JPH05213748A - Isosorbide dinitrate plaster - Google Patents
Isosorbide dinitrate plasterInfo
- Publication number
- JPH05213748A JPH05213748A JP4766292A JP4766292A JPH05213748A JP H05213748 A JPH05213748 A JP H05213748A JP 4766292 A JP4766292 A JP 4766292A JP 4766292 A JP4766292 A JP 4766292A JP H05213748 A JPH05213748 A JP H05213748A
- Authority
- JP
- Japan
- Prior art keywords
- isdn
- plaster
- patch
- emulsion polymer
- meth
- 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
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、例えば狭心症の発作予
防に有効な硝酸イソソルビド（以下、ＩＳＤＮと記す）
を基剤中に含有した経皮吸収投与型のＩＳＤＮ貼付剤に
関するものである。FIELD OF THE INVENTION The present invention relates to isosorbide dinitrate (hereinafter referred to as ISDN), which is effective in preventing seizures of angina, for example.
The present invention relates to a percutaneous absorption type ISDN patch containing the above.
【０００２】[0002]
【従来の技術】狭心症の発作を防止するために、ＩＳＤ
Ｎを徐々に経皮投与によって供給する医薬包帯（米国特
許第３７４２５１号明細書参照）が提案されている。こ
の包帯は、「(1) 裏打部材と；(2) 壁在中に固定された
冠血管拡張剤を含む独立した中間貯蔵層であって、その
壁材が薬物の透過性を有する薬物放出速度を制御する材
料から形成されており、長時間にわたって制御され、且
つ予め定めあれた速度で貯蔵層から皮膚へ治療に有効な
量の薬物を連続的に流される貯蔵層と；(3) 裏打部材か
ら離れて貯蔵層の一つの壁に位置している感圧性接着剤
表面；を積層してなる」ものであるが、その構成は複雑
な多層系であるとともに、薬物の放出は貯蔵層と感圧性
接着剤層との分配係数に依存するために、薬物の有効利
用率が少ない、即ち包帯中の薬物残存率が多いと言う欠
点を有するものであった。2. Description of the Related Art ISD is used to prevent attacks of angina.
A pharmaceutical dressing (see US Pat. No. 374251) in which N is gradually delivered by transdermal administration has been proposed. This dressing consists of "(1) a backing member; and (2) an independent intermediate reservoir containing a coronary vasodilator fixed in the wall, the wall of which is drug permeable and has a drug release rate. (3) a backing member formed of a material that controls the temperature of the backing layer, which is controlled for a long time and in which a therapeutically effective amount of a drug is continuously flowed from the storage layer to the skin at a predetermined rate; Layer of a pressure sensitive adhesive surface located on one wall of the reservoir away from the storage layer. ”Its construction is a complex multi-layer system, and the drug release is sensitive to the reservoir layer. Since it depends on the partition coefficient with the pressure-sensitive adhesive layer, it has a drawback that the effective utilization rate of the drug is low, that is, the residual rate of the drug in the bandage is high.
【０００３】一方、このような多層系の医薬包帯の欠点
を解決するため「水中で膨潤するアクリル及びメタクリ
ル酸アルキルエステルの共重合体からなるフィルムに活
性物質を含有させて経皮的に適用するものが提案されて
いる（西独国特許公開第２９２０５００号）。しかしな
がら、これは使用されるアクリル及びメタクリル酸アル
キルエステルが、低級アルキルエステルを共重合したも
のであって、長時間の使用によって粘着性が得られない
ほど膨潤するものであり、ＩＳＤＮを長時間徐々に供給
することができない欠点を有するものであった。On the other hand, in order to solve the drawbacks of such a multi-layered medical dressing, "a film made of a copolymer of acrylic and methacrylic acid alkyl ester which swells in water contains an active substance and is applied transdermally. However, this is because the acrylic and methacrylic acid alkyl ester used is a copolymer of a lower alkyl ester and is tacky when used for a long time. Was swelled to the extent that it could not be obtained, and had a drawback that ISDN could not be gradually supplied for a long time.
【０００４】そこで、製剤が外部からの水分などによっ
てほとんど膨潤せず、皮膚に所定期間確実に接着してお
り、貼付したまま入浴しても剥れることのない強い粘着
力のＩＳＤＮ貼付剤を得るため、水分に対して膨潤しな
い平均炭素数が４〜１３の（メタ）アクリル酸アルキル
エステルからなるＩＳＤＮ貼付剤が提案されている（特
開昭５７−１１６０１１号）。[0004] Therefore, an ISDN patch having a strong adhesive strength, in which the preparation hardly swells due to moisture from the outside or the like, is firmly adhered to the skin for a predetermined period of time and does not peel off even when bathed with the patch applied. Therefore, an ISDN patch comprising an (meth) acrylic acid alkyl ester having an average carbon number of 4 to 13 which does not swell with respect to water has been proposed (JP-A-57-116011).
【０００５】[0005]
【発明が解決しようとする課題】ところで、このような
ＩＳＤＮ貼付剤は、ＩＳＤＮを経皮より投与することが
目的であり、肩凝りや関節の炎症等の特定の患部という
ものはない。このため、関節などのように動きの激しい
個所に貼付する必要は全くない貼付剤であり、特別に強
い粘着力は必要ないものである。By the way, such an ISDN patch is intended for transdermal administration of ISDN, and there is no specific affected area such as stiff shoulder or inflammation of joint. Therefore, it is a patch that does not need to be applied to a place with a lot of movement such as a joint, and does not require a particularly strong adhesive force.
【０００６】また、ＩＳＤＮ貼付剤は、狭心症患者の発
作を抑制するために継続的に投与することが目的であ
り、加えて、患者によっては同じ個所に貼付しなければ
効果がなくなったり、効果が低下したりするのではない
かと言う理由で、常に一定の個所に貼付する場合が多
い。このため、肌荒れ，湿疹，カブレ，痒み等の副作用
が生じていた。[0006] The ISDN patch is intended to be continuously administered in order to suppress seizures in patients with angina. In addition, some patients may not be effective unless it is applied to the same site, In many cases, it is always affixed to a certain place because the effect may be reduced. For this reason, side effects such as rough skin, eczema, rash, and itching occurred.
【０００７】更に、「使用していると、ある程度赤くな
ったり、痒くなったりすることもある」という使用前の
患者に対する医師の忠告により、肌荒れ，湿疹，カブ
レ，痒み等を副作用として申告しない場合が多いのが現
状であり、副作用として把握されている報告件数以上
に、肌荒れ，湿疹，カブレ，痒み等の副作用があること
は充分に考えられることであり、患者にとってこれらの
副作用は深刻な問題であった。[0007] Furthermore, due to the doctor's advice to a patient before use that "there may be redness or itching to some extent when used", skin roughness, eczema, rash, itching, etc. are not reported as side effects. It is highly possible that there are many side effects such as rough skin, eczema, rash, itching, etc. beyond the number of reported cases as side effects, and these side effects are a serious problem for patients. Met.
【０００８】また、前述の水分に対して膨潤しない平均
炭素数が４〜１３の（メタ）アクリル酸アルキルエステ
ルは引火性が強く、製造上の危険性がある問題もあっ
た。Further, the above-mentioned (meth) acrylic acid alkyl ester having an average carbon number of 4 to 13 which does not swell with respect to water has a strong flammability, and there is a problem that there is a danger in production.
【０００９】本発明は、長期間継続して一定の個所に貼
付しても肌荒れ，湿疹，カブレ，痒み等の副作用が起り
難く、然も経皮吸収し易いＩＳＤＮ貼付薬を得ることを
目的とする。The object of the present invention is to obtain an ISDN patch which is less likely to cause side effects such as rough skin, eczema, rash, and itch even if it is continuously applied to a certain place for a long period of time and is easily transdermally absorbed. To do.
【００１０】[0010]
【課題を解決するための手段】本発明に係るＩＳＤＮ貼
付薬では、アルキル基の平均炭素数が４以上の（メタ）
アクリル酸アルキルエステルを主成分とする乳化重合物
と、ＩＳＤＮとを必須成分とする基剤を担持体上に形成
したものである。In the ISDN patch according to the present invention, the alkyl group has an average carbon number of 4 or more (meta).
An emulsion polymer having an acrylic acid alkyl ester as a main component and a base having ISDN as an essential component are formed on a support.
【００１１】具体的な前記乳化重合物の主成分の（メ
タ）アクリル酸アルキルエステルとして、（メタ）アク
リル酸ブチルエステルであるものを開示する。The specific (meth) acrylic acid alkyl ester as the main component of the emulsion polymer is disclosed as (meth) acrylic acid butyl ester.
【００１２】[0012]
【作用】本発明においては、アルキル基の平均炭素数が
４以上の（メタ）アクリル酸アルキルエステルを主成分
とする乳化重合物と、ＩＳＤＮとを必須成分とする基剤
を担持体上に形成したものであるため、乳化重合物が水
に膨脹するものであり、皮膚表面の発汗水分等を吸収す
ることにより、長期間継続して一定の個所に貼付して
も、肌荒れ，湿疹，カブレ，痒み等の副作用を抑える。In the present invention, an emulsion polymer mainly composed of a (meth) acrylic acid alkyl ester having an alkyl group having an average carbon number of 4 or more and a base containing ISDN as essential components are formed on a support. Since the emulsion polymer swells in water, it absorbs sweating water on the skin surface, so that even if it is applied to a certain place for a long period of time, it will cause rough skin, eczema, rash, It suppresses side effects such as itching.
【００１３】尚、血中へのＩＳＤＮの移行は、基剤に対
するＩＳＤＮの含有割合に依存するものである。即ち、
基剤中のＩＳＤＮ含有量が高いものほど、ＩＳＤＮの血
中濃度は高くなる。ところで、本ＩＳＤＮ貼付剤では、
乳化重合物が水に膨潤するため、ＩＳＤＮの基剤に対す
る存在割合が次第に減少する。この減少に伴い、ＩＳＤ
Ｎの血中濃度が低下する。このため、基剤に対するＩＳ
ＤＮの含有割合を増加させることによりこの欠点を解消
した。即ち、好ましくは基剤に対するＩＳＤＮの含有割
合を、膨潤した基剤に対するＩＳＤＮの含有割合に換算
したものを含有割合とした。The migration of ISDN into the blood depends on the content ratio of ISDN to the base. That is,
The higher the ISDN content in the base, the higher the blood concentration of ISDN. By the way, in this ISDN patch,
Since the emulsion polymer swells in water, the ratio of ISDN to the base gradually decreases. With this decrease, ISD
The blood concentration of N decreases. Therefore, the IS
This defect has been eliminated by increasing the DN content. That is, preferably, the content ratio was obtained by converting the content ratio of ISDN to the base material into the content ratio of ISDN to the swollen base material.
【００１４】更に、本ＩＳＤＮ貼付剤では、アルキル基
の平均炭素数が４以上の（メタ）アクリル酸アルキルエ
ステルを主成分とする乳化重合物を用いるため、引火性
が少なく、製造上危険が少ない。Further, in the present ISDN patch, since an emulsion polymer containing an alkyl (meth) acrylate having an alkyl group having an average carbon number of 4 or more as a main component is used, the flammability is low and the production risk is low. ..
【００１５】[0015]
【実施例】（実施例．１：ＩＳＤＮ貼付剤の作製） 次の通り、ＩＳ
ＤＮ貼付剤を作製した。（メタ）アクリル酸アルキルエ
ステルを主成分とする乳化重合物（商品名；プライマル
（ＮＦ−１）Ｎ−５８０，日本アクリル化学社製）２０
３８．８ｇ（乾燥時；１０５０ｇ）をスリーワンモータ
で攪拌しながら、２０％硝酸イソソルビド酢酸エチル
（中国化薬社製）溶液１０００ｍｌを徐々に添加し、１
時間攪拌して膏体を得た。これをＰＥＴ製の支持体に塗
工して乾燥させ、ライナーを貼着させてＩＳＤＮ貼付剤
（ＴＩＳ−１−Ａ）を得た（膏体塗工量５０ｇ／ｍ2 ，
ＩＳＤＮ８ｇ／ｍ2 ，膏体中ＩＳＤＮ濃度１６wt％）。[Examples] (Example. 1: Preparation of ISDN patch)
A DN patch was prepared. Emulsion polymer containing alkyl (meth) acrylate as a main component (trade name; Primal (NF-1) N-580, manufactured by Nippon Acrylic Chemical Co., Ltd.) 20
While stirring 38.8 g (dry; 1050 g) with a three-one motor, 1000 ml of a 20% ethyl isosorbide nitrate acetate (manufactured by Chugoku Kayaku Co., Ltd.) solution was gradually added, and 1
The mixture was stirred for a time to obtain a plaster. This was applied to a PET support and dried, and a liner was applied to obtain an ISDN patch (TIS-1-A) (coating amount: 50 g / m 2 ,
ISDN 8 g / m 2 , ISDN concentration in plaster 16% by weight).
【００１６】同様に、（メタ）アクリル酸アルキルエス
テルを主成分とする乳化重合物（商品名；プライマル
（ＮＦ−１）Ｎ−５８０，日本アクリル化学社製）１５
５３．４ｇ（乾燥時；８００ｇ）をスリーワンモータで
攪拌しながら、２０％硝酸イソソルビド酢酸エチル（中
国化薬社製）溶液１０００ｍｌを徐々に添加し、１時間
攪拌して膏体を得た。これをＰＥＴ製の支持体に塗工し
て乾燥させ、ライナーを貼着させてＩＳＤＮ貼付剤（Ｔ
ＩＳ−１−Ｂ）を得た（膏体塗工量４０ｇ／ｍ2，ＩＳ
ＤＮ８ｇ／ｍ2 ，膏体中ＩＳＤＮ濃度２０wt％）。Similarly, an emulsion polymer having an alkyl (meth) acrylate as a main component (trade name; Primal (NF-1) N-580, manufactured by Nippon Acrylic Chemical Co., Ltd.) 15
While stirring 53.4 g (dry; 800 g) with a three-one motor, 1000 ml of a 20% ethyl isosorbide nitrate acetate (manufactured by Chugoku Kayaku Co., Ltd.) solution was gradually added and stirred for 1 hour to obtain a plaster. This is applied to a PET support and dried, and a liner is applied to the ISDN patch (T
IS-1-B) was obtained (coating amount of coating 40 g / m 2 , IS
DN 8 g / m 2 , ISDN concentration in the plaster 20% by weight).
【００１７】（実施例．２：ＩＳＤＮ血中濃度の推移，
その１）健康な成人男子ボランティア６名を無作為に３
群（１群２名）に分け、前記ＴＩＳ−１−Ａ，ＴＩＳ−
１−Ｂ及び比較例の３種類のＩＳＤＮ貼付剤を、左前胸
部に薬剤１枚を貼付して血中のＩＳＤＮの推移を測定し
た。尚、貼付時間は２４時間とした。また、同様の実験
を３群と３種のＩＳＤＮ貼付剤とを変更して計３回行っ
た。尚、比較例として市販のＩＳＤＮ貼付剤（トーアエ
イヨー（株）製，商品名：フランドールテープＳ（以
下、ＦＴＳと記す））を用いた。 Example 2: Transition of ISDN blood concentration,
Part 1) randomly selected 6 healthy adult male volunteers
It is divided into groups (2 persons in 1 group), and the TIS-1-A and TIS-
Three types of ISDN patches of 1-B and Comparative Example were pasted with one drug on the left precordial region, and the transition of ISDN in blood was measured. The application time was 24 hours. Further, the same experiment was conducted three times in total by changing the three groups and the three types of ISDN patches. In addition, as a comparative example, a commercially available ISDN patch (manufactured by Toa Eiyo Co., Ltd., trade name: Flandre Tape S (hereinafter referred to as FTS)) was used.
