KR102571958B1 - Stable fat-soluble active ingredient compositions, microcapsules and methods for their preparation and uses - Google Patents

Abstract

The present invention provides a stable fat-soluble active ingredient composition, microcapsules and a method for preparing and using the same, wherein the fat-soluble active ingredient composition comprises tocopherol, vitamin C palmitate and a fat-soluble active ingredient; Here, the weight ratio of tocopherol and vitamin C palmitate is 2 to 8: 1, and both the weight ratio of the combination of tocopherol and vitamin C palmitate and the fat-soluble active ingredient are 7 to 13: 100. In the present invention, a novel antioxidant combination having improved stability of a fat-soluble active ingredient without fear of prohibition of use is obtained by selecting an antioxidant combination and adjusting the ratio and preparation amount.

Description

Stable fat-soluble active ingredient compositions, microcapsules and methods for their preparation and uses

The present invention relates to a novel non-polluting antioxidant composition capable of improving vitamin A ester, and more particularly, to a stable fat-soluble active ingredient composition, microcapsules, and a preparation method and use thereof.

Vitamins are essential for the nutrition and production of animals and are very important for the metabolism, growth, development and health of organisms. Vitamin A is a very important member of the vitamin A ester family, which plays a very important functional role in terms of vision health, bone health, reproduction and cell division reproduction, and vitamin A deficiency in the human body is unimaginable.

Vitamin A is a pale yellow crystalline solid, insoluble in water, soluble in fat and various fat solvents, and easily deteriorated and destroyed when exposed to light, heat, and oxygen. As a result, it is prepared and used as a microcapsule powder.

As a microencapsulation embedding technology, in general, vitamin A ester, which is a core material, is melted to form an oil phase, and a water phase is formed by dissolving high molecular materials, small molecule fillers, emulsifiers, etc. After drying or cross-linking by spray drying, the finished microcapsule product is finally obtained.

In the process of preparing the vitamin A ester microcapsules by the above method, an antioxidant must be added to prevent the vitamin A ester from being oxidized. Antioxidants such as ethoxyquinoline, tert-butylhydroxytoluene, and tert-butylhydroxyanisole, which are currently commonly used, have potential in the international food and feed industry. Because of its risky effects, its use tends to be limited and even banned.

There are some non-polluting, safe and healthy antioxidants in the food and feed industry, and there is no fear of use restrictions or bans, including tocopherol and vitamin C palmitate. Tocopherol is a fat-soluble antioxidant that effectively inhibits the formation of active oxides during fat oxidation, so it is essential for the normal growth and development of animals. Vitamin C palmitate is a very effective oxygen scavenger and synergist, and is evaluated as a nutritious, non-toxic, highly effective and safe food additive by the World Health Organization (WHO) Food Additives Committee, and is the only food additive in China that can be used in infant food. It is an antioxidant that can be used in food and has effects such as antioxidant, food (fat) color protection, and nutritional enhancement.

Chinese patent CN102362864 (B) describes a method for improving the dispersibility and bulk density of vitamin A or vitamin D3 microcapsules. Here, the antioxidant used is tocopherol or vitamin C palmitate.

Chinese patent CN102176833(A) describes a method for preparing a stable, ready-to-use emulsion. Here, the antioxidant is tocopherol, tert-butylhydroxytoluene, tert-butylhydroxyanisole, ascorbic acid or ethoxyquinoline. Here, the emulsifier is ascorbyl palmitate (vitamin C palmitate).

Chinese patent CN103181566 (A) describes a powdered preparation of vitamin A esters. Here, the water-soluble antioxidant may be ascorbic acid or a salt thereof, for example, sodium ascorbate or the like. Fat-soluble antioxidants include tocopherol; ascorbic acid esters of fatty acids such as ascorbyl palmitate or stearate; BHT; BHA; propylgallate; It may be ethoxyquinoline.

Chinese patent CN1279112 (A) describes a composition in which fat-soluble substances are included in a carbohydrate matrix. Here, the antioxidant is selected from sodium ascorbate, ascorbyl palmitate, dl-tocopherol, mixed tocopherols, lecithin, and mixtures thereof.

For the antioxidants according to the above patent data including tocopherol and vitamin C palmitate, the use of antioxidant combination is not mentioned at all, it is mentioned alone, and the specific dosage and ratio of antioxidants are not clearly explained.

Antioxidants such as ethoxyquinoline, tert-butylhydroxytoluene, and tert-butylhydroxyanisole, which are currently commonly used, are limited in use and even banned in the international food and feed industry due to their potential risk effects. there is

An object of the present invention is to eliminate the concerns about the limited use of antioxidants such as ethoxyquinoline, tert-butylhydroxytoluene, and tert-butylhydroxyanisole, by using existing fat-soluble active ingredients (eg, vitamin A esters) ) Regarding the insufficiency of the microcapsule production process, the present invention is to obtain a novel antioxidant combination with improved stability of fat-soluble active ingredient microcapsules without fear of prohibition of use, by selecting the antioxidant combination and adjusting the ratio and preparation amount.

In a first aspect of the present invention, the present invention comprises tocopherol, vitamin C palmitate and fat-soluble active ingredients, the weight ratio of tocopherol and vitamin C palmitate is 2 to 8: 1, the combination of tocopherol and vitamin C palmitate A stable fat-soluble active ingredient composition is provided in which the weight ratio of the fat-soluble active ingredient and the fat-soluble active ingredient are both 7 to 13:100.

In the solution of the method for producing a fat-soluble active ingredient composition according to the present invention, preferably, the fat-soluble active ingredient composition is a complex of tocopherol and vitamin C palmitate, a complex of tocopherol and sodium ascorbate, and sodium ascorbate and vitamin C. It is one of the complexes of C palmitate.

In the solution of the fat-soluble active ingredient composition according to the present invention, the weight ratio of tocopherol and vitamin C palmitate is preferably 3 to 7:1.

In the solution of the fat-soluble active ingredient composition according to the present invention, the weight ratio of tocopherol and vitamin C palmitate is more preferably 4-6: 1.

In the solution of the fat-soluble active ingredient composition according to the present invention, the weight ratio of the combination of tocopherol and vitamin C palmitate to the fat-soluble active ingredient is preferably 8-12:100.

In the solution of the fat-soluble active ingredient composition according to the present invention, more preferably, the weight ratio of the combination of tocopherol and vitamin C palmitate to the fat-soluble active ingredient is 9 to 11:100.

In the solution of the fat-soluble active ingredient composition according to the present invention, more preferably, the tocopherol includes one or more of synthetic or natural α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol.

In the solution of the fat-soluble active ingredient composition according to the present invention, the fat-soluble active ingredient is preferably selected from the group consisting of vitamin A, vitamin D, vitamin K, carotenoids and highly unsaturated fatty acids or esters thereof. More preferably, the vitamin A includes a vitamin A ester. Most preferably, the vitamin A ester is vitamin A acetate, or vitamin A palmitate, vitamin A propionate, or vitamin AD ₃ or a mixture thereof. Here, vitamin _AD3 is a mixture of vitamin A ester and vitamin D3.

In a second aspect of the present invention, the present invention further provides fat-soluble active ingredient microcapsules containing the fat-soluble active ingredient composition.

In a third aspect of the present invention, the present invention further provides the use of the fat-soluble active ingredient composition in the manufacture of foods, beverages, animal feeds, cosmetics or pharmaceuticals.

In the fourth aspect of the present invention, the present invention provides: 1) mixing and melting fat-soluble active ingredients and antioxidants according to a certain weight ratio at 45 to 85 ° C. under nitrogen gas protection to form oil phase A of fat-soluble active ingredient molten oil Step 1) - The antioxidants are tocopherol and vitamin C palmitate, and the fat-soluble active ingredient is at least one selected from the group consisting of vitamin A, vitamin D, vitamin K, carotenoids, highly unsaturated fatty acids and their esters -; Step 2) obtaining phase B by dissolving gelatin or modified starch, which is a low molecular weight filler, and glucose or white sugar in water at 60 to 70° C. under the protection of nitrogen gas; Under nitrogen gas protection, oil phase A obtained in step 1) and aqueous phase B obtained in step 2) were blended under sealed conditions, followed by high shear emulsification, degassing and homogenization to obtain an emulsion; step 3); and step 4) of obtaining fat-soluble active ingredient microcapsules by spray pelleting the emulsion obtained in step 3) and then fluidizing and drying the emulsion.

In the solution according to the present invention, the fat-soluble active ingredient microcapsules obtained in step 4) are preferably cross-linked to obtain water-repellent fat-soluble active ingredient microcapsules.

In the solution according to the present invention, the weight ratio of the solution of the aqueous phase B is preferably 30 to 50 wt %.

In the present invention, “improvement of stability” refers to fat-soluble active ingredients (vitamin A, vitamin D, vitamin K, coenzyme Q10, carotenoids and highly unsaturated fatty acids or their esters) by adding antioxidants (tocopherol and vitamin C palmitate) according to the present invention. selected from the group consisting of) improving the stability of molten oil or emulsion or microcapsules, that is, the antioxidants (tocopherol and vitamin C palmitate) can effectively retard the oxidation of fat-soluble active ingredients, thereby increasing the antioxidant effect. improve It can be evaluated in the following simple way.

The highly unsaturated fatty acids or their esters of the present invention refer to C12-25 straight chain highly unsaturated fatty acids or their acetates, glycerides, and phosphates, preferably linoleic acid, linolenic acid, EPA and DHA.

Put the oil-soluble active ingredient molten oil into a sampling bottle, seal it, protect it from light, store it at 40 ° C, and measure its content after 0, 2, 4, and 6 days, respectively, and the content retention rate after 6 days is 96 % exceeded.

Put the oil-soluble active ingredient emulsion into a sampling bottle, seal it, protect it from light, store it at 40 ° C, and measure its content after 0 weeks, 1 week, 2 weeks, and 3 weeks, respectively. After 3 weeks, its content retention rate is 95% exceeded.

Put microcapsules of fat-soluble active ingredients in a sampling bottle, seal it, protect it from light, store it at 40 ° C, and measure its content after 0 weeks, 2 weeks, 4 weeks, and 6 weeks, respectively. After 6 weeks, its content retention rate is 94 % exceeded.

The specific experimental methods of "selection" and "regulation" in the present invention are to find the optimal combination of antioxidants by orthogonal experimental methods.

Orthogonal test method is to use a well-arranged table-orthogonal table to design the test as a whole, comprehensively compare, and conduct statistical analysis to find relatively good production conditions with the minimum number of experiments to realize the best production process effect. Orthogonal experiment first needs to find an orthogonal table corresponding to the experimental element level. After setting the experiment table, the data must be processed by conducting the experiment according to the table. Test data processing is very important because the number of tests is greatly reduced. Data analysis can find one best data first from all experimental data, and of course, these data are not the best data, but they are definitely the data closest to the best data. Subsequently, the experimental results of each level are obtained by adding the experimental values of the same level in each tolerance, and the optimal elements can be obtained from this table, and the change trend of the elements can be obtained compared to the previous elements, so that additional tests can be performed. to guide Calculations such as the variance and variance between test values at different levels for each element give the sensitivity of this element. Next, determine the next test, also according to the statistical data, and reduce the experimental range until the final optimal value is determined.

In the solution of the preparation method of the fat-soluble active ingredient composition according to the present invention, the weight ratio of the combination of tocopherol and vitamin C palmitate to the fat-soluble active ingredient is 5 to 13:100, preferably 7 to 13:100. In the solution of the preparation method of the fat-soluble active ingredient composition according to the present invention, the ratio of tocopherol and vitamin C palmitate, the ratio of tocopherol and sodium ascorbate, and the ratio of vitamin C palmitate and sodium ascorbate are 1: 1, respectively. ~ 1:10, preferably 2 ~ 8:1.

The present invention has the following advantages. 1) All antioxidants used in the present invention are safe, non-polluting, and healthy food additives, eliminating concerns that antioxidants such as ethoxyquinoline, tert-butylhydroxytoluene, and tert-butylhydroxyanisole may be used in a limited manner. can do. 2) By selecting an antioxidant combination and adjusting the ratio and preparation amount, a novel antioxidant combination with improved stability of microcapsules of a fat-soluble active ingredient (for example, vitamin A ester) is obtained without fear of prohibition of use.

The present invention will be further described with reference to the following examples, which are only for explaining the technical solutions of the present invention and do not limit the present invention.

Example 1

Under nitrogen gas protection, vitamin A crystals, vitamin C palmitate and α-tocopherol were melted at 75° C. and blended into a vitamin A molten oil. The weights of vitamin A, vitamin C palmitate, and α-tocopherol were determined according to the urea level setting table in Table 1 and the orthogonal experimental batch table in Table 2. Vitamin A molten oil was put into a sampling bottle, protected from light, stored at 40 ° C, and its content was measured after 0, 2, 4, and 6 days, respectively.

Element level settings table

Note: Percentage values in the table are the ratio of antioxidants to vitamin A.

Table 2. Orthogonal experimental layout table test number test factor A B One One One 2 One 2 3 One 3 4 2 2 5 2 3 6 2 One 7 3 3 8 3 One 9 3 2

The results of the 2nd, 4th, and 6th days were analyzed, and with the comprehensive judgment as the final experimental result, an extreme difference analysis was conducted on the content retention rate, and the master-servant relationship and the preferred combination were selected.

Content Retention Orthogonal Experimental Analysis Table

Analyzing the results of the orthogonal experiment tables in Tables 2 and 3, it is tocopherol that has a major effect on the stability of the vitamin A content, followed by vitamin C palmitate. Overall, the most preferred combination is A3B2, that is, 2% It is vitamin C palmitate + 8% α-tocopherol.

Example 2

Under nitrogen gas protection, a mixture of vitamin A palmitate, vitamin C palmitate and β-tocopherol was melted at 65° C. and blended into a vitamin A palmitate molten oil. A gelatin glucose aqueous solution was formulated by dissolving gelatin and glucose in water at 65°C. Under high shear conditions, vitamin A palmitate molten oil was poured into the aqueous solution and emulsified, degassed and homogenized to obtain a stable emulsion. The vitamin A palmitate emulsion was placed in a sampling bottle, sealed, protected from light, and stored at 40° C., and its content was measured after 0 weeks, 1 week, 2 weeks, and 3 weeks, respectively. The emulsion content retention data of different antioxidant formulation ratios are shown in Table 4 below.

Statistical Table of Retention Rates of Different Antioxidants in Vitamin A Palmitate Emulsion number β-tocopherol Vitamin C Palmitate Retention rate of vitamin A palmitate content 0 weeks 1 week 2 weeks 3 weeks One 2.0% 0.0% 100% 92.5% 90.0% 86.1% 2 4.0% 0.0% 100% 92.2% 89.8% 86.5% 3 6.0% 0.0% 100% 92.9% 89.7% 87.5% 4 8.0% 0.0% 100% 93.0% 90.2% 88.2% 5 10.0% 0.0% 100% 93.1% 90.1% 89.5% 6 0.0% 0.5% 100% 92.6% 89.6% 85.8% 7 0.0% 1.0% 100% 92.8% 88.9% 85.9% 8 0.0% 1.5% 100% 92.7% 89.5% 86.5% 9 0.0% 2.0% 100% 93.0% 89.6% 86.8% 10 0.0% 2.5% 100% 92.8% 89.4% 86.6% 11 5.0% 2.5% 100% 97.2% 94.8% 92.8% 12 6.0% 2.0% 100% 97.6% 95.9% 93.6% 13 8.0% 2.0% 100% 98.5% 96.8% 95.2% 14 10.0% 2.0% 100% 98.4% 96.9% 95.3% 15 9.6% 1.6% 100% 98.3% 96.7% 95.1% 16 10.0% 1.4% 100% 97.8% 96.2% 94.2% 17 10.0% 1.2% 100% 97.5% 95.8% 93.3%

As can be clearly seen from the data in Table 4, within the blending ratio range according to the present invention, the content retention rate of vitamin A palmitate emulsion was relatively high.

Example 3

Under nitrogen gas protection, 50 kg of vitamin A acetate crystals, 0.5 kg of vitamin C palmitate and 3.5 kg of synthetic mixed tocopherols were melted at 85° C. to blend a vitamin A acetate molten oil. 75 kg of gelatin and 50 kg of glucose were dissolved in 130 kg of water at 60° C. to form a 49% aqueous gelatin glucose solution.

Under high-speed shear conditions, vitamin A acetate molten oil was poured into the aqueous phase solution, emulsified, degassed, and homogenized to obtain a stable emulsion, which was transferred to a starch mold, spray pelletized, fluidized and dried, and crosslinked at high temperature to obtain a 218 kg water-repellent liquid. Vitamin A acetate microcapsules were obtained. As a result of HPLC analysis, the vitamin A acetate content was 520,000 IU/g, and the microencapsulation yield was 95%. Vitamin A ester microcapsules were placed in a sampling bottle, sealed, protected from light, and stored at 40° C. After 6 weeks, the vitamin A ester content was 490,000 IU/g, and the content retention rate was 94.2%.

Example 4

Under nitrogen gas protection, 50 kg of coenzyme Q10 crystals, 0.5 kg of vitamin C palmitate and 3 kg of natural γ-tocopherol were melted at 45° C. to blend coenzyme Q10 oil. 75 kg of gelatin and 50 kg of glucose were dissolved in 130 kg of water at 70 °C to form a 49% gelatin glucose aqueous solution.

Under high-speed shear conditions, coenzyme Q10 oil is poured into the aqueous phase solution, emulsified, degassed, and homogenized to obtain a stable emulsion, transferred to a starch mold, spray pelletized, fluidized and dried, and crosslinked at high temperature to obtain 218 kg of water-repellent coenzyme Q10 microcapsules were obtained. As a result of HPLC analysis, the coenzyme Q10 content was 52% and the microencapsulation yield was 95%. Coenzyme Q10 microcapsules were placed in a sampling bottle, sealed, protected from light, and stored at 40 ° C. After 6 weeks, the coenzyme Q10 content was 49% and the content retention rate was 94.2%.

Examples 5 to 11

The method is the same as in Example 1, and different fat-soluble active ingredient oils are prepared, and the measured retention rates are shown in Table 5 below.

Example fat-soluble active ingredient Tocopherol VC Palmitate Fat-soluble active ingredient retention rate category weight ratio 0 weeks 1 week 2 weeks 3 weeks 5 vitamin K α 5.0% 2.5% 100% 98.3% 97.6% 97.0% 6 Lutein β 6.0% 2.0% 100% 98.6% 97.9% 97.0% 7 astaxanthin γ 8.0% 2.0% 100% 98.7% 97.8% 96.5% 8 lycopene synthesis 10.0% 2.0% 100% 98.1% 96.5% 95.1% 9 DHA Acetate natural 9.6% 1.6% 100% 98.5% 97.8% 96.3% 10 Linoleic acid glyceride mix 10.0% 1.4% 100% 97.8% 96.6% 96.4% 11 Linolenic acid phosphate mix 10.0% 1.2% 100% 98.0% 96.3% 95.2%

As can be clearly seen from the data in Table 5, within the blending ratio range according to the present invention, the content retention rate of the fat-soluble active ingredient was relatively high.

Although the present invention has been described with the above embodiments, the present invention is not limited to the specific embodiments and implementation methods described above, and the specific embodiments and implementation methods in this specification are intended to help those skilled in the art to practice the present invention. For this purpose, the scope of the present invention to the extent that various changes can be made by anyone skilled in the art in the field to which the present invention belongs, without departing from the gist of the present invention, as claimed by those skilled in the art in the following claims. intended to belong to

Claims (10)

A fat-soluble active ingredient microcapsule containing a fat-soluble active ingredient composition for improving the stability of the fat-soluble active ingredient,
The fat-soluble active ingredient composition includes a combination of tocopherol and vitamin C palmitate, and a fat-soluble active ingredient, the weight ratio of tocopherol and vitamin C palmitate is 2 to 8: 1, tocopherol and vitamin C palmitate. The weight ratio of the combination of C palmitate and the fat-soluble active ingredient is 7 to 13: 100,
The fat-soluble active ingredient is at least one selected from the group consisting of linoleic acid glyceride and linolenic acid phosphate, fat-soluble active ingredient microcapsules. According to claim 1,
Fat-soluble active ingredient microcapsules, characterized in that the weight ratio of tocopherol and vitamin C palmitate is 3 to 7: 1. According to claim 2,
Fat-soluble active ingredient microcapsules, characterized in that the weight ratio of tocopherol and vitamin C palmitate is 4 to 6: 1. According to claim 1,
A fat-soluble active ingredient microcapsule, characterized in that the weight ratio of the combination of tocopherol and vitamin C palmitate to the fat-soluble active ingredient is 8-12: 100. According to claim 4,
A fat-soluble active ingredient microcapsule, characterized in that the weight ratio of the combination of tocopherol and vitamin C palmitate to the fat-soluble active ingredient is 9-11: 100. A method for preparing the fat-soluble active ingredient microcapsules according to any one of claims 1 to 5,
Step 1) of blending and melting fat-soluble active ingredients and antioxidants at 45 to 85° C. under nitrogen gas protection to form oil phase A of fat-soluble active ingredients molten oil - the antioxidants are a combination of tocopherol and vitamin C palmitate; The weight ratio of tocopherol and vitamin C palmitate is 2 to 8: 1, the fat-soluble active ingredient is at least one selected from the group consisting of linoleic acid glyceride and linolenic acid phosphate, and the combination of tocopherol and vitamin C palmitate and the fat-soluble active ingredient The weight ratio is 7 ~ 13: 100 - ;
Step 2) obtaining phase B by dissolving gelatin or modified starch, which is a low molecular weight filler, and glucose or white sugar in water at 60 to 70° C. under the protection of nitrogen gas;
Under nitrogen gas protection, oil phase A obtained in step 1) and aqueous phase B obtained in step 2) were blended under sealed conditions, followed by high shear emulsification, degassing and homogenization to obtain an emulsion; step 3); and
A method for producing fat-soluble active ingredient microcapsules comprising step 4) of obtaining fat-soluble active ingredient microcapsules by spray pelleting the emulsion obtained in step 3) and then fluidizing and drying the emulsion. According to claim 6,
A method for preparing fat-soluble active ingredient microcapsules, characterized in that the fat-soluble active ingredient microcapsules obtained in step 4) are crosslinked at high temperature. delete delete delete