JPS61277622A - Composition for active vitamin d3 preparation - Google Patents
Composition for active vitamin d3 preparationInfo
- Publication number
- JPS61277622A JPS61277622A JP11673485A JP11673485A JPS61277622A JP S61277622 A JPS61277622 A JP S61277622A JP 11673485 A JP11673485 A JP 11673485A JP 11673485 A JP11673485 A JP 11673485A JP S61277622 A JPS61277622 A JP S61277622A
- Authority
- JP
- Japan
- Prior art keywords
- active vitamin
- triacetin
- solution
- composition
- vitamin
- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】 〈産業上の利用分野〉 本発明は活性型ビタミンＤ、＠製剤用組成物に関する。[Detailed description of the invention] <Industrial application field> TECHNICAL FIELD The present invention relates to active vitamin D, a composition for formulation.
更に詳細には、本発明は活性型ビグ４フＤ、類をトリア
セチンに溶解せしめてなる活性型ビタミンＤ、類製剤用
組成物であって、活性型ビタミンＤ、類の安定性が著し
く優れた組成物に関する。More specifically, the present invention provides a composition for preparation of active vitamin D, which is prepared by dissolving active vitamin D, etc. in triacetin, and which exhibits extremely excellent stability of active vitamin D, etc. Regarding the composition.
〈従来技術とその問題点〉
１α−ヒトａキシビタミンＤ８，１α、２５−ジヒドロ
キシビタミンＤ３等の活性型ビタミンＤ、類は、小腸で
のカルシウムの吸収を促進し、また骨カルシウムの溶出
を促進して血清カルシウム濃度を高める作用を有し、骨
粗鬆症。<Prior art and its problems> Active vitamin D, such as 1α-human axyvitamin D8, 1α, and 25-dihydroxyvitamin D3, promote calcium absorption in the small intestine and also promote the elution of bone calcium. It has the effect of increasing serum calcium concentration and preventing osteoporosis.
骨軟化症等の骨疾患の優れた治療薬として知られている
。It is known as an excellent therapeutic agent for bone diseases such as osteomalacia.
しかしながらこれらの活性製ビタミンＤ、類は、元、熱
等に対して極めて不安定であるため、活性型ビタミンＤ
、類を安定な形態で製剤に供することが重要である。However, these active forms of vitamin D are extremely unstable when exposed to heat, etc.
It is important to provide pharmaceutical products in a stable form.
活性型ビタミンＤ、類を安定化せしめた医薬品組成物と
しては、例えば活性型ビタミンＤ。Examples of pharmaceutical compositions containing stabilized active vitamin D include active vitamin D.
類を脂肪酸のトリグリセライドに溶解せしめた組成物（
特開昭５２−１３０９０５号公報）９活性凰ビタミンＤ
、類をポリビニルピロリドンに分散せしめた組成物（特
開昭５８−２０６５３３号公報）などが知られている。A composition prepared by dissolving the following compounds in fatty acid triglyceride (
9 active vitamin D
, etc. are known, such as a composition (Japanese Unexamined Patent Application Publication No. 58-206533) in which polyvinylpyrrolidone is dispersed.
これらの医薬品組成物に加えて、活性製ビタミンＤ３類
の安定化が図られた、他の新たな組成物の開発も望まれ
ている。In addition to these pharmaceutical compositions, it is also desired to develop other new compositions in which active vitamin D3s are stabilized.
〈問題点を解決するための手段〉
本発明者は、活性型ビタミンＤ、類の安定性が優れた活
性盤ビタミンＤ、類裂剤用組成物を得ることを目的とし
て鋭意研究した結果、活性型ビタミンＤ、類？トリアセ
チンに溶解して得られる組成物が、これらの目的を達成
し得ることを見出し本発明に到達したものである。<Means for Solving the Problems> As a result of intensive research aimed at obtaining a composition for an active form of vitamin D and a fission agent with excellent stability of active vitamin D, the present inventor found that Type vitamin D, kind? The present invention was achieved by discovering that a composition obtained by dissolving in triacetin can achieve these objectives.
即ち、本発明は、活性型ビタミンＤ３類をトリアセチン
に溶解せしめてなる活性型ビタミンＤ３類製剤用組成物
である。That is, the present invention is a composition for an active vitamin D3 preparation, which is prepared by dissolving active vitamin D3 in triacetin.
本発明で対象とする活性型ビタミンＤ、類としては、例
えば１α−ヒトａキシビタミンＤ、。The active vitamin D targeted by the present invention includes, for example, 1α-human axyvitamin D.
１α、２５−ジヒドロキシビタミンＤ３，１α。1α,25-dihydroxyvitamin D3,1α.
２４−ジヒドロキシビタミンＤ８．１α、２４．２５−
トリヒトａキシビタミンＤ８，１α−ヒトａキシ−２４
−オキソビタミンＤ８．１α−ヒドロキシ−２６，２６
，２６，２７１２７，２７−ヘキサフルオａビタミンＤ
８，１α−ヒドロキシビタミンＤｓ ２６１２３−ラ
クトンなどの１α位に水酸基を有する活性型ビタミンＤ
、類：２４゜２５−ジヒドロキシビタミンＤ、、２４−
ヒトａキシビタミンＤ、、２５−ヒトａキシビタミンＤ
８．ビタミンＤ、−２６，２３−ラクトンなどの１α位
に水酸基を有しない活性型ビタミンＤ、類が挙げられる
゛。これらの活性型ビタミンＤ、類は公知の化合物であ
り、公知の方法によつ℃製造し得る〔有機合成化学、第
３７巻。24-dihydroxyvitamin D8.1α, 24.25-
Trihuman axyvitamin D8,1α-human axy-24
-Oxovitamin D8.1α-hydroxy-26,26
,26,27127,27-hexafluora vitamin D
8,1α-Hydroxyvitamin Ds Active vitamin D having a hydroxyl group at the 1α position such as 26123-lactone
, Class: 24゜25-dihydroxyvitamin D, , 24-
human axyvitamin D, 25-human axyvitamin D
8. Examples include active vitamin D, which does not have a hydroxyl group at the 1α position, such as vitamin D and -26,23-lactone. These active forms of vitamin D are known compounds and can be produced by known methods [Organic Synthetic Chemistry, Vol. 37].
４９．７５５（１９７９）；有機合成化学、第３７巻、
腐１０，８０９（１９７９））。49.755 (1979); Organic Synthetic Chemistry, Volume 37,
10, 809 (1979)).
本発明で用いるトリアセチンは、１，２．３−トリヒト
ミキシプロパンの三酢酸エステルであり、グリセリルト
リアセテートとも命名されるものである。Triacetin used in the present invention is a triacetic acid ester of 1,2,3-trihuman mixipropane, and is also named glyceryl triacetate.
本発明の組成物は、活性盤ビタミンＤ、類をトリアセチ
ンに溶解することによって得られる。溶解せしめる方法
としては、活性型ビタミンＤ、類をそのままトリアセチ
ンに加えて溶解してもよく、あるいは、活性型ビタミン
Ｄ。The composition of the present invention is obtained by dissolving activated vitamin D, etc. in triacetin. As a method for dissolving active vitamin D, active vitamin D may be added to triacetin as it is and dissolved, or active vitamin D may be dissolved.
類をメタノール、エタノール等の有機溶媒に溶解せしめ
た後にトリアセチンに加え℃、次いで該有機溶媒な留去
する方法等を採用してもよい。Alternatively, a method may be adopted in which the compound is dissolved in an organic solvent such as methanol or ethanol, and then added to triacetin at °C, and then the organic solvent is distilled off.
活性型ビタミンＤ、類のトリアセチン中の濃度は、通常
０．０１μ９〜２００μｊｌ／１１である。The concentration of active vitamin D in triacetin is usually 0.01μ9 to 200μjl/11.
本発明の組成物は、活性凰ビタミンｏｓ ｔｅａの安定
性が著しく改善されたものであり、活性型ビタミンＤ、
類裏剤用として有効である。The composition of the present invention has significantly improved stability of activated vitamin ostea, and contains active vitamin D,
Effective as a backing agent.
本発明の組成物は、通常の製剤化工程に付すことによっ
て活性型ビタミンＤ３類製剤とすることができる。The composition of the present invention can be made into an active vitamin D3 preparation by subjecting it to normal formulation steps.
例えば、本発明の組成物をソフトカプセル皮膜中に光櫨
することによって軟カプセル剤とすることができる。あ
るいは本発明の組成物に必要にＬじて保存剤等を株加し
皮下もしくは筋内内投与用注射剤としてもよい。For example, the composition of the present invention can be made into a soft capsule by coating it in a soft capsule film. Alternatively, the composition of the present invention may be prepared as an injection for subcutaneous or intramuscular administration by adding a preservative or the like as necessary.
〈発明の効果〉
本発明によれば、以上に詳述した如く、活性製ビタミン
Ｄ、類の安定性が著しく改善された組成物が得られ、か
かる組成物は活性型ビタミンＤ３類製剤用として極めて
有用であφ。<Effects of the Invention> According to the present invention, as detailed above, a composition in which the stability of active vitamin D is significantly improved can be obtained, and such a composition can be used for active vitamin D3 preparations. It's extremely useful.
〈実施例〉 以下本発明を実施例により更に詳細に説明する。<Example> The present invention will be explained in more detail below with reference to Examples.
実施例１
１α−ヒドロキシビタミンＤ、（１α−０ＨＤ、）０．
１ダな窒素気流下にトリアセチン１５．９に溶解して溶
液とする。この４液の熱安定性を添付図面の第１図に示
した。対照物として１α−ＯＨＤ、のダイズ油溶液を用
いた。すなわち上記溶液と対照物を４０℃に保存し、時
間の経過とともに、１α−０ＨＩ）、の残存率を調べた
ものである。その結果を第１図に示した。図中白丸は本
発明の溶液を示しており、黒丸は対照物を示している。Example 1 1α-Hydroxyvitamin D, (1α-0HD,) 0.
It is dissolved in 15.9 g of triacetin under a nitrogen stream to form a solution. The thermal stability of these four liquids is shown in Figure 1 of the accompanying drawings. A soybean oil solution of 1α-OHD was used as a control substance. That is, the above solution and the control substance were stored at 40°C, and the residual rate of 1α-0HI) was investigated over time. The results are shown in Figure 1. In the figure, white circles indicate the solution of the present invention, and black circles indicate the control.
第１図より明らかな通り、上記溶液の場合にはｌα−０
ＨＤ、の残存率が長時間にわたり低下せず平衡に達する
のに対し、対照物で残存率が時局の経過とともに順次低
下している。As is clear from Figure 1, in the case of the above solution, lα-0
The survival rate of HD does not decrease over a long period of time and reaches an equilibrium, whereas the survival rate of the control substance gradually decreases over time.
明らかに、本発明の溶液は熱安定性が向上していること
がわかる。It is clearly seen that the solutions of the present invention have improved thermal stability.
実施例２
１α−０ＨＤ、０．１〜をＮ素気流下にトリアセチン１
５．９に溶解して溶液とする。この溶液に酸素ガスを通
じた際の】α−ｏＨＤ、の安定性ン添付図面の第２図（
白丸と黒丸の表示は第１図に同じ）に示した。対照物と
してｌα−０）ＩＤ。Example 2 1α-0HD, 0.1~ was added to triacetin 1 under N gas flow
5.9 to make a solution. The stability of α-oHD when oxygen gas is passed through this solution is shown in Figure 2 of the attached drawings (
The white circles and black circles are the same as in Figure 1). lα-0) ID as a control.
のダイズ油溶液を用いた。すなわち上記溶液と対照物に
遮光下酸素ガスな４０ｄ／分の流速で通じ、時間の経過
とともに、１α−０）ＩＤ、の残存率を調べたものであ
る。七の結果、第２図より明らかな通り、本発明の溶液
の場合にしては１α−０）ＩＤ、の残存率はほとんど低
下しないのに対し対照物では残存率が８時間後には９６
％。A soybean oil solution was used. That is, oxygen gas was passed through the solution and the reference material at a flow rate of 40 d/min under light shielding, and the residual rate of 1α-0) ID was investigated over time. As is clear from Figure 2, in the case of the solution of the present invention, the residual rate of 1α-0) ID hardly decreased, whereas in the control solution, the residual rate decreased to 96% after 8 hours.
%.
１６時間後には９０％にまで着しく低下している。明ら
かに本発明の溶液は酸素に対する安定性が向上している
ことがわかる。After 16 hours, it had dropped to 90%. It is clearly seen that the solution of the present invention has improved stability against oxygen.
実施例３
１ ａ 、 ２４ （Ｒ）−ジヒドロキシＶＤ、（１１
２４（Ｒ） −（ＯＨ）ＩＤ３） ０゜１〜を窒素気
流下にトリアセチン１５１！に溶解して溶液とする。こ
の溶液の熱安定性ｗｆＡ付図面の第３図（図中、白丸と
黒丸の表示は第１図に同じンに示した。対照物として１
、２４ （Ｒ） ’ （ＯＨ）ｔＤａのダイズ油
溶′ｒＬな用（・た。Example 3 1 a, 24 (R)-dihydroxy VD, (11
24(R) -(OH)ID3) Triacetin 151! Dissolve in to make a solution. The thermal stability of this solution is shown in Figure 3 of the drawing with wfA (in the figure, white circles and black circles are shown in the same position as in Figure 1.
, 24 (R) '(OH)tDa of soybean oil solution'rL (・ta).
丁なわち上記溶液と゛対照物を４０℃に保存し、時間の
経過とともに１．２４−（矧−（ＯＨ）ｔＤｓの残存率
をｌべたものである。その結果、第３図より明らかな通
り、本発明の溶液の場合には１ 、２４− （Ｒ） −
（ＯＨ）、Ｄ、の残存率が長時間にわたり低下せず平衡
に達するのに対し、対照物では時間の経過とともに残存
率が低下し℃いる。明らかに、本発明のＭ液は熱安定性
が向上していることがわかる。In other words, the above solution and the control substance were stored at 40°C, and the residual rate of 1.24-(矧-(OH)tDs was plotted over time. As is clear from Fig. 3), , 1,24-(R)- in the case of the solution of the invention
The residual rates of (OH) and D do not decrease over a long period of time and reach equilibrium, whereas the residual rates of the control substance decrease with the passage of time. It is clearly seen that the M liquid of the present invention has improved thermal stability.
実施例４
１ ｔ ２４− （Ｒ） −（ＯＨ）ｔＤ、０．１〜を
窒素気流下にトリアセチン１５ＩＩに溶解して浴、液と
する。この溶液に酸素ガスを通じた際の１．２４−（Ｒ
） −（Ｏｆ（）ｔＤｓ の安定性を添付図面の第４図
（図中、白丸と黒丸の表示は、第１図に同じ）に示した
。Example 4 1t24-(R)-(OH)tD, 0.1~ is dissolved in triacetin 15II under a nitrogen stream to form a bath or a liquid. When oxygen gas was passed through this solution, 1.24-(R
) -(Of()tDs stability is shown in FIG. 4 of the attached drawings (in the figure, the white circles and black circles are the same as in FIG. 1).
対照物として１．２４−（■−（ＯＨ）ｔ Ｄｓのダイ
ズ油溶液を用いた。A soybean oil solution of 1.24-(■-(OH)tDs) was used as a control.
すなわち、上記溶成と対照物に遮光下酸素ガスを４０Ｍ
／分の流速で通じ、時間の経過とともに１ ＋ ２４
（Ｒ） ＜０Ｈ）ｔＤｓの残存率ｔｔｖ４ヘタモの
である。その結果、第４図より明らかな通り、本発明の
溶液の場合には１ 、２４− ｔＲｌ −（ＯＨ）ｔＤ
ａの残存率はほとんど低下しないのに対し、対照物では
残存率が８時間後には９１チ、１６時間後には８６％に
低下している。明らかに本発明の溶液は酸素に対する安
定性が向上し℃いることがわかる。That is, 40M of oxygen gas was added to the above-mentioned melt and the control object under light shielding.
/min flow rate and over time 1 + 24
(R) <0H) The survival rate of tDs is that of ttv4 hetamo. As a result, as is clear from FIG. 4, in the case of the solution of the present invention, 1,24-tRl-(OH)tD
The residual rate of A hardly decreased, whereas the residual rate of the control substance decreased to 91% after 8 hours and to 86% after 16 hours. It is clearly seen that the solution of the present invention has improved stability against oxygen.
添付図面の第１図は本発明により得られた１α−ヒトミ
キシコレカルシフェロール（１α−０ＨＤ、）の溶液お
よび対照物としての１α−０ＨＤ、のダイズ油溶液の４
０°Ｃにおける熱安定性を示したものである。
添付図面の第２図は、本発明により得られた１α−０Ｈ
Ｄ、のトリアセチン溶液および対照物としての１α−Ｃ
ＨＤ３のダイズ油俗液の酸素に対する安定性な示したも
のである。
添付図面の第３図は、本発明により得られた１、２４−
（Ｒ１−ジヒドロキシコレカルシフェロール、（１、２
４−（Ｒ） −（ＯＨ）、Ｄ、 ） のトリアセチン溶
液および対照物としての１，２４−（８）−（ＯＨ）＊
Ｄｓのダイズ油溶液の４０℃における熱安定性を示し
たものである。
添付図面の第４図は、本発明により得られた１、２４−
（■−（ＯＨ）ｔ Ｄｓのトリアセチン溶液および対照
物としての１．２４−を刊−（ＯＨ）ｔ Ｄａのダイズ
油溶液の酸素に対する安定性を示したものである。
ス □、。
一一２
第１団
笛２図
第３胆
第４０FIG. 1 of the accompanying drawings shows a solution of 1α-human mixicholecalciferol (1α-0HD) obtained according to the present invention and a soybean oil solution of 1α-0HD as a control substance.
This shows thermal stability at 0°C. FIG. 2 of the accompanying drawings shows 1α-0H obtained according to the present invention.
D, triacetin solution and 1α-C as a control.
This shows the stability of HD3 soybean oil liquid against oxygen. FIG. 3 of the accompanying drawings shows 1,24-
(R1-dihydroxycholecalciferol, (1,2
Triacetin solution of 4-(R)-(OH),D, ) and 1,24-(8)-(OH)* as control
This figure shows the thermal stability of a soybean oil solution of Ds at 40°C. FIG. 4 of the accompanying drawings shows 1,24-
(■-(OH)tDs triacetin solution and 1.24- as a control substance)-(OH)tDa soybean oil solution are shown to have stability against oxygen. 2. 1st danbue 2 fig. 3 vol. 40
Claims (1)
なる活性型ビタミンＤ＿３類製剤用組成物。A composition for an active vitamin D_3 preparation, which is obtained by dissolving active vitamin D_3 in triacetin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11673485A JPS61277622A (en) | 1985-05-31 | 1985-05-31 | Composition for active vitamin d3 preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11673485A JPS61277622A (en) | 1985-05-31 | 1985-05-31 | Composition for active vitamin d3 preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS61277622A true JPS61277622A (en) | 1986-12-08 |
Family
ID=14694462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11673485A Pending JPS61277622A (en) | 1985-05-31 | 1985-05-31 | Composition for active vitamin d3 preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61277622A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117958437A (en) * | 2024-03-28 | 2024-05-03 | 中国农业大学 | Vitamin D with improved solubility3And a method for preparing the same |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52130905A (en) * | 1976-04-23 | 1977-11-02 | Chugai Pharmaceut Co Ltd | Medicinal composition |
| JPS5753329A (en) * | 1980-09-18 | 1982-03-30 | Nippon Steel Corp | Continuous manufacture of multilayer pipe |
| JPS58167509A (en) * | 1982-03-22 | 1983-10-03 | アツプ・ジヨン・リミテツド | Gelated pge2/triacetin solution |
| JPS6064917A (en) * | 1983-09-21 | 1985-04-13 | Okada Raifu Corp:Kk | Antitumor agent and its preparation |
-
1985
- 1985-05-31 JP JP11673485A patent/JPS61277622A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS52130905A (en) * | 1976-04-23 | 1977-11-02 | Chugai Pharmaceut Co Ltd | Medicinal composition |
| JPS5753329A (en) * | 1980-09-18 | 1982-03-30 | Nippon Steel Corp | Continuous manufacture of multilayer pipe |
| JPS58167509A (en) * | 1982-03-22 | 1983-10-03 | アツプ・ジヨン・リミテツド | Gelated pge2/triacetin solution |
| JPS6064917A (en) * | 1983-09-21 | 1985-04-13 | Okada Raifu Corp:Kk | Antitumor agent and its preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117958437A (en) * | 2024-03-28 | 2024-05-03 | 中国农业大学 | Vitamin D with improved solubility3And a method for preparing the same |
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