JPH10330250A - Menatetrenone oily formulation - Google Patents
Menatetrenone oily formulationInfo
- Publication number
- JPH10330250A JPH10330250A JP16196097A JP16196097A JPH10330250A JP H10330250 A JPH10330250 A JP H10330250A JP 16196097 A JP16196097 A JP 16196097A JP 16196097 A JP16196097 A JP 16196097A JP H10330250 A JPH10330250 A JP H10330250A
- Authority
- JP
- Japan
- Prior art keywords
- weight
- parts
- menatetrenone
- pharmaceutical composition
- fatty acid
- 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
- 235000009491 menaquinone-4 Nutrition 0.000 title claims description 32
- 239000011676 menaquinone-4 Substances 0.000 title claims description 32
- DKHGMERMDICWDU-GHDNBGIDSA-N menaquinone-4 Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 DKHGMERMDICWDU-GHDNBGIDSA-N 0.000 title claims description 32
- 229960005481 menatetrenone Drugs 0.000 title claims description 32
- 239000000203 mixture Substances 0.000 title abstract description 17
- 238000009472 formulation Methods 0.000 title description 7
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 28
- 229930195729 fatty acid Natural products 0.000 claims abstract description 28
- 239000000194 fatty acid Substances 0.000 claims abstract description 28
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 235000011187 glycerol Nutrition 0.000 claims abstract description 17
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 16
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 16
- 235000013871 bee wax Nutrition 0.000 claims abstract description 14
- 239000012166 beeswax Substances 0.000 claims abstract description 14
- 239000010685 fatty oil Substances 0.000 claims abstract description 12
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 10
- 235000010445 lecithin Nutrition 0.000 claims abstract description 10
- 239000000787 lecithin Substances 0.000 claims abstract description 10
- 229940067606 lecithin Drugs 0.000 claims abstract description 10
- 239000004094 surface-active agent Substances 0.000 claims abstract description 10
- -1 sucrose fatty acid ester Chemical class 0.000 claims description 28
- 239000007901 soft capsule Substances 0.000 claims description 21
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 15
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 claims description 10
- 229930006000 Sucrose Natural products 0.000 claims description 10
- 229960005078 sorbitan sesquioleate Drugs 0.000 claims description 10
- 239000005720 sucrose Substances 0.000 claims description 10
- 229960004793 sucrose Drugs 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 abstract description 2
- 230000002439 hemostatic effect Effects 0.000 abstract description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 abstract 1
- 239000007765 cera alba Substances 0.000 abstract 1
- 235000010965 sucrose esters of fatty acids Nutrition 0.000 abstract 1
- 239000001959 sucrose esters of fatty acids Substances 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 18
- 229940068968 polysorbate 80 Drugs 0.000 description 10
- 239000002775 capsule Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 4
- 239000002285 corn oil Substances 0.000 description 4
- 235000005687 corn oil Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 150000003722 vitamin derivatives Chemical class 0.000 description 4
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 235000019485 Safflower oil Nutrition 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 235000005713 safflower oil Nutrition 0.000 description 3
- 239000003813 safflower oil Substances 0.000 description 3
- 241001237745 Salamis Species 0.000 description 2
- 239000008157 edible vegetable oil Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004667 medium chain fatty acids Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000015175 salami Nutrition 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 235000019737 Animal fat Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、止血機能の改善に
臨床上広く使用されているメナテトレノンの経口投与用
組成物に関する。より具体的には、本発明は、メナテト
レノンの経口投与用軟カプセル製剤のための内容液組成
物、及びこれを含有する軟カプセル剤に関する。TECHNICAL FIELD The present invention relates to a composition for oral administration of menatetrenone which is widely used clinically for improving hemostatic function. More specifically, the present invention relates to a content solution composition for a soft capsule formulation for oral administration of menatetrenone, and a soft capsule containing the same.
【０００２】[0002]
【従来の技術】出血及び低プロトロンビン症に有効なビ
タミンＫ剤であるメナテトレノンは、水に難溶の結晶又
は油状の化合物であり、これを油に懸濁又は溶解させた
内服用製剤が知られている。2. Description of the Related Art Menatetrenone, a vitamin K agent effective for bleeding and hypoprothrombinosis, is a crystalline or oily compound that is hardly soluble in water, and an oral preparation in which this is suspended or dissolved in oil is known. ing.
【０００３】[0003]
【発明が解決しようとする課題】本発明は、メナテトレ
ノン軟カプセル剤の製造における取扱を容易にし且つ経
口投与後における迅速な溶解性を与えるための、メナテ
トレノン含有内容液及びこれを含んだ軟カプセル剤を提
供することを目的とする。SUMMARY OF THE INVENTION An object of the present invention is to provide a menatetrenone-containing content liquid and a soft capsule containing the same to facilitate handling in the manufacture of menatetrenone soft capsules and to provide rapid solubility after oral administration. The purpose is to provide.
【０００４】[0004]
【課題を解決するための手段】すなわち本発明は、メナ
テトレノン含有製剤であって、（ａ）食用脂肪油、及び
（ｂ）モノオレイン酸ポリオキシエチレンソルビタン、
セスキオレイン酸ソルビタン及びショ糖脂肪酸エステル
よりなる群より選ばれる界面活性剤を含んでなる担体中
に、メナテトレノンが含有されていることを特徴とする
医薬組成物、及び該医薬組成物を含有する軟カプセル剤
を提供する。That is, the present invention provides a menatetrenone-containing preparation, which comprises (a) an edible fatty oil, and (b) polyoxyethylene sorbitan monooleate;
A pharmaceutical composition characterized by containing menatetrenone in a carrier comprising a surfactant selected from the group consisting of sorbitan sesquioleate and sucrose fatty acid ester, and a softener containing the pharmaceutical composition. Provide capsules.
【０００５】上記界面活性剤は単独又は混合系で使用す
ることができる。これらの界面活性剤のＨＬＢは、他の
成分の種類及び相対的添加量に応じて適宜設定してよ
い。またこれらの界面活性剤のうち特に好ましいのはモ
ノオレイン酸ポリオキシエチレンソルビタン及びショ糖
脂肪酸エステルであり、取り分け好ましいのはモノオレ
イン酸ポリオキシエチレンソルビタンである。The above surfactants can be used alone or in a mixture. The HLB of these surfactants may be appropriately set according to the types and relative amounts of other components. Of these surfactants, particularly preferred are polyoxyethylene sorbitan monooleate and sucrose fatty acid ester, and particularly preferred are polyoxyethylene sorbitan monooleate.
【０００６】上記医薬組成物は更に、ミツロウ若しくは
サラシミツロウ及び／又はグリセリン脂肪酸モノエステ
ルを含むことができる。これらは何れも上記医薬品組成
物の流動性を軟カプセル剤の成型に適したものにするの
に役立ち、またｏ／ｏ型乳化系をより安定化させ、脂溶
性のメナテトレノン吸収を補助する効果をも有すること
が確認された。[0006] The pharmaceutical composition may further comprise beeswax or beeswax and / or glycerin fatty acid monoester. All of these help to make the fluidity of the pharmaceutical composition suitable for molding a soft capsule, stabilize the o / o emulsification system, and assist the absorption of fat-soluble menatetrenone. It was confirmed that it also had.
【０００７】上記医薬組成物はまた、レシチンを含有し
てよい。レシチンもまた、流動性を改善し、乳化系を安
定に保つほか、脂溶性のメナテトレノンの溶解を補助す
る効果を有する。[0007] The pharmaceutical composition may also contain lecithin. Lecithin also has the effect of improving the flowability, keeping the emulsified system stable and assisting the dissolution of the fat-soluble menatetrenone.
【０００８】メナテトレノン１重量部に対して、該食用
脂肪油の量は0.2 乃至１０重量部の範囲にあることが好
ましく、0.5 乃至７重量部であることが更に好ましい。[0008] The amount of the edible fatty oil is preferably in the range of 0.2 to 10 parts by weight, more preferably 0.5 to 7 parts by weight, based on 1 part by weight of menatetrenone.
【０００９】また、グリセリン脂肪酸モノエステル、ミ
ツロウ又はサラシミツロウを使用する場合、メナテトレ
ノン１重量部に対し、グリセリン脂肪酸エステル及びミ
ツロウ又はサラシミツロウの量は、それぞれ0.1 乃至５
重量部の範囲にあることが好ましく、0.2 乃至２重量部
の範囲にあることが更に好ましい。When glycerin fatty acid monoester, beeswax or beeswax is used, the amount of glycerin fatty acid ester and beeswax or beeswax is 0.1 to 5 parts by weight per 1 part by weight of menatetrenone.
It is preferably in the range of parts by weight, more preferably in the range of 0.2 to 2 parts by weight.
【００１０】また、メナテトレノン１重量部に対し、モ
ノオレイン酸ポリオキシエチレンソルビタン、セスキオ
レイン酸ソルビタン及びショ糖脂肪酸エステルよりなる
群より選ばれる界面活性剤の総量は0.05乃至５重量部の
範囲にあることが好ましく、0.1 乃至2.5 重量部の範囲
にあるのが更に好ましい。The total amount of a surfactant selected from the group consisting of polyoxyethylene sorbitan monooleate, sorbitan sesquioleate and sucrose fatty acid ester is in the range of 0.05 to 5 parts by weight per 1 part by weight of menatetrenone. More preferably, it is in the range of 0.1 to 2.5 parts by weight.
【００１１】本明細書において、「食用脂肪油」は、毒
物を含有せず且つ特殊の生理作用を有しない食用に供す
ることのできる動物脂肪油及び植物脂肪油、及び食用に
供することのできる合成されたものであってよいその他
の脂肪酸トリグリセリドをいう。食用脂肪油の例として
は、例えば胡麻油、オリーブ油、綿実油、落花生油、サ
フラワー油、中鎖脂肪酸トリグリセリド等が挙げられる
がこれらに限られない。As used herein, "edible fatty oil" refers to edible animal fat oils and vegetable fat oils which do not contain toxic substances and have no special physiological action, and edible synthetic fats. Refers to other fatty acid triglycerides that may be used. Examples of edible oils include, but are not limited to, sesame oil, olive oil, cottonseed oil, peanut oil, safflower oil, medium chain fatty acid triglycerides, and the like.
【００１２】上記医薬組成物を含んだ軟カプセルの製造
において、使用する軟カプセル皮膜としては慣用のもの
を使用してよい。カプセル皮膜への組成物の充填もまた
通常の方法で行うことができる。In the production of a soft capsule containing the above-mentioned pharmaceutical composition, a conventional soft capsule film may be used. The filling of the capsule shell with the composition can also be carried out in the usual way.
【００１３】[0013]
【実施例】以下に代表的な実施例の幾つかを挙げて本発
明を更に具体的に説明する。 〔実施例１〕 軟カプセル剤 下記の内容液の処方比率に従い、食用脂肪油であるトウ
モロコシ油にグリセリン脂肪酸エステル及びサラシミツ
ロウを加え、60〜70℃に加温して溶解した。これにポリ
ソルベート80及びメナテトレノンを加えて攪拌しながら
冷却し、カプセル内容液を得た。この液を常法に従い軟
カプセル皮膜に充填し、軟カプセル剤を得た。EXAMPLES The present invention will be described more specifically with reference to some typical examples. Example 1 Soft Capsules According to the formulation ratio of the following liquid contents, glycerin fatty acid ester and salami beeswax were added to corn oil, which is an edible fatty oil, and dissolved by heating to 60 to 70 ° C. Polysorbate 80 and menatetrenone were added thereto, and the mixture was cooled with stirring to obtain a capsule content liquid. This liquid was filled in a soft capsule film according to a conventional method to obtain a soft capsule.
【００１４】[0014]
【表１】 （内容液） メナテトレノン ・・・・・・・・・・・ １５重量部 トウモロコシ油 ・・・・・・・・・・・ ７４重量部 グリセリン脂肪酸モノエステル* ・・・・ ５重量部 サラシミツロウ ・・・・・・・・・・・ ５重量部ポリソルベート８０ ・・・・・・・・・ １重量部 合計 １００重量部* グリセリン脂肪酸モノエステルとしては、炭素数18の
飽和脂肪酸のエステルであるポエムＰ−200 （理研ビタ
ミン）を使用した。[Table 1] (Content liquid) Menatetrenone ・ ・ ・ 15 parts by weight Corn oil ・ ・ ・ 74 parts by weight Glycerin fatty acid monoester *・ ・ ・ 5 parts by weight 5 parts by weight Polysorbate 80 5 parts by weight Polysorbate 80 1 part by weight Total 100 parts by weight * As glycerin fatty acid monoester, saturated fatty acid having 18 carbon atoms is used. Poem P-200 (RIKEN vitamin) which is an ester was used.
【００１５】〔実施例２〕 軟カプセル剤 下記の内容液の処方比率に従い、食用脂肪油であるトウ
モロコシ油にレシチン、ポリソルベート８０及びセスキ
オレイン酸ソルビタンを加え、60〜70℃に加温した。こ
れにメナテトレノンを加えて攪拌しながら冷却し、カプ
セル内容液を得た。この液を常法に従い軟カプセル皮膜
に充填し、軟カプセル剤を得た。Example 2 Soft Capsule In accordance with the formulation ratio of the following contents, lecithin, polysorbate 80 and sorbitan sesquioleate were added to corn oil, which is an edible fatty oil, and heated to 60 to 70 ° C. Menatetrenone was added thereto, and the mixture was cooled with stirring to obtain a capsule content liquid. This liquid was filled in a soft capsule film according to a conventional method to obtain a soft capsule.
【００１６】[0016]
【表２】 （内容液） メナテトレノン ・・・・・・・・・・・ １５重量部 トウモロコシ油 ・・・・・・・・・・・ ６５重量部 レシチン ・・・・・・・・・・・・・・ ５重量部 ポリソルベート８０ ・・・・・・・・・ １１重量部セスキオレイン酸ソルビタン ・・・・・ ４重量部 合計 １００重量部[Table 2] (Content liquid) Menatetrenone ・ ・ ・ 15 parts by weight Corn oil ・ ・ ・ 65 parts by weight lecithin 5 parts by weight Polysorbate 80 11 parts by weight Sorbitan sesquioleate 4 parts by weight Total 100 parts by weight
【００１７】〔実施例３〕下記の内容液の処方比率に従
い、食用脂肪油として中鎖脂肪酸トリグリセリドを用
い、実施例１と同様に操作して軟カプセル剤を得た。Example 3 A soft capsule was obtained in the same manner as in Example 1 except that medium-chain fatty acid triglyceride was used as an edible fatty oil in accordance with the following formulation ratio of the liquid contents.
【００１８】[0018]
【表３】 〔内容液〕 メナテトレノン ・・・・・・・・・・・ １５重量部 中鎖脂肪酸トリグリセリド ・・・・・・ ４９重量部 グリセリン脂肪酸モノエステル* ・・・ ８重量部 サラシミツロウ ・・・・・・・・・・・ ８重量部 レシチン ・・・・・・・・・・・・・・ ５重量部 ポリソルベート８０ ・・・・・・・・・ １１重量部セスキオレイン酸ソルビタン ・・・・・ ４重量部 合計 １００重量部* グリセリン脂肪酸モノエステルとしては、ポエムＰ−
200 （理研ビタミン）を使用した。[Table 3] [Content liquid] Menatetrenone 15 parts by weight Medium-chain fatty acid triglyceride 49 parts by weight Glycerin fatty acid monoester * 8 parts by weight 8 parts by weight Lecithin 5 parts by weight Polysorbate 80 11 parts by weight sorbitan sesquioleate ... 4 parts by weight total 100 parts by weight * Poem P- as glycerin fatty acid monoester
200 (RIKEN vitamin) was used.
【００１９】〔実施例４〕 軟カプセル剤 下記の内容液の処方比率に従い、食用脂肪油であるサフ
ラワー油にグリセリン脂肪酸モノエステル及びショ糖脂
肪酸エステルを加え、60〜70℃に加温して溶解する。こ
れにポリソルベート８０、セスキオレイン酸ソルビタン
及びメナテトレノンを加えて攪拌しながら冷却し、カプ
セル内容液を得た。この液を常法に従い軟カプセル皮膜
に充填し、軟カプセル剤を得た。Example 4 Soft Capsules According to the formulation ratio of the following liquid contents, glycerin fatty acid monoester and sucrose fatty acid ester were added to safflower oil, which is an edible fatty oil, and heated to 60 to 70 ° C. Dissolve. Polysorbate 80, sorbitan sesquioleate and menatetrenone were added thereto, and the mixture was cooled with stirring to obtain a capsule content liquid. This liquid was filled in a soft capsule film according to a conventional method to obtain a soft capsule.
【００２０】[0020]
【表４】 （内容液） メナテトレノン ・・・・・・・・・・・ １５重量部 サフラワー油 ・・・・・・・・・・・・ ６０重量部 グリセリン脂肪酸モノエステル*1 ・・・ １０重量部 ショ糖脂肪酸エステル*2 ・・・・・・・ ２重量部 ポリソルベート８０ ・・・・・・・・・ ８重量部セスキオレイン酸ソルビタン ・・・・・ ５重量部 合計 １００重量部*1 グリセリン脂肪酸モノエステルとしては、ポエムＰ
−200 （理研ビタミン）を使用した。*2 ショ糖脂肪酸エステルとしては、ＤＫエステルＦ−
10（第一工業製薬）（ショ糖エステル：ＨＬＢ約１：結
合脂肪酸；ステアリン酸70％，パルミチン酸30％：モノ
エステル０％，ジ・トリ・ポリエステル100 ％）を使用
した。[Table 4] (Content liquid) Menatetrenone ・ ・ ・ 15 parts by weight Safflower oil ・ ・ ・ ・ ・ ・ 60 parts by weight Glycerin fatty acid monoester * 1・ ・ ・10 parts by weight of sucrose fatty acid ester * 2 ......... 2 parts by weight of polysorbate 80 ......... 8 parts by weight of sorbitan sesquioleate ..... 5 parts by weight per 100 parts by weight * 1 Poem P is a glycerin fatty acid monoester.
-200 (RIKEN vitamin) was used. * 2 As sucrose fatty acid ester, DK ester F-
10 (Daiichi Kogyo Seiyaku) (sucrose ester: HLB about 1: bound fatty acid; stearic acid 70%, palmitic acid 30%: monoester 0%, di-tripolyester 100%).
【００２１】〔実施例５〕下記の内容液の処方比率に従
い、食用脂肪油である落花生油に、グリセリン脂肪酸モ
ノエステルにショ糖脂肪酸エステル及びサラシミツロウ
を加えて60〜70℃に加温して溶解させた。これにポリソ
ルベート８０、セスキオレイン酸ソルビタン、レシチン
及びメナテトレノンを加えて攪拌しながら冷却し、カプ
セル内容液を得た。この液を常法に従い軟カプセル皮膜
に充填し、軟カプセル剤を得た。Example 5 In accordance with the following composition ratio of the liquid contents, glycerin fatty acid monoester, sucrose fatty acid ester and salami beeswax were added to edible oil peanut oil and heated to 60 to 70 ° C. Dissolved. Polysorbate 80, sorbitan sesquioleate, lecithin and menatetrenone were added thereto, and the mixture was cooled with stirring to obtain a capsule content liquid. This liquid was filled in a soft capsule film according to a conventional method to obtain a soft capsule.
【００２２】[0022]
【表５】 （内容液） メナテトレノン ・・・・・・・・・・・ １５重量部 落花生油 ・・・・・・・・・・・・・・ ５７重量部 グリセリン脂肪酸モノエステル* ・・・・ ５重量部 ショ糖脂肪酸エステル ・・・・・・・・ ２重量部 サラシミツロウ ・・・・・・・・・・・・ ５重量部 ポリソルベート８０ ・・・・・・・・・・ ８重量部 セスキオレイン酸ソルビタン ・・・・・・ ５重量部レシチン ・・・・・・・・・・・・・・・ ３重量部 合計 １００重量部*1 グリセリン脂肪酸モノエステルとしては、ポエムＰ
−200 （理研ビタミン）を使用した。[Table 5] (Content liquid) Menatetrenone… 15 parts by weight Peanut oil… 57 parts by weight Glycerin fatty acid monoester *・ ・ ・5 parts by weight sucrose fatty acid ester 2 parts by weight Beeswax 5 parts by weight Polysorbate 80 8 parts by weight Part Sorbitan sesquioleate 5 parts by weight Lecithin 3 parts by weight Total 100 parts by weight * 1 As glycerin fatty acid monoester, Poem P
-200 (RIKEN vitamin) was used.
【００２３】〔溶出試験〕各実施例の処方につき、日本
薬局方溶出試験法第２法により、製剤からのメナテトレ
ノンの溶出試験を実施した。結果を、縦軸に溶出率
（％）、横軸に時間をとって図１に示す。図より明らか
な通り、何れの実施例の製剤も良好・迅速な溶出挙動を
示した。[Dissolution Test] With respect to the formulations of the respective examples, a dissolution test of menatetrenone from the preparation was carried out according to the Japanese Pharmacopoeia Dissolution Test Method 2, Method 2. The results are shown in FIG. 1 with the elution rate (%) on the vertical axis and time on the horizontal axis. As is clear from the figure, the preparations of all Examples exhibited good and rapid dissolution behavior.
【００２４】[0024]
【発明の効果】本発明のメナテトレノン含有医薬組成物
は、軟カプセル剤の製剤化に際してメナテトレノンと担
体との混和性に優れ、且つ投与後の溶解性にも優れてい
る。Industrial Applicability The pharmaceutical composition containing menatetrenone of the present invention has excellent miscibility between menatetrenone and a carrier in the preparation of soft capsules, and also has excellent solubility after administration.
【図１】 実施例の製剤からのメナテトレノンの溶出挙
動を示すグラフ。FIG. 1 is a graph showing the dissolution behavior of menatetrenone from the preparations of Examples.
Claims (10)
ン酸ポリオキシエチレンソルビタン、セスキオレイン酸
ソルビタン及びショ糖脂肪酸エステルよりなる群より選
ばれる界面活性剤を含んでなる担体中に、メナテトレノ
ンが含有されていることを特徴とする医薬組成物。1. A carrier comprising (a) an edible fatty oil and (b) a surfactant selected from the group consisting of polyoxyethylene sorbitan monooleate, sorbitan sesquioleate and sucrose fatty acid ester, A pharmaceutical composition comprising menatetrenone.
／又はグリセリン脂肪酸モノエステルを含有することを
特徴とする、請求項１の医薬組成物。2. The pharmaceutical composition according to claim 1, wherein said carrier contains beeswax or beeswax and / or glycerin fatty acid monoester.
徴とする、請求項１又は２の医薬組成物。3. The pharmaceutical composition according to claim 1, wherein said carrier further contains lecithin.
剤の量が0.05乃至５重量部である、請求項１乃至３の何
れかの医薬組成物。4. The pharmaceutical composition according to claim 1, wherein the amount of the surfactant is 0.05 to 5 parts by weight based on 1 part by weight of menatetrenone.
油の量が0.2 乃至12重量部であることを特徴とする、請
求項１乃至４の何れかの医薬組成物。5. The pharmaceutical composition according to claim 1, wherein the amount of the edible fatty oil is 0.2 to 12 parts by weight based on 1 part by weight of menatetrenone.
脂肪酸モノエステル及びミツロウ又はサラシミツロウの
量がそれぞれ0.1 乃至５重量部であることを特徴とす
る、請求項２の医薬組成物。6. The pharmaceutical composition according to claim 2, wherein the amount of glycerin fatty acid monoester and beeswax or beeswax is 0.1 to 5 parts by weight per 1 part by weight of menatetrenone.
徴とする、請求項６の医薬組成物。7. The pharmaceutical composition according to claim 6, wherein said carrier further contains lecithin.
剤の量が0.05乃至５重量部である、請求項６又は７の医
薬組成物。8. The pharmaceutical composition according to claim 6, wherein the amount of the surfactant is 0.05 to 5 parts by weight based on 1 part by weight of menatetrenone.
油の量が0.2 乃至12重量部であることを特徴とする、請
求項６乃至８の何れかの医薬組成物。9. The pharmaceutical composition according to claim 6, wherein the amount of the edible fatty oil is 0.2 to 12 parts by weight per 1 part by weight of menatetrenone.
含有する軟カプセル剤。10. A soft capsule containing the pharmaceutical composition according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16196097A JPH10330250A (en) | 1997-06-03 | 1997-06-03 | Menatetrenone oily formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16196097A JPH10330250A (en) | 1997-06-03 | 1997-06-03 | Menatetrenone oily formulation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10330250A true JPH10330250A (en) | 1998-12-15 |
Family
ID=15745348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16196097A Pending JPH10330250A (en) | 1997-06-03 | 1997-06-03 | Menatetrenone oily formulation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH10330250A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001128643A (en) * | 1999-11-08 | 2001-05-15 | Nihon Yakugyo:Kk | Soft capsule enclosing mastic oil solution |
| JP2005075804A (en) * | 2003-09-03 | 2005-03-24 | Toyo Capsule Kk | Medicinal composition including menatetrenone |
| JP2006504628A (en) * | 2002-04-19 | 2006-02-09 | ビオグルト ビオガルデ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | Matrix containing bioactive phospholipid-containing components |
| JP2009079011A (en) * | 2007-09-27 | 2009-04-16 | Riken Vitamin Co Ltd | Liquid composition for filling soft capsule |
| WO2011027605A1 (en) * | 2009-09-07 | 2011-03-10 | 理研ビタミン株式会社 | Liquid composition to be filled in soft capsules |
-
1997
- 1997-06-03 JP JP16196097A patent/JPH10330250A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001128643A (en) * | 1999-11-08 | 2001-05-15 | Nihon Yakugyo:Kk | Soft capsule enclosing mastic oil solution |
| JP4601100B2 (en) * | 1999-11-08 | 2010-12-22 | 三生医薬株式会社 | Soft capsule containing mastic oil |
| JP2006504628A (en) * | 2002-04-19 | 2006-02-09 | ビオグルト ビオガルデ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | Matrix containing bioactive phospholipid-containing components |
| JP2005075804A (en) * | 2003-09-03 | 2005-03-24 | Toyo Capsule Kk | Medicinal composition including menatetrenone |
| JP2009079011A (en) * | 2007-09-27 | 2009-04-16 | Riken Vitamin Co Ltd | Liquid composition for filling soft capsule |
| WO2011027605A1 (en) * | 2009-09-07 | 2011-03-10 | 理研ビタミン株式会社 | Liquid composition to be filled in soft capsules |
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