JPH0525049A - Stable 1alpha-hydroxyvitamin d preparation - Google Patents
Stable 1alpha-hydroxyvitamin d preparationInfo
- Publication number
- JPH0525049A JPH0525049A JP16323890A JP16323890A JPH0525049A JP H0525049 A JPH0525049 A JP H0525049A JP 16323890 A JP16323890 A JP 16323890A JP 16323890 A JP16323890 A JP 16323890A JP H0525049 A JPH0525049 A JP H0525049A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxyvitamin
- 1alpha
- preparation
- solution
- dihydroxyvitamin
- 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
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は安定な１α−ヒドロキシビタミンＤ類 製剤に関する。Detailed Description of the Invention [Industrial application field] The present invention is a stable 1α-hydroxyvitamin D Regarding the formulation.
コレカルシフェロール（ビタミンＤ３）は生体内 で代謝を受け、その構造中の１α位及び２５位の 炭素が水酸化されて１α，２５−ジヒドロキシビ タミンＤ３となり、生理活性を発現するといわれ ている。It is said that cholecalciferol (vitamin D 3 ) is metabolized in vivo, and the carbons at the 1α-position and 25-position in the structure are hydroxylated to 1α, 25-dihydroxyvitamin D 3 and exhibit physiological activity. There is.
現時点では、この１α，２５−ジヒドロキシビ タミンＤ３がビタミンＤとしては最も生理活性の 高い代謝産物であるとされており、ビタミンＤ代 謝異常患者に対して医療上高い評価が得られてい る。At present, 1α, 25-dihydroxyvitamin D 3 is considered to be the most physiologically active metabolite of vitamin D, and is highly evaluated medically for patients with abnormal vitamin D metabolism.
また、このものの類似化合物として、１α−位 に水酸基を有する１α−ヒドロキシビタミンＤ３、 １α，２４−ジヒドロキシビタミンＤ３、１α， ２４，２５−トリヒドロキシビタミンＤ３等の １α−ヒドロキシビタミンＤ類が合成され、これ らは１α，２５−ジヒドロキシビタミンＤ３と同 様な生理活性を有することから、活性型ビタミン Ｄ３類として臨床への応用が期待されている。In addition, 1α-hydroxyvitamin Ds such as 1α-hydroxyvitamin D 3 , 1α, 24-dihydroxyvitamin D 3 , 1α, 24,25-trihydroxyvitamin D 3 and the like having a hydroxyl group at the 1α-position are similar compounds to these compounds. There are combined, we l [alpha], 25-because it has a similar physiological activity as dihydroxyvitamin D 3, clinical applications are expected as an active vitamin D 3 compounds.
この１α−ヒドロキシビタミンＤ類は生理活性 が高いので、１回の投与量は０．５μｇと極めて少量 であるため、患者に対して正確な投与量を保障し、 かつ投与が容易な剤型としては、油性基剤に溶解 し、軟カプセルとするのが好ましい。 This 1α-hydroxyvitamin D is bioactive The dose is 0.5 μg, which is a very small amount. Assures accurate dosing for the patient, And as a dosage form that is easy to administer, it is dissolved in an oily base. However, soft capsules are preferred.
しかしながら、１α−ヒドロキシビタミンＤ類 は何れも熱及び光に対して不安定で酸化され易い ので、一般に使用されている油性基剤に溶解して 軟カプセルとしたのみでは保存中に活性が低下し てしまう。このため、従来、油性基剤を予め光照 射して安定化しておく方法、あるいは剤皮にター ル色素等の紫外線吸収剤を含有させておくなどの 方法がとられていた。 However, 1α-hydroxyvitamin Ds Are unstable to heat and light and are easily oxidized So it can be dissolved in commonly used oily bases Only soft capsules have reduced activity during storage Will end up. Therefore, conventionally, the oily base was previously illuminated. To stabilize by irradiating, Such as containing an ultraviolet absorber such as a pigment The method was taken.
しかしながら、油性基剤を予め光照射すること は操作が煩雑であると共にコスト高の原因となり、 また紫外線吸収剤の使用は、人体に対する悪影響 を考慮すると好ましくない。 However, pre-irradiate the oil base with light. Operation is complicated and causes high cost, Also, the use of UV absorbers has a negative effect on the human body. Is not preferable considering.
斯かる実情において、本発明者は鋭意研究を行 った結果、１α−ヒドロキシビタミンＤ類を特定 の油性基剤を用いて溶解すれば、酸化され難い安 定な軟カプセル剤が得られることを見出し、本発 明を完成した。 Under such circumstances, the present inventor has conducted diligent research. As a result, 1α-hydroxyvitamin Ds were identified If it is dissolved using the oily base of It was found that a definite soft capsule could be obtained, Completed Ming.
