KR20130083822A - Aqueous formulation of vitamins and preparation method thereof - Google Patents

Abstract

Aqueous vitamin preparations and methods for making the same are disclosed. By weight, the aqueous formulation is liposome, 1.89-5.85 parts vitamin A, 2-4 parts vitamin D, 1-3 parts vitamin E, 1-2 parts vitamin K, 4-6 parts vitamin B1 , 2 to 4 parts by weight of vitamin B2, 2 to 6 parts by weight of vitamin B6, 1 to 2 parts by weight of vitamin B12, 1 to 6 parts by weight of vitamin C, 2 to 4 parts by weight of vitamin H, 1 to 2 parts by weight of folic acid and a solubilizing agent Contains raw material components of.

Description

Aqueous vitamin preparation and its manufacturing method {AQUEOUS FORMULATION OF VITAMINS AND PREPARATION METHOD THEREOF}

The present invention relates to vitamin additives in the art of animal aquaculture, in particular vitamin aqueous preparations and methods for their preparation.

Vitamins, which are organic matter essential for the normal functioning of an organism, are either not synthesized in the organism or can be synthesized in very small amounts, which means that food intake is required. do. Vitamins play an important role in regulating the metabolism of organisms and maintaining their physiological functions and are widely involved in the various chemical reactions of metabolism in vivo, mainly in the form of coenzymes and catalysts. Thus ensuring the normal cellular structure and function of the tissues and organs of the organism and maintaining good health and normal activity of the animal, the lack of vitamins can lead to metabolism disorders and Moreover, it negatively affects the health and normal biological activity of the animal.

Vitamins can be classified into liposoluble vitamins and water-soluble vitamins based on their solubility. The fat soluble vitamins directly participate in and influence a variety of effects, in particular certain metabolic processes, and the fat soluble vitamins also bind to receptors in the cell to affect specific gene expression. . As the name implies, the water soluble vitamin is soluble in water and insoluble in fats and organic solvents, and the intake of the large amount of the water soluble vitamin generally may not result in accumulation and positioning. In addition, most of the water-soluble vitamins participate in the operation of various enzyme systems in the form of coenzymes or prosthetic groups, and therefore they are extremely important in the various links of intermediate metabolism. Do. Obviously, both the fat soluble vitamin and the water soluble vitamin have a pronounced effect on the health of the animal body, but, however, since the fat soluble vitamin can only be dissolved in liposoluble substances, the practical application ( The utility rate of the fat soluble vitamins in practical applications is low, and in particular, methods of producing homogeneous and stable aqueous formulations from the fat soluble vitamins and the water soluble vitamins have always been difficult in the growing industry and are urgent. Should be solved. There are many disadvantages in presently known methods such as few active ingredients in aqueous formulations, unstable aqueous formulations and complex processes.

The present invention aims to overcome the shortcomings in the prior art and to provide a homogenized and stable vitamin aqueous formulation.

The vitamin aqueous formulation is liposome, 1.89 to 5.85 parts by weight of vitamin A, 2 to 4 parts by weight of vitamin D, 1 to 3 parts by weight of vitamin E, 1 to 2 parts by weight of vitamin K, 4 to 6 parts by weight of vitamin B1, 2 to 4 Parts by weight of vitamin B2, 2 to 6 parts by weight of vitamin B6, 1 to 2 parts by weight of vitamin B12, 1 to 6 parts by weight of vitamin C, 2 to 4 parts by weight of vitamin H, 1 to 2 parts by weight of folic acid and solubilizer Contains raw materials for solubilizer.

The liposome is 0 to 10 parts by weight of soybean lecithin, 0 to 15 parts by weight of LA-phosphatidylcholine distearoyl, 0 to 40 parts by weight of sorbitol and 5 parts by weight of cholesterol Raw materials of

The solubilizer is formed by mixing polyethylene glycol 6000 and polyvinyl pyrrolidone in a weight ratio of 2: 1.

The present invention also aims to provide a process for the preparation of an aqueous vitamin preparation, which comprises the following steps:

(1) Preparation of liposomes

Mixing one or more of soy lecithin, L-A-phosphatidylcholine distearoyl and sorbitol with cholesterol, and then adding the mixture into the reaction vessel and reacting at a temperature of 20 to 65 ° C. for 30 to 45 minutes;

(2) Preparation of fat-soluble vitamin solution

Preparing a fat-soluble vitamin solution by dissolving vitamin A, vitamin D, vitamin E, vitamin K, and a solubilizer in an organic solvent, that is, a mixed solution of trichloromethane and ethanol;

(3) Preparation of Water-Soluble Vitamin Solution

Preparing a water-soluble vitamin solution by dissolving vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin H and folic acid in PBS buffer solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution is dissolved in the liposomes, the organic solvent is removed by means of vacuum evaporation, and then the water-soluble vitamin solution is added thereto, followed by normal temperature for 2 to 4 hours. Leaving at room temperature;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product;

.

In addition, the finished product applied to the treatment in step (5) is also subjected to filtration by 0.45-micron micropore filter membrane.

 In addition, in step (1), there are 0 to 10 parts by weight of soy lecithin, 0 to 15 parts by weight of L-A-phosphatidylcholine distearoyl, 0 to 40 parts by weight of sorbitol and 5 parts by weight of cholesterol.

In addition, the solubilizing agent in the step (2) is formed by mixing polyethylene glycol 6000 and polyvinylpyrrolidone in a weight ratio of 2: 1.

In addition, the volume ratio of the trichloromethane to the ethanol in the step (2) is 2: 1.

In addition, the pH value of the PBS buffer in step (3) is 6.0 to 7.4, and the temperature of the buffer is 30 to 45 ℃.

In addition, the vacuum evaporation condition in step (4) is that the organic solvents are removed by means of vacuum evaporation at 50 ° C. or lower.

The present invention has the following advantages and positive effects:

In the present invention, fat soluble vitamins are coated in the microcapsule structure of liposomes and are homogenized with the water soluble vitamins and form a stable aqueous formulation. The aqueous formulations have stable storage characteristics for a long period of time, smaller particle diameters and cellular structures of the components, and activate the organism's autoimmune function after introduction into the animal body, thereby Maintain a higher immunity level of; On the one hand, it is possible to effectively store multiple vitamins in the organism, avoiding the loss and insufficient utilization of vitamins in metabolic processes, significantly improving the utilization and conversion rate of feed, and the antibodies of animal organisms. This results in improved antibody levels and improved disease resistance.

The present invention will be described in more detail below with reference to embodiments which are considered to be illustrative rather than restrictive, and therefore do not limit the scope of the present invention.

The present invention aims to overcome the shortcomings in the prior art and to provide a homogenized and stable vitamin aqueous formulation. The vitamin aqueous formulation is liposome, 1.89 to 5.85 parts by weight of vitamin A, 2 to 4 parts by weight of vitamin D, 1 to 3 parts by weight of vitamin E, 1 to 2 parts by weight of vitamin K, 4 to 6 parts by weight of vitamin B1, 2 to 4 Raw materials of parts by weight of vitamin B2, 2 to 6 parts by weight of vitamin B6, 1 to 2 parts by weight of vitamin B12, 1 to 6 parts by weight of vitamin C, 2 to 4 parts by weight of vitamin H, 1 to 2 parts by weight of folic acid and solubilizer Include.

The liposomes comprise 0 to 10 parts by weight of soy lecithin, 0 to 15 parts by weight of L-A-phosphatidylcholine distearoyl, 0 to 40 parts by weight of sorbitol and 5 parts by weight of cholesterol. The solubilizer is formed by mixing polyethylene glycol 6000 and polyvinylpyrrolidone in a weight ratio of 2: 1.

Example 1

The method for preparing the vitamin aqueous formulation comprises the following steps:

(1) Preparation of liposomes

Mixing 10 g soy lecithin with 5 g cholesterol, and then adding the mixture into the reaction vessel and reacting at a temperature of 20 ° C. for 30 to 45 minutes;

(2) Preparation of fat-soluble vitamin solution

11 million IU (International Unit, 3.78 g) of Vitamin A, 160 million IU (4 g) of Vitamin D, 2000 IU (2 g) of Vitamin E, 1000 IU (1 g) of Vitamin K, 10 g of Polyethylene Glycol 6000 and 5 g of Polyvinylpi Preparing a fat-soluble vitamin solution by dissolving lollidon in an organic solvent, that is, a mixed solution of trichloromethane and ethanol (the weight ratio of the trichloromethane to the ethanol is 2: 1);

(3) Preparation of Water-Soluble Vitamin Solution

4 g of vitamin B1, 4 g of vitamin B2, 2 g of vitamin B6, 2 g of vitamin B12, 4 g of vitamin C, 2 g of vitamin H, and 2 g of folic acid were dissolved in a PBS buffer solution having a pH value of 6.0 and a temperature of 30 ° C. To prepare a water-soluble vitamin solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution is dissolved in the liposomes, the organic solvent (trichloromethane and ethanol) is removed by means of vacuum evaporation at 50 ° C., 0.08 MPa or less, and then the water-soluble vitamin solution is added thereto. Subsequent to 2 hours at normal temperature;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product, and wherein the grain diameter of solid particles in the finished product is 0.1 micron to 0.4 micron;

(6) removing harmful bacteria from the finished product by means of filtration with a 0.45 micron microporous filtration membrane, and subsequently canning and sealing;

.

Example 2

The method for preparing the vitamin aqueous formulation comprises the following steps:

(1) Preparation of liposomes

Mixing 10 g soy lecithin and 20 g sorbitol with 5 g cholesterol, and then adding the mixture into the reaction vessel and reacting at a temperature of 65 ° C. for 30 to 45 minutes;

(2) Preparation of fat-soluble vitamin solution

5500000 IU (1.89 g) of vitamin A, 160 000 000 IU (4 g) of vitamin D, 2000 IU (2 g) of vitamin E, 1000 IU (1 g) of vitamin K, 10 g of polyethylene glycol 6000 and 5 g of polyvinylpyrrolidone in an organic solvent, That is, dissolving in a mixed solution of trichloromethane and ethanol (weight ratio of the trichloromethane to the ethanol is 2: 1) to prepare a fat-soluble vitamin solution;

(3) Preparation of Water-Soluble Vitamin Solution

4 g of vitamin B1, 2 g of vitamin B2, 2 g of vitamin B6, 1 g of vitamin B12, 6 g of vitamin C, 2 g of vitamin H, and 2 g of folic acid were dissolved in PBS buffer having a pH value of 7.4 and a temperature of 45 ° C. To prepare a water-soluble vitamin solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution is dissolved in the liposome, the organic solvent (trichloromethane and ethanol) is removed by means of vacuum evaporation at 50 ° C., 0.08 to 0.1 MPa or less, and then the water-soluble vitamin solution is added thereto. Adding and subsequently leaving at normal temperature for 4 hours;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product, and the particle diameter of the solid particles in the finished product is 0.1 micron to 0.4 micron;

(6) removing harmful bacteria from the finished product by means of filtration with a 0.45 micron microporous filtration membrane, and then placing in a can and sealing;

.

Example 3

The method for preparing the vitamin aqueous formulation comprises the following steps:

(1) Preparation of liposomes

5 g soy lecithin, 5 g LA-phosphatidylcholine distearoyl and 20 g sorbitol are mixed with 5 g cholesterol, and then the mixture is added into the reaction vessel and reacted at a temperature of 55 ° C. for 30 to 45 minutes. ;

(2) Preparation of fat-soluble vitamin solution

11000000 IU (3.78 g) of vitamin A, 160 000 000 IU (4 g) of vitamin D, 2000 IU (2 g) of vitamin E, 2000 IU (2 g) of vitamin K, 10 g of polyethylene glycol 6000 and 5 g of polyvinylpyrrolidone in an organic solvent, That is, dissolving in a mixed solution of trichloromethane and ethanol (weight ratio of the trichloromethane to the ethanol is 2: 1) to prepare a fat-soluble vitamin solution;

(3) Preparation of Water-Soluble Vitamin Solution

4 g of vitamin B1, 2 g of vitamin B2, 6 g of vitamin B6, 2 g of vitamin B12, 4 g of vitamin C, 2 g of vitamin H, and 2 g of folic acid were dissolved in PBS buffer with a pH of 7.0 and a temperature of 32 ° C. To prepare a water-soluble vitamin solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution is dissolved in the liposome, the organic solvent (trichloromethane and ethanol) is removed by means of vacuum evaporation at 50 ° C., 0.08 to 0.09 MPa or less, and then the water-soluble vitamin solution is added thereto. Adding and subsequently leaving at normal temperature for 3.5 hours;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product, and the particle diameter of the solid particles in the finished product is 0.1 micron to 0.4 micron;

(6) removing harmful bacteria from the finished product by means of filtration with a 0.45 micron microporous filtration membrane, and then placing in a can and sealing;

.

Example 4

The method for preparing the vitamin aqueous formulation comprises the following steps:

(1) Preparation of liposomes

10 g of L-A-phosphatidylcholine distearoyl and 40 g of sorbitol are mixed with 5 g of cholesterol, and then the mixture is added into the reaction vessel and reacted at a temperature of 45 ° C. for 30 to 45 minutes;

(2) Preparation of fat-soluble vitamin solution

11000000 IU (3.78 g) of vitamin A, 80 000 000 IU (2 g) of vitamin D, 2000 IU (2 g) of vitamin E, 2000 IU (2 g) of vitamin K, 10 g of polyethylene glycol 6000 and 5 g of polyvinylpyrrolidone in an organic solvent, That is, dissolving in a mixed solution of trichloromethane and ethanol (weight ratio of the trichloromethane to the ethanol is 2: 1) to prepare a fat-soluble vitamin solution;

(3) Preparation of Water-Soluble Vitamin Solution

4 g of vitamin B1, 4 g of vitamin B2, 6 g of vitamin B6, 2 g of vitamin B12, 1 g of vitamin C, 4 g of vitamin H, and 1 g of folic acid were dissolved in PBS buffer solution having a pH of 6.5 and a temperature of 41 ° C. To prepare a water-soluble vitamin solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution was dissolved in the liposomes, the organic solvent (trichloromethane and ethanol) was removed by means of vacuum evaporation at 50 ° C., 0.09 MPa or less, and then the water-soluble vitamin solution was added thereto. Subsequent to standing at normal temperature for 2.5 hours;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product, and the particle diameter of the solid particles in the finished product is 0.1 micron to 0.4 micron;

(6) removing harmful bacteria from the finished product by means of filtration with a 0.45 micron microporous filtration membrane, and then placing in a can and sealing;

.

Example 5

The method for preparing the vitamin aqueous formulation comprises the following steps:

(1) Preparation of liposomes

Mixing 15 g of L-A-phosphatidylcholine distearoyl with 5 g of cholesterol, and then adding the mixture into the reaction vessel and reacting at a temperature of 25 ° C. for 30 to 45 minutes;

(2) Preparation of fat-soluble vitamin solution

17000000 IU (5.85 g) of vitamin A, 160 000 000 IU (4 g) of vitamin D, 2000 IU (2 g) of vitamin E, 1000 IU (1 g) of vitamin K, 10 g of polyethylene glycol 6000 and 5 g of polyvinylpyrrolidone in an organic solvent, That is, dissolving in a mixed solution of trichloromethane and ethanol (weight ratio of the trichloromethane to the ethanol is 2: 1) to prepare a fat-soluble vitamin solution;

(3) Preparation of Water-Soluble Vitamin Solution

6 g of vitamin B1, 4 g of vitamin B2, 6 g of vitamin B6, 2 g of vitamin B12, 4 g of vitamin C, 2 g of vitamin H, and 2 g of folic acid were dissolved in PBS buffer having a pH value of 6.8 and a temperature of 37 ° C. To prepare a water-soluble vitamin solution;

(4) Preparation of Vitamin Aqueous Formulations

The fat-soluble vitamin solution is dissolved in the liposomes, the organic solvent (trichloromethane and ethanol) is removed by means of vacuum evaporation at 50 ° C., 0.08 MPa or less, and then the water-soluble vitamin solution is added thereto. Subsequent to 4 hours at normal temperature;

(5) homogenization of the vitamin aqueous formulation

Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product, and the particle diameter of the solid particles in the finished product is 0.1 micron to 0.4 micron;

(6) removing harmful bacteria from the finished product by means of filtration with a 0.45 micron microporous filtration membrane, and then placing in a can and sealing;

.

The results of the analysis for the vitamin aqueous formulations in Examples 1-5 are shown in Table 1 (test for stability of aqueous formulations after long term storage), Table 2 (average content for fat-soluble components of aqueous formulations after long term storage). Analysis) and Table 3 (physical sign analysis for animals after use of aqueous vitamin preparations):

time 1 month 3 months 6 months 12 months 18 months Example 1 Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Example 2 Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Example 3 Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Example 4 Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Example 5 Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow Homogenized And Stable Yellow

From the results in Table 1 it is clear that the vitamin aqueous formulation has stable properties after long term storage.

time 1 month(%) 3 months(%) 6 months(%) 12 months (%) 18 months (%) Vitamin A 99.97 99.95 99.95 99.94 99.93 Vitamin D 99.94 99.93 99.93 99.91 99.91 Vitamin E 99.96 99.95 99.93 99.93 99.91 Vitamin K 99.99 99.97 99.97 99.95 99.95

From the results in Table 2 it is clear that the vitamin aqueous formulation has a sufficient amount of fat soluble components after long term storage.

