JP3091913B2 - Photostabilized ubidecarenone-containing composition and method for producing the same - Google Patents

Description

The present invention relates to a light-stabilized ubidecarenone-containing composition and a method for producing the same. More specifically, the present invention relates to ubidecarenone with oil yellow OB (yellow No. 3), Sudan II
A light-stabilized ubidecarenone-containing composition comprising at least one dye selected from the group consisting of (red No. 5) and tartrazine (yellow No. 4) (hereinafter simply referred to as “dye” for convenience); It relates to the manufacturing method.

[Background Art] Ubidecarenone is a biochemically located substance in the electron transport system of cardiac mitochondria and plays an important role in energy production. Clinically, chronic hypertension, ischemic heart disease, and valvular heart disease It has been found that the substance is an effective substance for improving congestive symptoms and angina symptoms caused by deterioration of cardiac function such as diseases, and has been widely used clinically. Conventionally, ubidecarenone is often marketed exclusively in the form of a solid preparation for oral administration, and this form itself has contributed to ease of administration in patients and to enable widespread use of ubidecarenone.

[Problems to be Solved by the Invention] Raw ubidecarenone powder is a fat-soluble substance that is solid at room temperature with a melting point of 48 to 52 ° C, and is usually an orange-yellow powder. However, ubidecarenone is unstable to light, and gradually decomposes and turns brown when irradiated with light. Therefore, there is a need for a technical means for stabilizing ubidecarenone against light.

[Means for Solving the Problems] As a result of earnest studies, the present inventors have found that when a dye is added to ubidecarenone, ubidecarenone can be stably protected against light irradiation, and the present invention has been completed. .

Accordingly, it is an object of the present invention to provide a light-stabilized ubidecarenone-containing composition comprising a compound of ubidecarenone and a dye.

Another object of the present invention is to provide a method for producing a light-stabilized ubidecarenone-containing powder, which comprises blending a dye with ubidecarenone and spray-drying, freeze-drying or stirring granulation.

Other objects of the present invention will become apparent from the following description.

About the mixing ratio of the dye to ubidecarenone,
Although there is no particular limitation, for 100 parts by weight of ubidecarenone,
1 to 50 parts by weight of the dye is preferred.

When the composition of the present invention is produced, its operation is generally carried out as follows.

That is, a poorly water-soluble (oil-based) ubidecarenone bulk powder is dissolved in an oil-based carrier such as propylene glycol dicaprate or tetraglycerol hexacaprate or castor oil to form a solution. Was added and emulsified by a high-speed homogenizer to obtain a dye-containing ubidecarenone oily carrier solution,
This is spray-dried, so-called "dry emulsion"
And

A dry emulsion can also be obtained by a freeze drying method or a stirring granulation method instead of the spray drying method.

The solution can be used as a light-stabilized composition as it is without spray drying.

The light stability test is generally performed as follows based on the Japanese Pharmacopoeia.

A sample is collected in a petri dish (4 cm in diameter), covered with a film (for example, polyvinylidene chloride), and irradiated with ultraviolet light from a height of 30 cm by a fluorescent chemical lamp. After the irradiation, the photostability is determined by measuring the amount of remaining ubidecarenone relative to the content of ubidecarenone in the sample before irradiation (residual rate).

The ubidecarenone content was measured by taking a sample in a test tube, adding a mixed solution of methanol / chloroform (2: 1) thereto, and shaking with a horizontal shaker. After centrifugation, the supernatant is diluted with the mixture, and the amount of ubidecarenone (Uc) is determined by HPLC (high performance liquid chromatography).

[Action] The attached drawing shows that ubidecarenone is used as a pigment as oil yellow OB (Yellow No. 3) or Sudan II (Red No. 5)
The photostability of a composition prepared by combining [oil-soluble dye] or tartrazine (Yellow No. 4) [water-soluble dye], or a combination thereof with a composition containing no dye (control = control) is shown. FIG. The horizontal axis indicates the light irradiation time (hour), and the vertical axis indicates the residual rate (%) of photostability. From this graph, the light stabilizing effect of the composition obtained by blending the dye with ubidecarenone is recognized.

