JPS6377821A - Stable prostaglandin e composition - Google Patents
Stable prostaglandin e compositionInfo
- Publication number
- JPS6377821A JPS6377821A JP22323086A JP22323086A JPS6377821A JP S6377821 A JPS6377821 A JP S6377821A JP 22323086 A JP22323086 A JP 22323086A JP 22323086 A JP22323086 A JP 22323086A JP S6377821 A JPS6377821 A JP S6377821A
- Authority
- JP
- Japan
- Prior art keywords
- prostaglandin
- composition
- polyvinyl pyrrolidone
- agent
- present
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 15
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 title claims abstract description 12
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 13
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 13
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 229920001223 polyethylene glycol Polymers 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 6
- 239000002202 Polyethylene glycol Substances 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 239000010409 thin film Substances 0.000 abstract description 2
- 230000000767 anti-ulcer Effects 0.000 abstract 1
- 239000003146 anticoagulant agent Substances 0.000 abstract 1
- 229960004676 antithrombotic agent Drugs 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 6
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- BGKHCLZFGPIKKU-UHFFFAOYSA-N (13E,15S)-15-hydroxy-9-oxo-prosta-10,13-dienoic acid Natural products CCCCCC(O)C=CC1C=CC(=O)C1CCCCCCC(O)=O BGKHCLZFGPIKKU-UHFFFAOYSA-N 0.000 description 1
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000003721 gunpowder Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、ブ【ＪスタブランジンＥの安定な組成物、さ
らに詳しくは、プロスタグランジンＥにポリビニルピロ
リドンを配合したことを特徴とする安定なプロスタグラ
ンジンＥ組成物に関４”ろ。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a stable composition of stablandin E, more specifically, a stable prostaglandin characterized by blending prostaglandin E with polyvinylpyrrolidone. 4" regarding the Gin E composition.
技術的背景
プロスタグランジン（ＰＣ）はブロスタン酸を基本ｉ１
格とする一群の物質の総称であり、その中で、ブ「Ｉス
タン酸の５１環上にβ−ヒドロキンケトン構造を何才ろ
乙のはプロスタグランジンＥ（１）ＧＥ）と呼ばれる。Technical background Prostaglandin (PC) is based on brostanic acid.
It is a general term for a group of substances that have a β-hydroquine ketone structure on the 51st ring of stanoic acid (prostaglandin E(1)GE).
Ｐｃ Ｆ、は血圧降下剤、胃ｈｆ瘍治療剤、血栓治療剤
、避妊または陣痛誘発剤として有用である。しかし、Ｐ
ＧＥは酸やアルカリ、あるいは熱に対して極めて不安定
であり、容易に脱水反応を起こしてプロスタグランジン
Ａになり、次いて異性化してプロスタグランジンＢにな
ることが知られている。Pc F is useful as an antihypertensive agent, a therapeutic agent for gastric HF ulcers, a therapeutic agent for blood clots, a contraceptive agent, or an agent for inducing labor. However, P
It is known that GE is extremely unstable to acids, alkalis, or heat, and easily undergoes a dehydration reaction to become prostaglandin A, which is then isomerized to become prostaglandin B.
従って、ＰＧＥを医薬品として製剤化する場合には、そ
の安定性を改善する必要がある。Therefore, when formulating PGE as a drug, it is necessary to improve its stability.
近年、このＰＥＧの分解を抑える目的で、たとえばセル
ロース誘導体、植物油、酸エステル、デオキシコール酸
などの種々の物質を安定化剤として配合することが提案
されているが、いずれら満足な結果は得られていない。In recent years, it has been proposed to incorporate various substances such as cellulose derivatives, vegetable oils, acid esters, and deoxycholic acid as stabilizers in order to suppress the decomposition of PEG, but none of these methods have yielded satisfactory results. It has not been done.
発明の目的
そこで、本発明者°らは、ＰＧＥの安定化について鋭、
０検討を行った結果、ＰＧＥにポリビニルピロリドンを
配合することにより著しく安定化されることを見い出し
、本発明を完成するに至った。Purpose of the Invention Therefore, the present inventors have made in-depth research into the stabilization of PGE.
As a result of conducting 0 studies, it was found that by blending polyvinylpyrrolidone with PGE, it was significantly stabilized, and the present invention was completed.