【００１８】図１は各種ＩＳＤＮ貼付剤での平均ＩＳＤ
Ｎ血中濃度の経時変化を示す線図である。図において、
実線がＴＩＳ−１−Ａ、一点鎖線がＴＩＳ−１−Ｂ、点
線がＦＴＳを示し、各々は１群（２名）３回の計６名分
の平均である。FIG. 1 shows the average ISD of various ISDN patches.
It is a diagram which shows the time-dependent change of the N blood concentration. In the figure,
The solid line indicates TIS-1-A, the alternate long and short dash line indicates TIS-1-B, and the dotted line indicates FTS, and each is the average of 6 times for 3 times per group (2 people).
【００１９】図に示す通り、本発明のＴＩＳ−１−Ａ及
びＴＩＳ−１−ＢはＦＴＳと比べても同等かそれ以上の
ＩＳＤＮ血中濃度が得られることが分かった。尚、各群
各実験各々について、貼付状態及び貼付後の皮膚の状態
を観察したが、各々貼付状態は良好であり、皮膚の状態
に別段変化はなかった。As shown in the figure, it was found that TIS-1-A and TIS-1-B of the present invention can obtain ISDN blood concentrations equivalent to or higher than those of FTS. For each experiment in each group, the state of application and the state of the skin after application were observed, but the state of application was good and there was no particular change in the state of the skin.
【００２０】（実施例．３：ＩＳＤＮ血中濃度の推移，
その２）健康な成人男子ボランティア２０名を募り、１
群１０名の２群に分け、３日間の休薬期間をおいたクロ
スオーバ法により、実施例（ＴＩＳ−１−Ａ） １枚
中、日本薬局方ＩＳＤＮ４０ｍｇ含有）と比較例（ＦＴ
Ｓ １枚中、日本薬局方ＩＳＤＮ４０ｍｇ含有）との貼
付剤を左前又は右前胸部に薬剤１枚を貼付し、一定期間
毎に血中のＩＳＤＮ濃度を測定し、血中濃度下面積（Ａ
ＵＣ）及び最高血中濃度（Ｃmax ）について分散分析に
より統計学的処理を行い、両剤における生物学的同等性
の判定を行った。 Example 3: Transition of ISDN blood concentration,
2) Call for 20 healthy adult male volunteers, 1
Group (10 people) was divided into 2 groups, and a crossover method with a 3-day washout period was used to carry out Example (TIS-1-A) 1 sheet containing 40 mg of Japanese Pharmacopoeia ISDN) and Comparative Example (FT).
A patch with the Japanese Pharmacopoeia ISDN 40 mg is included in 1 sheet of S, and 1 sheet of the drug is applied to the left front or right precordial chest, and the ISDN concentration in the blood is measured at regular intervals, and the area under the blood concentration (A
UC) and the maximum blood concentration (C max ) were statistically processed by analysis of variance to determine the bioequivalence of both agents.
【００２１】４８時間貼付し、貼付前，貼付後１，３，
６，９，１２，２４，３６及び４８時間目，更に剥離後
２，４，８時間の血中濃度を測定した。尚、除去後１時
間に貼付部分の皮膚状態を観察した。表１は個々の実施
例及び比較例でのＩＳＤＮの血中濃度推移を示し、表２
は実施例及び比較例でのＩＳＤＮの平均血中濃度推移を
示し、図２は表２の線図である。また、実施例及び比較
例のＡＵＣ，Ｃmax 及びＴmax （平均値）を表３に示
す。Sticking for 48 hours, before sticking, after sticking 1,3
Blood levels were measured at 6, 9, 12, 24, 36 and 48 hours, and at 2, 4 and 8 hours after peeling. In addition, the skin condition of the applied part was observed 1 hour after the removal. Table 1 shows changes in the blood concentration of ISDN in each Example and Comparative Example, and Table 2
Shows the transition of the average blood concentration of ISDN in Examples and Comparative Examples, and FIG. 2 is a diagram of Table 2. Table 3 shows AUC, C max and T max (average values) of the examples and comparative examples.
