JPH01242521A - Antiphlogistic analgesic composition having high percutaneous absorption - Google Patents
Antiphlogistic analgesic composition having high percutaneous absorptionInfo
- Publication number
- JPH01242521A JPH01242521A JP6893088A JP6893088A JPH01242521A JP H01242521 A JPH01242521 A JP H01242521A JP 6893088 A JP6893088 A JP 6893088A JP 6893088 A JP6893088 A JP 6893088A JP H01242521 A JPH01242521 A JP H01242521A
- Authority
- JP
- Japan
- Prior art keywords
- inflammatory
- urea
- analgesic composition
- aliphatic alcohol
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 22
- 238000010521 absorption reaction Methods 0.000 title claims abstract description 16
- 239000002260 anti-inflammatory agent Substances 0.000 title claims abstract description 11
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 6
- 230000001741 anti-phlogistic effect Effects 0.000 title abstract 2
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000004202 carbamide Chemical class 0.000 claims abstract description 16
- 229940124599 anti-inflammatory drug Drugs 0.000 claims abstract description 12
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical class C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical class O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 15
- 230000001760 anti-analgesic effect Effects 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 230000003637 steroidlike Effects 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 20
- 238000002360 preparation method Methods 0.000 abstract description 14
- 239000000654 additive Substances 0.000 abstract description 2
- 239000006071 cream Substances 0.000 abstract description 2
- 239000006185 dispersion Substances 0.000 abstract description 2
- 239000003906 humectant Substances 0.000 abstract description 2
- 239000006210 lotion Substances 0.000 abstract description 2
- 239000007921 spray Substances 0.000 abstract description 2
- 239000004094 surface-active agent Substances 0.000 abstract description 2
- 239000002562 thickening agent Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 4
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 abstract 2
- 239000000126 substance Substances 0.000 abstract 2
- 230000002421 anti-septic effect Effects 0.000 abstract 1
- 239000002552 dosage form Substances 0.000 abstract 1
- 229920000642 polymer Polymers 0.000 abstract 1
- 230000004936 stimulating effect Effects 0.000 abstract 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 30
- 229960001259 diclofenac Drugs 0.000 description 23
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 229960000905 indomethacin Drugs 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 14
- 210000003491 skin Anatomy 0.000 description 12
- 239000008363 phosphate buffer Substances 0.000 description 9
- 230000000699 topical effect Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 8
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 7
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- -1 aliphatic alcohols Chemical class 0.000 description 6
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 241000270295 Serpentes Species 0.000 description 4
- 206010040880 Skin irritation Diseases 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 4
- 229960000890 hydrocortisone Drugs 0.000 description 4
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 4
- 229960000991 ketoprofen Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000036556 skin irritation Effects 0.000 description 4
- 231100000475 skin irritation Toxicity 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960001067 hydrocortisone acetate Drugs 0.000 description 2
- 229940099578 hydrogenated soybean lecithin Drugs 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UUOUOERPONYGOS-CLCRDYEYSA-N Fluocinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 UUOUOERPONYGOS-CLCRDYEYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 125000000017 cortisol group Chemical group 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- UIWVCFJFLGUTJB-UHFFFAOYSA-N decanoic acid propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCCCC(O)=O.CCCCCCCCCC(O)=O.CCCCCCCCCC(O)=O UIWVCFJFLGUTJB-UHFFFAOYSA-N 0.000 description 1
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000007764 o/w emulsion Substances 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
- 230000035699 permeability Effects 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- HTJXMOGUGMSZOG-UHFFFAOYSA-N tiaramide Chemical compound C1CN(CCO)CCN1C(=O)CN1C(=O)SC2=CC=C(Cl)C=C21 HTJXMOGUGMSZOG-UHFFFAOYSA-N 0.000 description 1
- 229950010302 tiaramide Drugs 0.000 description 1
- PFENFDGYVLAFBR-UHFFFAOYSA-N tinoridine Chemical compound C1CC=2C(C(=O)OCC)=C(N)SC=2CN1CC1=CC=CC=C1 PFENFDGYVLAFBR-UHFFFAOYSA-N 0.000 description 1
- 229950010298 tinoridine Drugs 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、抗炎症薬の経皮吸収性を高めた消炎鎮痛薬組
成物に関する。さらに詳しくは、抗炎症薬、水素添加リ
ン脂質、尿素、炭素数６以上の脂肪族アルコール及び水
を含有する、経皮吸収性に優れ、皮膚刺激がなく、使用
感のよい新規の消炎鎮痛薬組成物に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an anti-inflammatory and analgesic composition with enhanced percutaneous absorption of the anti-inflammatory drug. More specifically, it is a novel anti-inflammatory analgesic drug that contains anti-inflammatory drugs, hydrogenated phospholipids, urea, aliphatic alcohols with 6 or more carbon atoms, and water, has excellent transdermal absorption, does not cause skin irritation, and is easy to use. The present invention relates to a composition.
〔従来の技術及び発明が解決しようとする課題］従来、
抗炎症薬の経皮投与製剤としては、カルボキシビニルポ
リマーを水に溶解して増粘させた基剤に薬物を溶解させ
たものや、水中油型エマルションからなる基剤に薬物を
溶解又は懸濁させたものなどが市販されている。しかし
ながら、これらの市販品は、いずれも経皮吸収性が十分
でないばかりが、皮膚刺激性等の副作用の点で問題点が
多い。特にジクロフェナックは優れた消炎鎮痛効果があ
るにもががねらず、他の非ステロイド系薬物に比べて経
皮による吸収性が悪いため、経皮投与製剤の開発はほと
んどなされていない。[Prior art and problems to be solved by the invention] Conventionally,
Transdermal preparations for anti-inflammatory drugs include those in which the drug is dissolved in a base made by dissolving carboxyvinyl polymer in water to increase its viscosity, and those in which the drug is dissolved or suspended in a base consisting of an oil-in-water emulsion. There are commercially available products that are made with this method. However, all of these commercially available products not only have insufficient percutaneous absorption, but also have many problems in terms of side effects such as skin irritation. In particular, diclofenac has excellent anti-inflammatory and analgesic effects but is not easily absorbed through the skin compared to other non-steroidal drugs, so there has been little development of transdermal preparations.
また、非ステロイド系消炎鎮痛薬の吸収性を向上させる
ためにリン脂質を併用する発明が開示されているが（特
開昭６１−１７２８３１号公報）、ある程度の吸収性の
改善が見られるものの、臨床適用上からは満足のいくも
のではない。In addition, an invention has been disclosed in which phospholipids are used in combination to improve the absorption of non-steroidal anti-inflammatory analgesics (Japanese Patent Application Laid-open No. 172831/1983), but although some improvement in absorption is observed, This is not satisfactory from a clinical application point of view.
消炎鎮痛剤の開発は、今後、高齢化社会に向かってます
ます要望が高まっていき、高齢化社会においては、循環
器障害や精神性障害治療薬に加えて、リウマチ疾患治療
薬の必要性が高まっている。また、その治療期間が長期
化し、特にリウマチ疾患を有する患者では、痛みによる
不眠により精神的ストレスが高まり、社会生活の不安を
誘起する。Demand for the development of anti-inflammatory analgesics will increase as we move towards an aging society, and in addition to drugs to treat cardiovascular disorders and mental disorders, there will also be a need for drugs to treat rheumatic diseases. It's increasing. In addition, the treatment period is prolonged, and especially in patients with rheumatic diseases, mental stress increases due to insomnia due to pain, leading to anxiety in social life.
従って、このような欠点を解消し、製剤からの薬物の経
皮吸収性が優れた消炎鎮痛剤の開発が強く望まれている
。すなわち、痛みのある局所に塗布したときにただちに
経皮吸収され、効果を発揮するような製剤の開発が望ま
れている。Therefore, it is strongly desired to develop an anti-inflammatory and analgesic drug that overcomes these drawbacks and has excellent transdermal absorption of the drug from its formulation. That is, it is desired to develop a formulation that is immediately absorbed transdermally and exerts its effects when applied to a painful area.
本発明者らは、薬物の放出性がよく経皮吸収性の優れた
消炎鎮痛剤を開発すべく鋭意研究を重ねた結果、本発明
を完成するに至った。The present inventors have completed the present invention as a result of extensive research to develop an anti-inflammatory analgesic with good drug release and transdermal absorption.
すなわち、皮膚との親和性がよく皮膚の水分保持能力に
優れた水素添加リン脂質に着目し、水素添加リン脂質、
尿素及び水と薬物を共存させることにより薬物の経皮吸
収が促進されることを確認した。さらに、この系に炭素
数６以上の脂肪族アルコールを添加することにより、薬
物の経皮吸収が一段と促進されることを見出した。In other words, we focused on hydrogenated phospholipids, which have a good affinity with the skin and have excellent skin moisture retention ability.
It was confirmed that transdermal absorption of the drug was promoted by allowing the drug to coexist with urea and water. Furthermore, it has been found that by adding an aliphatic alcohol having 6 or more carbon atoms to this system, transdermal absorption of the drug is further promoted.
本発明は、以上の知見をもとにして完成されたものであ
り、抗炎症薬、水素添加リン脂質、尿素、炭素数６以上
の脂肪族アルコール及び水を含有してなることを特徴と
する、経皮吸収性に優れ、皮膚刺激がなく使用域のよい
新規なる消炎鎮痛剤を提供せんとするものである。The present invention was completed based on the above findings, and is characterized by containing an anti-inflammatory drug, a hydrogenated phospholipid, urea, an aliphatic alcohol having 6 or more carbon atoms, and water. The present invention aims to provide a new anti-inflammatory analgesic agent that has excellent transdermal absorption, does not cause skin irritation, and can be used over a wide range of applications.
本発明に用いられる水素添加リン脂質としては、大豆、
トウモロコシ、綿実、卵黄、牛脳等の動植物から抽出し
たリン脂質類を定法により水素添加したもの、又は化学
的に合成したホスファチジルコリン、ホスファチジルエ
タノールアミン、ホスファチジルイノシトール、ホスフ
ァチジルセリン及びスフィンゴリン脂質等が挙げられ、
それぞれの水素添加リン脂質を単独で使用しても、また
２種以上を混合して使用してもよい。Hydrogenated phospholipids used in the present invention include soybean,
Examples include phospholipids extracted from animals and plants such as corn, cottonseed, egg yolk, and bovine brain, hydrogenated by a conventional method, or chemically synthesized phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingophospholipids. is,
Each of the hydrogenated phospholipids may be used alone or in combination of two or more.
本発明で使用される脂肪族アルコールとしては、オクタ
ツール、イソオクタツール、デカノール、ドデカノール
、テトラデカノール、ヘキサデカノール、ステアリルア
ルコール、オレイルアルコール、イソステアリルアルコ
ール、オクチルドデカノール等の炭素数６以上の飽和又
は不飽和の直鎖又は分岐のアルコール類が挙げられる。Examples of aliphatic alcohols used in the present invention include octatool, isooctatoul, decanol, dodecanol, tetradecanol, hexadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyldodecanol, and the like having 6 or more carbon atoms. Examples include saturated or unsaturated straight-chain or branched alcohols.
本発明で使用される抗炎症薬としては、消炎鎮痛作用を
有する薬物であればどんなものでも使用できる。かかる
薬物の具体例としては、ジクロフェナック、フルフェナ
ム酸、インドメタシン、アスピリン、アミノピリン、ア
ンチピリン、フェニルブタシン、イブプロフェン、フル
ルビプロフェン、ケトプロフェン、チノリジン、チアラ
ミド等の非ステロイド系抗炎症薬、フルオシノロンアセ
トニド、酢酸デキサメタシン、吉草酸ベタメタシン、プ
レドニゾロン、ヒドロコルチゾン、酢酸ヒドロコルチゾ
ン、醋酸プロピオン酸ヒドロコルチゾンなどの副腎皮質
ホルモン（ステロイド系抗炎症薬）等が挙げられる。As the anti-inflammatory drug used in the present invention, any drug can be used as long as it has anti-inflammatory and analgesic effects. Examples of such drugs include non-steroidal anti-inflammatory drugs such as diclofenac, flufenamic acid, indomethacin, aspirin, aminopyrine, antipyrine, phenylbutacin, ibuprofen, flurbiprofen, ketoprofen, tinoridine, tialamide, fluocinolone acetate, etc. Examples include adrenocortical hormones (steroidal anti-inflammatory drugs) such as dexamethacin acetate, betamethacin valerate, prednisolone, hydrocortisone, hydrocortisone acetate, and hydrocortisone acetate propionate.
これらの薬物はそのまま使用してもよいが、必要に応じ
て酸やアルカリで中和した塩として使用することもでき
る。These drugs can be used as they are, but if necessary, they can also be used as salts neutralized with acids or alkalis.
本発明の消炎鎮痛薬組成物に使用する水素添加リン脂質
の濃度には特に制限はないが、１〜２０重量％が適当で
ある。さらに好ましくは、３〜１０重量％が適当である
。又、配合する尿素及び脂肪族アルコールの濃度は、薬
物の経皮吸収を促進することができる濃度であればよく
、通常は、製剤中にそれぞれ１〜ＩＯ重量％の割合で添
加される。The concentration of hydrogenated phospholipid used in the anti-inflammatory and analgesic composition of the present invention is not particularly limited, but is suitably 1 to 20% by weight. More preferably, 3 to 10% by weight is appropriate. The concentrations of urea and aliphatic alcohol to be blended may be such that they can promote transdermal absorption of the drug, and are usually added to the formulation at a rate of 1 to 10% by weight, respectively.
本発明の消炎鎮痛薬組成物は、抗炎症薬、水素添加リン
脂質、尿素、炭素数６以上の脂肪族アルコール及び水を
必須成分として含有していればよく、ローシヨン剤、ゲ
ル剤、クリーム剤、スプレー剤、バンプ剤等、どんな形
態で使用してもよい。又、上記必須成分の他に炭化水素
、高級アルコール脂肪酸エステル、多価アルコール脂肪
酸エステル等の油性成分や、多価アルコールを併用する
と効果的である。薬物の溶解性が悪い場合には、エタノ
ール等の低級アルコール類、プロピレングリコール等の
多価アルコール類を必要量添加しても差し支えはない。The anti-inflammatory analgesic composition of the present invention may contain an anti-inflammatory drug, hydrogenated phospholipid, urea, aliphatic alcohol having 6 or more carbon atoms, and water as essential components, and may be a lotion, a gel, or a cream. It may be used in any form such as , spray, bump, etc. In addition to the above-mentioned essential components, it is effective to use oily components such as hydrocarbons, higher alcohol fatty acid esters, polyhydric alcohol fatty acid esters, and polyhydric alcohols in combination. If the solubility of the drug is poor, there is no problem in adding a required amount of lower alcohols such as ethanol or polyhydric alcohols such as propylene glycol.
さらに、必要に応じて高分子増粘剤、界面活性剤等の分
散助剤、保湿剤、防腐剤等の添加物を配合することがで
きる。Furthermore, additives such as polymeric thickeners, dispersion aids such as surfactants, humectants, and preservatives may be blended as necessary.
本発明の消炎鎮痛薬組成物は、配合成分による相乗作用
により従来の消炎鎮痛剤に比べて薬物の経皮吸収性が格
段に高められ、薬物がを効に作用し、少量の投与で十分
にその効果を発揮させることができる。又、生体成分の
１種であろ水素添加リン脂質を使用しているため、皮Ｉ
５への親和性に優れ、使用感も非常によい。さらに、安
全性が非常に高く、粘膜刺激、皮膚刺激、消化管障害等
の副作用もまったくないばかりか、薬物による副作用も
軽減できる。The anti-inflammatory and analgesic composition of the present invention has a synergistic effect of the ingredients, and the transdermal absorption of the drug is much higher than that of conventional anti-inflammatory and analgesics. The effect can be demonstrated. In addition, since we use hydrogenated phospholipids, which are a type of biological component, skin I
5, and has a very good usability. Furthermore, it is extremely safe, with no side effects such as mucous membrane irritation, skin irritation, or gastrointestinal disorders, and can also reduce drug-induced side effects.
以下、実施例を挙げて本発明を具体的に説明するが、本
発明はこれらの実施例に限定されるものではない。EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to these Examples.
比較例１
ジクロフェナックＮａ塩１００ ｍｇをエタノール１０
．０ｇに溶解し、これに０．１１１リン酸緩衝液８９．
９ｇを加えてジクロフェナック水溶液を調製した。Comparative Example 1 100 mg of diclofenac Na salt was added to 10 mg of ethanol.
．． Dissolve in 0.0 g and add 0.111 phosphate buffer 89.
A diclofenac aqueous solution was prepared by adding 9 g.
比較例２
ジクロフェナックＮａ塩１００ ｍｇをエタノール１０
．０ ｇに溶解し、これに０．１Ｍリン酸緩衝液８３．
４ｇを加えてジクロフェナック水溶液を調製した。Comparative Example 2 100 mg of diclofenac Na salt was added to 10 mg of ethanol.
．． Dissolve in 0.0 g and add 0.1M phosphate buffer 83.
4 g was added to prepare a diclofenac aqueous solution.
この水溶液に水素添加大豆リン脂質（ヨウ素価＝３．５
） ６．５ｇを加えて８０’Ｃに加温した後、ホモミキ
サーを用いて、８０００ ｒｐｍで１０分間撹拌した後
、撹拌しながら室温まで冷却してジクロフェナック対照
液を調製した。Add hydrogenated soybean phospholipid (iodine value = 3.5) to this aqueous solution.
) After adding 6.5 g and heating to 80'C, the mixture was stirred at 8000 rpm for 10 minutes using a homomixer, and then cooled to room temperature while stirring to prepare a diclofenac control solution.
比較例３
ジクロフェナックＮａ塩１００ ｍｇをエタノール１０
．０ｇに溶解し、これに０．１Ｍリン酸緩衝液７８．４
ｇを加えてジクロフェナック水溶液を調製した。Comparative Example 3 100 mg of diclofenac Na salt was added to 10 mg of ethanol.
．． Dissolve in 0g and add 0.1M phosphate buffer 78.4 to this.
g to prepare a diclofenac aqueous solution.
この水溶液に水素添加大豆リン脂質（ヨウ素価＝３．５
） ６．５ｇ、尿素５．０ｇを加えて８０″Ｃに加温し
た後、ホモミキサーを用い、８０００ ｒｐｍで１０分
間撹拌した。これをゆっ（り撹拌しながら室温まで冷却
して尿素含有ジクロフェナック対照液を調製した。Add hydrogenated soybean phospholipid (iodine value = 3.5) to this aqueous solution.
) and 5.0 g of urea were added and heated to 80''C, followed by stirring at 8000 rpm for 10 minutes using a homomixer. A control solution was prepared.
実施例１
ジクロフェナックＮａ塩１００■をエタノール１０、０
ｇに溶解し、これに０．１Ｍリン酸緩衝液７１．９ｇ
を加えてジクロフェナック水溶液を調製した。Example 1 Diclofenac Na salt 100μ was mixed with ethanol 10.0
g, and add 71.9 g of 0.1M phosphate buffer to this.
was added to prepare a diclofenac aqueous solution.
この水溶液に水素添加大豆リン脂質（ヨウ素価＝３．５
） ６．５ｇ、デカノール６．５ｇ及び尿素５．０ｇを
加えて８０°Ｃに加温した後、超音波ホモジナイザーに
より１０分間ホモジナイズした。これをゆっくり撹拌し
ながら室温まで冷却してジクロフェナック外用剤を調製
した。Add hydrogenated soybean phospholipid (iodine value = 3.5) to this aqueous solution.
), 6.5 g of decanol, and 5.0 g of urea were added, heated to 80°C, and then homogenized for 10 minutes using an ultrasonic homogenizer. This was cooled to room temperature while being slowly stirred to prepare a diclofenac topical preparation.
実験例１
比較例１、比較例２、比較例３及び実施例１で調製した
ジクロフェナック外用剤の経皮吸収性について次の方法
で比較検討した。Experimental Example 1 The transdermal absorbability of the diclofenac topical preparations prepared in Comparative Example 1, Comparative Example 2, Comparative Example 3, and Example 1 was comparatively investigated using the following method.
体重１６０〜１８０ ｇのウィスター系雄性ラット（−
群５匹）をバリカンで除毛し、ベンドパルビタールで麻
酔した後、背部皮膚を剥ぎ取った。Male Wistar rats weighing 160-180 g (-
After removing the hair from the animals (group of 5 animals) with clippers and anesthetizing them with bendoparbital, the dorsal skin was peeled off.
剥ぎ取った皮膚をフランツ型拡散セル（直径２．６ｃｍ
）に固定し、ドナー側に試料１ｇ（ジクロフェナックＮ
ａ塩含ｆｆｉ１ｍｇ）を塗布し、レセプター側にＯ，１
Ｍリン酸緩衝液を満たした。実験中レセプター側は３７
°Ｃを保ち、マグネチックスクーラーで撹拌した。所定
時間ごとにレセプター側から５０ＩＪＩずつサンプリン
グし、ジクロフェナック含量を高速液体クロマトグラフ
ィーを用いて定法により定量した。その結果を第１図に
示す。The peeled skin was placed in a Franz-type diffusion cell (2.6 cm in diameter).
), and 1 g of sample (diclofenac N) was fixed on the donor side.
Apply 1 mg of salt-containing ffi) to the receptor side, and
Filled with M phosphate buffer. During the experiment, the receptor side was 37
The mixture was maintained at °C and stirred using a magnetic cooler. Samples of 50 IJI were taken from the receptor side at predetermined intervals, and the diclofenac content was determined by a standard method using high performance liquid chromatography. The results are shown in FIG.
第１図に示すごとく、本発明品は対照の比較品に比べて
ジクロフェナックＮａ塩の皮膚透過性が優れており、水
素添加リン脂質、尿素、炭素数６以上の脂肪族アルコー
ル及び水が共存することにより、その相乗作用による有
効性が確認された。As shown in Figure 1, the product of the present invention has better skin permeability of diclofenac Na salt than the comparison product, and hydrogenated phospholipid, urea, aliphatic alcohol with 6 or more carbon atoms, and water coexist. As a result, the effectiveness of the synergistic action was confirmed.
実施例２
インドメタシン１００ ｍｇをエタノール１０．０ ｇ
に溶解し、これに０．１Ｍリン酸緩衝液７６．９ｇを加
えてインドメタシンの水溶液を調製した。この水溶液に
水素添加大豆リン脂質（ヨウ素価−７）５．０ｇ、オク
タツール５．０ｇ及び尿素３．０ｇを加えて８０℃に加
温した後、ホモミキサーを用い、１１００００ｒｐで１
０分間撹拌した。これをゆっくり撹拌しながら室温まで
冷却してインドメタシン外用剤を調製した。Example 2 100 mg of indomethacin and 10.0 g of ethanol
and 76.9 g of 0.1M phosphate buffer was added thereto to prepare an aqueous solution of indomethacin. To this aqueous solution, 5.0 g of hydrogenated soybean phospholipid (iodine value -7), 5.0 g of octatool, and 3.0 g of urea were added and heated to 80°C.
Stirred for 0 minutes. This was cooled to room temperature while being slowly stirred to prepare an indomethacin topical preparation.
実施例３
インドメタシン１００■をエタノールＩＯ，Ｏｇに溶解
し、これに０．１Ｍリン酸緩衝液６９．９ ｇ及び尿素
３．０ ｇを加えた後、加温しインドメタシンの水溶液
を調製した。この水溶液に水素添加大豆リン脂質（ヨウ
素価＝７）５．０ｇ、デカノール５．０ｇ及びトリカプ
リン酸グリセリンにッコール トリニスター Ｆ−８１
０） ７．０ｇを加えて８０°Ｃに加温した後、ホモミ
キサーを用い、１１００００ｒｐで１０分間撹拌した。Example 3 100 ml of indomethacin was dissolved in IO, Og of ethanol, 69.9 g of 0.1M phosphate buffer and 3.0 g of urea were added thereto, and heated to prepare an aqueous solution of indomethacin. This aqueous solution contains 5.0 g of hydrogenated soybean phospholipid (iodine value = 7), 5.0 g of decanol, and glycerin tricaprate.
0) After adding 7.0 g and heating to 80°C, the mixture was stirred at 110,000 rpm for 10 minutes using a homomixer.
これをゆっくり撹拌しながら室温まで冷却してインドメ
タシン外用剤を調製した。This was cooled to room temperature while being slowly stirred to prepare an indomethacin topical preparation.
実施例４
インドメタシン１００ ｍｇをエタノール１０．０ ｇ
に溶解し、これにＯ，１Ｍリン酸緩衝液６９．９ ｇ及
び尿素３．０ｇを加えた後、加温してインドメタシンの
水溶液を調製した。水素添加大豆リン脂質（ヨウ素価＝
７）５．０ｇ、ドデカノール５．０ｇ及びトリカプリン
酸グリセリンにッコールトリエスター Ｆ−８１０）
７．０ｇを混合した後、８０°Ｃに加温して透明に溶解
した。この混合物をインドメタシン水溶液に加えて、超
音波ホモジナイザーを用い１０分間ホモジナイズした。Example 4 100 mg of indomethacin and 10.0 g of ethanol
After adding 69.9 g of O, 1M phosphate buffer and 3.0 g of urea, the mixture was heated to prepare an aqueous solution of indomethacin. Hydrogenated soybean phospholipids (iodine value =
7) 5.0g, dodecanol 5.0g and glycerin tricapric acid with Coccor Triester F-810)
After mixing 7.0 g, the mixture was heated to 80°C and dissolved transparently. This mixture was added to an aqueous indomethacin solution and homogenized for 10 minutes using an ultrasonic homogenizer.
これをゆっくり撹拌しながら室温まで冷却してインドメ
タシン外用剤を調製した。This was cooled to room temperature while being slowly stirred to prepare an indomethacin topical preparation.
実験例２
実施例２、実施例３及び実施例４で調製したインドメタ
シン外用剤の経皮吸収性について、実験例１の方法に準
じて検討した。なお、対照としては比較例２のジクロフ
ェナックをインドメタシンに代えて調製したインドメタ
シン対照液を使用した。その結果を第２図、第３図及び
第４図に示す。Experimental Example 2 The transdermal absorbability of the indomethacin topical preparations prepared in Examples 2, 3, and 4 was investigated according to the method of Experimental Example 1. As a control, an indomethacin control solution prepared by replacing diclofenac with indomethacin in Comparative Example 2 was used. The results are shown in FIGS. 2, 3, and 4.
いずれの場合も、水素添加大豆レシチンのみを添加した
場合に比べて顕著に皮膚透過性が促進されることが確認
された。In both cases, it was confirmed that skin permeability was significantly promoted compared to when only hydrogenated soybean lecithin was added.
実施例５
ジクロフェナック０．５ｇ、水素添加大豆レシチン６．
０ｇ、尿素３．０ｇ及びテトラデカノール３．０ｇを０
．１Ｍリン酸緩衝液８４．５ ｇに加えて８０°Ｃに加
温した後、ホモミキサーを用いて１１００００ｒｐで１
５分間撹拌する。撹拌しながら室温まで冷却してゲル状
の外用剤を調製した。Example 5 Diclofenac 0.5g, hydrogenated soybean lecithin 6.
0g, urea 3.0g and tetradecanol 3.0g
．． Add to 84.5 g of 1M phosphate buffer, warm to 80°C, and mix at 110,000 rpm using a homomixer.
Stir for 5 minutes. A gel-like external preparation was prepared by cooling to room temperature while stirring.
実施例６
ジクロフェナックをケトプロフェンに代えて、実施例５
に準じてゲル状のケトプロフェン外用剤をｔＭ製した。Example 6 Example 5 by replacing diclofenac with ketoprofen
A gel-like ketoprofen topical preparation was manufactured by tM in accordance with the above.
実施例７
ジクロフェナックをヒドロコルチゾンに代えて、実施例
５に準じてゲル状のヒドロコルチゾン外用剤を調製した
。Example 7 A gel-like hydrocortisone topical preparation was prepared according to Example 5, except that diclofenac was replaced with hydrocortisone.
実験例３
実施例５、実施例６及び実施例７で調製したゲル状外用
剤の経皮吸収性について、ラット皮膚の代わりに角質層
モデルとして脱皮したヘビ皮を使用して実験例１の方法
に準じて評価した。Experimental Example 3 Regarding the transdermal absorption of the gel-like external preparations prepared in Examples 5, 6, and 7, the method of Experimental Example 1 was conducted using shed snake skin as a stratum corneum model instead of rat skin. It was evaluated according to.
対照としては、それぞれの薬物について比較例１及び比
較例２に準じて調製した水溶液及び対照液を使用した。As controls, aqueous solutions and control solutions prepared according to Comparative Examples 1 and 2 for each drug were used.
その結果を第５図、第６図及び第７図に示す。The results are shown in FIGS. 5, 6, and 7.
第５図〜第７図に示すように、いずれの薬物においても
水溶液や水素添加リン脂質のみを含有する対照液に比べ
て、本発明品は極めて優れた経皮透過性を示し、本発明
品の有用性が確認された。As shown in Figures 5 to 7, the products of the present invention exhibited extremely superior transdermal permeability compared to aqueous solutions and control solutions containing only hydrogenated phospholipids for all drugs. The usefulness of this was confirmed.
第１図はジクロフェナックＮａ塩含有外用剤を適用シた
ときのラット皮膚を透過したジクロフェナックＮａ塩量
の経時変化を示す図面、第２図〜第４図はインドメタシ
ン含有外用剤を適用しタトキのラット皮膚を透過したイ
ンドメタシン量の経時変化を示す図面、第５図はヘビ皮
を透過したジクロフェナックＮａ塩量の経時変化を示す
図面、第６図はヘビ皮を透過したケトプロフェン量の経
時変化を示す図面、第７図はヘビ皮を透過したヒドロコ
ルチゾン量の経時変化を示す図面である。Figure 1 shows the time course of the amount of diclofenac Na salt that permeated through the skin of rats when a topical preparation containing diclofenac Na salt was applied. Figure 5 shows the change in the amount of indomethacin that permeated through the skin over time, Figure 5 shows the change in the amount of diclofenac Na salt that permeated through the snake skin over time, and Figure 6 shows the change in the amount of ketoprofen that permeated through the snake skin over time. , FIG. 7 is a diagram showing the change over time in the amount of hydrocortisone that permeated through snake skin.
Claims (1)
の脂肪族アルコール及び水を含有してなることを特徴と
する経皮吸収性を高めた消炎鎮痛薬組成物。 ２、水素添加リン脂質がホスファチジルコリン、ホスフ
ァチジルエタノールアミン、ホスファチジルイノシトー
ル、ホスファチジルセリン及びスフィンゴリン脂質類か
ら選ばれた１種又は２種以上の混合物である請求項１記
載の消炎鎮痛薬組成物。 ３、脂肪族アルコールが飽和又は不飽和の直鎖又は分岐
アルコールから選ばれた少なくとも１種である請求項１
記載の消炎鎮痛薬組成物。 ４、抗炎症薬が非ステロイド系抗炎症薬及び／又はステ
ロイド系抗炎症薬である請求項１記載の消炎鎮痛薬組成
物。[Scope of Claims] 1. An anti-inflammatory and analgesic composition with enhanced percutaneous absorption, characterized by containing an anti-inflammatory drug, a hydrogenated phospholipid, urea, an aliphatic alcohol having 6 or more carbon atoms, and water. thing. 2. The anti-inflammatory analgesic composition according to claim 1, wherein the hydrogenated phospholipid is one or a mixture of two or more selected from phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingophospholipids. 3. Claim 1, wherein the aliphatic alcohol is at least one selected from saturated or unsaturated linear or branched alcohols.
The anti-inflammatory analgesic composition described. 4. The anti-inflammatory and analgesic composition according to claim 1, wherein the anti-inflammatory drug is a nonsteroidal anti-inflammatory drug and/or a steroidal anti-inflammatory drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6893088A JPH01242521A (en) | 1988-03-23 | 1988-03-23 | Antiphlogistic analgesic composition having high percutaneous absorption |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6893088A JPH01242521A (en) | 1988-03-23 | 1988-03-23 | Antiphlogistic analgesic composition having high percutaneous absorption |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01242521A true JPH01242521A (en) | 1989-09-27 |
Family
ID=13387869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6893088A Pending JPH01242521A (en) | 1988-03-23 | 1988-03-23 | Antiphlogistic analgesic composition having high percutaneous absorption |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01242521A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991012821A1 (en) * | 1990-03-02 | 1991-09-05 | Shiseido Company, Ltd. | Oil-in-water emulsion composition containing nonsteroidal antiphlogistic analgesic |
| ES2047456A1 (en) * | 1992-07-31 | 1994-02-16 | Postigo Herrando | Cosmetic compsn. - contains retinoic acid, beta-methasone di-propionate, urea and excipient |
| WO1996029988A1 (en) * | 1995-03-24 | 1996-10-03 | George Elmer Roentsch | Topical formulation for local delivery of a pharmaceutically active agent |
| US5861170A (en) * | 1991-12-20 | 1999-01-19 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Acetylsalicyclic acid-containing transdermal application system for antithrombotic therapy |
| US6011052A (en) * | 1996-04-30 | 2000-01-04 | Warner-Lambert Company | Pyrazolone derivatives as MCP-1 antagonists |
| US6368618B1 (en) | 1999-07-01 | 2002-04-09 | The University Of Georgia Research Foundation, Inc. | Composition and method for enhanced transdermal absorption of nonsteroidal anti-inflammatory drugs |
| JP2005314254A (en) * | 2004-04-28 | 2005-11-10 | Pola Chem Ind Inc | External preparation for skin which is suitable as quasi-drug |
| JP2008163010A (en) * | 2006-12-06 | 2008-07-17 | Rohto Pharmaceut Co Ltd | Skin preparation |
| JP2010270299A (en) * | 2009-04-23 | 2010-12-02 | Nihon Univ | Oil gel consisting of reverse string micelle based on lecithin and urea |
| JP2013500239A (en) * | 2009-07-24 | 2013-01-07 | ミーカ ファルマ ゲゼルシャフト フュア ディー エントヴィックルング ウント フェアマルクトゥング ファルマツォイティッシャー プロドゥクテ ミット ベシュレンクテル ハフツング | Foamable liquid composition containing an active agent and method for producing or developing the same |
| EP4529917A1 (en) * | 2023-09-27 | 2025-04-02 | Andros Pharmaceuticals Co., Ltd. | Topical delivery compositions comprising non-steroidal anti-inlammatory drugs |
-
1988
- 1988-03-23 JP JP6893088A patent/JPH01242521A/en active Pending
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991012821A1 (en) * | 1990-03-02 | 1991-09-05 | Shiseido Company, Ltd. | Oil-in-water emulsion composition containing nonsteroidal antiphlogistic analgesic |
| US5256691A (en) * | 1990-03-02 | 1993-10-26 | Shiseido Company Ltd. | Oil-in-water type emulsified composition comprising non-steroidal antiphlogistic and analgesic drug |
| US5861170A (en) * | 1991-12-20 | 1999-01-19 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Acetylsalicyclic acid-containing transdermal application system for antithrombotic therapy |
| US6264978B1 (en) | 1991-12-20 | 2001-07-24 | Lts Lohmann Therapie-Systeme Gmbh & Co. Kg | Transdermal application system containing acetylsalicylic acid for antithrombotic therapy and cancer prophylaxis |
| ES2047456A1 (en) * | 1992-07-31 | 1994-02-16 | Postigo Herrando | Cosmetic compsn. - contains retinoic acid, beta-methasone di-propionate, urea and excipient |
| WO1996029988A1 (en) * | 1995-03-24 | 1996-10-03 | George Elmer Roentsch | Topical formulation for local delivery of a pharmaceutically active agent |
| US5654337A (en) * | 1995-03-24 | 1997-08-05 | II William Scott Snyder | Topical formulation for local delivery of a pharmaceutically active agent |
| US6011052A (en) * | 1996-04-30 | 2000-01-04 | Warner-Lambert Company | Pyrazolone derivatives as MCP-1 antagonists |
| US6368618B1 (en) | 1999-07-01 | 2002-04-09 | The University Of Georgia Research Foundation, Inc. | Composition and method for enhanced transdermal absorption of nonsteroidal anti-inflammatory drugs |
| JP2005314254A (en) * | 2004-04-28 | 2005-11-10 | Pola Chem Ind Inc | External preparation for skin which is suitable as quasi-drug |
| JP2008163010A (en) * | 2006-12-06 | 2008-07-17 | Rohto Pharmaceut Co Ltd | Skin preparation |
| JP2010270299A (en) * | 2009-04-23 | 2010-12-02 | Nihon Univ | Oil gel consisting of reverse string micelle based on lecithin and urea |
| JP2013500239A (en) * | 2009-07-24 | 2013-01-07 | ミーカ ファルマ ゲゼルシャフト フュア ディー エントヴィックルング ウント フェアマルクトゥング ファルマツォイティッシャー プロドゥクテ ミット ベシュレンクテル ハフツング | Foamable liquid composition containing an active agent and method for producing or developing the same |
| US9693956B2 (en) | 2009-07-24 | 2017-07-04 | Mika Pharma Gmbh | Liquid compositions capable of foaming and including active agents, and methods for making or developing same |
| EP4529917A1 (en) * | 2023-09-27 | 2025-04-02 | Andros Pharmaceuticals Co., Ltd. | Topical delivery compositions comprising non-steroidal anti-inlammatory drugs |
| WO2025066019A1 (en) * | 2023-09-27 | 2025-04-03 | Andros Pharmaceuticals Co., Ltd. | Topical delivery compositions comprising non-steroidal anti-inflammatory drugs |
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