JP4480206B2

JP4480206B2 - Oil and fat-containing sustained release suppositories

Info

Publication number: JP4480206B2
Application number: JP22615299A
Authority: JP
Inventors: 敏仁鷹取; 正昭森
Original assignee: Sumitomo Dainippon Pharma Co Ltd
Current assignee: Sumitomo Pharma Co Ltd
Priority date: 1999-08-10
Filing date: 1999-08-10
Publication date: 2010-06-16
Anticipated expiration: 2019-08-10
Also published as: JP2001048778A

Description

【０００１】
【発明の属する技術分野】
本発明は医薬製剤、特に油性基剤の融点を変化させることの少ない高融点の油脂成分を含有する徐放性坐剤に関する。
【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。
【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。
【０００４】
特開平６−２９８６６７号公報には、ポリグリセリン脂肪酸エステルと油性基剤の混合物が徐放性を有し、油性基剤として硬化油およびグリセリン脂肪酸エステルが例示されているが、これらは単独で徐放化を促進させることを示唆する記述は全くない。また、特開平９−２０６８６号公報および特開平９−５２８４７号公報には、硬化油を配合した経口投与を目的とした徐放性製剤が記載されているが、硬化油を徐放化剤として坐剤に使用しているとの記述はない。
【０００５】
【発明が解決しようとする課題】
油性基剤中に均一に分散もしくは混合可能な徐放化成分、即ち、高融点の油脂成分を油性基剤に配合する方法が考えられるが、その場合、通常、高融点の油脂成分を配合することによって油性基剤の融点が上昇し、そのために体温で油性基剤を融解させることが困難になり、その結果、患者に坐剤を投与しても安定した徐放性を示さないことが一般に知られている。
【０００６】
【課題を解決するための手段】
そこで、本発明者らは油性基剤の融点をほとんど変えずに目的の徐放化を達成するために配合する油脂成分の特性について種々検討した結果、高融点の特定の油脂成分を用いれば、油性基剤の融点をほとんど変化させずに目的とする徐放性を示す徐放性坐剤が得られることを見いだし、本発明を完成した。
【０００７】
本発明によれば、主薬成分である薬物および油性基剤並びに該油性基剤の融点を変化させることが少ない高融点の油脂成分を含有する徐放性坐剤が提供される。
【０００８】
「油性基剤の融点を変化させることが少ない高融点の油脂成分」とは、油性基剤に一定量加えても該油性基剤の融点がほとんど変化しないような、単独での融点が約５５℃以上であり、油性基剤と均一に混和し、混合物は該油性基剤の融点（第１融点）と油脂成分の融点（第２融点）の２つの融点が観察される油脂成分を意味する。このとき、第１融点は該油性基剤の融点からほとんど変化せず、第２融点は第１融点よりも約１０℃以上高い所になだらかな融点として認められる。このような性質を示す油脂成分としては、例えば硬化ヒマシ油（融点約８０℃），硬化綿実油（融点約６９℃），硬化ヤシ油（融点約５９℃），硬化ダイズ油（融点約６８℃）などの硬化油、ミツロウ（融点約６０〜約６７℃）、カルナウバロウ（融点約８０〜約８６℃）、グリセリン脂肪酸エステル（融点約６９℃）、ソルビタン脂肪酸エステル（融点約５９℃）、マイクロクリスタリンワックス（融点約５８〜約９８℃）が挙げられる。このような性質を有する油脂成分であれば目的とする徐放性を達成することができ、本発明に用いられる油性基剤の融点を変化させることが少ない高融点の油脂成分（以下、「本発明に用いられる油脂成分」と称することもある）に含まれる。油脂成分の融点は約６０℃以上が好ましく、硬化油の硬化ヒマシ油は特に融点が高く（融点約８０℃）、少量で硬化が期待できるので特に好ましい。また、ミツロウ（融点約６０〜約６７℃）も別の好ましい油脂成分である。
【０００９】
前記の硬化ヒマシ油としては、例えば、ラブリワックス１０１（フロイント産業）、カスターワックスＡ（日本油脂）、ヒマシ硬化油ＦＣ−９０８（川研ファインケミカル）が挙げられる。
【００１０】
前記のミツロウとしては、例えば、脱臭紺印晒ミツロウ、紺印晒ミツロウ、精製ミツロウ（三木化学工業）、晒ミツロウ（野田ワックス）が挙げられる。
【００１１】
本発明に用いられる薬物は、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が、例えば、麻薬性鎮痛剤の塩酸モルヒネ、硫酸モルヒネ、合成麻薬性鎮痛剤の塩酸ペチジン、非麻薬性鎮痛剤のペンタゾシン、臭化水素酸エプタゾシン、塩酸ブプレノルフィン、モルヒネ関連化合物である鎮咳剤のリン酸コデイン、リン酸ジヒドロコデイン、麻薬拮抗剤の塩酸ナロキソン、非ステロイド性抗炎症薬のアセトアミノフェン、ジクロフェナックナトリウムが挙げられる。上記薬物の中で坐剤成分としてよく使われる塩酸モルヒネおよび硫酸モルヒネが好ましい。本発明の坐剤における薬物の含量は、通常、約１５％以下であるが、約１〜１０重量％が好ましく、約２〜約５重量％が特に好ましい。
【００１２】
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）〕、カカオ脂等が挙げられる。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。これらの油性基剤は、坐剤の基剤としての性質からして通常体温付近の融点を有するが、体温付近から若干低めの融点（約３０〜約３７℃）のものが好ましく、特に融点が３４〜３５℃の各種のウィテプゾールが好ましい。
【００１３】
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。
【００１４】
本発明の徐放性坐剤は、油性基剤および本発明に用いられる油脂成分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、油脂成分の種類によって異なるが、通常約４０〜約９５℃であり、好ましい油脂成分の硬化ヒマシ油を用いる場合には約８５〜約９０℃が好ましく、別の好ましい油脂成分のミツロウを用いる場合には約６５〜約７０℃が好ましい。
【００１５】
本発明の坐剤において、本発明に用いられる油脂成分は、通常約１〜約３０重量％、好ましくは約２〜約２０重量％を占め、残余を薬物、油性基剤およびほかの補助成分が占めることになる。
【００１６】
本発明の坐剤において、油脂成分が好ましい油脂成分である硬化ヒマシ油の場合には、硬化ヒマシ油が通常約１〜約２０重量％、好ましくは約１〜約１５重量％、特に好ましくは約２〜約１０重量％を占め、残余を薬物、油性基剤およびほかの補助成分が占めることになる。
【００１７】
本発明の坐剤において、油脂成分が好ましい油脂成分であるミツロウの場合には、ミツロウは通常約５〜約３０重量％、好ましくは約１０〜約２０重量％を占め、残余を薬物、油性基剤およびほかの補助成分が占めることになる。
【００１８】
【発明の実施の形態】
本発明の徐放性坐剤の好ましい形態としては、以下の成分を含有する形態が挙げられる。
【００１９】
１．油脂成分が硬化ヒマシ油である形態
（１）薬物約２〜約５重量％
（２）硬化ヒマシ油約２〜約１０重量％
（３）油性基剤残余の重量％
【００２０】
２．油脂成分がミツロウである形態
（１）薬物約２〜約５重量％
（２）ミツロウ約１０〜約２０重量％
（３）油性基剤残余の重量％
【００２１】
上記好ましい形態において、薬物として塩酸モルヒネ又は硫酸モルヒネが好ましく、油性基剤としては融点が約３０〜約３７℃のものが好ましい。
【００２２】
【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。
【００２３】
実施例１：
処方−：
【００２４】
【表１】

