WO2004024138A1 - Solid preparation containing dioctyl sodium sulfosuccinate - Google Patents

Solid preparation containing dioctyl sodium sulfosuccinate Download PDF

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Publication number
WO2004024138A1
WO2004024138A1 PCT/JP2003/011585 JP0311585W WO2004024138A1 WO 2004024138 A1 WO2004024138 A1 WO 2004024138A1 JP 0311585 W JP0311585 W JP 0311585W WO 2004024138 A1 WO2004024138 A1 WO 2004024138A1
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Prior art keywords
solid preparation
mass
enteric coating
core particles
preparation according
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PCT/JP2003/011585
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French (fr)
Japanese (ja)
Inventor
Kaoru Wada
Mitsuru Itoh
Kazuo Amano
Keiko Hosoda
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Taisho Pharmaceutical Co.,Ltd.
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Priority to JP2004535937A priority Critical patent/JPWO2004024138A1/en
Priority to AU2003262060A priority patent/AU2003262060A1/en
Publication of WO2004024138A1 publication Critical patent/WO2004024138A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/225—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats

Definitions

  • the present invention relates to a formulation containing dioctyl sodizulfosuccinate.
  • Dioctylsodium sulfosuccinate is known as a laxative. Its effect is to act directly on hard stools in the intestine to penetrate water, soften and swell the stool, thereby promoting excretion.
  • dioctylsodium sulfosuccinate is a waxy substance, it is known that it is difficult to prepare a general colon-proximal release-type preparation coated with an enteric coating or the like. Therefore, an oral drug containing conventional dioctylsodium sulfosuccinate is not effective as a direct effect because it is released at the upper part of the digestive tract after oral administration.
  • An object of the present invention is to provide a solid preparation in which dioctylsodium sulfosuccinate is released in the vicinity of the large intestine at the site of action and has an effective cathartic effect. Disclosure of the invention
  • the present inventors have conducted various studies to solve the problems, and as a result, granulated a powder containing dioctylsodium sulphosuccinate and light citric anhydride, and produced the obtained granules or the granules.
  • an enteric coating By applying an enteric coating to the tablet obtained in this manner, it was found that an excellent preparation in which dimethyltyl sulfosuccinate was released in the vicinity of the large intestine was obtained, and the present invention was completed. That is, the present invention is a solid preparation characterized in that an enteric coating is applied to core particles containing dioctylsodium sulfosuccinate and light citric anhydride.
  • the core particle is an object to be coated with an enteric coating, and is a granule obtained by kneading and granulating a powder containing dioctylsodium sulfosuccinate and light gay anhydride, or a tablet thereof. Tablets and the like can be used.
  • magnesium stearate it is preferable to mix magnesium stearate with light gay anhydride at the same time in view of workability at the time of tableting.
  • the enteric coating may be any of those commonly used for enteric coating, and particularly, methacrylic acid copolymer (L, S, LD), hydroxypropyl methylcellulose phthalate, hydroxypropyl methyl Cell opening—A component selected from the group consisting of acetate succinate, carboxymethylethyl cellulose and cellulose acetate phthalate is preferred. They can be used alone or as a mixture of two or more.
  • the coating amount when the enteric coating is directly coated on the core particles is preferably 1 to 30% by mass based on the mass of the core particles.
  • an enteric capsule may be used as the enteric coating.
  • the granules of the core particles are filled into an enteric capsule to form a capsule.
  • dioctyl sodizulfosuccinate and other active ingredients having a purging action in the same granules or in separate granules, and to mix them and blend them, since the purging action can be expected to be improved, which is preferable.
  • Pisacodyl is preferable as another active ingredient having a purgative effect in terms of the effect, and its compounding amount is preferably 3 to 15 mg in a daily dose.
  • pisacodyl was hardly soluble, so that sufficient effects could not be obtained even when it was added to the preparation.
  • visacodyl was simultaneously added to dioctyl sodium sulfosuccinate. It has also been found that this improves the solubility. Therefore, synergistic effects can be expected by simultaneously combining visacodyl and dioctylsodium sulfosuccinate in the present invention as compared with the case where each is administered alone. Therefore, in the present invention, a formulation in which pisacodyl is simultaneously added to the core particles is more preferable.