EXAMPLES Next, the present invention will be described more specifically with reference to examples.
However, the present invention is not limited to only these examples.

Example 1 A red-yellow oil-soluble dye was dissolved in an oil carrier solution of ubidecarenone, the following additives were added, and the mixture was emulsified and spray-dried to obtain a light-stabilized ubidecarenone-containing composition.

Oil phase Ubidecarenone 0.25 g Oil yellow (Y-3) (oil-soluble dye) 0.1 g Propylene glycol dicaprate (oil carrier) 20 g Water phase Spherical silica (excipient) 5 g Polyoxyethylene polyoxypropylene glycol (surfactant) 2g Purified water Make up 1000g in total.

The changes in the photostability over time of the obtained composition (marked with 経 時) are plotted and shown in the drawing. A control without the addition of a dye (x) is also shown. by this,
The photostability effect of the present invention was clearly demonstrated.

Example 2 The same light-stabilized ubidecarenone-containing composition was obtained as in Example 1 except that Red No. 5 (Sudan II, R-5) was used instead of oil yellow (Y-3).

 The photostability (marked by □) of the obtained composition is shown in the drawing.

Example 3 A light-stabilized ubidecarenone-containing composition was obtained in the same manner as in Example 1, except that a water-soluble dye was used instead of the oil-soluble dye.

Oil phase Ubidecarenone 1 g Tetraglycerol hexacaprate (oil carrier) 20 g Water phase ZS-50001T (excipient) 50 g Polyoxyethylene polyoxypropylene glycol (surfactant) 2 g Tartrazine (Y-4) (water-soluble dye) 0.1 g Purified water Amount of 1000 g in total Here, "ZS-50001T" is obtained by using silica particles containing titanium oxide as base particles and attaching zirconium to the surface thereof.

 The photostability (△) of the obtained composition is shown in the drawing.

Example 4 A light-stabilized ubidecarenone-containing composition was obtained in the same manner as in Example 1, except that an oil-soluble dye and a water-soluble dye were used in combination.

Oil phase Ubidecarenone 1 g Oil yellow (Y-3) (oil-soluble pigment) 0.05 g Tetraglycerol hexacaprate (oil carrier) 20 g Water phase Light anhydrous silicic acid (excipient) 20 g Polyoxyethylene polyoxypropylene glycol (surfactant) Agent) 2 g Tartrazine (Y-4) (water-soluble dye) 0.05 g Purified water Amount of 1000 g in total The photostability (marked by ●) of the obtained composition is shown in the drawing. A synergistic effect of photostability due to the combined use of the oil-soluble dye and the water-soluble dye was observed.

Example 5 In the same manner as in Example 1, except that 20 g of light anhydrous silicic acid was used instead of spray-drying and freeze-drying was performed to obtain similar results.

Example 6 In the same manner as in Example 1 except that in this case, instead of spray drying, stirring granulation was performed using lactose as a core substance, and similar results were obtained.

Example 7 A solution composition was obtained in the same manner as in Example 1, except that spray drying was not performed in this case.

[Brief description of the drawings]

The drawing is a graph showing the light stability of a composition in which various dyes are blended with ubidecarenone and that in which no dye is blended.

Continuation of front page (56) References JP-A-61-280424 (JP, A) JP-A-59-161314 (JP, A) JP-A-60-11125 (JP, A) JP-A-57-54116 (JP) , A) JP-A-2-29778 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 31/122 C07C 46/10 C07C 50/28 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A light stabilization comprising blending ubidecarenone with at least one dye selected from the group consisting of Oil Yellow OB (Yellow No. 3), Sudan II (Red No. 5) and Tartrazine (Yellow No. 4). Ubidecarenone-containing composition. 2. A blend of ubidecarenone with at least one dye selected from the group consisting of Oil Yellow OB (Yellow No. 3), Sudan II (Red No. 5) and Tartrazine (Yellow No. 4), spray drying and freezing. A method for producing a light-stabilized ubidecarenone-containing powder, comprising drying or stirring and granulating.