JP2002104958A - Lipophilic vitamin preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a lipophilic vitamin preparation stable under acidic conditions in the inside of the stomach, etc., capable of making lipophilic vitamins reach the intestinal tract being an absorption part in a high ratio without decomposition when orally administered and to provide a method capable of simply producing the preparation. SOLUTION: This granular lipophilic vitamin preparation comprises substantially 0.1-50 wt.% of a lipophilic vitamin, 49.8-99.8 wt.% of oil and fat wax and 0.1-10 wt.% of a stabilizer. This method for producing the granular lipophilic vitamin preparation is provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a lipophilic vitamin preparation and a method for producing the same.

[0002]

2. Description of the Related Art Lipophilic vitamins are absorbed into the body through the intestinal tract when taken orally, but are unstable and easily decomposed under acidic conditions such as in the stomach, so that lipophilic vitamins reach the intestinal tract. Conventionally, as a formulation designed in, a formulation obtained by forming an emulsion containing a lipophilic vitamin, gelatin and a reducing sugar, forming the resulting emulsion into fine particles, followed by drying and heat treatment is known ( JP-A-63-25
No. 8807).

[0003]

However, the preparation obtained by the above method is still not sufficiently stable under acidic conditions and requires complicated operations such as drying and heat treatment. Have a problem.

[0004] An object of the present invention is to enable lipophilic vitamins that are stable under acidic conditions such as the inside of the stomach to reach the intestinal tract, which is the site of absorption, without being decomposed at a high rate when ingested orally. It is an object of the present invention to provide a lipophilic vitamin preparation and to provide a method for producing the preparation more easily.

[0005]

That is, the present invention provides a method for producing a liquid crystal display comprising:
A granular lipophilic vitamin preparation (hereinafter referred to as the present preparation) consisting essentially of 50 parts by weight of lipophilic vitamin, 49.8 to 99.8 parts by weight of fat wax and 0.1 to 10 parts by weight of stabilizer. And a method for producing a granular lipophilic vitamin preparation.

[0006]

DETAILED DESCRIPTION OF THE INVENTION The lipophilic vitamins that can be used in the present invention include vitamin A (vitamin A1, vitamin A2, vitamin A3, etc.) and vitamin D (vitamin D).
2, vitamin D3, provitamin D2, provitamin D
3), Vitamin E, Vitamin K (Vitamin K1, Vitamin K2, etc.), β-carotene and the like, and derivatives thereof such as Vitamin A acetate, Vitamin A palmitate, Vitamin E acetate and the like. Can also. These may be present alone or in a mixture of two or more in the present formulation. The content of the lipophilic vitamin in the present preparation is 0.1 to 50% by weight, preferably 10 to 50% by weight.

[0007] The fat wax in the present invention is at normal temperature,
Animal fats and oils having a freezing point of usually 60 to 98 ° C,
Hard oils such as vegetable oil wax, mineral oil wax, higher fatty acid, higher fatty acid salt, higher fatty acid ester and the like.

[0008] Animal fats and oils include, for example, animal fats and oils, hard waxes, beef tallow, hardened tallow, beeswax, and the like. Soybean oil,
Hardened palm oil, hardened cottonseed oil, carnauba wax can be mentioned, as mineral oil waxes, for example, normal paraffin wax, isoparaffin wax,
Examples of the oxidized petroleum wax include higher fatty acids such as palmitic acid and stearic acid having 8 to 22 carbon atoms.
The higher fatty acid salts include fatty acid salts having 12 to 22 carbon atoms such as sodium palmitate and potassium stearate. The higher fatty acid esters include glycerin fatty acid ester and sucrose fatty acid ester. And higher fatty acid esters such as sorbitan fatty acid esters and propylene glycol fatty acid esters. These may be present alone or in a mixture of two or more in the present formulation. The content of the solid fat wax in the present preparation is 49.8 to 99.8% by weight, preferably 50 to 90% by weight.

[0009] Stabilizers which can be used in the present invention include, for example, hydroxyanisole (BHA), butylated hydrotoluene (BHT), 6-ethoxy-1,2-dihydro-
Phenolic antioxidants such as 2,2,4-trimethylquinoline (ethoxyquin), ascorbic acid antioxidants such as ascorbic acid, sodium ascorbate, ascorbic acid ethyl ester, and ascorbic acid methyl ester; Examples include antioxidants / excipients such as monosaccharides such as glucose and fructose, oligosaccharides such as maltose and sucrose, and polysaccharides such as maltodextrin. These may be used alone or in a mixture of two or more. It may be present in the formulation. The content of the stabilizer in the preparation is 0.1
-10% by weight, preferably 2-10% by weight.

The present preparation may contain water and the like as long as the characteristics of the present preparation are not impaired. The content of water in the preparation is usually 5% by weight or less.

The present preparation is usually about 10 to 2000 μm,
It is preferably a granular material of about 50 to 1000 μm, and its shape is usually a so-called bead shape (small sphere). In this preparation, the lipophilic vitamin and the stabilizer exist in a state of being dispersed or dissolved in the fat wax.

This preparation is insoluble in water and has a special hardener,
There is no need to add additives such as cross-linking agents. In addition, the present formulation also has stability to pressurized conditions, and hardly causes destruction of the present formulation, which is a problem in further formulation using the present formulation (for example, pelletization and encapsulation including the present formulation). . The formulation can be used as an additive to foodstuffs and pharmaceuticals, as well as animal feed. Further, as described above, the present formulation is insoluble and stable in the stomach, but decomposes in the intestine, particularly in the small intestine, and releases the lipophilic vitamin which is the active ingredient.

In the present preparation, a predetermined amount of a lipophilic vitamin, an oil wax and a stabilizer are mixed at a temperature higher than the freezing point of the oil wax to form an emulsion or a solution. And the solidified droplets (hereinafter referred to as the present method). The freezing point of the fat wax is a temperature at which the fat wax solidifies, and is a temperature specific to the fat wax used.

The formation of an emulsion or a solution can be carried out by mixing a lipophilic vitamin, a fat wax and a stabilizer at a temperature higher than the freezing point of the fat wax, usually about 100 ° C. or lower. It can be carried out by stirring using a mixer such as a one-motor, so that a uniform emulsion or solution can be obtained.

As a method of making the emulsion or the solution into small droplets, a method of dropping the emulsion or the solution can be exemplified. The emulsion or the solution is dropped by, for example, a dryer equipped with an atomizer for spraying the emulsion or solution by a variable flow pump (a fluidized bed equipped with an atomizer for spraying in consideration of solidification of the droplets in the next step). It is preferred to use a drier.) And spraying the inside of the drier with a spray atomizer or the like. The size can be adjusted, and for example, a droplet having a particle size of about 50 to 300 μm can be obtained. It is necessary that the dropping be performed at a temperature equal to or higher than the freezing point of the fat wax in the emulsion or solution in order to easily perform the dropping.

The droplets of the emulsion or solution thus dropped can be solidified, for example, by cooling to a temperature below the freezing point of the fat wax in a space, and the present preparation is obtained.

For example, the above-mentioned droplets of the emulsion or the solution are solidified while maintaining the state of the fine particles, and then, for example, in a fluidized bed dryer equipped with an atomizer until the state of the fine particles is permanently established. Is collected on a flowing non-reactive powder or a bed having the powder, and then sieved with the powder so that the solidified fine particles are separated and held from each other. As a non-reactive powder that can be used in the present invention,
For example, raw starch obtained from potato, corn and the like, modified starch such as oxidized starch, acetylated starch, methylated starch, carboxymethylated starch, silicic acid, silicic acid derivative and the like can be mentioned. Preferably, it is raw starch obtained from potato or corn.

In the present method, the preparation can also be produced by forming the emulsion or solution, making the emulsion or solution small, and solidifying the small droplets in water. In this method, the formation of the emulsion or solution and the dropletization of the emulsion or solution are carried out, for example, in water.
A predetermined amount of lipophilic vitamin, fat wax and stabilizer,
The mixing can be carried out at a temperature above the freezing point, usually below the boiling point of water, under stirring conditions. The mixing can be carried out, for example, by stirring using a mixer such as a Suriwan motor, whereby a dispersion in which the emulsion or the solution droplets are dispersed in water can be obtained. . The amount of water is usually 20 to 1000 times the weight of the emulsion or solution. Then, the dispersion is slowly cooled from the vicinity of the solidification point of the solid fat wax under stirring, and then cooled to room temperature, whereby the droplets can be solidified. After solidification, a particulate lipophilic vitamin preparation having a water content of usually 5% by weight or less can be obtained by, for example, filtration or the like, and can be subjected to a drying treatment, if necessary.

According to the present method, the present preparation can be efficiently produced by a simple fluidized drying apparatus or a water bath apparatus without requiring a complicated particle collecting / drying apparatus conventionally required. .

[0020]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the examples. Example 1 75 g of hardened rapeseed oil (manufactured by Kawaken Fine Co., Ltd.) was dissolved in a warm water bath by ripening to about 80 ° C. while stirring. While stirring this solution, 25 g of crystalline vitamin A acetate (2,90) previously melted with 10 g of BHT at a temperature of about 70 ° C.
(0.00IU / g vitamin A activity) and 0.2 g of vitamin D3 were added, and the mixture was stirred until sufficiently dispersed to form an emulsion. While stirring this emulsion, it was pressurized with a peristaltic pump in a fluidized bed drier (manufactured by Paulette), and the water content of the emulsion was previously measured using a spray atomizer.
Added to 300 g of flowing potato starch dried to 5%. The emulsion is dropped into a potato starch bed, the thus obtained granular lipophilic vitamin preparation is collected in potato starch, the granular lipophilic vitamin preparation is separated by a 170 mesh sieve, and the present preparation remaining on the sieve 1 was collected. Formulation 1 thus obtained is insoluble in water, has a particle size of 750-80 microns, a moisture content of 1% and a vitamin A content of 550,000 IU / g.
Had activity.

Examples 2 to 5 Instead of hard rapeseed oil, beef tallow (Example 2) and paraffin wax (trade name: Paraffin wax No.
155) (Example 3), except that beeswax (Example 4) and carbana wax (Example 5) were used, respectively.
Preparations 2 to 5 were obtained in the same manner as described above. Each of the obtained formulations was 488,000 IU / g (Example 2), 498,0
It had vitamin A activity of 00 IU / g (Example 3), 500,500 IU / g (Example 4), and 502,000 IU / g (Example 5).

Example 6 38 g of hardened rapeseed oil (manufactured by Kawaken Fine Co., Ltd.) was ripened at about 80 ° C. in a warm water bath with stirring to dissolve. While stirring the solution, 12.5 g of crystalline vitamin A acetate (2,900,000 IU / g vitamin A activity) and 0.1 g of vitamin D3 previously melted together with 5 g of BHA at a temperature of about 70 ° C. were added, Stirring was continued until it was sufficiently dispersed to obtain an emulsion. The emulsion was dropped into a spray drier (manufactured by Niro Corporation) attached to a high-speed disk atomizer while stirring, using a peristaltic pump.
About 300 g of potato starch dried to -5% was added to the dryer. The rotation speed of the atomizer was 10,000 rpm, and the air temperature at the dryer inlet was 25 degrees. The emulsion is dropped into a potato starch bed, the resulting granular lipophilic vitamin preparation at the bottom of the dryer is collected, the granular lipophilic vitamin preparation is separated by a 170 mesh sieve, and the present preparation 6 remaining on the sieve is removed. Was collected.

Example 7 This preparation 7 was obtained in the same manner as in Example 6 except that the amount of hard rapeseed oil was 33 g, vitamin D3 was not used, and 5 g of BHA and 5 g of sucrose were used instead of 5 g of BHA.

Example 8 This preparation 8 was obtained in the same manner as in Example 6 except that the amount of hard rapeseed oil was 33 g, and 5 g of sucrose and 5 g of ascorbic acid palmitate were used instead of 5 g of BHA.

Example 9 This preparation 9 was obtained in the same manner as in Example 8 except that sucrose was not added.

Example 10 75 g of paraffin wax (manufactured by Nippon Seiro Co., Ltd., trade name: Paraffin Wax No. 150) was added to warm water of 80 ° C. or higher while stirring and suspended. To this, crystalline vitamin A acetate 25 previously melted with 10 g of BHT
g (2,900,000 IU / g vitamin A activity) and stirred at 80 ° C. until fully dispersed. After forming a uniform dispersion, the mixture was cooled to room temperature at a rate of about 2 ° C./min with stirring. The formulation was obtained by removing water from the dispersion by filtration. Formulation 10 had substantially the same particle size as Formulation 1 and had a vitamin A activity of 505,000 IU / g.

Example 11 This preparation 11 was prepared in the same manner as in Example 10 except that hard rapeseed oil was used instead of paraffin wax, ethoxyquin was used instead of BHT, and the amount of vitamin A acetate was changed to 15 g.
I got This preparation 11 had a particle diameter almost the same as that of this preparation 1, and had a vitamin A activity of 505,000 IU / g.

Test Example 1 100 mg of the sample described in Table 1 was added to 2 ml of 0.5% hydrochloric acid aqueous solution.
Shake at 50 ° C. for 24 hours. After shaking, the sample was visually observed for dissolution or breakage. After silent observation, the sample liquid was centrifuged (2500 rpm, 10 minutes) to remove the upper liquid layer,
The solids were collected, and the sample analysis standards were annotated (3rd edition). Vitamin A analysis was performed according to the method of the Japan Association of Science Feedstuffs to determine the content of vitamin A. From the results, the residual ratio of vitamin A in the preparation was determined. All of the present preparations 1 to 4 even after the shaking,
There was almost no change in its shape. Table 1 shows the results.

