JP6067337B2 - 涙やけまたはヨダレやけの抑制剤 - Google Patents
涙やけまたはヨダレやけの抑制剤 Download PDFInfo
- Publication number
- JP6067337B2 JP6067337B2 JP2012246573A JP2012246573A JP6067337B2 JP 6067337 B2 JP6067337 B2 JP 6067337B2 JP 2012246573 A JP2012246573 A JP 2012246573A JP 2012246573 A JP2012246573 A JP 2012246573A JP 6067337 B2 JP6067337 B2 JP 6067337B2
- Authority
- JP
- Japan
- Prior art keywords
- tears
- acid
- chelate compound
- lactoferrin
- coloring
- 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
- 239000003112 inhibitor Substances 0.000 title claims description 17
- 208000010201 Exanthema Diseases 0.000 title 1
- 201000005884 exanthem Diseases 0.000 title 1
- 206010037844 rash Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 32
- 239000013522 chelant Substances 0.000 claims description 27
- 239000011701 zinc Substances 0.000 claims description 24
- 229910052751 metal Inorganic materials 0.000 claims description 23
- 239000002184 metal Substances 0.000 claims description 23
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052725 zinc Inorganic materials 0.000 claims description 11
- 206010013642 Drooling Diseases 0.000 claims description 10
- 208000008630 Sialorrhea Diseases 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 10
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 5
- 241000282465 Canis Species 0.000 claims description 4
- 241000282324 Felis Species 0.000 claims description 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
- 238000012360 testing method Methods 0.000 description 24
- 102000010445 Lactoferrin Human genes 0.000 description 21
- 108010063045 Lactoferrin Proteins 0.000 description 21
- 210000004209 hair Anatomy 0.000 description 21
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 21
- 229940078795 lactoferrin Drugs 0.000 description 21
- 235000021242 lactoferrin Nutrition 0.000 description 21
- 238000004040 coloring Methods 0.000 description 19
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 19
- 239000000243 solution Substances 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 13
- 241000282472 Canis lupus familiaris Species 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000012790 confirmation Methods 0.000 description 7
- 125000001311 dihydrolipoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(S[H])([H])C([H])([H])C([H])([H])S[H] 0.000 description 7
- 229910052742 iron Inorganic materials 0.000 description 7
- 238000002845 discoloration Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- -1 alkali metal salts Chemical class 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000003889 eye drop Substances 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- RHJKTCFGPGZIBP-UHFFFAOYSA-N 1-[6,8-bis(sulfanyl)octanoylamino]ethanesulfonic acid;sodium Chemical compound [Na].OS(=O)(=O)C(C)NC(=O)CCCCC(S)CCS RHJKTCFGPGZIBP-UHFFFAOYSA-N 0.000 description 2
- JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010023644 Lacrimation increased Diseases 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000008206 alpha-amino acids Nutrition 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000004317 lacrimation Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- HSARCAKRDFJMNW-UHFFFAOYSA-N 1-aminoethanesulfonic acid;2-aminoethanesulfonic acid Chemical group CC(N)S(O)(=O)=O.NCCS(O)(=O)=O HSARCAKRDFJMNW-UHFFFAOYSA-N 0.000 description 1
