JPS6139924B2 - - Google Patents
Info
- Publication number
- JPS6139924B2 JPS6139924B2 JP51130435A JP13043576A JPS6139924B2 JP S6139924 B2 JPS6139924 B2 JP S6139924B2 JP 51130435 A JP51130435 A JP 51130435A JP 13043576 A JP13043576 A JP 13043576A JP S6139924 B2 JPS6139924 B2 JP S6139924B2
- Authority
- JP
- Japan
- Prior art keywords
- lecithin
- ethanol
- emulsion
- fat
- water
- 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
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- 239000000839 emulsion Substances 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 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 description 20
- 229940067606 lecithin Drugs 0.000 claims description 20
- 239000000787 lecithin Substances 0.000 claims description 20
- 235000010445 lecithin Nutrition 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 239000012071 phase Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 8
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 7
- 238000004945 emulsification Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000001804 emulsifying effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229940083466 soybean lecithin Drugs 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229930003799 tocopherol Natural products 0.000 description 4
- 239000011732 tocopherol Substances 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000008158 vegetable oil Substances 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical class COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 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 description 3
- 235000009491 menaquinone-4 Nutrition 0.000 description 3
- 239000011676 menaquinone-4 Substances 0.000 description 3
- 229960005481 menatetrenone Drugs 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 235000012424 soybean oil Nutrition 0.000 description 3
- 239000003549 soybean oil Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 235000017471 coenzyme Q10 Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000011772 phylloquinone Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- 229960004747 ubidecarenone Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 2
- PFRQBZFETXBLTP-RCIYGOBDSA-N 2-[(2e,6e,10e,14e,18e)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-1-yl]-3-methyl-1,4-dihydronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-RCIYGOBDSA-N 0.000 description 1
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- -1 Nikkol HCO-50 Chemical compound 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000019175 phylloquinone Nutrition 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 description 1
- 229960001898 phytomenadione Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Description
本発明はレシチンおよびエタノールを用いて製
造した、脂溶性薬物の安定な乳化液に関するもの
である。
従来、脂溶性薬物の液剤として、非イオン性界
面活性剤を多量に用いた可溶化型の製剤が多用さ
れてきたが、最近では合成界面活性剤の人体に対
する副作用が問題となつてきている。そこで本発
明者等は、合成界面活性剤ではなく、天然物質で
比較的安全性の高いレシチンを用いて乳化型の製
剤を製造する事を試みた。これまでレシチンを用
いて脂溶性薬物を乳化した例としては、ゲフアル
ナートをレシチンで乳化した例（特開昭50−
126821）、およびビタミンＥまたはそのエステル
をレシチンおよび植物油を用いて乳化した例（特
開昭49−50124）などが知られている。しかし、
これらの方法で脂溶性薬物の乳化を行なう際に
は、レシチンの乳化力が弱いので加圧乳化機とい
う特殊な装置を必要とし、しかも得られた乳化液
の長期安定性は十分とは言えない。本発明者等
は、より安定な脂溶性薬物の乳化液を製造すべく
研究した結果、レシチンと脂溶性薬物をエタノー
ルに溶解し、この溶液を水へ加えて乳化すれば安
定な乳化液が得られる事を見い出し本発明を完成
した。前記特開昭49−50124号公報には、場合に
よりレシチンをエタノールに溶解して用いる事が
記載されているが、本発明の構成とは異なつてい
る。該方法は植物油を必須成分とし、エタノール
は所望により乳化前に留去するのに対し、本発明