  • a solvent in which dioctylsodium sulfosuccinate is dissolved It is preferable to mix a hydrophilic polymer in terms of the properties of the obtained granules.
  • water-soluble polymer to be blended here those usually used as a binder can be used. Preferred examples thereof include hydroxypropylcellulose, polyvinylpyrrolidone and hydroxypropylmethylcell mouth.
  • the mixing amount of the water-soluble polymer is preferably from 0.1 to 0.3 part by mass with respect to 1 part by mass of octylsodium sulfosuccinate.
  • 0.5 to 1.5 parts by weight, preferably 0.6 to 1.3 parts by weight, of light gay anhydride is preferably added to 1 part by weight of dioctylsodium sulfosuccinate. More preferred. If the amount is more than 1.5 parts by mass, an excessive fine powder resulting from excess light acid anhydride may cause trouble during tableting.
  • magnesium stearate is preferably used in an amount of from 0.05 to 0.5 part by mass, more preferably from 0.1 to 0.3 part by mass, per part by mass of dioctylsodium sulfosuccinate.
  • the core particles of the present invention are produced as follows.
  • Dioctylsodium sulfosuccinate is dissolved in a solvent such as water or ethanol to form a solution.
  • the solution is added while spraying or all at once, and a powder obtained by mixing light caustic anhydride and, if necessary, magnesium stearate is granulated to obtain a powder.
  • FIG. 1 is a diagram showing the results of a dissolution test of Examples and Comparative Examples, in which the vertical axis represents the dissolution rate, and the horizontal axis represents time and pH.
  • 960 g of dioctylsodium sulfosuccinate and 200 g of hydroxypropylcellulose were dissolved in alcohol, and mixed with 960 g of light caustic anhydride and 288 g of magnesium stearate. After kneading and granulating with the powder, drying and sizing, granules B were obtained. Granule A, Granule B, 30 g of magnesium stearate and 30 g of light anhydrous calcium acid were added and mixed. The obtained granules were tableted to give tablets having a tablet diameter of 5 mm and a tablet weight of 5 O mg. This was used as a nuclear particle.
  • Test example 1 A core particle tablet produced in the same manner as in Example 1 was used as a comparative example.
  • Test example 1 A core particle tablet produced in the same manner as in Example 1 was used as a comparative example.
  • DSS Dioctyl sodium sulfosuccinate Coexistence of hosuccinate as evident from the table Showed that the solubility of pisacodyl was significantly improved.
  • the present invention makes it possible to efficiently release dioctylsodium sulfosuccinate into the vicinity of the large intestine, which is the site of action, and is therefore useful as an effective laxative.

Abstract

Dioctyl sodium sulfosuccinate, which is a waxy substance and thus can be hardly processed into a common preparation being coated with an enteric film or the like and thus released around the large intestine, is released at the upper part of the digestive tract and, therefore, is not highly efficacious from the viewpoint of its direct action. Accordingly, it is intended to provide a solid preparation from which dioctyl sodium sulfosuccinate is released around the large intestine (i.e., the action site) to exert a favorable purgative effect. Namely, a solid preparation characterized in that core particles containing granules, which are obtained by granulating a powder containing light silicic anhydride with the use of a solution containing dioctyl sodium sulfosuccinate, are coated with an enteric film.