Indicators Of utilization of supply
Improving(%) Weight gain
Indicators(%) Immune level How to apply



object Example 1 26.81 15.25 height Soluble in water or used as spraying material Example 2 28.45 16.56 height Soluble in water or used as spraying material Example 3 26.73 15.61 height Soluble in water or used as spraying material Example 4 27.85 16.38 height Soluble in water or used as spraying material Example 5 28.96 16.22 height Soluble in water or used as spraying material

From the results in Table 3, after the vitamin aqueous formulations have been used in poultry and livestock, the utilization of the feed, weight gain and immune levels have been significantly increased relative to the mean, and the vitamin aqueous formulations can be used directly and are simple in operation. It is obvious that it is convenient and convenient.

In summary, the present invention has stable properties and sufficient content of effective ingredients after long term storage, markedly improves the utilization and conversion rate of the feed, improves the antibody level and disease resistance of the organism, is easy to apply and is poor in fat-soluble vitamins. Solve problems such as absorption and use and inconvenient application.

Claims (10)

The aqueous formulation is liposome, 1.89-5.85 parts vitamin A, 2-4 parts vitamin D, 1-3 parts vitamin E, 1-2 parts vitamin K, 4-6 parts vitamin B1, 2-4 parts Vitamin B2, 2 to 6 parts by weight of vitamin B6, 1 to 2 parts by weight of vitamin B12, 1 to 6 parts by weight of vitamin C, 2 to 4 parts by weight of vitamin H, 1 to 2 parts by weight of folic acid and solubilizing agent A vitamin aqueous formulation, characterized in that. The method of claim 1,
A vitamin aqueous formulation, wherein the liposome comprises 0 to 10 parts by weight of soy lecithin, 0 to 15 parts by weight of LA-phosphatidylcholine distearoyl, 0 to 40 parts by weight of sorbitol and 5 parts by weight of cholesterol. The method of claim 1,
The solubilizing agent is formed by mixing polyethylene glycol 6000 and polyvinylpyrrolidone in a weight ratio of 2: 1. Steps below:
(1) Preparation of liposomes
Mixing one or more of soy lecithin, LA-phosphatidylcholine distearoyl and sorbitol with cholesterol, and then adding the mixture into the reaction vessel and reacting at a temperature of 20 to 65 ° C. for 30 to 45 minutes;
(2) Preparation of fat-soluble vitamin solution
Preparing a fat-soluble vitamin solution by dissolving vitamin A, vitamin D, vitamin E, vitamin K, and a solubilizer in an organic solvent, that is, a mixed solution of trichloromethane and ethanol;
(3) Preparation of Water-Soluble Vitamin Solution
Dissolving vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin H and folic acid in PBS buffer to prepare a water-soluble vitamin solution;
(4) Preparation of Vitamin Aqueous Formulations
Dissolving the fat soluble vitamin solution in the liposomes, removing the organic solvent by means of vacuum evaporation, and subsequently adding the water soluble vitamin solution to it and subsequently leaving it at normal temperature for 2 to 4 hours. ;
(5) homogenization of the vitamin aqueous formulation
Treating the vitamin aqueous formulation after standing with a colloid mill to obtain a finished product;
Method for producing an aqueous vitamin preparation, characterized in that comprises a. 5. The method of claim 4,
The method of producing an aqueous vitamin preparation, characterized in that the finished product applied to the treatment in step (5) is also subjected to filtration by 0.45 micron microporous filtration membrane. 5. The method of claim 4,
0 to 10 parts by weight of soy lecithin, 0 to 15 parts by weight of LA-phosphatidylcholine distearoyl, 0 to 40 parts by weight of sorbitol and 5 parts by weight of cholesterol are prepared in the step (1). Way. 5. The method of claim 4,
In the step (2), the solubilizer is formed by mixing polyethylene glycol 6000 and polyvinylpyrrolidone in a weight ratio of 2: 1. 5. The method of claim 4,
Method of producing an aqueous vitamin preparation, characterized in that the volume ratio of the trichloromethane to the ethanol in the step (2) is 2: 1. 5. The method of claim 4,
The pH value of the PBS buffer solution in step (3) is 6.0 to 7.4, and the temperature of the buffer solution is characterized in that the preparation method of the vitamin aqueous formulation of 30 to 45 ℃. 5. The method of claim 4,
The method of producing an aqueous vitamin preparation, characterized in that the organic solvent is removed by means of vacuum evaporation in the step (4) vacuum evaporation conditions below 50 ℃.