すなわち、本発明は、１α−ヒドロキシビタミ ンＤ類を、実質的に不飽和酸を含まないリノール 酸エチルに溶解して軟カプセル剤皮中に充填した １α−ヒドロキシビタミンＤ類製剤を提供するも のである。 That is, the present invention relates to 1α-hydroxyvitamin Linols containing substantially no unsaturated acid Dissolved in ethyl acidate and filled in soft capsule skin Providing 1α-hydroxyvitamin D preparations Of.
本発明において、リノール酸エチルは、よく精 製された不飽和脂肪酸を実質的に含まないものが 用いられ、市販品を使用することもできる。 In the present invention, ethyl linoleate is well purified. Made with unsaturated fatty acids It is used, and a commercially available product can also be used.
また、１α−ヒドロキシビタミンＤ類としては、 １α−ヒドロキシビタミンＤ３又は１α，２５− ジヒドロキシビタミンＤ３を用いるのが好ましい。As the 1α-hydroxyvitamin Ds, 1α-hydroxyvitamin D 3 or 1α, 25-dihydroxyvitamin D 3 is preferably used.
本発明の製剤は油性基剤として上記のリノール 酸エチルを使用する以外は、自体公知の方法によ って製造することができ、例えば、１α−ヒドロ キシビタミンＤ類０．５μｇをリノール酸エチル中 （例えば0.1g程度）に溶解させ、得られた溶液を 常法により軟カプセル剤皮中に充填すれば本発明 のビタミンＤ類軟カプセル剤が得られる。 The formulation of the present invention has the above-mentioned linole as an oily base. A method known per se except that ethyl acetate is used. Can be produced by, for example, 1α-hydro 0.5 μg of xyvitamin D in ethyl linoleate (For example, about 0.1 g) and dissolve the resulting solution The present invention is obtained by filling a soft capsule skin by a conventional method. Vitamin D type soft capsules are obtained.
本発明に用いられるリノール酸エチルは高脂血 症用薬として臨床上用いられる医薬品であり、厚 生省医薬品再評価によれば、臨床用量は１日３〜 ６ｇである。ビタミンＤ類の１回の投与量が0.5 μｇということを考慮すれば、本発明の製剤におけ るリノール酸エチルの服用量は、１日0.3g以下と なり、臨床用量の１／１０以下となるため薬効発 現は無く、賦形剤として問題無く用い得る。 The ethyl linoleate used in the present invention has high lipemia. It is a drug used clinically as a symptomatic drug. According to the Ministry of Life drug re-evaluation, the clinical dose is 3 ~ per day. It is 6 g. One dose of Vitamin D is 0.5 In view of μg, the formulation of the present invention The daily dose of ethyl linoleate is less than 0.3g Since the clinical dose is 1/10 or less, the drug is effective It does not exist and can be used as an excipient without any problem.
尚、本発明の製剤中には、更に安定性を増す目 的で、ジブチルヒドロキシトルエン又はブチルヒ ドロキシアニソール等の抗酸化剤を配合すること が可能である。 It should be noted that the formulation of the present invention should have a further stability. Dibutyl hydroxytoluene or butyl ether Blending antioxidants such as droxyanisole Is possible.
叙上の如くして得られる本発明の１α−ヒドロ キシビタミンＤ類製剤は長期間保存しても安定で あり、またその製造法も極めて簡単である。 1α-hydro of the present invention obtained as described above Xyvitamin D preparations are stable even after long-term storage There is also a very simple manufacturing method.
次に実施例を挙げて説明する。 Next, examples will be described.
実施例１ １α，２５−ジヒドロキシビタミンＤ３0.5mg をリノール酸エチル（９７％以上、ガスクロ工業 製）１００ｇに窒素ガス気流下にて溶解してカプ セル充填液とし、常法に従ってゼラチンとグリセ リンより成るカプセル剤皮を用いて、１α，２５ −ジヒドロキシビタミンＤ３軟カプセルを得た。Example 1 0.5 mg of 1α, 25-dihydroxyvitamin D 3 was dissolved in 100 g of ethyl linoleate (97% or more, manufactured by Gascro Industrial Co., Ltd.) under a nitrogen gas stream to give a capsule filling liquid, which was composed of gelatin and glycerin according to a conventional method. Using the capsule skin, 1α, 25-dihydroxyvitamin D 3 soft capsules were obtained.
これを従来用いられている油性溶剤（ODO、日清 製油社製の中鎖脂肪酸トリグリセライド）を用い て、紫外線照射をせずに同一の方法で製造した軟 カプセルと、自然昼光を含む室内散乱光下で同一 条件にて放置し、実験開始時を１００％としたと きの残存率を測定した。 This is a conventional oily solvent (ODO, Nisshin) Medium-chain fatty acid triglyceride manufactured by Oil Refinery) The same method without UV irradiation. Identical to capsules under indoor scattered light including natural daylight If you leave it under the conditions and set the start of the experiment to 100% The residual rate of mushrooms was measured.
その結果は表１のとおりである。 The results are shown in Table 1.
Claims (2)
的に不 飽和酸を含まないリノール酸エチルに溶解して軟 カプセル剤皮中に充填した１α−ヒドロキシビタ ミンＤ類製剤。1. A 1α-hydroxyvitamin D preparation in which 1α-hydroxyvitamin Ds are dissolved in ethyl linoleate containing substantially no unsaturated acid and filled in a soft capsule skin.
ヒドロ キシビタミンＤ３又は１α，２５−ジヒドロキシ ビタミンＤ３である請求項１記載の１α−ヒドロ キシビタミンＤ類製剤。2. The 1α-hydroxyvitamin Ds are 1α-
The 1α-hydroxyvitamin D preparation according to claim 1, which is hydroxyvitamin D 3 or 1α, 25-dihydroxyvitamin D 3 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16323890A JPH0525049A (en) | 1990-06-21 | 1990-06-21 | Stable 1alpha-hydroxyvitamin d preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16323890A JPH0525049A (en) | 1990-06-21 | 1990-06-21 | Stable 1alpha-hydroxyvitamin d preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0525049A true JPH0525049A (en) | 1993-02-02 |
Family
ID=15769968
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16323890A Pending JPH0525049A (en) | 1990-06-21 | 1990-06-21 | Stable 1alpha-hydroxyvitamin d preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0525049A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2814369A1 (en) * | 2000-09-27 | 2002-03-29 | Spmd | Preparation of encapsulated cholecalciferol solutions in oil, for prevention and treatment of osteoporosis |
| FR2893847A1 (en) * | 2005-11-30 | 2007-06-01 | Galderma Sa | Composition i.e. liquid at ambient temperature, useful e.g. to treat acne, psoriasis, scleroderma and pigmentation disorders, comprises a vitamin D derivative in solubilized form and an oil phase composed of oil in an excipient |
| KR20180132879A (en) | 2016-05-18 | 2018-12-12 | 엔오케이 가부시키가이샤 | Sealing structure using annular pocket and sealing device |
| WO2020045564A1 (en) * | 2018-08-30 | 2020-03-05 | 三菱瓦斯化学株式会社 | Photodegradation inhibitor, beverage containing this, and photodegradation inhibition method |
-
1990
- 1990-06-21 JP JP16323890A patent/JPH0525049A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2814369A1 (en) * | 2000-09-27 | 2002-03-29 | Spmd | Preparation of encapsulated cholecalciferol solutions in oil, for prevention and treatment of osteoporosis |
| FR2893847A1 (en) * | 2005-11-30 | 2007-06-01 | Galderma Sa | Composition i.e. liquid at ambient temperature, useful e.g. to treat acne, psoriasis, scleroderma and pigmentation disorders, comprises a vitamin D derivative in solubilized form and an oil phase composed of oil in an excipient |
| WO2007063255A1 (en) * | 2005-11-30 | 2007-06-07 | Galderma S.A. | Composition in the form of a spray containing a vitamin d derivative and an oil phase |
| KR20180132879A (en) | 2016-05-18 | 2018-12-12 | 엔오케이 가부시키가이샤 | Sealing structure using annular pocket and sealing device |
| WO2020045564A1 (en) * | 2018-08-30 | 2020-03-05 | 三菱瓦斯化学株式会社 | Photodegradation inhibitor, beverage containing this, and photodegradation inhibition method |
| JPWO2020045564A1 (en) * | 2018-08-30 | 2021-08-12 | 三菱瓦斯化学株式会社 | Photodegradation inhibitor, beverage containing it, and photodegradation suppression method |
| EP3845074A4 (en) * | 2018-08-30 | 2021-10-27 | Mitsubishi Gas Chemical Company, Inc. | Photodegradation inhibitor, beverage containing this, and photodegradation inhibition method |
| TWI823998B (en) * | 2018-08-30 | 2023-12-01 | 日商三菱瓦斯化學股份有限公司 | Photodegradation inhibitor, beverage containing the same and method for inhibiting photodegradation |
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