Description

明細書 ジォクチルソジゥムスルホサクシネート配合固形製剤 技術分野  Description Solid preparation containing dioctylsodium sulfosuccinate
本発明はジォクチルソジゥムスルホサクシネートを配合した製剤に関する。 背景技術  The present invention relates to a formulation containing dioctyl sodizulfosuccinate. Background art
ジォクチルソジゥムスルホサクシネ一トは瀉下薬として知られている。 その作 用は腸内で硬便に直接作用して水を浸透させ、 便を軟化、 膨潤させることにより 排泄を促進させるものである。 しかし、 ジォクチルソジゥムスルホサクシネート はロウ状物質であることから、 腸溶性被膜などで被覆する一般的な大腸近位放出 型の製剤にはしにくいことが知られている。 そのため、 従来のジォクチルソジゥ ムスルホサクシネー卜を配合した内服薬剤は、 経口投与後、 消化管の上部で放出 されることから直接作用としては効果的ではなかつた。  Dioctylsodium sulfosuccinate is known as a laxative. Its effect is to act directly on hard stools in the intestine to penetrate water, soften and swell the stool, thereby promoting excretion. However, since dioctylsodium sulfosuccinate is a waxy substance, it is known that it is difficult to prepare a general colon-proximal release-type preparation coated with an enteric coating or the like. Therefore, an oral drug containing conventional dioctylsodium sulfosuccinate is not effective as a direct effect because it is released at the upper part of the digestive tract after oral administration.
従来ジォクチルソジゥムスルホサクシネートを配合した製剤を製造する技術と して、 ジォクチルソジゥムスルホサクシネートおよび微粉末を特殊な条件で粉末 化する技術 （日本国特許特開平 2 - 2 5 5 6 1 3 ) などが知られているが、 ジォ クチルソジゥムスルホサクシネートを作用部位の大腸近位で放出させる技術は知 られていない。  Conventionally, as a technology for producing a preparation containing dioctylsodium sulfosuccinate, a technology for pulverizing dioctylsodium sulfosuccinate and fine powder under special conditions (Japanese Patent Application Laid-open No. -255 613), but there is no known technique for releasing dioctylsodium sulfosuccinate at the site of action near the large intestine.
本発明はジォクチルソジゥムスルホサクシネートが作用部位の大腸近位で放出 され、 効果的な瀉下効果を有する固形製剤の提供を目的とする。 発明の開示  An object of the present invention is to provide a solid preparation in which dioctylsodium sulfosuccinate is released in the vicinity of the large intestine at the site of action and has an effective cathartic effect. Disclosure of the invention
本発明者らは課題を解決するために種々検討した結果、 ジォクチルソジゥムス ルホサクシネートおよび軽質無水ケィ酸を配合した粉体を造粒し、得られた顆粒、 もしくはその顆粒を製錠して得られた錠剤に対して腸溶性被膜を施すことにより、 ジォクチルソジゥムスルホサクシネートが大腸付近で放出される、 優れた製剤が 得られることを見出し本発明を完成した。 すなわち本発明は、 ジォクチルソジゥムスルホサクシネートおよび軽質無水ケ ィ酸を含む核粒子に、 腸溶性被膜が施されていることを特徴とする固形製剤で.あ る。 The present inventors have conducted various studies to solve the problems, and as a result, granulated a powder containing dioctylsodium sulphosuccinate and light citric anhydride, and produced the obtained granules or the granules. By applying an enteric coating to the tablet obtained in this manner, it was found that an excellent preparation in which dimethyltyl sulfosuccinate was released in the vicinity of the large intestine was obtained, and the present invention was completed. That is, the present invention is a solid preparation characterized in that an enteric coating is applied to core particles containing dioctylsodium sulfosuccinate and light citric anhydride.
本発明で核粒子とは腸溶性被膜を施す対象物であり、 ジォクチルソジゥムスル ホサクシネートおよび軽質無水ゲイ酸を配合した粉体を練合造粒した顆粒、 もし くはそれを製錠した錠剤などを用いることができる。  In the present invention, the core particle is an object to be coated with an enteric coating, and is a granule obtained by kneading and granulating a powder containing dioctylsodium sulfosuccinate and light gay anhydride, or a tablet thereof. Tablets and the like can be used.
本発明では軽質無水ゲイ酸と共にステアリン酸マグネシウムを同時に配合する と打錠時の作業性の点で好ましい。  In the present invention, it is preferable to mix magnesium stearate with light gay anhydride at the same time in view of workability at the time of tableting.