【００２２】[0022]
【表１】 [Table 1]
【００２３】[0023]
【表２】 [Table 2]
【００２４】[0024]
【表３】 [Table 3]
【００２５】ＩＳＤＮの最高血中濃度は実施例，比較例
それぞれ薬剤貼付10.65 及び10.80時間後に認められ、
その後24時間目では、実施例は2.090 ng/ml ，比較例は
1.915 ng/ml を示し、48時間目では実施例は1.343 ng/m
l ，比較例は1.353 ng/ml と安定した濃度を示した。ま
た、薬剤を除去した48時間目以降は速やかに減少した。[0025] The maximum blood concentration of ISDN was found in 10.65 hours and 10.80 hours after drug application in Examples and Comparative Examples, respectively.
At 24 hours after that, the example was 2.090 ng / ml, and the comparative example was
1.915 ng / ml, and at 48 hours the example was 1.343 ng / m
Comparative example showed a stable concentration of 1.353 ng / ml. In addition, it decreased rapidly after 48 hours after the drug was removed.
【００２６】ＡＵＣの平均値は実施例及び比較例それぞ
れ86.641，83.880 ng/ml・hr で、その差は比較例に対し
て3.29％となり、20％以内であった。Ｃmax の平均値は
ＴＩＳ−１及びＦＴＳ各々 2.454 ng/ml， 2.473 ng/ml
で、その鎖は対象薬剤ＦＴＳに対して0.77％となり、20
％以内であった。２×２ラタン方格によるＡＵＣの分散
分析を行った結果を表４に、Ｃmax の分散分析を行った
結果を表５に示す。The average values of AUC were 86.641 and 83.880 ng / ml · hr for Examples and Comparative Examples, respectively, and the difference was 3.29% with respect to the Comparative Examples, which was within 20%. The average values of C max are 2.454 ng / ml and 2.473 ng / ml for TIS-1 and FTS, respectively.
Then, the chain is 0.77% of the target drug FTS, 20
It was within%. Table 4 shows the results of AUC analysis of variance based on the 2 × 2 rattan square, and Table 5 shows the results of Cmax analysis of variance.
【００２７】[0027]
【表４】 [Table 4]
【００２８】[0028]
【表５】 [Table 5]
【００２９】以上のような実施例において、比較例投与
群の２例（表１ No.2,8 ）で貼付中頭重感ないし頭重
を、１例（表１ No.4 ）でテープ除去後軽度皮膚発赤
を、１例（表１ No.7 ）で掻痒感を認めた。また、実施
例投与群の３例（表１ No.11,13,16）で貼付中頭重感な
いし頭重を、１例（表１ No.13）で咽頭痛、くしゃみ、
軽度鼻出血などの症状を２例（表１ No.1,10）で投与前
よりの花粉症の症状を認めた。[0029] In the above examples, the feeling of head weight or head weight of the patch in 2 cases (Table 1, No. 2, 8) of the comparative administration group was slight after tape removal in 1 case (Table 1, No. 4). Itching of skin was observed in one case (No. 7 in Table 1). In addition, 3 cases (Table 1 No.11, 13, 16) of the administration group of the Example showed a feeling of middle head weight or head weight when applied, and 1 case (Table 1 No. 13) had sore throat, sneezing,
Symptoms such as mild epistaxis were observed in 2 cases (No. 1, 10 in Table 1) before the administration.
【００３０】[0030]
【発明の効果】本発明は以上説明したとおり、アルキル
基の平均炭素数が４以上の（メタ）アクリル酸アルキル
エステルを主成分とする乳化重合物と、ＩＳＤＮとを必
須成分とする基剤を担持体上に形成したものであるた
め、乳化重合物が水に膨脹ものであり、皮膚表面の発汗
水分等を吸収することにより、長期間継続して一定の個
所に貼付しても、肌荒れ，湿疹，カブレ，痒み等の副作
用を抑える。As described above, the present invention provides an emulsion polymer mainly composed of a (meth) acrylic acid alkyl ester having an alkyl group having an average carbon number of 4 or more, and a base containing ISDN as an essential component. Since it is formed on the carrier, the emulsion polymer is swellable in water, and absorbs sweating water on the skin surface, so that even if it is applied to a certain place continuously for a long period of time, rough skin, It suppresses side effects such as eczema, rash, and itching.
【００３１】尚、血中へのＩＳＤＮの移行は、基剤に対
するＩＳＤＮの含有割合に依存するものである。即ち、
基剤中のＩＳＤＮ含有量が高いものほど、ＩＳＤＮの血
中濃度は高くなる。ところで、本ＩＳＤＮ貼付剤では、
乳化重合物が水に膨潤するため、ＩＳＤＮの基剤に対す
る存在割合が次第に減少する。この減少に伴い、ＩＳＤ
Ｎの血中濃度が低下する。このため、基剤に対するＩＳ
ＤＮの含有割合を増加させることによりこの欠点を解消
した。即ち、好ましくは基剤に対するＩＳＤＮの含有割
合を、膨潤した基剤に対するＩＳＤＮの含有割合に換算
したものを含有割合とした。The migration of ISDN into the blood depends on the content ratio of ISDN to the base. That is,
The higher the ISDN content in the base, the higher the blood concentration of ISDN. By the way, in this ISDN patch,
Since the emulsion polymer swells in water, the ratio of ISDN to the base gradually decreases. With this decrease, ISD
The blood concentration of N decreases. Therefore, the IS
This defect has been eliminated by increasing the DN content. That is, preferably, the content ratio was obtained by converting the content ratio of ISDN to the base material into the content ratio of ISDN to the swollen base material.
【００３２】更に、本ＩＳＤＮ貼付剤では、アルキル基
の平均炭素数が４以上の（メタ）アクリル酸アルキルエ
ステルを主成分とする乳化重合物を用いるため、引火性
が少なく、製造上危険が少ないという効果がある。Further, in the present ISDN patch, since an emulsion polymer mainly composed of an alkyl (meth) acrylate ester having an alkyl group having an average carbon number of 4 or more is used, the flammability is low and the production risk is low. There is an effect.
【図１】実施例１での平均ＩＳＤＮ血中濃度の経時変化
を示す線図である。FIG. 1 is a diagram showing the time course of the mean ISDN blood concentration in Example 1.
【図２】実施例２での平均ＩＳＤＮ血中濃度推移の線図
である。FIG. 2 is a diagram showing changes in mean ISDN blood concentration in Example 2.
Claims (2)
タ）アクリル酸アルキルエステルを主成分とする乳化重
合物と、硝酸イソソルビドとを必須成分とする基剤を担
持体上に形成したことを特徴とする硝酸イソソルビド貼
付剤。1. A base material comprising, as essential components, an emulsion polymer mainly composed of a (meth) acrylic acid alkyl ester having an alkyl group having an average carbon number of 4 or more, and isosorbide dinitrate are formed on a carrier. An isosorbide dinitrate patch characterized by:
リル酸アルキルエステルが、（メタ）アクリル酸ブチル
エステルであることを特徴とする硝酸イソソルビド貼付
剤。2. An isosorbide dinitrate patch, wherein the (meth) acrylic acid alkyl ester as a main component of the emulsion polymer is (meth) acrylic acid butyl ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4766292A JPH05213748A (en) | 1992-02-04 | 1992-02-04 | Isosorbide dinitrate plaster |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4766292A JPH05213748A (en) | 1992-02-04 | 1992-02-04 | Isosorbide dinitrate plaster |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05213748A true JPH05213748A (en) | 1993-08-24 |
Family
ID=12781479
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4766292A Pending JPH05213748A (en) | 1992-02-04 | 1992-02-04 | Isosorbide dinitrate plaster |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH05213748A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007161631A (en) * | 2005-12-13 | 2007-06-28 | Alcare Co Ltd | Patch for body surface and method for producing the same |
-
1992
- 1992-02-04 JP JP4766292A patent/JPH05213748A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007161631A (en) * | 2005-12-13 | 2007-06-28 | Alcare Co Ltd | Patch for body surface and method for producing the same |
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