Preparation method of C6-24 structure fat emulsion injection

Abstract

The invention discloses a preparation method of a fat emulsion injection with a C6-24 structure. According to the method, residual oxygen and dissolved oxygen are strictly controlled in the preparation process, unsaturated fatty acid in the structural fat emulsion injection (C6-24) is prevented from being oxidized, impurities such as peroxides, aldehydes and ketones are reduced, and the medication safety is improved; by controlling the flow rate of oil-water mixing, the emulsifying effect is improved, the uniformity of emulsion particles is improved, and the long-term stability of the injection is effectively ensured, so that the product quality is good.

Description

Technical Field

[0001] This invention belongs to the field of injection preparation technology, specifically relating to a structural fat emulsion injection (C 6~24 ) and its preparation method. Background Technology

[0002] Structured fat emulsion injection (C 6~24 As an important component of parenteral nutrition mixtures, fat emulsions are administered intravenously to provide energy and essential fatty acids to adult patients with difficulty eating. Based on the carbon chain length and saturation level of fatty acids, commonly used parenteral nutrition fat emulsions in clinical practice are mainly classified into five categories: long-chain fat emulsions, medium / long-chain fat emulsions, fish oil fat emulsions, structured fat emulsions, and multi-oil fat emulsions. Structured fat emulsion injections (C...) 6~24 The main component is a structured triglyceride, a mixture formed by the chemical reaction of equimolar amounts of long-chain and medium-chain triglycerides. It provides linoleic acid and linolenic acid through long-chain fatty acids to prevent essential fatty acid deficiency, and provides energy through the metabolic substrates of long-chain and medium-chain fatty acids. Developed by Fresenius Kabi AB, this product was first launched in Sweden in 1998 and approved for import into China in 2006 under the brand name "Structolipid".

[0003] Fat emulsion injections typically contain unsaturated fatty acids, which are prone to oxidation upon contact with air during use, generating peroxides, aldehydes, ketones, and other oxidative impurities, leading to lesions in multiple organs, including the nervous system, cardiovascular system, and liver. Furthermore, during long-term storage, high temperatures, oxygen, and light exposure can accelerate emulsion particle aggregation, increasing the risk of vascular embolism. Existing fat emulsion injections suffer from particle size changes during stability maintenance and are prone to oxidation, increasing the risk of adverse drug reactions and reducing treatment safety. To address these issues, this invention provides a structural fat emulsion injection (C... 6~24 The preparation method involves controlling the nitrogen replacement operation and oil-water mixing flow rate of the preparation system to obtain a structured fat emulsion injection (C). 6~24 The quality is stable and the safety is consistent. Summary of the Invention

[0004] To overcome the limitations of existing technologies for structural fat emulsion injections (C 6~24 To address the issues of poor stability and harm to patient health, this invention provides a structured fat emulsion injection (C... 6~24 The preparation method improves stability, ensures drug safety, and features a simple preparation process, low cost, and ease of industrial production.

[0005] The structured fat emulsion injection (C) 6~24 The preparation method includes the following steps: Open the main nitrogen valve to purge the chemical tank and system pipelines with nitrogen.

[0006] Add water for injection to the aqueous phase tank, heat, add glycerol (for injection) and stir until well mixed, then add 1 mol / L sodium hydroxide solution to adjust the pH value.

[0007] Add the structured triglyceride to the oil phase tank, heat, add egg yolk lecithin (for injection), and shear the solution until clear.

[0008] The oil phase and water phase are mixed by an emulsification pump and pumped into transfer tank I. After being brought to the prepared volume, the primary emulsion is circulated and emulsified between transfer tank I and the primary emulsion tank, with nitrogen protection throughout the process.

[0009] The colostrum is homogenized by circulating between the transfer tank I and the colostrum tank using a homogenizer, with nitrogen continuously introduced during the feeding process.

[0010] The drug solution was subjected to intermediate determination, filtered, and then filled and sterilized.

[0011] After nitrogen purging of the dosing tank and system pipelines, the residual oxygen is ≤1%.

[0012] The heating temperature of the aqueous phase tank is 70℃~90℃, and the pH value of the aqueous phase is adjusted to 10.4~11.0.

[0013] The oil phase tank is heated to a temperature of 70℃~90℃ and the oil phase tank is sheared for 2 hours.

[0014] During the preparation of the colostrum, the flow meter parameters for the oil phase and water phase were controlled (water phase flow rate setpoint: 1835.0 kg / h, oil phase flow rate setpoint: 270.0 kg / h), the emulsification was performed 3 times, and the dissolved oxygen in the colostrum was ≤1000 ppb.

[0015] Homogenization pressure and number of cycles: secondary pressure 120 bar, primary pressure 300 bar, homogenization 3 times; secondary pressure 120 bar, primary pressure 700 bar, homogenization 5 times, dissolved oxygen in the drug solution ≤1000 ppb.

[0016] The residual oxygen in the sterilization process control cabinet is ≤1%, and the sterilization conditions are 121℃×12min.

