JP7270465B2 - Method for photostabilizing vitamin B12s - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for photostabilizing vitamin _B12s , which inhibits degradation of vitamins _B12 due to light exposure.

Vitamin _B12 is a kind of water-soluble vitamins and is an essential nutrient for sustaining life. Symptoms of vitamin _B12 deficiency, megaloblastic anemia, tapeworm, pernicious anemia, malabsorption syndrome, asthenopia _, nutritional anemia, anemia of pregnancy, neuralgia, etc. It is known to be effective in preventing or improving skin irritation, improving rough skin, etc., and is used in food and drink, oral care products, pharmaceuticals, cosmetics, and the like. On the other hand, vitamin _B12s are known to be easily decomposed by exposure to light, and in order to put products containing vitamin _B12s into practical use, it is necessary to provide vitamin _B12s with photostability. has become essential.

Conventionally, various reports have been made on formulation techniques for imparting photostability to vitamin _B12 . For example, US Pat. No. 6,300,002 discloses that formulations containing vitamin B ₁₂ and butanol can impart photostability to vitamin B ₁₂ . Moreover, Patent Document 2 discloses that a vitamin composition containing vitamin B ₁₂ and a vitamin stabilizer having a specific phenylpropene carbonyl structure can impart photostability to vitamin B ₁₂ . Further, Patent Document 3 discloses that vitamin B ₁₂ is light-stabilized by adding cyclodextrin or a derivative thereof to vitamin B ₁₂ .

In this way, conventionally, formulation technology for photo-stabilization of vitamin _B12 has been studied, but in recent years, the demand for product diversification and quality improvement has increased. Therefore, it is desired to develop a new technique for photo-stabilization of vitamin _B12 .

WO2008/113483 JP 2007-125018 A JP-A-4-49239

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for photostabilizing vitamin _B12s capable of suppressing decomposition of vitamin _B12s due to exposure to light.

As a result of intensive studies in order to solve the above problems, the present inventors added _{polyoxyethylene} sorbitan fatty acid ester to a composition containing vitamin _B12 , and By setting the ethylene sorbitan fatty acid ester to 10 parts by weight or less, the decomposition of vitamin _B12 can be suppressed even when exposed to light under harsh conditions, and the photostabilizing effect on vitamin _B12 is remarkably remarkable. I found that it is played in The present invention has been completed through further studies based on such findings.

That is, the present invention provides inventions in the following aspects.
Section 1. A method for photo-stabilization of vitamin _B12 , comprising adding polyoxyethylene sorbitan fatty acid ester to a composition containing vitamin _B12 in a ratio of 10 parts by weight or less per 1 part by weight of vitamin _B12 .
Section 2. Item 2. The method for photostabilizing vitamin B ₁₂ compounds according to item 1, wherein the composition containing vitamin B ₁₂ compounds further contains vitamin E compounds.
Item 3. Item 3. A method for photostabilizing vitamin B ₁₂ compounds according to Item 2, wherein 0.00125 to 1000 parts by weight of vitamin E compounds are contained per 1 part by weight of vitamin B ₁₂ compounds.
Section 4. Item 4. The method for photostabilizing vitamin B ₁₂ according to any one of items 1 to 3, wherein the composition containing vitamin B ₁₂ is an aqueous composition.

According to the present invention, decomposition of vitamin _B12s due to exposure to light can be suppressed, so that it is possible to improve the storage stability of various products containing vitamins _B12 .

The photostabilization method of the present invention is a method for suppressing the decomposition of vitamin _B12s due to exposure to light, and comprises 10 parts by weight per 1 part by weight of vitamins _B12s in a composition containing vitamins _B12s . It is characterized by containing polyoxyethylene sorbitan fatty acid ester in the following ratio. The optical stabilization method of the present invention will be described in detail below.