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 description 1
- 208000010772 Dog disease Diseases 0.000 description 1
- 206010013647 Drowning Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- TWLLPUMZVVGILS-UHFFFAOYSA-N Ethyl 2-aminobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N TWLLPUMZVVGILS-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 229960002749 aminolevulinic acid Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000720 eyelash Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
例えば、涙液中のラクトフェリンは涙やけ発症の原因であることが報告されている(非特許文献4)。また、ラクトフェリンの赤色発色には、ラクトフェリン−鉄イオン錯体が寄与することが報告されている(非特許文献5、特許文献1)。
(1)下式(I)で表される金属キレート化合物またはその薬理学上許容可能な塩を含有する、非ヒト哺乳動物の涙やけまたは涙やけの抑制剤:
(2)N−結合のアミノ酸がヒスチジンである、(1)に記載の抑制剤。
(3)N−結合のアミノC1〜C7アルキルスルホン酸が、アミノエチルスルホン酸である、(1)または(2)に記載の抑制剤。
(4)非ヒト哺乳動物が、イヌ科動物またはネコ科動物である、(1)〜(3)のいずれかに記載の抑制剤。
であり、さらに好ましくイヌ科動物またはネコ科動物であり、さらに一層好ましくはイヌまたはネコである。
水1 mLからなるサンプルNo.1、ラクトフェリン約3mgおよび水1 mL混合したサンプルNo.2、鉄粉末約7mgおよび水1 mL混合したサンプルNo.3、ならびに、ラクトフェリン約3mg、鉄粉末約7mgおよび水1 mL混合したサンプルNo.4をそれぞれ調製した。次に、これらのサンプルを室温下で1週間静置し、色の変化を観察した。
なお、色の変化は、専門パネル3名により以下の基準に従って評価した。
5 全く着色は感じられない(溶液に透明感を感じる)
4 着色は感じられない
3 わずかに着色が感じられる
2 着色が感じられる
1 強く着色が感じられる
ラクトフェリンおよび鉄による涙やけの検討1
試験例1に記載した組成で調製した溶液(サンプルNo.4)を1週間室温で静置し溶液の着色を確認した。次に、この溶液に刈り取ったラットの体毛を浸し3ヶ月室温下で静置した。その3ヶ月後、ラットの体毛を溶液から取り出し、ろ紙上に置き、付着物が確認できなくなるまで水で洗浄した。次に、室温下で乾燥させ、体毛の染色状況を観察した。
白色だったラットの体毛は、薄い褐色に染色された。この着色は白色体毛を有する哺乳動物に見られる涙やけの着色と同様であった。このように、ラクトフェリンと鉄を含有する着色溶液によってラット体毛が染色されたことから、鉄イオンと結合したラクトフェリンが涙やけの原因の1つであることが確認された。
ラクトフェリンおよび鉄による涙やけの検討2
白色犬の体毛を用いる以外、試験例2と同様の手法により試験を行い、体毛染色状況を観察した。
白色だったイヌの体毛は、薄い褐色に染色された。この着色は涙やけの着色と同様であった。このように、ラクトフェリンと鉄を含有する着色溶液によってイヌの体毛が染色されたことから、鉄イオンと結合したラクトフェリンが涙やけの原因の1つであることが確認された。
ラクトフェリン約3mgおよび鉄粉末約7mgを含有する溶液中DHL-His-Zn濃度が0.055mg/mL〜2.21mg/mLであるサンプルNo.5〜9を調製し、1週間静置した。次に、得られた溶液の着色状態を観察し、試験例1と同様の手法により着色評価を行った。
ラクトフェリン約3mgおよび鉄粉末約7mgを含有する溶液中DHL-Tau- Zn濃度が3.9mg/mlであるサンプルNo.10を調製し、1週間静置した。次に、得られた溶液の着色状態を観察し、試験例1と同様の手法によりサンプルNo.4(コントロールとの比較により着色評価を行った。
ラクトフェリン約3mgおよび鉄粉末約7mgを含有する溶液中市販品の涙やけ抑制剤1mlを添加したサンプルNo.11〜13を調製し、1週間静置した。次に、得られた溶液の着色状態を観察し、試験例1と同様の手法によりサンプルNo.4(コントロールとの比較により着色評価を行った。
なお、市販品は、サンプルNo.11は涙やけイヤー(商標)(トーラス株式会社)、サンプルNo.12はワンレイ 涙やけクリーナー(商標)(牧産業株式会社)およびサンプルNo.13はEye Envy(商標)NR(Eye envy社)を用いた。
DHL-His-Znを含有するローション剤(DHL-His-Zn 0.1重量%含有、溶媒−水)と、DHL-His-Znを含有するクリーム剤(DHL-His-Zn 0.5重量%含有、基剤−ポリアクリルアミド)を用意した。次に、涙やけを有するイヌ(犬種:MIX(マルチーズとプードル)、年齢5ヶ月、メス)の変色した毛に、少なくとも1日2回ローション剤およびクリーム剤を塗布することを4週間継続した。
試験前(A)では目の周りの毛は着色しているのに対して、試験後(B)では目の周りの着色はほぼ消失していた。
Claims (4)
- 下式(I)で表される金属キレート化合物またはその薬理学上許容可能な塩を含有する、非ヒト哺乳動物の涙やけまたはヨダレやけの抑制剤:
- N−結合のアミノ酸がヒスチジンである、請求項1に記載の抑制剤。
- N−結合のアミノC1〜C7アルキルスルホン酸が、アミノエチルスルホン酸である、請求項1または2に記載の抑制剤。
- 前記非ヒト哺乳動物が、イヌ科動物またはネコ科動物ある、請求項1〜3のいずれか一項に記載の抑制剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012246573A JP6067337B2 (ja) | 2012-08-20 | 2012-11-08 | 涙やけまたはヨダレやけの抑制剤 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012181814 | 2012-08-20 | ||
JP2012181814 | 2012-08-20 | ||
JP2012246573A JP6067337B2 (ja) | 2012-08-20 | 2012-11-08 | 涙やけまたはヨダレやけの抑制剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014058494A JP2014058494A (ja) | 2014-04-03 |
JP6067337B2 true JP6067337B2 (ja) | 2017-01-25 |
Family
ID=50615326