は植物油を用いなく、またエタノールも最後まで
除去しない。レシチン、エタノールを用いて脂溶
性薬物の乳化液を製造する際に、さらに植物油を
添加すると、かえつて乳化液の安定性が悪くなる
事を後述の実施例２において示した。
本発明は、脂溶性薬物１重量部およびレシチン
0.1〜10重量部をエタノール１〜50重量部に溶解
し、次いでこれを水に加えて乳化した脂溶性薬物
の乳化液である。さらに、乳化液の安定性の点か
ら、各成分の特に好ましい配合割合は、脂溶性薬
物１重量部に対し、レシチン0.2〜３重量部およ
びエタノール５〜20重量部である。
本発明の脂溶性薬物としては、例えば、フイト
ナジオン（ビタミンK1）、メナテトレノン（ビタ
ミンK2）、コエンザイムＱ同族体、トコフエロー
ル類およびその誘導体、ゲフアルナートなどがあ
げられる。またレシチンとしては、大豆レシチ
ン、卵黄レシチンのいずれを用いても良い。
本発明において、脂溶性薬物およびレシチンを
エタノールに溶解した溶液を水に加えて乳化する
際には、従来のレシチンを用いた乳化の際に行な
つている加圧乳化機を用いた高せん断力下での乳
化は必要でなく、通常の撹拌乳化で十分に安定な
乳化液を得ることができる。
本発明において撹拌乳化を行なう際、脂溶性薬
物とレシチンのエタノール溶液を、単に水に添加
するのではなく、管を通して水中へ加圧注入する
方法を採れば、より粒径の微細な安定な乳化液を
得る事ができる。また、本発明に用いるレシチン
の一部を予め水に溶解して乳化を行なつても良
い。
本発明の乳化液の製造においては、必要によ
り、等張化剤、緩衝剤、溶解補助剤、他の乳化
剤、矯味剤、矯臭剤、防腐剤、安定化剤等をさら
に適宜配合する事ができる。
本発明の乳化液は、通常、調製時には平均0.5
μ以下の直径を持つ微細な乳化粒子から成り、加
熱滅菌に耐え、経時的な物理的安定性にすぐれて
いるものである。
次に実施例を示し、本発明をさらに詳しく説明
する。
実施例 １
表に示す脂溶性薬物、レシチン、エタノール、
その他の添加剤を55〜60℃の水浴上で加温溶解し
た。
これを同温度に加熱した５％ブドウ糖含有注射
用蒸留水中に添加して乳化し、全量100mlとし
た。乳化は、本発明試料１〜５は油相を水相に加
圧注入し、プロペラ式撹拌機を用いて300rpmで
５分間処理して行ない、対照試料６〜10は油相と
水相をT.K.ホモミキサー（商品名、特殊機化工
業K.K.）を用いて4000rpmで10分間処理して行
なつた。
得られた乳化液を、ミリポアフイルターを用い
て過した。
液をアンプルに分注して熔閉した後、100℃
で60分間加熱滅菌した。
上記方法で得られた乳化液、およびこれを室温
にて６ケ月放置したものについて、肉眼による観
察（外観）および電子顕微鏡による粒子径の観察
を行なつた。下記の表に示すように本発明の乳化
液は対照のものより安定性が優れている。
The present invention relates to a stable emulsion of a fat-soluble drug prepared using lecithin and ethanol. Conventionally, solubilized preparations containing large amounts of nonionic surfactants have been frequently used as liquid preparations for fat-soluble drugs, but recently the side effects of synthetic surfactants on the human body have become a problem. Therefore, the present inventors attempted to produce an emulsion-type preparation using lecithin, which is a natural substance and has relatively high safety, instead of a synthetic surfactant. As an example of emulsifying a fat-soluble drug using lecithin, there is an example of emulsifying gefalnate with lecithin (Japanese Unexamined Patent Application Publication No. 1989-1999).
126821), and an example in which vitamin E or its ester is emulsified using lecithin and vegetable oil (Japanese Patent Application Laid-Open No. 49-50124). but,
When emulsifying fat-soluble drugs using these methods, a special device called a pressure emulsifier is required because the emulsifying power of lecithin is weak, and the long-term stability of the resulting emulsion is not sufficient. . As a result of research to produce a more stable emulsion of fat-soluble drugs, the present inventors discovered that by dissolving lecithin and fat-soluble drugs in ethanol and emulsifying this solution by adding it to water, a stable emulsion can be obtained. He discovered that this could be done and completed the present invention. JP-A-49-50124 discloses that lecithin is used after being dissolved in ethanol in some cases, but this is different from the structure of the present invention. While this method uses vegetable oil as an essential component and ethanol is optionally distilled off before emulsification, the present invention does not use vegetable oil and does not remove ethanol to the end. It was shown in Example 2 below that when vegetable oil is further added when producing an emulsion of a fat-soluble drug using lecithin and ethanol, the stability of the emulsion worsens. The present invention provides 1 part by weight of a fat-soluble drug and lecithin.
An emulsion of a fat-soluble drug is obtained by dissolving 0.1 to 10 parts by weight in 1 to 50 parts by weight of ethanol, and then adding this to water to emulsify. Furthermore, from the viewpoint of stability of the emulsion, a particularly preferred blending ratio of each component is 0.2 to 3 parts by weight of lecithin and 5 to 20 parts by weight of ethanol per 1 part by weight of the fat-soluble drug. Examples of the fat-soluble drugs of the present invention include phytonadione (vitamin K 1 ), menatetrenone (vitamin K 2 ), coenzyme Q analogues, tocopherols and their derivatives, and gefalnate. Further, as the lecithin, either soybean lecithin or egg yolk lecithin may be used. In the present invention, when a solution of a fat-soluble drug and lecithin dissolved in ethanol is added to water and emulsified, high shear force is applied using a pressurized emulsifier, which is used in conventional emulsification using lecithin. Emulsification below is not necessary, and a sufficiently stable emulsion can be obtained by ordinary stirring emulsification. When performing stirring emulsification in the present invention, instead of simply adding the ethanol solution of the fat-soluble drug and lecithin to water, if a method is adopted in which the ethanol solution is injected under pressure into water through a tube, stable emulsification with finer particle size can be achieved. liquid can be obtained. Further, a part of the lecithin used in the present invention may be dissolved in water in advance and emulsified. In the production of the emulsion of the present invention, isotonic agents, buffers, solubilizing agents, other emulsifiers, flavoring agents, flavoring agents, preservatives, stabilizers, etc. can be further added as appropriate. . The emulsion of the present invention usually has an average of 0.5
It consists of fine emulsified particles with a diameter of less than μ, can withstand heat sterilization, and has excellent physical stability over time. EXAMPLES Next, the present invention will be explained in more detail with reference to Examples. Example 1 Fat-soluble drugs shown in the table, lecithin, ethanol,
Other additives were dissolved by heating on a water bath at 55-60°C. This was added to distilled water for injection containing 5% glucose heated to the same temperature and emulsified to make a total volume of 100 ml. Emulsification was carried out for samples 1 to 5 of the present invention by injecting the oil phase into the aqueous phase under pressure and treating it for 5 minutes at 300 rpm using a propeller stirrer, and for control samples 6 to 10, the oil phase and the aqueous phase were mixed at TK. The treatment was carried out using a homomixer (trade name, Tokushu Kika Kogyo KK) at 4000 rpm for 10 minutes. The resulting emulsion was passed through a Millipore filter. After dispensing the liquid into ampoules and melting them, heat them to 100℃.
sterilized by heating for 60 minutes. The emulsion obtained by the above method and the emulsion left at room temperature for 6 months were observed with the naked eye (appearance) and the particle size was observed with an electron microscope. As shown in the table below, the emulsion of the present invention has better stability than the control.
【表】【table】
【表】
実施例 ２
レシチンおよびエタノールを用いてビタミンＥ
アセテートの乳化液を製造した。対照として、大
豆油を用いた例を示す。配合量および製造法を次
に示す。[Table] Example 2 Vitamin E using lecithin and ethanol
An acetate emulsion was produced. As a control, an example using soybean oil is shown. The blending amount and manufacturing method are shown below.
【表】
本発明の処方および対照２の処方では、ビタミ
ンＥアセテート、エタノール、卵黄レシチンおよ
び大豆油（対照２のみ）を55〜60℃で加温溶解
し、これを同温度のグリセリンを溶解した注射用
蒸留水中へ撹拌下（300rpm）に加圧注入して乳
化した。対照１および３の処方では、ビタミンＥ
アセテートと大豆油の混液に卵黄レシチンまたは
卵黄レシチンのエタノール溶液を加え、対照１で
はそのまま、対照３では50℃以下の減圧下でエタ
ノールを留去した後、グリセリンを溶解した注射
用蒸留水中へ撹拌下に加え、ホモミキサーで粗乳
化し、マントンガウリン加圧乳化機を用いて4000
ポンドの圧力で乳化した。
得られた各乳化液をミアポリフイルターで過
し、アンプルに分注して熔閉した後、100℃で60
分間加熱滅菌した。各乳化液の製造直後の状態、
および室温または40℃で保存後の安定性を調べ
た。結果を次の表に示す。[Table] In the formulation of the present invention and the formulation of Control 2, vitamin E acetate, ethanol, egg yolk lecithin, and soybean oil (Control 2 only) were dissolved by heating at 55 to 60°C, and this was dissolved in glycerin at the same temperature. The mixture was injected into distilled water for injection under pressure and stirring (300 rpm) to emulsify. Controls 1 and 3 formulations contain vitamin E
Egg yolk lecithin or an ethanol solution of egg yolk lecithin was added to a mixture of acetate and soybean oil, and for Control 1, the ethanol was distilled off under reduced pressure at 50°C or less, and then stirred into distilled water for injection in which glycerin had been dissolved. Coarsely emulsify with a homo mixer, and use a Manton Gaulin pressure emulsifier to
Emulsified under pounds of pressure. Each emulsion obtained was filtered through a Mia Poly filter, dispensed into ampoules and melted, and then heated at 100℃ for 60 minutes.
Heat sterilized for minutes. The state of each emulsion immediately after production,
and the stability after storage at room temperature or 40°C was investigated. The results are shown in the table below.
【表】
実施例 ３
メナテトレノン ４ｇ
精製大豆レシチン １ｇ
エタノール 36ｇ
マクロゴール400 50ｇ
ブドウ糖 50ｇ注射用蒸留水 全量1000ml
メナテトレノン、精製大豆レシチン、エタノー
ル、マクロゴール400を約60℃の水浴上で加温溶
解し油相とした。また、ブドウ糖を注射用蒸留水
に溶解し約60℃に加温して水相とした。油相を水
相へ撹拌下（300rpm）に加圧注入して乳化し
た。乳化液をミリポアフイルターで過し、アン
プルに分注して熔閉した後、100℃で60分間加熱
滅菌して注射剤とした。
実施例 ４
天然トコフエロール濃縮物（大豆起原） 10 ｇ
卵黄レシチン １ ｇ
大豆レシチン ２ ｇ
エタノール 40 ｇ
プロピレングリコール 30 ｇ
エチルパラペン 0.5ｇ精製水 全量1000 ml
天然トコフエロール濃縮物、卵黄レシチン、エ
タノール、プロピレングリコールを約60℃の水浴
上で加温溶解し油相とした。一方、大豆レシチ
ン、エチルパラペンを精製水に溶解し、約70℃に
加温して水相とした。油相を水相へ撹拌下
（300rpm）に加圧注入して乳化液を得た。本乳化
液は天然トコフエロールの食品添加用の剤型とし
て好ましい。
実施例 ５
ユビデカレノン ２ ｇ
精製卵黄レシチン 0.5ｇ
ニツコールHCO−50（商標、日光ケミカルズ
社） 0.5ｇ
エタノール 32 ｇ
氷酢酸 ２ ｇ
キシリトール 25 ｇ
0.1N水酸化ナトリウム 適量注射用蒸留水 全量1000 ml
ユビデカレノン、精製卵黄レシチン、ニツコー
ルHCO−50、エタノール、氷酢酸を混合溶解
し、約40℃に加温して油相とした。一方、キシリ
トールを注射用蒸留水に溶解し、約45℃に加温し
て水相とした。油相を水相へ撹拌下（300rpm）
に加圧注入して乳化した。乳化液に0.1N水酸化
ナトリウムを加えてPH6.0に調整した。次いで、
ミリポアフイルターで過し、アンプルに分注し
て熔閉した後、100℃で60分間加熱滅菌して注射
剤とした。[Table] Example 3 Menatetrenone 4g Purified soybean lecithin 1g Ethanol 36g Macrogol 400 50g Glucose 50g Distilled water for injection Total volume 1000ml Menatetrenone , purified soybean lecithin, ethanol, and Macrogol 400 were heated and dissolved in a water bath at about 60°C to make an oil. It was a phase. In addition, glucose was dissolved in distilled water for injection and heated to about 60°C to form an aqueous phase. The oil phase was injected into the water phase under pressure and stirring (300 rpm) to emulsify it. The emulsion was filtered through a Millipore filter, dispensed into ampoules and sealed, and then heat sterilized at 100°C for 60 minutes to prepare an injection. Example 4 Natural tocopherol concentrate (soybean origin) 10 g Egg yolk lecithin 1 g Soybean lecithin 2 g Ethanol 40 g Propylene glycol 30 g Ethylparapen 0.5 g Purified water Total volume 1000 ml Natural tocopherol concentrate, egg yolk lecithin, ethanol, propylene glycol was dissolved by heating on a water bath at about 60°C to form an oil phase. On the other hand, soybean lecithin and ethyl paraben were dissolved in purified water and heated to about 70°C to form an aqueous phase. The oil phase was injected into the water phase under pressure and stirring (300 rpm) to obtain an emulsion. This emulsion is preferable as a food additive formulation of natural tocopherols. Example 5 Ubidecarenone 2 g Purified egg yolk lecithin 0.5 g Nitsukor HCO-50 (trademark, Nikko Chemicals) 0.5 g Ethanol 32 g Glacial acetic acid 2 g Xylitol 25 g 0.1N sodium hydroxide Appropriate amount Distilled water for injection Total volume 1000 ml Ubidecarenone, purified Egg yolk lecithin, Nikkol HCO-50, ethanol, and glacial acetic acid were mixed and dissolved, and heated to about 40°C to form an oil phase. On the other hand, xylitol was dissolved in distilled water for injection and heated to about 45°C to form an aqueous phase. Stirring the oil phase into the water phase (300 rpm)
was injected under pressure to emulsify. 0.1N sodium hydroxide was added to the emulsion to adjust the pH to 6.0. Then,
The mixture was passed through a Millipore filter, dispensed into ampoules and melted, and then heat sterilized at 100°C for 60 minutes to prepare an injection.
Claims (1)
重量部をエタノール１〜50重量部に溶解し、次い
でこれを水に加えて乳化した脂溶性薬物の乳化
液。 ２ 脂溶性薬物１重量部に対し、レシチン0.2〜
３重量部およびエタノール５〜20重量部を用い
る、特許請求の範囲第１項記載の乳化液。[Claims] 1. 1 part by weight of a fat-soluble drug and 0.1 to 10 parts of lecithin
An emulsion of a fat-soluble drug prepared by dissolving 1 to 50 parts by weight of ethanol and then adding the same to water to emulsify. 2 Lecithin 0.2 to 1 part by weight of fat-soluble drug
3 parts by weight and 5 to 20 parts by weight of ethanol, the emulsion according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13043576A JPS5356315A (en) | 1976-11-01 | 1976-11-01 | Emulsified solution of fat soluble drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13043576A JPS5356315A (en) | 1976-11-01 | 1976-11-01 | Emulsified solution of fat soluble drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5356315A JPS5356315A (en) | 1978-05-22 |
| JPS6139924B2 true JPS6139924B2 (en) | 1986-09-06 |
Family
ID=15034156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13043576A Granted JPS5356315A (en) | 1976-11-01 | 1976-11-01 | Emulsified solution of fat soluble drugs |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5356315A (en) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5775916A (en) * | 1980-10-29 | 1982-05-12 | Nippon Chemiphar Co Ltd | Coenzyme q pharmaceutical and its preparation |
| JPS57209216A (en) * | 1981-06-19 | 1982-12-22 | Daigo Eiyou Kagaku Kk | Compound fat-soluble vitamin injection capable of being medicated by venoclysis and its preparation |
| JPS588010A (en) * | 1981-07-08 | 1983-01-18 | Eisai Co Ltd | Ubidecarenone-containing ribosome |
| JPS58113127A (en) * | 1981-12-28 | 1983-07-05 | Ajinomoto Co Inc | Aqueous solution containing ubidecarenone |
| JPS58162517A (en) * | 1982-03-19 | 1983-09-27 | Green Cross Corp:The | Fat-soluble vitamin-containing fatty emulsion |
| JPS5910511A (en) * | 1982-07-07 | 1984-01-20 | Eisai Co Ltd | Aqueous solution containing fat-soluble substance |
| SE8206744D0 (en) * | 1982-11-26 | 1982-11-26 | Fluidcarbon International Ab | PREPARATION FOR CONTROLLED RELEASE OF SUBSTANCES |
| JPS6025918A (en) * | 1983-07-25 | 1985-02-08 | Ajinomoto Co Inc | Aqueous solution containing fat-soluble drug |
| JPS6051104A (en) * | 1983-08-30 | 1985-03-22 | Ajinomoto Co Inc | Vitamin e-containing aqueous solution |
| NO157596C (en) * | 1983-12-16 | 1988-09-27 | Alf Lange | DEVICE FOR PRESENTATION OF INFORMATION. |
| CH661438A5 (en) * | 1984-04-09 | 1987-07-31 | Seuref Ag | Pharmaceutical compositions acting antianossica and metabolic brain. |
| JPS63188624A (en) * | 1987-01-29 | 1988-08-04 | Maruzen Kasei Kk | Vitamin e-containing aqueous solution |
| CA1323306C (en) * | 1987-03-05 | 1993-10-19 | Mircea C. Popescu | Pharmacological agent-lipid solution preparation |
| US5154930A (en) * | 1987-03-05 | 1992-10-13 | The Liposome Company, Inc. | Pharmacological agent-lipid solution preparation |
| JP2521467B2 (en) * | 1987-04-17 | 1996-08-07 | 株式会社コーセー | Translucent lotion |
| US5376381A (en) * | 1988-02-25 | 1994-12-27 | The Liposome Company, Inc. | Integrity protected gelatin |
| CA1339029C (en) * | 1988-06-20 | 1997-04-01 | Hiroyuki Kakoki | Transparent composition |
| JPH0681739B2 (en) | 1988-07-11 | 1994-10-19 | エーザイ株式会社 | Aqueous liquid containing fat-soluble vitamin K |
| WO1992007571A1 (en) * | 1990-11-06 | 1992-05-14 | Nippon Shinyaku Co., Ltd. | Process for producing fat emulsion |
| US5534502A (en) * | 1990-11-06 | 1996-07-09 | Nippon Shinyaku Co. Ltd. | Process for producing fat emulsion |
| JP3742602B2 (en) * | 2001-05-09 | 2006-02-08 | 株式会社カネカ | Stable solution of reduced coenzyme Q |
| US8080097B2 (en) | 2003-11-06 | 2011-12-20 | Hewlett-Packard Development Company, L.P. | System and a method for the creation of edible, optically invisible images |
| JP5103608B2 (en) * | 2006-02-10 | 2012-12-19 | 国立大学法人名古屋大学 | Pharmaceutical composition for treatment or prevention of liver cancer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB122967A (en) * | 1918-04-04 | 1919-02-13 | Herbert William Hole | Improvements in Pencil Sharpeners. |
-
1976
- 1976-11-01 JP JP13043576A patent/JPS5356315A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB122967A (en) * | 1918-04-04 | 1919-02-13 | Herbert William Hole | Improvements in Pencil Sharpeners. |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5356315A (en) | 1978-05-22 |
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