JPH0629180B2 - Compositions containing menatetrenone with improved absorption - Google Patents
Compositions containing menatetrenone with improved absorptionInfo
- Publication number
- JPH0629180B2 JPH0629180B2 JP61138298A JP13829886A JPH0629180B2 JP H0629180 B2 JPH0629180 B2 JP H0629180B2 JP 61138298 A JP61138298 A JP 61138298A JP 13829886 A JP13829886 A JP 13829886A JP H0629180 B2 JPH0629180 B2 JP H0629180B2
- Authority
- JP
- Japan
- Prior art keywords
- acid ester
- menatetrenone
- oil
- propylene glycol
- glycerin
- 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
Description
【発明の詳細な説明】 ａ．産業上の利用分野 本発明は止血機能の改善に有効な医薬品として臨床上広
く使用されているメナテトレノンの経口投与における吸
収性を著しく改善した組成物に関するものである。DETAILED DESCRIPTION OF THE INVENTION a. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition of menatetrenone, which is clinically widely used as a drug effective in improving the hemostatic function, with markedly improved oral absorbability.
ｂ．従来技術の説明 メナテトレノンは黄色結晶または油状のビタミンＫ剤で
あり、出血および低プロトロンビン症に有効な薬剤とし
て知られている。しかしながら、水に難溶であるため経
口投与後の体内吸収性、即ち吸収速度と吸収量において
問題があり、救急止血など医療現場における必要性から
強く、その改良が望まれていた。b. Description of the Prior Art Menatetrenone is a yellow crystalline or oily vitamin K agent, and is known as an effective drug for bleeding and hypoprothrombinosis. However, since it is poorly soluble in water, it has a problem in absorbability in the body after oral administration, that is, in absorption rate and absorption amount, and it is strongly demanded in the medical field such as emergency hemostasis, and its improvement has been desired.
ｃ．発明が解決しようとする問題点 本発明はこのような経口投与時のメナテトレノンの吸収
性を改善するものである。c. Problems to be Solved by the Invention The present invention improves the absorbability of menatetrenone during such oral administration.
ｄ．問題点を解決するための手段 本発明者らは鋭意研究の結果、メナテトレノンにプロピ
レングリコールモノ脂肪酸エステル，又はグリセリンモ
ノ脂肪酸エステル，又はソルビタンモノ脂肪酸エステ
ル，あるいは之らの２種以上の混合物及び植物油又は合
成油を添加した組成物が優れた吸収促進性をもたらすこ
とを知り、本発明を完成した。d. Means for Solving the Problems As a result of earnest research, the present inventors have found that propylene glycol monofatty acid ester, glycerin monofatty acid ester, or sorbitan monofatty acid ester is added to menatetrenone, or a mixture of two or more kinds of them and vegetable oil or The inventors have completed the present invention, knowing that a composition containing a synthetic oil provides excellent absorption promoting properties.
プロピレングリコールモノ脂肪酸エステルとしては、プ
ロピレングリコールモノカプリル酸エステルまたはプロ
ピレングリコールモノオレイン酸エステルが好ましく、
具体的なＰＭＫまたはＰＭＯ〔いずれも日光ケミカル
（株）の商品名〕が入手可能なものとして挙げられる。The propylene glycol monofatty acid ester is preferably propylene glycol monocaprylic acid ester or propylene glycol monooleic acid ester,
Specific examples of PMK or PMO (both trade names of Nikko Chemical Co., Ltd.) are available.
グリセリンモノ脂肪酸エステルとしては、グリセリンモ
ノカプリン酸エステルまたはグリセリンモノオレイン酸
エステルが好ましく、ＭＧＫまたはＭＧＯ〔いずれも日
光ケミカル（株）の商品名〕が入手可能なものとして挙
げられる。As the glycerin monofatty acid ester, glycerin monocaprate ester or glycerin monooleate ester is preferable, and MGK or MGO [both are trade names of Nikko Chemical Co., Ltd.] can be mentioned.