[0017] This invention avoids the problems associated with structural fat emulsion injections (C) by strictly controlling residual oxygen and dissolved oxygen during the preparation process. 6~24 The oxidation of unsaturated fatty acids in the solution reduces the production of impurities such as peroxides, aldehydes, and ketones, thus improving medication safety. Furthermore, by controlling the flow rate of the oil-water mixture, the emulsification effect is improved, the uniformity of the emulsion particles is enhanced, and the long-term stability of the injection solution is effectively guaranteed. These advantages contribute to the high quality of the product of this invention. Detailed Implementation

[0018] To better understand and implement this invention, specific embodiments of the invention will be described below. It should be noted that the embodiments described below are exemplary and are only used to explain the invention, and should not be construed as limiting the invention. Example 1

[0019] The structural fat emulsion injection (C) of this embodiment 6~24 The prescription is as follows:

[0020] The structural fat emulsion injection (C) of this embodiment 6~24 The preparation method is as follows: Open the main nitrogen valve to purge the dosing tank and system pipelines with nitrogen until the residual oxygen level is ≤1%.

[0021] Add water for injection to the aqueous phase tank, heat to 70℃~90℃, add the prescribed amount of glycerol (for injection) and stir to mix well, then add 1 mol / L sodium hydroxide solution to adjust the pH to 10.5.

[0022] Add the structured triglyceride to the oil phase tank, heat to 70℃~90℃, add egg yolk lecithin (for injection), shear for 2 hours, and clarify for later use.

[0023] Control the flow meter parameters of the oil phase and water phase (water phase flow setpoint: 1835.0 kg / h, oil phase flow setpoint: 270.0 kg / h). The oil phase and water phase are mixed by the emulsification pump and pumped into the transfer tank I. After being brought to the prepared volume, the primary emulsion is circulated and emulsified 3 times between the transfer tank I and the primary emulsion tank. Nitrogen protection is maintained throughout the process, and the dissolved oxygen is controlled to be ≤1000 ppb.

[0024] The colostrum is homogenized by circulating between the transfer tank I and the colostrum tank using a homogenizer. The secondary pressure is 120 bar, the primary pressure is 300 bar, and the homogenization is repeated 3 times. The secondary pressure is 120 bar, the primary pressure is 700 bar, and the homogenization is repeated 5 times. Nitrogen gas is continuously introduced during the feeding process to control the dissolved oxygen in the drug solution to ≤1000 ppb.

[0025] The liquid medicine was tested for intermediates, filtered, and then filled. The product was sterilized at 121℃ for 12 minutes, and the residual oxygen in the sterilization cabinet was controlled to be ≤1%.

[0026] Three batches of structured fat emulsion injection (C) prepared in the example were used. 6~24 The samples were stored under accelerated conditions (40℃±2℃, 25%±5%) for 6 months, and then their properties, milk particles, peroxide value, and methoxyaniline value were tested. The results are shown in Table 1. Table 1

[0027] Three batches of structured fat emulsion injections (C) prepared in the examples6~24 The sample was stored under accelerated conditions (40℃±2℃, 25%±5%) for 6 months, and there were no significant changes in milk particles, peroxide value, and methoxyaniline value.

[0028] By controlling the nitrogen purging operation and oil-water mixing flow rate of the formulation system, the structure of the fat emulsion injection (C) was improved. 6~24 The stability of the structured fat emulsion injection (C) was improved. 6~24 The product quality of the product is thus demonstrated. Therefore, the present invention is feasible, and the structural fat emulsion injection (C) it provides is effective. 6~24 The preparation method has the characteristics of good stability, simple preparation process and low cost, which makes it easy to industrialize.

[0029] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A type of C 6~24 A method for preparing a structured fat emulsion injection, characterized in that, Includes the following steps: (1) Open the main nitrogen valve to purge the dosing tank and system pipelines with nitrogen; (2) Add water for injection to the aqueous phase tank, heat, add glycerol and stir to mix, and add 1 mol / L sodium hydroxide solution to adjust the pH value; (3) Add structured triglycerides to the oil phase tank, heat, add egg yolk lecithin, and shear the solution until clear; (4) The oil phase and water phase are mixed by an emulsification pump and pumped into a transfer tank. After being brought to the prepared volume, the primary emulsion is circulated between the transfer tank and the primary emulsion tank for emulsification, with nitrogen protection throughout the process. (5) The colostrum is homogenized by a homogenizer between the transfer tank and the colostrum tank, and nitrogen is continuously introduced during the feeding process; (6) The drug solution is subjected to intermediate determination, filtered, and then filled and sterilized.

2. The preparation method according to claim 1, characterized in that, After nitrogen purging of the dosing tank and system pipelines, the residual oxygen is ≤1%.

3. The preparation method according to claim 1, characterized in that, The heating temperature of the aqueous phase tank is 70℃~90℃, and the pH value of the aqueous phase is adjusted to 10.4~11.

0.

4. The preparation method according to claim 1, characterized in that, The oil phase tank is heated to a temperature of 70℃~90℃ and the oil phase tank is sheared for 2 hours.

5. The preparation method according to claim 1, characterized in that, During the preparation of the colostrum, the flow meter parameters for the oil and water phases were controlled as follows: water phase flow rate setpoint: 1835.0 kg / h; oil phase flow rate setpoint: 270.0 kg / h; emulsification was performed 3 times; and the dissolved oxygen in the colostrum was ≤1000 ppb.

6. The preparation method according to claim 1, characterized in that, Homogenization pressure and number of cycles: secondary pressure 120 bar, primary pressure 300 bar, homogenization 3 times; secondary pressure 120 bar, primary pressure 700 bar, homogenization 5 times, dissolved oxygen in the drug solution ≤1000 ppb.

7. The preparation method according to claim 1, characterized in that, The residual oxygen in the sterilization process control cabinet is ≤1%, and the sterilization conditions are 121℃×12min.

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