JP3053408B2 - Stabilized oil-soluble vitamin-containing composition - Google Patents

Description

The present invention relates to a carotenoid and vitamin K or coenzyme Q
And a hydrocarbon organic solvent solution composition containing:

[Conventional technology]

Since many oil-soluble vitamins are unstable to light, heat or oxidation, various stabilizing methods have been attempted in formulating these compounds.

For example, vitamin K ₁ (phyloquinone) and vitamin K ₂
When formulating (menaquinone), vitamin K dissolved in a fat or oil base may be encapsulated in a colored capsule for the purpose of blocking light, or a stabilizer may be added (Japanese Patent Publication No. 42-4062). ) And so on.

In the case of preparations such as vitamin A and coenzyme Q, measures such as using a stabilizer or blocking light or oxygen by means such as encapsulation are taken to stabilize these compounds. ing.

[Problems to be solved by the invention]

As described above, in a preparation containing an oil-soluble vitamin as an active ingredient, attempts to stabilize these compounds against light have been made from various angles, but none of these are satisfactory. Therefore, the development of an excellent stabilizing means for the

[Means for solving the problem]

Thus, the present inventors have studied the stability of vitamin K and coenzyme Q to light among the oil-soluble vitamins. As a result, by adding carotenoid as a stabilizer to vitamin K or coenzyme Q, The inventors have found that the stability of these compounds to light can be dramatically improved and completed the present invention. That is, the present invention relates to a stabilized hydrocarbon organic solvent solution composition containing vitamin K or coenzyme Q containing a carotenoid as a stabilizer.

One specific embodiment of the composition of the present invention is a stabilized vitamin K-containing composition comprising vitamin K, a carotenoid and, if necessary, an oil component and other known additives on pharmaceuticals. it can.

As another specific embodiment of the composition of the present invention, a solubilizing solution comprising vitamin K, a carotenoid, a solubilizing agent, water and, if necessary, an oil component and other well-known additives on pharmaceuticals is mentioned. be able to.

Still another specific embodiment of the composition of the present invention is an emulsion comprising vitamin K, a carotenoid, an emulsifier, water and, if necessary, an oil component and other known additives on pharmaceuticals. it can.

Vitamin K stabilized by the present invention includes vitamin K, that is, vitamin K ₁ , vitamin K ₂ ,
K _3, vitamin K _4, vitamin K _5, vitamin K _6, vitamin K ₇
And examples of coenzyme Q include CoQ ₇ , CoQ ₈ , CoQ ₉ and CoQ ₁₀ . These vitamin K or coenzyme Q can be stabilized with a stabilizer alone or as a combination of two or more.

In the present invention, carotenoids used as stabilizers include α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene, cryptoxanthin,
Lutein, zeaxanthin, rhodoxanthin, canthaxanthin, capsanthin, crocetin, squalene, β
-Ionone and the like. These carotenoids can be used alone or in combination of two or more.

These carotenoids are added in an effective amount as a stabilizing agent to vitamin K or coenzyme Q. Preferably, the carotenoid is obtained from 0.01% by weight or more based on vitamin K or coenzyme Q. It may be added in an amount up to the limit of solubility in the substance.

The method for producing the composition of the present invention may be any method as long as vitamin K or coenzyme Q and the carotenoid are uniformly mixed. For example, vitamin K may be added to an oil component or an organic solvent.
Alternatively, it is made by dissolving coenzyme Q and carotenoid at a predetermined ratio. In mixing the two, it is also possible to stir and mix what has been heated to a molten state.

The oil component is an animal oil, a vegetable oil, a hydrocarbon oil, a synthetic glyceride oil and the like, and specific examples thereof include various fish oils such as sardine oil, saury oil, squid oil, herring oil, and various vegetable oils such as Soybean oil, rapeseed oil, corn oil, corn germ oil, cottonseed oil, olive oil, safflower oil, sesame oil, etc., hydrocarbon oils, liquid paraffin, Nikko Chemical products squalane, squalene-EX, synceran 30, etc., and synthetic glycerides, for example Examples include medium-chain fatty acid triglycerides called MCT. However, any substance may be used as long as it dissolves the carotenoid, but the present inventors have found that it is most preferable to use a hydrocarbon organic solvent, particularly hexane, as the organic solvent.

The above-described composition containing vitamin K or coenzyme Q is prepared by adding a stabilized amount of carotenoid to an oil component in which vitamin K or coenzyme Q is dissolved, or dissolving a desired amount in an oil component in which carotenoid is dissolved. It can be prepared by adding and dissolving vitamin K or coenzyme Q, or by mixing and dissolving the three simultaneously. Any method can be used as long as a homogeneous mixture can be prepared. If necessary, well-known additives in pharmaceutical preparations can be added to the composition containing vitamin K or coenzyme Q.

Emulsifiers used in preparing an emulsion, which is one of the compositions of the present invention, include phospholipids (eg, egg yolk phospholipids, soybean phospholipids, other modified phospholipids, etc.), glycerin fatty acid esters, Glycerin fatty acid ester, decaglycerin fatty acid ester, sorbitan fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene Castor oil, polyoxyethylene hardened castor oil, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin fatty acid ester, and the like. Phospholipids are preferred.

