JPH05271076A - Anti-inflammatory analgesic external preparation - Google Patents
Anti-inflammatory analgesic external preparationInfo
- Publication number
- JPH05271076A JPH05271076A JP6834392A JP6834392A JPH05271076A JP H05271076 A JPH05271076 A JP H05271076A JP 6834392 A JP6834392 A JP 6834392A JP 6834392 A JP6834392 A JP 6834392A JP H05271076 A JPH05271076 A JP H05271076A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- indomethacin
- external preparation
- inflammatory analgesic
- acetate
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、有効成分としてインド
メタシンを含有する消炎鎮痛外用剤に関するものであ
る。更に詳しくは、ビタミンＥまたはビタミンＥアセテ
ートを配合し優れた消炎鎮痛効果を示す外用製剤に関す
るものである。TECHNICAL FIELD The present invention relates to an anti-inflammatory analgesic external preparation containing indomethacin as an active ingredient. More specifically, it relates to an external preparation containing vitamin E or vitamin E acetate and exhibiting an excellent anti-inflammatory and analgesic effect.
【０００２】[0002]
【従来の技術】非ステロイド系消炎鎮痛剤のインドメタ
シンは、優れた抗炎症作用を有しているため、整形外科
領域で一般に使用されている。しかしながら、インドメ
タシンは経口投与の場合消化器、坐薬の場合直腸等に激
しい副作用を示すことがある。このためインドメタシン
の副作用の軽減を図るべく、軟膏剤、液剤、パップ剤等
の局所適用製剤が開発されてきている。これらの局所適
用製剤は、経口製剤と同程度の薬理効果を得るために、
脂肪酸エステル、アルコール類、テルペン類等をインド
メタシンの経皮吸収促進剤として配合している（特開平
２−１４２７２７号公報、特開平２−１９６７１８号公
報）。BACKGROUND OF THE INVENTION Indomethacin, which is a non-steroidal anti-inflammatory drug, has been widely used in the orthopedic field because of its excellent anti-inflammatory effect. However, indomethacin may show severe side effects in the digestive tract when orally administered and in the rectum when suppository. Therefore, topical preparations such as ointments, liquids and poultices have been developed in order to reduce the side effects of indomethacin. These topically applied preparations have the same pharmacological effects as oral preparations.
Fatty acid esters, alcohols, terpenes and the like are blended as a percutaneous absorption enhancer of indomethacin (JP-A-2-142727, JP-A-2-196718).
【０００３】[0003]
【発明が解決しようとする課題】経皮吸収促進剤は薬物
の経皮吸収性を高めるが、これらの吸収促進剤は皮膚の
バリヤー性を低下させるため皮膚刺激性を有する。また
一般に、経皮吸収促進効果の高いものほど皮膚刺激性は
高い。しかしながら、経口製剤と同程度の薬理効果を得
るには経皮吸収促進剤を多量に配合する必要があり、未
だ実用性に問題点が残っているのが現状である。The transdermal absorption enhancers enhance the transdermal absorbability of drugs, but these absorption enhancers have skin irritation because they reduce the barrier properties of the skin. Generally, the higher the effect of promoting percutaneous absorption, the higher the skin irritation. However, in order to obtain a pharmacological effect comparable to that of an oral preparation, it is necessary to add a large amount of a percutaneous absorption enhancer, and there is still a problem in practical use.
【０００４】[0004]
【課題を解決するための手段】本発明者らは前述の問題
点を解決するため鋭意研究した結果、インドメタシンを
含有する消炎鎮痛外用軟膏、クリームおよび液剤にビタ
ミンＥまたはビタミンＥアセテートを配合することによ
り、インドメタシンの抗炎症効果を良好かつ安全に発揮
させ得ることを見い出し、本発明を完成するにいたっ
た。Means for Solving the Problems As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that vitamin E or vitamin E acetate is added to anti-inflammatory analgesic external ointments, creams and solutions containing indomethacin. As a result, it was found that the anti-inflammatory effect of indomethacin can be exhibited satisfactorily and safely, and the present invention was completed.