【００２５】
実施例２：
処方−：
【００２６】
【表２】

【００２７】
製法−：
それぞれ上記実施例１および２の処方の１５倍量を用いた。硬化ヒマシ油（カスターワックスＡ，日本油脂製）とウィテプゾールＨ−１５を約８５℃で溶融し、塩酸モルヒネを分散させ、これを坐剤用コンテナに充填し、冷却してそれぞれ徐放性坐剤を得た。
【００２８】
実施例３：
処方−：
【００２９】
【表３】

製法−：
【００３０】
それぞれ上記処方の１５倍量を用いた。硬化ヒマシ油（カスターワックスＡ，日本油脂製）とウィテプゾールＷ−３５を約８５℃で溶融し、塩酸モルヒネを分散させ、これを坐剤用コンテナに充填し、冷却して徐放性坐剤を得た。
【００３１】
実施例４：
処方−：
【００３２】
【表４】

【００３３】
製法−：
実施例３と同様に処理して徐放性坐剤を得た。
【００３４】
実施例５：
処方−：
【００３５】
【表５】

【００３６】
実施例６：
処方−：
【００３７】
【表６】

【００３８】
実施例７：
処方−：
【００３９】
【表７】

製法−：
【００４０】
それぞれ上記実施例５、６および７の処方１５倍量を用いた。ミツロウ（脱臭紺印晒ミツロウ，三木化学工業製）とウィテプゾールＨ−１５を約７０℃で溶融し、塩酸モルヒネを分散させ、これを坐剤用コンテナに充填し、冷却して徐放性坐剤を得た。
【００４１】
比較例：特定の油脂成分を入れない処方
処方−：
【００４２】
【表８】

【００４３】
製法−：
ウィテプゾールＨ−１５を約４０℃で溶融し、塩酸モルヒネを分散させ、これを坐剤用コンテナに充填し、１５〜２０℃で冷却して坐剤を得た。
【００４４】
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。
【００４５】
試験例１：
各種油脂成分の融点およびウィテプゾールＨ-１５中に各種油脂成分を１０重量％混合したときの第２融点を表９に示す。
【００４６】
【表９】

【００４７】
ウィテプゾールの融点は３４〜３５℃で油脂成分混合後もほとんど変化せず、表９に示す油脂成分はいずれもウィテプゾールの融点から約１０℃以上高い第２融点を示した。
【００４８】
試験例２：実施例１〜７および比較例Ａの坐剤からの塩酸モルヒネの放出試験を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（ｐＨ７．４）を９００ｍｌ用い、セルの回転速度は２５ｒｐｍであり、温度は３７℃とした。その結果を図１および図２に示す。
【００４９】
図１から明らかなように、特定の油脂成分である硬化ヒマシ油を配合した実施例１〜４の坐剤は、硬化ヒマシ油を含有しない比較例の坐剤よりも明らかに良好な徐放性を示している。
【００５０】
図２から明らかなように、特定の油脂性成分であるミツロウを配合した実施例５〜７の坐剤は、ミツロウを含有しない比較例の坐剤よりも明らかに良好な徐放性を示している。
【００５１】
【発明の効果】
本発明の坐剤は、薬物と油性基剤に、さらに該油性基剤の融点を変化させることが少ない高融点の油脂成分を適量含有させることを特徴とし、坐剤からの薬物の放出性を任意に制御できる優れた徐放性坐剤である。さらに、本発明の坐剤の製造方法は簡便であり、本発明に用いられる油脂成分を徐放化成分として採用することによっても製造工程が複雑化することはない。
【図面の簡単な説明】
【図１】図１は実施例１〜４の坐剤および比較例の坐剤からの塩酸モルヒネの溶出パターンを示す。
【図２】図２は実施例５〜７の坐剤および比較例の坐剤からの塩酸モルヒネの溶出パターンを示す。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a pharmaceutical preparation, particularly a sustained-release suppository containing a high melting point oil and fat component which hardly changes the melting point of an oily base.
[0002]
[Prior art]
Suppositories are relatively easy to administer to patients who have a low rate of drug degradation in vivo by the route of administration, are not affected by diet, and are difficult to administer orally as well as children and the elderly. It is frequently used for reasons such as what it can do. However, on the other hand, when a drug is administered rectally, there are drawbacks such as the risk of side effects due to a sudden rise in plasma concentration and the difficulty of administering it several times a day. Various attempts have been made in the past as such drawbacks can be solved by slow release of the suppository. In general, a suppository is sustained-released by incorporating a specific formulation component (sometimes referred to as a sustained-release component).
[0003]
However, most sustained-release components do not melt together when heated with an oily base and are in a dispersed state. Therefore, in the entire production process, if the controlled release component is not considered to be uniformly dispersed in the oily base, localization of the controlled release component occurs, and as a result, the extent of controlled release between the production lots. Differences can occur.
[0004]
In JP-A-6-298667, a mixture of a polyglycerin fatty acid ester and an oily base has sustained release properties, and examples of the oily base include hardened oil and glycerin fatty acid ester. There are no statements that suggest promoting liberation. JP-A-9-20686 and JP-A-9-52847 describe sustained-release preparations for oral administration containing hardened oil, but hardened oil is used as a sustained-release agent. There is no description that it is used for suppositories.
[0005]
[Problems to be solved by the invention]
A controlled release component that can be uniformly dispersed or mixed in the oily base, that is, a method of blending a high melting point fat component into the oil base is conceivable. In that case, a high melting point fat component is usually blended. As a result, the melting point of the oily base is increased, which makes it difficult to melt the oily base at body temperature, and as a result, it does not show stable sustained release even when a suppository is administered to a patient. Are known.
[0006]
[Means for Solving the Problems]
Therefore, as a result of various studies on the characteristics of the fat and oil component to be blended in order to achieve the desired sustained release without changing the melting point of the oily base, the present inventors have used a specific fat and oil component having a high melting point, The inventors have found that a sustained-release suppository exhibiting the desired sustained-release property can be obtained with almost no change in the melting point of the oily base, thereby completing the present invention.
[0007]
ADVANTAGE OF THE INVENTION According to this invention, the sustained-release suppository containing the high-melting-point oil-fat component which hardly changes the melting | fusing point of the drug and oil base which are main ingredient components, and this oil-based base is provided.
[0008]
“A high melting point oil and fat component that hardly changes the melting point of the oily base” means that the melting point of the oily base hardly changes even when a certain amount is added to the oily base. It is equal to or higher than ° C. and is uniformly mixed with the oily base, and the mixture means an oil / fat component in which two melting points, a melting point of the oily base (first melting point) and a melting point of the fat / oil component (second melting point) are observed. . At this time, the first melting point hardly changes from the melting point of the oily base, and the second melting point is recognized as a gentle melting point at about 10 ° C. higher than the first melting point. Examples of the oil and fat component exhibiting such properties include hydrogenated castor oil (melting point: about 80 ° C), hardened cottonseed oil (melting point: about 69 ° C), hardened coconut oil (melting point: about 59 ° C), and hardened soybean oil (melting point: about 68 ° C). Hardened oil such as beeswax (melting point: about 60 to about 67 ° C), carnauba wax (melting point: about 80 to about 86 ° C), glycerin fatty acid ester (melting point: about 69 ° C), sorbitan fatty acid ester (melting point: about 59 ° C), microcrystalline wax (Melting point: about 58 to about 98 ° C.). The oil and fat component having such properties can achieve the desired sustained release, and the oil component having a high melting point (hereinafter referred to as “this”) that hardly changes the melting point of the oil base used in the present invention. It may be referred to as “fat and fat component used in the invention”). The melting point of the fat and oil component is preferably about 60 ° C. or higher, and the hardened castor oil is particularly preferable because it has a particularly high melting point (melting point: about 80 ° C.) and can be cured in a small amount. Beeswax (melting point: about 60 to about 67 ° C.) is another preferred fat and oil component.
[0009]
Examples of the hardened castor oil include Loveli wax 101 (Freund Sangyo), Custer wax A (Nippon Yushi), and castor hardened oil FC-908 (Kawaken Fine Chemical).
[0010]
Examples of the beeswax include deodorized thumbprint bleached beeswax, thumbprint bleached beeswax, refined beeswax (Miki Chemical Industry), and bleached beeswax (Noda wax).
[0011]
The drug used in the present invention may be water-soluble, poorly water-soluble, or any other property, and the type thereof is not particularly limited. For example, narcotic analgesic morphine hydrochloride, morphine sulfate, synthetic narcotic analgesic Petitidine hydrochloride, non-narcotic analgesic pentazocine, eptazosin hydrobromide, buprenorphine hydrochloride, morphine-related antitussive codeine phosphate, dihydrocodeine phosphate, narcotic antagonist naloxone hydrochloride, nonsteroidal anti-inflammatory drug Acetaminophen and diclofenac sodium are mentioned. Of the above drugs, morphine hydrochloride and morphine sulfate, which are often used as suppository components, are preferred. The content of the drug in the suppository of the present invention is usually about 15% or less, preferably about 1 to 10% by weight, particularly preferably about 2 to about 5% by weight.
[0012]
Moreover, the kind of oily base is not particularly limited as in the case of drugs, and any conventionally used one can be used. Examples of oily bases include mixtures of higher fatty acid ester triglycerides / diglycerides / monoglycerides [for example, various witepsol (Hurtz), various novatas (Henkel), various pharmasols (Japanese fats and oils), isocacao (Kao)] And medium chain fatty acid ester triglyceride [for example, miglyol (Dynamite Nobel)], cacao butter and the like. These oily bases are used alone or in the form of a mixture. These oily bases usually have a melting point around body temperature due to the properties of a suppository base, but those having a slightly lower melting point (about 30 to about 37 ° C.) are preferred, especially the melting point. Various witepsol of 34-35 degreeC are preferable.
[0013]
In addition, auxiliary components such as antioxidants, absorption promoters and mucosal protective agents are blended as necessary.
[0014]
The sustained-release suppository of the present invention heats a mixture comprising an oily base and the oil and fat component used in the present invention to obtain a uniform melt, disperses the drug therein, fills a predetermined container, and cools. Can be manufactured. The heating temperature varies depending on the type of fat and oil component, but is usually about 40 to about 95 ° C., and preferably about 85 to about 90 ° C. when the hardened castor oil of the preferred fat and oil component is used. When using, about 65 to about 70 ° C is preferred.
[0015]
In the suppository of the present invention, the fat and oil component used in the present invention usually accounts for about 1 to about 30% by weight, preferably about 2 to about 20% by weight, and the remainder is a drug, an oily base and other auxiliary components. Will occupy.
[0016]
In the suppository of the present invention, in the case of hydrogenated castor oil, in which the oil and fat component is a preferred oil and fat component, the hydrogenated castor oil is usually about 1 to about 20% by weight, preferably about 1 to about 15% by weight, particularly preferably about 2 to about 10% by weight, with the balance being drug, oily base and other auxiliary ingredients.
[0017]
In the suppository of the present invention, when beeswax is a preferred fat component, the beeswax usually accounts for about 5 to about 30% by weight, preferably about 10 to about 20% by weight, with the balance being the drug, oily group Agent and other auxiliary ingredients.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
Preferred forms of the sustained release suppository of the present invention include forms containing the following components.
[0019]
1. Form in which oil and fat component is hydrogenated castor oil (1) Drug about 2 to about 5% by weight
(2) Hardened castor oil about 2 to about 10% by weight
(3) Oily base remaining weight%
[0020]
2. Form in which oil and fat component is beeswax (1) Drug about 2 to about 5% by weight
(2) About 10 to 20% by weight of beeswax
(3) Oily base remaining weight%
[0021]
In the preferred form, morphine hydrochloride or morphine sulfate is preferred as the drug, and an oily base having a melting point of about 30 to about 37 ° C. is preferred.
[0022]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.
[0023]
Example 1 :
Formula-:
[0024]
[Table 1]

[0025]
Example 2 :
Formula-:
[0026]
[Table 2]

[0027]
Production method:
15 times the prescriptions of Examples 1 and 2 above were used, respectively. Cured castor oil (castor wax A, manufactured by Nippon Oil & Fats) and Witepsol H-15 are melted at about 85 ° C., morphine hydrochloride is dispersed, filled into a suppository container, cooled, and each sustained release suppository. Got.
[0028]
Example 3
Formula-:
[0029]
[Table 3]

Production method:
[0030]
15 times the amount of the above formulation was used. Hardened castor oil (Caster Wax A, manufactured by Nippon Oil & Fats) and Witepsol W-35 are melted at about 85 ° C., morphine hydrochloride is dispersed, filled into a suppository container, cooled, and a sustained release suppository is obtained. Obtained.
[0031]
Example 4 :
Formula-:
[0032]
[Table 4]

[0033]
Production method:
A sustained-release suppository was obtained by the same treatment as in Example 3.
[0034]
Example 5 :
Formula-:
[0035]
[Table 5]

[0036]
Example 6 :
Formula-:
[0037]
[Table 6]

[0038]
Example 7 :
Formula-:
[0039]
[Table 7]

Production method:
[0040]
15 times the prescriptions of Examples 5, 6 and 7 were used. Melt beeswax (deodorized cocoon bleached beeswax, manufactured by Miki Chemical Industry Co., Ltd.) and Witepsol H-15 at about 70 ° C., disperse morphine hydrochloride, fill this into a suppository container, cool, and slowly release suppository Got.
[0041]
Comparative Example : Prescription Formula without Specific Oil Components-:
[0042]
[Table 8]

[0043]
Production method:
Witepsol H-15 was melted at about 40 ° C. to disperse morphine hydrochloride, filled into a suppository container, and cooled at 15 to 20 ° C. to obtain a suppository.
[0044]
In the following, the sustained release effect of the suppository of the present invention will be described by giving experimental examples.
[0045]
Test example 1 :
Table 9 shows the melting points of various fats and oils and the second melting point when 10 wt% of the various fats and oils are mixed in Witepsol H-15.
[0046]
[Table 9]

[0047]
The melting point of witepsol was 34 to 35 ° C. and hardly changed even after the fat and oil components were mixed, and all of the fat and oil components shown in Table 9 exhibited a second melting point higher by about 10 ° C. than the melting point of witepsol.
[0048]
Test Example 2 : The release test of morphine hydrochloride from the suppositories of Examples 1 to 7 and Comparative Example A was performed using a PTSW type suppository release tester (rotary cell method). As the release phase solution, 900 ml of 0.02M phosphate buffer (pH 7.4) was used, the rotation speed of the cell was 25 rpm, and the temperature was 37 ° C. The results are shown in FIG. 1 and FIG.
[0049]
As is apparent from FIG. 1, the suppositories of Examples 1 to 4 blended with hardened castor oil, which is a specific fat and oil component, are clearly better sustained release than the suppositories of the comparative examples not containing hardened castor oil. Is shown.
[0050]
As is clear from FIG. 2, the suppositories of Examples 5 to 7 containing beeswax, which is a specific oily and fat component, showed clearly better sustained release than the suppositories of Comparative Examples not containing beeswax. Yes.
[0051]
【The invention's effect】
The suppository of the present invention is characterized by containing an appropriate amount of an oil component having a high melting point that hardly changes the melting point of the oily base in the drug and the oily base. It is an excellent sustained-release suppository that can be arbitrarily controlled. Furthermore, the manufacturing method of the suppository of this invention is simple, and a manufacturing process is not complicated by employ | adopting the fats and oils component used for this invention as a sustained release component.
[Brief description of the drawings]
FIG. 1 shows the elution pattern of morphine hydrochloride from the suppositories of Examples 1 to 4 and the suppository of Comparative Example.
FIG. 2 shows the elution pattern of morphine hydrochloride from the suppositories of Examples 5 to 7 and the suppository of Comparative Example.

Claims

A sustained-release suppository obtained by dispersing a drug in a uniform melt consisting of a mixture of a higher fatty acid ester triglyceride / diglyceride / monoglyceride and beeswax in an amount of 5 to 30% by weight of the sustained-release suppository and cooling.

The sustained-release suppository according to claim 1, wherein the content of beeswax is 10 to 20% by weight.

The sustained-release suppository according to claim 1 or 2, wherein the uniform melt can be obtained by heating to 65 to 70 ° C.

The sustained-release suppository according to any one of claims 1 to 3, wherein the higher fatty acid ester triglyceride / diglyceride / monoglyceride mixture has a melting point of 30 to 37 ° C.

The sustained-release suppository according to any one of claims 1 to 4, wherein the drug is morphine hydrochloride or morphine sulfate.

The sustained release suppository according to any one of claims 1 to 5, wherein the mixture of higher fatty acid ester triglyceride / diglyceride / monoglyceride is Witepsol (registered trademark).

A mixture of a higher fatty acid ester triglyceride / diglyceride / monoglyceride and a mixture of beeswax in an amount of 5 to 30% by weight of a sustained release suppository is heated to obtain a uniform melt, in which the drug is dispersed, and in a predetermined container A method for producing a sustained-release suppository, which is filled in and cooled.