JPS63225316A - Composition for exodermal administration - Google Patents
Composition for exodermal administrationInfo
- Publication number
- JPS63225316A JPS63225316A JP132987A JP132987A JPS63225316A JP S63225316 A JPS63225316 A JP S63225316A JP 132987 A JP132987 A JP 132987A JP 132987 A JP132987 A JP 132987A JP S63225316 A JPS63225316 A JP S63225316A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- indomethacin
- diazepam
- administration
- skin
- 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 24
- 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 claims abstract description 36
- 229960000905 indomethacin Drugs 0.000 claims abstract description 18
- -1 dicyclohexyl Chemical compound 0.000 claims abstract description 16
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229960003529 diazepam Drugs 0.000 claims abstract description 14
- 150000004040 pyrrolidinones Chemical class 0.000 claims abstract description 7
- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Chemical compound CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000002334 glycols Chemical class 0.000 claims abstract description 6
- YHQGMYUVUMAZJR-UHFFFAOYSA-N α-terpinene Chemical compound CC(C)C1=CC=C(C)CC1 YHQGMYUVUMAZJR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- SGVUHPSBDNVHKL-UHFFFAOYSA-N (+-)-trans-1,3-Dimethyl-cyclohexan Natural products CC1CCCC(C)C1 SGVUHPSBDNVHKL-UHFFFAOYSA-N 0.000 claims abstract description 3
- SGVUHPSBDNVHKL-OCAPTIKFSA-N (1r,3s)-1,3-dimethylcyclohexane Chemical compound C[C@H]1CCC[C@@H](C)C1 SGVUHPSBDNVHKL-OCAPTIKFSA-N 0.000 claims abstract description 3
- WSTYNZDAOAEEKG-UHFFFAOYSA-N Mayol Natural products CC1=C(O)C(=O)C=C2C(CCC3(C4CC(C(CC4(CCC33C)C)=O)C)C)(C)C3=CC=C21 WSTYNZDAOAEEKG-UHFFFAOYSA-N 0.000 claims abstract description 3
- VYBREYKSZAROCT-UHFFFAOYSA-N alpha-myrcene Natural products CC(=C)CCCC(=C)C=C VYBREYKSZAROCT-UHFFFAOYSA-N 0.000 claims abstract description 3
- GGBJHURWWWLEQH-UHFFFAOYSA-N butylcyclohexane Chemical group CCCCC1CCCCC1 GGBJHURWWWLEQH-UHFFFAOYSA-N 0.000 claims abstract description 3
- IYQYZZHQSZMZIG-UHFFFAOYSA-N tricyclo[5.2.1.0(2.6)]deca-3,8-diene, 4.9-dimethyl Chemical compound C1C2C3C=C(C)CC3C1C=C2C IYQYZZHQSZMZIG-UHFFFAOYSA-N 0.000 claims abstract description 3
- XOKSLPVRUOBDEW-UHFFFAOYSA-N pinane Chemical compound CC1CCC2C(C)(C)C1C2 XOKSLPVRUOBDEW-UHFFFAOYSA-N 0.000 claims abstract 4
- 229930006728 pinane Natural products 0.000 claims abstract 2
- 150000001298 alcohols Chemical class 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 5
- CRSBERNSMYQZNG-UHFFFAOYSA-N 1-dodecene Chemical compound CCCCCCCCCCC=C CRSBERNSMYQZNG-UHFFFAOYSA-N 0.000 claims description 4
- 230000002500 effect on skin Effects 0.000 claims description 4
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 claims description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 claims description 2
- 229940069096 dodecene Drugs 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 16
- JRZJOMJEPLMPRA-UHFFFAOYSA-N 1-nonene Chemical compound CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract description 6
- 239000004615 ingredient Substances 0.000 abstract description 5
- QNLZIZAQLLYXTC-UHFFFAOYSA-N 1,2-dimethylnaphthalene Chemical compound C1=CC=CC2=C(C)C(C)=CC=C21 QNLZIZAQLLYXTC-UHFFFAOYSA-N 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 4
- OCKPCBLVNKHBMX-UHFFFAOYSA-N butylbenzene Chemical compound CCCCC1=CC=CC=C1 OCKPCBLVNKHBMX-UHFFFAOYSA-N 0.000 abstract description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 abstract description 4
