JP3203056B2 - Composition for transdermal absorption preparation of betahistine mesylate and transdermal absorption preparation - Google Patents
Composition for transdermal absorption preparation of betahistine mesylate and transdermal absorption preparationInfo
- Publication number
- JP3203056B2 JP3203056B2 JP21614392A JP21614392A JP3203056B2 JP 3203056 B2 JP3203056 B2 JP 3203056B2 JP 21614392 A JP21614392 A JP 21614392A JP 21614392 A JP21614392 A JP 21614392A JP 3203056 B2 JP3203056 B2 JP 3203056B2
- Authority
- JP
- Japan
- Prior art keywords
- transdermal absorption
- composition
- absorption preparation
- carbon atoms
- preparation
- 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.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、メシル酸ベタヒスチン
の経皮吸収製剤用組成物および経皮吸収製剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for percutaneous absorption of betahistine mesylate and a percutaneous absorption preparation.
【０００２】[0002]
【従来の技術】メシル酸ベタヒスチンは、メニエル症候
群の治療薬および予防薬として用いられており、めまい
発作が起きたときの治療およびこの発作の予防のために
現在主として経口で投与されている。発作を予防するた
めにこの薬物を投与する用法は１日３回食後服用となっ
ているが、このような頻繁な服用の煩わしさから患者を
開放して患者に精神的な安らぎを与えるためには、１日
１回程度の適用で効力が長期間持続する剤形の開発が望
まれている。１日１回程度の適用で薬物の作用を長期間
持続させることができる投与部位として、近年、皮膚が
注目されており、本発明者は、皮膚を投与経路とするメ
シル酸ベタヒスチンの経皮吸収製剤を開発することを意
図した。BACKGROUND OF THE INVENTION Betahistine mesylate is used as a therapeutic and prophylactic agent for Meniere's syndrome, and is currently administered orally mainly for the treatment of vertigo attacks and the prevention of these attacks. This drug is administered three times a day after meals to prevent seizures. However, in order to relieve the patient from the trouble of such frequent doses and to give the patient mental comfort. It is desired to develop a dosage form that is effective once a day and has long-lasting efficacy. In recent years, skin has been attracting attention as an administration site capable of sustaining the action of a drug for a long period of time by application once a day, and the present inventors have proposed transdermal absorption of betahistine mesylate using the skin as an administration route. It was intended to develop a formulation.
【０００３】[0003]
【発明が解決しようとする課題】しかし、皮膚は生体を
外界から守るための防御膜でもあるので、一般に皮膚か
ら薬物を吸収させることは容易でなく、小さな皮膚面積
に対する適用によってメシル酸ベタヒスチンの十分な治
療効果を得るためには、メシル酸ベタヒスチンの皮膚透
過性を促進する基剤を用いて経皮吸収製剤を調製する必
要がある。However, since the skin is also a protective film for protecting the living body from the outside world, it is generally not easy to absorb the drug from the skin, and the application of betahistine mesylate to small skin areas is not sufficient. In order to obtain an excellent therapeutic effect, it is necessary to prepare a transdermal preparation using a base that promotes skin permeability of betahistine mesylate.
【０００４】[0004]
【課題を解決するための手段】本発明者は、上記の状況
に鑑みて種々研究を重ねた結果、メシル酸ベタヒスチン
のための経皮吸収製剤用組成物および経皮吸収製剤の基
材として、炭素原子数１０〜２０を有する脂肪族アルコ
ールおよび／または炭素原子数１０〜２０を有する脂肪
族アルコールの乳酸エステルを用いると、メシル酸ベタ
ヒスチンの高い皮膚透過性が得られることを見出した。Means for Solving the Problems The present inventor has made various studies in view of the above situation, and as a result, as a composition for a transdermal absorption preparation for betahistine mesylate and a base material of the transdermal absorption preparation, It has been found that when an aliphatic alcohol having 10 to 20 carbon atoms and / or a lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms is used, high skin permeability of betahistine mesylate can be obtained.
【０００５】本発明は、上記知見に基づいて発明された
もので、メシル酸ベタヒスチンの高い皮膚透過性を有す
る経皮吸収製剤用組成物および経皮吸収製剤を提供する
ことを目的とし、（１）メシル酸ベタヒスチンならびに
炭素原子数１０〜２０を有する脂肪族アルコールおよび
／または炭素原子数１０〜２０を有する脂肪族アルコー
ルの乳酸エステルを含む経皮吸収製剤用組成物、および
（２）メシル酸ベタヒスチンならびに炭素原子数１０〜
２０を有する脂肪族アルコールおよび／または炭素原子
数１０〜２０を有する脂肪族アルコールを有する乳酸エ
ステルを含む経皮吸収製剤に係るものである。The object of the present invention is to provide a composition for percutaneous absorption preparations and a percutaneous absorption preparation having high skin permeability of betahistine mesylate, which was invented on the basis of the above findings. A) Betahistine mesylate and a composition for transdermal absorption preparations comprising a fatty alcohol having 10 to 20 carbon atoms and / or a lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms, and (2) betahistine mesylate And 10 to 10 carbon atoms
The present invention relates to a percutaneous absorption preparation containing a lactic acid ester having an aliphatic alcohol having 20 and / or an aliphatic alcohol having 10 to 20 carbon atoms.
【０００６】炭素原子数１０〜２０を有する脂肪族アル
コールとしては、医薬用添加物として使用できる全ての
炭素原子数１０〜２０を有する脂肪族アルコールが使用
できるが、好ましくはラウリルアルコール、ミリスチル
アルコールまたはセチルアルコール、特に好ましくはラ
ウリルアルコールが使用される。その配合量は、一般
に、本発明組成物または製剤１ｇあたり、１〜３００ｍ
ｇ、好ましくは５〜２００ｍｇ、特に１０〜１００ｍｇ
である。As the aliphatic alcohol having 10 to 20 carbon atoms, all aliphatic alcohols having 10 to 20 carbon atoms which can be used as a pharmaceutical additive can be used, and preferably, lauryl alcohol, myristyl alcohol or Cetyl alcohol, particularly preferably lauryl alcohol, is used. The compounding amount is generally 1 to 300 m per 1 g of the composition or preparation of the present invention.
g, preferably 5-200 mg, especially 10-100 mg
It is.
【０００７】炭素原子数１０〜２０を有する脂肪族アル
コールの乳酸エステルとしては、医薬用添加物として使
用できる全ての炭素原子数１０〜２０を有する脂肪族ア
ルコールの乳酸エステルが使用できるが、好ましくは、
乳酸ラウリル、乳酸ミリスチルまたは乳酸セチル、特に
好ましくは乳酸セチルが使用される。その配合量は、一
般に、本発明組成物または製剤１ｇあたり、１〜３００
ｍｇ、好ましくは５〜２００ｍｇ、特に１０〜１００ｍ
ｇである。As the lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms, all the lactic acid esters of an aliphatic alcohol having 10 to 20 carbon atoms which can be used as a pharmaceutical additive can be used. ,
Lauryl lactate, myristyl lactate or cetyl lactate, particularly preferably cetyl lactate, is used. The compounding amount is generally 1 to 300 per 1 g of the composition or preparation of the present invention.
mg, preferably 5-200 mg, especially 10-100 m
g.
【０００８】これらのアルコールおよびアルコールの乳
酸エステルは、いずれも単独でまたは２種以上を組み合
わせて使用することができる。さらに、本発明組成物ま
たは製剤は、医薬品の基剤として使用できる物質、例え
ば、水、植物油、鉱物油、高分子感圧接着剤および／ま
たは低級アルコール類を含むこともできる。These alcohols and lactic acid esters of alcohols can be used alone or in combination of two or more. In addition, the compositions or preparations according to the invention can also contain substances which can be used as pharmaceutical bases, for example water, vegetable oils, mineral oils, polymeric pressure-sensitive adhesives and / or lower alcohols.
【０００９】本発明の経皮吸収製剤用組成物は、溶液、
分散物、懸濁物、乳化物または半固形物状態にあること
ができる。本発明の経皮吸収製剤は、液剤、テープ剤、
軟膏剤、パップ剤またはプラスター剤の形にあることが
できる。The composition for transdermal absorption preparation of the present invention comprises a solution,
It can be in a dispersion, suspension, emulsion or semi-solid state. The transdermal absorption preparation of the present invention is a liquid preparation, a tape preparation,
It can be in the form of an ointment, poultice or plaster.
【００１０】本発明の経皮吸収製剤用組成物または製剤
は、例えば、炭素原子数１０〜２０を有する脂肪族アル
コールおよび／または炭素原子数１０〜２０を有する脂
肪族アルコールの乳酸エステルにメシル酸ベタヒスチン
を添加しそして混合することにより、あるいは、高分子
感圧接着剤にメシル酸ベタヒスチンならびに炭素原子数
１０〜２０を有する脂肪族アルコールおよび／または炭
素原子数１０〜２０を有する脂肪族アルコールの乳酸エ
ステルを添加しそして混合することにより製造される。
また、テープ剤の形の本発明による経皮吸収製剤は、慣
用のテープ剤の調製方法である溶媒キャスティング法に
より製造することができる。[0010] The composition or preparation for percutaneous absorption of the present invention may be, for example, a fatty acid having 10 to 20 carbon atoms and / or a lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms to mesyl acid. By adding and mixing betahistine, or in a polymeric pressure-sensitive adhesive, betahistine mesylate and lactic acid of an aliphatic alcohol having 10 to 20 carbon atoms and / or an aliphatic alcohol having 10 to 20 carbon atoms. Produced by adding and mixing esters.
The transdermally absorbable preparation of the present invention in the form of a tape can be produced by a solvent casting method which is a conventional preparation method of a tape.
【００１１】[0011]
【実施例】以下、本発明を実施例を参照して更に詳細に
説明するが、本発明はこれらの実施例に限定されない。EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
【００１２】実施例１ 表１に示される配合で、スチレン−イソプレン−スチレ
ン共重合体に、メシル酸ベタヒスチン、ラウリルアルコ
ール、乳酸セチルおよびロジンエステルを添加しそして
混合する。得られる本発明組成物１および２ならびに比
較組成物１１ｇをクロロホルム１ｍｌに溶解した溶液
を、乾燥時の厚さが１１０μｍになるように、ポリエチ
レンテレフタレートフィルム上にアプリケータを用いて
塗布してテープ剤を調製した。Example 1 To a styrene-isoprene-styrene copolymer with the formulation shown in Table 1, betahistine mesylate, lauryl alcohol, cetyl lactate and rosin ester are added and mixed. A solution prepared by dissolving 11 g of the resulting compositions 1 and 2 of the present invention and 11 g of the comparative composition in 1 ml of chloroform was applied on a polyethylene terephthalate film using an applicator so that the thickness when dried became 110 μm, and the tape was prepared. Was prepared.
【００１３】 表１ 成分 本発明組成物１ 本発明組成物２ 比較組成物１ メシル酸ベタヒスチン ２０ ２０ ２０ スチレン−イソプレン ４６ ４６ ４９ −スチレン共重合体 ロジンエステル ２９ ２９ ３１ ラウリルアルコール ５ ０ ０ 乳酸セチル ０ ５ ０ （単位：ｗ％） 次いで、ヘアレスラット腹部摘出皮膚を縦型拡散セル
（有効透過面積：１ｃｍ 2 ）に挟んで、その真皮側セル
に水４．５ｍｌを入れ、３７℃で攪拌しながら、摘出皮
膚の角質層側に本発明組成物１から調製した本発明製剤
１または２、あるいは比較組成物１から調製した比較製
剤１を適用し、そして真皮側にそれぞれ移行したメシル
酸ベタヒスチンの量を経時的に測定した。結果を表２に
示す。Table 1 Ingredients The present invention composition 1 The present invention composition 2 Comparative composition 1 Betahistine mesylate 20 20 20 Styrene-isoprene 46 46 49-styrene copolymer Rosin ester 29 29 31 Lauryl alcohol 500 0 Cetyl lactate 0 50 (unit: w%) Then, the skin of the abdominal excision of a hairless rat was placed in a vertical diffusion cell.
(Effective transmission area: 1cm Two), Between the dermal cells
Put 4.5 ml of water in the skin and stir at 37 ° C while removing the skin
The preparation of the present invention prepared from the composition 1 of the present invention on the stratum corneum side of the skin
1 or 2, or a comparative product prepared from comparative composition 1
Mesyl applied with agent 1 and transferred to the dermis side
The amount of betahistine acid was measured over time. Table 2 shows the results
Show.
【００１４】 表２ 経過 累積透過量（μ／ｃｍ2 ） 時間 本発明製剤１ 本発明製剤２ 比較製剤１ ２ ５３ １１１ ３１ ４ ９７ ２２３ ５９ ６ ２６５ ３２５ １５４ ８ ３７９ ４３７ ２１９ １０ ５０１ ５７５ ２９２ ２４ １０４２ １１８７ ５９５ 表２に示される結果から明らかなように、ラウリルアル
コールまたは乳酸セチルの添加によって、メシル酸ベタ
ヒスチンの皮膚透過が促進され、その結果、単位面積あ
たりの高い薬物皮膚透過速度を得ることができた。Table 2 Elapsed cumulative permeation amount (μ / cm 2 ) Time Formulation 1 of the present invention Formulation 2 of the present invention Comparative formulation 1 253 111 31 4 97 223 59 6 265 325 154 8 379 437 219 10 501 575 292 242 1042 1187 595 As is clear from the results shown in Table 2, the addition of lauryl alcohol or cetyl lactate promoted the skin permeation of betahistine mesylate, and as a result, a high drug skin permeation rate per unit area could be obtained. .
【００１５】[0015]
【発明の効果】以上述べた説明から明らかなように、本
発明によれば、メシル酸ベタヒスチンの高い皮膚透過
性、即ち、単位面積あたりの高い薬物皮膚透過速度を得
ることができる。すなわち、本発明によれば、メシル酸
ベタヒスチンを小さな面積で皮膚に適用しても、十分な
治療効果を得るのに好都合なメシル酸ベタヒスチンの経
皮吸収製剤用組成物および経皮吸収製剤が提供される。As is apparent from the above description, according to the present invention, high skin permeability of betahistine mesylate, that is, a high drug skin permeation rate per unit area can be obtained. That is, according to the present invention, even when betahistine mesylate is applied to the skin in a small area, a composition for a transdermal absorption preparation of betahistine mesylate and a transdermal absorption preparation which are convenient for obtaining a sufficient therapeutic effect are provided. Is done.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭61−249934（ＪＰ，Ａ) 特開 平２−131426（ＪＰ，Ａ) 特開 平２−124824（ＪＰ，Ａ) 特開 平４−91022（ＪＰ，Ａ) 特開 平２−174716（ＪＰ，Ａ) 特開 昭55−154915（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 31/4402 A61K 47/10 A61K 47/14 A61P 1/08 ＣＡ（ＳＴＮ)────────────────────────────────────────────────── ─── Continuation of front page (56) References JP-A-61-249934 (JP, A) JP-A-2-131426 (JP, A) JP-A-2-124824 (JP, A) JP-A-4- 91022 (JP, A) JP-A-2-174716 (JP, A) JP-A-55-154915 (JP, A) (58) Fields investigated (Int. Cl. 7 , DB name) A61K 31/4402 A61K 47 / 10 A61K 47/14 A61P 1/08 CA (STN)
Claims (2)
数１０〜２０を有する脂肪族アルコールおよび／または
炭素原子数１０〜２０を有する脂肪族アルコールの乳酸
エステルを含む経皮吸収製剤用組成物。1. A composition for percutaneous absorption preparation comprising betahistine mesylate and an aliphatic alcohol having 10 to 20 carbon atoms and / or a lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms.
数１０〜２０を有する脂肪族アルコールおよび／または
炭素原子数１０〜２０を有する脂肪族アルコールの乳酸
エステルを含む経皮吸収製剤。2. A transdermal preparation comprising betahistine mesylate and an aliphatic alcohol having 10 to 20 carbon atoms and / or a lactic acid ester of an aliphatic alcohol having 10 to 20 carbon atoms.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21614392A JP3203056B2 (en) | 1992-08-13 | 1992-08-13 | Composition for transdermal absorption preparation of betahistine mesylate and transdermal absorption preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21614392A JP3203056B2 (en) | 1992-08-13 | 1992-08-13 | Composition for transdermal absorption preparation of betahistine mesylate and transdermal absorption preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0665102A JPH0665102A (en) | 1994-03-08 |
| JP3203056B2 true JP3203056B2 (en) | 2001-08-27 |
Family
ID=16683951
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21614392A Expired - Fee Related JP3203056B2 (en) | 1992-08-13 | 1992-08-13 | Composition for transdermal absorption preparation of betahistine mesylate and transdermal absorption preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3203056B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118356397A (en) * | 2017-02-02 | 2024-07-19 | 欧托拉农股份有限公司 | Intranasal compositions comprising betahistine |
-
1992
- 1992-08-13 JP JP21614392A patent/JP3203056B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0665102A (en) | 1994-03-08 |
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