 2004-02-26 | The Gov. Of The U.S. Of America As Represented By The Sec. Of The Dept. Of Health & Human Services | Method of treating ischemia/reperfusion injury with nitroxyl donors |
NO335366B1 (no) | 2002-07-26 | 2014-12-01 | Algipharma As | Mutantstamme Pf201 av Pseudomonas fluorescens og anvendelse derav i alginatproduksjon,samt fremgangsmåte for fremstilling derav. |
NO20023581D0 (no) | 2002-07-26 | 2002-07-26 | Fmc Biopolymer As | Nye mutantstammer av Pseudomonas fluorescens og varianter derav, metoder for produksjon og bruk derav til produksjon avalginat |
ATE533513T1 (de) | 2002-09-06 | 2011-12-15 | Cerulean Pharma Inc | Polymere auf basis von cyclodextrin zur verabreichung von an diese kovalent gebundene arzneimittel |
US20050009789A1 (en) | 2003-05-13 | 2005-01-13 | The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Service | Cyclooxygenase inhibition with nitroxyl |
JP2005047979A (ja) | 2003-07-30 | 2005-02-24 | Dainippon Ink & Chem Inc | 多分岐ポリマーの製造方法、及び多分岐ポリマー |
SG113562A1 (en) | 2004-01-12 | 2005-08-29 | Agency Science Tech & Res | Polyalkyleneimine-graft-biodegradable polymers for delivery of bioactive agents |
AU2006211173A1 (en) | 2005-01-28 | 2006-08-10 | Pinnacle Pharmaceuticals, Inc. | Beta-cyclodextrin derivatives as antibacterial agents |
EP3556401A1 (en) | 2005-05-27 | 2019-10-23 | The University of North Carolina at Chapel Hill | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications |
GB0515550D0 (en) | 2005-07-29 | 2005-09-07 | Univ Strathclyde | Inactivation of staphylococcus species |
WO2007053292A2 (en) | 2005-10-31 | 2007-05-10 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Polysaccharide-derived nitric oxide-releasing carbon-bound diazeniumdiolates |
JP2009523584A (ja) | 2006-01-24 | 2009-06-25 | ミリメッド・アクティーゼルスカブ | Ph依存性薬物放出を有する医療デバイス |
US7854923B2 (en) | 2006-04-18 | 2010-12-21 | Endomedix, Inc. | Biopolymer system for tissue sealing |
GB0707096D0 (en) | 2007-04-12 | 2007-05-23 | Ntnu Technology Transfer As | Method |
CN101049513B (zh) | 2007-05-13 | 2010-05-19 | 刘万顺 | 水溶性壳聚糖基纤维止血愈创材料及其制备方法和应用 |
ITMI20071341A1 (it) | 2007-07-05 | 2009-01-06 | Fidia Farmaceutici | Derivati di acido ialuronico contenenti gruppi in grado di rilasciare no |
US8399005B2 (en) | 2007-10-12 | 2013-03-19 | University Of North Carolina At Chapel Hill | Use of nitric oxide to enhance the efficacy of silver and other topical wound care agents |
RS55933B1 (sr) | 2007-11-27 | 2017-09-29 | Algipharma As | Upotreba alginatnih oligomera u borbi protiv biofilmova |
US20090222088A1 (en) | 2008-02-29 | 2009-09-03 | Medtronic Vascular, Inc. | Secondary Amine Containing Nitric Oxide Releasing Polymer Composition |
US20090232863A1 (en) | 2008-03-17 | 2009-09-17 | Medtronic Vascular, Inc. | Biodegradable Carbon Diazeniumdiolate Based Nitric Oxide Donating Polymers |
US8841440B2 (en) | 2008-04-01 | 2014-09-23 | Cornell University | Organo-soluble chitosan salts and chitosan-derived biomaterials prepared thereof |
EP2398761A4 (en) | 2009-02-18 | 2015-11-04 | Bezwada Biomedical Llc | CONTROLLED RELEASE OF NITRIC OXIDE AND MEDICINES FROM FUNCTIONALIZED MACROMERS AND OLIGOMERS |
GB0904941D0 (en) | 2009-03-23 | 2009-05-06 | Ntnu Technology Transfer As | Composition |
WO2010120905A2 (en) | 2009-04-15 | 2010-10-21 | Board Of Trustees Of Michigan State University | Novel nano-probes for molecular imaging and targeted therapy of diseases |
US9539233B2 (en) | 2009-05-04 | 2017-01-10 | Aridis Pharmaceuticals Inc. | Gallium formulation for the treatment and prevention of infectious diseases |
AU2010255543B2 (en) | 2009-06-03 | 2016-02-18 | Algipharma As | Alginate oligomers for use in overcoming multidrug resistance in bacteria |
GB0909529D0 (en) | 2009-06-03 | 2009-07-15 | Algipharma Ipr As | Alginate oligomers for the inhibition of microbial adherence to surfaces |
GB0909557D0 (en) | 2009-06-03 | 2009-07-15 | Algipharma Ipr As | Anti-microbial alginate oligomers |
US9957341B2 (en) | 2009-06-09 | 2018-05-01 | William Chambers | Biodegradable absorbent material and method of manufacture |