すなわち、本発明は、プロスタグランジンＥにポリビニ
ルビ〔１リドンを配合することを特徴とする安定なプロ
スタグランジンＥ組成物を提ｆＪ％するものである。That is, the present invention provides a stable prostaglandin E composition characterized by blending polyvinylvinyridone with prostaglandin E.
発明の構成および幼果
本発明によって安定化されるＰＧＥとしては、たとえば
プロスタグランジンＥ、（ＰＧＥ、）、プロスタグラン
ジンＥ２ＣＰＧＥ２）などが挙げられる。Structure of the Invention and Young Fruit Examples of the PGE stabilized by the present invention include prostaglandin E, (PGE, ), prostaglandin E2CPGE2), and the like.
本発明組成物は、以下のようにして製造ずろことができ
る。すなわち、ポリビニルピロリドンを好ましくは１〜
５０％（重量％、以下同じ）、より好ましくは１０〜３
０％、さらに所望によりポリエチレングリコールを好ま
しくは１〜１０％、より好ましくは２〜５％含汀する有
機溶媒に、ポリビニルピロリドンの１ ／ ２ Ｆｆｌ
以下、好ましくは１／１０〜Ｉ／＋０００量のＰＧＩＤ
を加え、均一に混合した後、たとえば薄膜状に展延し、
溶媒を除去する。The composition of the present invention can be manufactured as follows. That is, polyvinylpyrrolidone is preferably 1-
50% (wt%, same below), more preferably 10-3
1/2 Ffl of polyvinylpyrrolidone in an organic solvent containing 0%, and further preferably 1 to 10%, more preferably 2 to 5% of polyethylene glycol if desired.
Below, preferably 1/10 to I/+000 amount of PGID
After adding and mixing uniformly, spread it into a thin film, for example,
Remove solvent.
本発明組成物の製造に用いろ何機溶媒としては、ＰＧＥ
およびポリビニルピロリドンの両者を溶解することがで
きる溶媒、好ましくはエタノールを用いる。The solvent used for producing the composition of the present invention is PGE.
and polyvinylpyrrolidone, preferably ethanol.
本発明の組成物は後記安定性試験に６示されろとよｊす
、顕菖７なブ〔ｌスタグランノンＦＣ安定化りＪ果をｆ
Ｉ″４゛る。本発明のｔｎ成酸物そのままで、または通
常の１匁薬７Ｆ１体を用いて常法によって製剤化するご
とにより、プロスタグランジンＥの安定性が改善された
種々の製剤、ｆ二とえば、錠剤、カプセル剤、貼付剤、
ｔ〕ミ射剤などを得ることができる。The composition of the present invention has a significant effect on stabilizing stagranone FC, as shown in the stability test described below.
Various formulations with improved stability of prostaglandin E by formulating the tn synthetic acid of the present invention as it is or by using a conventional 1-monme drug 7F1 by a conventional method. , f2 For example, tablets, capsules, patches,
t] Gunpowder, etc. can be obtained.
以下に実施例、比較例および実験例を挙げて本発明をさ
らに詳しく説明するが、本発明はこれらに限定されろも
のではない。The present invention will be explained in more detail below with reference to Examples, Comparative Examples, and Experimental Examples, but the present invention is not limited thereto.
及貫倒−１
ポリビニルピロリドンを３０％およびポリエチレングリ
コールを３％含Ｙｒオろエタノール溶液【ＯｇにＰ Ｇ
Ｅ ｔ ３０ 、ｗｇを加え、よく攪拌した後、展延
し、次いで４０°Ｃの乾燥機中で３０分間放置して溶媒
をＦＦ：１故さＵ゛、厚さ約８０μｍのフィルム状１■
【酸物を得ろ。And-Kan-1 Yr ethanol solution containing 30% polyvinylpyrrolidone and 3% polyethylene glycol [Og to PG
After adding E t 30 and wg and stirring well, it was spread, and then left in a dryer at 40°C for 30 minutes to remove the solvent.
[Get the acid.
彩彫
ポリビニルピロリドンを３０％およびポリエチレングリ
コールを３％含有ずろエタノール溶液１ｇ （、：Ｐ
Ｇ Ｅ ｔ ３０ ｍｇを加えた後、実施例１と同様に
してフィルム状組成物を得る。1 g of ethanol solution containing 30% Saibori polyvinylpyrrolidone and 3% polyethylene glycol (,:P
After adding 30 mg of G E t , a film-like composition is obtained in the same manner as in Example 1.
及皇鯉エ
ポリビニルピロリドンを３０％およびポリエチレングリ
コールを３％含有ずろエタノール溶液■ＯｇにＰＣＢ、
３０η９を加えた後、実施例１と同様にしてフィルム状
組成物を得る。Okikoi Ethanol solution containing 30% polyvinylpyrrolidone and 3% polyethylene glycol
After adding 30η9, a film-like composition is obtained in the same manner as in Example 1.
比較例Ｉ
ボリヒニルアルコールＩｇを水３ｇに溶解した溶液にＰ
ＧＥ２１０ｍｇを加え、よく攪拌した後、展延し、次い
て・１０℃の乾燥機中で２時間放置し、溶媒を揮散させ
てフィルム状組成物を得る。Comparative Example I In a solution of borihinyl alcohol Ig dissolved in 3 g of water
After adding 210 mg of GE and stirring thoroughly, the mixture was spread and then left in a dryer at 10° C. for 2 hours to volatilize the solvent to obtain a film composition.
比較例２
酢酸フタル酸セルロース１ｇをエタノール２ｇに溶解し
た溶液に、ＰＧＩＥｚｌＯｎを加え、よく攪拌した後、
展延し、次いて１１０℃の乾燥機中で３０分間放置し、
溶媒を揮散さＵてフィルム状Ｉ■戎物を得る。Comparative Example 2 PGIEzlOn was added to a solution of 1 g of cellulose acetate phthalate dissolved in 2 g of ethanol, and after stirring well,
Spread it out, then leave it in a dryer at 110°C for 30 minutes,
The solvent is evaporated to obtain a film-like product.
Ｘ騨刀工
実施例１〜３および比較例１および２て得たフィルムを
それぞれＩ Ｃｍ２に切り人す、これらとＰＧＥ、弔品
を１００°Ｃて２４時間加熱した後、液体クロマトグラ
フィーを用いてＩ’） Ｇ Ｅの残１′７量を定量した
。液体りＯマドグラフィーは、オクタデンルンリル化ン
リカゲルを充填したカラムを用い、Ｋ１１２Ｐ ０４（
９ｇ／１２）−アセトニ）・リル混液を移動用とし、１
９５ｎｍにて検出した。結果を第１表に示す。The films obtained in Examples 1 to 3 and Comparative Examples 1 and 2 were each cut into I cm2 pieces, and after heating these, PGE, and the funeral gift at 100 ° C. for 24 hours, using liquid chromatography. I') The remaining 1'7 amount of G was quantified. Liquid phosphorography uses a column packed with octadenolyl silica gel, and K112P 04 (
9g/12)-acetoni)・Ril mixture was used for transportation, and 1
Detection was performed at 95 nm. The results are shown in Table 1.
第１表Table 1
Claims (1)
配合することを特徴とする安定なプロスタグランジンＥ
組成物。(1) Stable prostaglandin E characterized by blending polyvinylpyrrolidone with prostaglandin E
Composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22323086A JPS6377821A (en) | 1986-09-19 | 1986-09-19 | Stable prostaglandin e composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP22323086A JPS6377821A (en) | 1986-09-19 | 1986-09-19 | Stable prostaglandin e composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6377821A true JPS6377821A (en) | 1988-04-08 |
Family
ID=16794831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP22323086A Pending JPS6377821A (en) | 1986-09-19 | 1986-09-19 | Stable prostaglandin e composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6377821A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994020856A1 (en) * | 1993-03-09 | 1994-09-15 | Middlesex Sciences, Inc. | Macromolecular microparticles and methods of production |
| JP2019529467A (en) * | 2016-10-06 | 2019-10-17 | スキャンポ・アーゲーＳｕｃａｍｐｏ ＡＧ | Multi-layer beads for pharmaceutical applications |
-
1986
- 1986-09-19 JP JP22323086A patent/JPS6377821A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994020856A1 (en) * | 1993-03-09 | 1994-09-15 | Middlesex Sciences, Inc. | Macromolecular microparticles and methods of production |
| US5578709A (en) * | 1993-03-09 | 1996-11-26 | Middlesex Sciences, Inc. | Macromolecular microparticles and methods of production |
| EP0809110A1 (en) * | 1993-03-09 | 1997-11-26 | Middlesex Sciences, Inc. | Macromolecular microparticles and methods of production |
| JP2019529467A (en) * | 2016-10-06 | 2019-10-17 | スキャンポ・アーゲーＳｕｃａｍｐｏ ＡＧ | Multi-layer beads for pharmaceutical applications |
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