Further, as the solubilizing agent used when preparing the solubilizing solution, the above-mentioned emulsifier can be appropriately used according to the purpose.

The above-mentioned emulsion and solubilized liquid can be prepared according to a known method using a usual stirring means, for example, a homogenizer, a stirrer or the like.

Stabilized vitamin K or coenzyme Q according to the invention
The containing composition can be formulated according to well-known means for formulation. Examples of preparations include liquids (eg, injections, syrups, etc.), solids (eg, tablets, granules, etc.), semi-solids (eg, ointments, creams, etc.), capsules (eg, , Hard capsules and soft capsules).

Well-known additives for formulation include stabilizers other than carotenoids, bulking agents such as lactose, starch, crystalline cellulose, synthetic aluminum silicate and the like, coloring agents such as tar pigments, titanium oxide, yellow iron oxide, red iron oxide And sweeteners such as sucrose, sodium saccharin, D-xylose, sorbitol, mannitol, and the like, and flavors such as aliphatic alcohols, aromatic alcohols, and aromatic aldehydes.

Since the vitamin K or coenzyme Q-containing composition of the present invention is stabilized against the degradation of vitamin K or coenzyme Q by light, the decrease in titer is small even after long-term storage, Can be used with high reliability.

The composition thus obtained can be used, for example, as a drug, an animal drug, a feed additive, a nutritional supplement and the like.

Hereinafter, the present invention will be described in detail with reference to examples.

Separately in Example 1 n-hexane 25ml vitamin K ₂ and vitamin
K ₁ to 25mg added samples (hereinafter these respective Control Examples E, Control Example F hereinafter) and the sample added with β- carotene 1.5mg to each of the sample (hereinafter these respective samples E and F
) Was prepared.

Each of these samples is placed at a distance of 30 minutes from the light source to the sample surface.
Irradiated with white fluorescent light for 8 hours at lux of 2000 lux in cm.

Every hour during the irradiation, a part of the sample was taken out, and the residual ratio (%) of vitamin K ₂ and vitamin K _{1 in} the sample was measured by high performance liquid chromatography.

 The results obtained are shown in Table 1 below.

Example 2 A sample in which 25 mg of vitamin A acetate was added to 25 ml of n-hexane (control example), a sample in which 2 mg of β-carotene was added to the above sample (hereinafter referred to as sample G), and 4 mg
(Hereinafter referred to as Sample H) was prepared.

Each of these samples was irradiated with an illuminance of 2000 lux with a self-color fluorescent lamp for 24 hours as in Example 1.

During the irradiation, a part of the sample was taken out at intervals shown in the following table, and the residual ratio (%) of vitamin A acetate in the sample was measured by high performance liquid chromatography.

 The results obtained are shown in Table 2 below.

Example 3 A sample prepared by adding 25 mg of ubidecarenone (CoQ ₁₀ ) to 25 ml of n-hexane (control example) and 0.775 mg of β-
A sample to which carotene was added (hereinafter referred to as sample I) was prepared.

Each of these samples was irradiated with an illuminance of 2000 lux with a self-color fluorescent lamp for 24 hours as in Example 1.

During irradiation, remove a part of the sample at the intervals shown in the table below,
The residual ratio (%) of ubidecarenone in the sample was measured by high performance liquid chromatography.

 The results obtained are shown in Table 3 below.

Example 4 n-hexane 25ml sample of vitamin K ₂ 25 mg (the comparison), canthaxanthin each 1.58mg to the sample, the sample was added lycopene 1.5 mg (hereinafter these respective samples J, and K Call) was prepared.

Each of these samples was irradiated with a white fluorescent lamp for 8 hours at an illuminance of 2000 lux in the same manner as in Example 1.

A part of the sample was taken out every hour during irradiation, and the residual ratio (%) of vitamin K _{2 in} the sample was measured by high performance liquid chromatography.

 The results obtained are shown in Table 4 below.

From the above results, canthaxanthin and lycopene is effective as a stabilizer to prevent the degradation of vitamin K ₂ by light.

Example 5 A sample in which 25 mg of vitamin K ₂ was added to 25 ml of n-hexane (control example) and 0.3 mg of β-carotene were added to the above samples, respectively.
0.316 mg canthaxanthin, 0.3 mg lycopene, and
Samples to which 0.3 mg of γ-carotene was added (hereinafter referred to as samples L, M, N, and O, respectively) were prepared.

Each of these samples was irradiated with a white fluorescent lamp for 8 hours at an illuminance of 2000 lux in the same manner as in Example 1.

A part of the sample was taken out every hour during irradiation, and the residual ratio (%) of vitamin K _{2 in} the sample was measured by high performance liquid chromatography.

 The results obtained are shown in Table 5 below.

Continuation of the front page (56) References JP-A-63-165322 (JP, A) JP-A-63-255229 (JP, A) British Patent Application Publication 2120939 (GB, A) British Patent Application Publication 1375436 (GB, A) (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K 31/12 A61K 47/06 CA (STN) MEDLINE (STN)

Claims (1)

(57) [Claims] 1. A carotenoid and vitamin K or coenzyme Q
And a hydrocarbon-based organic solvent solution composition comprising: