Lutein microcapsule formulation and preparation method thereof

Abstract

A lutein microcapsule formulation and preparation method thereof, the formulation comprising the following ingredients: lutein crystals, a water-soluble emulsifier, an oil-soluble antioxidant, a wall material, a filler, a water-soluble antioxidant, and purified water. The preparation method comprises: dissolving the lutein crystals and the oil-soluble antioxidant in the water-soluble emulsifier to obtain an oil phase; adding the wall material, the water-soluble antioxidant, and the filler to the purified water to obtain a water phase; adding the oil phase to the water phase, grinding to obtain a particle size of the liquid emulsion of less than 100 nm, and granulating.

Claims

1. A lutein microcapsule formulation comprising lutein, wherein the lutein microcapsule formulation is prepared from raw materials comprising the following ingredients in parts by weight: 1 part of lutein in crystal form, 0.1-0.5 parts of oil-soluble antioxidant, 0.3-1.0 parts of water-soluble emulsifier, 3.0-4.0 parts of wall material, 4.0-5.0 parts of filler, 0.2-1.0 parts of water-soluble antioxidant, and 8.0-12.5 parts of purified water, wherein the lutein microcapsule formulation is prepared by a method comprising: 1) melting the lutein, of the raw materials, in the water-soluble emulsifier which is added with the oil-soluble antioxidant to obtain an oil phase; 2) adding the wall material, the water-soluble antioxidant and the filler into the purified water at 50-80 ° C., and then stirring and dissolving to obtain a water phase; and 3) adding the oil phase into the water phase and stirring, then coarse grinding through a colloid mill, and fine grinding through a sand mill, wherein when the lutein microcapsule formulation is dispersed in water in combination with the coarse grinding, lutein microcapsules having a particle diameter of 100 nm or less are produced, and wherein when the lutein microcapsule formulation is placed in a chamber for six months under conditions of 40 ° C. and RH 75%, the lutein microcapsule formulation has a content retention rate of 97% or higher.

2. The formulation according to claim 1, characterized in that, the raw materials comprise the following ingredients in parts by weight: 1 part of lutein in crystal form, 0.1-0.3 parts of oil-soluble antioxidant, 0.5-1.0 parts of water-soluble emulsifier, 3.5-3.75 parts of wall material, 4.5-4.75 parts of filler, 0.5-0.8 parts of water-soluble antioxidant, and 10-11.5 parts of purified water.

3. The formulation according to claim 1, characterized in that, the oil-soluble antioxidant is natural vitamin E or rosemary extract.

4. The formulation according to claim 1, characterized in that, the water-soluble emulsifier has an HLB value of 13 or more, and comprises one or more water-soluble emulsifier selected from the group consisting of polyglycerol fatty acid ester, sucrose fatty acid ester, polysorbate-80, polyoxyethylene sorbitan fatty acid ester, and combinations thereof.

5. The formulation according to claim 1, characterized in that, the wall material is one or two of acacia and octenyl succinate starch ester.

6. The formulation according to claim 1, characterized in that, the filler is one or two of iso-maltol, sucrose and glucose.

7. The formulation according to claim 1, characterized in that, the water-soluble antioxidant is a mixture of ascorbic acid and tea polyphenol or a mixture of ascorbic acid and oligomeric procyanidin.

8. The formulation according to claim 2, characterized in that, the oil-soluble antioxidant is natural vitamin E or rosemary extract.

9. The formulation according to claim 2, characterized in that, the water-soluble emulsifier has an HLB value of 13 or more, and comprises one or more water-soluble emulsifier selected from the group consisting of polyglycerol fatty acid ester, sucrose fatty acid ester, polysorbate-80, polyoxyethylene sorbitan fatty acid ester, and combinations thereof.

10. The formulation according to claim 2, characterized in that, the wall material is one or two of acacia and octenyl succinate starch ester.

11. The formulation according to claim 2, characterized in that, the filler is one or two of iso-maltol, sucrose and glucose.

12. The formulation according to claim 1, wherein when 0.1000g of the lutein microcapsule formulation is placed in a 100 ml volumetric flask, added with purified water for dissolving, and diluted with purified water to 100 ml to create a sample, when a black and white pattern of a Secchi disc is attached to a bottom of a 50 ml colorimetric tube, and when the sample is poured into the 50 ml colorimetric tube until the black and white pattern at the bottom becomes invisible, a height of a liquid level in the 50 ml colorimetric tube is 13.7 cm or more.

13. The formulation according to claim 1, wherein melting the lutein comprises melting the lutein at 160-180 ° C.

14. A preparation method of the formulation according to claim 1, characterized in that, the method comprises the steps of: 1) melting the lutein crystal in the water-soluble emulsifier which is added with the oil-soluble antioxidant to obtain an oil phase; 2) adding the wall material, the water-soluble antioxidant and the filler into the purified water at 50-80° C., and then stirring and dissolving to obtain a water phase; and 3) adding the oil phase into the water phase and stirring well, then coarse grinding through a colloid mill, and fine grinding through a sand mill such that the ground emulsion particles have a particle diameter of 100 nm or less, and allowing the emulsion to be one-step granulated by a spray-starch fluidized bed drying process to obtain a spherical microcapsule formulation having a particle diameter of 40 mesh to 100 mesh.

15. The method according to claim 14, characterized in that, the method comprises the steps of: 1) melting the lutein crystal at 140° C. -180° C. in the water-soluble emulsifier which is added with the oil-soluble antioxidant to obtain an oil phase; 2) adding the wall material, the water-soluble antioxidant and the filler into the purified water at 50-80° C., and then stirring and dissolving for 30-60 minutes to obtain a water phase; and 3) adding the oil phase into the water phase and stirring well, then coarse grinding through a colloid mill, and fine grinding through a sand mill whose grinding medium has a particle diameter of 0.5-1.0 mm and which has a rotation speed of 1500-2000 rpm, such that the ground emulsion particles have a particle diameter of 100 nm or less, and then allowing the emulsion to be one-step granulated by a spray-starch fluidized bed drying process to obtain a spherical microcapsule formulation having a particle diameter of 40 mesh to 100 mesh.

Description

SPECIFIC MODES FOR CARRYING OUT THE EMBODIMENTS

(1) The following examples are intended to illustrate the invention, but not intended to limit the scope of the invention.

(2) The rosemary extract is a natural antioxidant extracted from the plant rosemary, wherein the content of the active ingredient carnosic acid is not less than 20%. The rosemary extract is purchased from Henan Senyuan Herbary Natural Products Co., Ltd.

Example 1: Lutein Microcapsule Formulation

(3) 1. 20 g of lutein crystals with a lutein content of 80% and 2 g of rosemary extract (about 0.1 times of lutein) were added to 20 g of polyglycerol fatty acid ester (about 1 time of lutein), heated to 165° C. and kept for 5 min until they were completely melted to obtain an oil phase, wherein the vessel for melting was protected by nitrogen.

(4) 2. 75 g of acacia (about 3.75 times of lutein), 95 g of iso-maltol (about 4.75 times of lutein), and a mixture of 5 g of ascorbic acids and 5 g of tea polyphenol (totaling about 0.5 times of lutein) were dissolved into 230 g of purified water (about 11.5 times of lutein) at 75° C. for 0.5 hours, and kept at the same temperature to give a water phase.

(5) 3. The oil phase at 165° C. was slowly added into the water phase at 75° C. under shear stirring with a rotation speed of >10000rpm, stirred for 0.5 hour, and then cooled to room temperature to obtain a mixed liquor.

(6) 4. The mixed liquor was passed through a colloid mill, and then ground by a sand mill at a speed of 1900 rpm for 0.5 hours. The detection result of the particle diameter is 95 nm.

(7) 5. The mixed liquor was granulated by spray-starch fluidized bed drying after being ground, wherein inlet air temperature for spraying was 120° C., and the blast temperature of the starch fluidized bed was 75° C. 270 g lutein microcapsule formulation with the lutein content of 5% was obtained.

Example 2: Lutein Microcapsule Formulation

(8) 1. 40 kg of lutein crystals with a lutein content of 80% and 4 kg of rosemary extract (about 0.1 times of lutein) were added to 40 kg of polysorbate-80 (about 1 time of lutein), heated to 160° C. and kept for 10 min until they were completely melted to obtain an oil phase, wherein the vessel for melting was protected by nitrogen.

(9) 2. 150 kg of acacia (about 3.75 times of lutein), 190 kg of sucrose (about 4.75 times of lutein), and a mixture of 10 kg of ascorbic acids and 10 kg of oligomeric procyanidin (totaling about 0.5 times of lutein) were dissolved into 450 kg of purified water (about 11.25 times of lutein) at 70° C. for 45 min, and kept at the same temperature to give a water phase.

(10) 3. The oil phase at 160° C. was slowly added into the water phase at 75° C. under shear stirring with a rotation speed of ≥10000rpm, stirred for 0.5 hour, and then cooled to room temperature to obtain a mixed liquor.

(11) 4. The mixed liquor was passed through a colloid mill, and then ground by a sand mill at a speed of 2000 rpm for 1 hour. The detection result of the particle diameter is 90 nm.

(12) 5. The mixed liquor was granulated by spray-starch fluidized bed drying after being ground, which gives 540 kg lutein microcapsule formulation with the lutein content of 5%.

Example 3: Lutein Microcapsule Formulation

(13) 1. 27 kg of lutein crystals with a lutein content of 80% and 3 kg of vitamin E (about 0.11 times of lutein) were added to 27 kg of sucrose fatty acid ester (about 1 time of lutein), heated to 170° C. and kept for 10 min until they were completely melted to obtain an oil phase, wherein the vessel for melting was protected by nitrogen.

(14) 2. 100 kg of octenyl succinate starch ester (about 3.70 times of lutein), 128 kg of sucrose (about 4.74 times of lutein), and a mixture of 7.5 kg of ascorbic acids and 7.5 kg of tea polyphenol (totaling about 0.56 times of lutein) were dissolved into 300 kg of purified water at 70° C. for 45 min, and kept at the same temperature to give a water phase.

(15) 3. The oil phase at 170° C. was slowly added into the water phase at 75° C. under shear stirring with a rotation speed of ≥10000rpm, stirred for 0.5 hour, and then cooled to room temperature to obtain a mixed liquor.

(16) 4. The mixed liquor was passed through a colloid mill, and then ground by a sand mill at a speed of 1800 rpm for 1 hour. The detection result of the particle diameter is 100 nm.

(17) 5. The mixed liquor was granulated by spray-starch fluidized bed drying after being ground, which gives 360 kg lutein microcapsule formulation with the lutein content of 5%.

Experimental Example: Investigation of Stability and Water Solubility

(18) 1. Samples: the microcapsules of Examples 1-3, the microcapsules of Comparative Examples 1-5, wherein:

Comparative Example 1

(19) prepared according to the method provided in Example 1 of CN200580031802.8 (CN101023140A);

Comparative Example 2

(20) prepared according to the method provided in Example 1 of CN200810137559.3 (CN101433528A);

Comparative Example 3

(21) prepared according to the method provided in Example 1 of CN201110232047.7 (CN102258499A);

Comparative Example 4

(22) prepared according to the method provided in Example 1 of CN200610154617.4 (CN101177540B); and

Comparative Example 5

(23) prepared according to the method provided in Example 6 of CN201310392763.0 (CN103406079A).

(24) 2. Investigation methods:

(25) Stability: the lutein microcapsules prepared in Examples 1-3 and Comparative Examples 1-5 were placed directly in a drug stability test chamber, kept under the conditions of 40° C. and RH 75% in dark and then measured for the initial contents of the samples and the contents after being kept for 6 months, and then the content retention rate was calculated.

(26) Water solubility: 0.1000 g of lutein microcapsule sample was weighed and placed in a 100 ml volumetric flask, added with purified water for dissolving (ultrasonic treatment was conducted if necessary,), and diluted with purified water to 100 ml. A black and white pattern similar to a Secchi's disc was attached to the bottom of a 50 ml colorimetric tube, then the dissolved sample was poured into the colorimetric tube until the pattern at the bottom could not be seen clearly, and the height of the liquid level in the colorimetric tube was recorded at this time point. The test was repeated for three times, and the average value was calculated.

(27) 3. The test results are shown in Table 1.

(28) TABLE-US-00001 TABLE 1 Test results The content retention rates (%) after standing under the conditions of 40° C. and Transparency RH 75% for 6 months (cm) Example 1 98.2 13.75 Example 2 98.0 13.80 Example 3 97.9 14.05 Comparative Example 1 78.8 8.6 Comparative Example 2 82.4 11.2 Comparative Example 3 85.6 13.2 Comparative Example 4 95.2 13.5 Comparative Example 5 92.5 9.2

(29) The results in Table 1 showed that, the retention rates of the microcapsules after standing for 6 months were 97% or more of Examples 1-3, while the highest retention rate of the microcapsules of Comparative Examples 1-5 was 92.5%, which is lower than those of Examples 1-3; and the transparencies of the microcapsules of Examples 1-3 were 13.7 cm or more, and the highest transparency of the microcapsules of Comparative Examples was 13.5 cm.

(30) The results showed that: the stability of the lutein microcapsules provided by the present invention was superior to that of the comparative patent applications, and the transparency of the aqueous dispersion also ranked in upper level, which can meet the actual production needs.

INDUSTRIAL APPLICABILITY

(31) The invention provides a highly stable lutein microcapsule formulation which is easy to be industrially produced and provided with a shape of microsphere. The formulation and the preparation method thereof do not use the organic solvent, which improves the safety of the product; the lutein crystal is melted in the water-soluble emulsifier without using the edible oil, after in combination with further grinding, it allows the microcapsules to have a particle diameter of 100 nm or less, so that the aqueous dispersion of the product is clear and transparent; by using starch for one-step granulation to obtain spherical microcapsule, the effect of secondary embedding can be achieved to improve the stability, and the drawbacks of the powder prepared by the spray drying method, such as poor resistance to pressure, unsuitability for tabletting (poor fluidity), and unsuitability for filling hard capsules can be overcome.