CN1765882A - Preparation method of water-soluble vitamin D2 - Google Patents

Abstract

The invention relates to preparation field of water-soluble vitamin D2, which comprises: adding the medical or food vitamin D2 or vitamin D2 obtained by irradiating ergosterin to break its ninth and tenth bonds into emulsifier of glyceryl fatty acid ester dissolved in ethanol to prepare emulsion of D2; heating and dissolving the macromolecular material, such as glucose, adding sucrose fatty acid ester as emulsifier to stir and obtain the emulsion of carrier reagent for D2; mixing said two solution; drying, pulverizing, and obtaining the product, or as capsule or tablet. This product can be used as drug or food or feed addictive diluted by water with any proportion.

Description

Preparation method of water-soluble vitamin D2

technical field

The invention relates to the field of vitamin _D2 , in particular to the field of preparation methods of water-soluble vitamin _D2 .

Background technique

Vitamin D ₂ is one of the trace organic compounds necessary for humans and animals to maintain normal life activities and health. Medicines, foods and feeds can be supplemented with vitamin D ₂ to meet the regular intake of humans or animals from the outside world. Vitamin _D2 is the main natural form of vitamin D found in plants. (referring to Chinese patent 95118188.2). Vitamins are divided into two categories according to their solubility, namely fat-soluble vitamins (A, D, E, K), etc., or water-soluble vitamins (B ₁ , B ₂ , B ₆ , B ₁₂ , folic acid, niacin and vitamin C)] wait. [See Chapter 15 of "Medicinal Chemistry", 1. The classification of vitamins (Wang Shuxia, Department of Agriculture and Medicine, Central TV University). Since vitamin _D2 is insoluble in water but soluble in fat and fat solvents, it often coexists with lipids in food, and is also closely related to the absorption of lipids when absorbed in the intestinal tract. When humans or animals malabsorb lipids, Absorption of fat-soluble vitamin _D2 decreases, causing a corresponding deficiency. In medicine, the main indications of vitamin D ₂ include three aspects, 1. It is used for the prevention and treatment of vitamin D deficiency. Such as: absolute vegetarians, parenteral nutrition patients, pancreatic insufficiency with malabsorption syndrome, hepatobiliary diseases (liver function damage, cirrhosis, obstructive jaundice), small intestinal diseases (fatty diarrhea, regional enteritis, long-term diarrhea), gastric Excision etc. 2. For chronic hypocalcemia, hypophosphatemia, rickets and osteomalacia with chronic renal insufficiency, familial hypophosphatemia and hypoparathyroidism (postoperative, idiopathic or pseudo Hypoparathyroidism) treatment. 3. For the treatment of acute, chronic and potential postoperative tetany and idiopathic tetany. The characteristics of vitamin _D2 deficiency in animals are as follows: when vitamin _D2 is insufficient, even if calcium and phosphorus are sufficient, animals cannot make good use of them, and the deposition of calcium, phosphorus, and magnesium in bones will decrease; Osteogenesis is obstructed, rickets and chondrosis appear, tooth dysplasia, and growth retardation; adult animals suffer from osteoporosis, easy fractures, and joint deformation; excessive vitamin _D2 deficiency during pregnancy can cause congenital deformities in newborn pups. It can also suffer itself; vitamin _D deficiency in poultry can reduce egg production and hatchability, with thin and brittle eggshells. Therefore, vitamin D ₂ supplementation is even more necessary under the conditions of modern mechanized artificial large-scale animal feeding. However, excessive use of vitamin D ₂ is harmful. According to relevant medical data, taking large doses of vitamin D 2 in a short period of time or taking excessive doses of vitamin D ₂ for a long time can lead to severe poisoning reactions. Hypercalcemia caused by vitamin _D2 poisoning can cause systemic vascular calcification, renal calcium precipitation and other soft tissue calcification, resulting in hypertension and renal failure. The above adverse reactions mostly occur in hypercalcemia and hypercalcemia. Phosphate. Children can cause growth stagnation, which is often seen after long-term application of vitamin D ₂ 1800 units per day, and the toxic dose may vary due to individual differences. Even after daily application of 10,000 units for more than several months, it can cause toxic reactions to normal adults. Vitamin D ₂ poisoning can cause death due to renal and cardiovascular failure. Excessive intake of vitamin D ₂ in pregnant animals can cause fetal malformation, animal vitamin D ₂ poisoning manifests as hypercalciuria, anorexia, nausea and vomiting, thirst, polyuria, fatigue, joint pain and general disorientation, excessive vitamin D ₂ causes Hypercalcemia causes excess calcium to deposit in the heart, blood vessels, joints, pericardium, or intestinal wall, leading to heart failure, stiff joints or intestinal disorders, and even death. The two main forms of vitamin D are vitamin D ₂ and vitamin D ₃ , which are generally believed to exhibit similar biological activities and have the same metabolic effects (ie, activation and catabolism), but some data suggest that; "The toxicity of vitamin D ₃ 10 to 20 times that of vitamin D ₂ , this is because vitamin D ₃ is easily metabolized into 25-hydroxy-D ₃ , Trunnel et al. (1990) fed 15 7 to 10-day-old dairy calves and hybrid cattle D, A and E complex, 1 million units of vitamin D and 880,000 units of vitamin E per day. As a result, all the cattle showed symptoms such as lack of energy, anorexia, hair loss, and difficulty in walking, and 6 of them died after feeding for 13 to 27 days. Three of them were dissected and found that there were reddish-brown deposits on the inner surface of the pulmonary artery and the liver was slightly discolored. Six of the eight cattle were examined for blood chemistry, and 25-hydroxy-D ₃ and calcium ² in plasma were found The concentration of ⁺ all increased significantly." (See Huang Tao, Chen Xibin, Sheng Jinpeng, etc., authors of "The Safety of Fat-Soluble Vitamin Additives", China Aquaculture Network). According to the National Standard of the People's Republic of China GB14880-94 "Hygienic Standards for the Use of Food Nutrition Fortifiers", the scope of use and the amount per kilogram of vitamin D (D ₂ or D ₃ ) are limited to: 10-40 μg for milk and milk drinks, 125 μg for margarine ～156μg, dairy products 63～125μg, food for infants and young children 50～100μg (1μg vitamin D=40 units of vitamin D). The national standard for vitamin D as a safe feed addition is vitamin D (IU/kg), 114-240 for pigs, 200-500 for chickens, and 400-900 for ducks. Since the dosage of vitamin D is in μg, when fat-soluble vitamin D ₂ is mixed with food or feed, it is difficult to control the dosage and it is not easy to mix evenly, resulting in unqualified products. Therefore, the products added with vitamin D ₂ in the domestic food or feed industry Very few. The current annual consumption of vitamin _D2 in the world is about 1800 tons, of which about 70% are used as feed additives. my country's annual demand is about 100 tons. Now the global vitamin D ₂ market is dominated by BASF, Roche, and Nissin Chemical, mainly supplying the European and Japanese markets. These vitamin manufacturing giants sell more than 40% of their global vitamin sales through multidimensional and premixed materials. end customers. According to the novelty search report provided by the Sichuan Provincial Patent Information Center, the search results of Chinese and foreign patent databases show that no technical information on water-soluble vitamin _D2 has been found.

Purpose of the invention:

The purpose of the present invention is to solve the above-mentioned problem that fat-soluble vitamin _D2 exists, adopts emulsifier to make fat-soluble vitamin _D2 (medical grade, food grade vitamin _D2 , or use ergosterol to make 9, 10 bond breaking and obtain Vitamin D ₂ crude product), make water-soluble vitamin D ₂ method that can dissolve in water:

Contents of the invention

The preparation method of water-soluble vitamin _D of the present invention carries out as follows:

(1) Emulsification of Vitamin D ₂

Dissolve the emulsifier in ethanol, and then add vitamin _D2 , wherein the ratio of vitamin _D2 to emulsifier and ethanol is 1: (0.2-0.5): 2 (g:g:ml) to form an emulsion of vitamin _D2 .

(2) Emulsification of vitamin _D2 carrier preparation

Heat and dissolve the macromolecular substance or synthetic biodegradable macromolecular substance in water, then add an emulsifier and stir evenly, wherein the weight ratio of the carrier preparation to the emulsifier is 1: (0.01-0.02) to obtain the vitamin D ₂ carrier preparation of emulsion.

(3) mixed emulsification

Adjust the temperature of the emulsified solution of the vitamin D ₂ carrier preparation to 65° C. to 75° C., add the emulsified liquid of vitamin D ₂ and stir well to obtain a mixed emulsified liquid of vitamin D ₂ , that is, liquid water-soluble vitamin D ₂ .

The preferred scheme of the preparation method of the water-soluble vitamin _D2 of the present invention is that the vitamin _D2 added in the step (1) is the crude product of vitamin _D2 obtained by breaking the 9 and 10 bonds with ergosterol through irradiation.

The better scheme of the preparation method of water-soluble vitamin _D of the present invention is to increase the following steps after step (3):

(4) dry

Put the vitamin _D2 mixed emulsion into a drying box to dry to obtain lumpy or granular water-soluble vitamin _D2 ;

(5) Grinding and pulverizing the dried massive or granular water-soluble vitamin D ₂ into powder to obtain powdery water-soluble vitamin D ₂ .

The preparation method of water-soluble vitamin _D of the present invention can also be carried out as follows:

(1) Emulsification of Vitamin D ₂

Dissolve the emulsifier in ethanol, and then add vitamin D ₂ , wherein the ratio of vitamin D ₂ to emulsifier and ethanol is 1: (8-10): (8-10) (g:g:ml) to form vitamin D ₂ emulsions.

(2) Mix and stir the vitamin D ₂ emulsion and the carrier preparation evenly to obtain a vitamin D ₂ mixed emulsion, that is, liquid water-soluble vitamin D ₂ .

The emulsifier used in the above steps is a surfactant containing a hydrophilic group and a lipophilic group, most of which are esters. Commonly used are glycerin fatty acid ester, sucrose fatty acid ester, sorbitol fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene fatty acid sorbitol ester, polyoxyethylene fatty acid glyceride, etc. Emulsifiers such as sodium lauryl sulfate and polyvinylpyrrolidone can also be used.

The macromolecular substances used in the above steps are glucose, calcium lactate, calcium gluconate, etc., and the synthetic biodegradable macromolecular substances are liposomes, β-cyclodextrin, agarose beads, etc.

By adopting the method of the present invention, fat-soluble vitamin _D2 can be made into water-soluble vitamin _D2 which can be dissolved in water in any required ratio, and can be made into liquid, powder, capsule or tablet, which can satisfy Application requirements for vitamin _D2 in medicine, food, feed and other fields.

specific embodiment

Example 1:

(1) Emulsification of Vitamin D ₂

Dissolve 20g of glycerin fatty acid ester in 200ml of ethanol, then add 100g of vitamin _D2 , stir to form an emulsion of vitamin _D2 ;

(2) Emulsification of vitamin _D2 carrier preparation

Heat 1000g of glucose with distilled water to dissolve, then add 1% sucrose fatty acid ester and stir evenly to obtain an emulsion of vitamin _D2 carrier preparation;

(3) mixed emulsification

Adjust the temperature of the emulsified solution of the vitamin _D2 carrier preparation to 65°C, then add the emulsified liquid of vitamin _D2 , and stir well to obtain a mixed emulsified liquid of vitamin _D2 , which is a liquid water-soluble vitamin _D2 product, which can be directly used as Used as an additive for medicine, food or feed, it can be uniformly released with water in any desired ratio.

Example 2

(1) Emulsification of Vitamin D ₂

Dissolve 50g of glycerin fatty acid ester in 200ml of ethanol, then add 100g of vitamin _D2 , stir to form an emulsion of vitamin _D2 ;

(2) Emulsification of vitamin _D2 carrier preparation

Add 2000g of glucose to distilled water, heat, dissolve and concentrate to make glucose syrup with a sugar content of more than 90%, then add 2% sucrose fatty acid ester and stir evenly to obtain an emulsion of vitamin _D2 carrier preparation;

(3) mixed emulsification

Adjust the temperature of the emulsion of the vitamin _D2 carrier preparation to 75°C, then add the emulsion of vitamin _D2 , and stir well to obtain a mixed emulsion of vitamin _D2 , that is, a liquid water-soluble vitamin _D2 product, which can be directly used as Used as an additive for medicine, food or feed, it can be uniformly released with water in any desired ratio.

Example 3

(1) Emulsification of Vitamin D ₂

Dissolve 20g of glycerol fatty acid ester in 200ml of ethanol, then add 100g of vitamin _D2 crude product obtained by irradiating 9 and 10 bonds with ergosterol, and stir to form a vitamin _D2 emulsion;

(2) Emulsification of vitamin _D2 carrier preparation

Heat 1000g of glucose with distilled water to dissolve, then add 1% sucrose fatty acid ester and stir evenly to obtain an emulsion of vitamin _D2 carrier preparation;

(3) mixed emulsification

Adjust the temperature of the emulsified solution of the vitamin _D2 carrier preparation to 65°C, then add the emulsified liquid of vitamin _D2 , and stir well to obtain a mixed emulsified liquid of vitamin _D2 , which is a liquid water-soluble vitamin _D2 product, which can be directly used as Used as an additive for medicine, food or feed, it can be uniformly released with water in any desired ratio.

Example 4

(1) Emulsification of Vitamin D ₂

Dissolve 50g of glycerin fatty acid ester in 200ml of ethanol, then add 100g of vitamin _D2 , stir to form an emulsion of vitamin _D2 ;

(2) Emulsification of vitamin _D2 carrier preparation

Add 2000g of glucose to distilled water, heat, dissolve and concentrate to make glucose syrup with a sugar content of more than 90%, then add 2% sucrose fatty acid ester and stir evenly to obtain an emulsion of vitamin _D2 carrier preparation;

(3) mixed emulsification

Adjust the temperature of the emulsion of the vitamin _D2 carrier preparation to 75°C, then add the emulsion of vitamin _D2 , and stir well to obtain a mixed emulsion of vitamin _D2 , that is, a liquid water-soluble vitamin _D2 product, which can be directly used as Used as an additive for medicine, food or feed, it can be uniformly released with water in any desired ratio.

(4) dry

Put the vitamin _D2 mixed emulsion into a drying box to dry to obtain lumpy or granular water-soluble vitamin _D2 ;

(5) Grinding and pulverizing the dried massive or granular water-soluble vitamin D ₂ into powder to obtain powdery water-soluble vitamin D ₂ .

Example 5

(1) Emulsification of Vitamin D ₂

Add 1000g of polyvinylpyrrolidone to dissolve in 1000ml of ethanol, then add 50g of sodium lauryl sulfate, stir and mix evenly, then add 200ml of ethanol solution containing 100g of vitamin _D2 , stir and mix evenly to obtain an emulsion of vitamin _D2 ;

(2) mixed emulsification

Mix 2850 g of carrier preparation dextrin with vitamin D ₂ emulsion and stir evenly to obtain liquid water-soluble vitamin D ₂ .

Example 6

(1) Emulsification of Vitamin D ₂

Add 750g of polyvinylpyrrolidone to dissolve in 800ml of ethanol, then add 50g of sodium lauryl sulfate, stir and mix evenly, then add 200ml of ethanol solution containing 100g of vitamin _D2 , stir and mix evenly to obtain an emulsion of vitamin _D2 ;

(2) mixed emulsification

Mix and stir 4100 g of carrier preparation dextrin and vitamin D ₂ emulsion evenly to obtain liquid water-soluble vitamin D ₂ .

(3) dry

Put the vitamin _D2 mixed emulsion into a drying box to dry to obtain lumpy or granular water-soluble vitamin _D2 ;

(4) Grinding and pulverizing the dried massive or granular water-soluble vitamin D ₂ into powder to obtain powdery water-soluble vitamin D ₂ .

Claims (6)

1, a kind of preparation method of water-soluble vitamin _D2 is characterized in that: the method is carried out as follows: (1) Emulsification of Vitamin D ₂ Dissolve the emulsifier in ethanol, and then add vitamin _D2 , wherein the ratio of vitamin _D2 to emulsifier and ethanol is 1: (0.2-0.5): 2 (g:g:ml) to form an emulsion of vitamin _D2 ; (2) Emulsification of vitamin _D2 carrier preparation Heat and dissolve the macromolecular substance or synthetic biodegradable macromolecular substance in water, then add an emulsifier and stir evenly, wherein the weight ratio of the carrier preparation to the emulsifier is 1: (0.01-0.02) to obtain the vitamin D ₂ carrier preparation of emulsion. (3) mixed emulsification Adjust the temperature of the emulsified solution of the vitamin D ₂ carrier preparation to 65° C. to 75° C., add the emulsified liquid of vitamin D ₂ and stir well to obtain a mixed emulsified liquid of vitamin D ₂ , that is, liquid water-soluble vitamin D ₂ . 2. The method according to claim 1, characterized in that: the vitamin _D2 added in step (1) is crude vitamin _D2 obtained by cleaving the bonds at positions 9 and 10 with ergosterol through irradiation. 3. The method according to claim 1 or 2, characterized in that the following steps are added after step (3): (4) dry Put the vitamin _D2 mixed emulsion into a drying box to dry to obtain lumpy or granular water-soluble vitamin _D2 ; (5) Grinding and pulverizing the dried massive or granular water-soluble vitamin D ₂ into powder to obtain powdery water-soluble vitamin D ₂ . 4. The method according to claim 3, characterized in that the emulsifier is a surfactant containing hydrophilic groups and lipophilic groups, most of which are esters; commonly used are glycerin fatty acid esters, sucrose fatty acid esters, Sorbitan fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene fatty acid sorbitan ester, polyoxyethylene fatty acid glyceride, etc.; emulsifiers such as sodium lauryl sulfate and polyvinylpyrrolidone can also be used. 5. A method for preparing water-soluble vitamin _D2 , characterized in that: the method is carried out as follows: (1) Emulsification of Vitamin D ₂ Dissolve the emulsifier in ethanol, and then add vitamin D ₂ , wherein the ratio of vitamin D ₂ to emulsifier and ethanol is 1: (8-10): (8-10) (g:g:ml) to form vitamin D ₂ emulsions. (2) Mix and stir the vitamin D ₂ emulsion and the carrier preparation evenly to obtain a vitamin D ₂ mixed emulsion, that is, liquid water-soluble vitamin D ₂ . 6. The method according to claim 5, wherein the following steps are added after step (2): (3) dry Put the vitamin _D2 mixed emulsion into a drying box to dry to obtain lumpy or granular water-soluble vitamin _D2 ; (4) Grinding and pulverizing the dried massive or granular water-soluble vitamin D ₂ into powder to obtain powdery water-soluble vitamin D ₂ .