JP6507127B2 - Foaming composition - Google Patents
Foaming composition Download PDFInfo
- Publication number
- JP6507127B2 JP6507127B2 JP2016139345A JP2016139345A JP6507127B2 JP 6507127 B2 JP6507127 B2 JP 6507127B2 JP 2016139345 A JP2016139345 A JP 2016139345A JP 2016139345 A JP2016139345 A JP 2016139345A JP 6507127 B2 JP6507127 B2 JP 6507127B2
- Authority
- JP
- Japan
- Prior art keywords
- poe
- hlb
- pop
- glycol
- less
- 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
- 239000000203 mixture Substances 0.000 title claims description 130
- 238000005187 foaming Methods 0.000 title claims description 28
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 99
- 239000011550 stock solution Substances 0.000 claims description 60
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 53
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical class OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 40
- 239000003380 propellant Substances 0.000 claims description 29
- 239000002736 nonionic surfactant Substances 0.000 claims description 26
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 13
- JPPRXACMNPYJNK-UHFFFAOYSA-N 1-docosoxydocosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCCCCCC JPPRXACMNPYJNK-UHFFFAOYSA-N 0.000 claims description 11
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 claims description 10
- 239000003125 aqueous solvent Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- -1 polyoxyethylene Polymers 0.000 claims description 8
- 239000004359 castor oil Substances 0.000 claims description 7
- 235000019438 castor oil Nutrition 0.000 claims description 7
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 6
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- 229940075529 glyceryl stearate Drugs 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 4
- 150000005215 alkyl ethers Chemical class 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 claims description 3
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 claims description 3
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000005639 Lauric acid Substances 0.000 claims description 3
- ONAIRGOTKJCYEY-UHFFFAOYSA-N Sucrose monostearate Chemical compound CCCCCCCCCCCCCCCCCC(O)=O.OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(CO)O1 ONAIRGOTKJCYEY-UHFFFAOYSA-N 0.000 claims description 3
- GCSPRLPXTPMSTL-IBDNADADSA-N [(2s,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[C@@]1([C@]2(CO)[C@H]([C@H](O)[C@@H](CO)O2)O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GCSPRLPXTPMSTL-IBDNADADSA-N 0.000 claims description 3
- NPTLAYTZMHJJDP-KTKRTIGZSA-N [3-[3-[3-[3-[3-[3-[3-[3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropoxy]-2-hydroxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)COCC(O)CO NPTLAYTZMHJJDP-KTKRTIGZSA-N 0.000 claims description 3
- 235000013871 bee wax Nutrition 0.000 claims description 3
- 239000012166 beeswax Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 3
- 125000005313 fatty acid group Chemical group 0.000 claims 1
- 239000006260 foam Substances 0.000 description 58
- 239000004094 surface-active agent Substances 0.000 description 56
- 210000003491 skin Anatomy 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000000443 aerosol Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000005755 formation reaction Methods 0.000 description 9
- 239000003915 liquefied petroleum gas Substances 0.000 description 9
- 239000003021 water soluble solvent Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000007921 spray Substances 0.000 description 8
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Polymers FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 6
- 229920001287 Chondroitin sulfate Polymers 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000009471 action Effects 0.000 description 5
- 229940059329 chondroitin sulfate Drugs 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 208000017520 skin disease Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 229920000136 polysorbate Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010040880 Skin irritation Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000002628 heparin derivative Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229960003511 macrogol Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000003595 mist Substances 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 230000036620 skin dryness Effects 0.000 description 3
- 230000036556 skin irritation Effects 0.000 description 3
- 231100000475 skin irritation Toxicity 0.000 description 3
- 239000001589 sorbitan tristearate Substances 0.000 description 3
- 235000011078 sorbitan tristearate Nutrition 0.000 description 3
- 229960004129 sorbitan tristearate Drugs 0.000 description 3
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
- 230000001180 sulfating effect Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 229920002642 Polysorbate 65 Polymers 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000003254 anti-foaming effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 2
- 229940043276 diisopropanolamine Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000037336 dry skin Effects 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 239000004088 foaming agent Substances 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- GTABBGRXERZUAH-UHFFFAOYSA-N hexadecan-1-ol;2-methyloxirane;oxirane Chemical compound C1CO1.CC1CO1.CCCCCCCCCCCCCCCCO GTABBGRXERZUAH-UHFFFAOYSA-N 0.000 description 2
- XJNUECKWDBNFJV-UHFFFAOYSA-N hexadecyl 2-ethylhexanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)C(CC)CCCC XJNUECKWDBNFJV-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 2
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 229940099511 polysorbate 65 Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 230000019635 sulfation Effects 0.000 description 2
- 238000005670 sulfation reaction Methods 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- SAMYFBLRCRWESN-UHFFFAOYSA-N 16-methylheptadecyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(C)C SAMYFBLRCRWESN-UHFFFAOYSA-N 0.000 description 1
- COPFWAGBXIWZNK-UHFFFAOYSA-N 2,3-bis(6-methylheptanoyloxy)propyl 6-methylheptanoate Chemical compound CC(C)CCCCC(=O)OCC(OC(=O)CCCCC(C)C)COC(=O)CCCCC(C)C COPFWAGBXIWZNK-UHFFFAOYSA-N 0.000 description 1
- IUGOPULVANEDRX-UHFFFAOYSA-N 2-ethylhexane-1,1-diol Chemical compound CCCCC(CC)C(O)O IUGOPULVANEDRX-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- BGRXBNZMPMGLQI-UHFFFAOYSA-N 2-octyldodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC BGRXBNZMPMGLQI-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 125000005274 4-hydroxybenzoic acid group Chemical class 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 208000001034 Frostbite Diseases 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 229920001499 Heparinoid Polymers 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 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 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 208000001126 Keratosis Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 206010024453 Ligament sprain Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 206010044074 Torticollis Diseases 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940094517 chondroitin 4-sulfate Drugs 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000003676 hair preparation Substances 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 239000002554 heparinoid Substances 0.000 description 1
- SFFVATKALSIZGN-UHFFFAOYSA-N hexadecan-7-ol Chemical compound CCCCCCCCCC(O)CCCCCC SFFVATKALSIZGN-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000018197 inherited torticollis Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940113915 isostearyl palmitate Drugs 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 229940073665 octyldodecyl myristate Drugs 0.000 description 1
- BARWIPMJPCRCTP-UHFFFAOYSA-N oleic acid oleyl ester Natural products CCCCCCCCC=CCCCCCCCCOC(=O)CCCCCCCC=CCCCCCCCC BARWIPMJPCRCTP-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- BARWIPMJPCRCTP-CLFAGFIQSA-N oleyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC BARWIPMJPCRCTP-CLFAGFIQSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229940093932 potassium hydroxide Drugs 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000037307 sensitive skin Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 201000005060 thrombophlebitis Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、皮膚に使用するための起泡性組成物に関する。より具体的には、容器から噴出される原液が泡状となる起泡性組成物に関する。 The present invention relates to a foamable composition for use on the skin. More specifically, the present invention relates to a foamable composition in which the undiluted solution ejected from a container becomes foamy.
局所皮膚を治療するための外用薬として、軟膏剤、クリーム剤、ローション剤等が使用されている。ローション剤は、前記三剤型の中でも、べたつきが少なく、さっぱりとした使用感の剤型であるが、垂れやすく、広範囲への塗布には向いていない。他方、軟膏・クリームは垂れにくく、四肢・体幹部など体表面積の広い部分で使われるが、べたつきが多く、使用感が悪い。 Ointments, creams, lotions and the like are used as external preparations for treating topical skin. Among the three-part type, the lotion is a form with little stickiness and a refreshing feeling of use, but it is easy to drip and is not suitable for application to a wide area. On the other hand, ointments and creams are difficult to drip and are used in parts with a wide surface area such as limbs and trunks, but they are sticky and have a bad feeling of use.
使用感が良好で、且つ、広範囲の塗布に適した剤型の候補として、原液が容器から霧状または泡状に噴出されるスプレー剤が検討されている。
例えば、特許文献1には、霧状に噴霧される組成物として、水性成分および油性成分を含有する均一な原液と、炭素数3〜5の炭化水素を主成分とする噴射剤とからなる均一なエアゾール組成物が開示されている。特許文献1の発明は、「油性成分と水性成分の分離が非常に速く、噴射途中で分離するものがあり、均一な組成で噴射できない場合がある」という従来の問題点を解決するために、前記原液中の油性成分の含有量を多量(原液中50〜90重量%)にすることによって、原液およびエアゾール組成物の均一性を確保している。
As a candidate for a dosage form that has a good feeling of use and is suitable for a wide range of applications, sprays in which the stock solution is sprayed from the container in the form of a mist or a foam are being considered.
For example, Patent Document 1 discloses, as a composition to be sprayed in the form of a mist, a homogeneous stock solution containing an aqueous component and an oily component, and a propellant consisting mainly of a hydrocarbon having 3 to 5 carbon atoms. Various aerosol compositions are disclosed. The invention of Patent Document 1 solves the conventional problem that "the separation of the oily component and the aqueous component is very fast, some are separated in the middle of the injection, and the injection may not be performed with a uniform composition". The uniformity of the stock solution and the aerosol composition is secured by increasing the content of the oil component in the stock solution (50 to 90% by weight in the stock solution).
しかしながら、特許文献1のエアゾール組成物は、油性成分(油性溶媒等)を多量に含むため、べとつきが強く、使用感に劣るという問題がある。
べとつきを抑え、使用感を向上させるためには、油性溶媒の含有率が低く、水性溶媒(水等)の含有率が高い水系の起泡性組成物が好ましい。
However, since the aerosol composition of Patent Document 1 contains a large amount of an oil component (oil solvent and the like), there is a problem that the stickiness is strong and the feeling in use is inferior.
In order to suppress stickiness and to improve the feeling of use, a water-based foamable composition having a low content of an oily solvent and a high content of an aqueous solvent (such as water) is preferable.
また、特許文献1のエアゾール組成物は、噴射剤を多量に含み、霧状に噴霧される組成物であるため、目的とする皮膚以外にも飛散することが多いという問題や、患者が飛散した成分を吸い込むという問題がある。
これに対し、起泡性の組成物(いわゆるフォーム剤)を使用することが考えられるが、起泡性の組成物は、低温で保管した際に起泡性が悪化する(泡が安定に形成されない・泡が出ない)という問題がある。
In addition, the aerosol composition of Patent Document 1 contains a large amount of a propellant and is a composition to be sprayed in the form of a mist, and therefore, the problem that the composition often scatters other than the target skin and the patient scatters There is a problem of inhaling ingredients.
On the other hand, although it is conceivable to use a foamable composition (so-called foam agent), the foamable composition is deteriorated in foamability when stored at low temperature (foam is stably formed) There is a problem that it does not occur.
これに関して、特許文献2は、噴出される原液が泡状となり、その泡の質、及び持続性に優れ、更に低温下においても泡の形成性が良好で、使用時にべたつきのないエアゾール組成物を開示している。しかしながら、特許文献2の組成物は、泡の持続が求められる用途(頭髪用化粧料、シェービングフォーム等)のために開発された組成物であるため、皮膚治療用の起泡性組成物としては適していない。 In this regard, Patent Document 2 discloses that the undiluted solution to be jetted is foamy, and the quality and durability of the foam is excellent, and further, the foam composition is excellent in foamability even at low temperatures, and an aerosol composition free of stickiness at the time of use It is disclosed. However, since the composition of Patent Document 2 is a composition developed for applications where hair foam is required to be maintained (hair cosmetics, shaving foam, etc.), it is a foamable composition for skin treatment. Not suitable.
すなわち、皮膚疾患に使用する起泡性組成物は、皮膚に噴射後、形成された泡が速やかに消える(崩壊する)ほうが好ましい。これは、皮膚上で泡が持続すると、泡をこすって破泡させる必要があるため塗布に時間がかかり、且つ、均一に塗布しにくいという問題があるためである。 That is, in the foamable composition used for skin diseases, it is preferable that the formed foam quickly disappears (disintegrates) after being jetted to the skin. This is because when the foam is sustained on the skin, the application is time-consuming because the foam needs to be scraped and broken, and it is difficult to apply uniformly.
下記特許文献3〜5には、破泡させなくても自ら消泡する起泡性組成物が開示されている。しかしながら、特許文献3〜5および、上述した特許文献2に具体的に開示されている組成物は、エタノール等の低級アルコール(炭素数1〜3の脂肪族アルコール)を含む。低級アルコールは、消泡を促進する効果があるが、皮膚に刺激を与える恐れがあるため、皮膚治療用の起泡性組成物は、低級アルコールを含まないほうが好ましい。 The following patent documents 3 to 5 disclose a foamable composition which defoams by itself even if the foam is not broken. However, the compositions specifically disclosed in Patent Documents 3 to 5 and Patent Document 2 described above include lower alcohols (aliphatic alcohols having 1 to 3 carbon atoms) such as ethanol. Although lower alcohols have an effect of promoting antifoaming, since they may irritate the skin, the foamable composition for skin treatment preferably does not contain lower alcohols.
したがって本発明は、皮膚疾患の治療に適した起泡性組成物であって、容器から原液が泡状に噴出され、使用時にべたつきが少なく、更に低温下においても泡の形成性が良好な起泡性組成物を提供することを課題とする。 Therefore, the present invention is a foamable composition suitable for treatment of skin diseases, wherein the stock solution is spouted from the container in the form of foam, the stickiness is small at the time of use, and foam formation is good even at low temperatures. It is an object of the present invention to provide a foamable composition.
本発明者らは、上記課題を解決するために、起泡性組成物について検討を繰り返した結果、水性溶媒(水および多価アルコール等)を70重量%以上含み、低級アルコールを含まない液状組成物に、起泡剤として二種類の界面活性剤を添加して調製した原液(発泡可能な液体組成物)によって、前記課題を解決できることを見い出し、本発明を完成した。 The present inventors repeated studies on a foamable composition to solve the above problems, and as a result, a liquid composition containing 70% by weight or more of an aqueous solvent (such as water and polyhydric alcohol) and containing no lower alcohol It has been found that the above-mentioned problems can be solved by a stock solution (foamable liquid composition) prepared by adding two kinds of surfactants as a foaming agent to a product to complete the present invention.
すなわち、本発明は、原液、あるいは、原液と噴射剤とからなる起泡性組成物であって、前記原液が、
HLB(hydrophile-lipophile balance) 5以上11未満のノニオン界面活性剤と、HLB 11以上30以下のノニオン界面活性剤とを含むこと、
水性溶媒を70重量%以上含むこと、
低級アルコールを含まないこと
を特徴とする。
That is, the present invention relates to a stock solution or a foaming composition comprising the stock solution and a propellant, wherein the stock solution is
HLB (hydrophile-lipophile balance) containing 5 or more and 11 or less nonionic surfactants and HLB 11 or more and 30 or less nonionic surfactants
Containing 70% by weight or more of an aqueous solvent,
It is characterized by containing no lower alcohol.
本発明に係る起泡性組成物は、原液中の水性溶媒の含有率が70重量%以上であるため、べたつきが少なく、使用感に優れている。また、本発明に係る組成物は低級アルコールを含有しないため、皮膚患部への刺激が少ない。また、本発明に係る起泡性組成物は、2種類の界面活性剤、すなわちHLB 5以上11未満のノニオン界面活性剤(親油性界面活性剤)と、HLB 11以上30以下のノニオン界面活性剤(親水性界面活性剤)を含むことにより、低温で保管した場合にも優れた泡形成性を示し、且つ、泡の持続時間が短い。 Since the content of the aqueous solvent in the stock solution is 70% by weight or more, the foamable composition according to the present invention is less sticky and is excellent in the feeling in use. In addition, since the composition according to the present invention does not contain a lower alcohol, there is less irritation to the skin affected area. In addition, the foaming composition according to the present invention includes two types of surfactants, that is, a nonionic surfactant with HLB 5 to 11 (lipophilic surfactant) and a nonionic surfactant with HLB 11 to 30. By including the (hydrophilic surfactant), it exhibits excellent foamability even when stored at low temperature, and the duration of foam is short.
前記原液は、ヘパリン類似物質を含むことが特に好ましい。
ヘパリン類似物質を含む起泡性組成物は、ヘパリン類似物質を含まない起泡性組成物と比べ、泡だれや液だれが生じにくいため、有毛部へも塗布しやすい。
It is particularly preferred that the stock solution comprises heparin analogues.
Foaming compositions containing heparin analogues are easier to apply to hair as they are less prone to foaming and dripping than foaming compositions containing no heparin analogues.
前記原液は、油性溶媒を含まないことが好ましい。油性溶媒を含まない起泡性組成物は、べたつきが非常に少なく、使用感に優れている。 The stock solution preferably does not contain an oily solvent. The foamable composition containing no oily solvent has very little stickiness and is excellent in feeling in use.
また、本発明に係る起泡性組成物は、前記原液と噴射剤とからなることが好ましい。 Moreover, it is preferable that the foamable composition which concerns on this invention consists of the said undiluted | stock solution and a propellant.
また、前記HLB 5以上11未満のノニオン界面活性剤は、モノステアリン酸POE(6)ソルビタン[ポリソルベート61]、トリステアリン酸POE(20)ソルビタン[ポリソルベート65]、POE・POPグリコール(重量平均分子量3650、POP分子量2750、EO含有率20%)、ステアリン酸グリセリル、POE(5)硬化ヒマシ油、トリオレイン酸デカグリセリル、POE(2)セチルエーテル[セテス-2]、POE(42)POP(67)グリコール、テトラオレイン酸POE(6)ソルビット[テトラオレイン酸ソルベス-6]、ショ糖ステアリン酸エステル(モノエステル50%)、POE(1)POP(8)セチルエーテル、POE(20)ソルビットミツロウ、モノステアリン酸POE(5)グリセリル、POE(2)ラウリルエーテル[ラウレス-2]、自己乳化型モノステアリン酸グリセリン、および、モノオレイン酸POE(6)ソルビタンからなる群より選択されることが好ましく、
前記HLB 11以上30以下のノニオン界面活性剤は、モノオレイン酸デカグリセリル、モノステアリン酸デカグリセリル、POE(20)POP(8)セチルエーテル[PPG-8 セテス-20]、POE(50)硬化ヒマシ油、テトラオレイン酸POE(60)ソルビット、オレイン酸POE(20)ソルビタン[ポリソルベート80]、モノステアリン酸ポリエチレングリコール(25E.O.)、POE(15)セチルエーテル[セテス15]、 POE(20)ベへニルエーテル[ベヘネス-20]、ラウリン酸POE(20)ソルビタン[ポリソルベート20]、モノステアリン酸POE(15)グリセリル、POE(54)POP(39)グリコール、ショ糖ラウリン酸エステル(モノエステル80%)、POE(20)ステアリルエーテル、POE(197)POP(67)グリコール、POE(200)POP(67)グリコール、POE(300)POP(55)グリコール、POE(200)POP(40)グリコール、および、POE(160)POP(30)グリコールからなる群より選択されることが好ましい。
なお、POEはポリオキシエチレン、POPはポリオキシプロピレン、E.O.はエチレンオキサイドの略である。また、丸括弧内の数字およびハイフン後の数値は付加モル数を示す。
The above-mentioned nonionic surfactants having HLB 5 or more and 11 or less are monostearic acid POE (6) sorbitan [polysorbate 61], tristearic acid POE (20) sorbitan [polysorbate 65], POE · POP glycol (weight average molecular weight 3650) , POP molecular weight 2750, EO content 20%), glyceryl stearate, POE (5) hydrogenated castor oil, decaglyceryl trioleate, POE (2) cetyl ether [cetes-2], POE (42) POP (67) Glycol, tetraoleic acid POE (6) sorbite [tetraoleic acid sorbes-6], sucrose stearic acid ester (monoester 50%), POE (1) POP (8) cetyl ether, POE (20) sorbite beeswax, mono It is preferable to be selected from the group consisting of POE (5) glyceryl stearate, POE (2) lauryl ether [laures-2], self-emulsifying glyceryl monostearate, and POE (6) sorbitan monooleate,
The above-mentioned HLB 11 to 30 nonionic surfactants include decaglyceryl monooleate, decaglyceryl monostearate, POE (20) POP (8) cetyl ether [PPG-8 ceteth-20], POE (50) cured castor Oil, tetraoleate POE (60) sorbite, oleic acid POE (20) sorbitan [polysorbate 80], polyethylene glycol monostearate (25 E.O.), POE (15) cetyl ether [cetes 15], POE (20) Behenyl ether [Behenes-20], lauric acid POE (20) sorbitan [polysorbate 20], monostearic acid POE (15) glyceryl, POE (54) POP (39) glycol, sucrose laurate (mono ester 80% ), POE (20) stearyl ether, POE (197) POP (67) glycol, POE (200) POP (67) glycol, POE (300) POP (55) glycol, POE (200) POP (40) glycol, and It is preferred to be selected from the group consisting of: POE (160) POP (30) glycol.
POE is an abbreviation of polyoxyethylene, POP is polyoxypropylene, and EO is ethylene oxide. Also, the numbers in the parentheses and the numbers after the hyphen indicate the number of added moles.
また、前記原液は、ヘパリン類似物質を0.1〜1重量%含み、油性溶媒を含まないことが特に好ましい。 Further, it is particularly preferable that the stock solution contains 0.1 to 1% by weight of heparin analogue and does not contain an oily solvent.
また、HLB 5以上11未満のノニオン界面活性剤が、脂肪酸ポリオキシエチレンソルビタンであり、前記HLB 11以上30以下のノニオン界面活性剤が、ポリオキシエチレンアルキルエーテルであることがより好ましく、また、
前記HLB 5以上11未満のノニオン界面活性剤が、トリステアリン酸POE(20)ソルビタンであり、前記HLB 11以上30以下のノニオン界面活性剤が、POE(20)ベへニルエーテルであることが特に好ましい。
Further, it is more preferable that the nonionic surfactant having HLB 5 or more and 11 or less is fatty acid polyoxyethylene sorbitan, and the nonionic surfactant having HLB 11 or more and 30 or less is polyoxyethylene alkyl ether, and
It is particularly preferable that the above-mentioned HLB 5 to 11 nonionic surfactant is POE (20) sorbitan tristearate and the above HLB 11 to 30 nonionic surfactant is a POE (20) behenyl ether. .
本発明に係る起泡性組成物は、噴射される原液が泡状となり、泡の持続時間が短いため、広範囲への塗布に適している。また、使用時にべたつきが少なく、さらに低温下においても泡の形成性が良好である。また、原液中に低級アルコールを含まないため、皮膚刺激性が少ない。 The foamable composition according to the present invention is suitable for a wide range of applications because the undiluted solution to be injected is foamy and the duration of the foam is short. Also, it is less sticky when used, and foam formation is good even at low temperatures. Also, since the stock solution does not contain lower alcohol, there is little skin irritation.
本発明に係る起泡性組成物は、原液を泡状にして皮膚に噴霧するためのスプレー剤として使用する。なお、前記原液とは、発泡可能な液体組成物を意味する。本発明に係る起泡性組成物は、容器に充填した噴射剤と共に原液を噴霧する外用エアゾール剤として使用することも、噴射剤を使用せずポンプにより容器内の原液を噴霧するポンプスプレー剤として使用することも可能である。 The foamable composition according to the present invention is used as a spray for foaming the stock solution and spraying it onto the skin. In addition, the said undiluted | stock solution means the foamable liquid composition. The foamable composition according to the present invention can be used as an external aerosol agent for spraying a stock solution together with a propellant filled in a container, or as a pump spray agent for spraying a stock solution in a container by a pump without using a propellant. It is also possible to use.
本発明に係る起泡性組成物は、低級アルコール(エタノール等の炭素数1〜3の脂肪族一価アルコール)を含まないため、皮膚への刺激性が低い。したがって、本発明に係る起泡性組成物は、過敏な状態の皮膚(例えば乾燥やアトピー等によりバリア機能が低下した皮膚)を治療するための局所用医薬組成物として適している。本発明に係る組成物は特に、乾燥性皮膚疾患、アトピー性皮膚炎、乾癬等の皮膚疾患を治療するのに適している。 The foamable composition according to the present invention has low irritation to the skin because it does not contain lower alcohol (C1-C3 aliphatic monohydric alcohol such as ethanol). Therefore, the foamable composition according to the present invention is suitable as a topical pharmaceutical composition for treating highly sensitive skin (for example, skin whose barrier function has been reduced due to dryness, atopy, etc.). The compositions according to the invention are particularly suitable for treating skin diseases such as dry skin disease, atopic dermatitis, psoriasis and the like.
本発明に係る起泡性組成物は、原液のみからなってもよく、原液と噴射剤とからなってもよい。原液のみからなる起泡性組成物は、ポンプにより容器内の原液を噴霧する、いわゆるポンプスプレー剤として使用することができ、原液と噴射剤とからなる起泡性組成物は、容器に充填した噴射剤と共に原液を噴霧する、いわゆる外用エアゾール剤として使用することができる。より好ましい組成物は、原液と噴射剤とからなる起泡性組成物である。噴射剤を含む起泡性組成物中における原液と噴射剤の重量比は、原液:噴射剤=90〜97:10〜3 (原液と噴射剤の合計は100となる)が好ましい。組成物中の噴射剤が3重量%未満であると、組成物の噴出が不十分になる。他方、組成物中の噴射剤が多すぎると、皮膚の乾燥を誘発するため、噴射剤の量はできるだけ少ない方が好ましい。
従って、原液と噴射剤のより好ましい重量比は、90〜96.5:10〜3.5(特に、92〜96.5:8〜3.5)であり、特に好ましい重量比は92〜96:8〜4であり、さらに好ましい重量比は94〜96:6〜4である。
The foaming composition according to the present invention may be composed of only the stock solution, or may be composed of the stock solution and a propellant. The foamable composition consisting only of the stock solution can be used as a so-called pump spray agent which sprays the stock solution in the container by a pump, and the foamable composition consisting of the stock solution and the propellant is filled in the container It can be used as a so-called external aerosol for spraying a stock solution with a propellant. A more preferred composition is a foamable composition consisting of a stock solution and a propellant. The weight ratio of the undiluted solution to the propellant in the foaming composition containing the propellant is preferably undiluted solution: propellant = 90 to 97: 10-3 (the total of undiluted solution and propellant is 100). If the amount of propellant in the composition is less than 3% by weight, the composition will not be jetted sufficiently. On the other hand, it is preferred that the amount of propellant be as low as possible, as too much propellant in the composition will induce skin dryness.
Accordingly, a more preferable weight ratio of the undiluted solution to the propellant is 90 to 96.5: 10 to 3.5 (in particular, 92 to 96.5: 8 to 3.5), and a particularly preferable weight ratio is 92 to 96: 8 to 4, and more preferably The preferred weight ratio is 94-96: 6-4.
本発明で用いられる二種類の界面活性剤のうち一種は、HLB 5以上11未満のノニオン界面活性剤(親油性界面活性剤)であり、もう一種は、HLB 11以上30以下のノニオン界面活性剤(親水性界面活性剤)である。本発明に係る各界面活性剤の好ましい例を表1aおよび表1bに示す。
前記親油性界面活性剤の好ましい例として、ポリソルベート類(脂肪酸ポリオキシエチレンソルビタン)や、POE・POPグリコール(重量平均分子量3650、POP分子量2750、EO含有率20%)(HLB 5.5)、ステアリン酸グリセリル(HLB 6.0)、POE(5)硬化ヒマシ油(HLB 6.0)、トリオレイン酸デカグリセリル(HLB 7.0)、POE(2)セチルエーテル(セテス-2:HLB 8.0)、POE(42)POP(67)グリコール(HLB 8.0)、テトラオレイン酸POE(6)ソルビット(テトラオレイン酸ソルベス-6:HLB 8.5)、ショ糖ステアリン酸エステル(モノエステル50%)(HLB 9.0)、POE(1)POP(8)セチルエーテル(HLB 9.5)、POE(20)ソルビットミツロウ(HLB 9.5)、モノステアリン酸POE(5)グリセリル(HLB 9.5)、POE(2)ラウリルエーテル(ラウレス-2:HLB 9.5)、自己乳化型モノステアリン酸グリセリン(HLB 10.0)、およびモノオレイン酸POE(6)ソルビタン(HLB 10.0)が挙げられる。
前記親油性界面活性剤は、HLBが6以上11未満であることがより好ましく、HLBが8以上11未満であることが特に好ましく、HLBが9以上11未満であることがさらに好ましい。好ましい実施形態では、前記親油性界面活性剤は、モノステアリン酸POE(6)ソルビタン(ポリソルベート61:HLB 9.5)およびトリステアリン酸POE(20)ソルビタン(ポリソルベート65:HLB 10.5)からなる群より選択されるポリソルベートであり、特に好ましくは、トリステアリン酸POE(20)ソルビタンである。
As preferable examples of the above-mentioned lipophilic surfactant, polysorbates (fatty acid polyoxyethylene sorbitan), POE · POP glycol (weight average molecular weight 3650, POP molecular weight 2750, EO content 20%) (HLB 5.5), glyceryl stearate (HLB 6.0), POE (5) hydrogenated castor oil (HLB 6.0), decaglyceryl trioleate (HLB 7.0), POE (2) cetyl ether (cetes-2: HLB 8.0), POE (42) POP (67) Glycol (HLB 8.0), tetraoleic acid POE (6) sorbite (tetraoleic acid sorbes-6: HLB 8.5), sucrose stearic acid ester (monoester 50%) (HLB 9.0), POE (1) POP (8) Cetyl ether (HLB 9.5), POE (20) Sorbit beeswax (HLB 9.5), POE monostearate (5) glyceryl (HLB 9.5), POE (2) lauryl ether (Laures-2: HLB 9.5), self-emulsifying mono Examples include glyceryl stearate (HLB 10.0), and POE (6) sorbitan monooleate (HLB 10.0).
The lipophilic surfactant more preferably has an HLB of 6 to less than 11, particularly preferably 8 to less than 11, and still more preferably 9 to less than 11. In a preferred embodiment, the lipophilic surfactant is selected from the group consisting of POE (6) sorbitan monostearate (polysorbate 61: HLB 9.5) and POE tristearate (20) sorbitan (polysorbate 65: HLB 10.5) Polysorbate, particularly preferably POE tristearate (20) sorbitan.
前記原液中の、前記親油性界面活性剤の含有率は、0.1〜1.0重量%が好ましい。前記含有率が0.1重量%未満では、泡の形成性が良くないという問題があり、前記含有率が高すぎると、べとつきが増すという問題がある。より好ましい含有率は0.2〜0.8重量%であり、特に好ましい含有率は0.3〜0.7重量%である。前記親油性界面活性剤は、一種のみを用いてもよく、複数を併用してもよい。 The content of the lipophilic surfactant in the stock solution is preferably 0.1 to 1.0% by weight. If the content is less than 0.1% by weight, there is a problem that the foamability is not good, and if the content is too high, there is a problem that stickiness is increased. A more preferable content is 0.2 to 0.8% by weight, and a particularly preferable content is 0.3 to 0.7% by weight. The lipophilic surfactant may be used alone or in combination of two or more.
前記親水性界面活性剤の好ましい例として、モノオレイン酸デカグリセリル(HLB 12.0)、モノステアリン酸デカグリセリル(HLB 12.0)、POE(20)POP(8)セチルエーテル(PPG-8 セテス-20:HLB 12.5)、POE(50)硬化ヒマシ油(HLB 13.5)、テトラオレイン酸POE(60)ソルビット(HLB 14.0)、オレイン酸POE(20)ソルビタン(ポリソルベート80:HLB 15.0)、モノステアリン酸ポリエチレングリコール(25E.O.)(HLB 15.0)、POE(15)セチルエーテル(セテス15:HLB 15.5)、POE(20)ベへニルエーテル(ベヘネス-20:HLB 16.5)、ラウリン酸POE(20)ソルビタン(ポリソルベート20:HLB 16.9)、モノステアリン酸POE(15)グリセリル(HLB 13.5)、POE(54)POP(39)グリコール(HLB 16.0)、ショ糖ラウリン酸エステル(モノエステル80% HLB 16.0)、POE(20)ステアリルエーテル(HLB 18.0)、POE(197)POP(67)グリコール(HLB 22.0)、POE(200)POP(67)グリコール(HLB 22.0)、POE(300)POP(55)グリコール(HLB 27.0)、POE(200)POP(40)グリコール(HLB 28.0)およびPOE(160)POP(30)グリコール(HLB 29.0)からなる群より選択される界面活性剤が挙げられる。
前記親水性界面活性剤としては、HLB 11以上18以下の界面活性剤がより好ましく、HLB 12以上17以下の界面活性剤が特に好ましく、HLB 15以上17以下の界面活性剤がさらに好ましい。特に好ましい親水性界面活性剤の例として、ポリオキシエチレンアルキルエーテル(特にPOE(20)ベへニルエーテル)、および、POE(20)POP(8)セチルエーテル、オレイン酸POE(20)ソルビタン(ポリソルベート80)が挙げられる。
特に、POE(20)ベへニルエーテルを用いると、起泡性組成物を低温で保管した場合にも、非常に優れた泡形成性が得られる。
Preferred examples of the hydrophilic surfactant include decaglyceryl monooleate (HLB 12.0), decaglyceryl monostearate (HLB 12.0), POE (20) POP (8) cetyl ether (PPG-8 ceteth-20: HLB 12.5) POE (50) hydrogenated castor oil (HLB 13.5), tetraoleic acid POE (60) Sorbit (HLB 14.0), oleic acid POE (20) sorbitan (polysorbate 80: HLB 15.0), polyethylene glycol monostearate (25E) .O.) (HLB 15.0), POE (15) cetyl ether (cetes 15: HLB 15.5), POE (20) behenyl ether (Behenes-20: HLB 16.5), lauric acid POE (20) sorbitan (polysorbate 20: HLB 16.9), POE (15) glyceryl monostearate (HLB 13.5), POE (54) POP (39) glycol (HLB 16.0), sucrose laurate (monoester 80% HLB 16.0), POE (20) stearyl Ether (HLB 18.0), POE (197) POP (67) glycol (HLB 22.0), POE (200) POP (67) glycol (HLB 22.0), POE (300) Surfactants selected from the group consisting of POP (55) glycol (HLB 27.0), POE (200) POP (40) glycol (HLB 28.0) and POE (160) POP (30) glycol (HLB 29.0) are mentioned .
The hydrophilic surfactant is more preferably a surfactant of HLB 11 or more and 18 or less, particularly preferably a surfactant of HLB 12 or more and 17 or less, still more preferably a surfactant of HLB 15 or more and 17 or less. Examples of particularly preferred hydrophilic surfactants include polyoxyethylene alkyl ethers (especially POE (20) behenyl ether), and POE (20) POP (8) cetyl ether, oleic acid POE (20) sorbitan (polysorbate 80) Can be mentioned.
In particular, when POE (20) behenyl ether is used, very excellent foam formation can be obtained even when the foamable composition is stored at a low temperature.
前記原液中の、前記親水性界面活性剤の含有率は、0.1〜1.0重量%が好ましい。前記含有率が0.1重量%未満では、泡の形成性が良くないという問題があり、前記含有率が高すぎると、べとつきが増すという問題がある。より好ましい含有率は0.2〜0.8重量%であり、特に好ましい含有率は0.3〜0.7重量%である。前記親水性界面活性剤は、一種のみを用いてもよく、複数を併用してもよい。 The content of the hydrophilic surfactant in the stock solution is preferably 0.1 to 1.0% by weight. If the content is less than 0.1% by weight, there is a problem that the foamability is not good, and if the content is too high, there is a problem that stickiness is increased. A more preferable content is 0.2 to 0.8% by weight, and a particularly preferable content is 0.3 to 0.7% by weight. The hydrophilic surfactant may be used alone or in combination of two or more.
本発明に係る原液は、上述した親油性および親水性界面活性剤以外の界面活性剤を含まないことが好ましい。なお、皮膚刺激性を考慮すると、界面活性剤の量はできるだけ少ない方が好ましいため、前記原液中の界面活性剤の総量は2重量%(より好ましくは1.5重量%)以下であることが特に好ましい。 The stock solution according to the present invention preferably does not contain a surfactant other than the above-mentioned lipophilic and hydrophilic surfactants. In view of skin irritation, the amount of surfactant is preferably as small as possible, so the total amount of surfactant in the stock solution is particularly preferably 2% by weight (more preferably 1.5% by weight) or less. .
本発明に係る原液は、水性溶媒を70重量%以上含む。前記水性溶媒は、水(好ましくは精製水)のみ、あるいは、水と水溶性溶媒とからなる。水溶性溶媒の例として、グリセリン、1,3-ブチレングリコール、ジプロピレングリコールおよびプロピレングリコール等の多価アルコールや、D-ソルビトールや、数平均分子量100〜500のポリエチレングリコール(「日本薬局方」または「医薬品添加物規格」に規定される規格のマクロゴール200、400等)が挙げられる。また、水に少しだけ溶解する溶媒(例えば、トリアセチン、2-エチルヘキサンジオール等の高極性油)も、水に溶解可能な量であれば、本発明に係る水溶性溶媒として使用することができる。本発明で使用できる特に好ましい水溶性溶媒は、グリセリンおよびマクロゴール200である。また、グリセリンおよびポリエチレングリコール(マクロゴール)を併用することにより、使用感の良い組成物を得ることができる。 The stock solution according to the present invention contains 70% by weight or more of an aqueous solvent. The aqueous solvent comprises only water (preferably purified water) or water and a water-soluble solvent. Examples of water-soluble solvents include polyhydric alcohols such as glycerin, 1,3-butylene glycol, dipropylene glycol and propylene glycol, D-sorbitol, and polyethylene glycols having a number average molecular weight of 100 to 500 ("Japanese Pharmacopoeia" or Macrogol 200, 400, etc. of the standard defined in the "pharmaceutical additive standard". In addition, solvents that are only slightly soluble in water (for example, highly polar oils such as triacetin and 2-ethylhexanediol) can also be used as water-soluble solvents according to the present invention, as long as they can be dissolved in water. . Particularly preferred water-soluble solvents that can be used in the present invention are glycerin and macrogol 200. In addition, by combining glycerin and polyethylene glycol (macrogol), a composition having a good feeling in use can be obtained.
原液中の水性溶媒(水および水溶性溶媒)の含有率は、80重量%以上(80〜99重量%)がより好ましく、90重量%以上が特に好ましく、95重量%以上がさらに好ましい。また、原液中の水の含有率は、65〜92重量%が好ましく、70〜92重量%がより好ましく、75〜92重量%が特に好ましい。また、原液中の水溶性溶媒の含有率は、1〜30重量%が好ましく、5〜25重量%がより好ましく、5〜22重量%が特に好ましい。前記水溶性溶媒は、一種のみを用いてもよく、複数を併用してもよい。 The content of the aqueous solvent (water and water-soluble solvent) in the stock solution is more preferably 80% by weight or more (80 to 99% by weight), particularly preferably 90% by weight or more, and still more preferably 95% by weight or more. Moreover, 65 to 92 weight% is preferable, as for the content rate of the water in a undiluted | stock solution, 70 to 92 weight% is more preferable, and its 75 to 92 weight% is especially preferable. Moreover, 1 to 30 weight% is preferable, as for the content rate of the water-soluble solvent in a undiluted | stock solution, 5 to 25 weight% is more preferable, and 5 to 22 weight% is especially preferable. The water-soluble solvent may be used alone or in combination of two or more.
本発明に係る原液は、油性溶媒の含有率が低い方が、べたつきを低減できるため好ましい。したがって、油性溶媒の含有率は20重量%以下が好ましい。ここで、油性溶媒とは、水に溶けにくいため(典型的には、20℃での水への溶解率が1重量%以下)、本発明に係る組成物に含まれている水性溶媒に溶けきらない物質を意味する。本発明で使用できる油性溶媒の例として、イソステアリルアルコール、オレイン酸オレイル、ミリスチン酸イソプロピル、オクチルドデカノール、ミリスチン酸オクチルドデシル、ヘキシルデカノール、イソステアリン酸、トリイソオクタン酸グリセリン、ヒマシ油、オリーブ油、中鎖脂肪酸トリグリセリド、オレイルアルコール、オレイン酸、2-エチルヘキサン酸セチル、イソステアリルパルミテート、2-エチルヘキサン酸セチル、スクワラン、軽質流動パラフィン、流動パラフィン、スクワレン、白色ワセリン、ゲル化炭化水素等が挙げられる。前記油性溶媒は、一種のみを用いてもよく、複数を併用してもよい。 In the stock solution according to the present invention, it is preferable that the content of the oil-based solvent is low because stickiness can be reduced. Therefore, the content of the oily solvent is preferably 20% by weight or less. Here, since the oily solvent is hardly soluble in water (typically, the rate of dissolution in water at 20 ° C. is 1% by weight or less), it is soluble in the aqueous solvent contained in the composition according to the present invention It means an unclean substance. Examples of oily solvents that can be used in the present invention are isostearyl alcohol, oleyl oleate, isopropyl myristate, octyldodecanol, octyldodecyl myristate, hexyldecanol, isostearic acid, glycerin triisooctanoate, castor oil, olive oil, medium-chain fatty acid Examples thereof include triglyceride, oleyl alcohol, oleic acid, cetyl 2-ethylhexanoate, isostearyl palmitate, cetyl 2-ethylhexanoate, squalane, light liquid paraffin, liquid paraffin, squalene, white petrolatum, gelled hydrocarbon and the like. The oily solvent may be used alone or in combination of two or more.
原液中の油性溶媒の含有率は、15重量%以下が好ましく、10重量%以下がより好ましく、5重量%以下が特に好ましく、2重量%以下がさらに好ましい。特に好ましい原液は、油性溶媒を含まない。 The content of the oily solvent in the stock solution is preferably 15% by weight or less, more preferably 10% by weight or less, particularly preferably 5% by weight or less, and still more preferably 2% by weight or less. Particularly preferred stock solutions do not contain oily solvents.
本発明に係る原液は、ヘパリン類似物質(ヘパリノイド:多硫酸化コンドロイチン硫酸)を含むことが特に好ましい。
前記ヘパリン類似物質は、コンドロイチン硫酸(コンドロイチン4硫酸、コンドロイチン6硫酸等)に、化学的に硫酸基を導入することによって合成することができる。本発明に係るヘパリン類似物質としては、日本薬局方外医薬品規格に記載のヘパリン類似物質が好ましい。
It is particularly preferable that the stock solution according to the present invention contains heparin analogue (heparinoid: polysulfated chondroitin sulfate).
The heparin analogue can be synthesized by chemically introducing a sulfate group into chondroitin sulfate (chondroitin 4 sulfate, chondroitin 6 sulfate, etc.). The heparin analogues according to the present invention are preferably heparin analogues described in the Pharmaceutical Standards outside the Japanese Pharmacopoeia.
また、本発明のヘパリン類似物質は、必要に応じ、ナトリウム、カリウム等のアルカリ金属の水酸化物若しくは炭酸塩、又はアミン類等を用いる造塩反応により得られる生理学的に許容される塩形態として使用することもできる。 In addition, the heparin analogue of the present invention is, if necessary, a hydroxide or carbonate of an alkali metal such as sodium or potassium, or a physiologically acceptable salt obtained by a salt formation reaction using amines or the like. It can also be used.
また、本発明のヘパリン類似物質が有する硫酸基の数は特に限定されないが、本発明のヘパリン類似物質は、単糖当たり、通常平均0.55〜5個、好ましくは平均0.6〜2.9個、より好ましくは平均0.7〜2個の硫酸基を有する。 Further, the number of sulfate groups contained in the heparin analogue of the present invention is not particularly limited, but the heparin analogue of the present invention usually has an average of 0.55 to 5 per monosaccharide, preferably an average of 0.6 to 2.9, more preferably It has an average of 0.7 to 2 sulfate groups.
本発明で用いられるヘパリン類似物質又はその塩の分子量は、特に限定されないが、数平均分子量で10,000〜100,000程度、より好ましくは10,000〜75,000、特に好ましくは10,000〜50,000であることが望ましい。 The molecular weight of the heparin analogue or the salt thereof used in the present invention is not particularly limited, but it is desirable that the number average molecular weight is about 10,000 to 100,000, more preferably 10,000 to 75,000, and particularly preferably 10,000 to 50,000.
コンドロイチン硫酸に硫酸基を導入する方法としては、既知の方法、例えば、コンドロイチン硫酸と硫酸化剤を適当な溶媒中で加温し、反応させる方法が挙げられる。硫酸化剤としては、多硫酸化の目的を達成することができるものであれば特に限定されないが、無水硫酸とピリジン若しくはトリエチルアミン等の錯体を使用することが好ましい。コンドロイチン硫酸と硫酸化剤の使用割合は、所望のヘパリン類似物質の硫酸化率(又は硫黄含有率)及び反応条件に従って任意に選択することができるが、一般に、コンドロイチン硫酸1重量部に対して硫酸化剤2〜10重量部となるような割合で使用する。溶媒としては、例えば、ジメチルホルムアミド等の親プロトン性溶媒を挙げることができる。反応温度、反応時間としては、所望の硫酸化率が達成できる限り特に限定されないが、例えば、40〜90℃で30分〜20日間程度反応させる。 Examples of a method for introducing a sulfate group into chondroitin sulfate include known methods, for example, a method in which chondroitin sulfate and a sulfating agent are heated and reacted in an appropriate solvent. The sulfating agent is not particularly limited as long as it can achieve the purpose of polysulfation, but it is preferable to use an anhydrous sulfuric acid and a complex such as pyridine or triethylamine. The proportions of chondroitin sulfate and sulfating agent used can be optionally selected according to the desired sulfation rate (or sulfur content) of heparin analogues and reaction conditions, but generally, sulfuric acid is used per 1 wt part of chondroitin sulfate The agent is used in a proportion of 2 to 10 parts by weight. As the solvent, for example, a protic solvent such as dimethylformamide can be mentioned. The reaction temperature and the reaction time are not particularly limited as long as the desired degree of sulfation can be achieved. For example, the reaction is carried out at 40 to 90 ° C. for about 30 minutes to 20 days.
上述のようにして生成したヘパリン類似物質は、各種の修飾多糖類で常用されている精製操作により精製することができる。例えば、中和、透析による脱塩、有機溶媒添加による沈殿を回収する操作、凍結乾燥による回収操作などが挙げられる。 The heparin analogues produced as described above can be purified by purification procedures commonly used with various modified polysaccharides. For example, neutralization, desalting by dialysis, operation of recovering precipitates by addition of organic solvent, recovery operation by lyophilization and the like can be mentioned.
前記原液に、前記ヘパリン類似物質を添加することにより、起泡性組成物を皮膚に噴射した後に生じる泡だれ(または液だれ)を抑制することができる。前記泡だれ抑制効果は、原液中のヘパリン類似物質の含有率がごく少量(0.5重量%以下)でも得られる。例えば有毛部である頭部は、泡だれや液だれが生じやすいため、頭部に噴射した起泡性組成物が目に流れ落ちる危険性があるが、ヘパリン類似物質を含む本発明に係る起泡性組成物は、液だれや泡だれが生じにくいため、頭皮のような有毛部への適用にも適している。 By adding the heparin analogue to the stock solution, it is possible to suppress bubbles (or drips) that occur after the foamable composition is sprayed onto the skin. The antifoaming effect can be obtained even when the content of heparin analogue in the stock solution is very small (0.5% by weight or less). For example, there is a risk that the foamable composition jetted to the head may fall off the eye because the head, which is a hairy part, is prone to foaming and dripping. Foaming compositions are also suitable for application to hair like scalp, as they are resistant to dripping and foaming.
原液中に含まれるヘパリン類似物質の含有率は、0.1〜1重量%が好ましく、0.1〜0.5重量%がより好ましく、0.2〜0.4重量%が特に好ましい。 0.1 to 1 weight% is preferable, as for the content rate of the heparin analog contained in a undiluted | stock solution, 0.1 to 0.5 weight% is more preferable, and 0.2 to 0.4 weight% is especially preferable.
また、ヘパリン類似物質を含む起泡性組成物は、ヘパリン類似物質が、血液凝固抑制作用、血流量増加作用、血腫消退促進作用、角質水分保持増強作用および線維芽細胞増殖抑制作用を有するため、乾燥性皮膚疾患、皮脂欠乏症、進行性指掌角皮症、凍瘡、肥厚性瘢痕・ケロイド、血行障害に基づく疼痛と炎症性疾患(注射後の硬結並びに疼痛)、血栓性静脈炎(痔核を含む)、外傷(打撲、捻挫、挫傷)後の腫脹・血腫・腱鞘炎・筋肉痛・関節炎、筋性斜頸等の皮膚疾患の治療用組成物としても適している。 In addition, the foaming composition containing a heparin analogue has a blood coagulation suppression action, a blood flow increase action, a hematomammonia withdrawal promotion action, a stratum corneum water retention enhancement action, and a fibroblast cell proliferation suppressive action, the heparin analogue substance, Dry skin disease, sebum deficiency, progressive palmar keratoderma, frostbite, hypertrophic scar / keloid, pain and inflammatory diseases based on hematologic disorders (induration and pain after injection), thrombophlebitis (including hemorrhoid) It is also suitable as a composition for treating skin diseases such as swelling, hematoma, tendonitis, myalgia, arthritis, and muscular torticollis after trauma (collision, sprain, contusion).
本発明に係る起泡性組成物の有効成分は、上述したヘパリン類似物質(水溶性)であってもよく、その他の水溶性薬物であってもよく、脂溶性の薬物であってもよく、それらの組み合わせであってもよい。前記有効成分は、一種であっても、二種以上であってもよい。本発明に係る起泡性組成物は、水性溶媒の含有率が高いため、水溶性薬物を有効成分とすることがより好ましい。 The active ingredient of the foamable composition according to the present invention may be the above-mentioned heparin analogue (water-soluble), another water-soluble drug, or a lipid-soluble drug. It may be a combination of them. The active ingredient may be one kind or two or more kinds. The foamable composition according to the present invention preferably contains a water-soluble drug as an active ingredient because the content of the aqueous solvent is high.
本発明に係る好ましい原液の例として、ヘパリン類似物質を含み、HLB 6以上11未満の脂肪酸ポリオキシエチレンソルビタン、および、HLB 11以上18以下のポリオキシエチレンアルキルエーテルを含む原液が挙げられる。特に好ましい原液は、ヘパリン類似物質を含み、且つ、トリステアリン酸POE(20)ソルビタンおよびPOE(20)ベへニルエーテルを含む。 As an example of a preferable stock solution according to the present invention, a stock solution containing a heparin analogue and containing HLB 6 to 11 fatty acid polyoxyethylene sorbitan and HLB 11 to 18 polyoxyethylene alkyl ether can be mentioned. Particularly preferred stock solutions contain heparin analogues and contain POE (20) sorbitan tristearate and POE (20) behenyl ether.
本発明に係る起泡性組成物は、噴射剤を含まないポンプスプレー剤として使用することも、噴射剤を含む外用エアゾール剤として使用することもできる。ポンプスプレー剤は、基本的に、気密容器、ポンプ本体、アクチュエーター、キャップ、原液から構成され、外用エアゾール剤は、基本的に、内圧に耐える耐圧性容器、バルブ、アクチュエーター、原液および噴射剤から構成される。
本発明で用いられる噴射剤(プロペラント)としては、液化ガス、圧縮ガスが挙げられ、前記液化ガスとしては、炭素数3〜5の炭化水素(プロパン、n-ブタン、i-ブタン等)を主成分とする液化石油ガス(LPG)、ジメチルエーテル、フッ化炭化水素が挙げられ、圧縮ガスとしては、炭酸ガス、窒素、亜酸化窒素が挙げられる。特に好ましい噴射剤は、液化石油ガスである。
The foamable composition according to the present invention can be used as a propellant-free pump spray or as an external aerosol containing a propellant. The pump spray is basically composed of an airtight container, a pump body, an actuator, a cap and a stock solution, and the external aerosol is basically composed of a pressure resistant container that can withstand the internal pressure, a valve, an actuator, a stock solution and a propellant. Be done.
The propellant (propellant) used in the present invention includes liquefied gas and compressed gas, and as the liquefied gas, hydrocarbons having 3 to 5 carbon atoms (propane, n-butane, i-butane, etc.) Examples thereof include liquefied petroleum gas (LPG), dimethyl ether and fluorinated hydrocarbon which are main components, and examples of compressed gas include carbon dioxide gas, nitrogen and nitrous oxide. A particularly preferred propellant is liquefied petroleum gas.
本発明に係る原液は、ポリビニルピロリドンを含まないことが好ましい。ポリビニルピロリドンは、泡を安定化する作用を持ち、泡の持続性を高めるため、起泡性組成物を皮膚に噴射した後、生じた泡が消えるまで時間がかかる恐れがある。 The stock solution according to the present invention preferably does not contain polyvinyl pyrrolidone. Polyvinyl pyrrolidone has the effect of stabilizing the foam, and in order to enhance the persistence of the foam, it may take a long time for the generated foam to disappear after the foaming composition is sprayed onto the skin.
また、本発明に係る原液は、セチルアルコール、ステアリルアルコール等の常温で固体の高級アルコール(脂肪アルコール)を含まないことが好ましい。固形高級アルコールは、泡の持続性を高める可能性があるためである。 The stock solution according to the present invention preferably does not contain a higher alcohol (fatty alcohol) which is solid at normal temperature, such as cetyl alcohol and stearyl alcohol. This is because solid higher alcohols may increase the durability of the foam.
本発明に係る原液は、3〜12の範囲のpH値を有することが好ましい。より好ましいpH値は4〜10である。 The stock solution according to the present invention preferably has a pH value in the range of 3-12. More preferable pH value is 4-10.
原液を上記範囲のpH値に調節するためのpH調節剤としては、低pH領域に調節するために使用されるものとして、リン酸二水素カリウム、クエン酸などが挙げられ、高pH領域に調節するため使用されるものとして、水酸化ナトリウム、水酸化カリウム、乳酸ナトリウム、クエン酸ナトリウム、L-アルギニン、ジイソプロパノールアミンなどが挙げられる。特に好ましいpH調節剤として、リン酸二水素カリウム、水酸化カリウム、クエン酸ナトリウム、クエン酸、ジイソプロパノールアミン、エデト酸ナトリウム等が挙げられる。 As a pH regulator for adjusting the stock solution to a pH value in the above range, potassium dihydrogen phosphate, citric acid and the like can be mentioned as those used to adjust to a low pH region, and it is adjusted to a high pH region As sodium chloride, potassium hydroxide, sodium lactate, sodium citrate, L-arginine, diisopropanolamine and the like can be mentioned. Particularly preferable pH adjusters include potassium dihydrogen phosphate, potassium hydroxide, sodium citrate, citric acid, diisopropanolamine, sodium edetate and the like.
本発明に係る原液は、上記成分の他に、保存剤(防腐剤)、酸化防止剤、安定化剤、紫外線吸収剤等、皮膚用外用剤に一般的に使用される添加剤を含むことができる。 The stock solution according to the present invention may contain, in addition to the above components, additives generally used for external preparations for skin such as preservatives (antiseptics), antioxidants, stabilizers, UV absorbers, etc. it can.
上記保存剤の例としては、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル等のパラオキシ安息香酸エステル(パラベン類)、安息香酸ナトリウム、フェノキシエタノールなどが挙げられる。上記保存剤は、一種のみを用いてもよく、複数を併用してもよい。組成物における保存剤の含有率は、0.01〜1重量%の範囲とすることが好ましく、0.1〜0.5重量%の範囲とすることがより好ましい。2重量%を越えた場合は、製剤としての安全性が危惧されるおそれがある。 Examples of the preservative include parahydroxybenzoic acid esters (parabens) such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate and propyl parahydroxybenzoate, sodium benzoate, phenoxyethanol and the like. The preservative may be used alone or in combination of two or more. The content of the preservative in the composition is preferably in the range of 0.01 to 1% by weight, and more preferably in the range of 0.1 to 0.5% by weight. If it exceeds 2% by weight, the safety as a preparation may be concerned.
本発明に係る組成物の皮膚への塗布量・塗布頻度は、皮膚疾患の種類、症状の程度、患部の範囲、患者の年齢・体重、有効成分の種類および濃度等に応じて、適宜調節すればよい。有効成分が0.1〜1重量%のヘパリン類似物質の場合は、1日1〜4回、適量の組成物を患部に噴射すればよい。 The amount and frequency of application of the composition according to the present invention to the skin may be appropriately adjusted according to the type of skin disease, degree of symptoms, range of affected area, age and weight of patient, type and concentration of active ingredients, etc. Just do it. When the active ingredient is 0.1 to 1% by weight of heparin analogue, an appropriate amount of the composition may be jetted to the affected area 1 to 4 times a day.
なお、先行する段落において、本発明の組成物で使用できる必須成分および任意成分の好ましい化合物名を記載してきたが、本発明の組成物には、これらを任意に組み合わせて得られる組成物が含まれ、且つ、必須成分および任意成分について記載した重量%を任意に組み合わせて得られる組成物も含まれる。また、数値範囲が複数記載されている場合、各数値範囲の上限値または下限値も任意に組み合わせ可能である。 In the preceding paragraph, although preferred compound names of essential components and optional components that can be used in the composition of the present invention have been described, the composition of the present invention includes compositions obtained by optionally combining these. And compositions obtained by optionally combining the percentages by weight described for the essential components and optional components. Further, when a plurality of numerical ranges are described, the upper limit value or the lower limit value of each numerical range may be arbitrarily combined.
以下、実施例により本発明をより詳細に説明するが、本発明は実施例により限定されるものではない。 Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited by the examples.
[実施例1]起泡性組成物の調製
下記の表2および表3に示す組成を有する原液95.5gに、LPG(液化石油ガス)4.5gを加えて混和し、起泡性組成物を調製した。
試験で使用したヘパリン類似物質は、日本薬局方外医薬品成分規格に記載されているヘパリン類似物質に該当する市販品である。
このようにして調製されたNo.1〜26の組成物のpH値は6.28〜6.66であった。なお、pH調節剤を添加したNo.23およびNo.25のpH値は6.43であった。
[Example 1] Preparation of foamable composition 4.5 g of LPG (liquefied petroleum gas) is added to 95.5 g of the stock solution having the composition shown in the following Table 2 and Table 3 and mixed to prepare a foamable composition did.
The heparin analogue used in the test is a commercial product corresponding to the heparin analogue described in the Japanese Pharmacopoeia Standard for Pharmaceutical Ingredients.
The pH values of the compositions of Nos. 1 to 26 thus prepared were 6.28 to 6.66. The pH value of No. 23 and No. 25 to which the pH adjuster was added was 6.43.
[低温保管時の泡形成性]
上述のようにして調製した表2および表3の起泡性組成物について、5℃で保管した際の泡形成性を評価した。
具体的には、内圧に耐える耐圧性の缶に、起泡性組成物を充填し、バルブとアクチュエーターを取り付けた後、5℃で1〜27週間保管し、その後、前記容器を上下に10回撹拌し、撹拌の直後(0分後)、2分後、5分後に起泡性組成物を缶から適量噴射し、目視により泡質の観察を行った。
0分、2分および5分後に噴射し、すべての時点でボリュームのある泡が形成された場合を「○(泡形成能良好)」とし、0分、2分、5分後のいずれかの時点において、ボリュームのある泡が形成されなかった場合、あるいは、泡そのものが噴霧されない場合を「×(泡形成能不良)」と評価した。
結果を以下に示す。なお、表中の数値は重量%を示す。
[Foam formation at low temperature storage]
The foam forming properties when stored at 5 ° C. were evaluated for the foamable compositions of Tables 2 and 3 prepared as described above.
Specifically, after filling the foamable composition in a pressure-resistant can that withstands the internal pressure, attaching a valve and an actuator, the container is stored for 1 to 27 weeks at 5 ° C., and then the container is vertically repeated 10 times Immediately after the stirring (after 0 minutes), after 2 minutes and after 5 minutes, the foamable composition was sprayed from the can in an appropriate amount, and observation of foam quality was performed visually.
Sprayed after 0 minutes, 2 minutes and 5 minutes, and when a bubble with a large volume was formed at all time points, it is regarded as "○ (good foam forming ability)" and either 0 minutes, 2 minutes or 5 minutes When no bulky foam was formed at that time, or no foam itself was sprayed, it was evaluated as "poor (poor foam formation ability)".
The results are shown below. The numerical values in the table indicate% by weight.
表2および表3に示すように、HLB値5以上11未満のノニオン界面活性剤(以下、親油性面活性剤と称する)を単独で使用した場合(No.1〜No.3)、低温保管時の泡形成性が悪かった。これは、親油性界面活性剤は水に不溶性の成分であり、低温下で凝集しやすいため、5℃で保管中に凝集が進行し、LPGを原液中に十分に分散させることができなかったためと考えられる。
これに対し、親油性界面活性剤と、HLB値11以上30以下のノニオン界面活性剤(以下、親水性界面活性剤と称する)を併用した場合(No.5〜No.26)は、低温で保管した際にも優れた泡形成性を示した。これは、親水性界面活性剤が親油性界面活性剤の凝集を防ぎ、さらには親水性界面活性剤も起泡剤として機能することから、低温での起泡性が改善されたためと考えられる。特に、親水性界面活性剤として、POE(20)ベへニルエーテルを使用した場合、5℃で27週間(約6か月)保管しても、優れた泡形成性を有することが確認された(No.23〜25)。市販のフォーム剤の中には、「低温保管を避ける」「低温保管時に泡が出ない場合は、温めた後に使用する」と使用上の注意が喚起されているものもあるが、本発明に係る組成物はこのような注意は必要ないため、患者にとって利便性が高い。
As shown in Tables 2 and 3, when a nonionic surfactant having an HLB value of 5 or more and less than 11 (hereinafter referred to as a lipophilic surfactant) is used alone (No. 1 to No. 3), low temperature storage The foam formation at the time was bad. This is because the lipophilic surfactant is a component insoluble in water and tends to aggregate at low temperatures, so aggregation progressed during storage at 5 ° C. and LPG could not be sufficiently dispersed in the stock solution it is conceivable that.
In contrast, when a lipophilic surfactant and a nonionic surfactant having an HLB value of 11 or more and 30 or less (hereinafter referred to as a hydrophilic surfactant) are used in combination (No. 5 to No. 26), the temperature is low at low temperatures. It also showed excellent foamability when stored. It is considered that this is because the hydrophilic surfactant prevents aggregation of the lipophilic surfactant, and further, the hydrophilic surfactant also functions as a foaming agent, so that the foaming property at low temperature is improved. In particular, when POE (20) behenyl ether was used as the hydrophilic surfactant, it was confirmed to have excellent foam-forming properties even when stored at 5 ° C. for 27 weeks (about 6 months) ( No. 23-25). Some of the commercially available foams have been used to warn of their use: "Avoid storage in cold storage" and "Use after warming if foam does not appear during storage in cold storage". Such a composition is highly convenient for the patient because such a caution is not necessary.
また、親水性界面活性剤を単独で使用した場合(No.4)、泡が速やかに崩壊しない(泡切れが悪い)という問題が見られた。泡が速やかに崩壊しないと、皮膚に使用した時に、泡残りが多く、泡が消えるまで塗擦を繰り返す必要あるため、皮膚治療用の起泡性組成物として不向きである。なお、No.4は泡切れが悪かったため、泡形成性は試験しなかった。
これに対し、二種類の界面活性剤を併用した組成物(No.5〜No.26)から形成された泡は速やかに崩壊し、皮膚上に塗り広げやすく、皮膚患部の治療に適した物性を有することが確認された。
In addition, when the hydrophilic surfactant was used alone (No. 4), there was a problem that the foam did not disintegrate quickly (foam breakage was bad). If the foam does not disintegrate quickly, when used on the skin, it is unsuitable as a foamable composition for skin treatment because it has a large amount of foam residue and it is necessary to repeat rubbing until the foam disappears. In addition, No. 4 was not tested for foamability because the foam breakage was bad.
On the other hand, the foam formed from the composition (No. 5 to No. 26) in which the two types of surfactants are used in combination disintegrates rapidly and spreads easily on the skin, and the physical properties suitable for treating the affected area of the skin. It was confirmed to have
さらに、上記各起泡性組成物は、油性溶媒を含まないため、べたつきが少なく、使用感が良かった。
また、LPG(液化石油ガス)の量が多いと、皮膚の乾燥を誘発するおそれがあるが、前記起泡性組成物は、LPGの量が4.5重量%と低量である。また、エタノール等の低級アルコールも、揮発性が高いため、皮膚の乾燥を誘発するおそれがあるが、前記起泡性組成物は低級アルコールを含まない。
さらに、界面活性剤も皮膚刺激の原因となり得るが、本発明にかかる起泡性組成物(No.5〜No.26)は、界面活性剤の量が低量(合計0.78〜1.04重量%)でも、安定に泡を形成することができる。
したがって、本発明に係る起泡性組成物は、皮膚への刺激性が少なく、安全性が高いことが示唆される。
Furthermore, since each of the foamable compositions described above does not contain an oily solvent, it is less sticky and has a good feeling in use.
Moreover, when the amount of LPG (liquefied petroleum gas) is large, there is a possibility that skin dryness may be induced, but in the foaming composition, the amount of LPG is as low as 4.5% by weight. In addition, although lower alcohols such as ethanol also have high volatility, they may cause skin dryness, but the foamable composition does not contain lower alcohols.
Furthermore, although the surfactant may also cause skin irritation, the foaming composition (No. 5 to No. 26) according to the present invention has a low amount of surfactant (total 0.78 to 1.04% by weight) However, the foam can be stably formed.
Therefore, it is suggested that the foamable composition according to the present invention is less irritating to the skin and has high safety.
[実施例2]親水性界面活性剤を単独で使用した時の泡崩壊性の検討
上述したように、親水性界面活性剤を単独使用した場合(No.4)、泡の崩壊速度が遅いことが確認されたので、他の親水性界面活性剤を単独使用した場合についても試験を行った。具体的には、下記の親水性界面活性剤を使用した以外は、No.4と同じ組成を有する起泡性組成物を調製し、当該起泡性組成物を4名のパネラーの皮膚に噴射した際の泡の崩壊速度を観察した。4名のパネラー全員が、泡が速やかに崩壊すると評価した場合を「○(泡崩壊性良好)」、泡が速やかに崩壊しないと評価したパネラーが1名でもいた場合を「×(泡崩壊性不良)」とした。
結果を表4にまとめる。
[Example 2] Examination of foam disintegratability when hydrophilic surfactant is used alone As described above, when hydrophilic surfactant is used alone (No. 4), the rate of foam collapse is slow Were also tested, and tests were also conducted when other hydrophilic surfactants were used alone. Specifically, a foamable composition having the same composition as No. 4 was prepared except that the following hydrophilic surfactant was used, and the foamable composition was sprayed onto the skin of four panelists. The rate of foam collapse was observed. When all the four panelists evaluated that the foam disintegrates quickly, "○ (good foam disintegrability)", and when only one panelist evaluated that the foam does not disintegrate quickly, "X (foam disintegrability Bad).
The results are summarized in Table 4.
表4に示すように、親水性界面活性剤を単独で使用した場合は、泡が速やかに崩壊しない傾向があることが分かった。これに対し、親水性界面活性剤と親油性界面活性剤を併用した場合(No.5〜No.26)は、泡の持続性は観察されなかったので、親水性界面活性剤を単独で使用するより、親油性界面活性剤と併用することが好ましいことが分かった。 As shown in Table 4, it was found that when the hydrophilic surfactant was used alone, the foam tended not to disintegrate quickly. On the other hand, when the hydrophilic surfactant and the lipophilic surfactant were used in combination (No. 5 to No. 26), the durability of the foam was not observed, so the hydrophilic surfactant was used alone. It has been found that it is preferable to use in combination with a lipophilic surfactant rather than
[実施例3]ヘパリン類似物質の有無が泡だれに与える影響
上記表2および表3に示す起泡性組成物から、ヘパリン類似物質を除くと、組成物を皮膚に噴射した後、泡だれ(液だれ)が生じやすい傾向が観察されたため、ヘパリン類似物質の有無が泡だれに与える影響を検討した。
具体的には、泡だれの簡易試験として繁用されている流動性試験を行った。試験は、仰角45度で2種の板を用い、これに起泡性組成物(液体)の適量を塗布または滴下した後、板上の20cm距離を、組成物(液体)が移動する際に要する時間(秒)を計測することによって行った。結果を表5に示す。表5中の各成分の数値は、重量%を示す。
[Example 3] The effect of the presence or absence of a heparin analogue on foaming by removing the heparin analogue from the foamable composition shown in Table 2 and Table 3 above, after the composition is sprayed onto the skin, the foam ( Since a tendency toward the occurrence of dripping was observed, the influence of the presence or absence of heparin analogues on foaming was examined.
Specifically, a fluidity test frequently used as a simple test of foam was conducted. In the test, two plates are used at an elevation angle of 45 degrees, and after applying or dropping an appropriate amount of a foamable composition (liquid) thereto, the composition (liquid) moves 20 cm over the plate, It carried out by measuring the time (seconds) required. The results are shown in Table 5. The numerical values of the respective components in Table 5 indicate% by weight.
表5に示されるように、ヘパリン類似物質を含まない組成物の移動時間と比べて、ヘパリン類似物質を含む組成物の移動時間は、約3〜9秒(約18〜35%)長かった(すなわち、液だれの速度が約18〜35%遅くなった)。液だれの速度が遅くなると、起泡性組成物を噴射して泡を形成した後の泡だれの速度(あるいは泡が消泡して生じた液の液だれ速度)も遅くなる。したがって、本発明に係る組成物に、ヘパリン類似物質をごく微量(0.3重量%)添加することによって、泡だれおよび液だれが生じにくくなることが確認された。
この傾向は、外用エアゾールタイプ(噴射剤有り)、ポンプスプレータイプ(噴射剤無し)どちらの場合でも同様であった。なお、ヘパリン類似物質の有無によって、組成物の粘度、稠度等の物理的性質に差異は見られなかった。
この結果から、微量のヘパリン類似物質を添加することによって、泡だれ/液だれのし難いフォーム剤を提供できることが分かった。従って、ヘパリン類似物質を含む本発明の組成物は、頭髪に適用した場合でも、目に流れ落ちにくい等の利点があり、医療現場におけるアドヒアランスの向上が期待できる。
As shown in Table 5, the migration time of the composition containing heparin analogue was about 3 to 9 seconds (about 18 to 35%) longer than the migration time of the composition not containing heparin analogue ( That is, the speed of dripping was reduced by about 18 to 35%). As the speed of the dripping slows down, the speed of the bubble after the foamable composition is jetted to form a foam (or the speed of dripping of the liquid formed due to the foam disappearing) also slows down. Therefore, it was confirmed that the addition of a very small amount (0.3% by weight) of a heparin analogue to the composition according to the present invention makes it less likely to cause foaming and dripping.
This tendency was similar in both the external aerosol type (with propellant) and the pump spray type (without propellant). There were no differences in the physical properties such as viscosity and consistency of the composition depending on the presence or absence of heparin analogues.
From this result, it was found that the addition of a trace amount of heparin analogue can provide a foam which is resistant to foaming / dipping. Therefore, the composition of the present invention containing a heparin analogue has the advantage of being hard to run off even when applied to hair, and it can be expected to improve adherence in the medical field.
[実施例4]起泡性組成物中のヘパリン類似物質の安定性
本発明に係る起泡性組成物中における、ヘパリン類似物質の安定性(保管後の残存率)を確認した(n=3)。試験した起泡性組成物の組成を表6に、安定性試験の結果を表7に示す。なお、表6中の数値は、重量%を示す。
Example 4 Stability of Heparin-Like Substance in Foaming Composition The stability (remaining ratio after storage) of the heparin-like substance in the foamable composition according to the present invention was confirmed (n = 3 ). Table 6 shows the composition of the foamable composition tested, and Table 7 shows the result of the stability test. The numerical values in Table 6 indicate% by weight.
表7に示すように、本発明に係る起泡性組成物は、加速条件(40℃/75%RH)で保管した場合にも、ヘパリン類似物質の有意な含量低下を認めなかった。特に、親水性界面活性剤として、POE(20)ベへニルエーテルを用いた場合(No.35)は、加速条件で27週間(約6か月)保管した場合も、ヘパリン類似物質の有意な含量低下を認めなかった。このことから、本発明に係る起泡性組成物は、ヘパリン類似物質を安定に保つことができることが分かった。したがって、本発明に係る組成物は、ヘパリン類似物質を主薬(有効成分)とした場合、高い主薬安定性を示すことが実証された。
また、No.34の組成物について、低温(5℃)保管時の泡形成性を確認したところ、5℃で27週間保管した後でも、ボリュームのある泡が形成され、良好な泡形成能を有することが確認された。
As shown in Table 7, the foamable composition according to the present invention did not show a significant reduction in the content of heparin analogues even when stored under accelerated conditions (40 ° C./75% RH). In particular, when POE (20) behenyl ether is used as the hydrophilic surfactant (No. 35), a significant content of heparin analogues even when stored for 27 weeks (about 6 months) under accelerated conditions There was no decline. From this, it was found that the foamable composition according to the present invention can keep the heparin analogue stable. Therefore, it has been demonstrated that the composition according to the present invention exhibits high primary drug stability when using a heparin analogue as a main drug (active ingredient).
Moreover, when the foam-forming property at low temperature (5 ° C.) storage was confirmed for the composition No. 34, even after storage for 27 weeks at 5 ° C., a foam having a volume was formed, and a good foam-forming ability was obtained. It was confirmed to have.
[実施例5]起泡性組成物の調製
親油性界面活性剤として様々な界面活性剤を使用して、表8および表9に示す組成を有する組成物を調製し、さらに、親水性界面活性剤として、様々な界面活性剤を使用して、表10に示す組成を有する組成物を調製し、低温(5℃)で1週間保管した場合の泡形成性を確認した。なお、表中の数値は重量%を示す。また、各組成物のpH値は6.4〜6.6の範囲となった。
Example 5 Preparation of a Foaming Composition Using various surfactants as lipophilic surfactants, compositions having the compositions shown in Tables 8 and 9 are prepared, and hydrophilic surfactants are further prepared. Various surfactants were used as an agent to prepare a composition having the composition shown in Table 10, and the foamability when stored at low temperature (5 ° C.) for one week was confirmed. The numerical values in the table indicate% by weight. The pH value of each composition was in the range of 6.4 to 6.6.
表8〜表10に示す様々な親油性界面活性剤と親水性界面活性剤を組み合わせて、起泡性組成物を製造したが、いずれの組成物も、低温で一週間保管した場合でも、良好な泡形成性を示した。また、形成された泡は速やかに崩壊することが確認された。 Although various lipophilic surfactants and hydrophilic surfactants shown in Table 8 to Table 10 were combined to produce a foamable composition, any composition was good even when stored at low temperature for one week Showed good foam formation. In addition, it was confirmed that the formed foam disintegrates quickly.
[実施例6]起泡性組成物の調製
水溶性溶媒の量や種類、および、原液と噴射剤の割合を変更した場合の、低温保管時の泡形成性を確認するために、表11に示す組成を有する組成物を調製し、低温(5℃)で保管した場合の泡形成性を確認した。なお、表中の数値は重量%を示す。また、各組成物のpH値は6.4〜6.6の範囲となった。
[Example 6] Preparation of foaming composition In order to confirm the foam-forming property at low temperature storage when the amount and type of the water-soluble solvent, and the ratio of the stock solution and the propellant are changed, Table 11 A composition having the composition shown was prepared and confirmed to have foamability when stored at a low temperature (5 ° C.). The numerical values in the table indicate% by weight. The pH value of each composition was in the range of 6.4 to 6.6.
表11に示すように、親油性界面活性剤としてトリステアリン酸POE(20)ソルビタンを、親水性界面活性剤としてPOE(20)ベヘニルエーテルを使用した原液は、水溶性溶媒の種類や量を変更した場合や、原液と噴射剤の割合を変更した場合にも、低温保管時に優れた泡形成性を示した。また、形成された泡は速やかに崩壊することが確認された。 As shown in Table 11, a stock solution using POE (20) sorbitan tristearate as a lipophilic surfactant and POE (20) behenyl ether as a hydrophilic surfactant changes the type and amount of water-soluble solvent Also in the case where the ratio of the undiluted solution and the propellant was changed, excellent foam formation was shown at the time of low temperature storage. In addition, it was confirmed that the formed foam disintegrates quickly.
Claims (9)
前記原液が、
HLB 5以上11未満のノニオン界面活性剤と、HLB 11以上30以下のノニオン界面活性剤を含むこと、
水性溶媒を70重量%以上含むこと、
ヘパリン類似物質を含むこと、
低級アルコールを含まないこと
を特徴とする、起泡性組成物。 An undiluted solution or an effervescent composition comprising an undiluted solution and a propellant, for applying to skin,
The stock solution is
HLB containing 5 or more and 11 or less nonionic surfactants and HLB 11 or more and 30 or less nonionic surfactants
Containing 70% by weight or more of an aqueous solvent,
Containing heparin analogues,
Foaming composition characterized in that it contains no lower alcohol.
前記HLB 11以上30以下のノニオン界面活性剤が、モノオレイン酸デカグリセリル、モノステアリン酸デカグリセリル、POE(20)POP(8)セチルエーテル、POE(50)硬化ヒマシ油、テトラオレイン酸POE(60)ソルビット、オレイン酸POE(20)ソルビタン、モノステアリン酸ポリエチレングリコール(25E.O.)、POE(15)セチルエーテル、POE(20)ベへニルエーテル、ラウリン酸POE(20)ソルビタン、モノステアリン酸POE(15)グリセリル、POE(54)POP(39)グリコール、ショ糖ラウリン酸エステル(モノエステル80%)、POE(20)ステアリルエーテル、POE(197)POP(67)グリコール、POE(200)POP(67)グリコール、POE(300)POP(55)グリコール、POE(200)POP(40)グリコール、および、POE(160)POP(30)グリコールからなる群より選択される、請求項1〜5のいずれか1項に記載の起泡性組成物。 Said HLB 5 or more and less than 11 nonionic surfactants are monostearic acid POE (6) sorbitan, tristearic acid POE (20) sorbitan, POE.POP glycol (weight average molecular weight 3650, POP molecular weight 2750, EO content 20% ), Glyceryl stearate, POE (5) hydrogenated castor oil, decaglyceryl trioleate, POE (2) cetyl ether, POE (42) POP (67) glycol, tetraoleate POE (6) sorbit, sucrose stearic acid Ester (50% of mono ester), POE (1) POP (8) cetyl ether, POE (20) sorbite beeswax, POE (5) glyceryl monostearate, POE (2) lauryl ether, self-emulsifiable glyceryl monostearate, And monooleic acid POE (6) sorbitan is selected from the group consisting of
Said HLB 11 or more and 30 or less nonionic surfactants are decaglyceryl monooleate, decaglyceryl monostearate, POE (20) POP (8) cetyl ether, POE (50) hydrogenated castor oil, tetraoleic acid POE (60 ) Sorbit, POE oleic acid (20) sorbitan, polyethylene glycol monostearate (25E.O.), POE (15) cetyl ether, POE (20) behenyl ether, lauric acid POE (20) sorbitan, monostearic acid POE (15) Glyceryl, POE (54) POP (39) glycol, sucrose laurate (mono ester 80%), POE (20) stearyl ether, POE (197) POP (67) glycol, POE (200) POP ( 67) Any one of the preceding claims, wherein the glycol is selected from the group consisting of glycol, POE (300) POP (55) glycol, POE (200) POP (40) glycol, and POE (160) POP (30) glycol. The foamable composition according to any one of the preceding claims.
The HLB 5 or more and less than 11 nonionic surfactant is fatty acid polyoxyethylene sorbitan, The said HLB 11 or more and 30 or less nonionic surfactant is a polyoxyethylene alkyl ether in any one of Claims 1-6 . The foamable composition according to item 1.
The HLB 5 or more and less than 11 nonionic surfactants are tristearic acid POE (20) sorbitan, and the HLB 11 or more and 30 or less nonionic surfactants are POE (20) behenyl ethers. foaming composition according to any one of 1-6.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014093412 | 2014-04-30 | ||
JP2014093412 | 2014-04-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015091815A Division JP5988406B2 (en) | 2014-04-30 | 2015-04-28 | Foaming composition |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016180012A JP2016180012A (en) | 2016-10-13 |
JP6507127B2 true JP6507127B2 (en) | 2019-04-24 |
Family
ID=54785032
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015091815A Active JP5988406B2 (en) | 2014-04-30 | 2015-04-28 | Foaming composition |
JP2016139345A Active JP6507127B2 (en) | 2014-04-30 | 2016-07-14 | Foaming composition |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015091815A Active JP5988406B2 (en) | 2014-04-30 | 2015-04-28 | Foaming composition |
Country Status (1)
Country | Link |
---|---|
JP (2) | JP5988406B2 (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5988406B2 (en) * | 2014-04-30 | 2016-09-07 | マルホ株式会社 | Foaming composition |
JP6697257B2 (en) * | 2014-12-24 | 2020-05-20 | 株式会社ポーラファルマ | Method for designing external composition for screen former |
EP3473243B1 (en) * | 2016-06-16 | 2023-03-22 | Pola Pharma Inc. | Foam and screen foamer composition |
JP6928760B2 (en) * | 2016-06-16 | 2021-09-01 | サンファーマ株式会社 | Foam, composition for screen formers, and how to evaluate them |
US11696886B2 (en) * | 2017-05-31 | 2023-07-11 | Shiseido Company, Ltd. | Cosmetic |
JP7301536B2 (en) * | 2018-12-25 | 2023-07-03 | 小林製薬株式会社 | external composition |
KR20210109515A (en) * | 2018-12-27 | 2021-09-06 | 라이온 가부시키가이샤 | Compositions for external use on the skin and aerosols |
WO2020161771A1 (en) * | 2019-02-04 | 2020-08-13 | マルホ株式会社 | Skin composition |
JP6884441B1 (en) * | 2020-07-30 | 2021-06-09 | アピ株式会社 | Topical composition |
JP2022060165A (en) * | 2020-10-02 | 2022-04-14 | 花王株式会社 | Carbonated aerosol topical skin application |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2546794B2 (en) * | 1987-01-26 | 1996-10-23 | 鐘紡株式会社 | Foam self-injection lotion composition |
JPH02123193A (en) * | 1988-11-01 | 1990-05-10 | Kao Corp | Detergent composition |
JPH0812517A (en) * | 1994-06-29 | 1996-01-16 | Kao Corp | Foamable composition |
US7153492B2 (en) * | 2001-04-12 | 2006-12-26 | Medicarb Ab | Effervescent solid composition of matter |
US20060093655A1 (en) * | 2004-10-20 | 2006-05-04 | Lillian Bar | Method for making a reinforced absorbable multilayered hemostatic wound dressing |
US8580860B2 (en) * | 2007-02-23 | 2013-11-12 | Gojo Industries, Inc. | Foamable alcoholic composition |
JP2013170145A (en) * | 2012-02-21 | 2013-09-02 | Kao Corp | Skin cosmetic composition |
JP5988406B2 (en) * | 2014-04-30 | 2016-09-07 | マルホ株式会社 | Foaming composition |
-
2015
- 2015-04-28 JP JP2015091815A patent/JP5988406B2/en active Active
-
2016
- 2016-07-14 JP JP2016139345A patent/JP6507127B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
JP5988406B2 (en) | 2016-09-07 |
JP2015221783A (en) | 2015-12-10 |
JP2016180012A (en) | 2016-10-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6507127B2 (en) | Foaming composition | |
ES2299258T3 (en) | SPONGE COMPOUND. | |
JP4864428B2 (en) | Non-aerosol foam composition and foam using the composition | |
AU2009211147A1 (en) | Substantially non-aqueous foamable petrolatum based pharmaceutical and cosmetic compositions and their uses | |
AU2007356328A1 (en) | Stable non-alcoholic foamable pharmaceutical emulsion compositions with an unctuous emollient and their uses | |
CA2899206C (en) | Compositions for transdermal delivery of mtor inhibitors | |
CN113164511A (en) | Foaming external composition | |
JP2016130224A (en) | External composition | |
KR20090057044A (en) | Emulsion composition with good feeling of use | |
JP5554005B2 (en) | Foam skin application | |
CA2740418C (en) | Salicylic acid composition | |
WO2016104618A1 (en) | Medical dermatological preparation for external use | |
JP2011084490A (en) | Foamed skin liniment | |
JP2017088569A (en) | Cosmetic | |
KR20150102727A (en) | Water-in-oil type emulsion composition | |
JP6832059B2 (en) | Emulsified composition | |
JP6275877B2 (en) | Topical heparin formulation | |
KR101874530B1 (en) | Skin cleansing composition ejected with sherbet-like state and article for skin creansing comprising the same | |
WO2022131081A1 (en) | Emulsified composition for external application | |
JP4965884B2 (en) | O / W type emulsion formulation containing prednisolone valerate acetate | |
JP7348014B2 (en) | Foaming aerosol composition | |
JP2023074499A (en) | Spray-type external composition | |
JP5507600B2 (en) | O / W type emulsion formulation containing prednisolone valerate acetate | |
CN115919745A (en) | Topical pharmaceutical composition in the form of a gel comprising at least amitriptyline for the treatment of coronavirus-induced neuropathic pain | |
CN115919746A (en) | Topical pharmaceutical composition in the form of a gel comprising at least amitriptyline for the treatment of neuropathic phantom limb pain |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171026 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180704 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180719 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181029 |
|
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: 20190320 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190401 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6507127 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 |