ソルビタンモノ脂肪酸エステルとしては、ソルビタンモ
ノカプリン酸エステルが好ましく、ＳＭＫ〔日光ケミカ
ル（株）の商品名〕が入手可能なものとして挙げられ
る。As the sorbitan monofatty acid ester, sorbitan monocapric acid ester is preferable, and SMK [trade name of Nikko Chemical Co., Ltd.] is mentioned as available.
これらプロピレングリコールモノ脂肪酸エステル，グリ
セリンモノ脂肪酸エステル，およびソルビタンモノ脂肪
酸エステルは、その二者以上を併用してもよい。Two or more of these propylene glycol monofatty acid ester, glycerin monofatty acid ester, and sorbitan monofatty acid ester may be used in combination.
植物油としては綿実油、落花生油、胡麻油、オリーブ油
等が好ましい例として示される。Preferred vegetable oils are cottonseed oil, peanut oil, sesame oil, olive oil and the like.
合成油としてはカプロン酸，カプリル酸，カプリン酸，
ラウリン酸等の脂肪酸のプロピレングリコールジエステ
ルあるいはＯＤＯ（Octyl Decyltri-Glyceride）等の合
成グリセリン脂肪酸エステルが好ましい例として示され
る。Synthetic oils include caproic acid, caprylic acid, capric acid,
Preferred examples are propylene glycol diesters of fatty acids such as lauric acid or synthetic glycerin fatty acid esters such as ODO (Octyl Decyltri-Glyceride).
メナテトレノンとプロピレングリコールモノ脂肪酸エス
テル，またはグリセリンモノ脂肪酸エステル，またはソ
ルビタンモノ脂肪酸エステル，またはそれらの２以上の
混合物、との配合割合はメナテトレノン１重量部に対し
0.1〜６０重量部、好ましくは0.5〜１０重量部、また植
物油又は合成油はメナテトレノン１重量部に対し0.1〜
６０重量部、好ましくは0.5〜１０重量部を加えればよ
い。The mixing ratio of menatetrenone and propylene glycol monofatty acid ester, glycerin monofatty acid ester, sorbitan monofatty acid ester, or a mixture of two or more thereof is based on 1 part by weight of menatetrenone.
0.1 to 60 parts by weight, preferably 0.5 to 10 parts by weight, and vegetable oil or synthetic oil is 0.1 to 1 part by weight of menatetrenone.
60 parts by weight, preferably 0.5 to 10 parts by weight may be added.
これら本発明組成物に、結晶セルロースあるいはデンプ
ン等の懸濁安定化剤や、組成物を成形するための賦形剤
等を任意に選択して添加することもできる。A suspension stabilizer such as crystalline cellulose or starch, an excipient for molding the composition, and the like can be optionally selected and added to these compositions of the present invention.
メナテトレノンが室温では固体であることから本発明組
成物は基本的には液状で提供される。この液状物質につ
いて当業界では透明なものを油性溶液，不透明なものを
油性懸濁液と呼び、両者を併せて油性液と総称するが、
この場合油性とは必らずしも組成的に液状油含有の有無
を問わない。Since menatetrenone is solid at room temperature, the composition of the present invention is basically provided in liquid form. Regarding this liquid substance, in the art, a transparent one is called an oily solution, an opaque one is called an oily suspension, and both are collectively called an oily liquid.
In this case, it is not necessarily oily, and it does not matter whether the composition contains liquid oil or not.
しかしながら、これら油性液をある種の粉体に吸着させ
て製した粉末，さらに該粉末を処理して得られる顆粒，
錠剤，糖衣剤，硬カプセル剤等も同様に本発明組成物の
製剤形態である。また、これら油性液に、ある種の糖等
を添加して得られるシロツプ剤，あるいはこれらを直接
カプセルに充填して得られるカプセル剤等も同じく本発
明組成物の製剤形態である。However, powders produced by adsorbing these oily liquids to certain powders, and granules obtained by processing the powders,
Tablets, dragees, hard capsules, and the like are also formulations of the composition of the present invention. A syrup preparation obtained by adding a certain sugar or the like to these oily liquids, or a capsule preparation obtained by directly filling these into a capsule is also a formulation form of the composition of the present invention.
即ち本発明組成物としては油性液を基本とするあらゆる
製剤形態が含まれる。That is, the composition of the present invention includes all formulation forms based on an oily liquid.
本発明組成物はこれら目的とする製剤形態に応じて常法
により製造することができる。The composition of the present invention can be produced by a conventional method according to the intended formulation form.
実施例 以下の実施例をもつて本発明を更に具体的に説明する。EXAMPLES The present invention will be described more specifically with reference to the following examples.
実施例１： プロピレングリコールジカプリン酸エステル２０ｇにメ
ナテトレノン３０ｇを加えて溶解せしめ、プロピレング
リコールモノオレイン酸エステル１００ｇを加え、加温
下において高速攪拌機を用いて激しく攪拌し、分散液を
得た。これを検体試料１とする。また、更にこの分散液
を充填してソフトカプセル剤とした。Example 1: 30 g of menatetrenone was added to and dissolved in 20 g of propylene glycol dicaprate ester, 100 g of propylene glycol monooleate ester was added, and the mixture was vigorously stirred under heating with a high-speed stirrer to obtain a dispersion liquid. This is designated as sample sample 1. Further, this dispersion was filled to obtain a soft capsule.
実施例２： プロピレングリコールジカプリル酸エステル８ｇにメナ
テトレノン３ｇを分散せしめ、プロピレングリコールモ
ノオレイン酸エステル４ｇを加え、加温下において高速
攪拌機を用いて激しく攪拌し、分散液を得た。これを検
体試料２とする。Example 2: 3 g of menatetrenone was dispersed in 8 g of propylene glycol dicaprylate, 4 g of propylene glycol monooleate was added, and the mixture was vigorously stirred using a high speed stirrer under heating to obtain a dispersion liquid. This is designated as sample sample 2.
実施例３： プロピレングリコールジカプリン酸エステル２ｇにメナ
テトレノン３ｇを分散せしめ、グリセリンモノオレイン
酸エステル１０ｇを加え、加温下において高速攪拌機を
用いて激しく攪拌し分散液を得た。これを検体試料３と
する。Example 3: 3 g of menatetrenone was dispersed in 2 g of propylene glycol dicapric acid ester, 10 g of glycerin monooleate was added, and the mixture was vigorously stirred under heating with a high-speed stirrer to obtain a dispersion liquid. This is designated as sample sample 3.
実施例４： プロピレングリコールジカプリン酸エステル５ｇにメナ
テトレノン３ｇを分散しせめ、グリセリンモノオレイン
酸エステル７ｇを加え、加温下において高速攪拌機を用
いて激しく攪拌し、分散液を得た。これを検体試料４と
する。Example 4: 3 g of menatetrenone was dispersed in 5 g of propylene glycol dicaprate ester, 7 g of glycerin monooleate ester was added, and the mixture was vigorously stirred using a high-speed stirrer under heating to obtain a dispersion liquid. This is designated as sample sample 4.
実施例５： 綿実油５ｇにメナテトレノン３ｇとグリセリンモノオレ
イン酸エステル７ｇを加え、加温下において高速攪拌機
を用いて激しく攪拌し分散液を得た。Example 5: 3 g of menatetrenone and 7 g of glycerin monooleate were added to 5 g of cottonseed oil, and the mixture was vigorously stirred under heating with a high-speed stirrer to obtain a dispersion liquid.
実施例６： ＯＤＯ５ｇにメナテトレノン３ｇとグリセリンモノオレ
イン酸エステル７ｇを加え、加温下において高速攪拌機
を用いて激しく攪拌し溶液を得た。Example 6: To 5 g of ODO, 3 g of menatetrenone and 7 g of glycerin monooleate were added, and the mixture was vigorously stirred with heating using a high speed stirrer to obtain a solution.
実施例 対照試料の調製 メナテトレノン３ｇをプロピレングリコールジカプリン
酸エステル１２ｇに分散せしめたものを対照試料Ａ、メ
ナテトレノン３ｇをプロピレングリコールモノオレイン
酸エステル１２ｇに分散せしめたものを対照試料Ｂ、メ
ナテトレノン３ｇをグリセリンモノオレイン酸エステル
１２ｇに分散せしめたものを対照試料Ｃとした。Example Preparation of Control Samples 3 g of menatetrenone dispersed in 12 g of propylene glycol dicaprate ester was a control sample A, 3 g of menatetrenone was dispersed in 12 g of propylene glycol monooleate ester, a control sample B, and 3 g of menatetrenone were glycerin. Control sample C was prepared by dispersing 12 g of monooleic acid ester.
実験方法 １６時間絶食させた雄性ＳＤ系ラットにBollmanの方法
〔J.L.Bollman et.al.,J.Lab.Clin.Med.，３３ １３４
９（１９６６）〕を改良した手法でリンパ液採取手術を
施した。Experimental method Bollman's method [JL Bollman et.al., J.Lab.Clin.Med., 33 134] was applied to male SD rats that had been fasted for 16 hours.
9 (1966)] was performed to perform lymphatic fluid collection surgery.
手術後は自由摂食として２０日間リンパ液の流出状況を
観察し、リンパ液の流出が良好なラツトのみを使用し
た。メナテトレノン0.5mg相当量の各試料を動物用小型
カプセルに充填し、経口ゾンデを使用して投与後、直ち
に水１mlを与えた。投与後１０時間は絶食とした。After the operation, the outflow of lymph was observed for 20 days as free feeding, and only rats with good outflow of lymph were used. A small amount of each sample corresponding to 0.5 mg of menatetrenone was filled in a small animal capsule, and 1 ml of water was given immediately after administration using an oral probe. Fasted 10 hours after administration.
各試料につき７乃至１０匹のラツトを使用した。Seven to ten rats were used for each sample.
リンパ液は２４時間目まで採取し、下記条件の高速液体
クロマトグラフイー法によつてリンパ液中のメナテトレ
ノン量を測定した。The lymph was collected until the 24th hour, and the amount of menatetrenone in the lymph was measured by the high performance liquid chromatography method under the following conditions.
高速液体クロマトグラフイー法における条件： 充填剤：Nucleosil Ｃ１８ カラム：４．６mm×１５cm 移動相：メタノール／水＝１００／３ 流速：１ml/min 吸光値：２４８nm ｅ．発明の効果 結果を図１および図２に示す。Conditions for high performance liquid chromatography: Packing agent: Nucleosil C 18 column: 4.6 mm × 15 cm Mobile phase: methanol / water = 100/3 Flow rate: 1 ml / min Absorbance value: 248 nm e. Effects of the Invention The results are shown in FIGS. 1 and 2.
図１は対照試料Ａ及びＢならびに検体試料１及び２を投
与した場合、図２は対照試料Ａ及びＣならびに検体試料
３及び４を投与した場合におけるメナテトレノン溶液に
対する吸収比をそれぞれ示す。FIG. 1 shows the absorption ratios to the menatetrenone solution when the control samples A and B and the sample samples 1 and 2 were administered, and FIG. 2 shows the control samples A and C and the sample samples 3 and 4 respectively.
これらのデータから本発明組成物の検体試料１〜４が対
照試料Ａ、Ｂ及びＣに対し、メナテトレノンの経口投与
による吸収性を著しく改善していることがわかる。From these data, it can be seen that the sample samples 1 to 4 of the composition of the present invention have significantly improved the absorbability of oral administration of menatetrenone to the control samples A, B and C.
図１及び図２は投与後２４時間経過の間における種々の
処方についてのメナテトレノン溶液に対する吸収比を示
す。1 and 2 show the absorption ratio of various formulations to menatetrenone solution during the 24 hours after administration.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭58−13508（ＪＰ，Ａ) 特開 昭56−18914（ＪＰ，Ａ) 特開 昭57−4916（ＪＰ，Ａ) 特開 昭57−42616（ＪＰ，Ａ) 新製剤開発システム総合技術−基剤・添 加物篇−Ｐ．201〜208 Ｒ＆Ｄプランニン グ発行（昭和60年７月12日) ─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-58-13508 (JP, A) JP-A-56-18914 (JP, A) JP-A-57-4916 (JP, A) JP-A-57- 42616 (JP, A) New formulation development system comprehensive technology-Bases and additives-P. 201-208 R & D planning issued (July 12, 1985)
Claims (5)
モノ脂肪酸エステル及びソルビタンモノ脂肪酸エステル
のうちの１種又はそれ以上と； 植物油又は合成油 とを必須の成分とするメナテトレノン含有組成物。1. A menatetrenone-containing composition comprising menatetrenone and one or more of propylene glycol monofatty acid ester, glycerin monofatty acid ester and sorbitan monofatty acid ester; and vegetable oil or synthetic oil as essential components.
リーブ油である特許請求の範囲第１項記載の組成物。2. The composition according to claim 1, wherein the vegetable oil is cottonseed oil, peanut oil, sesame oil or olive oil.
エステル又は合成グリセリン脂肪酸エステルである特許
請求の範囲第１項記載の組成物。3. The composition according to claim 1, wherein the synthetic oil is propylene glycol difatty acid ester or synthetic glycerin fatty acid ester.
である特許請求の範囲第１項又は第３項記載の組成物。4. The composition according to claim 1, wherein the fatty acid is caprylic acid and / or oleic acid.
ングリコールモノ脂肪酸エステル、グリセリンモノ脂肪
酸エステル及びソルビタンモノ脂肪酸エステルのうちの
１種又はそれ以上が0.1ないし６０重量部、植物油又は
合成油が0.1ないし６０重量部である特許請求の範囲第
１項記載の組成物。5. One part or more of propylene glycol monofatty acid ester, glycerin monofatty acid ester and sorbitan monofatty acid ester is 0.1 to 60 parts by weight, and vegetable oil or synthetic oil is 0.1 to 60 parts by weight with respect to 1 part by weight of menatetrenone. The composition of claim 1 which is parts by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61138298A JPH0629180B2 (en) | 1986-06-16 | 1986-06-16 | Compositions containing menatetrenone with improved absorption |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61138298A JPH0629180B2 (en) | 1986-06-16 | 1986-06-16 | Compositions containing menatetrenone with improved absorption |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62294612A JPS62294612A (en) | 1987-12-22 |
| JPH0629180B2 true JPH0629180B2 (en) | 1994-04-20 |
Family
ID=15218610
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61138298A Expired - Lifetime JPH0629180B2 (en) | 1986-06-16 | 1986-06-16 | Compositions containing menatetrenone with improved absorption |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0629180B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5447729A (en) * | 1994-04-07 | 1995-09-05 | Pharmavene, Inc. | Multilamellar drug delivery systems |
| CN1113650C (en) * | 1997-07-29 | 2003-07-09 | 法玛西雅厄普约翰美国公司 | Self-emulsifying formulation forlipophilic compounds |
| JP2001294523A (en) * | 2000-04-12 | 2001-10-23 | Nisshin Seifun Group Inc | Composition for vitamin k deficiency |
| JP3980851B2 (en) * | 2001-08-30 | 2007-09-26 | 有限会社ゴトーコーポレーション | Solid preparation, method for producing the same, and food |
| KR100533458B1 (en) | 2002-07-20 | 2005-12-07 | 대화제약 주식회사 | Composition for solubilization of paclitaxel and preparation method thereof |
| JP2005075804A (en) * | 2003-09-03 | 2005-03-24 | Toyo Capsule Kk | Medicinal composition including menatetrenone |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5618914A (en) * | 1979-07-25 | 1981-02-23 | Eisai Co Ltd | Ubidecarenone composition having good absorbability |
| JPS574916A (en) * | 1980-05-28 | 1982-01-11 | Furointo Sangyo Kk | Activation of medical preparation |
| JPS5813508A (en) * | 1981-07-14 | 1983-01-26 | Taiho Yakuhin Kogyo Kk | Drug containing polyglycerol ester of fatty acid |
-
1986
- 1986-06-16 JP JP61138298A patent/JPH0629180B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| 新製剤開発システム総合技術−基剤・添加物篇−Ｐ．２０１〜２０８Ｒ＆Ｄプランニング発行（昭和６０年７月１２日） |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62294612A (en) | 1987-12-22 |
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