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethylcyclohexane Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 abstract description 4
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 abstract description 4
- 235000010290 biphenyl Nutrition 0.000 abstract description 2
- 239000004305 biphenyl Substances 0.000 abstract description 2
- XTVMZZBLCLWBPM-UHFFFAOYSA-N tert-butylcyclohexane Chemical compound CC(C)(C)C1CCCCC1 XTVMZZBLCLWBPM-UHFFFAOYSA-N 0.000 abstract description 2
- CFJYNSNXFXLKNS-UHFFFAOYSA-N p-menthane Chemical compound CC(C)C1CCC(C)CC1 CFJYNSNXFXLKNS-UHFFFAOYSA-N 0.000 abstract 4
- 229930004008 p-menthane Natural products 0.000 abstract 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N Methylcyclohexane Natural products CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 abstract 1
- 238000010521 absorption reaction Methods 0.000 description 13
- 235000019441 ethanol Nutrition 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000002390 adhesive tape Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000010224 hepatic metabolism Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- FMZUHGYZWYNSOA-VVBFYGJXSA-N (1r)-1-[(4r,4ar,8as)-2,6-diphenyl-4,4a,8,8a-tetrahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol Chemical compound C([C@@H]1OC(O[C@@H]([C@@H]1O1)[C@H](O)CO)C=2C=CC=CC=2)OC1C1=CC=CC=C1 FMZUHGYZWYNSOA-VVBFYGJXSA-N 0.000 description 1
- VYXHVRARDIDEHS-UHFFFAOYSA-N 1,5-cyclooctadiene Chemical compound C1CC=CCCC=C1 VYXHVRARDIDEHS-UHFFFAOYSA-N 0.000 description 1
- 239000004912 1,5-cyclooctadiene Substances 0.000 description 1
- HECLRDQVFMWTQS-RGOKHQFPSA-N 1755-01-7 Chemical compound C1[C@H]2[C@@H]3CC=C[C@@H]3[C@@H]1C=C2 HECLRDQVFMWTQS-RGOKHQFPSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229940087101 dibenzylidene sorbitol Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003106 tissue adhesive Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、インドメタシンまたはジアゼノ々ムを生体内
へ効率よく経皮吸収させるための外皮投与用組成物およ
び経皮吸収を促進する方法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a composition for dermal administration for efficient transdermal absorption of indomethacin or diazenom into a living body, and a method for promoting transdermal absorption.
従来、薬物を外皮に投与する場合は殺菌、消毒、鎮痛、
鎮痒、消炎など外皮またはその直下の皮下組織等、局所
的に作用することを目的とするものであった。また、全
身的作用を目的とする場合は、経口や注射による投与が
従来よりおこなわれてきた。Conventionally, when administering drugs to the outer skin, sterilization, disinfection, analgesia,
They were intended to act locally, such as on the outer skin or the subcutaneous tissue directly beneath it, such as antipruritic and antiinflammatory properties. Furthermore, when systemic effects are desired, administration has conventionally been carried out orally or by injection.
ところが、経口投与の場合は、吸収後、肝−次代謝を受
けやすいことや、吸収が不十分であったり、また効果の
持続を図るには一次的に、必要以上に高濃度の体内濃度
になる欠点があった。また、インドメタシンのように、
経口投与によって、副作用として胃腸障害を生起する例
もある。However, in the case of oral administration, it is easy to undergo hepatic metabolism after absorption, absorption may be insufficient, and to maintain the effect, the concentration in the body may be higher than necessary. There was a drawback. Also, like indomethacin,
In some cases, oral administration causes gastrointestinal disorders as a side effect.
一方、注射による投与は速やかな吸収が得られるが、医
師等の専門家を必要とする。On the other hand, administration by injection allows rapid absorption, but requires a specialist such as a doctor.
近年、上記副作用や欠点を改善するため、全身作用を目
的とする経皮投与が提案されている。薬物を経皮投与し
た場合、薬効の持続化が容易であ。In recent years, in order to improve the above-mentioned side effects and drawbacks, transdermal administration aimed at systemic effects has been proposed. When a drug is administered transdermally, it is easy to maintain its efficacy.
ること、薬物の生体内コントロールが可能になることや
皮膚組織から血流に入るため肝−次代謝を受けにくいな
どの利点がある。しかしながら、正常皮膚は本来、異物
の生体内への侵入を防ぐバリアー機能を持っているため
、皮膚を経由して薬物を投与するのは局所作用を目的と
する投与に限られていた。そのため、全身作用を目的と
する場合には、経皮吸収促進剤が必要であり、近年各種
のものが提案されているが、効果・安全性・使用感の点
で、未だ十分とはいえない。特に、従来の経皮吸収促進
剤は、インドメタシンおよびジアゼパムに対しては効果
が少ない、また、インドメタシンに関しては炭素数１０
のテルペノイド類を溶解補助剤として使用することが提
案されているが（特開昭５８−１８９１１５号公報）イ
ンドメタシンの溶解度を高めて含有量を向上させること
を目的としたもので、直接的にインドメタシンの吸収促
進を目的としたものではない、また、本願出願人は、ハ
ロゲンで５Ｆ換されていてもよい炭素数５〜２０の飽和
炭化水素、炭素数１２〜１８の脂肪族カルボン酸のアル
コールエステル及びエーテルと低級アルコールとを組み
合わせた組成物を提案しており、この組成物によっても
薬物の経皮吸収が促進されることを開示しているが（特
開昭５８−５５４１１公報）、インドメタシンおよびジ
アゼパムに関して、さらに優れた経皮吸収を促進する組
成物が待望されている。It has the advantages of being able to control the drug in vivo, and because it enters the bloodstream through the skin tissue, it is less susceptible to hepatic metabolism. However, since normal skin originally has a barrier function to prevent foreign substances from entering the body, administration of drugs through the skin has been limited to administration for the purpose of local action. Therefore, when aiming for a systemic effect, a transdermal absorption enhancer is necessary, and various drugs have been proposed in recent years, but they are still not sufficient in terms of effectiveness, safety, and usability. . In particular, conventional transdermal absorption enhancers have little effect on indomethacin and diazepam, and indomethacin has a carbon number of 10
It has been proposed (Japanese Unexamined Patent Publication No. 189115/1989) to use terpenoids as a solubilizing agent, but the purpose is to increase the solubility of indomethacin and increase its content. The present applicant is not intended to promote the absorption of saturated hydrocarbons having 5 to 20 carbon atoms, which may be 5F-substituted with halogen, or alcohol esters of aliphatic carboxylic acids having 12 to 18 carbon atoms. proposed a composition in which indomethacin and a lower alcohol are combined, and discloses that this composition also promotes the transdermal absorption of drugs (Japanese Unexamined Patent Publication No. 58-55411). Regarding diazepam, there is a long-awaited composition that promotes even better transdermal absorption.
本発明の目的は、インドメタシンおよびジアゼパムの経
皮吸収を高めうる外皮投与用組成物を提供するものであ
る。An object of the present invention is to provide a composition for dermal administration that can enhance the transdermal absorption of indomethacin and diazepam.
本発明の他の目的は、インドメタシンおよびジアゼパム
の経皮吸収を高める方法を提供することである。Another object of the present invention is to provide a method of increasing transdermal absorption of indomethacin and diazepam.
本発明者らは、かかる目的を達成するために鋭意研究し
た結果、インドメタシンおよびジアゼパム（■成分）と
いう特定の薬物が、特開昭５８−５５４１１公報には全
く開示のない後述する特定化合物（■成分）と低級アル
コール、グリコール類およびピロリドン類から選ばれた
少なくとも１種の溶解剤（■成分）とよりなる組成物の
存在下に経皮投与すると、速やかに経皮的に血流中へ吸
収されること、および当該■成分および■成分よりなる
組成物がインドメタシンまたはジアゼパムを製剤化する
に当たっての基剤の一要素として使用しうろことを見出
した。As a result of intensive research to achieve this objective, the present inventors have discovered that the specific drugs, indomethacin and diazepam (component (■)), are the specific compounds (■ When administered transdermally in the presence of a composition consisting of component) and at least one solubilizing agent selected from lower alcohols, glycols, and pyrrolidones (component), it is rapidly absorbed transdermally into the bloodstream. It has been found that the composition consisting of component (1) and component (2) can be used as an element of a base in formulating indomethacin or diazepam.
本発明はかかる新知見に基づいて完成されたものであり
、下記■成分、（２）成分および■成分を含有してなる
外皮投与用組成物を提供するものである。The present invention was completed based on this new knowledge, and provides a composition for dermal administration containing the following components (1), (2), and (2).
■インドメタシンまたはジアゼパム。■Indomethacin or diazepam.
■１−ノネン、ｐ−メンクン、α−テルピネン、ｎ−ブ
チルシクロヘキサン、ｔ−ブチルシクロヘキサン、ジペ
ンテン、ビナン、エチルシクロヘキサン、ビフェニール
、ｎ−ブチルベンゼン、ミルセン、メチルシクロペンタ
ジェンダイマー、シス−１，３−ジメチルシクロヘキサ
ン、ジシクロヘキシル、ジメチルナフタレン、ρ−シメ
ン、ジシクロペンタジェン、１．５−シクロオクタジエ
ン、シクロオクタン、イソオクタン、１−ドデセン、１
−フェニル−１−シクロヘキサンから選ばれる少なくと
も一種の化合物。■1-Nonene, p-mencune, α-terpinene, n-butylcyclohexane, t-butylcyclohexane, dipentene, vinylane, ethylcyclohexane, biphenyl, n-butylbenzene, myrcene, methylcyclopentadiene dimer, cis-1,3 -dimethylcyclohexane, dicyclohexyl, dimethylnaphthalene, ρ-cymene, dicyclopentadiene, 1,5-cyclooctadiene, cyclooctane, isooctane, 1-dodecene, 1
-At least one compound selected from phenyl-1-cyclohexane.
■低級アルコール、グリコール類およびピロリドン類か
ら選ばれる少なくとも１種の溶解剤。■At least one solubilizer selected from lower alcohols, glycols, and pyrrolidones.
本発明における溶解剤としては、低級アルコール、グリ
コール類およびピロリドン類から選ばれる少なくとも一
種が使用される。As the solubilizing agent in the present invention, at least one selected from lower alcohols, glycols, and pyrrolidones is used.
低級アルコールとしては、メチルアルコール、エチルア
ルコール、ｎ−プロピルアルコール、１ＳＯ−プロピル
アルコール、ｎ−ブチルアルコール、１ｓｏ−ブチルア
ルコール、３１１１Ｃ−ブチルアルコール、ｔ−ブチル
アルコール、ｎ−アミルアルコール、１ｓｏ−アミルア
ルコールなどの炭素数１〜５の脂肪族１価アルコールが
好適なものとして挙げられる。Examples of lower alcohols include methyl alcohol, ethyl alcohol, n-propyl alcohol, 1SO-propyl alcohol, n-butyl alcohol, 1so-butyl alcohol, 3111C-butyl alcohol, t-butyl alcohol, n-amyl alcohol, and 1so-amyl alcohol. Preferred examples include aliphatic monohydric alcohols having 1 to 5 carbon atoms.
グリコール類としてはプロピレングリコールやエチレン
グリコールなどの如きアルキレングリコール（アルキレ
ン部分は炭素数２または３のものが好ましい）が好適な
ものとして挙げられる。Suitable glycols include alkylene glycols (the alkylene moiety preferably has 2 or 3 carbon atoms) such as propylene glycol and ethylene glycol.
ピロリドン類としてはＮ−メチルピロリドンなどのよう
にアルキル置換ピロリドンが好適であり、Ｗ換基として
のアルキル基としては、たとえばメチル、エチル、ｎ−
プロピル、１ｓｏ−プロピル、ｎ−ブチル、５ｅｃ−ブ
チル、ｔ−ブチル等のような炭素数１〜４の低級アルキ
ル基が好ましい。Preferred pyrrolidones include alkyl-substituted pyrrolidones such as N-methylpyrrolidone, and examples of alkyl groups as W substituents include methyl, ethyl, n-
Lower alkyl groups having 1 to 4 carbon atoms are preferred, such as propyl, 1so-propyl, n-butyl, 5ec-butyl, t-butyl, and the like.
本発明組成物におけ名答成分の配合割合は、好ましくは
次の通りである。すなわち、（２）成分と■成分との重
量比は通常５：９５〜７５：２５であり、好ましくは１
０：９０〜３０ニア０である。The blending ratio of the name components in the composition of the present invention is preferably as follows. That is, the weight ratio of component (2) and component (2) is usually 5:95 to 75:25, preferably 1
0:90-30 near 0.
また、■成分の配合量は、所望の薬効を奏するのに十分
な量であればよく、それは患者の体重、症状などによっ
て異なるものであり、これら条件に応じて適宜選択すれ
ばよく、（２）成分および■成分の合計に対して、好ま
しくは、０．０１〜２０重量％、特に好ましくは０．２
〜１０重量％である。なお、本発明組成物の皮膚塗布面
積を増減することによって、薬物の使用量を調整できる
ので、かならずしも上記の配合量に限定されるものでは
ない。In addition, the amount of component (2) to be blended may be sufficient as long as it is sufficient to achieve the desired medicinal effect, and it will vary depending on the patient's weight, symptoms, etc., and may be selected appropriately according to these conditions. Preferably 0.01 to 20% by weight, particularly preferably 0.2% by weight, based on the total of components ) and (1).
~10% by weight. Incidentally, since the amount of drug to be used can be adjusted by increasing or decreasing the area of skin application of the composition of the present invention, it is not necessarily limited to the above-mentioned amount.
本発明に係る外用医薬組成物は、そのまま、あるいは製
薬上許容される既知の成分などを添加して、軟膏剤、硬
膏剤、ローション剤、粘着テープ剤、含浸剤、ゲル剤な
どの非乳化性の外用製剤として外皮に投与される。含浸
剤としては、たとえば、当該組成分を適当な吸着体（ガ
ーゼ、ろ紙、多孔質膜等）に吸着させたものが挙げられ
、これは一般に外科用粘着テープで固定することによっ
て外皮に適用される。また、ゲル剤としては、たとえば
ジベンジリデンソルビトール（例、ゲルオールＤ（新日
本理化社製）〕を用いてゲル状となし、支持体上に展着
したものなどがあげられる。The external pharmaceutical composition according to the present invention can be used as it is or with the addition of known pharmaceutically acceptable ingredients to form non-emulsifying agents such as ointments, plasters, lotions, adhesive tapes, impregnating agents, and gels. It is administered to the skin as an external preparation. Examples of impregnating agents include those in which the relevant components are adsorbed onto a suitable adsorbent (gauze, filter paper, porous membrane, etc.), which is generally applied to the skin by fixing it with surgical adhesive tape. Ru. Further, examples of the gel agent include those formed into a gel form using dibenzylidene sorbitol (eg, Gelol D (manufactured by Shin Nihon Rika Co., Ltd.)) and spread on a support.
また粘着テープ剤の粘着性基剤としては、アクリル系共
重合物、ポリビニルエーテル化合物、ゴム系粘着性混合
物など自体既知のものが挙げられる。In addition, examples of the adhesive base for the adhesive tape include those known per se, such as acrylic copolymers, polyvinyl ether compounds, and rubber adhesive mixtures.
その他の外用製剤も自体既知の手段にて容易に調製する
ことができる。Other external preparations can also be easily prepared by means known per se.
以下実施例、実験例などによって本発明をより具体的に
説明するが、本発明はこれらによって何等限定されるも
のではない。The present invention will be explained in more detail below using Examples, Experimental Examples, etc., but the present invention is not limited by these in any way.
実施例１〜２８
（１）■成分 １重量％
（２）■成分 １０重量％
（３）■成分 ８９重量％
ｆｌｌ、（２）及び（３）として第１表に示したものを
各々用いて、まず（１１、（２）を混合し、さらに（３
）を加えることによって調製した。Examples 1 to 28 (1) ■Component 1% by weight (2) ■Component 10% by weight (3) ■Component 89% by weight , first mix (11, (2), then (3)
) was prepared by adding.
比較例１〜２
（１）■成分 １重量％
（２）ｎ−ヘキサン １０重量％
（３）■成分 ８９重量％
ｆｌｌ、（２）及び（３）として第１表に示したものを
各々用いて、まず（１）、（３）を混合し、さらに（２
）を加えることによって調製した。Comparative Examples 1 to 2 (1) ■Component 1% by weight (2) n-hexane 10% by weight (3) ■Component 89% by weight Those shown in Table 1 were used as flI, (2) and (3), respectively. First, mix (1) and (3), then (2)
) was prepared by adding.
対照処方 ｆｌｌ薬物 １重量％ （２）■成分 ９９重量％ ｆｌｌと（２）を混合することにより調製した。Control formulation fll drug 1% by weight (2) ■Ingredients 99% by weight It was prepared by mixing flll and (2).
実験例１
実施例１〜２８および比較例１〜２の組成物における■
成分、即ち薬物の皮膚透過量を切除したラット腹部皮膚
を使用して測定し、第１表には実施例１〜２８の結果を
、また第２表には比較例１〜２の結果を示した。Experimental Example 1 ■ in the compositions of Examples 1 to 28 and Comparative Examples 1 to 2
The skin permeation amount of the drug component, that is, the drug, was measured using excised rat abdominal skin, and Table 1 shows the results of Examples 1 to 28, and Table 2 shows the results of Comparative Examples 1 to 2. Ta.
なお、第１表および第２表中の促進率は次のことを意味
する。Note that the promotion rates in Tables 1 and 2 mean the following.
促進率−Ａ／Ｂ
Ａ：実施例処方における薬物の皮膚透過量Ｂ：対照処方
における薬物の皮膚透過量（測定方法）
皮膚の表側に相当する部分が上記組成物と接し、皮膚の
裏側に相当する部分が生理食塩水に接するようにラット
皮膚をガラス製透過セルに取りつけ、生理食塩水中に透
過してきた薬物を高速液体クロマトグラフィーにて定量
した。なお、インドメタシンは４時間後、ジアゼパムは
２４時間後に測定した。Acceleration rate - A/B A: Amount of drug permeated through the skin in the example formulation B: Amount of drug permeated through the skin in the control formulation (Measurement method) The part corresponding to the front side of the skin is in contact with the above composition, and the part corresponding to the back side of the skin The rat skin was attached to a glass transmission cell so that the exposed part was in contact with the saline, and the drug that had permeated into the saline was quantified using high-performance liquid chromatography. Note that indomethacin was measured after 4 hours, and diazepam was measured after 24 hours.
（作用・効果）
本発明で使用される■成分および■成分よりなる組成物
の存在下、インドメタシンまたはジアゼパムを外皮投与
すれば、これら薬物の経皮吸収が著しく促進されるもの
であり、本発明の組成物を経皮投与すればインドメタシ
ンおよびジアゼパムが速やかに経皮吸収される。(Action/Effect) If indomethacin or diazepam is administered through the skin in the presence of the composition consisting of the component (■) and the component (■) used in the present invention, the percutaneous absorption of these drugs will be significantly promoted. When this composition is administered transdermally, indomethacin and diazepam are rapidly absorbed transdermally.
従って、本発明に従えば医師等の専門家を必要とせず、
また胃腸障害を来すことなく、さらには肝−次代用をう
けることなくインドメタシンおよびジアゼパムが、速や
かにかつ持続的に血中に吸収されてその目的とする薬理
活性が達成される。Therefore, according to the present invention, there is no need for experts such as doctors,
Moreover, indomethacin and diazepam are rapidly and sustainably absorbed into the blood without causing gastrointestinal disorders, and furthermore, without undergoing hepatic substitution, and their intended pharmacological activity is achieved.
（以下余白）(Margin below)
Claims (1)
てなる外皮投与用組成物。 （１）インドメタシンまたはジアゼパム。 （２）１−ノネン ｐ−メンタン α−テルピネン ｎ−ブチルシクロヘキサン ｔ−ブチルシクロヘキサン ジペンテン ピナン エチルシクロヘキサン ビフェニール ｎ−ブチルベンゼン ミルセン メチルシクロペンタジエンダイマー シス−１，３−ジメチルシクロヘキサン ジシクロヘキシル ジメチルナフタレン ｐ−シメン ジシクロペンタジエン １，５−シクロオクタジエン ジクロオクタン イソオクタン １−フェニル−１−シクロヘキサン １−ドデセン から選ばれる少なくとも一種の化合物。 （３）低級アルコール、グリコール類およびピロリドン
類から選ばれる少なくとも１種の溶解剤。[Scope of Claims] A composition for dermal administration comprising the following components (1), (2) and (3). (1) Indomethacin or diazepam. (2) 1-Nonene p-menthane α-terpinene n-butylcyclohexane t-butylcyclohexane dipentene pinane ethylcyclohexane biphenyl n-butylbenzene myrcene methylcyclopentadiene dimer cis-1,3-dimethylcyclohexane dicyclohexyldimethylnaphthalene p-cymendi At least one compound selected from cyclopentadiene 1,5-cyclooctadiene dichlorooctane isooctane 1-phenyl-1-cyclohexane 1-dodecene. (3) At least one solubilizer selected from lower alcohols, glycols, and pyrrolidones.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61-251127 | 1986-10-21 | ||
| JP25112786 | 1986-10-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63225316A true JPS63225316A (en) | 1988-09-20 |
Family
ID=17218072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP132987A Pending JPS63225316A (en) | 1986-10-21 | 1987-01-07 | Composition for exodermal administration |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63225316A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02193932A (en) * | 1989-01-23 | 1990-07-31 | Freunt Ind Co Ltd | Percutaneous and transmucosal absorbefacient and percutaneous and transmucosal pharmaceutical |
| WO2003077879A1 (en) * | 2002-03-15 | 2003-09-25 | Cognis Deutschland Gmbh & Co. Kg | Oil bodies for cosmetic compositions containing cyclohexylcyclohexane |
| EP1421929A2 (en) * | 2002-11-21 | 2004-05-26 | Cognis Deutschland GmbH & Co. KG | Emollients and cosmetic preparations |
| JP2010513500A (en) * | 2006-12-20 | 2010-04-30 | シェーリング−プラウ・リミテッド | Pharmaceutical compositions and methods for treating inflammation in cattle and other animals |
-
1987
- 1987-01-07 JP JP132987A patent/JPS63225316A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02193932A (en) * | 1989-01-23 | 1990-07-31 | Freunt Ind Co Ltd | Percutaneous and transmucosal absorbefacient and percutaneous and transmucosal pharmaceutical |
| JP2905210B2 (en) * | 1989-01-23 | 1999-06-14 | フロイント産業株式会社 | Transdermal and transmucosal absorption enhancers and transdermal and transmucosal preparations |
| WO2003077879A1 (en) * | 2002-03-15 | 2003-09-25 | Cognis Deutschland Gmbh & Co. Kg | Oil bodies for cosmetic compositions containing cyclohexylcyclohexane |
| US7572435B2 (en) | 2002-03-15 | 2009-08-11 | Cognis Ip Management Gmbh | Oil bodies for cosmetic compositions containing cyclohexyl cyclohexane |
| EP1421929A2 (en) * | 2002-11-21 | 2004-05-26 | Cognis Deutschland GmbH & Co. KG | Emollients and cosmetic preparations |
| EP1421929A3 (en) * | 2002-11-21 | 2004-11-24 | Cognis Deutschland GmbH & Co. KG | Emollients and cosmetic preparations |
| US7638662B2 (en) | 2002-11-21 | 2009-12-29 | COGNIS IP Management | Emollients and cosmetic preparations |
| JP2010513500A (en) * | 2006-12-20 | 2010-04-30 | シェーリング−プラウ・リミテッド | Pharmaceutical compositions and methods for treating inflammation in cattle and other animals |
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