CA2671595A1 (en) | 2009-07-09 | 2011-01-09 | Ping I. Lee | Controlled nitric oxide delivery from aqueous s-nitrosothiol conjugated polymers and their complexes |
US8551456B2 (en) * | 2010-03-05 | 2013-10-08 | University Of Dayton | Combination therapy and methods for treating bacterial biofilms |
EP2547660B1 (en) | 2010-03-19 | 2015-01-07 | The United States Of America, As Represented By The Secretary, Department of Health and Human Services | Nitroxyl (hno) releasing compounds and uses thereof in treating diseases |
KR101272351B1 (ko) * | 2010-04-23 | 2013-06-07 | 이화여자대학교 산학협력단 | 새로운 카나마이신 화합물, 카나마이신 생산 스트렙토마이세스 속 미생물 및 카나마이신의 생산 방법 |
KR101255337B1 (ko) | 2010-10-04 | 2013-04-16 | 한국과학기술연구원 | 온도 감응성 합성 고분자를 이용한 일산화질소 전달체 |
WO2012116177A2 (en) | 2011-02-24 | 2012-08-30 | Colorado State University Research Foundation | Materials for modulating biological responses and methods of making |
GB201116010D0 (en) | 2011-09-15 | 2011-10-26 | Algipharma As | Use of alginate oligomers to enhance the effects of antifungal agents |
KR101385280B1 (ko) * | 2012-05-23 | 2014-04-16 | 한국과학기술원 | 역상 현탁중합과 전구체를 이용한 가교된 하이퍼브랜치 폴리아미도아민 입자의 제조 방법 |
US9017653B2 (en) | 2012-06-14 | 2015-04-28 | The Board Of Regents Of The University Of Texas System | Nitric oxide-releasing compositions and methods |
KR20150125663A (ko) | 2013-03-08 | 2015-11-09 | 알러간, 인코포레이티드 | 사이클로스포린 a 스테로이드 켤레물 |
GB201322777D0 (en) | 2013-12-20 | 2014-02-05 | Algipharma As | Use of alginate oligomers as blood anticoagulants |
CA2934950A1 (en) | 2013-12-23 | 2015-07-02 | Norwegian University Of Science And Technology | Uses of oligouronates in cancer treatment |
WO2015128495A1 (en) | 2014-02-28 | 2015-09-03 | Algipharma As | Use of alginate oligomers in the treatment of cystic fibrosis and other conditions associated with defective cftr ion channel function |
GB201415381D0 (en) | 2014-08-29 | 2014-10-15 | Algipharma As | Inhalable powder formulations of alginate oligomers |
EP3215140A4 (en) | 2014-11-06 | 2018-05-02 | The Arizona Board of Regents On Behalf of the University of Arizona | Compositions and methods of diazeniumdiolate-based prodrugs for treating cancer |
GB201504878D0 (en) | 2015-03-23 | 2015-05-06 | Algipharma As | Use of alginate oligomers and CFTR modulators in the treatment of conditions associated with CFTR dysfuntion |
US11170451B2 (en) | 2015-10-02 | 2021-11-09 | Not So Forgetful, LLC | Apparatus and method for providing gift recommendations and social engagement reminders, storing personal information, and facilitating gift and social engagement recommendations for calendar-based social engagements through an interconnected social network |
GB201517639D0 (en) | 2015-10-06 | 2015-11-18 | Algipharma As | Use of alginate oligomers to treat or prevent microbial overgrowth in the intestinal tract |
CN106046382B (zh) | 2016-05-25 | 2018-10-09 | 暨南大学 | 一种装载一氧化氮的阳离子聚合物及其制备方法和应用 |
EP3523367A4 (en) | 2016-10-07 | 2020-06-03 | The University Of North Carolina At Chapel Hill | HYPERRAMIFIED POLYESTERS MEDIATED BY S-NITROSOTHIOL |
AU2018205823A1 (en) | 2017-01-03 | 2019-07-18 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing alginates as biodegradable antibacterial scaffolds and methods pertaining thereto |
WO2018178902A1 (en) | 2017-03-28 | 2018-10-04 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto |
US20200332061A1 (en) | 2017-11-15 | 2020-10-22 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing hyperbranched compounds as antibacterial scaffolds and methods pertaining thereto |
EP3762039A4 (en) | 2018-03-06 | 2021-12-22 | The University of North Carolina at Chapel Hill | NITRIC OXIDE RELEASING CYCLODEXTRINS AS BIODEGRADABLE ANTIBACTERIAL SCAFFOLDS AND RELATED PROCESSES |
US11102301B2 (en) | 2018-07-12 | 2021-08-24 | Sap Se | PCA-based scoring of the similarity of damage patterns of operational assets |
JP2022516461A (ja) | 2018-12-28 | 2022-02-28 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 一酸化窒素放出抗菌性ポリマーおよびそれから製造された足場、ならびにそれに関する方法 |
