JPWO2020158643A1 - External agent - Google Patents
External agent Download PDFInfo
- Publication number
- JPWO2020158643A1 JPWO2020158643A1 JP2020569605A JP2020569605A JPWO2020158643A1 JP WO2020158643 A1 JPWO2020158643 A1 JP WO2020158643A1 JP 2020569605 A JP2020569605 A JP 2020569605A JP 2020569605 A JP2020569605 A JP 2020569605A JP WO2020158643 A1 JPWO2020158643 A1 JP WO2020158643A1
- Authority
- JP
- Japan
- Prior art keywords
- acid
- tranexamic acid
- crystallization
- tranexamic
- mass
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims abstract description 44
- 229960000401 tranexamic acid Drugs 0.000 claims abstract description 38
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 34
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 238000002360 preparation method Methods 0.000 claims abstract description 21
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 19
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 16
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims abstract description 14
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 14
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 13
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims abstract description 12
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract description 11
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 11
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 11
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 11
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 11
- 239000004220 glutamic acid Substances 0.000 claims abstract description 11
- 239000004475 Arginine Substances 0.000 claims abstract description 10
- 239000004471 Glycine Substances 0.000 claims abstract description 10
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000004473 Threonine Substances 0.000 claims abstract description 10
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 10
- 235000009697 arginine Nutrition 0.000 claims abstract description 10
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 9
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 claims description 22
- 229940026510 theanine Drugs 0.000 claims description 9
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 5
- 229940079889 pyrrolidonecarboxylic acid Drugs 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 abstract description 26
- 230000008025 crystallization Effects 0.000 abstract description 26
- -1 tranexamic acid cetyl ester Chemical class 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 239000002537 cosmetic Substances 0.000 description 9
- 229960002989 glutamic acid Drugs 0.000 description 9
- 229960005261 aspartic acid Drugs 0.000 description 8
- 229960002429 proline Drugs 0.000 description 8
- 229960003121 arginine Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229960002898 threonine Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 229960001153 serine Drugs 0.000 description 6
- 239000006210 lotion Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
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- 239000000467 phytic acid Substances 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 150000005846 sugar alcohols Polymers 0.000 description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
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- 238000010191 image analysis Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 229940058015 1,3-butylene glycol Drugs 0.000 description 2
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- DATAGRPVKZEWHA-UHFFFAOYSA-N L-gamma-glutamyl-n-ethylamine Natural products CCNC(=O)CCC(N)C(O)=O DATAGRPVKZEWHA-UHFFFAOYSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
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- 229910052700 potassium Inorganic materials 0.000 description 2
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- 210000004761 scalp Anatomy 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
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- YSRSBDQINUMTIF-SNVBAGLBSA-N (2r)-decane-1,2-diol Chemical compound CCCCCCCC[C@@H](O)CO YSRSBDQINUMTIF-SNVBAGLBSA-N 0.000 description 1
- 229940015975 1,2-hexanediol Drugs 0.000 description 1
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- JVONGXDERNPTPQ-UHFFFAOYSA-N 2-(hydroxymethyl)-3,5,5-trimethylcyclohexan-1-ol Chemical compound CC1CC(C)(C)CC(O)C1CO JVONGXDERNPTPQ-UHFFFAOYSA-N 0.000 description 1
- PDHFSBXFZGYBIP-UHFFFAOYSA-N 2-[2-(2-hydroxyethylsulfanyl)ethylsulfanyl]ethanol Chemical compound OCCSCCSCCO PDHFSBXFZGYBIP-UHFFFAOYSA-N 0.000 description 1
- DSKYSDCYIODJPC-UHFFFAOYSA-N 2-butyl-2-ethylpropane-1,3-diol Chemical compound CCCCC(CC)(CO)CO DSKYSDCYIODJPC-UHFFFAOYSA-N 0.000 description 1
- QWGRWMMWNDWRQN-UHFFFAOYSA-N 2-methylpropane-1,3-diol Chemical compound OCC(C)CO QWGRWMMWNDWRQN-UHFFFAOYSA-N 0.000 description 1
- XPFCZYUVICHKDS-UHFFFAOYSA-N 3-methylbutane-1,3-diol Chemical compound CC(C)(O)CCO XPFCZYUVICHKDS-UHFFFAOYSA-N 0.000 description 1
- FNQIYTUXOKTMDM-UHFFFAOYSA-N 3-phenoxypropane-1,2-diol Chemical compound OCC(O)COC1=CC=CC=C1 FNQIYTUXOKTMDM-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N 5-oxoproline Chemical compound OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- 229930182844 L-isoleucine Natural products 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 229920001273 Polyhydroxy acid Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 241001522306 Serinus serinus Species 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- BMRWNKZVCUKKSR-UHFFFAOYSA-N butane-1,2-diol Chemical compound CCC(O)CO BMRWNKZVCUKKSR-UHFFFAOYSA-N 0.000 description 1
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 1
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- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 description 1
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- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
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- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
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- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
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- 230000002087 whitening effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
Abstract
（Ａ）トラネキサム酸、トラネキサム酸誘導体及びこれらの塩から選ばれる１種以上、及び、（Ｂ）アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、これらの誘導体、並びにこれら及びこれらの誘導体の塩から選ばれる１種以上を含有する外用剤とすることで、トラネキサム酸の結晶化を抑制することができる。(A) tranexamic acid, one or more selected from tranexamic acid derivatives and salts thereof, and (B) arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and Crystallization of tranexamic acid can be suppressed by using an external preparation containing at least one selected from these and salts of these derivatives.
Description
本発明は、トラネキサム酸を含有する外用剤に関するものである。 The present invention relates to an external preparation containing tranexamic acid.
トラネキサム酸は、止血作用や抗炎症作用を有し、歯磨剤、医薬品等に広く使用されている。また、荒れ肌改善作用や美白作用を有し、化粧品等の皮膚又は毛髪用外用剤としても使用されている。 Tranexamic acid has a hemostatic effect and an anti-inflammatory effect, and is widely used in dentifrices, pharmaceuticals and the like. It also has a rough skin improving effect and a whitening effect, and is also used as an external preparation for skin or hair such as cosmetics.
しかしながら、トラネキサム酸は水溶性である一方で非常に結晶性が高く、水分の蒸発により、容易に結晶が析出するという課題があった。このようなトラネキサム酸の結晶化抑制の方法としては、フィチン酸（特許文献１：特開２０１８−４８０９７号公報）、ポリヒドロキシ酸（特許文献２：特開２０１３−１２１９５５号公報）等を併用する方法が提案されている。しかしながら、トラネキサム酸の結晶化抑制効果にさらに優れた方法が望まれていた。 However, while tranexamic acid is water-soluble, it has a very high crystallinity, and there is a problem that crystals are easily precipitated by evaporation of water. As such a method for suppressing the crystallization of tranexamic acid, phytic acid (Patent Document 1: JP-A-2018-48097), polyhydroxy acid (Patent Document 2: JP-A-2013-121955) and the like are used in combination. A method has been proposed. However, a method having a further excellent effect of suppressing the crystallization of tranexamic acid has been desired.
本発明は上記事情に鑑みなされたもので、トラネキサム酸の結晶化抑制効果を有する外用剤を提供することを目的とする。 The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an external preparation having an effect of suppressing crystallization of tranexamic acid.
本発明者らは、上記目的を達成するため鋭意検討した結果、特定のアミノ酸を併用することで、顕著なトラネキサム酸の結晶化抑制効果が得られることを知見し、本発明をなすに至ったものである。 As a result of diligent studies to achieve the above object, the present inventors have found that a remarkable effect of suppressing crystallization of tranexamic acid can be obtained by using a specific amino acid in combination, and have completed the present invention. It is a thing.
従って、本発明は下記外用剤を提供する。以下、成分名として化粧品表示名称を使用する場合がある。
１．（Ａ）トラネキサム酸、トラネキサム酸誘導体及びこれらの塩から選ばれる１種以上、及び、
（Ｂ）アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、これらの誘導体、並びにこれら及びこれらの誘導体の塩から選ばれる１種以上
を含有する外用剤。
２．（Ｂ）成分が、アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、テアニン、ピロリドンカルボン酸、及びこれらの塩から選ばれる１種以上である１記載の外用剤。Therefore, the present invention provides the following external preparations. Hereinafter, the cosmetic label name may be used as the ingredient name.