本発明で腸溶性被膜とはェンテリックコ一ティングに一般的に用いられるもの を使用することができるが、 特にメタクリル酸コポリマー （L、 S、 L D )、 ヒド ロキシプロピルメチルセルロースフタレ一ト、 ヒドロキシプロピルメチルセル口 —スァセテ一トサクシネート、 カルポキシメチルェチルセルロースおよび酢酸フ タル酸セルロースからなる群から選ばれる成分が好ましい。 それらは単独または 2種以上を混合させて用いることができる。  In the present invention, the enteric coating may be any of those commonly used for enteric coating, and particularly, methacrylic acid copolymer (L, S, LD), hydroxypropyl methylcellulose phthalate, hydroxypropyl methyl Cell opening—A component selected from the group consisting of acetate succinate, carboxymethylethyl cellulose and cellulose acetate phthalate is preferred. They can be used alone or as a mixture of two or more.
腸溶性被膜を直接核粒子に被覆する際の被覆量は、 核粒子の質量に対して 1〜 3 0質量％が好ましい。  The coating amount when the enteric coating is directly coated on the core particles is preferably 1 to 30% by mass based on the mass of the core particles.
また、本発明では腸溶性被膜として、腸溶性のカプセルを用いることもできる。 その場合は核粒子の顆粒などを腸溶性のカプセルに詰めカプセル剤とする。  In the present invention, an enteric capsule may be used as the enteric coating. In such a case, the granules of the core particles are filled into an enteric capsule to form a capsule.
本発明では特にジォクチルソジゥムスルホサクシネ一トと他の瀉下作用のある 活性成分を同顆粒中、 もしくは別顆粒とし、 これを混合して配合すると瀉下作用 の向上が期待できるので好ましい。 他の瀉下作用のある活性成分としては効果の 点でピサコジルが好ましく、 その配合量は 1 日投与量で 3〜1 5 mgが好ましい。  In the present invention, in particular, it is preferable to mix dioctyl sodizulfosuccinate and other active ingredients having a purging action in the same granules or in separate granules, and to mix them and blend them, since the purging action can be expected to be improved, which is preferable. . Pisacodyl is preferable as another active ingredient having a purgative effect in terms of the effect, and its compounding amount is preferably 3 to 15 mg in a daily dose.
ここで、 ピサコジルは難溶性のため、 製剤に配合しても十分な効果が得られな いことがあったが、 本発明でビザコジルをジォクチルソジゥムスルホサクシネ一 トと同時配合することにより溶解度が向上することも見出した。 したがって、 本 発明でビザコジルとジォクチルソジゥムスルホサクシネートを同時配合すること により、それぞれ単独に投与する場合に比べて相乗効果が期待できる。そのため、 本発明では核粒子にピサコジルを同時配合した処方がより好ましい。  Here, pisacodyl was hardly soluble, so that sufficient effects could not be obtained even when it was added to the preparation.However, in the present invention, visacodyl was simultaneously added to dioctyl sodium sulfosuccinate. It has also been found that this improves the solubility. Therefore, synergistic effects can be expected by simultaneously combining visacodyl and dioctylsodium sulfosuccinate in the present invention as compared with the case where each is administered alone. Therefore, in the present invention, a formulation in which pisacodyl is simultaneously added to the core particles is more preferable.
本発明では、 ジォクチルソジゥムスルホサクシネートを溶解させる溶媒に水溶 性高分子を配合すると、 得られる顆粒の性状の点で好ましい。 According to the present invention, a solvent in which dioctylsodium sulfosuccinate is dissolved It is preferable to mix a hydrophilic polymer in terms of the properties of the obtained granules.
ここで配合する水溶性高分子は、 結合剤として通常用いられるものを使用する ことができるが、 好ましいものとしてヒドロキシプロピルセルロース、 ポリビニ ルピロリ ドンおよびヒドロキシプロピルメチルセル口一スをあげることができる。 水溶性高分子の配合量は、 ジォクチルソジゥムスルホサクシネート 1質量部に対 し 0 . 1〜 0 . 3質量部が好ましい。  As the water-soluble polymer to be blended here, those usually used as a binder can be used. Preferred examples thereof include hydroxypropylcellulose, polyvinylpyrrolidone and hydroxypropylmethylcell mouth. The mixing amount of the water-soluble polymer is preferably from 0.1 to 0.3 part by mass with respect to 1 part by mass of octylsodium sulfosuccinate.
