JP2787364B2 - Fat-soluble vitamin injection - Google Patents
Fat-soluble vitamin injectionInfo
- Publication number
- JP2787364B2 JP2787364B2 JP2083177A JP8317790A JP2787364B2 JP 2787364 B2 JP2787364 B2 JP 2787364B2 JP 2083177 A JP2083177 A JP 2083177A JP 8317790 A JP8317790 A JP 8317790A JP 2787364 B2 JP2787364 B2 JP 2787364B2
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- fat
- amount
- present
- polysorbate
- 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
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Description
【発明の詳細な説明】 産業上の利用分野 本発明は脂溶性ビタミン注射液、より詳しくはビタミ
ンＡ、ビタミンＤ、ビタミンＥ及びビタミンＫを含有す
る安定な注射液、特に無菌化のために通常実施される蒸
気滅菌に対して安定な注射液に関する。The present invention relates to a fat-soluble vitamin injection, more particularly a stable injection containing vitamin A, vitamin D, vitamin E and vitamin K, especially for sterilization. It relates to an injection which is stable against the steam sterilization performed.
従来の技術 近年、手術後等における栄養の経口摂取が困難な患者
に対する栄養管理は経中心静脈栄養による高カロリー輸
液療法により行なわれており、該療法の発達に伴い、必
須ビタミンの同時投与が常識化されてきている。このた
め高カロリー輸液に添加される総合ビタミン剤も様々な
形態で開発されている。しかして、必須ビタミンはその
物理化学的性質上、脂溶性ビタミンと水溶性ビタミンと
に大別され、また副作用として脂溶性ビタミン過剰症が
知られていることから、上記脂溶性ビタミンは水溶性ビ
タミンに比べて投与に際する配慮が必要とされ、上記高
カロリー輸液に添加される総合ビタミン剤は脂溶性ビタ
ミンと水溶性ビタミンとが分割された形態が望ましいと
考えられる。上記水溶性ビタミンは注射剤としての水性
組成物とするために組成上特殊な配慮を必要としない
が、脂溶性ビタミンの水性液化には当然なんらかの可溶
化剤の利用が必須となる。従来該可溶化剤としてはポリ
オキシエチレン硬化ヒマシ油類及びポリオキシエチレン
ソルビタン脂肪酸エステル類が汎用されている。しかし
ながら、近年ポリオキシエチレン硬化ヒマシ油類はその
非経口投与によってアナフィラキシー型のショック症状
をもたらす疑義（The Imformed Prescriber Vol.1,No.
2,9,1986等）がもたれており、可溶化剤としてポリオキ
シエチレン硬化ヒマシ油類を含有する脂溶性ビタミン注
射液について、他の安全な可溶化剤を使用した組成への
変更が望まれている。2. Description of the Related Art In recent years, nutritional management for patients who have difficulty in taking nutrition orally after surgery or the like has been performed by high-calorie infusion therapy by transcentral parenteral nutrition. It is becoming. Therefore, multivitamin preparations added to high-calorie infusions have been developed in various forms. The essential vitamins are roughly classified into fat-soluble vitamins and water-soluble vitamins due to their physicochemical properties, and the fat-soluble vitamins are known to be fat-soluble vitamins as side effects. Therefore, it is necessary to give consideration to administration, and it is considered that the multivitamin preparation to be added to the high calorie infusion preferably has a form in which a fat-soluble vitamin and a water-soluble vitamin are divided. Although the above water-soluble vitamin does not require special consideration in composition in order to form an aqueous composition as an injection, the use of some solubilizing agent is indispensable for the aqueous liquefaction of fat-soluble vitamin. Conventionally, polyoxyethylene hydrogenated castor oils and polyoxyethylene sorbitan fatty acid esters have been widely used as the solubilizer. However, recently, polyoxyethylene hydrogenated castor oils are suspected of causing anaphylactic shock symptoms by parenteral administration (The Imformed Prescriber Vol. 1, No.
2,9,1986), and it is desired that the fat-soluble vitamin injection solution containing polyoxyethylene hydrogenated castor oil as a solubilizing agent be changed to a composition using another safe solubilizing agent. ing.
発明が解決しようとする問題点 本発明者らは、ポリオキシエチレン硬化ヒマシ油類に
代わり得る可溶化剤につき種々の検討を行なった結果、
ポリオキシエチレンソルビタン脂肪酸エステル類に高い
可溶化力のあることを見出し、各種ポリオキシエチレン
ソルビタン脂肪酸エステルの利用により、脂溶性ビタミ
ンの可溶化に成功した。しかるに、之等可溶化剤の水溶
液の曇点は90〜95℃と低く、之等を可溶化剤として調製
した脂溶性ビタミン水溶液につき、注射剤製造のための
滅菌操作を施すべく曇点を上回る温度に加熱すると、白
濁乃至二層分離することが明らかとなった。またこの曇
点は電解質の添加により下がる傾向を示し、通常注射液
のpH安定化のために加える緩衝剤を添加した場合、該緩
衝剤が電解質であるため、曇点が下がり、これを含まな
いときに比べて白濁乃至二層分離をもたらす温度が低く
なる傾向を示した。従ってポリオキシエチレンソルビタ
ン脂肪酸エステル類を可溶化剤として用い且つ緩衝剤と
して２〜10mMの電解質を含有する脂溶性ビタミン水溶液
は、低温では安定であるものの30〜50℃以上の温度で経
時的に白濁するばかりか、その液が注射液として無菌で
あることを保証するため、95℃以上の高温で蒸気滅菌を
実施した場合、白濁乃至二層分離して、注射液としては
使用に耐えないものとなった。Problems to be Solved by the Invention The present inventors have conducted various studies on solubilizing agents that can be substituted for polyoxyethylene hydrogenated castor oils,
They found that polyoxyethylene sorbitan fatty acid esters have high solubilizing power, and succeeded in solubilizing fat-soluble vitamins by using various polyoxyethylene sorbitan fatty acid esters. However, the cloud point of the aqueous solution of the solubilizing agent is as low as 90 to 95 ° C., and exceeds the cloud point of the fat-soluble vitamin aqueous solution prepared as the solubilizing agent in order to perform a sterilization operation for manufacturing an injection. When heated to a temperature, it became clear that the mixture became cloudy or separated into two layers. Also, this cloud point tends to decrease due to the addition of the electrolyte, and when a buffer added to stabilize the pH of the injection solution is usually added, since the buffer is an electrolyte, the cloud point is lowered and the cloud point is not included. There was a tendency that the temperature at which white turbidity or two-layer separation was caused was lower than sometimes. Thus, a fat-soluble vitamin aqueous solution containing polyoxyethylene sorbitan fatty acid esters as a solubilizing agent and containing 2 to 10 mM of an electrolyte as a buffer is stable at low temperatures but becomes cloudy over time at a temperature of 30 to 50 ° C. or more. In addition, to ensure that the solution is sterile as an injectable solution, if steam sterilization is carried out at a high temperature of 95 ° C or higher, it will be opaque or separated into two layers and cannot be used as an injectable solution. became.
問題点を解決するための手段 本発明者らは緩衝剤を含有する脂溶性ビタミン水溶液
を蒸気滅菌したときの白濁乃至二層分離を解消する目的
で更に鋭意研究を重ねた結果、緩衝剤を含有し、ポリオ
キシエチレンソルビタン脂肪酸エステル類を可溶化剤と
して添加した脂溶性ビタミン水溶液に更に可溶化安定剤
としてポリエチレングリコール類及び糖類を併用添加す
ることにより、蒸気滅菌操作に対しても白濁乃至二層分
離等の物理的変化がなく、しかも長期間の保存に対して
安定な所望の注射液が得られることを見出し、ここに本
発明を完成するに至った。Means for Solving the Problems The inventors of the present invention have conducted intensive studies for the purpose of eliminating cloudiness or two-phase separation when a fat-soluble vitamin aqueous solution containing a buffer is subjected to steam sterilization. By adding together polyethylene glycols and saccharides as solubilizing stabilizers to a fat-soluble vitamin aqueous solution to which polyoxyethylene sorbitan fatty acid esters are added as a solubilizing agent, it becomes opaque to two layers even for steam sterilization operation. The present inventors have found that a desired injection solution free from physical changes such as separation and stable for long-term storage can be obtained, and the present invention has been completed.
即ち本発明は脂溶性ビタミンとしてビタミンＡ、ビタ
ミンＤ、ビタミンＥ及びビタミンＫを含有し、緩衝剤と
して有機酸及びその塩並びに無機酸及びその塩のうちか
ら選ばれる少なくとも一種を含有し、且つ可溶化剤とし
てポリオキシエチレンソルビタン脂肪酸エステル類並び
に可溶化安定剤としてポリエチレングリコール類及び糖
類を含有することを特徴とする脂溶性ビタミン注射液に
係る。That is, the present invention contains vitamin A, vitamin D, vitamin E and vitamin K as fat-soluble vitamins, and contains at least one selected from organic acids and salts thereof and inorganic acids and salts thereof as buffering agents. The present invention relates to a fat-soluble vitamin injection solution containing polyoxyethylene sorbitan fatty acid esters as a solubilizing agent and polyethylene glycols and saccharides as a solubilizing stabilizer.
本発明の脂溶性ビタミン注射液に用いられる脂溶性ビ
タミンにはビタミンＡ、ビタミンＤ、ビタミンＥ及びビ
タミンＫが包含される。之等のビタミンの配合量及び配
合比率には特に限定はないが、各ビタミンにつき人の１
日の必要量を補える量とするのが望ましい。それぞれの
配合量の具体例としてはビタミンＡでは1000〜5000ビタ
ミンＡ単位、ビタミンＤでは100〜1000IU、ビタミンＥ
では５〜20IU、ビタミンＫでは0.2〜10mgの範囲を望ま
しく例示できる。The fat-soluble vitamin used in the fat-soluble vitamin injection solution of the present invention includes vitamin A, vitamin D, vitamin E and vitamin K. There are no particular restrictions on the amounts and proportions of these vitamins, but one per person for each vitamin.
It is desirable that the amount be sufficient to cover the daily requirement. Specific examples of the amount of each are as follows: 1000-5000 vitamin A units for vitamin A, 100-1000 IU for vitamin D, vitamin E
The range is preferably 5 to 20 IU, and the range of vitamin K is preferably 0.2 to 10 mg.
本発明で緩衝剤として使用する有機酸としてはクエン
酸、酢酸、酒石酸、マレイン酸、フマル酸、グルタミン
酸等を例示でき、有機塩酸としてはそれらのナトリウム
塩、カリウム塩等を例示できる。また無機酸としてはり
ん酸等を、無機酸塩としてはナトリウム塩、カリウム塩
等を例示できる。緩衝剤の配合量は水溶液中２〜150m
M、好ましくは５〜10mMの範囲とされるのがよい。Examples of the organic acid used as a buffer in the present invention include citric acid, acetic acid, tartaric acid, maleic acid, fumaric acid, glutamic acid and the like, and examples of the organic hydrochloric acid include sodium salts and potassium salts thereof. Examples of the inorganic acid include phosphoric acid, and examples of the inorganic acid salt include a sodium salt and a potassium salt. The amount of buffering agent is 2-150m in aqueous solution
M, preferably 5 to 10 mM.
可溶化剤のポリオキシエチレンソルビタン脂肪酸エス
テルとしてはポリソルベート20、ポリソルベート21、ポ
リソルベート40、ポリソルベート60、ポリソルベート6
1、ポリソルベート65、ポリソルベート80、ポリソルベ
ート81、ポリソルベート85等及び之等の混合物が挙げら
れ、注射剤としての安全性の面からはポリソルベート2
0、ポリソルベート80等が好ましい。該可溶化剤の配合
量範囲はポリソルベート20では配合脂溶性ビタミン全量
の０〜１倍、好ましくは0.1〜0.6倍、ポリソルベート80
では配合脂溶性ビタミン全量の0.8倍〜５倍、好ましく
は1.6〜３倍とするのが適当である。As polyoxyethylene sorbitan fatty acid ester of solubilizer, polysorbate 20, polysorbate 21, polysorbate 40, polysorbate 60, polysorbate 6
1, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85, and the like, and mixtures thereof.From the viewpoint of safety as an injection, polysorbate 2
0, polysorbate 80 and the like are preferred. The compounding range of the solubilizer in polysorbate 20 is 0 to 1 times, preferably 0.1 to 0.6 times, the total amount of the fat-soluble vitamin compounded, and polysorbate 80 is used.
In this case, it is appropriate to set the total amount of the fat-soluble vitamin to 0.8 to 5 times, preferably 1.6 to 3 times the total amount.
可溶化安定剤のポリエチレングリコール類としてはあ
らゆる分子量のポリエチレングリコールを使用できる。
本発明注射液の調製の容易さ等を考慮すると、ポリエチ
レングリコール300、ポリエチレングリコール400等に代
表される液状ポリエチレングリコールが好ましい。その
添加量は水溶液中に0.1〜20w/v％、好ましくは0.5〜4w/
v％添加される量とするのがよい。また糖類としてはブ
ドウ糖、果糖、乳糖、しょ糖、マルトース、デキストラ
ン、マソニトール、キシリトール、ソルビトール等を例
示できる。特に水溶液中での糖の安定性を考慮すれば上
記糖としては非還元糖が好ましい。その添加量は水溶液
中に0.1〜20w/v％、好ましくは２〜8w/v％添加量とする
のがよい。尚上記可溶化剤及び可溶化安定剤の配合量は
ビタミンの配合量と種類に応じて適宜増減するのが望ま
しい。As the polyethylene glycol as a solubilizing stabilizer, polyethylene glycol of any molecular weight can be used.
In consideration of the ease of preparation of the injection solution of the present invention, liquid polyethylene glycol represented by polyethylene glycol 300, polyethylene glycol 400 and the like is preferable. The addition amount is 0.1 to 20 w / v% in the aqueous solution, preferably 0.5 to 4 w / v.
v% It is good to be added amount. Examples of sugars include glucose, fructose, lactose, sucrose, maltose, dextran, massonitol, xylitol, sorbitol and the like. Particularly, considering the stability of the saccharide in an aqueous solution, a non-reducing saccharide is preferable as the saccharide. The amount of addition is 0.1 to 20 w / v%, preferably 2 to 8 w / v% in the aqueous solution. It is desirable that the amount of the solubilizing agent and the solubilizing stabilizer is appropriately increased or decreased according to the amount and type of the vitamin.
本発明注射剤の調製は常法に従うことができる。代表
的調製法としては、例えば脂溶性ビタミンを可溶化剤に
溶解し、それを注射用水に溶解し、更に可溶化安定剤及
び緩衝剤を加えて溶解後、必要に応じ水酸化ナトリウム
等のpH調整剤にてpHを６〜７に調整する方法を例示でき
る。かくして得られる薬液は必要に応じて過し、容器
に小分けして密封後、105℃で60分間又は110℃で40分間
蒸気滅菌して所望の注射液とされる。Preparation of the injection of the present invention can be performed according to a conventional method. Typical preparation methods include, for example, dissolving a fat-soluble vitamin in a solubilizer, dissolving it in water for injection, further adding a solubilizing stabilizer and a buffer, and dissolving the resulting mixture. A method of adjusting the pH to 6 to 7 with a regulator can be exemplified. The medicinal solution thus obtained is used as needed, divided into small containers, sealed, and steam-sterilized at 105 ° C for 60 minutes or 110 ° C for 40 minutes to obtain a desired injection solution.
発明の効果 本発明の脂溶性ビタミン注射液は蒸気滅菌によっても
全く変化を示さず、また40℃、４カ月放置後においても
何ら光透過率の低下も認めず、勿論上記蒸気滅菌後に白
濁乃至二層分離もなく、極めて安定性に優れたものであ
る。Effects of the Invention The fat-soluble vitamin injection solution of the present invention shows no change even by steam sterilization, does not show any decrease in light transmittance even after standing at 40 ° C. for 4 months, and of course, shows no cloudiness or turbidity after steam sterilization. There is no layer separation, and it is extremely excellent in stability.
実 施 例 以下、本発明を更に詳しく説明するため、実施例及び
比較例を挙げる。EXAMPLES Hereinafter, examples and comparative examples will be given in order to explain the present invention in more detail.
実施例 １ ビタミンＡ（パルミチン酸レチノール） 3300ビタミンＡ単位、ビタミンＤ（コレカルシフェロ
ール）200IU、ビタミンＥ（酢酸トコフェロール）10m
g、ビタミンＫ（フィトナジオン）2mgをポリソルベート
80 40mg及びポリソルベート20 8mgに溶かした後、これ
に70℃以上に加熱した注射用水を加えて溶かし、更にポ
リエチレングリコール400 40mg、ソルビトール280mg、
無水クエン酸0.4mg及びクエン酸ナトリウム5.35mgを加
えて溶かし、全量を4mlとした。得られた薬液をアンプ
ルに密封し、蒸気滅菌して、本発明品を得た。Example 1 Vitamin A (Retinol palmitate) 3300 Vitamin A units, Vitamin D (Cholecalciferol) 200 IU, Vitamin E (Tocopherol acetate) 10 m
g, vitamin K (phytonadione) 2mg with polysorbate
After dissolving in 80 40 mg and polysorbate 208 mg, water for injection heated to 70 ° C. or higher was added and dissolved, and polyethylene glycol 400 40 mg, sorbitol 280 mg,
0.4 mg of anhydrous citric acid and 5.35 mg of sodium citrate were added and dissolved to make a total volume of 4 ml. The obtained drug solution was sealed in an ampoule and steam-sterilized to obtain the product of the present invention.
実施例 ２ 実施例１におけるポリエチレングリコール400の量を2
0mg、ソルビトールの量を240mgとし、他は同様にして本
発明品を得た。Example 2 The amount of polyethylene glycol 400 in Example 1 was changed to 2
The product of the present invention was obtained in the same manner except that the amount of sorbitol was 0 mg and the amount of sorbitol was 240 mg.
実施例 ３ 実施例１におけるポリエチレングリコール400の量を8
0mg、ソルビトールの量を160mgとし、他は同様にして本
発明品を得た。Example 3 The amount of polyethylene glycol 400 in Example 1 was changed to 8
The product of the present invention was obtained in the same manner except that the amount of sorbitol was 0 mg and the amount of sorbitol was 160 mg.
実施例 ４ 実施例１におけるポリエチレングリコール400の量を1
20mg、ソルビトールの量を120mgとし、他は同様にして
本発明品を得た。Example 4 The amount of polyethylene glycol 400 in Example 1 was changed to 1
The product of the present invention was obtained in the same manner except that the amount of sorbitol was 20 mg and the amount of sorbitol was 120 mg.
実施例 ５ 実施例１においてソルビトールの代りにマンニトール
280mgを用い、他は同様にして本発明品を得た。Example 5 In Example 1, mannitol was used instead of sorbitol
The product of the present invention was obtained in the same manner except that 280 mg was used.
実施例 ６ 実施例１においてソルビトールの代りにキシリトール
280mgを用い、他は同様にして本発明品を得た。Example 6 Xylitol instead of sorbitol in Example 1
The product of the present invention was obtained in the same manner except that 280 mg was used.
実施例 ７ 実施例１においてポリエチレングリコール400の代り
にポリエチレングリコール300 40mgを用い、他は同様に
して本発明品を得た。Example 7 A product of the present invention was obtained in the same manner as in Example 1 except that 40 mg of polyethylene glycol 300 was used instead of polyethylene glycol 400.
実施例 ８ 実施例１におけるポリソルベート20の量を12mg、ポリ
ソルベート80の量を60mgとし、他は同様にして本発明品
を得た。Example 8 The product of the present invention was obtained in the same manner as in Example 1 except that the amount of polysorbate 20 was 12 mg and the amount of polysorbate 80 was 60 mg.
実施例 ９ 実施例１におけるポリソルベート20の量を12mg、ポリ
ソルベート80の量を60mgとし、またポリエチレングリコ
ール400の代りにポリエチレングリコール300の40mgを用
い、他は同様にして本発明品を得た。Example 9 The product of the present invention was obtained in the same manner as in Example 1, except that the amount of polysorbate 20 was 12 mg, the amount of polysorbate 80 was 60 mg, and that 40 mg of polyethylene glycol 300 was used instead of polyethylene glycol 400.
実施例 10 実施例１におけるビタミンＡの量を2000ビタミンＡ単
位、ビタミンＫの量を5mgとし、他は同様にして本発明
品を得た。Example 10 The product of the present invention was obtained in the same manner as in Example 1 except that the amount of vitamin A was 2000 vitamin A units and the amount of vitamin K was 5 mg.
実施例 11 実施例１におけるビタミンＡの量を1000ビタミンＡ単
位、ビタミンＤの量を100IUとし、他は同様にして本発
明品を得た。Example 11 The product of the present invention was obtained in the same manner as in Example 1 except that the amount of vitamin A was 1,000 vitamin A units and the amount of vitamin D was 100 IU.
実施例 12 実施例１におけるビタミンＥの量を5mg、ビタミンＫ
の量を0.2mgとし、他は同様にして本発明品を得た。Example 12 The amount of vitamin E in Example 1 was 5 mg,
Was set to 0.2 mg, and the others were obtained in the same manner.
実施例 13 実施例１におけるビタミンＤの量を1000IU、ビタミン
Ｅの量を15mgとし、他は同様にして本発明品を得た。Example 13 The product of the present invention was obtained in the same manner as in Example 1, except that the amount of vitamin D was 1000 IU and the amount of vitamin E was 15 mg.
実施例 14 実施例１におけるビタミンＡの量を5000ビタミンＡ単
位、ビタミンＫの量を10mgとし、他は同様にして本発明
品を得た。Example 14 The product of the present invention was obtained in the same manner as in Example 1 except that the amount of vitamin A was 5000 vitamin A units and the amount of vitamin K was 10 mg.
比較例 １ 実施例１においてポリエチレングリコール400及びソ
ルビトールを添加使用しない以外は同様にして比較品を
得た。Comparative Example 1 A comparative product was obtained in the same manner as in Example 1 except that polyethylene glycol 400 and sorbitol were not used.
比較例 ２ 実施例１においてポリソルベート20、ポリエチレング
リコール400及びソルビトールを添加使用しない以外は
同様にして比較品を得た。Comparative Example 2 A comparative product was obtained in the same manner as in Example 1 except that polysorbate 20, polyethylene glycol 400 and sorbitol were not used.
比較例 ３ 実施例１においてポリエチレングリコール400及びソ
ルビトールの代りにプロピレングリコール600mgを用
い、他は同様にして比較品を得た。Comparative Example 3 A comparative product was obtained in the same manner as in Example 1, except that 600 mg of propylene glycol was used instead of polyethylene glycol 400 and sorbitol.
比較例 ４ 実施例１においてポリエチレングリコール400及びソ
ルビトールの代りにグリセリン360mgを用い、他は同様
にして比較品を得た。Comparative Example 4 A comparative product was obtained in the same manner as in Example 1, except that 360 mg of glycerin was used instead of polyethylene glycol 400 and sorbitol.
比較例 ５ 実施例１においてポリエチレングリコール400の代り
にプロピレングリコール40mgを用い、他は同様にして比
較品を得た。Comparative Example 5 A comparative product was obtained in the same manner as in Example 1, except that 40 mg of propylene glycol was used instead of polyethylene glycol 400.
〈安定性試験〉 上記各実施例で調製された本発明品試料群並びに比較
群として可溶化安定剤を添加せずに調製した試料、可溶
化剤の組成を本発明の範囲外で調製した試料及び溶解補
助剤として知られているプロピレングリコールを添加し
た試料の夫々を、110℃で40分間の条件で蒸気滅菌し、
注射液の外観変化を観察すると共に、40℃で４カ月間保
存し、640nmの光透過率を測定した。<Stability test> Samples of the present invention sample group prepared in each of the above examples and a sample prepared without adding a solubilizing stabilizer as a comparative group, and a sample prepared with a solubilizer composition outside the scope of the present invention And each of the samples to which propylene glycol, which is known as a solubilizing agent, was added, was steam-sterilized at 110 ° C. for 40 minutes,
While observing the appearance change of the injection solution, it was stored at 40 ° C. for 4 months, and the light transmittance at 640 nm was measured.
結果を下記第１表に示す。 The results are shown in Table 1 below.
上記第１表より明らかな通り、本発明による試料群は
蒸気滅菌においても全く変化を示さなかったと共に40
℃、４カ月放置後においても640nmの光透過率の低下も
なかったが、比較群はいずれも蒸気滅菌後白濁乃至二層
分離を示すか、40℃、４カ月放置後の640nmの光透過率
が低下して白濁を示した。 As is clear from Table 1 above, the sample group according to the present invention did not show any change even in steam sterilization.
There was no decrease in light transmittance at 640 nm even after standing at 4 ° C. for 4 months, but all of the comparative groups showed opacity to two-layer separation after steam sterilization, or light transmittance at 640 nm after standing at 40 ° C. for 4 months. Decreased to show cloudiness.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 ＦＩ Ａ６１Ｋ 47/34 Ａ６１Ｋ 47/34 Ｇ (56)参考文献 特開 昭58−65212（ＪＰ，Ａ) 特開 昭61−17512（ＪＰ，Ａ) (58)調査した分野(Int.Cl.6，ＤＢ名) A61K 9/08 - 9/107 A61K 47/12,47/26,47/34 A61K 31/07,31/355,31/59──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 6 Identification code FI A61K 47/34 A61K 47/34 G (56) References JP-A-58-65212 (JP, A) JP-A-61-17512 ( JP, A) (58) Fields investigated (Int. Cl. 6 , DB name) A61K 9/08-9/107 A61K 47 / 12,47 / 26,47 / 34 A61K 31 / 07,31 / 355,31 / 59
Claims (1)
ンＤ、ビタミンＥ及びビタミンＫを含有し、緩衝剤とし
て有機酸及びその塩並びに無機酸及びその塩のうちから
選ばれる少なくとも一種を含有し、且つ可溶化剤として
ポリオキシエチレンソルビタン脂肪酸エステル類並びに
可溶化安定剤としてポリエチレングルコール類及び糖類
を含有することを特徴とする脂溶性ビタミン注射液。1. A fat-soluble vitamin containing vitamin A, vitamin D, vitamin E and vitamin K, a buffer containing at least one selected from organic acids and salts thereof and inorganic acids and salts thereof, and A fat-soluble vitamin injection solution comprising a polyoxyethylene sorbitan fatty acid ester as a solubilizing agent and polyethylene glycols and saccharides as a solubilizing stabilizer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2083177A JP2787364B2 (en) | 1990-03-29 | 1990-03-29 | Fat-soluble vitamin injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2083177A JP2787364B2 (en) | 1990-03-29 | 1990-03-29 | Fat-soluble vitamin injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03279324A JPH03279324A (en) | 1991-12-10 |
| JP2787364B2 true JP2787364B2 (en) | 1998-08-13 |
Family
ID=13795011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2083177A Expired - Lifetime JP2787364B2 (en) | 1990-03-29 | 1990-03-29 | Fat-soluble vitamin injection |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2787364B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL103224A (en) * | 1992-09-18 | 1998-08-16 | Teva Pharma | Stabilized pharmaceutical compositions containing derivatives of vitamins d2 and d3 |
| UA72189C2 (en) * | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Aqueous suspensions of 9-hydroxy-risperidone fatty acid esters provided in submicron form |
| AU4061599A (en) * | 1998-06-10 | 1999-12-30 | Wakamoto Pharmaceutical Co., Ltd. | Aqueous preparations containing hardly soluble drug |
| JP4713706B2 (en) * | 2000-03-14 | 2011-06-29 | テルモ株式会社 | Container with fat-soluble vitamin solubilizer |
| CN105663145A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin injection liquid for animals and preparing method and use method thereof |
| CN105663144A (en) * | 2016-01-06 | 2016-06-15 | 施维雅(青岛)生物制药有限公司 | Fat-soluble vitamin water-based preparation for animals and preparing method and use method thereof |
| CN114533672B (en) * | 2022-03-03 | 2023-12-26 | 南京臣功制药股份有限公司 | Vitamin K 1 Nanoemulsion and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5865212A (en) * | 1981-10-12 | 1983-04-18 | Asahi Denka Kogyo Kk | Pharmaceutical composition |
| JPS6117512A (en) * | 1984-07-03 | 1986-01-25 | Ss Pharmaceut Co Ltd | Low-hemolysis vitamin e injection solution |
-
1990
- 1990-03-29 JP JP2083177A patent/JP2787364B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH03279324A (en) | 1991-12-10 |
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