JP7737124B2 - Preparations containing poorly water-soluble substances - Google Patents

Description

The present invention relates to a preparation containing a poorly water-soluble substance that can be effectively added and incorporated into processed foods containing water.

Dietary nutrients, such as vitamins, can be broadly divided into two categories: water-soluble and water-insoluble. Because beverages and other processed foods contain large amounts of water, it is easy to incorporate water-soluble ingredients such as vitamin C. However, poorly water-soluble ingredients such as vitamin E, coenzyme Q10, curcumin, and astaxanthin, when incorporated as is, tend to float or precipitate, necessitating formulation processing such as emulsification and dispersion. The stability of an emulsion or dispersion is inversely proportional to the square of the particle size of the ingredient, as known as Stokes' equation. Therefore, to stably incorporate poorly water-soluble substances into processed foods, formulations with smaller particle sizes are required. Furthermore, Desai et al. have discussed the effective cellular uptake of small emulsion particles using emulsified bovine serum albumin particles (Non-Patent Document 1), and similar effects are expected for poorly water-soluble substances as well.

Regarding the microparticulation of such poorly water-soluble substances, technologies have been published that combine emulsifiers such as polyglycerol fatty acid esters, sugar esters, and lecithin with polyhydric alcohols to microparticulate poorly water-soluble substances such as curcumin and coenzyme Q10. However, the particle sizes specifically disclosed are those of the original solution, which do not reflect the blending conditions in processed foods. Even in diluted solutions that take blending into consideration, the particle sizes are 100 nm or larger in emulsion systems and 200 nm or larger in dispersion systems, and neither technology can be considered sufficient for microparticulation. (Patent Documents 1-3)

Furthermore, technology has been disclosed that combines polyglycerol fatty acid esters, sugar esters, lecithin, and monoglycerides to reduce the size of coenzyme Q10 emulsion particles to 65.5 nm (Patent Document 4), and technology has been disclosed that uses thickening polysaccharides such as gum ghatti to reduce the size of curcuminoid particles to 190 nm (Patent Document 5). However, neither of these technologies takes into consideration their incorporation into processed foods, or their stability after incorporation is sufficient, making them insufficient as micronization technologies.

Furthermore, formulation technologies have been published that solubilize poorly water-soluble substances using amphipathic solvents such as polysorbates, polyethylene glycols, and alcohols. However, these technologies only address the particle size of the solubilized formulation and do not take into account its use in processed foods. They also investigate formulations with high concentrations of around 20%, which is not a realistic formulation. (Patent Documents 6-8)

M. P. Desai et al, Pharmaceutical Res. 14, 1568 (1997)

Japanese Patent Application Laid-Open No. 2009-201371 Special Publication No. 2006-134970 JP 2013-56858 A Japanese Patent Application Laid-Open No. 2008-245588 JP 2014-118391 A Special Publication No. 2012-510466 JP 2016-505579 A JP 2016-34918 A

The object of the present invention is to provide a preparation containing a poorly water-soluble substance that can be effectively incorporated into processed foods containing water.

The inventors conducted extensive research to solve the above-mentioned problems and discovered that poorly water-soluble ingredients can be effectively incorporated into processed foods containing water, particularly by using a poorly water-soluble substance-containing formulation in which the average emulsified particle size of the water-diluted product is 60 nm or less when the formulation is an emulsion system, or an average dispersed particle size of the water-diluted product is 150 nm or less when the formulation is a dispersion system, and by containing one or more emulsifiers with an HLB of 10 to 16 and/or water and a polyhydric alcohol as the continuous phase, the poorly water-soluble ingredient can be effectively incorporated into processed foods containing water, leading to the completion of the present invention.

That is, the poorly water-soluble substance-containing formulation of the present invention is an emulsion-based poorly water-soluble substance-containing formulation, characterized in that the average emulsified particle size of the aqueous solution obtained by diluting the formulation with water at a dilution ratio of 10 to 100,000 times is 60 nm or less, and a dispersion-based poorly water-soluble substance-containing formulation, characterized in that the average dispersed particle size of the aqueous solution obtained by diluting the formulation with water at a dilution ratio of 10 to 100,000 times is 150 nm or less. In particular, the present invention relates to a poorly water-soluble substance-containing formulation that contains one or more emulsifiers having an HLB of 10 to 16 and/or water and a polyhydric alcohol as a continuous phase. Compared to conventional techniques for formulating poorly water-soluble substances, this new technology is characterized by its superior in terms of appearance and penetration in processed foods containing water, allowing for the effective addition and incorporation of poorly water-soluble substances in the field of processed foods containing water.

The present invention has excellent compatibility and penetration in aqueous processed foods, allowing for the effective addition and incorporation of poorly water-soluble substances in aqueous processed foods.

The poorly water-soluble substance used in the present invention is not particularly limited in type, as long as it is usable as a food or food additive. Examples include curcuminoids, isoprenoid quinones, tocopherols, and carotenoids, and one or more of these can be used.

The content of the poorly water-soluble substance in the poorly water-soluble substance-containing formulation of the present invention is preferably 0.05 to 40% by weight, more preferably 0.1 to 35% by weight, and even more preferably 0.2 to 30% by weight, based on the total weight of the formulation. If the amount is less than 0.05% by weight, the effect of the formulation will be insufficient, and if it exceeds 40% by weight, the viscosity of the formulation will increase, which is undesirable.

One embodiment of the poorly water-soluble substance-containing formulation of the present invention is an emulsion-based formulation containing a poorly water-soluble substance, which is typically diluted before use. The formulation is diluted with water at a dilution ratio of 10 to 100,000 times, preferably 20 to 50,000 times, to produce a water-diluted solution with an average emulsion particle size of 60 nm or less. In the case of an emulsion-based formulation, a particle size exceeding 60 nm is undesirable, as it reduces the effectiveness of incorporation into processed foods. The average emulsion particle size can be measured by laser light scattering.

Another aspect of the poorly water-soluble substance-containing formulation of the present invention is a poorly water-soluble substance-containing dispersion formulation that contains a poorly water-soluble substance and is typically diluted before use. The formulation is diluted with water at a dilution ratio of 10 to 100,000 times, preferably 20 to 50,000 times, to produce a water-diluted solution with an average dispersed particle size of 150 nm or less. In the case of a dispersion, a particle size exceeding 150 nm is undesirable, as it reduces the effectiveness of incorporation into processed foods. The average dispersed particle size can be measured by laser light scattering.

The emulsifier used in the present invention can be any type that is used in foods. Examples include polyglycerin esters, monoglycerin esters, sugar esters, sorbitan esters, lecithins, thickening polysaccharides, etc. These can be added alone or in combination of two or more types. Among these, emulsifiers having an HLB of 10 to 16 are preferred. Emulsifiers with an HLB of less than 10 or more than 16 may not exhibit sufficient emulsifying and dispersing properties and are therefore not preferred.
Here, HLB indicates the hydrophilic-hydrophobic balance used in the field of surfactants, and for example, the following calculation formula (Kawakami formula) can be used.
HLB=7+11.7log(M _W /M _O )
Here, _Mw is the molecular weight of the hydrophilic group, and _M0 is the molecular weight of the hydrophobic group. Alternatively, the HLB value listed in a catalog or the like may be used.

The content of the emulsifier used in the present invention is preferably 0.01 to 40% by weight, more preferably 0.1 to 35% by weight, and even more preferably 0.5 to 30% by weight, based on the total weight of the formulation. If the amount is less than 0.01% by weight, the emulsifying and dispersing effects will be insufficient, while if it exceeds 40% by weight, problems such as an increased viscosity of the formulation or a limited amount of poorly water-soluble substances will occur, which is undesirable.

In the formulation containing a poorly water-soluble substance of the present invention, the continuous phase is an aqueous phase component (aqueous solvent), preferably water. In this case, it is preferable to add a polyhydric alcohol to the aqueous phase component for the purposes of adjusting the interfacial tension and assisting in the dissolution of the emulsifier.

The polyhydric alcohols used in the present invention can be any type that is used in foods, such as propylene glycol, glycerin, maltitol, reduced starch syrup, lactitol, palatinite, erythritol, mannitol, and sorbitol. These can be added alone or in combination of two or more. Of these, glycerin is most preferred in terms of ensuring the fluidity of the composition.

The content of the polyhydric alcohol used in the present invention is preferably 0.01 to 70% by weight, more preferably 0.05 to 65% by weight, and even more preferably 0.1 to 60% by weight, based on the total weight of the formulation. If the amount is less than 0.01% by weight, a stable formulation may not be obtained, and if it exceeds 70% by weight, problems such as limiting the amount of poorly water-soluble substances that can be incorporated may occur, which is undesirable.

The poorly water-soluble substance-containing preparation of the present invention can be blended with known food or food additive ingredients, as long as the effects of the present invention are not impaired. For example, base components such as oils, alcohols, and waxes can be blended, and additive components such as preservatives, flavorings, chelating agents, antioxidants, specific gravity adjusters, and viscosity adjusters can be blended.

The machinery used to produce the poorly water-soluble substance-containing formulation of the present invention is not particularly limited, and machines such as mixers, agitators, dispersers, homomixers, homogenizers, high-pressure homogenizers, ultra-high-pressure homogenizers, ball mills, colloid mills, planetary mills, and wet OB mills can be used alone or in combination.

While the method for producing a formulation containing a poorly water-soluble substance of the present invention is not necessarily limited, one suitable production method involves first emulsifying and dispersing the poorly water-soluble substance and other ingredients of the formulation in a continuous phase using a homomixer, homogenizer, ultrasound, or the like (for example, homogenizing the formulation for 30 to 60 minutes at 4000 to 6000 rpm using a homomixer), followed by 4 to 10 repeated high-pressure homogenization steps at 30 to 70 MPa. Using this method, a formulation containing a poorly water-soluble substance that exhibits a dispersed phase with the average particle size specified in the present invention when diluted with water can be efficiently produced.

The form of the poorly water-soluble substance-containing formulation of the present invention is not particularly limited as long as it does not impair the effects of the present invention. While typical preparation methods often use a liquid formulation, it can also be used by mixing it with an excipient and powdering it through spray drying or freeze drying.

The present invention will now be described in detail using examples, but the present invention is not limited to these examples.

[Example 3, Reference Examples 1 to 3 , Comparative Examples 1 to 4]
In the present Examples, Comparative Examples, and Reference Examples, the polyglycerin fatty acid esters used were Decaglyn 1-SV (product name: decaglycerin monostearate ester), Decaglyn 1-PV EX (product name: decaglycerin monopalmitate ester), and Decaglyn 1-L (product name: decaglycerin monolaurate ester), the sorbitan fatty acid esters used were TL-10 (product name: polysorbate 20) and SP-10V (product name: sorbitan monopalmitate) (all manufactured by Nikko Chemicals), and the lecithin used was SLP Paste Lyso (manufactured by Tsuji Oil Mills).

[Preparation Example: Preparation of Turmeric Extract]
One kg of dried turmeric rhizome was crushed in a hammer mill, to which 10 times the amount of ethanol was added, followed by a 24-hour soaking treatment in a cool, dark place. After soaking, the solution was filtered off and the solvent was removed using a rotary evaporator. 10 times the amount of water was added to the resulting extract, which was then thoroughly stirred. The precipitate was then filtered off and collected. This precipitate was thoroughly dried in an oven at 70°C and then pulverized in a ball mill, yielding 130 g of turmeric extract containing 95% curcuminoids.

[ Reference Example 1 , Comparative Example 1: Turmeric extract preparation]
The turmeric extract containing 95% curcuminoid was blended according to the composition shown in Table 1 and homogenized for 30 minutes at 6,000 rpm using a homomixer to prepare Comparative Example 1. The turmeric extract preparation of Reference Example 1 was further pulverized using a planetary ball mill with 2 mm zirconia beads, 0.3 mm zirconia beads, and 0.03 mm zirconia beads.

[ Reference Example 2, Comparative Example 2: Coenzyme Q10 preparation]
Coenzyme Q10 (manufactured by Kaneka Corporation) was used to compound the ingredients in the composition shown in Table 1, and the mixture was subjected to homogenization treatment at 6000 rpm for 30 minutes using a homomixer to prepare Comparative Example 2. For Reference Example 2, the mixture was further subjected to high-pressure homogenization treatment six times under conditions of 60 MPa.

[Example 3, Comparative Example 3: Mixed tocopherol preparation]
Mixed tocopherol (manufactured by Mitsubishi Chemical Foods Corporation) containing 70% tocopherol was used to compound the ingredients shown in Table 1, and the mixture was homogenized for 30 minutes at 6,000 rpm using a homomixer to prepare Comparative Example 3. The mixture of Example 3 was further subjected to four high-pressure homogenization treatments at 60 MPa.

[Reference Example 3 , Comparative Example 4: Astaxanthin preparation]
An oil containing 12.5% astaxanthin (manufactured by Biogenic) was used to blend the composition shown in Table 1, and the mixture was subjected to homogenization treatment at 6,000 rpm for 30 minutes using a homomixer to prepare Comparative Example 4. Reference Example 3 was further subjected to six high-pressure homogenization treatments at 60 MPa.

[Particle size measurement]
Each of the preparations of Example 3, Reference Examples 1 to 3 , and Comparative Examples 1 to 4 was diluted with water to a concentration of 0.1%, and the average particle size (nm) was measured by the laser light scattering method.

[Evaluation of Dispersion Appearance]
The appearance of the water diluted solutions of Example 3, Reference Examples 1 to 3 , and Comparative Examples 1 to 4 was checked and rated according to the following criteria.
⊚: High transparency, preferably very little effect on appearance due to water as a solvent.
Good: Transparent, and little effect on appearance from water as a solvent.
Δ: Cloudiness is felt, and the appearance is affected by water, which is the solvent.
×: Clearly cloudy, with a large impact on appearance.

As is clear from Table 1, when the formulation is an emulsion system, the average particle size of the water-diluted product is 60 nm or less, and when the formulation is a dispersion system, Example 3 and Reference Examples 1 to 3 , in which the average particle size of the water-diluted product is 150 nm or less, have little effect on the transparency of the dilution water and show good blendability.

[Example 5, Comparative Example 5: Evaluation of coloring of takuan]
Each of the preparations from Reference Example 1 and Comparative Example 1 was added at 1% to commercially available lightly pickled vegetables to create Example 5 and Comparative Example 5, respectively. Then, radishes cut with a knife were soaked in each solution, and the coloring state was visually confirmed. Example 5 clearly showed a faster coloring rate and good penetration into the radish tissue.

[Example 6, Comparative Example 6: Evaluation of coloring properties of kamaboko]
The preparations of Reference Example 3 and Comparative Example 4 were diluted with water to 1% to prepare Example 6 and Comparative Example 6, respectively. A commercially available white kamaboko was cut with a knife and immersed in each solution, and the coloring state was visually confirmed. It was clear that Example 6 colored faster and showed better coloring properties for the kamaboko.

Claims (6)

An emulsion-based poorly water-soluble substance-containing preparation containing a poorly water-soluble substance,
the average emulsion particle size of the water-diluted solution obtained by diluting the formulation with water at a dilution ratio of 10 to 100,000 times is 60 nm or less;
the poorly water-soluble substance is a tocopherol,
the content of the poorly water-soluble substance is 8 to 40% by weight based on the total weight of the preparation;
Contains one or more emulsifiers having an HLB of 10 or more and 16 or less,
the content of the emulsifier is 0.01 to 40% by weight based on the total weight of the formulation;
The formulation contains, as a continuous phase, water and a polyhydric alcohol,
The polyhydric alcohol is selected from the group consisting of propylene glycol, glycerin, maltitol, reduced starch syrup, lactitol, palatinit, erythritol, mannitol, and sorbitol;
The preparation contains a poorly water-soluble substance, the preparation comprising a medium-chain fatty acid triglyceride. The preparation containing a poorly water-soluble substance according to claim 1, wherein the polyhydric alcohol is glycerin. The formulation containing a poorly water-soluble substance according to claim 1 or 2, wherein the content of the polyhydric alcohol is 50 to 60% by weight of the entire formulation. The preparation containing a poorly water-soluble substance according to claim 1 or 2, wherein the emulsifier exhibiting an HLB of 10 or more and 16 or less is a polyglycerol fatty acid ester and/or a sorbitan fatty acid ester. A formulation containing a poorly water-soluble substance as described in claim 4 , wherein the polyglycerin fatty acid ester is at least one selected from the group consisting of decaglycerin monostearate, decaglycerin monopalmitate, and decaglycerin monolaurate. 5. The preparation containing a poorly water-soluble substance according to claim 4 , wherein the sorbitan fatty acid ester is polysorbate 20 or sorbitan monopalmitate.