1. 1. (A) One or more selected from tranexamic acid, tranexamic acid derivatives and salts thereof, and
(B) An external preparation containing one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts of these and derivatives thereof.
2. 2. (B) The external preparation according to 1.
本発明によれば、顕著なトラネキサム酸の結晶化抑制効果を有する外用剤を提供することができる。これにより、トラネキサム酸の効果が十分に発揮できると共に、外用剤の外観も良く、使用感も良好なものとなる。 According to the present invention, it is possible to provide an external preparation having a remarkable tranexamic acid crystallization inhibitory effect. As a result, the effect of tranexamic acid can be fully exerted, the appearance of the external preparation is good, and the feeling of use is also good.
以下、本発明について詳細に説明する。
[（Ａ）成分]
（Ａ）成分は、トラネキサム酸、トラネキサム酸誘導体及びこれらの塩から選ばれる１種以上であり、１種単独で又は２種以上を適宜組み合わせて用いることができる。トラネキサム酸は、トランス−４−アミノメチルシクロヘキサン−１−カルボン酸である。トラネキサム酸誘導体としては、トラネキサム酸セチルエステル等のエステル誘導体、トラネキサム酸メチルアミド等のアミド誘導体等が挙げられる。塩としては、特に限定されず、例えば、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アルミニウム、鉄、亜鉛等の金属塩、アンモニウム、モノエタノールアミン、ジエタノールアミン、トリエタノールアミン、ステアリルアミン等の有機アミン塩等が挙げられる。Hereinafter, the present invention will be described in detail.
[(A) component]
The component (A) is one or more selected from tranexamic acid, tranexamic acid derivatives and salts thereof, and one kind alone or two or more kinds can be used as appropriate. Tranexamic acid is a trans-4-aminomethylcyclohexane-1-carboxylic acid. Examples of the tranexamic acid derivative include an ester derivative such as tranexamic acid cetyl ester and an amide derivative such as tranexamic acid methylamide. The salt is not particularly limited, and is, for example, an alkali metal salt such as sodium and potassium, an alkaline earth metal salt such as calcium and magnesium, a metal salt such as aluminum, iron and zinc, ammonium, monoethanolamine, diethanolamine and tri. Examples thereof include organic amine salts such as ethanolamine and stearylamine.
（Ａ）成分の含有量は特に限定されないが、外用剤中１〜５質量％が好ましく、１〜２質量％がより好ましい。 The content of the component (A) is not particularly limited, but is preferably 1 to 5% by mass, more preferably 1 to 2% by mass in the external preparation.
［（Ｂ）成分］
（Ｂ）成分は、アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、これらの誘導体、並びにこれら及びこれらの誘導体の塩から選ばれる１種以上であり、１種単独で又は２種以上を適宜組み合わせて用いることができる。[(B) component]
The component (B) is one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts of these and derivatives thereof, and one type alone. Or two or more of them can be used in combination as appropriate.
上記アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸（ＧＡＢＡ）は、アミノ酸であり、Ｄ体、Ｌ体又はＤＬ体でもよい。これらの誘導体としては、アミノ酸中の水素原子が、アルキル基、アルケニル基、アリール基等で置換されたエステル誘導体；水酸基の水素原子が、アシル基で置換されたエステル誘導体；水酸基の水素原子が、アルキル基、アルケニル基、アリール基等で置換されたエーテル誘導体；アミノ基の水素原子が、アシル基で置換されたアミド誘導体；アミノ基の水素原子が、アルキル基、アルケニル基、アリール基等で置換されたアミン誘導体等が挙げられる。具体的には、グルタミン酸の誘導体である、テアニン、ピロリドンカルボン酸等が挙げられる。 The above-mentioned arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine and γ-aminobutyric acid (GABA) are amino acids and may be D-form, L-form or DL-form. Examples of these derivatives include an ester derivative in which a hydrogen atom in an amino acid is substituted with an alkyl group, an alkenyl group, an aryl group, or the like; an ester derivative in which a hydrogen atom of a hydroxyl group is substituted with an acyl group; An ether derivative substituted with an alkyl group, an alkenyl group, an aryl group, etc .; an amide derivative in which the hydrogen atom of the amino group is substituted with an acyl group; the hydrogen atom of the amino group is substituted with an alkyl group, an alkenyl group, an aryl group, etc. The above-mentioned amine derivative and the like can be mentioned. Specific examples thereof include theanine and pyrrolidone carboxylic acid, which are derivatives of glutamic acid.