本発明において、 軽質無水ゲイ酸はジォクチルソジゥムスルホサクシネート 1 質量部に対して 0 . 5〜 1 . 5質量部の配合が好ましく、 0 . 6〜 1 . 3質量部の 配合がさらに好ましい。 1 . 5質量部を超えて配合すると、余剰の軽質無水ケィ酸 などに起因する微粉末により、 打錠時に障害が発生することがあるからである。 本発明においてステアリン酸マグネシウムはジォクチルソジゥムスルホサクシ ネート 1質量部に対して 0 . 0 5〜 0 . 5質量部が好ましく、 0 . 1〜 0 . 3質量部 の配合がより好ましい。  In the present invention, 0.5 to 1.5 parts by weight, preferably 0.6 to 1.3 parts by weight, of light gay anhydride is preferably added to 1 part by weight of dioctylsodium sulfosuccinate. More preferred. If the amount is more than 1.5 parts by mass, an excessive fine powder resulting from excess light acid anhydride may cause trouble during tableting. In the present invention, magnesium stearate is preferably used in an amount of from 0.05 to 0.5 part by mass, more preferably from 0.1 to 0.3 part by mass, per part by mass of dioctylsodium sulfosuccinate.
本発明の核粒子は以下のように製造される。  The core particles of the present invention are produced as follows.
ジォクチルソジゥムスルホサクシネ一トを水、 エタノールなどの溶媒に溶解し て溶液とする。 その溶液を噴霧しながらもしくは一括に添加し、 軽質無水ケィ酸 および必要があればステアリン酸マグネシウムを混合した粉体を造粒して粉体を 得る。  Dioctylsodium sulfosuccinate is dissolved in a solvent such as water or ethanol to form a solution. The solution is added while spraying or all at once, and a powder obtained by mixing light caustic anhydride and, if necessary, magnesium stearate is granulated to obtain a powder.
得られた粉体に、 必要があれば通常の医薬品製造に使用される他の薬効成分、 添加剤などを加え、 常法により、 混合、 粉砕、 造粒等の工程を経て、 顆粒剤、 錠 剤などの形態の核粒子を得ることができる。 '  If necessary, add other medicinal ingredients and additives used in normal pharmaceutical manufacturing to the obtained powder, and mix, pulverize, granulate, etc., in the usual manner, and then granules and tablets A core particle in the form of an agent or the like can be obtained. '
本発明の核粒子は錠剤とすることもできるが、 一般的に錠剤を製造する際に滑 沢剤であるステアリン酸マグネシウムを高濃度で配合すると、 得られた錠剤は物 性が低いことが知られている。 しかし、 本発明ではステアリン酸マグネシウムを 粉体中に練り込むことにより、 造粒後に打錠した際にもその錠剤物性、 特に崩壊 性や錠剤硬度が低下すること無く配合することができる。 したがって腸溶性被膜 を施したフィルム綻剤も優れた物性のものを得ることができる。 図面の簡単な説明 第 1図は、 実施例および比較例の溶出性試験の結果を示した図であり、 縦軸に溶 出率、 横軸に時間および p Hを示した。 発明を実施するための最良の形態 Although the core particles of the present invention can be made into tablets, it is generally known that when a tablet is produced by mixing a high concentration of magnesium stearate as a lubricant, the obtained tablets have low physical properties. Have been. However, in the present invention, the magnesium stearate is kneaded into the powder, so that the tablet can be blended without reducing the physical properties of the tablet, particularly the disintegration and the tablet hardness, even after tableting after granulation. Therefore, a film breaker coated with an enteric coating can also have excellent physical properties. BRIEF DESCRIPTION OF THE FIGURES FIG. 1 is a diagram showing the results of a dissolution test of Examples and Comparative Examples, in which the vertical axis represents the dissolution rate, and the horizontal axis represents time and pH. BEST MODE FOR CARRYING OUT THE INVENTION
以下、 実施例、 比較例および試験例により本発明をさらに詳細に説明する。 実施例 1  Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples. Example 1
[内核錠の製造]  [Manufacture of core tablets]
ピサコジル 6 0 0 g、乳糖 1 2 4 8 g、 ヒドロキシプロピルセル口一ス 6 3 2 g、 低置換度ヒドロキシプロピルセルロース 9 3 2 gおよび軽質無水ゲイ酸 1 2 0 gを混合して得られた粉体に、 精製水を造粒溶媒として攪拌造粒し乾燥し 顆粒 Aとした。  It was obtained by mixing 600 g of pisacodyl, 124 488 g of lactose, 632 g of hydroxypropyl cellulose, 9332 g of low-substituted hydroxypropylcellulose and 120 g of light gay anhydride. The powder was stirred and granulated using purified water as a granulating solvent, and dried to obtain granules A.
次にジォクチルソジゥムスルホサクシネート 9 6 0 gおよびヒドロキシプロ ピルセル口一ズ 2 0 0 gをアルコールに溶解し、軽質無水ケィ酸 9 6 0 g ステ ァリン酸マグネシウム 2 8 8 gの混合粉体と共に練合造粒を行い、乾燥、整粒後、 顆粒 Bを得た。 顆粒 A、 顆粒 B、 ステアリン酸マグネシウム 3 0 gおよび軽質無 水ケィ酸 3 0 gを添加して混合した。 得られた顆粒を打錠して、 錠径 5 mm、 1錠 重量 5 O mgの錠剤を得た。 これを核粒子とした。  Next, 960 g of dioctylsodium sulfosuccinate and 200 g of hydroxypropylcellulose were dissolved in alcohol, and mixed with 960 g of light caustic anhydride and 288 g of magnesium stearate. After kneading and granulating with the powder, drying and sizing, granules B were obtained. Granule A, Granule B, 30 g of magnesium stearate and 30 g of light anhydrous calcium acid were added and mixed. The obtained granules were tableted to give tablets having a tablet diameter of 5 mm and a tablet weight of 5 O mg. This was used as a nuclear particle.
[腸溶性被膜の製造]  [Manufacture of enteric coating]
タルク 1 6 7 g、クェン酸トリェチル 3 1 g、メタクリル酸コポリマ一（S、 L混合物） 3 3 5 gおよびヒドロキシプロピルセル口一ス 6 7 gをアルコールに 分散溶解させた。 コーティング装置に内核錠を入れ、 腸溶性被膜液をスプレーコ 一ティングし、 1錠当たり約 1 O m gまで腸溶性被膜層を施し本発明の固形製剤 を得た。 比較例  167 g of talc, 31 g of triethyl citrate, 33 g of methacrylic acid copolymer (a mixture of S and L) and 67 g of hydroxypropyl cell mouth were dispersed and dissolved in alcohol. The core tablet was placed in the coating apparatus, and the enteric coating solution was spray-coated, and the enteric coating layer was applied to about 1 Omg per tablet to obtain the solid preparation of the present invention. Comparative example
実施例 1と同様にして製造した核粒子の錠剤を比較例として用いた。 試験例 1  A core particle tablet produced in the same manner as in Example 1 was used as a comparative example. Test example 1
実施例および比較例で得られた製剤を、 日局溶出試験法第 3法フロースルーセ ル法にて、 溶出試験液の p Hを 1. 2、 6. 5 5、 7. 2 1、 6. 7 1に変化さ せ、 経時的にサンプリングし、 H P L Cにてジォクチルソジゥムスルホサクシネ ートを定量し、 溶出率を求めた。 その結果を図 1に示した。 The preparations obtained in Examples and Comparative Examples were used for The pH of the dissolution test solution was changed to 1.2, 6.55, 7.21, and 6.71 by the HPLC method, samples were taken over time, and octylsodium was analyzed by HPLC. Sulfosuccinate was quantified and the elution rate was determined. The results are shown in FIG.
図 1から明らかなように、 実施例 1より、 ジォクチルソジゥムスルホサクシネ 一トは胃内を想定した低い PHでは溶出せず、 PH7. 2 1の小腸下部で溶出を 開始し、 比較例に比べて、 より作用部位に近いところで放出させることができる ことが判った。 試験例 2  As is clear from FIG. 1, from Example 1, dioctylsodium sulfosuccinate was not eluted at a low PH assumed in the stomach, but started to elute in the lower intestine of PH7.21. It was found that the drug could be released closer to the site of action than in the comparative example. Test example 2
以下の方法により、 ピサコジルとジォクチルソジゥムスルホサクシネ一トを同 時配合した際の溶解性を測定した。  The solubility of pisacodyl and dioctylsodium sulfosuccinate at the same time was measured by the following method.
ビザコジルを精製水に分散させ、 一定条件下で 5時間振とうさせた液を SOOOmin"1, 5minの条件にて遠心分離した。 その後、 上澄液を採取し HPLCにてビ サコジル含量を定量した。 Bizakojiru dispersed in purified water and centrifuged a solution was shaken for 5 hours under constant conditions at SOOOmin "1, 5min condition. Then, to quantify the collected HPLC Nitebi Sakojiru content supernatant .
同様にして、 濃度が 0.07%、 0.14%、 0.35%となるようにジォクチルソジゥム スルホサクシネートを添加した溶液にピサコジルを分散させ、 5時間振とうさせ た液を 3000min— 5minの条件にて遠心分離した。 その後、 上澄液を採取し HPLC にてビザコジル含量を定量した。 結果を表 1に示した。  Similarly, disperse pisacodyl in a solution containing dioctylsodium sulfosuccinate at a concentration of 0.07%, 0.14%, and 0.35%, and shake for 5 hours. Was centrifuged. Thereafter, the supernatant was collected and the content of visacodyl was determined by HPLC. The results are shown in Table 1.
表 1  table 1
Figure imgf000006_0001
Figure imgf000006_0001
DSS:ジォクチルソジゥムスルホサクシネート 表から明らかなように ホサクシネー卜が共存すること によりピサコジルの溶解度が大幅に向上することがわかった。 産業上の利用可能性 DSS: Dioctyl sodium sulfosuccinate Coexistence of hosuccinate as evident from the table Showed that the solubility of pisacodyl was significantly improved. Industrial applicability
本発明によりジォクチルソジゥムスルホサクシネートを作用部位である大腸近 位に効率的に放出させることが可能になったので、 効果的な瀉下薬として有用で ある。  INDUSTRIAL APPLICABILITY The present invention makes it possible to efficiently release dioctylsodium sulfosuccinate into the vicinity of the large intestine, which is the site of action, and is therefore useful as an effective laxative.

Claims

請求の範囲 The scope of the claims
1 . ジォクチルソジゥムスルホサクシネートおよび軽質無水ゲイ酸を含む核粒子 に、 腸溶性被膜が施されていることを特徴とする固形製剤。 1. A solid preparation, characterized in that core particles containing dioctylsodium sulfosuccinate and light gay anhydride are provided with an enteric coating.
2 . 核粒子中に、 さらにビザコジルを含むことを特徴とする 1記載の固形製剤。 2. The solid preparation according to 1, wherein the core particle further contains visacodyl.
3 . 核粒子中に、 さらにステアリン酸マグネシウムを含む 1 または 2に記載の固 形製剤。 3. The solid preparation according to 1 or 2, further comprising magnesium stearate in the core particles.
4 . 腸溶性被膜の被覆量が、 核粒子の質量に対して 1〜 3 0質量％である 1〜 3 のいずれかに記載の固形製剤。 4. The solid preparation according to any one of 1 to 3, wherein the coating amount of the enteric coating is 1 to 30% by mass based on the mass of the core particles.
5 . 腸溶性被膜が、 メタクリル酸コポリマー L、 メタクリル酸コポリマー S、 メ タクリル酸コポリマー L D、 ヒドロキシプロピルメチルセルロースフタレート、 ヒドロキシプロピルメチルセルロースァセテ一トサクシネート、 カルポキシメチ ルェチルセルロースおよび酢酸フタル酸セルロースから選ばれる少なくとも 1種 である 1〜4のいずれかに記載の固形製剤。 5. The enteric coating is at least one selected from methacrylic acid copolymer L, methacrylic acid copolymer S, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose and cellulose acetate phthalate. The solid preparation according to any one of 1 to 4, which is a species.