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012246573A Active JP6067337B2 (ja) | 2012-08-20 | 2012-11-08 | 涙やけまたはヨダレやけの抑制剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6067337B2 (ja) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63253013A (ja) * | 1987-04-08 | 1988-10-20 | Ichimaru Pharcos Co Ltd | メラニン生成抑制剤 |
FR2751538B1 (fr) * | 1996-07-26 | 1998-09-11 | Oreal | Utilisation de derives de l'acide n,n'-dibenzyl ethylenediamine n,n'-diacetique comme agents depigmentants |
JP2002068978A (ja) * | 2000-08-25 | 2002-03-08 | Taisho Pharmaceut Co Ltd | 涙染色症候群治療用点眼薬 |
-
2012
- 2012-11-08 JP JP2012246573A patent/JP6067337B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2014058494A (ja) | 2014-04-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Oja et al. | Pharmacology of taurine | |
EP4331668A3 (en) | Compounds for inhibiting nlrp3 and uses thereof | |
JP4113957B2 (ja) | テトラフルオロベンジル誘導体及びこれを含有する急性及び退行性脳神経系疾患の予防及び治療用薬学的組成物 | |
ES2758554T3 (es) | Aminoácidos gama para tratamiento de trastornos oculares | |
ES2700213T3 (es) | Preparación farmacológica para uso tópico que contiene N-palmitoil-vainillamida | |
DE502006001941D1 (de) | Verwendung der SALZE, ANLAGERUNGS- UND KOMPLEXVERBINDUNGEN DER GUANIDINOESSIGSÄURE | |
ITMI20111033A1 (it) | Procedimento per la preparazione di una composizione comprendente complessi metallici in matrice organica oleosa | |
US9421190B2 (en) | Compositions comprising amino acids for prevention and/or treatment of renal disorders | |
US9480704B2 (en) | Topically administered strontium-containing complexes for treating pain, pruritis and inflammation | |
JP6067337B2 (ja) | 涙やけまたはヨダレやけの抑制剤 | |
RU2477722C1 (ru) | Способ получения литиевой соли коменовой кислоты и применение ее как антиоксидантного стресс- и нейропротекторного средства | |
US6451761B1 (en) | N′N′-dichlorinated omega-amino acids and uses thereof | |
KR100278533B1 (ko) | 아미노산 유도체 및 항활성산소제 | |
BR112021015580A2 (pt) | Composição de aspersão de agente aversivo | |
Jeong et al. | Nanocrystals continuously releasing nitric oxide: Promoting cell migration and increasing cell survival against oxidative stress | |
Rana et al. | Supplementation of ascorbic acid prevents oxidative damages in arsenic-loaded hepatic tissue of rat: an ex vivo study | |
Tekuri et al. | Determination of median lethal dose of zinc chloride in wistar rat | |
TWI704127B (zh) | 富勒烯衍生物及其用途 | |
AR042295A1 (es) | Sales fumarato cristalinas de furo [ 2,3- c ] piridinilcarboxamida sustituida con 1- azabiciclo [ 2. 2. 2 ] octilo y composiciones y preparaciones de las mismas | |
ES2547699T3 (es) | L-carnitina para suprimir la cristalización | |
TW200808717A (en) | Skin whitening agent containing zinc as active ingredient | |
JP3736405B2 (ja) | アミノ酸誘導体及び抗活性酸素剤 | |
JP2015089877A (ja) | αリポ酸誘導体含有粘稠性製剤 | |
DE399904C (de) | Verfahren zur Herstellung von organischen Quecksilberverbindungen | |
Saransaari | 8 Taurine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150714 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160531 |
|
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: 20161122 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161221 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6067337 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |