JP3241162B2 - Sustained-release suppositories - Google Patents
Sustained-release suppositoriesInfo
- Publication number
- JP3241162B2 JP3241162B2 JP11106193A JP11106193A JP3241162B2 JP 3241162 B2 JP3241162 B2 JP 3241162B2 JP 11106193 A JP11106193 A JP 11106193A JP 11106193 A JP11106193 A JP 11106193A JP 3241162 B2 JP3241162 B2 JP 3241162B2
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- Japan
- Prior art keywords
- hlb
- fatty acid
- acid ester
- suppositories
- sustained
- 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.)
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Description
【０００１】[0001]
【産業上の利用分野】本発明は医薬製剤、特に徐放性坐
剤の分野に関する。FIELD OF THE INVENTION The present invention relates to the field of pharmaceutical preparations, especially sustained release suppositories.
【０００２】[0002]
【従来の技術】坐剤は、その投与経路からして生体内で
の薬物の分解率が低く、しかも食事の影響を受けないこ
と、および小児や老人のみならず経口投与が困難な患者
にも比較的容易に投与できること、等の理由により頻繁
に利用されている。しかし、一方では、薬物を直腸投与
するとき、急激な血漿中濃度の立ち上がりによる副作用
発現の危険性や日に何回も投与することの困難性といっ
た欠点が指摘されている。このような欠点は坐剤を徐放
化することにより解決されるとして、従来から種々の試
みがなされている。一般に坐剤は、特定の製剤化成分
（徐放化成分ということもある）を配合することにより
徐放化されている。2. Description of the Related Art Suppositories have a low rate of decomposition of drugs in vivo due to the route of administration, and are not affected by diet, and are suitable not only for children and the elderly but also for patients who are difficult to administer orally. It is frequently used because it can be administered relatively easily. However, on the other hand, it has been pointed out that when a drug is administered rectally, there is a danger that side effects occur due to a sudden rise in plasma concentration and that it is difficult to administer the drug many times a day. Various attempts have hitherto been made assuming that such disadvantages can be solved by sustained release of suppositories. In general, suppositories are controlled-release by incorporating a specific formulation component (sometimes referred to as a sustained-release component).
【０００３】しかし、ほとんどの徐放化成分は、油性基
剤とともに加熱しても、共に溶融せず、分散した状態に
なる。従って、全製造工程において、徐放化成分が油性
基剤中に均一に分散するように配慮しなければ、徐放化
成分の局在化がおこり、ひいては製造ロット間において
徐放化の程度に差が生じることがある。[0003] However, most of the sustained-release components, even when heated together with the oleaginous base, do not melt together and are in a dispersed state. Therefore, in all the manufacturing steps, unless care is taken to disperse the sustained-release component uniformly in the oily base, localization of the sustained-release component occurs, and thus the degree of sustained release between production lots. Differences may occur.
【０００４】[0004]
【発明が解決しようとする課題】本発明が解決しようと
する課題は、油性基剤とともに加熱した場合、ともに溶
融して均一な系となり、しかも徐放効果にすぐれ、生体
にとって安全で粘膜を刺激せず、そして目的とする坐剤
の製造工程を複雑化しない新規な徐放化成分を見出すこ
とにある。The problem to be solved by the present invention is that when heated together with an oily base, the two melt together to form a uniform system, and have excellent sustained release effects, are safe for living organisms and stimulate mucous membranes. An object of the present invention is to find a new sustained-release component which does not complicate the production process of the intended suppository.
【０００５】[0005]
【課題を解決するための手段】本発明者らは坐剤の徐放
化を図る為の成分として、ＨＬＢが８以下のポリグリセ
リン脂肪酸エステルを選択すれば、前記課題が解決しう
る、との知見を得て本発明を完成した。Means for Solving the Problems The present inventors can solve the above-mentioned problems by selecting a polyglycerol fatty acid ester having an HLB of 8 or less as a component for sustained release of a suppository. The present invention has been completed based on the findings.
【０００６】本発明は、薬物とＨＬＢが８以下のポリグ
リセリン脂肪酸エステルおよび油性基剤からなる徐放性
坐剤に関する。The present invention relates to a sustained release suppository comprising a drug, a polyglycerol fatty acid ester having an HLB of 8 or less, and an oily base.
【０００７】ポリグリセリン脂肪酸エステルは、グリセ
リンの脱水縮合により形成されたポリグリセリンとステ
アリン酸の如き脂肪酸とのエステル化物であり、今まで
坐剤における製剤化成分のひとつとして用いられたこと
はない。[0007] Polyglycerin fatty acid ester is an esterified product of polyglycerin formed by dehydration condensation of glycerin and a fatty acid such as stearic acid, and has never been used as one of the components formulated in suppositories.
【０００８】本発明における徐放化成分たるポリグリセ
リン脂肪酸エステルとしては、ＨＬＢが８以下のものな
らばいずれでもよいが、好ましくは６以下、特に好まし
くは２〜５のものが使用される。ＨＬＢがこの範囲を逸
脱するときは、後記試験例（図１）に示すように徐放化
が図れない。The polyglycerol fatty acid ester as the sustained-release component in the present invention may be any one having an HLB of 8 or less, preferably 6 or less, particularly preferably 2 to 5 HLB. When the HLB is out of this range, sustained release cannot be achieved as shown in the test example (FIG. 1) described later.
【０００９】ポリグリセリン脂肪酸エステルの構造から
いえば、４〜１０個のグリセリン残基ならびに３〜１０
個のステアリン酸残基から構成されるものが好ましく用
いられる。具体的には、日光ケミカルズ株式会社から市
販されているテトラグリセリルトリステアレート（ＨＬ
Ｂ＝約４）、テトラグリセリルペンタステアレート（Ｈ
ＬＢ＝約２）、ヘキサグリセリルトリステアレート（Ｈ
ＬＢ＝約６）、ヘキサグリセリルペンタステアレート
（ＨＬＢ＝約３）、デカグリセリルトリステアレート
（ＨＬＢ＝約８）、デカグリセリルペンタステアレート
（ＨＬＢ＝約５）、デカグリセリルヘプタステアレート
（ＨＬＢ＝約４）、デカグリセリルデカステアレート
（ＨＬＢ＝約３）などが挙げられ、なかでもテトラグリ
セリルペンタステアレート、ヘキサグリセリルペンタス
テアレート、デカグリセリルヘプタステアレート、デカ
グリセリルデカステアレートが特に好適である。In terms of the structure of the polyglycerol fatty acid ester, 4 to 10 glycerin residues and 3 to 10
Those composed of two stearic acid residues are preferably used. Specifically, tetraglyceryl tristearate (HL) commercially available from Nikko Chemicals Co., Ltd.
B = about 4), tetraglyceryl pentastearate (H
LB = about 2), hexaglyceryl tristearate (H
LB = about 6), hexaglyceryl pentastearate (HLB = about 3), decaglyceryl tristearate (HLB = about 8), decaglyceryl pentastearate (HLB = about 5), decaglyceryl heptastearate (HLB = About 4), decaglyceryl decastearate (HLB = about 3), among which tetraglyceryl pentastearate, hexaglyceryl pentastearate, decaglyceryl heptastearate, and decaglyceryl decastearate are particularly preferred. .
【００１０】薬物は、水可溶性、水難溶性、そのほかい
ずれの性質を有するものでもよく、その種類は特に限定
されない。[0010] The drug may be water-soluble, hardly water-soluble, or any other property, and the type thereof is not particularly limited.
【００１１】また、油性基剤の種類も、薬物と同様に特
に限定されず、従来から使用されているものがいずれも
使用可能である。油性基剤としては、例えば、高級脂肪
酸エステルトリグリセリド／ジグリセリド／モノグリセ
リドの混合物〔例えば各種のウィテプゾール（ヒュルツ
社）、各種のノバタ（ヘンケル社）、各種のファーマゾ
ール（日本油脂）、イソカカオ（花王）〕や中鎖脂肪酸
エステルトリグリセライド〔例えば、ミグリオール（ダ
イナマイトノーベル社）〕、グリセリン脂肪酸エステ
ル、カカオ脂、硬化油、トウモロコシ油、流動パラフィ
ン、ワセリン等があげられる。これらの油性基剤は単独
もしくは混合物の形で用いられる。The type of the oily base is not particularly limited as well as the drug, and any of those conventionally used can be used. As the oily base, for example, a mixture of higher fatty acid ester triglyceride / diglyceride / monoglyceride [for example, various Witepsol (Hurz), various Novata (Henkel), various pharmazole (Nippon Yushi), isokacao (Kao)] And medium-chain fatty acid ester triglycerides (eg, Miglyol (Dynamite Nobel)), glycerin fatty acid ester, cocoa butter, hardened oil, corn oil, liquid paraffin, petrolatum, and the like. These oily bases are used alone or in the form of a mixture.
【００１２】このほか酸化防止剤、吸収促進剤、粘膜保
護剤などの補助成分が必要に応じて配合される。[0012] In addition, auxiliary components such as antioxidants, absorption promoters, and mucosal protective agents may be added as necessary.
【００１３】本発明の坐剤は、油性基剤およびＨＬＢが
８以下であるポリグリセリン脂肪酸エステルからなる混
合物を加熱して均一な溶融物を得、これに薬物を溶解も
しくは分散し、所定のコンテナに充填し、冷却すること
により製造できる。加熱温度は８０℃以下、通常は６０
〜７０℃である。本発明の坐剤において、ポリグリセリ
ン脂肪酸エステルは５０重量％以下、好ましくは５−４
０重量％、特に好ましくは１０−３０重量％を占め、薬
物は２５重量％以下を占め、残余を油性基剤やほかの補
助成分が占めることになる。[0013] The suppository of the present invention is obtained by heating a mixture of an oily base and a polyglycerol fatty acid ester having an HLB of 8 or less to obtain a uniform melt, and dissolving or dispersing the drug in the melt. And cooled. Heating temperature is 80 ° C or less, usually 60
７０70 ° C. In the suppository of the present invention, the polyglycerin fatty acid ester is 50% by weight or less, preferably 5-4% by weight.
It will comprise 0% by weight, particularly preferably 10-30% by weight, the drug will comprise up to 25% by weight and the remainder will be made up of oily bases and other auxiliary ingredients.
【００１４】[0014]
【実施例】以下に実施例および比較例をあげて本発明を
更に詳細に説明する。The present invention will be described in more detail with reference to the following Examples and Comparative Examples.
【００１５】実施例 １： 処方−； ジクロフェナクナトリウム ２５ ｍｇ ヘキサグリセリルペンタステアレート(HLB= 約３) １７５ ｍｇ ウィテプゾールＨ−１５ ８７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；ポリグリセリン脂肪酸エステルと油性基剤を６
０−７０℃で溶融し、ジクロフェナクナトリウムを分散
させ、これを坐剤用コンテナに充填し、冷却して坐剤を
得た。 Example 1 : Formulation: Diclofenac sodium 25 mg Hexaglyceryl pentastearate (HLB = about 3) 175 mg Withepsol H-15 875 mg ────────────── Total 1000 mg Production method; 6 parts of polyglycerin fatty acid ester and oily base
It was melted at 0-70 ° C. to disperse diclofenac sodium, filled in a suppository container, and cooled to obtain a suppository.
【００１６】実施例 ２： 処方−； ジクロフェナクナトリウム ２５ ｍｇ ヘキサグリセリルペンタステアレート(HLB= 約３) ２５０ ｍｇ ウィテプゾールＨ−１５ ７２５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 2 : Formulation: Diclofenac sodium 25 mg Hexaglyceryl pentastearate (HLB = about 3) 250 mg Witepsol H-15 725 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００１７】実施例 ３： 処方−； ジクロフェナクナトリウム ２５ ｍｇ ヘキサグリセリルペンタステアレート(HLB= 約３) ３００ ｍｇ ウィテプゾールＨ−１５ ６７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 3 : Formulation: Diclofenac sodium 25 mg Hexaglyceryl pentastearate (HLB = about 3) 300 mg Withepsol H-15 675 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００１８】実施例 ４： 処方−； ジクロフェナクナトリウム ２５ ｍｇ テトラグリセリルペンタステアレート(HLB= 約２) １５０ ｍｇ ウィテプゾールＷ−３５ ８２５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 4 : Formulation: diclofenac sodium 25 mg tetraglyceryl pentastearate (HLB = about 2) 150 mg witepsol W-35 825 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００１９】実施例 ５： 処方−； ジクロフェナクナトリウム ２５ ｍｇ デカグリセリルデカステアレート(HLB= 約３) ２００ ｍｇ ウィテプゾールＳ−５５ ７７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 5 : Formulation: diclofenac sodium 25 mg decaglyceryl decastearate (HLB = about 3) 200 mg withepsol S-55 775 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２０】実施例 ６： 処方−； ジクロフェナクナトリウム ２５ ｍｇ デカグリセリルヘプタステアレート(HLB= 約４) １００ ｍｇ ウィテプゾールＨ−１５ ８７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 6 : Formulation: diclofenac sodium 25 mg decaglyceryl heptastearate (HLB = about 4) 100 mg withepsol H-15 875 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２１】実施例 ７： 処方−； ジクロフェナクナトリウム ２５ ｍｇ デカグリセリルヘプタステアレート(HLB= 約４) １５０ ｍｇ ウィテプゾールＨ−１５ ８２５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Example 7 : Formulation: diclofenac sodium 25 mg decaglyceryl heptastearate (HLB = about 4) 150 mg withepsol H-15 825 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２２】比較例 Ａ： 処方−； ジクロフェナクナトリウム ２５ ｍｇ ウィテプゾールＨ−１５ ９７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Comparative Example A : Formulation; diclofenac sodium 25 mg withepsol H-15 975 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２３】比較例 Ｂ： 処方−； ジクロフェナクナトリウム ２５ ｍｇ ヘキサグリセリルモノステアレート(HLB= 約11） １５０ ｍｇ ウィテプゾールＨ−１５ ８７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Comparative Example B : Formulation-Diclofenac sodium 25 mg Hexaglyceryl monostearate (HLB = about 11) 150 mg Witepsol H-15 875 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２４】比較例 Ｃ： 処方−； ジクロフェナクナトリウム ２５ ｍｇ デカグリセリルモノステアレート(HLB= 約14) １５０ ｍｇ ウィテプゾールＨ−１５ ８７５ ｍｇ ─────────────────────────────── 計 １０００ ｍｇ 製法−；実施例１と同様にして坐剤を得た。 Comparative Example C : Formulation-Diclofenac sodium 25 mg Decaglyceryl monostearate (HLB = about 14) 150 mg Witepsol H-15 875 mg計 Total 1000 mg Production method; suppositories were obtained in the same manner as in Example 1.
【００２５】[0025]
【発明の効果】本発明の坐剤は、徐放化成分たるポリグ
リセリン脂肪酸エステルの局在化がみられず、製造ロッ
ト間における徐放化効果に変動が少なく、しかも、生体
にとって安全で粘膜を刺激せず、さらには、徐放化成分
の添加量を変化すれば徐放化の程度が調節できる。そし
て、本発明の坐剤の製造方法は、簡便であり、特定の徐
放化成分を採用することにより製造工程が複雑化しな
い。以下に実験例をあげて本発明の坐剤の徐放化効果に
ついて説明する。EFFECT OF THE INVENTION The suppository of the present invention shows no localization of the polyglycerin fatty acid ester as a sustained-release component, little variation in the sustained-release effect between production lots, and is safe for living organisms and Is not stimulated, and the degree of sustained release can be adjusted by changing the amount of the sustained release component added. The method for producing a suppository of the present invention is simple and does not complicate the production process by employing a specific sustained-release component. Hereinafter, the sustained release effect of the suppository of the present invention will be described with reference to experimental examples.
【００２６】試験例：実施例１〜３および比較例Ａ、Ｂ
およびＣの坐剤からのジクロフェナクナトリウムの放出
試験をＰＴＳＷ型坐剤放出試験器（回転セル法）を用い
て行った。放出相溶液は０．０２Ｍリン酸緩衝液（ｐＨ
７．４）を９００ｍｌ用い、セルの回転速度は２５ｒｐ
ｍであり、温度は３７℃とした。その結果を図１に示
す。図１からも明かなようにＨＬＢが８以下のポリグリ
セリン脂肪酸エステルの配合により坐剤からの薬物放出
は添加量に応じて抑制された（実施例１〜３）。一方、
ポリグリセリン脂肪酸エステルを含有していない比較例
Ａの坐剤やＨＬＢが８以上のポリグリセリン脂肪酸エス
テルを配合した比較例Ｂ、Ｃの坐剤は徐放化されていな
い。 Test Examples : Examples 1-3 and Comparative Examples A and B
The release test of diclofenac sodium from the suppositories of Examples A and C was performed using a PTSW type suppository release tester (rotating cell method). The release phase solution was 0.02M phosphate buffer (pH
Use 7.4 ml of 7.4) and rotate the cell at 25 rpm
m and the temperature was 37 ° C. The result is shown in FIG. As is clear from FIG. 1, the release of the drug from the suppository was suppressed according to the amount of the addition of the polyglycerol fatty acid ester having an HLB of 8 or less (Examples 1 to 3). on the other hand,
The suppository of Comparative Example A containing no polyglycerin fatty acid ester and the suppositories of Comparative Examples B and C containing a polyglycerin fatty acid ester having an HLB of 8 or more were not sustained-released.
【００２７】[0027]
【図１】図１は坐剤からのジクロフェナクナトリウムの
溶出パターンを示す。FIG. 1 shows the elution pattern of diclofenac sodium from suppositories.
フロントページの続き (72)発明者 中村 康彦 兵庫県宝塚市中山桜台２丁目５番７号 (56)参考文献 特開 昭61−85332（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 47/14,9/02 Continuation of front page (72) Inventor Yasuhiko Nakamura 2-57-7 Nakayama Sakuradai, Takarazuka-shi, Hyogo (56) References JP-A-61-85332 (JP, A) (58) Fields investigated (Int. Cl. 7 , DB name) A61K 47/14, 9/02
Claims (4)
脂肪酸エステル（但し、ポリグリセリン脂肪酸モノエス
テルを除く）および油性基剤からなる徐放性坐剤。Claims: 1. A drug and a polyglycerin fatty acid ester having an HLB of 6 or less (however, polyglycerin fatty acid monoester).
Sustained- release suppositories consisting of telomer ) and an oily base.
ステアリン酸エステル（但し、ポリグリセリンステアリ
ン酸モノエステルを除く）および油性基剤からなる徐放
性坐剤。 2. A drug and a polyglycerin having an HLB of 8 or less.
Stearic acid ester (however, polyglycerin stearyl
(Excluding acid monoester) and oily base
Sex suppositories.
０個のグリセリン残基ならびに３〜１０個のステアリン
酸残基からなる請求項１または２記載の坐剤。3. The method according to claim 1, wherein the polyglycerol fatty acid ester is 4-1.
3. The suppository according to claim 1, which comprises 0 glycerin residues and 3 to 10 stearic acid residues.
リグリセリン脂肪酸エステル（但し、ポリグリセリン脂
肪酸モノエステルを除く）からなる混合物を加熱して均
一な溶融物を得、これに薬物を溶解もしくは分散し、所
定のコンテナに充填し、冷却することを特徴とする徐放
性坐剤の製造方法。4. An oily base and a polyglycerin fatty acid ester having an HLB of 6 or less (provided that polyglycerin
(Excluding fatty acid monoester) is heated to obtain a homogeneous melt, in which the drug is dissolved or dispersed, filled in a predetermined container, and cooled, Production method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11106193A JP3241162B2 (en) | 1993-04-13 | 1993-04-13 | Sustained-release suppositories |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11106193A JP3241162B2 (en) | 1993-04-13 | 1993-04-13 | Sustained-release suppositories |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06298667A JPH06298667A (en) | 1994-10-25 |
| JP3241162B2 true JP3241162B2 (en) | 2001-12-25 |
Family
ID=14551415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11106193A Expired - Fee Related JP3241162B2 (en) | 1993-04-13 | 1993-04-13 | Sustained-release suppositories |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3241162B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3420540B2 (en) * | 1999-01-29 | 2003-06-23 | 天藤製薬株式会社 | Suppository base and suppository |
| JP2001048809A (en) * | 1999-08-10 | 2001-02-20 | Dainippon Pharmaceut Co Ltd | Sustained release suppository containing polyglyceryl behenate |
| JP2005314241A (en) * | 2004-04-27 | 2005-11-10 | Tendou Seiyaku Kk | Suppository base controlling occurrence of crack/fragment and method for producing the same |
-
1993
- 1993-04-13 JP JP11106193A patent/JP3241162B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06298667A (en) | 1994-10-25 |
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