-
2018
- 2018-03-28 WO PCT/IB2018/052144 patent/WO2018178902A1/en unknown
- 2018-03-28 CA CA3055474A patent/CA3055474A1/en active Pending
- 2018-03-28 EP EP18775628.3A patent/EP3600338A4/en active Pending
- 2018-03-28 AU AU2018247167A patent/AU2018247167B2/en active Active
- 2018-03-28 JP JP2019553558A patent/JP7403152B2/ja active Active
- 2018-03-28 US US16/497,696 patent/US11723914B2/en active Active
- 2018-03-28 CN CN201880020987.XA patent/CN110461338A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010168390A (ja) | 1997-07-03 | 2010-08-05 | Usa Government | 新規な一酸化窒素放出アミジンおよびエナミン誘導ジアゼニウムジオレート、組成物およびそれらの用途、ならびにその製造方法 |
US20050085413A1 (en) | 2001-11-09 | 2005-04-21 | Betty Jin | Dimeric pharmaceutical compounds and their use |
JP2011509267A (ja) | 2008-01-10 | 2011-03-24 | ニコックス エス エイ | 神経因性疼痛を癒すためのアセトアミノフェンのニトロオキシ誘導体と抗痙攣剤とを含む組成物 |
WO2010037179A1 (en) | 2008-10-03 | 2010-04-08 | Glycan Biosciences Pty Ltd | Anionic conjugates of glycosylated bacterial metabolite |
JP2012512700A (ja) | 2008-12-19 | 2012-06-07 | メドトロニック ヴァスキュラー インコーポレイテッド | 一酸化窒素放出医療装置を作製するための乾質ジアゼニウムジオレート化方法 |
WO2013029009A1 (en) | 2011-08-24 | 2013-02-28 | Novan, Inc. | Tunable nitric oxide-releasing macromolecules having multiple nitric oxide donor structures |
JP2015524877A (ja) | 2012-08-17 | 2015-08-27 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 水溶性一酸化窒素放出ポリグルコサミンおよびそれらの使用 |
Also Published As
Publication number | Publication date |
---|---|
JP2020515688A (ja) | 2020-05-28 |
CN110461338A (zh) | 2019-11-15 |
EP3600338A1 (en) | 2020-02-05 |
CA3055474A1 (en) | 2018-10-04 |
US11723914B2 (en) | 2023-08-15 |
US20200030362A1 (en) | 2020-01-30 |
AU2018247167B2 (en) | 2024-05-16 |
EP3600338A4 (en) | 2020-10-28 |
WO2018178902A1 (en) | 2018-10-04 |
AU2018247167A1 (en) | 2019-09-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7403152B2 (ja) | 生分解可能な抗菌性スキャフォールドとしての一酸化窒素放出性ポリアミノグリコシドおよびそれに関する方法背景 | |
US11421044B2 (en) | Nitric oxide-releasing antibacterial polymers and scaffolds fabricated therefrom and methods pertaining thereto | |
EP3710514B1 (en) | Nitric oxide-releasing hyperbranched compounds as antibacterial scaffolds and methods pertaining thereto | |
US20210395191A1 (en) | Tunable nitric oxide-releasing macromolecules having multiple nitric oxide donor structures | |
US11672818B2 (en) | Nitric oxide-releasing cyclodextrins as biodegradable antibacterial scaffolds and methods pertaining thereto | |
AU2008218275B2 (en) | Bridged polycyclic compound based compositions for the inhibition and amelioration of disease | |
Yang et al. | Nitric oxide-releasing hyperbranched polyaminoglycosides for antibacterial therapy | |
CN114206325A (zh) | 用于生成一氧化氮的方法和组合物及其用途 | |
Fasiku et al. | Free radical-releasing systems for targeting biofilms | |
Yang | Nitric Oxide-Releasing Hyperbranched Polymers as Antibacterial Agents Against Dental Pathogens | |
Zhang | Novel Ciprofloxacin-Based Polymer-Antibiotic Conjugates as Antibacterial Additive in Dental Resin | |
Worley | Structure-activity characterization of nitric oxide-releasing dendrimers as dual-action antibacterial agents | |
WO2023220188A1 (en) | Nitric oxide-releasing glycosaminoglycans for wound healing |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210326 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210326 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220509 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220809 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221007 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221109 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230320 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230619 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230818 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230920 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231107 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231205 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7403152 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |