阅读说明：本技术 一种脂肪乳注射液的配方及其制备方法 (Formula of fat emulsion injection and preparation method thereof ) 是由 谭宏翔 任泽林 李杨 魏衍纲 于 2020-12-31 设计创作，主要内容包括：本发明公开一种脂肪乳注射液的配方及其制备方法。所述的脂肪乳注射液包含大豆油、蛋黄卵磷脂、甘油、油酸和氢氧化钠；按1000mL脂肪乳注射液计,包含大豆油90-110g、蛋黄卵磷脂11-13g、甘油20-26g、油酸0.4-0.6g,氢氧化钠调节水相的pH值为11.0-11.5。经测试,脂肪乳注射液在碱性条件下更加稳定,本发明在配制脂肪乳注射液中用氢氧化钠调节水相pH为11.0-11.5,使水相和油相乳化后得到的注射液最终pH在8.0-8.5之间,可提高脂肪乳水包油体系的稳定性。(The invention discloses a formula of a fat emulsion injection and a preparation method thereof. The fat emulsion injection comprises soybean oil, egg yolk lecithin, glycerol, oleic acid and sodium hydroxide; based on 1000mL of fat emulsion injection, the fat emulsion injection comprises 90-110g of soybean oil, 11-13g of egg yolk lecithin, 20-26g of glycerol and 0.4-0.6g of oleic acid, and the pH value of an aqueous phase is adjusted to 11.0-11.5 by sodium hydroxide. Tests prove that the fat emulsion injection is more stable under the alkaline condition, the pH value of a water phase is adjusted to 11.0-11.5 by using sodium hydroxide in the prepared fat emulsion injection, the final pH value of an injection obtained after the water phase and an oil phase are emulsified is 8.0-8.5, and the stability of a fat emulsion oil-in-water system can be improved.)

1. A fat emulsion injection, comprising soybean oil, egg yolk lecithin, glycerol, oleic acid, and sodium hydroxide; based on 1000mL of fat emulsion injection, the fat emulsion injection comprises 90-110g of soybean oil, 11-13g of egg yolk lecithin, 20-26g of glycerol and 0.4-0.6g of oleic acid, and the pH value of an aqueous phase is adjusted to 11.0-11.5 by sodium hydroxide.

2. A method for preparing fat emulsion injection, which is characterized by comprising the following steps:

(1) weighing soybean oil, yolk lecithin, glycerol and oleic acid according to the prescription amount respectively;

(2) preparing a water phase: adding the injection water and glycerol according to the prescription amount, stirring and mixing uniformly, filtering by a filter element with the diameter of 0.22 mu m, adjusting the pH value to 11.0-11.5 by using 0.1mol/L sodium hydroxide solution, keeping the temperature at 60-80 ℃ for later use, and continuously filling nitrogen for protection in the water phase preparation process;

(3) preparation of oil phase: adding soybean oil and oleic acid according to the formula amount, heating to 60-70 ℃, adding egg yolk lecithin, shearing until the solution is clear, and continuously filling nitrogen for protection in the oil phase preparation process;

(4) preparing colostrum: mixing the oil phase and the water phase by a shearing machine, and circularly emulsifying for 1-3 times to obtain primary emulsion;

(5) preparation of refined milk: homogenizing the primary emulsion at 500-700bar under high pressure for 4-7 times to obtain refined milk, and detecting properties, pH value and milk particle of the refined milk; and after the product is qualified, filling, sterilizing, and performing light inspection and packaging.

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a formula of a fat emulsion injection and a preparation method thereof.

Background

The fat emulsion injection is an energy supplement medicine, is mainly suitable for being one of components of intravenous nutrition, provides energy and essential fatty acid for organisms, is used for supplementing energy and essential fatty acid for parenteral nutrition, prevents and treats human essential fatty acid deficiency, and also provides essential fatty acid for patients who cannot maintain and recover normal essential fatty acid level by oral administration. Clinical tests prove that the glycerin fructose injection can achieve better effects on dehydration and intracranial pressure reduction treatment of patients with high intracranial pressure.

Soybean oil is the main nutrient component in the fat emulsion injection, egg yolk lecithin is the commonly used emulsifier of the fat emulsion injection, and the oil phase and the water phase form a stable oil-in-water system through the emulsification of the egg yolk lecithin. The instability of the oil-in-water system can cause the phenomena of demulsification, oil floating, layering and the like, and the safety and the curative effect of the product are influenced. The yolk lecithin is a lipophilic surfactant and has a strong emulsifying effect, but a small amount of floating oil possibly exists in the long-term storage process due to vibration, high temperature and the like, and a small amount of oleic acid is added as an auxiliary emulsifier to improve the stability of the emulsion. Oleic acid can form sodium oleate under the alkaline condition, the emulsifying effect of the sodium oleate is weaker than that of egg yolk lecithin, but the sodium oleate is a hydrophilic surfactant and can be acted together with the egg yolk lecithin in liquid medicine, so that the stability of the fat emulsion oil-in-water system can be greatly improved.

Disclosure of Invention

The invention aims to provide a formula of a fat emulsion injection and a preparation method thereof, so as to improve the long-term stability of the fat emulsion injection.

The fat emulsion injection comprises soybean oil, egg yolk lecithin, glycerol, oleic acid and sodium hydroxide; based on 1000mL of fat emulsion injection, the fat emulsion injection comprises 90-110g of soybean oil, 11-13g of egg yolk lecithin, 20-26g of glycerol and 0.4-0.6g of oleic acid, and the pH value of an aqueous phase is adjusted to 11.0-11.5 by sodium hydroxide.

The preparation method of the fat emulsion injection comprises the following steps:

(1) weighing soybean oil, yolk lecithin, glycerol and oleic acid according to the prescription amount respectively;

(2) preparing a water phase: adding the injection water and glycerol according to the prescription amount, stirring and mixing uniformly, filtering by a filter element with the diameter of 0.22 mu m, adjusting the pH value to 11.0-11.5 by using 0.1mol/L sodium hydroxide solution, keeping the temperature at 60-80 ℃ for later use, and continuously filling nitrogen for protection in the water phase preparation process;

(3) preparation of oil phase: adding soybean oil and oleic acid according to the formula amount, heating to 60-70 ℃, adding egg yolk lecithin, shearing until the solution is clear, and continuously filling nitrogen for protection in the oil phase preparation process;

(4) preparing colostrum: mixing the oil phase and the water phase by a shearing machine, and circularly emulsifying for 1-3 times to obtain primary emulsion;

(5) preparation of refined milk: homogenizing the primary emulsion at 500-700bar under high pressure for 4-7 times to obtain refined milk, and detecting properties, pH value and milk particle of the refined milk; and after the product is qualified, filling, sterilizing, and performing light inspection and packaging.

Tests prove that the fat emulsion injection is more stable under the alkaline condition, the pH value of a water phase is adjusted to 11.0-11.5 by using sodium hydroxide in the prepared fat emulsion injection, the final pH value of an injection obtained after the water phase and an oil phase are emulsified is 8.0-8.5, and the stability of a fat emulsion oil-in-water system can be improved.

Detailed Description

The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention.

Example 1

The raw material feeds are shown in table 1:

TABLE 1

Serial number	Raw materials	The feeding amount is g/1000ml
			1	Soybean oil	100
2	Egg yolk lecithin	12
			3	Glycerol	22.5
4	Oleic acid	0.5
			5	Sodium hydroxide	Proper amount of
6	Water for injection	Is added to 1000

The preparation method comprises the following steps:

1) weighing the soybean oil, the egg yolk lecithin, the glycerol and the oleic acid according to the prescription amount;

2) preparing a water phase: adding the injection water and glycerol according to the prescription amount, stirring and mixing uniformly, filtering by a filter element with the diameter of 0.22 mu m, and respectively adjusting the pH value to 9.0, 10.0, 11.0 and 11.5 by using 0.1mol/L sodium hydroxide solution; keeping the temperature at 80 ℃ for later use, and continuously filling nitrogen for protection in the water phase preparation process;

3) preparation of oil phase: adding soybean oil and oleic acid according to the prescription amount, heating to 70 ℃, adding egg yolk lecithin, shearing until the solution is clear, and continuously filling nitrogen for protection in the oil phase preparation process;

4) preparing colostrum: mixing the oil phase and the water phase with a shearing machine, and circularly emulsifying for 3 times to obtain primary emulsion;

5) preparation of refined milk: homogenizing the primary emulsion at high pressure of 500-700bar for 6 times to obtain refined milk, and detecting properties, pH value and milk particles of the refined milk;

6) after the determination is qualified, filling;

7) and (3) sterilization: 115-121 ℃, and ensuring that the F0 value is more than 12;

8) and (6) inspecting and packaging by using a lamp.

Example 2

The raw material feeds are shown in table 2:

TABLE 2

Serial number	Raw materials	The feeding amount is g/1000ml
			1	Soybean oil	100
2	Egg yolk lecithin	12
			3	Glycerol	22.5
4	Sodium hydroxide	Proper amount of
			5	Water for injection	Is added to 1000

The preparation method comprises the following steps:

1) weighing propofol, soybean oil, egg yolk lecithin, glycerol and oleic acid in the formula amount;

2) preparing a water phase: adding the injection water and glycerol according to the prescription amount, stirring and mixing uniformly, filtering by a filter element with the diameter of 0.22 mu m, and respectively adjusting the pH value to 10.0 by using 0.1mol/L sodium hydroxide; keeping the temperature at 80 ℃ for later use, and continuously filling nitrogen for protection in the water phase preparation process;

3) preparation of oil phase: adding soybean oil and oleic acid according to the prescription amount, heating to 70 ℃, adding egg yolk lecithin, shearing until the solution is clear, and continuously filling nitrogen for protection in the oil phase preparation process;

4) preparing colostrum: mixing the oil phase and the water phase at a certain proportion by a shearing machine, and circularly emulsifying for 3 times to obtain primary emulsion;

5) preparation of refined milk: homogenizing the primary emulsion for 6 times at 500-700bar to obtain refined emulsion, and taking the refined emulsion to detect properties, pH value and emulsion particles;

6) after the determination is qualified, filling;

7) and (3) sterilization: 115-121 ℃, and ensuring that the F0 value is more than 12;

8) and (6) inspecting and packaging by using a lamp.

The results are shown in the following table:

table 3: stability investigation result of fat emulsion injection

From the results of the stability studies in table 3, it can be seen that: the examination is carried out under the high-temperature test condition (60 +/-2 ℃), and the samples are taken for 5, 10 and 30 days; and detecting the appearance. Test results show that the stability of the fat emulsion injection is good in the process of 30-day stability investigation of influencing factors. The stability of the emulsion can be improved and the product quality can be ensured by adopting a proper pH value, formula amount of the stabilizer and preparation process.

The above is only a preferred embodiment of the present invention, and it should be noted that it is possible for those skilled in the art to make various changes and modifications without departing from the inventive concept of the present invention, and these are all protected by the present invention.