上記アミノ酸塩及びアミノ酸誘導体の塩としては、特に限定されず、例えば、ナトリウム、カリウム等のアルカリ金属塩、カルシウム、マグネシウム等のアルカリ土類金属塩、アルミニウム、鉄、亜鉛等の金属塩、アンモニウム、モノエタノールアミン、ジエタノールアミン、トリエタノールアミン、ステアリルアミン等の有機アミン塩等が挙げられる。 The salt of the amino acid salt and the salt of the amino acid derivative is not particularly limited, and for example, an alkali metal salt such as sodium and potassium, an alkaline earth metal salt such as calcium and magnesium, a metal salt such as aluminum, iron and zinc, ammonium, and the like. Examples thereof include organic amine salts such as monoethanolamine, diethanolamine, triethanolamine and stearylamine.
（Ｂ）成分としては、トラネキサム酸の結晶化抑制効果の点から、アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、テアニン、ピロリドンカルボン酸、及びこれらの塩が好ましい。 As the component (B), arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, theanine, pyrrolidonecarboxylic acid, and salts thereof are preferable from the viewpoint of the crystallization inhibitory effect of tranexamic acid. ..
グルタミン酸又はその塩と、γ−アミノ酪酸又はその塩との組み合わせ、γ−アミノ酪酸又はその塩とテアニンとの組み合わせにより、トラネキサム酸の結晶化抑制効果の相乗効果を得ることができる点から、これらの組み合わせが好ましい。 The combination of glutamic acid or a salt thereof and γ-aminobutyric acid or a salt thereof, or the combination of γ-aminobutyric acid or a salt thereof and theanine can obtain a synergistic effect of suppressing the crystallization of tranexamic acid. The combination of is preferable.
（Ｂ）成分の含有量は特に限定されないが、外用剤中０．０５〜５質量％が好ましく、０．１２５〜２質量％がより好ましく、０．２５〜１質量％がさらに好ましい。この範囲とすることで、トラネキサム酸の結晶化抑制効果がより向上する。 The content of the component (B) is not particularly limited, but is preferably 0.05 to 5% by mass, more preferably 0.125 to 2% by mass, still more preferably 0.25 to 1% by mass in the external preparation. Within this range, the effect of suppressing crystallization of tranexamic acid is further improved.
特に下記の成分又はその塩の場合は、下記範囲が特に好ましい。
アルギニン又はその塩：０．５〜２質量％
アスパラギン酸：０．１２５〜１質量％
グルタミン酸：０．１２５〜１質量％
グリシン：０．７５〜１．２５質量％
プロリン：１〜２質量％
セリン：０．２５〜１質量％
トレオニン：０．５〜１質量％
テアニン：０．１２５〜０．２５質量％
γ−アミノ酪酸：０．１２５〜０．２５質量％
ピロリドンカルボン酸：０．２５〜０．５質量％In particular, in the case of the following components or salts thereof, the following range is particularly preferable.
Arginine or its salt: 0.5-2% by mass
Aspartic acid: 0.125 to 1% by mass
Glutamic acid: 0.125 to 1% by mass
Glycine: 0.75-1.25% by mass
Proline: 1-2% by mass
Serin: 0.25 to 1% by mass
Threonine: 0.5-1% by mass
Theanine: 0.125-0.25% by mass
γ-Aminobutyric acid: 0.125 to 0.25% by mass
Pyrrolidone carboxylic acid: 0.25 to 0.5% by mass
（Ａ）：（Ｂ）で表される、（Ａ）成分と（Ｂ）成分との含有質量比は２０：１〜０．５：１が好ましく、１６：１〜１：１がより好ましく、８：１〜２：１がさらに好ましい。この範囲とすることで、トラネキサム酸の結晶化抑制効果がより向上する。 (A): The content mass ratio of the component (A) to the component (B) represented by (B) is preferably 20: 1 to 0.5: 1, more preferably 16: 1 to 1: 1. 8: 1 to 2: 1 is more preferable. Within this range, the effect of suppressing crystallization of tranexamic acid is further improved.
［任意成分］
本発明の外用剤には、本発明の効果を損なわない範囲で、外用剤に通常用いられる成分を適量配合することができる。このような成分としては、例えば、美白剤、抗老化剤、保湿剤、防腐剤、抗菌剤、酵素、植物抽出物等の機能性成分の他、油剤、界面活性剤、香料、色素、ｐＨ調整剤、精製水等の水等が挙げられる。これらは、それぞれ１種単独で又は２種以上を適宜組み合わせて、適量を用いることができる。[Arbitrary ingredient]
The external preparation of the present invention may contain an appropriate amount of components usually used for the external preparation as long as the effects of the present invention are not impaired. Examples of such components include functional components such as whitening agents, antiaging agents, moisturizers, preservatives, antibacterial agents, enzymes, and plant extracts, as well as oils, surfactants, fragrances, pigments, and pH adjustments. Examples include water such as agents and purified water. These can be used alone or in combination of two or more in appropriate amounts.
中でも、本発明の外用剤には多価アルコールを配合することが好ましい。多価アルコールは１種単独で又は２種以上を適宜組み合わせて用いることができる。多価アルコールとしては、イソペンチルジオール、エチルヘキサンジオール、カプリリルグリコール、グリコール、（Ｃ１５−１８）グリコール、（Ｃ２０−３０）グリコール、グリセリン、ジエチレングリコール、ジグリセリン、ジチアオクタンジオール、ジプロピレングリコール、チオグリセリン、１，１０−デカンジオール、デシレングリコール、トリエチレングリコール、トリメチルヒドロキシメチルシクロヘキサノール、フィタントリオール、フェノキシプロパンジオール、１，２−ブタンジオール、２，３−ブタンジオール、ブチルエチルプロパンジオール、１，３−ブチレングリコール等のＢＧ、ＰＧ、１，２−ヘキサンジオール、ヘキシレングリコール、ペンチレングリコール、メチルプロパンジオール、メンタンジオール、ラウリルグリコール等が挙げられる。 Above all, it is preferable to add a polyhydric alcohol to the external preparation of the present invention. The polyhydric alcohol may be used alone or in combination of two or more. Examples of the polyhydric alcohol include isopentyldiol, ethylhexanediol, caprylyl glycol, glycol, (C15-18) glycol, (C20-30) glycol, glycerin, diethylene glycol, diglycerin, dithiaoctanediol, and dipropylene glycol. Thioglycerin, 1,10-decanediol, decylene glycol, triethylene glycol, trimethylhydroxymethylcyclohexanol, phytantriol, phenoxypropanediol, 1,2-butanediol, 2,3-butanediol, butylethylpropanediol , BG such as 1,3-butylene glycol, PG, 1,2-hexanediol, hexylene glycol, pentylene glycol, methylpropanediol, mentandiol, laurylglycol and the like.
多価アルコールを配合する場合、その含有量は、外用剤中１．０〜３０．０質量％が好ましく、２．０〜３０．０質量％がより好ましい。 When the polyhydric alcohol is blended, the content thereof is preferably 1.0 to 30.0% by mass, more preferably 2.0 to 30.0% by mass in the external preparation.
外用剤としては、医薬品、医薬部外品、化粧品等特に限定されない。中でも皮膚用、頭髪用の外用剤に好適である。皮膚は、顔、頭皮、腕等の身体等、特に限定されないが、口腔内は含まない。外用剤の形態としては特に限定されず、液剤、懸濁剤、乳剤、クリーム剤、軟膏剤、ゲル剤、ローション剤、エアゾール剤等にすることができる。トラネキサム酸の結晶化抑制効果が期待される形態としては、液剤、ローション剤等が挙げられる。 The external preparation is not particularly limited to pharmaceuticals, quasi-drugs, cosmetics and the like. Above all, it is suitable for external preparations for skin and hair. The skin is not particularly limited to the body such as the face, scalp and arms, but does not include the oral cavity. The form of the external preparation is not particularly limited, and may be a liquid, a suspension, an emulsion, a cream, an ointment, a gel, a lotion, an aerosol, or the like. Examples of the form expected to suppress the crystallization of tranexamic acid include liquids and lotions.