[0029]

[Table 1]

[0030]

According to the present invention, it is stable under acidic conditions such as the inside of the stomach, and when ingested orally, lipophilic vitamins can reach the intestinal tract as an absorption site without being decomposed at a high rate. The present invention can provide a lipophilic vitamin preparation, and a method for more easily producing the preparation.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme court ゛ (Reference) A61K 31/592 A61K 31/592 31/593 31/593 47/08 47/08 47/22 47/22 47 / 26 47/26 47/36 47/36 47/44 47/44 A61P 3/02 102 A61P 3/02 102 109 109 F term (reference) 4C076 AA32 BB01 CC23 DD39Q DD59Q DD60Q DD67Q EE30Q EE55 FF36 4C086 AA02 BA09 DA14 MA03 MA05 MA07 MA08 MA41 MA52 NA03 ZC23 ZC29 4C206 AA02 BA05 CA10 CB28 MA03 MA05 MA11 MA13 MA17 MA28 MA61 MA72 NA03 ZC23 ZC29

Claims (10)

[Claims] (1) 0.1 to 50% by weight of a lipophilic vitamin,
9.8-99.8% by weight of fat wax and 0.1-1
A particulate lipophilic vitamin formulation consisting essentially of 0% by weight of a stabilizer. 2. The granular lipophilic vitamin preparation according to claim 1, wherein the granular lipophilic vitamin preparation is a bead lipophilic vitamin preparation at room temperature. 3. A granular lipophilic vitamin preparation according to claim 2, wherein the particle diameter is in the range of 10 to 2000 microns. 4. The lipophilic vitamin is vitamin A, vitamin A acetate, vitamin A palmitate, vitamin D.
2. The granular lipophilic vitamin preparation according to any one of claims 1 to 3, wherein the preparation is at least one selected from the group consisting of vitamin D3, vitamin E, vitamin E acetate, vitamin K and β-carotene. 5. The method according to claim 1, wherein the stabilizer is hydroxyanisole, butylated hydrotoluene, 6-ethoxy-1,2-dihydro-.
5. At least one selected from the group consisting of 2,2,4-trimethylquinoline, ascorbic acid, sodium ascorbate, ethyl ascorbate, methyl ascorbate, monosaccharides, oligosaccharides and polysaccharides. Granular lipophilic vitamin preparation according to any of the above 6. The method according to claim 1, wherein the granular lipophilic vitamin preparation comprises 0.1 to 50.
Parts by weight of a lipophilic vitamin, 49.8 to 99.8 parts by weight of a fat wax and 0.1 to 10 parts by weight of a stabilizer are mixed at a temperature above the freezing point of the fat wax to form an emulsion or solution. The granular lipophilic vitamin preparation according to any one of claims 1 to 5, which is obtained by making the emulsion or the solution into small droplets, and solidifying the small droplets. 7. The method according to claim 7, wherein the granular lipophilic vitamin preparation is dissolved in water at a concentration of 0.1%.
1 to 50 parts by weight of lipophilic vitamin, 49.8 to 99.8
Emulsion liquid obtained by mixing parts by weight of a fat wax and 0.1 to 10 parts by weight of a stabilizer at a temperature equal to or higher than the freezing point of the fat wax and substantially comprising lipophilic vitamins, solid fat wax and the stabilizer, and becoming small droplets Alternatively, the granulated lipophilic vitamin preparation according to any one of claims 1 to 5, which is obtained by forming a solution in water, and then cooling the solidified emulsion or solution. 8. An emulsion or solution is formed by mixing a lipophilic vitamin, an oil wax and a stabilizer at a temperature equal to or higher than the freezing point of the oil wax to form an emulsion or a solution. A method for producing a granular lipophilic vitamin preparation, comprising solidifying. 9. A droplet in the form of fine particles is formed by making the emulsion or solution into small droplets, and the droplets are solidified while maintaining the state of the fine particles, whereby the state of the fine particles is permanently established. Until the solidified fine particles are separated and held from each other until
9. The method according to claim 8, wherein the powder is collected on a flowing non-reactive powder or a bed having the powder. 10. A dropletized emulsion consisting essentially of a lipophilic vitamin, a solid fat wax and a stabilizer, wherein the lipophilic vitamin, solid fat wax and stabilizer are mixed in water at a temperature higher than the freezing point of the fat wax. A method for producing a granular lipophilic vitamin preparation, which comprises forming a liquid or a solution in water and then cooling to solidify the dropletized emulsion or solution.