CN101837009A - A kind of sodium selenite vitamin injection and preparation method thereof - Google Patents

Abstract

A sodium selenite vitamin injection and a preparation method thereof belong to veterinary medicine technology, and it is composed of vitamin A, vitamin D3, vitamin E, and sodium selenite as active ingredients through solubilizers Tween, Span, and polyoxyethylene castor oil. (35) Water-soluble injection made of preservative 2,6-di-tert-butyl-p-cresol; improve the nutritional status of dairy cows, enhance the physique of dairy cows, promote estrus, increase the rate of artificial insemination and conception, and prevent cows from metritis and postpartum afterbirth No less, promote the healthy development of calves, and prevent the occurrence of calf white muscle disease.

Description

A kind of sodium selenite vitamin injection and preparation method thereof

technical field

The invention belongs to veterinary medicine technology, and mainly relates to a sodium selenite vitamin injection and a preparation method thereof.

Background technique

Selenium and vitamins A, D, and E are special organic and inorganic elements necessary for dairy cows to maintain normal physiological activities, promote growth and development, and improve reproduction and production performance. If the dairy cow lacks the above substances, it will cause a series of reproductive and growth diseases such as ovarian hypoplasia, estrus, infertility, stillbirth, calf white muscle disease, growth failure, postpartum retained placenta, and high incidence of metritis, which will greatly affect the health of dairy cows. Production performance brings significant losses to the cattle industry. Generally, the methods of supplementing trace substances are oral administration and injection. Oral vitamins will be degraded in the rumen, and the absorption time is long and the effect is not good. Therefore, injection should be the best way to supplement vitamins and selenium. However, vitamins A, D, and E are fat-soluble substances, and sodium selenite, an inorganic substance for supplementing selenium, is a water-soluble substance. Now there are sodium selenite vitamin E injections and vitamin ADE injections on the market, and sodium selenite Making a compound water-soluble injection with vitamins A, D, and E requires the research of pharmaceutical processes such as solubilization and emulsification, and there is no product on the market now.

Contents of the invention

The object of the present invention is to provide a kind of sodium selenite vitamin injection and preparation method thereof, by solubilizing agent Tween 80, Span 80, polyoxyethylene castor oil (35) fat-soluble vitamin is dissolved in water and selenous Sodium phosphate is made into an aqueous injection, which achieves the simultaneous supplementation of selenium and vitamins A, D, and E to prevent reproductive and growth diseases in dairy cows. It has stable performance, high bioavailability, and is easy to use.

Technical scheme of the present invention is:

Sodium selenite vitamin injection is prepared from raw materials with the following weight ratio: vitamin A 10-80 million units, vitamin D ₃ 10-80 million units, vitamin E 1-10g, sodium selenite 0.5- 10g, Tween 80 1-400g, Span 80 1-400g, polyoxyethylene castor oil (35) 1-400g, benzyl alcohol 5-50g, 2,6-di-tert-butyl-p-cresol 1-5g, injection Water 400-800g.

The present invention also provides a preparation method of sodium selenite vitamin injection, comprising the steps of:

Weigh the raw materials containing the above weight ratio; mix vitamin A, vitamin D ₃ , vitamin E, benzyl alcohol, and 2,6-di-tert-butyl-p-cresol, put them in a 60°C water bath to dissolve them evenly, add part Water for injection, Span 80, Tween 80, and polyoxyethylene castor oil (35) are stirred to dissolve, and sodium selenite is dissolved in a small amount of water for injection and added therein, stirred evenly, added water for injection to the full amount, stirred evenly, and obtained light The yellow clear solution is filtered, subpackaged, sterilized, and obtained.

The advantages and beneficial effects of the invention are: selenium and vitamins A, D and E are supplemented together, preventing reproductive and growth diseases of dairy cows, stable drug effect, high bioavailability and convenient use.

Detailed ways

The present invention will be described in detail below with examples.

Example 1:

Weigh vitamin A 20 million units, vitamin D ₃ 20 million units, vitamin E 5g, sodium selenite 1g, Tween 80 150g, Span 80 50g, polyoxyethylene castor oil (35) 50g, benzyl alcohol 10g, 2,6-di-tert-butyl-p-cresol 2g; mix vitamin A, vitamin D ₃ , vitamin E, benzyl alcohol, and BHT, put in a water bath at 60°C to dissolve evenly, add part of water for injection and Span 80 , Tween 80, polyoxyethylene castor oil (35) are stirred to dissolve, sodium selenite is dissolved in a small amount of water for injection and added therein, stir well, add water for injection to the full amount, stir well, to obtain a light yellow clear solution, filter, Subpackage, sterilize, and get ready. Water for injection to 1000ml.

Example 2:

Weigh vitamin A 80 million units, vitamin D ₃ 10 million units, vitamin E 10g, sodium selenite 10g, Tween 80 100g, Span 80 100g, polyoxyethylene castor oil (35) 20g, benzyl alcohol 50g , 2,6-di-tert-butyl-p-cresol 4g; mix vitamin A, vitamin D ₃ , vitamin E, benzyl alcohol, and BHT, put them in a 60°C water bath to dissolve evenly, add some water for injection and Span 80, Tween 80 and polyoxyethylene castor oil (35) were stirred to dissolve, dissolved sodium selenite with a small amount of water for injection and added thereto, stirred well, added water for injection to the full amount, stirred well, and obtained a light yellow clear solution, filtered, and divided Pack, sterilize, and get ready. Water for injection to 1000ml.

Example 3:

Weigh vitamin A 10 million units, vitamin D 380 million units, vitamin E _2g , sodium selenite 1g, Tween 80 50g, Span 80 50g, polyoxyethylene castor oil (35) 200g, benzyl alcohol 30g, 2,6-di-tert-butyl-p-cresol 5g; mix vitamin A, vitamin D ₃ , vitamin E, benzyl alcohol, and BHT, put in a water bath at 60°C to dissolve evenly, add some water for injection and Span 80 , Tween 80, polyoxyethylene castor oil (35) are stirred to dissolve, sodium selenite is dissolved in a small amount of water for injection and added thereto, stir well, add water for injection to the full amount, stir well, to obtain a light yellow clear solution, filter, Subpackage, sterilize, and get ready. Water for injection to 1000ml.

Sodium selenite vitamin injection is subjected to following test:

1. Content determination test of active ingredients:

The active ingredients of the sodium selenite vitamin injection are sodium selenite, vitamin A, vitamin D ₃ and vitamin E. The present invention uses the self-drawn quality standard to detect the content of three consecutive batches of products of the above-mentioned active ingredients through an atomic absorption instrument, an ultraviolet spectrophotometer, a high-performance liquid chromatograph, and a gas chromatograph. The content should be 90.0%-110.0% of the labeled amount.

batch number Sodium selenite (marked amount %) Vitamin A (labeled amount %) Vitamin D ₃ (declared amount %) Vitamin E (labeled amount %) 080201 99.71 94.45 98.21 92.39 080202 99.58 96.28 98.50 94.11 080203 99.64 98.41 99.43 92.78

The above three batches of preparations are products of the same preparation process example, and the production input volume is 105% of the prescription volume. During the production process, vitamins and oxygen in the air are oxidatively degraded, and a certain amount of loss is a normal phenomenon. Based on the above data, the product process is reasonable and stable, and can be mass-produced.

2. Stability test: put the three batches of products according to the finished product packaging at a temperature of 25°C±2°C and a relative humidity of 60%±10% for 12 months, and take samples every 3 months. Months, 6 months, 9 months, and 12 months are tested according to the key inspection items of stability. After 12 months, samples were taken at 18 and 24 months for appearance and content testing.

Conclusion: The properties, content detection and sterility test of the present invention are all qualified, and meet the relevant requirements of "The Veterinary Pharmacopoeia of the People's Republic of China 2005 Edition".

4. Safety test

(1) Allergy test: 18 healthy guinea pigs were randomly divided into 3 groups of 6: sodium selenite vitamin injection group, 0.9% sodium chloride injection group, 5% egg white normal saline positive control group. Intraperitoneal injection of 0.5 ml/monkey with the above three reagents respectively. Then each group was divided into 2 groups, 3 rats in each group. The first group was injected with 2.0 ml/rat respectively from the saphenous vein of the hind limbs 14 days after the first injection; 2.0ml/piece. Observe whether there are any reactions such as scratching the nose with claws, sneezing, piloerection, convulsions, dyspnea, incontinence, shock and death after injection. Results: Within 15 minutes after challenge injection, the guinea pigs in the sodium chloride injection group had no allergic reactions such as scratching the nose, trembling or erecting hair, dyspnea, and shock. Guinea pigs in the 5% egg white normal saline group suffered from irritability, ear scratching, sneezing, dyspnea, and convulsions after challenge injection, and all died within 3 minutes. Sodium selenite vitamin injection had no symptoms and no allergic reaction on the 14th day and 21st day of attack, indicating that the sodium selenite vitamin injection guinea pig allergy test was negative.

(2) Hemolytic test: take 5ml of fresh rabbit blood, put it in a clean Erlenmeyer flask, stir it with a glass rod to remove fibrin, then transfer the defibrinated blood into a graduated centrifuge tube, add an appropriate amount of sodium chloride injection, shake well Centrifuge at 2000r/min for 5min, and then dilute the resulting red blood cells with sodium chloride injection to form a 2% suspension according to their volume. Add 0.1-0.5 ml of sodium selenite vitamin injection to 2% rabbit red blood cell suspension respectively, no obvious hemolysis or agglutination effect on red blood cells.

(3) Vascular stimulation test: 6 rabbits were taken and divided into 3 groups, with 2 rabbits in each group. Group 1 sodium selenite vitamin injection 1ml/kg; group 2 sodium selenite vitamin injection 2ml/kg; group 3 0.9% sodium chloride injection 2ml/kg. With aseptic operation method, each rabbit was injected slowly into the ear vein, once a day, for 6 consecutive days. The animals were killed, and the blood vessels at the ear injection site were observed with naked eyes for abnormal reactions such as congestion and blood stasis, and were recorded in detail, and 2 cm of vascular tissue near the heart of the ear vein was taken for pathological section examination. Results: 0.9% sodium chloride injection control group, large and small doses of sodium selenite vitamin injection were injected for 6 days, the endothelium of the venous lumen was intact, smooth muscle and adventitia were not thickened, and fibrous connective tissue around blood vessels was not edematous. No inflammatory cell infiltration.

(4) Intramuscular injection test: Take 4 rabbits, inject 1 mL of Lianbizhi sodium chloride injection into the quadriceps femoris of the left and right hind limbs respectively, and inject sodium chloride injection into the negative control group, and cut them open 48 hours later. Skin, visually observe whether there is congestion, edema, degeneration or necrosis at the injection site, and make pathological examination. Results: There was no significant change in the site of administration.

Conclusion: Sodium selenite vitamin injection has no allergic reaction to guinea pigs. It has no obvious hemolysis or aggregation effect on rabbit red blood cells. After intravenous infusion of sodium selenite vitamin injection in the rabbit's ear margin, the endothelium was intact and smooth, no inflammatory reaction was seen on the tube wall, and no thrombus was seen in the tube cavity, so the drug had no obvious stimulating effect on local venous vessels. There was no local irritation after intramuscular injection of the drug.

5. Application effect test

The inventor has carried out the application test of self-made sodium selenite vitamin injection in Harbin Xinglin animal husbandry dairy farm for nearly one year. 150 dairy cows with similar conditions were randomly divided into two groups. The control group was not treated. The test group was injected intramuscularly with 25ml of sodium selenite vitamin injection before breeding, 60 days before delivery, 30 days after delivery, and within 1 hour after delivery. . Results: Compared with the control group, postpartum paralysis in the experimental group decreased by 5 times; placenta retention decreased by 8 times; the average birth weight of calves increased by 1.4 kg; white muscle disease of calves decreased by 2 times; The incidence rate decreased by 27.3%. Uterine recovery time was shortened by an average of 2.8 days. The average interval between calving and estrus adaptation of dairy cows was shortened by 4.5 days.

Conclusion: Sodium selenite vitamin injection can improve the nutritional status of dairy cows, enhance the physical fitness of dairy cows, promote estrus, increase the rate of artificial insemination and conception, prevent metritis and postpartum retained placenta in dairy cows, promote the healthy development of calves, and prevent the occurrence of white muscle disease in calves. occur.

Claims (2)

1. sodium selenite vitamin injection, it is characterized in that: it is to be prepared from by following proportion raw material: vitamin A 1,000 ten thousand-8,000 ten thousand units, vitamin D ₃1,000 ten thousand-8,000 ten thousand units, vitamin E 1-10g, sodium selenite 0.5-10g, Tween 80 1-400g, sorbester p17 1-400g, polyoxyethylene castor oil (35) 1-400g, benzyl alcohol 5-50g, 2,6 ditertiary butyl p cresol 1-5g, water for injection 400-800g.

2. an a kind of sodium selenite vitamin injection preparation method as claimed in claim 1 is characterized in that this method comprises the steps: to take by weighing the raw material of weight ratio; With vitamin A, vitamin D ₃, vitamin E, benzyl alcohol, 2,6 ditertiary butyl p cresol mix, and places 60 ℃ of water-baths to make its dissolving evenly, adding part water for injection and sorbester p17, Tween 80, polyoxyethylene castor oil (35) stirring and dissolving obtain solution, to join in the above-mentioned solution with the sodium selenite after a small amount of water for injection dissolving, stir evenly, will remain water for injection and all add in the solution, stir evenly, get faint yellow clear and bright solution, filter packing, sterilization, promptly.