6 . ジォクチルソジゥムスルホサクシネート 1質量部に対する軽質無水ケィ酸の 配合量が 0 . 5〜 1 . 5質量部である 1〜 5のいずれかに記載の固形製剤。 6. The solid preparation according to any one of 1 to 5, wherein the blending amount of light caustic anhydride is 0.5 to 1.5 parts by mass with respect to 1 part by mass of dioctylsodium sulfosuccinate.
7 . ジォクチルソジゥムスルホサクシネート 1質量部に対するステアリン酸マグ ネシゥムの配合量が 0 . 0 5〜 0 . 5質量部である 1〜 6のいずれかに記載の固形 製剤。 7. The solid preparation according to any one of 1 to 6, wherein the amount of magnesium stearate is 0.05 to 0.5 part by mass relative to 1 part by mass of dioctylsodium sulfosuccinate.
8 . ジォクチルソジゥムスルホサクシネートを製剤全体の 1 0質量％以上配合し たことを特徴とする 1〜 7のいずれかに記載の固形製剤。 8. The solid preparation according to any one of 1 to 7, wherein dioctyl sodizulfosuccinate is incorporated in an amount of 10% by mass or more of the whole preparation.
9 . ジォクチルソジゥムスルホサクシネートを配合した溶液を用いて、 軽質無水 ケィ酸を配合した粉体を造粒した顆粒を含む核粒子に、 腸溶性被膜が施されてい ることを特徴とする固形製剤。 9. The core particles, including the granules obtained by granulating a powder containing light caustic anhydride, using a solution containing dioctylsodium sulfosuccinate, are coated with an enteric coating. Solid preparation.
1 0 . ジォクチルソジゥムスルホサクシネートを配合した溶液を用いて、 軽質無 水ゲイ酸を配合した粉体を造粒し、 得られた顆粒を含む核粒子に対して、 腸溶性 被膜を施すことを特徴とする固形製剤の製造方法。 10. Using a solution containing dioctylsodium sulfosuccinate, granulate a powder containing light anhydrous anhydrous genoic acid, and apply an enteric coating to the core particles containing the obtained granules. A method for producing a solid preparation, comprising:
PCT/JP2003/011585 2002-09-10 2003-09-10 Solid preparation containing dioctyl sodium sulfosuccinate WO2004024138A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007055969A (en) * 2005-08-26 2007-03-08 Taisho Pharmaceut Co Ltd Bisacodyl dissolution-improving agent
JP2012514624A (en) * 2009-01-09 2012-06-28 フォーワード・ファルマ・アクティーゼルスカブ Pharmaceutical formulations comprising one or more fumarate esters in an erosion matrix

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5799521A (en) * 1980-12-11 1982-06-21 Eisai Co Ltd Solid composition containing bisacodyl
JPH02255613A (en) * 1989-03-27 1990-10-16 Lion Corp Pharmaceutical containing dioctyl sodium sulfosuccinate blended therein
US5843479A (en) * 1993-02-26 1998-12-01 The Procter & Gamble Company Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5799521A (en) * 1980-12-11 1982-06-21 Eisai Co Ltd Solid composition containing bisacodyl
JPH02255613A (en) * 1989-03-27 1990-10-16 Lion Corp Pharmaceutical containing dioctyl sodium sulfosuccinate blended therein
US5843479A (en) * 1993-02-26 1998-12-01 The Procter & Gamble Company Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007055969A (en) * 2005-08-26 2007-03-08 Taisho Pharmaceut Co Ltd Bisacodyl dissolution-improving agent
JP2012514624A (en) * 2009-01-09 2012-06-28 フォーワード・ファルマ・アクティーゼルスカブ Pharmaceutical formulations comprising one or more fumarate esters in an erosion matrix
US11173123B2 (en) 2009-01-09 2021-11-16 Biogen Swiss Manufacturing Gmbh Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix

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