JPH0665645B2 - Self-emulsifying soft capsule drug solution - Google Patents
Self-emulsifying soft capsule drug solutionInfo
- Publication number
- JPH0665645B2 JPH0665645B2 JP60205681A JP20568185A JPH0665645B2 JP H0665645 B2 JPH0665645 B2 JP H0665645B2 JP 60205681 A JP60205681 A JP 60205681A JP 20568185 A JP20568185 A JP 20568185A JP H0665645 B2 JPH0665645 B2 JP H0665645B2
- Authority
- JP
- Japan
- Prior art keywords
- drug solution
- soft capsule
- self
- solution
- coq
- 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.)
- Expired - Lifetime
Links
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 本発明は自己乳化型軟カプセル薬液、更に詳細には、有
効薬効成分としてユビデカレノン（以下、「CoQ10」と
称することもある）を含有し、低温安定性がよく、しか
も生体内における吸収性が優れた自己乳化型軟カプセル
薬液に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention is a self-emulsifying soft capsule drug solution, more specifically, containing ubidecarenone (hereinafter sometimes referred to as “CoQ 10 ”) as an active drug component, and has good low temperature stability, Moreover, the present invention relates to a self-emulsifying soft capsule drug solution having excellent absorbability in vivo.
CoQ10は1957年に初めて牛の心筋から結晶として分離さ
れたもので、慢性化した高血圧症、虚血性心疾患、弁膜
疾患などの心機能低下によつて起る浮腫、肺うつ血、肝
腫脹、狭心症状の改善剤として、現在臨床において広く
使用されている。CoQ 10 was first isolated as crystals from bovine myocardium in 1957, and it caused edema, pulmonary depression, and swelling caused by hypofunction of the heart such as chronic hypertension, ischemic heart disease, and valvular disease. Currently, it is widely used clinically as an agent for improving angina symptoms.
CoQ10は錠剤、顆粒剤、カプセル剤等の剤形で市販され
ているが、吸収性、速効性等の点から軟カプセルにする
ことが望まれる。しかし、CoQ10の一回投与量である10m
gを油に溶解して可及的に小型（薬液量150mg）の軟カプ
セルを製造しようとすると、低温における薬液の安定性
が悪く、保存中にCoQ10の結晶が析出してくるという問
題点があつた。このため、従来は、CoQ10界面活性剤を
使用して中鎖脂肪酸のトリグリセライドに溶解して薬液
を調製する方法が行われている。しかし、この軟カプセ
ルは低温安定性はある程度改善されるが、生体内におけ
る吸収が劣るという欠点があつた。CoQ 10 is commercially available in the form of tablets, granules, capsules and the like, but it is desirable to make it into a soft capsule from the viewpoints of absorbability, fast-acting properties and the like. However, a single dose of CoQ 10 of 10m
When g is dissolved in oil to produce a soft capsule as small as possible (amount of drug solution is 150 mg), the stability of the drug solution at low temperature is poor and CoQ 10 crystals precipitate during storage. I got it. Therefore, conventionally, a method of preparing a drug solution by dissolving it in triglyceride of medium-chain fatty acid using a CoQ 10 surfactant has been performed. However, although this soft capsule has some improvement in low temperature stability, it has a drawback of poor absorption in vivo.
従つて、CoQ10を多量に含有せしめ薬液量を少なくする
ことができ、低温安定性に優れ、かつ生体内における吸
収がよい軟カプセル薬液の開発が望まれていた。Therefore, there has been a demand for the development of a soft capsule drug solution which can contain a large amount of CoQ 10 and can be reduced in the amount of the drug solution, which is excellent in low-temperature stability and is well absorbed in vivo.
斯かる実情において、本発明者は上記問題点を解決せん
と鋭意研究を行つた結果、溶剤として特定のポリグリセ
リン脂肪酸エステルを使用し、安定化剤としてジアセチ
ルカプリン酸グリセライドを配合すれば、上記条件を具
備した軟カプセル薬液が得られることを見出し、本発明
を完成した。In such an actual situation, the present inventor has conducted diligent research to solve the above-mentioned problems, and uses a specific polyglycerin fatty acid ester as a solvent, and if diacetylcapric acid glyceride is blended as a stabilizer, the above-mentioned conditions are satisfied. The present invention has been completed by finding that a soft capsule drug solution having the above can be obtained.
すなわち、本発明は、ユビデカレノン10重量部、デカグ
リセリルペンタオレート123〜135重量部及びジアセチル
カプリン酸グリセライド４〜16重量部を含有することを
特徴とする自己乳化型軟カプセル薬液を提供するもので
ある。That is, the present invention provides a self-emulsifying soft capsule drug solution containing 10 parts by weight of ubidecarenone, 123 to 135 parts by weight of decaglyceryl pentaoleate, and 4 to 16 parts by weight of glyceride diacetylcaprate. .
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
によつて得られたポリグリセリンと脂肪酸のエステル化
物であり、ポリグリセリンは１分子中に平均４個以上の
OH基を持っているため、脂肪酸の種類、モル比を変える
ことにより種々のポリグリセリン脂肪酸エステルが得ら
れる。本発明者はこれらの多くのポリグリセリン脂肪酸
エステルについて、CoQ10の溶解性を検討した結果、当
該脂肪酸がオレイン酸以外の場合には、CoQ10の溶解性
が悪く溶剤として不適当であつた。また、ポリグリセリ
ンオレイン酸エステルの中でも、生体内における吸収性
を検討すると、特にデカグリセリルペンタオレートが優
れた効果を有する。デカグリセリルペンタオレートの本
発明薬液中への配合量は、CoQ10を10重量部としたと
き、123〜135重量部とするのが好ましい。デカグリセリ
ルペンタオレートがこれより少ないと、低温安定性が低
下すると共に、生体内吸収も悪くなり好ましくない。ま
た、これを超えて配合しても更に効果の向上は認められ
ず、しかもカプセルが大型化されるので却つて好ましく
ない。Polyglycerin fatty acid ester is an esterified product of polyglycerin and fatty acid obtained by dehydration condensation of glycerin, and polyglycerin has an average of 4 or more in one molecule.
Since it has an OH group, various polyglycerin fatty acid esters can be obtained by changing the type and molar ratio of the fatty acid. As a result of examining the solubility of CoQ 10 in many of these polyglycerin fatty acid esters, the present inventors found that when the fatty acid was other than oleic acid, CoQ 10 had poor solubility and was unsuitable as a solvent. Further, among the polyglycerin oleic acid esters, decaglyceryl pentaoleate has a particularly excellent effect when its absorbability in vivo is examined. The amount of decaglyceryl pentaoleate to be added to the drug solution of the present invention is preferably 123 to 135 parts by weight when CoQ 10 is 10 parts by weight. If the amount of decaglyceryl pentaoleate is less than that, the low temperature stability is deteriorated and in vivo absorption is also unfavorable. Further, even if it is blended in excess of this range, no further improvement in the effect is observed, and the size of the capsule is increased, which is not preferable.
また、本発明においては、安定化剤としてジアセチルカ
プリン酸グリセライドを配合することが必要であり、こ
れが配合されないと低温安定性が悪く、保存中に結晶の
析出が生ずる。ジアセチルカプリン酸グリセライドは本
発明薬液中（CoQ10の10重量部としたとき）に４〜16重
量部になるように配合するのが好ましい。Further, in the present invention, it is necessary to blend diacetylcapric acid glyceride as a stabilizer, and if it is not blended, the low temperature stability is poor and crystals are precipitated during storage. It is preferable that the glyceride diacetylcaprate is blended in the liquid medicine of the present invention (when 10 parts by weight of CoQ 10 is used) in an amount of 4 to 16 parts by weight.
更にまた、比較的親水性の界面活性剤、例えばセスキオ
レイン酸ソルビタン等を添加すれば、なお一層上記効果
を向上させることができる。Furthermore, the effect can be further improved by adding a relatively hydrophilic surfactant such as sorbitan sesquioleate.
叙上の如く、本発明によれば、比較的少量の溶剤に多量
のCoQ10を安定に溶解させることができるので、小型の
軟カプセルを製造できると共に、これを生体内に投与し
た場合吸収がよいという利点を有する。As described above, according to the present invention, a large amount of CoQ 10 can be stably dissolved in a relatively small amount of solvent, so that a small soft capsule can be produced, and when it is administered in vivo, absorption is reduced. It has the advantage of being good.
次に実施例を挙げて説明する。 Next, examples will be described.
実施例１ CoQ10200mg（20カプセル分）を10ml容のビーカーに入
れ、セスキオレイン酸ソルビタン（SO−15）20mgを加
え、次に第１表に示す量に相当する量のデカグリセリル
ペンタオレート、ジアセチルカプリン酸グリセライド及
び／又は中鎖脂肪酸トリグリセライド（ミグリオール81
2,Dynamit Nobel社製）を加え、撹拌下加熱溶解した。C
oQ10が溶解した時点で撹拌をやめ、徐々に室温まで冷却
して薬液を得た。Example 1 200 mg of CoQ 10 (20 capsules) was placed in a 10 ml beaker, 20 mg of sorbitan sesquioleate (SO-15) was added, and then an amount of decaglyceryl pentaoleate corresponding to the amount shown in Table 1, Diacetylcapric acid glyceride and / or medium-chain fatty acid triglyceride (Miglyol 81
2, Dynamit Nobel) was added, and the mixture was heated and dissolved with stirring. C
When oQ 10 was dissolved, the stirring was stopped, and the solution was gradually cooled to room temperature to obtain a drug solution.
斯くして得た薬液について、低温安定性及び体内吸収性
を試験した。The drug solution thus obtained was tested for low temperature stability and absorbability in the body.
判定方法及び基準： 低温安定性 薬液を10ml容のサンプル瓶に入れ、−５℃〜40℃のサイ
クル試験を行い結晶の析出するまでの日数を観察した。Judgment Method and Criteria: Low Temperature Stability A chemical solution was placed in a 10 ml sample bottle, and a cycle test of −5 ° C. to 40 ° C. was performed to observe the number of days until crystal precipitation.
体内吸収性 薬液の体内での吸収性はコール酸ナトリウム水溶液への
分散性によつて調べることができる。Absorption in the body The absorption of the drug solution in the body can be examined by its dispersibility in an aqueous solution of sodium cholate.
0.1％コール酸ナトリウム水溶液及び0.5％コール酸ナト
リウム水溶液をそれぞれ10mlのビーカーに約5ml取り、
薬液２〜３滴を滴下し、ミクロスパーテルにて強く撹拌
した後、約30秒程度放置し溶液の性状を観察し、次の基
準で判定した。Approximately 5 ml each of 0.1% sodium cholate aqueous solution and 0.5% sodium cholate aqueous solution in a 10 ml beaker,
Two to three drops of the drug solution were dropped, and the solution was strongly stirred with a microspatel and then left for about 30 seconds to observe the properties of the solution and judged according to the following criteria.
×……薬液が水面に油滴となり浮いている △……薬液の一部が微細な油滴となり溶液中に浮いてい
る ○……溶液は淡黄色の乳化液となるが一部油滴となり溶
液水面に浮いている ◎……淡黄色の均一な乳化液となる 結果： × …… The chemical solution floats as an oil droplet on the water surface △ …… Part of the chemical solution becomes a fine oil droplet and floats in the solution ○ …… The solution becomes a pale yellow emulsion but partly becomes an oil droplet Floating on the surface of the solution ◎ …… The result is a uniform pale yellow emulsion.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 31/12 ＡＣＳ 9283−4Ｃ 47/14 Ｊ 7433−4Ｃ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location A61K 31/12 ACS 9283-4C 47/14 J 7433-4C
Claims (1)
ペンタオレート123〜135重量部及びジアセチルカプリン
酸グルセライド４〜16重量部を含有することを特徴とす
る自己乳化型軟カプセル薬液。1. A self-emulsifying soft capsule drug solution containing 10 parts by weight of ubidecarenone, 123 to 135 parts by weight of decaglyceryl pentaoleate, and 4 to 16 parts by weight of diacetylcapric acid glyceride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60205681A JPH0665645B2 (en) | 1985-09-18 | 1985-09-18 | Self-emulsifying soft capsule drug solution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60205681A JPH0665645B2 (en) | 1985-09-18 | 1985-09-18 | Self-emulsifying soft capsule drug solution |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6267019A JPS6267019A (en) | 1987-03-26 |
| JPH0665645B2 true JPH0665645B2 (en) | 1994-08-24 |
Family
ID=16510929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60205681A Expired - Lifetime JPH0665645B2 (en) | 1985-09-18 | 1985-09-18 | Self-emulsifying soft capsule drug solution |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0665645B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10202010355PA (en) | 2010-03-12 | 2020-11-27 | Berg Llc | Intravenous formulations of coenzyme q10 (coq10) and methods of use thereof |
| JP7022973B2 (en) * | 2017-07-31 | 2022-02-21 | 富士カプセル株式会社 | Compositions for filling soft capsules and soft capsules |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5581813A (en) * | 1978-12-16 | 1980-06-20 | Nisshin Flour Milling Co Ltd | Composition containing coenzyme q10 and its perparation |
| JPS5813508A (en) * | 1981-07-14 | 1983-01-26 | Taiho Yakuhin Kogyo Kk | Drug containing polyglycerol ester of fatty acid |
| JPS5877810A (en) * | 1981-11-01 | 1983-05-11 | Taiho Yakuhin Kogyo Kk | Oral drug composition containing polyglycerol unsaturated fatty acid ester |
-
1985
- 1985-09-18 JP JP60205681A patent/JPH0665645B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6267019A (en) | 1987-03-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |