JPH0528205B2 - - Google Patents
Info
- Publication number
- JPH0528205B2 JPH0528205B2 JP14868284A JP14868284A JPH0528205B2 JP H0528205 B2 JPH0528205 B2 JP H0528205B2 JP 14868284 A JP14868284 A JP 14868284A JP 14868284 A JP14868284 A JP 14868284A JP H0528205 B2 JPH0528205 B2 JP H0528205B2
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- phospholipid
- colanic acid
- solution
- 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.)
- Expired - Lifetime
Links
- 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 claims description 44
- 239000000243 solution Substances 0.000 claims description 31
- 229930003427 Vitamin E Natural products 0.000 claims description 21
- 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 claims description 21
- 235000019165 vitamin E Nutrition 0.000 claims description 21
- 239000011709 vitamin E Substances 0.000 claims description 21
- 229940046009 vitamin E Drugs 0.000 claims description 21
- RPKLZQLYODPWTM-KBMWBBLPSA-N cholanoic acid Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC(O)=O)C)[C@@]1(C)CC2 RPKLZQLYODPWTM-KBMWBBLPSA-N 0.000 claims description 17
- 150000003904 phospholipids Chemical class 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 7
- 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 6
- 239000000787 lecithin Substances 0.000 claims description 6
- 235000010445 lecithin Nutrition 0.000 claims description 6
- 229940067606 lecithin Drugs 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 238000001704 evaporation Methods 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 108010007979 Glycocholic Acid Proteins 0.000 description 4
- RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 4
- 229940099347 glycocholic acid Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- -1 glycodeoxycholic Chemical compound 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 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 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 235000004835 α-tocopherol Nutrition 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
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- SYHJFOOIEQALFE-HRDZVTJOSA-N (8R,9S,10R,13S,14S,17R)-15,16,16-trihydroxy-13-methyl-17-[(2R)-pentan-2-yl]-1,2,3,4,5,6,7,8,9,11,12,14,15,17-tetradecahydrocyclopenta[a]phenanthrene-10-carboxylic acid Chemical class C1CC2CCCC[C@]2(C(O)=O)[C@@H]2[C@@H]1[C@@H]1C(O)C(O)(O)[C@H]([C@H](C)CCC)[C@@]1(C)CC2 SYHJFOOIEQALFE-HRDZVTJOSA-N 0.000 description 1
- CSWRFCISTSMAHQ-VBTQOLOKSA-N (8S,9S,10R,13S,14S,17R)-16,16-dihydroxy-13-methyl-17-[(2R)-pentan-2-yl]-1,2,3,4,5,6,7,8,9,11,12,14,15,17-tetradecahydrocyclopenta[a]phenanthrene-10-carboxylic acid Chemical class C1CC2CCCC[C@]2(C(O)=O)[C@@H]2[C@@H]1[C@@H]1CC(O)(O)[C@H]([C@H](C)CCC)[C@@]1(C)CC2 CSWRFCISTSMAHQ-VBTQOLOKSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- 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 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010015031 Glycochenodeoxycholic Acid Proteins 0.000 description 1
- 108010035713 Glycodeoxycholic Acid Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- BHTRKEVKTKCXOH-UHFFFAOYSA-N Taurochenodesoxycholsaeure Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)CC2 BHTRKEVKTKCXOH-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[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)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[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 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 239000007979 citrate buffer Substances 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
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 239000008344 egg yolk phospholipid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- GHCZAUBVMUEKKP-GYPHWSFCSA-N glycochenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 GHCZAUBVMUEKKP-GYPHWSFCSA-N 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- BHTRKEVKTKCXOH-AYSJQVDDSA-N taurochenodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)C1C2C2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-AYSJQVDDSA-N 0.000 description 1
- AWDRATDZQPNJFN-VAYUFCLWSA-N taurodeoxycholic 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)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 AWDRATDZQPNJFN-VAYUFCLWSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- GHCZAUBVMUEKKP-UHFFFAOYSA-N ursodeoxycholic acid glycine-conjugate Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)CC2 GHCZAUBVMUEKKP-UHFFFAOYSA-N 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 150000003772 α-tocopherols Chemical class 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【発明の詳細な説明】
本発明はビタミンＥ、リン脂質及びコラン酸ま
たはその塩の水溶液に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an aqueous solution of vitamin E, phospholipids and colanic acid or a salt thereof.
ビタミンＥをコラン酸及びレシチンの混合ミセ
ル（micelles）に溶解させ得ることは公知であ
る。これらの公知の溶液はビタミンＥの少量のみ
を含有している。米国特許第3197368号において、
レシチンの量を基準にしてビタミンＥ（α−トコ
フエロール）の２％までを含有し得るレシチン及
びコラン酸のミセル溶液が記載されている。ドイ
ツ国特許出願公告明細書第2433173号においては、
溶液１当りビタミンE10mg及びリン脂質５ｇを
含有するリン脂質及びグリココール酸のミセル溶
液が記載されている。 It is known that vitamin E can be dissolved in mixed micelles of colanic acid and lecithin. These known solutions contain only small amounts of vitamin E. In U.S. Pat. No. 3,197,368,
Micellar solutions of lecithin and colanic acid are described which can contain up to 2% of vitamin E (α-tocopherol) based on the amount of lecithin. In German Patent Application Publication No. 2433173,
A micellar solution of phospholipids and glycocholic acid is described containing 10 mg of vitamin E and 5 g of phospholipids per solution.
例えば注射溶液を製造するために、実質的によ
り濃厚なビタミンＥの溶液を入手可能にする必要
性がある。 There is a need to make available substantially more concentrated solutions of vitamin E, for example for the production of injectable solutions.
本発明におけるビタミンＥ水溶液は、リン脂
質：コラン酸の比が約0.2〜0.9：１であり、そし
て溶液がリン脂質１モル当り少なくとも約100ｇ
のビタミンＥを含有することに特徴がある。 The aqueous vitamin E solution of the present invention has a phospholipid:colanic acid ratio of about 0.2 to 0.9:1, and the solution contains at least about 100 g per mole of phospholipid.
It is characterized by containing vitamin E.
リン脂質：コラン酸のモル比は好ましくは約
0.25〜0.5：１である。 The phospholipid:colanic acid molar ratio is preferably about
The ratio is 0.25 to 0.5:1.
本発明における溶液中に存在し得るコラン酸は
トリヒドロキシコラン酸、例えばコール酸、グリ
ココール酸及びタウロコール並びにジヒドロキシ
コラン酸、例えばデオキシコール酸、グリコデオ
キシコール、タウロデオキシコール酸、ケノデオ
キシコール酸、グリコケノデオキシコール酸及び
タウロケノデオキシコール酸である。グリココー
ル酸が好ましい。コラン酸塩は特にアルカリ塩、
例えばナトリウム塩である。 Collanic acids which may be present in the solution according to the invention are trihydroxycholanic acids, such as cholic acid, glycocholic acid and taurochol, and dihydroxycholanic acids, such as deoxycholic acid, glycodeoxycholic, taurodeoxycholic acid, chenodeoxycholic acid, glycochenodeoxycholic acid. acid and taurochenodeoxycholic acid. Glycocholic acid is preferred. Collanates are especially alkaline salts,
For example, sodium salt.
リン脂質の例はホスフアチド、例えばホスフア
チジルコリン、グリセリンエーテルホスフアチ
ド、ホスフアチジルエタノールアミン、ホスフア
チジルイノシトール、ホスフアチジルセリン、プ
ラスモロゲンまたはスフインゴマイエリンであ
る。ホスフアチジルコリン、例えば大豆レシチン
及び卵レシチンが好ましい。「ビタミンＥ」なる
用語には光学的活性及びラセミビタミンＥ（α−
トコフエロール）が包含されるものとする。 Examples of phospholipids are phosphatides, such as phosphatidylcholine, glycerinetherphosphatide, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, plasmogen or sphingomyelin. Phosphatidylcholines, such as soy lecithin and egg lecithin, are preferred. The term “vitamin E” includes optically active and racemic vitamin E (α-
tocopherols).
本発明における溶液には、該溶液を注射目的に
適応させるために、等張にする添加物を含ませる
ことができる。 Solutions according to the invention can contain additives to render them isotonic in order to adapt them for injection purposes.
等張にする添加物として、特に次のものが考え
られる：生理学的塩化ナトリウム及びグルコース
溶液、トリス（Tris）緩衝剤、リン酸塩緩衝剤、
クエン酸塩緩衝剤、グリシン緩衝剤、クエン酸塩
−リン酸塩混成緩衝剤等。本発明における注射溶
液の浸透圧はほぼ血液の浸透圧、即ち約
300mOsmにすべきであるが、しかし或る範囲内
で変えることができる。 The following are particularly conceivable as isotonic additives: physiological sodium chloride and glucose solutions, Tris buffers, phosphate buffers,
Citrate buffer, glycine buffer, citrate-phosphate mixed buffer, etc. The osmotic pressure of the injection solution in the present invention is approximately the osmotic pressure of blood, that is, approximately
It should be 300 mOsm, but can vary within certain ranges.
更に本発明における溶液には添加物、例えば保
存剤及び安定剤、並びに他の製薬学的活性物質、
例えば他のビタミン類、例えばビタミンＡ，Ｄ、
ビオチン、Ｂ群のビタミン類またはビタミンＣを
含ませることができる。安定性を改善するため
に、本発明における溶液には例えばエタノールを
含ませることができる。 Furthermore, the solutions according to the invention contain additives, such as preservatives and stabilizers, as well as other pharmaceutically active substances,
For example, other vitamins, such as vitamins A, D,
Biotin, group B vitamins or vitamin C can be included. To improve stability, the solutions according to the invention can contain, for example, ethanol.
本発明における溶液は混成ミセル溶液の製造に
対するそれ自体公知の方法において、例えばリン
脂質、コラン酸またはその塩及びビタミンＥを有
機溶媒に溶解し、そこですぐに該有機溶媒を蒸発
させ、次いで水並びに必要に応じて、等張にする
添加物及び更に成分を加えることによつて製造す
ることができる。有機溶媒として、溶解する成分
が十分に可溶性である溶媒、例えば低級アルカノ
ール、特にエタノールが考えられる。 The solution according to the invention is prepared in a manner known per se for the production of mixed micellar solutions, for example by dissolving phospholipids, colanic acid or its salts and vitamin E in an organic solvent, whereupon the organic solvent is evaporated and then water and If necessary, it can be prepared by adding isotonic additives and further ingredients. Possible organic solvents are solvents in which the components to be dissolved are sufficiently soluble, such as lower alkanols, especially ethanol.
特に好ましい方法は、コラン酸、好ましくはグ
リココラン酸をビタミンＥ及びレシチンのエタノ
ール性溶液に懸濁させ、その後、該コラン酸を塩
に転化するために必要量の塩基例えば水酸化ナト
リウムを加えることからなる。エタノールの量は
溶液の総容量を基準にして有利には約６〜８重量
％である。 A particularly preferred method consists of suspending colanic acid, preferably glycocholanic acid, in an ethanolic solution of vitamin E and lecithin, and then adding the necessary amount of base, such as sodium hydroxide, to convert the colanic acid into a salt. Become. The amount of ethanol is advantageously about 6-8% by weight, based on the total volume of the solution.
かくして得られる溶液を無菌にしそして／また
は凍結乾燥することができる。 The solution thus obtained can be sterilized and/or lyophilized.
本発明を以下の実施例によつて更に詳細に説明
する：
実施例 １
ｄ，ｌ−α−トコフエロールの10重量％メタノ
ール性溶液1.8ml、ホスホリポン
（PHOSPHOLIPON）100（大豆レシチン）の25
重量％エタノール性溶液0.76ml及びグルココラン
酸ナトリウムの10重量％メタノール性溶液3.9ml
を相互に混合した。溶媒を40℃で除去し、残渣を
水3.24mlで処理し、攪拌し、透明な溶液が得られ
た。この溶液を滅菌過し、そして120℃で20分
間滅菌したアンプル中に充填した。 The invention is illustrated in more detail by the following examples: Example 1 1.8 ml of a 10% by weight methanolic solution of d,l-α-tocopherol, 25 ml of PHOSPHOLIPON 100 (soybean lecithin)
0.76 ml of a wt% ethanolic solution and 3.9 ml of a 10 wt% methanolic solution of sodium glucocholanate.
were mixed with each other. The solvent was removed at 40° C. and the residue was treated with 3.24 ml of water and stirred to give a clear solution. This solution was sterilized and filled into ampoules that were sterilized at 120° C. for 20 minutes.
実施例 ２
ｄ，ｌ−α−トコフエロール50.0mgをエタノー
ル70.0mgに溶解した。かくして得られた溶液にレ
シチン53.4mgを溶解した。この溶液に注意してグ
リココール酸88.5mgを懸濁させた。その後、1.5
％（wt／vol）水酸化ナトリウム溶液506.5μを
加えた。この混合物を透明な溶液が得られるまで
攪拌し、次にこの溶液を1N塩酸の添加によつて
PH値６に調節し、そして注射用の水で1.0mlにし
た。Example 2 50.0 mg of d,l-α-tocopherol was dissolved in 70.0 mg of ethanol. 53.4 mg of lecithin was dissolved in the solution thus obtained. 88.5 mg of glycocholic acid was carefully suspended in this solution. then 1.5
% (wt/vol) sodium hydroxide solution was added. The mixture was stirred until a clear solution was obtained, and the solution was then diluted by addition of 1N hydrochloric acid.
The pH value was adjusted to 6 and the volume was made up to 1.0 ml with water for injection.
Claims (1)
の塩よりなり、リン脂質：コラン酸のモル比が約
0.2〜0.9：１であり、そしてリン脂質１モル当り
ビタミンＥを少なくとも約100ｇ含有することを
特徴とするビタミンＥの水性液剤。 ２ リン脂質：コラン酸のモル比が約0.25〜
0.5：１である特許請求の範囲第１項記載の水性
液剤。 ３ １当りビタミンＥを約10〜50ｇ含有する特
許請求の範囲第１項または第２項記載の水性液
剤。 ４ 全容量を基準にしてエタノールを６〜８重量
％を含有する特許請求の範囲第１〜３項のいずれ
かに記載の水性液剤。 ５ リン脂質、コラン酸またはその塩及びビタミ
ンＥを有機溶媒に溶解し、該溶媒を蒸発させ、次
いで水を加えることを特徴とするビタミンＥ、リ
ン脂質及びコラン酸またはその塩よりなり、リン
脂質：コラン酸のモル比が約0.2〜0.9：１であ
り、そしてリン脂質１モル当りビタミンＥを少な
くとも約100ｇ含有するビタミンＥの水性液剤の
製造方法。 ６ リン脂質：コラン酸のモル比が約0.25〜
0.5：１である特許請求の範囲第５項記載の方法。 ７ 水性液剤が１当りビタミンＥを約10〜50ｇ
を含有する特許請求の範囲第５項または第６項記
載の方法。 ８ コラン酸をビタミンＥ及びレシチンのエタノ
ール性溶液に懸濁させ、続いてコラン酸をその塩
に転化するために必要な量の塩基を加え、これに
よつてエタノールの量を溶液の総容量を基準にし
て６〜８重量％とすることを特徴とする特許請求
の範囲第５〜７項のいずれかに記載の方法。[Claims] 1. Consisting of vitamin E, phospholipid and colanic acid or a salt thereof, the molar ratio of phospholipid:colanic acid is approximately
0.2 to 0.9:1 and containing at least about 100 g of vitamin E per mole of phospholipid. 2 The molar ratio of phospholipid:colanic acid is approximately 0.25~
The aqueous solution according to claim 1, wherein the ratio is 0.5:1. 3. The aqueous liquid preparation according to claim 1 or 2, containing about 10 to 50 g of vitamin E per portion. 4. The aqueous liquid preparation according to any one of claims 1 to 3, which contains 6 to 8% by weight of ethanol based on the total volume. 5 A phospholipid consisting of vitamin E, phospholipid, colanic acid or a salt thereof, characterized by dissolving phospholipid, colanic acid or a salt thereof, and vitamin E in an organic solvent, evaporating the solvent, and then adding water. : A method for producing an aqueous solution of vitamin E, wherein the molar ratio of colanic acid is about 0.2 to 0.9:1 and contains at least about 100 g of vitamin E per mole of phospholipid. 6 The molar ratio of phospholipid: colanic acid is approximately 0.25 ~
A method according to claim 5, wherein the ratio is 0.5:1. 7. Approximately 10-50g of vitamin E per aqueous solution
The method according to claim 5 or 6, comprising: 8. Suspend colanic acid in an ethanolic solution of vitamin E and lecithin, then add the amount of base necessary to convert colanic acid to its salt, thereby reducing the amount of ethanol to the total volume of the solution. 8. The method according to any one of claims 5 to 7, characterized in that the amount is 6 to 8% by weight.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH4029/83-4 | 1983-07-22 | ||
| CH402983 | 1983-07-22 | ||
| CH2747/84-9 | 1984-06-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6042325A JPS6042325A (en) | 1985-03-06 |
| JPH0528205B2 true JPH0528205B2 (en) | 1993-04-23 |
Family
ID=4268474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14868284A Granted JPS6042325A (en) | 1983-07-22 | 1984-07-19 | Vitamin solution |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6042325A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62106018A (en) * | 1985-11-01 | 1987-05-16 | Santen Pharmaceut Co Ltd | Water-based preparation containing vitamin e in high concentration |
| JPS63188624A (en) * | 1987-01-29 | 1988-08-04 | Maruzen Kasei Kk | Vitamin e-containing aqueous solution |
| CN111867562B (en) * | 2018-03-07 | 2023-07-07 | 陈献 | Aqueous formulation of insoluble drug |
-
1984
- 1984-07-19 JP JP14868284A patent/JPS6042325A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6042325A (en) | 1985-03-06 |
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