外用剤、特に医薬部外品又は化粧品用の外用剤とする場合の用途としては、例えば、化粧水、乳液、クリーム、ジェル、美容液、日焼け止め用化粧料、パック、マスク、ハンドクリーム、ボディローション、ボディークリーム等の基礎化粧料；洗顔料、メイク落とし、ボディーシャンプー等の皮膚洗浄料；シャンプー、リンス、トリートメント等の頭皮及び毛髪化粧料；ファンデーション、リップ、マスカラ等のメイクアップ化粧料等が挙げられる。 Applications for external use, especially for non-medicinal products or cosmetics, include, for example, lotions, milky lotions, creams, gels, beauty liquids, sunscreen cosmetics, packs, masks, hand creams, and bodies. Basic cosmetics such as lotions and body creams; Skin cleaning agents such as washing pigments, makeup removers and body shampoos; Scalp and hair cosmetics such as shampoos, rinses and treatments; Makeup cosmetics such as foundations, lips and mascara Can be mentioned.
外用剤のｐＨは特に限定されず、２５℃で３〜８が好ましく、５．０〜７．０がより好ましい。 The pH of the external preparation is not particularly limited, and is preferably 3 to 8 at 25 ° C., more preferably 5.0 to 7.0.
[トラネキサム酸の結晶化抑制方法]
本発明は、（Ａ）トラネキサム酸、トラネキサム酸誘導体及びこれらの塩から選ばれる１種以上を含有する外用剤に、（Ｂ）アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、これらの誘導体、並びにこれら及びこれらの誘導体の塩から選ばれる１種以上を配合する、トラネキサム酸の結晶化抑制方法を提供する。また、上記（Ａ）成分と（Ｂ）成分とを含有するトラネキサム酸の結晶化抑制剤とすることもできる。それぞれ、好適な成分、配合量等は上記と同じである。[Method of suppressing crystallization of tranexamic acid]
The present invention comprises (A) tranexamic acid, a tranexamic acid derivative, and an external preparation containing one or more selected from these salts, and (B) arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-. Provided is a method for suppressing crystallization of tranexamic acid, which comprises one or more selected from aminobutyric acid, derivatives thereof, and salts thereof and derivatives thereof. Further, it can also be used as a crystallization inhibitor of tranexamic acid containing the above-mentioned component (A) and component (B). Suitable components, blending amounts, etc. are the same as above.
以下、実施例及び比較例を示し、本発明を具体的に説明するが、本発明は下記の実施例に制限されるものではない。なお、下記の例において特に明記のない場合は、組成の「％」は質量％、比率は質量比を示し、表中の各成分の量は純分換算した量である。 Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. Unless otherwise specified in the following examples, "%" in the composition indicates mass%, the ratio indicates mass ratio, and the amount of each component in the table is the amount converted to pure content.
下記成分について、表中に記載の濃度でトラネキサム酸の結晶化抑制試験を行った。結果を表中に併記する。
[試験例：トラネキサム酸の結晶化抑制]
（１）試験サンプル（ｐＨ３〜８）
下記組成の組成物を作製した。
トラネキサム酸 ２％
１，３−ブチレングリコール ３０％
サンプル 表中の記載濃度
精製水 残部
合計 １００％The following components were subjected to a crystallization inhibition test of tranexamic acid at the concentrations shown in the table. The results are also shown in the table.
[Test example: Inhibition of crystallization of tranexamic acid]
(1) Test sample (pH 3-8)
A composition having the following composition was prepared.
Tranexamic acid 2%
1,3-butylene glycol 30%
Concentrations listed in the sample table
Purified water balance
100% in total
（２）試験方法
上記組成物を下記プレートに３．０ｇ／ウェルで添加し、室温で２４時間保存後に下記（３）に記載の方法で画像解析を行った。
プレート
株式会社ステム社製
材質：ＰＳ（ポリスチレン）
プレートサイズ：１２８×８６×２０ｍｍ
型番：６穴（平底）
ウェル径×高さ（ｍｍ）：φ３３．５×１６．７(2) Test method The above composition was added to the following plate at 3.0 g / well, stored at room temperature for 24 hours, and then image analysis was performed by the method described in (3) below.
Plate manufactured by Stem Co., Ltd. Material: PS (polystyrene)
Plate size: 128 x 86 x 20 mm
Model number: 6 holes (flat bottom)
Well diameter x height (mm): φ33.5 x 16.7
（３）画像解析
・画像解析
スキャナ：Ｄｏｃｕ Ｃｅｎｔｅｒ−ＩＶ Ｃ５５７５（Ｆｕｊｉ Ｘｅｒｏｘ社製）
画像取り込み解像度：３００ｄｐｉ
画像解析ソフト：ＩｍａｇｅＪ（ｖｅｒ． １．５０ｉ）
画像のウェル内部の領域をＯｖａｌツールによって円形に選択し、Ａｎａｌｙｚｅ／ＭｅａｓｕｒｅでＭｅａｎ ｇｒａｙ ｖａｌｕｅを測定した。(3) Image analysis / image analysis Scanner: Docu Center-IV C5575 (manufactured by Fuji Xerox)
Image capture resolution: 300 dpi
Image analysis software: ImageJ (ver. 1.50i)
The area inside the well of the image was selected in a circle by the Oval tool, and the Mean gray value was measured by Meanize / Measurement.
（４）Ｍｅａｎ ｇｒａｙ ｖａｌｕｅの結果から、トラネキサム酸の結晶化抑制効果を下記基準で示す。数値が低いほど、トラネキサム酸の結晶化抑制効果が高いことを示す。
＋＋＋：２０未満
＋＋：２０以上４０未満
＋：４０以上６０未満
−：６０以上(4) From the results of Mean gray value, the crystallization inhibitory effect of tranexamic acid is shown by the following criteria. The lower the value, the higher the crystallization inhibitory effect of tranexamic acid.
+++: Less than 20 ++: 20 or more and less than 40 +: 40 or more and less than 60-: 60 or more
以下、略称を示す。
Ａｌａ：Ｌ−アラニン
Ａｒｇ：Ｌ−アルギニン
Ａｓｐ：Ｌ−アスパラギン酸
Ｃｙｓ：ＤＬ−システイン
Ｇｌｕ：Ｌ−グルタミン酸
Ｇｌｙ：Ｌ−グリシン
Ｈｉｓ：Ｌ−ヒスチジン
Ｉｌｅ：Ｌ−イソロイシン
Ｐｒｏ：Ｌ−プロリン
Ｓｅｒ：Ｌ−セリン
Ｔｈｒ：ＤＬ−トレオニン
Ｔｙｒ：Ｌ−チロシン
Ｐｏｌｙ−Ｌｙｓ：ポリ−Ｌ−リジン
Ｐｏｌｙ−ＰＡ：ポリリン酸Ｎａ
Ｔｈｅａｎｉｎｅ：Ｌ−テアニン
ＧＡＢＡ：γ−アミノ酪酸
ＰＣＡ：ＤＬ−ピロリドンカルボン酸Hereinafter, abbreviations are shown.
Ala: L-Alanine Arg: L-Arginine Asp: L-Cysteine Cys: DL-Cysteine Glu: L-Glycine Gly: L-Glycine His: L-Histidine Ile: L-Isoleucine Pro: L-Proline Ser: L- Serin Thr: DL-Threonine Tyr: L-tyrosine Poly-Lys: Poly-L-Glycine Poly-PA: Na polyphosphate
Theanine: L-Theanine GABA: γ-Aminobutyric Acid PCA: DL-Pyrrolidone Carboxylic Acid
Ａｓｐ０．５％、０．２５％、０．１２５％、フィチン酸０．１６％、ブランクの上記トラネキサム酸の結晶化抑制試験における、室温で２４時間保存後の写真を図１に示す。アスパラギン酸は、フィチン酸よりも高いトラネキサム酸の結晶化抑制効果を有することが確認された。 FIG. 1 shows photographs of the above tranexamic acid crystallization suppression test of Asp 0.5%, 0.25%, 0.125%, phytic acid 0.16%, and blank after storage at room temperature for 24 hours. It was confirmed that aspartic acid has a higher effect of suppressing the crystallization of tranexamic acid than phytic acid.
上記結果から、アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、テアニン、γ−アミノ酪酸、ピロリドンカルボン酸は、トラネキサム酸の結晶化抑制効果を有することが確認された。 From the above results, it was confirmed that arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, theanine, γ-aminobutyric acid, and pyrrolidonecarboxylic acid have the effect of suppressing the crystallization of tranexamic acid.
上記結果から、アラニン、システイン、ヒスチジン、イソロイシン、チロシン、ポリリジン、ポリリン酸ナトリウムには、トラネキサム酸の結晶化抑制効果は確認されなかった。 From the above results, alanine, cysteine, histidine, isoleucine, tyrosine, polylysine, and sodium polyphosphate were not confirmed to have an inhibitory effect on the crystallization of tranexamic acid.
表３の結果から、Ｇｌｕ：Ｌ−グルタミン酸とＧＡＢＡ：γ−アミノ酪酸とを併用することで、トラネキサム酸の結晶化抑制における相乗効果が確認された。
表４の結果から、合計量が０．１２５％となるように調整しているので、ＧＡＢＡとＴｈｅａｎｉｎｅとが相加効果の場合は「＋」となるが、「＋＋」となっているので、ＧＡＢＡ：γ−アミノ酪酸と、Ｔｈｅａｎｉｎｅ：Ｌ−テアニンを併用することで、トラネキサム酸の結晶化抑制における相乗効果が確認された。From the results in Table 3, the synergistic effect in suppressing the crystallization of tranexamic acid was confirmed by the combined use of Glu: L-glutamic acid and GABA: γ-aminobutyric acid.
From the results in Table 4, the total amount is adjusted to 0.125%, so if GABA and Theanine have an additive effect, it will be "+", but since it is "++", it will be "++". The combined use of GABA: γ-aminobutyric acid and Theanine: L-theanine confirmed a synergistic effect in suppressing the crystallization of tranexamic acid.
［実施例、比較例］
精製水に精製水以外の成分を混合溶解して調製し、表４に示す組成の化粧水を得た。化粧品表示名称で記載する。上記と同様の方法でトラネキサム酸の結晶化抑制効果を評価した。結果を表中に併記する。[Examples, comparative examples]
It was prepared by mixing and dissolving components other than purified water in purified water to obtain a cosmetic water having the composition shown in Table 4. Describe with the cosmetics label name. The crystallization inhibitory effect of tranexamic acid was evaluated by the same method as described above. The results are also shown in the table.
Claims (2)
（Ｂ）アルギニン、アスパラギン酸、グルタミン酸、グリシン、プロリン、セリン、トレオニン、γ−アミノ酪酸、これらの誘導体、並びにこれら及びこれらの誘導体の塩から選ばれる１種以上
を含有する外用剤。(A) One or more selected from tranexamic acid, tranexamic acid derivatives and salts thereof, and
(B) An external preparation containing one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts of these and derivatives thereof.
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| JPH0788292B2 (en) * | 1986-09-05 | 1995-09-27 | ライオン株式会社 | Oral composition |
| JPH11269034A (en) * | 1998-03-20 | 1999-10-05 | Shiseido Co Ltd | Skin prepafation for external use for improving acne |
| JP2000281556A (en) * | 1999-03-29 | 2000-10-10 | Shiseido Co Ltd | Skin preparation for external use |
| JP2002003373A (en) * | 2000-06-27 | 2002-01-09 | Shiseido Co Ltd | Skin care preparation |
| JP2002212072A (en) * | 2001-01-16 | 2002-07-31 | Matthias Rath | Synergistic composition comprising ascorbates and lysine for state related to extracellular matrix degeneration |
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| JP2010120920A (en) * | 2008-11-17 | 2010-06-03 | Masae Kurihara | Functionally fulfilled mail genital organ by compounding cream to be coated on mail genital organ with tranexamic acid and glutamic acid, and also visibly fulfilled mail genital organ by adding fish scale |
| EP2695605B1 (en) * | 2012-08-07 | 2017-05-03 | Parapharm Development Ltd. | Tranexamic acid composition |
| CN106456484A (en) * | 2014-06-30 | 2017-02-22 | 乐敦制药株式会社 | External preparation |
| JP6364322B2 (en) * | 2014-10-31 | 2018-07-25 | 株式会社コーセー | Cosmetic or skin preparation |
| JP6894207B2 (en) * | 2016-09-23 | 2021-06-30 | 日本精化株式会社 | Tranexamic acid-containing cosmetics or topical skin preparations |
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