[Vitamin _B12 ]
Vitamin _B12 refers to vitamin _B12 (cyanocobalamin), derivatives thereof, and salts thereof. The type of vitamin _B12 used in the present invention is not particularly limited as long as it can be incorporated into products such as food and drink, oral care products, pharmaceuticals and cosmetics. For example, derivatives of vitamin _B12 include methylcobalamin, hydroxocobalamin, adenosylcobalamin, aquacobalamin, and the like. Also, salts of vitamin _B12 and its derivatives include, for example, acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, Carboxylate salts such as lactate, tartrate and citrate; Organic sulfonates such as methanesulfonate, toluenesulfonate and tosylate; Inorganic acids such as hydrochloride, sulfate, nitrate and phosphate salts; organic amine salts such as methylamine, triethylamine and triethanolamine; alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium and magnesium;

These vitamin _B12s may be used singly or in combination of two or more.

Among these vitamin _B12s , cyanocobalamin is preferred.

In the photostabilization method of the present invention, the concentration of vitamin _B12s in the composition may be appropriately set according to the shape of the composition, the form of the product, etc. For example, 0.0001 to 0.2 % by weight, preferably 0.0002 to 0.02% by weight, more preferably 0.0002 to 0.002% by weight.

[Polyoxyethylene sorbitan fatty acid ester]
In the photostabilization method of the present invention, polyoxyethylene sorbitan fatty acid ester is blended at a ratio of 10 parts by weight or less per 1 part by weight of vitamin _B12s in order to stabilize vitamin _B12s .

Polyoxyethylene sorbitan fatty acid ester is a compound in which ethylene oxide is condensed with sorbitan fatty acid ester, which is a monoester, diester or triester of fatty acid and sorbitan. The number of carbon atoms in the fatty acid constituting the polyoxyethylene sorbitan fatty acid ester is, for example, 8-30, preferably 10-22, more preferably 12-18. The average number of added moles of ethylene oxide condensed to the polyoxyethylene sorbitan fatty acid ester is, for example, 6-160, preferably 6-60, and more preferably 6-30. Specific examples of polyoxyethylene sorbitan fatty acid esters include polysorbate 20 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 40 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 65 (polyoxyethylene (20) sorbitan tristearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate), polysorbate 85 (polyoxyethylene (20) sorbitan trioleate) ate), PEG-6 sorbitan stearate, PEG-20 sorbitan isostearate, PEG-6 sorbitan oleate, polysorbate 85 and the like.

These polyoxyethylene sorbitan fatty acid esters may be used singly or in combination of two or more.

Among these polyoxyethylene sorbitan fatty acid esters, polysorbate 80 is preferred from the viewpoint of more effectively stabilizing the vitamin _B12 group with light.

In the light stabilization method of the present invention, the ratio of vitamin _B12s and polyoxyethylene sorbitan fatty acid ester in the composition is 10 parts by weight or less of polyoxyethylene sorbitan fatty acid ester per 1 _part by weight of vitamin B12s. Any amount is sufficient, but the amount is preferably 1 to 10 parts by weight, more preferably 2.5 to 10 parts by weight.

In addition, in the photostabilization method of the present invention, the concentration of the polyoxyethylene sorbitan fatty acid ester in the composition may be appropriately set within a range that satisfies the above ratio. %, preferably 0.0025 to 0.1 wt%, more preferably 0.005 to 0.1 wt%.

[Vitamin E]
In the photostabilization method of the present invention, the composition containing vitamin _B12 may contain vitamin E in addition to the polyoxyethylene sorbitan fatty acid ester. By further including vitamin E in this way, it becomes possible to achieve photo-stabilization of vitamin _B12 more effectively.

Vitamin E refers to vitamin E (tocopherol, tocotrienol) and derivatives thereof. The type of vitamin E used in the present invention is not particularly limited as long as it can be blended in products such as food and drink, oral care products, pharmaceuticals and cosmetics. For example, tocopherols and tocotrienols may be α-, β-, γ-, and δ-, and may be d- or dl-forms. Examples of vitamin E derivatives include tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol linoleate, tocopherol linoleate, tocopherol nicotinate, and tocopherol (linoleate/oleate).

These vitamin E may be used singly or in combination of two or more.

Among these vitamin E, tocopherol derivatives, more preferably tocopherol acetate, are preferred from the viewpoint of more effectively stabilizing vitamin _B12 with light.

In the photostabilization method of the present invention, when the composition contains vitamin E, the ratio of vitamin _B12 to vitamin E is, for _example , 0 vitamin E per 1 part by weight of vitamin B12. 0.00125 to 1000 parts by weight, preferably 0.025 to 250 parts by weight, more preferably 2.5 to 250 parts by weight.

In addition, in the photostabilization method of the present invention, when vitamin E is contained in the composition, the concentration of vitamin E in the composition is, for example, 0.00025 to 0.1% by weight, preferably 0.1% by weight. 0005 to 0.05% by weight, more preferably 0.0005 to 0.005% by weight.

[Chelating agent]
In the photostabilization method of the present invention, the composition containing vitamin _B12 may further contain a chelating agent. The type of chelating agent used in the present invention is not particularly limited as long as it can be incorporated into products such as food and drink, oral care products, pharmaceuticals, and cosmetics. acids, salts thereof, and the like. Examples of the salt form include alkali metal salts such as sodium salts and potassium salts. These chelating agents may be used singly or in combination of two or more.

Among these chelating agents, edetic acid and salts thereof are preferred, and sodium edetate is more preferred.

Further, when a chelating agent is contained in the photostabilization method of the present invention, the concentration of the chelating agent in the composition is not particularly limited, but is, for example, 0.001 to 0.3% by weight, preferably 0.005. ~0.1% by weight, more preferably 0.01 to 0.1% by weight.

[Polyhydric alcohol]
In the photostabilization method of the present invention, the composition containing vitamin _B12 may further contain a polyhydric alcohol. Types of polyhydric alcohols used in the present invention include, for example, ethylene glycol, 1,3-butylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polypropylene glycol, glycerin and the like. These polyhydric alcohols may be used singly or in combination of two or more.

Among these polyhydric alcohols, propylene glycol is preferred.

Further, when a polyhydric alcohol is contained in the photostabilization method of the present invention, the concentration of the polyhydric alcohol in the composition is not particularly limited. to 5% by weight, more preferably 0.1 to 1% by weight.

[Other ingredients]
In the photostabilization method of the present invention, the composition containing vitamin _B12s contains various pharmacological ingredients, food materials, additives, etc., in addition to the above ingredients, depending on the shape and product form of the composition. ingredients may be included. Regarding the types of such ingredients, it is possible to appropriately select those that can be used according to the shape and product form of the composition containing vitamin _B12 . Agents (other than polyoxyethylene sorbitan fatty acid ester), oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, metallic soaps, monohydric lower alcohols, pH adjusters, buffers agents, antioxidants, UV inhibitors, preservatives, fragrances, powders, thickeners, pigments, and the like. These components may be used singly or in combination of two or more. Concentrations of these components are appropriately set according to the types of components used, the shape of the composition, the form of the product, and the like.

[Composition shape, product form, etc.]
In the photostabilization method of the present invention, the composition containing vitamin _B12s may be either an aqueous composition or a non-aqueous composition. In general, vitamin _B12s tend to be easily decomposed by light exposure in aqueous compositions, but according to the present invention, the decomposition of vitamin _B12s by light exposure can be effectively suppressed even in aqueous compositions. . In view of such effects of the present invention, an aqueous composition is a suitable example of a composition containing vitamin _B12 in the photostabilization method of the present invention.

An aqueous composition is a composition that contains water. Specifically, the concentration of water in the aqueous composition is 50% by weight or more, preferably 50 to 99.99% by weight, and more preferably 50 to 99.8% by weight. Examples of the form of the aqueous composition include liquid, gel, and paste.

When the composition containing vitamin B ₁₂ is an aqueous composition, its pH is, for example, 4.0-8.0, preferably 5.0-7.7, more preferably 5.5-7. 0 is mentioned.

A non-aqueous composition is a composition that is substantially free of water, except for water that is inevitably contained due to moisture absorption of ingredients. Examples of the shape of the non-aqueous composition include powder, granules, tablets, pills, ointment and the like.

In the photostabilization method of the present invention, the product form of the composition containing vitamin _B12 is not particularly limited, and examples thereof include food and drink, oral care products, pharmaceuticals, and cosmetics.

Examples of food and drink products include beverages such as soft drinks, alcoholic beverages, energy drinks, coffee, tea, milk, fruit juice drinks, and soft drinks; tablets, granules, powders, jellies, powders, suspensions, syrups, Supplements such as capsules (soft capsules, hard capsules); side dishes such as cheese, wieners, sausages, ham, processed seafood; ice cream, cookies, cakes, jelly, pudding, candy, chewing gum, yogurt, gummy, chocolate, Examples include confectionery such as biscuits.

Oral care products include, for example, dentifrices such as toothpaste, toothpaste, and liquid dentifrices; tooth creams; mouthwashes such as mouthwashes and gargles; adhesive films, gels, troches, tablets, chewables, oral ointments, and the like.

Pharmaceuticals include, for example, pharmaceuticals for internal use such as powders, granules, tablets, capsules, pills and liquids; pharmaceuticals for subcutaneous, intravascular or intraperitoneal administration such as infusions and injections; liquids (lotions, (including sprays, aerosols, and milky lotions), water-soluble ointments, oil-based ointments, creams, foams, gels, patches, eye drops, eye washes, and other pharmaceuticals for skin or mucous membranes. mentioned.

Examples of cosmetics include basic cosmetics such as ointments, creams, milky lotions, lotions, lotions, packs and gels; makeup cosmetics such as foundations, eye shadows, lipsticks and blushes.

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these.

Test example 1
An aqueous composition having the composition shown in Table 1 was prepared. A 500-ml transparent container (made of polyethylene terephthalate) was filled with 500 ml of the obtained aqueous composition and allowed to stand for 35 days in a room exposed to direct sunlight during the daytime (at a distance of 10 cm from a window on the south side). After standing still for 35 days, the appearance of the aqueous composition was visually observed, and the storage stability of cyanocobalamin was determined according to the following criteria. Since cyanocobalamin exhibits a pink color tone and fades when decomposed, in this test, the greater the fading, the more advanced the decomposition of cyanocobalamin.
<Storage stability of cyanocobalamin>
A: The color tone is equivalent to that immediately after production.
◯: Color fading is slightly observed compared to immediately after production, but within the allowable range.
x: Unacceptable fading clearly observed compared to immediately after production.
XX: Remarkable fading, almost colorless.

Table 1 shows the results. As a result, even when cyanocobalamin and polysorbate 80 coexist in the aqueous composition, when polysorbate 80 exceeds 10 parts by weight per 1 part by weight of cyanocobalamin, the decomposition of cyanocobalamin by light exposure could not be suppressed. On the other hand, it was confirmed that when polysorbate 80 coexists with cyanocobalamin in the aqueous composition and polysorbate 80 is 10 parts by weight or less per 1 part by weight of cyanocobalamin, the decomposition of cyanocobalamin due to exposure to light can be suppressed. It is also clear that when the aqueous composition contains cyanocobalamin, polysorbate 80 in an amount of 10 parts by weight or less per 1 part by weight of cyanocobalamin, and tocopherol acetate ester, the decomposition of cyanocobalamin due to exposure to light can be significantly suppressed. became.

Formulation Examples An aqueous composition having the composition shown in Table 2 was prepared. The storage stability of cyanocobalamin in the obtained aqueous compositions was evaluated in the same manner as in Test Example 1. As a result, the decomposition of cyanocobalamin due to light exposure could be effectively suppressed in all cases.

Claims (4)

A method for photo-stabilization of vitamin _B12 , comprising adding polyoxyethylene sorbitan fatty acid ester to a composition containing vitamin _B12 in a ratio of 10 parts by weight or less per 1 part by weight of vitamin _B12 . 2. The method for photostabilizing vitamin B ₁₂ according to claim 1, wherein the composition containing vitamin B ₁₂ is further made to contain vitamin E. 3. The method for photostabilizing vitamin B ₁₂ according to claim 2, wherein the amount of vitamin E to be contained is 0.00125 to 1000 parts by weight per 1 part by weight of vitamin B ₁₂ . 4. The method for photostabilizing vitamin B ₁₂ according to any one of claims 1 to 3, wherein the composition containing vitamin B ₁₂ is an aqueous composition.