【０００５】すなわち本発明は、インドメタシンを含有
する消炎鎮痛外用剤に経皮吸収促進剤とビタミンＥまた
はビタミンＥアセテートを配合することにより、経口に
投与した場合と同様の消炎鎮痛効果が得られかつ皮膚刺
激を軽減した製剤を提供するものである。本発明におい
て使用するインドメタシンの配合量としては、０．５〜
１．５重量％、ビタミンＥまたはビタミンＥアセテート
としては、０．５〜５重量％が望ましい。経皮吸収促進
剤としては、ミリスチン酸イソプロピル、パルミチン酸
イソプロピル、セバシン酸ジエチル、セバシン酸ジイソ
プロピル、アジピン酸ジイソプロピルなどの脂肪酸エス
テル、エタノール、プロピレングリコール、ポリエチレ
ングリコールなどのアルコール類、メントールなどのテ
ルペン類があげられる。より好ましい経皮吸収促進剤と
しては、アジピン酸ジイソプロピルがあげられ、その配
合量としては１〜１０重量％が望ましい。That is, according to the present invention, an anti-inflammatory analgesic external preparation containing indomethacin is combined with a percutaneous absorption enhancer and vitamin E or vitamin E acetate to obtain the same anti-inflammatory analgesic effect as when orally administered. It is intended to provide a preparation with reduced skin irritation. The amount of indomethacin used in the present invention is 0.5 to
1.5% by weight, preferably 0.5 to 5% by weight as vitamin E or vitamin E acetate. Transdermal absorption enhancers include isopropyl myristate, isopropyl palmitate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate and other fatty acid esters, alcohols such as ethanol, propylene glycol and polyethylene glycol, and terpenes such as menthol. can give. A more preferable percutaneous absorption enhancer is diisopropyl adipate, and its compounding amount is preferably 1 to 10% by weight.
【０００６】[0006]
【発明の効果】本発明で得られるインドメタシン、ビタ
ミンＥまたはビタミンＥアセテートおよび経皮吸収促進
剤を含有する消炎鎮痛外用剤は、経皮吸収に優れかつ皮
膚刺激がなく、筋肉痛、腰痛、関節痛、腱鞘炎、打撲、
捻挫などの整形外科領域における治療薬として有用であ
る。INDUSTRIAL APPLICABILITY The anti-inflammatory analgesic external preparation containing indomethacin, vitamin E or vitamin E acetate and the percutaneous absorption enhancer obtained in the present invention is excellent in percutaneous absorption and does not cause skin irritation, and causes muscle pain, low back pain and joints. Pain, tendonitis, bruise,
It is useful as a therapeutic drug in the field of orthopedics such as sprains.
【０００７】[0007]
【実施例】以下に実施例および試験例をあげ、本発明を
具体的に説明する。EXAMPLES The present invention will be specifically described with reference to Examples and Test Examples.
【０００８】実施例１ インドメタシン０．７５ｇにビタミンＥアセテート２
ｇ、アジピン酸ジイソプロピル３ｇ、中鎖脂肪酸トリグ
リセライド２５ｇ、ニッコール（ＴＳ−１０）６ｇ、ニ
ッコール（ＳＳ−１０）３ｇおよびニッコール（ＭＧＳ
−ＤＥＸ）８ｇを加え、７５℃に加温して溶解した。次
に、プロピレングリコール１０ｇ、クエン酸０．１ｇお
よびクエン酸ナトリウム０．０５ｇを水４２．１ｇに溶
解し、これと先の溶解液とを均一に乳化するまで攪拌し
てクリームを得た。Example 1 Vitamin E acetate 2 in 0.75 g of indomethacin
g, diisopropyl adipate 3 g, medium chain fatty acid triglyceride 25 g, Nikkor (TS-10) 6 g, Nikkor (SS-10) 3 g and Nikkor (MGS
-DEX) 8g was added and it heated and melt | dissolved at 75 degreeC. Next, 10 g of propylene glycol, 0.1 g of citric acid and 0.05 g of sodium citrate were dissolved in 42.1 g of water, and this and the above solution were stirred until they were uniformly emulsified to obtain a cream.
【０００９】実施例２ インドメタシン０．７５ｇにビタミンＥアセテート１
ｇ、アジピン酸ジイソプロピル１０ｇ、ニッコール（Ｔ
Ｓ−１０）４ｇ、ニッコール（ＴＳ−３０）２ｇ、ニッ
コール（ＳＳ−１０）３ｇおよびジブチルヒドロキシト
ルエン０．１ｇを加え、７０℃に加温して溶解した。次
に、ｌ−メントール０．２ｇをエタノール３５ｇと水４
３．９５ｇの混合液に溶解し、これと先の溶解液とを均
一に乳化するまで攪拌して液剤を得た。Example 2 Vitamin E acetate 1 to 0.75 g of indomethacin
g, diisopropyl adipate 10 g, Nikkor (T
4 g of S-10, 2 g of Nikkor (TS-30), 3 g of Nikkor (SS-10) and 0.1 g of dibutylhydroxytoluene were added and dissolved by heating at 70 ° C. Next, 0.2 g of 1-menthol was mixed with 35 g of ethanol and 4 g of water.
It was dissolved in 3.95 g of the mixed solution, and this solution and the above-mentioned dissolved solution were stirred until they were uniformly emulsified to obtain a liquid agent.
【００１０】比較例１ インドメタシン０．７５ｇにｌ−メントール３ｇ、ニッ
コール（ＴＳ−１０）５ｇ、アジピン酸ジイソプロピル
５ｇ、ミリスチン酸イソプロピル１０ｇを加え、７５℃
に加温して溶解した。この溶液にカルボキシビニルポリ
マー０．８ｇを水６５．０ｇに膨潤した液を加え、攪拌
して乳化した。次に、ジイソプロパノールアミン０．４
ｇを水１０ｇに溶解し、これと先の乳化物とを均一にな
るまで攪拌してクリームを得た。Comparative Example 1 To 0.75 g of indomethacin, 3 g of 1-menthol, 5 g of Nikkor (TS-10), 5 g of diisopropyl adipate and 10 g of isopropyl myristate were added, and the mixture was heated to 75 ° C.
It was heated and dissolved. A liquid obtained by swelling 0.8 g of carboxyvinyl polymer in 65.0 g of water was added to this solution, and the mixture was stirred to emulsify. Then, diisopropanolamine 0.4
g was dissolved in 10 g of water, and this and the above emulsion were stirred until they became uniform to obtain a cream.
【００１１】比較例２ 流動パラフィン３ｇにニッコール（ＴＳ−１０）０．５
ｇを加え、室温で攪拌し溶解した。これにカルボキシビ
ニルポリマー１ｇを水８５ｇに膨潤した液を加え、攪拌
して乳化した。次に、ジイソプロパノールアミン０．５
ｇを水９．２５ｇに溶かした溶液を加えて攪拌後、イン
ドメタシン０．７５ｇを加えて、均一に分散するまで攪
拌してクリームを得た。Comparative Example 2 0.5 g of Nikkor (TS-10) was added to 3 g of liquid paraffin.
g was added and dissolved at room temperature with stirring. A liquid obtained by swelling 1 g of carboxyvinyl polymer in 85 g of water was added thereto, and the mixture was stirred to emulsify. Then, diisopropanolamine 0.5
A solution prepared by dissolving g in 9.25 g of water was added and stirred, and then 0.75 g of indomethacin was added and stirred until uniformly dispersed to obtain a cream.
【００１２】試験例１ 実施例１および比較例１で得られた製剤について、ウサ
ギ４匹を用いてＤｒａｉｚ法（小川秀興ら、新しい皮膚
の生理と安全性、１９８３）により皮膚一次刺激性試験
を行った。その結果、実施例１と比較例１の皮膚一次刺
激性インデックスはそれぞれ０．５および０．９とな
り、実施例１は比較例１よりも経皮吸収促進剤により惹
起される皮膚刺激は軽減されていた。Test Example 1 The preparations obtained in Example 1 and Comparative Example 1 were subjected to a primary skin irritation test by the Draz method (Hideoki Ogawa et al., New Physiology and Safety of Skin, 1983) using 4 rabbits. went. As a result, the skin primary irritation indexes of Example 1 and Comparative Example 1 were 0.5 and 0.9, respectively, and Example 1 is less skin irritation caused by the transdermal absorption enhancer than Comparative Example 1. Was there.
【００１３】試験例２ 実施例１、比較例１および比較例２で得られた製剤につ
いて、打撲、捻挫、筋肉痛、腰痛、関節痛、腱鞘炎
（手、手首の痛み）、肘の痛み（テニス肘など）、肩こ
りを訴える患者５３例を対象に臨床試験を行った。用法
・用量としては、１日４回を限度として１日数回、適量
を患部に塗擦するように指示した。また、投与期間は原
則として２週間としたが、２週間以内に治癒した場合は
終了とし、その時点で評価を行った。評価は自・他覚症
状として自発痛、圧痛、運動痛、腫脹、局所熱感、疼痛
による運動制限等について「重度」、「中等度」、「軽
度」、「症状なし」の４段階にて観察し、投与終了時に
投与開始時と比較した各症状別改善度を「著名改善」、
「中等度改善」、「軽度改善」、「不変」、「悪化」の
５段階で評価した。その結果を全般改善度（％）として
表１に示す。これより経皮吸収促進剤を配合した実施例
１および比較例１は、経皮吸収促進剤を配合していない
比較例２に対し有効性が高かった。Test Example 2 Regarding the preparations obtained in Example 1, Comparative Example 1 and Comparative Example 2, bruise, sprain, muscle pain, back pain, arthralgia, tendonitis (pain of hand and wrist), elbow pain (tennis) A clinical study was conducted on 53 patients who complain of stiff shoulders (such as elbows). As for the usage and dose, the patient was instructed to apply an appropriate amount to the affected area several times a day with a limit of four times a day. In addition, the administration period was set to 2 weeks in principle, but if healing occurred within 2 weeks, it was terminated and the evaluation was performed at that time. The evaluation is based on the following four grades: "severe", "moderate", "mild" and "no symptoms" for spontaneous pain, tenderness, movement pain, swelling, local heat sensation, movement limitation due to pain, etc. Observed, "significant improvement" at the end of administration, the degree of improvement by each symptom compared to the start of administration,
The evaluation was made in five grades of "moderate improvement", "slight improvement", "unchanged" and "worse". The results are shown in Table 1 as the overall improvement rate (%). As a result, Example 1 and Comparative Example 1 containing the transdermal absorption enhancer were more effective than Comparative Example 2 containing no percutaneous absorption enhancer.
【００１４】[0014]
【表１】 [Table 1]
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 47/22 Ｅ 7433−4Ｃ (72)発明者 根本 正美 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification number Internal reference number FI Technical indication location A61K 47/22 E 7433-4C (72) Inventor Masami Nemoto 3-24-1 Takada, Toshima-ku, Tokyo No. Taisho Pharmaceutical Co., Ltd.
Claims (1)
ンＥアセテートを配合した消炎鎮痛外用剤1. An anti-inflammatory analgesic external preparation containing indomethacin and vitamin E or vitamin E acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP06834392A JP3740701B2 (en) | 1992-03-26 | 1992-03-26 | Anti-inflammatory analgesic topical |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP06834392A JP3740701B2 (en) | 1992-03-26 | 1992-03-26 | Anti-inflammatory analgesic topical |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004221100A Division JP2004307515A (en) | 2004-07-29 | 2004-07-29 | External anti-inflammatory preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05271076A true JPH05271076A (en) | 1993-10-19 |
| JP3740701B2 JP3740701B2 (en) | 2006-02-01 |
Family
ID=13371103
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP06834392A Expired - Lifetime JP3740701B2 (en) | 1992-03-26 | 1992-03-26 | Anti-inflammatory analgesic topical |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3740701B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995030420A1 (en) * | 1994-05-06 | 1995-11-16 | Alcon Laboratories, Inc. | Use of vitamin e tocopheryl derivatives in ophthalmic compositions |
| JP2019206496A (en) * | 2018-05-30 | 2019-12-05 | 小林製薬株式会社 | External pharmaceutical composition |
-
1992
- 1992-03-26 JP JP06834392A patent/JP3740701B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995030420A1 (en) * | 1994-05-06 | 1995-11-16 | Alcon Laboratories, Inc. | Use of vitamin e tocopheryl derivatives in ophthalmic compositions |
| AU684950B2 (en) * | 1994-05-06 | 1998-01-08 | Alcon Laboratories, Inc. | Use of vitamin E tocopheryl derivatives in ophthalmic compositions |
| JP2019206496A (en) * | 2018-05-30 | 2019-12-05 | 小林製薬株式会社 | External pharmaceutical composition |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3740701B2 (en) | 2006-02-01 |
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