Alkaline addition method for affecting stability of fat emulsion and application thereof

Abstract

This invention discloses a method for adding alkali to affect the stability of fat emulsions and its application, belonging to the field of pharmaceutical preparation. Its purpose is to solve the problem of how to influence the stability of fat emulsions. One objective of this application is to provide a method for adding alkali to affect the stability of fat emulsions. This method involves adding sodium hydroxide during the preparation of the oil phase to produce an oil phase, then mixing the oil phase with the aqueous phase and performing post-treatment to obtain the finished fat emulsion injection solution. This application, through improved process flow and experimental verification, has identified a new production process for fat emulsions. Furthermore, this invention divides the sodium hydroxide used in the preparation of the finished fat emulsion injection solution into two parts; this method facilitates the balance between PDI (Polydimethyl ether) and free oil, meeting corresponding application requirements. A second objective of this application is to claim protection for the application of the aforementioned alkali addition method, using this method to influence the stability of fat emulsions, thereby meeting the needs of practical applications.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical preparation preparation, specifically to a method and application of adding alkali to affect the stability of fat emulsions. More specifically, through reasonable control, this application provides a method and application of adding alkali to improve the stability of fat emulsions, which can improve the visual appearance of oil floating in fat emulsions, thereby improving the stability of fat emulsions. Background Technology

[0002] If visible oil floating is observed during the production of fat emulsions, the stability and emulsification degree of the emulsion need to be improved to ensure the stability and reliability of pharmaceutical preparations. The inventors' research has found that, considering various factors, the location of alkali addition during fat emulsion preparation also significantly affects the oil floating phenomenon.

[0003] Currently, there are four main ways to add sodium hydroxide during the production of fat emulsions.

[0004] The preparation process for the first method is as follows:

[0005] (1) Preparation of oil phase: Take one or more of soybean oil, olive oil, medium chain triglycerides, structured triglycerides and fish oil, or add fat-soluble drugs such as propofol, alprostadil, flurbiprofen ester, chlorvidimide, etc., heat to 60-90℃, add egg yolk lecithin, stir and disperse to obtain oil phase;

[0006] (2) Preparation of aqueous phase: Take glycerol, water-soluble substances and sodium hydroxide, add them to an appropriate amount of water for injection, stir to dissolve, and heat to 60℃~90℃ to obtain the aqueous phase;

[0007] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and homogenize several times under a certain pressure using a two-stage high-pressure homogenizer to obtain the emulsion.

[0008] The preparation process for the second method is as follows:

[0009] (1) Preparation of oil phase: Take one or more of soybean oil, olive oil, medium chain triglycerides, structured triglycerides and fish oil, or add lipophilic drugs such as propofol, alprostadil, flurbiprofen ester, chlorvidimide, etc., and heat to 60-90℃ to obtain the oil phase;

[0010] (2) Preparation of aqueous phase: Take glycerol, water-soluble substances and sodium hydroxide, add them to an appropriate amount of water for injection, stir to dissolve, heat to 60℃~90℃, then add egg yolk lecithin, stir to disperse, and the aqueous phase is obtained;

[0011] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and homogenize several times under a certain pressure using a two-stage high-pressure homogenizer to obtain the emulsion.

[0012] The preparation process for the third method is as follows:

[0013] (1) Preparation of oil phase: Take one or more of soybean oil, olive oil, medium chain triglycerides, structured triglycerides and fish oil, or add fat-soluble drugs such as propofol, alprostadil, flurbiprofen ester, chlorvidimide, etc., heat to 60-90℃, add egg yolk lecithin, stir and disperse to obtain oil phase;

[0014] (2) Preparation of aqueous phase: Take glycerol and water-soluble substances, add them to an appropriate amount of water for injection, stir to dissolve, and heat to 60℃~90℃ to obtain the aqueous phase;

[0015] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and homogenize several times under a certain pressure using a two-step high-pressure homogenizer to obtain the emulsion. Then add sodium hydroxide to adjust the pH value.

[0016] The preparation process for the fourth type is as follows:

[0017] (1) Preparation of oil phase: Take one or more of soybean oil, olive oil, medium chain triglycerides, structured triglycerides and fish oil, or add lipophilic drugs such as propofol, alprostadil, flurbiprofen ester, chlorvidimide, etc., and heat to 60-90℃ to obtain the oil phase;

[0018] (2) Preparation of aqueous phase: Take glycerol and water-soluble substances, add them to an appropriate amount of water for injection, stir to dissolve, heat to 60℃~90℃, then add egg yolk lecithin, stir to disperse, and the aqueous phase is obtained;

[0019] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and homogenize several times under a certain pressure using a two-step high-pressure homogenizer to obtain the emulsion. Then add sodium hydroxide to adjust the pH value.

[0020] Of the four preparation methods mentioned above, fat emulsions (including long-chain, medium-chain, fish oil, medium-chain fish oil, multiple oils, and drug-loaded emulsions) use sodium hydroxide to adjust the pH value. Sodium hydroxide is generally added entirely during the preparation of the aqueous phase (i.e., pre-alkali addition process, which adds it during aqueous phase preparation, including glycerol with water for injection). Sometimes, due to changes in raw materials, the pH value of the fat emulsion is measured after homogenization. If the pH value is lower than required, sodium hydroxide is added again to adjust the pH value (i.e., post-alkali addition process, where alkali is added after all homogenization is completed and stirred evenly). However, when using the same raw material again in the next batch, it is still added all at once during the preparation of the aqueous phase. This method of adding alkali has become the industry's established understanding.

[0021] Improving the stability of fat emulsions has always been a pressing need for those skilled in the art. For example, regarding the first preparation method, Chinese patent application CN120437056A discloses a method for preparing a fat emulsion injection, comprising the following steps: S1, under nitrogen protection, dissolving glycerol and a pH adjuster in water for injection, heating, stirring and dispersing to obtain an aqueous phase; S2, under nitrogen protection, dissolving egg yolk lecithin in oil, heating, shearing and stirring to dissolve, obtaining an oil phase; the oil includes soybean oil, the weight ratio of egg yolk lecithin to soybean oil is 3:50, and the temperature of the oil phase is 60-80℃; S3, under nitrogen protection, the oil phase and the aqueous phase are continuously fed into a shearing machine at a weight ratio of 1:2.5 to 1:3.5 to obtain a promulgated emulsion; S4, the promulgated emulsion is first homogenized under high pressure 2-3 times, then water for injection is added to the total volume, and then homogenized under low pressure once to obtain a final emulsion; S5, the final emulsion is filled under low oxygen conditions, filled with nitrogen, capped, and sterilized. The core of this solution lies in using a progressive multi-stage shearing head with a narrow-gap high-pressure design and a teeth-gripping mechanism to shear the colostrum. This multi-stage progressive shearing achieves higher shearing efficiency. The narrow gap and teeth-gripping mechanism create localized high pressure and high shear force. Simultaneously, the multi-stage stator and rotor force the material through the narrow gap step by step, ensuring all particles are uniformly stressed. This efficiently breaks down fat droplets, improves emulsification efficiency, and prevents uneven particle size distribution or large particle residue. This ensures the stability of the colostrum before homogenization and the effectiveness during homogenization, thereby guaranteeing the stability and shelf life of the fat emulsion injection product. Furthermore, the multi-stage progressive shearing achieves high shear force at lower speeds, reducing temperature rise and preventing fat oxidation or protein denaturation, thus ensuring product quality.

[0022] Chinese patent application CN121489870A discloses a method for preparing a C6-24 structured fat emulsion injection. The core of this method is to strictly control residual oxygen and dissolved oxygen during the preparation process to avoid oxidation of unsaturated fatty acids in the structured fat emulsion injection (C6-24), reduce the generation of impurities such as peroxides, aldehydes, and ketones, and improve the safety of medication.

[0023] How to influence the stability of fat emulsions has become an urgent problem to be solved. Summary of the Invention

[0024] The purpose of this invention is to provide a method and application for adding alkali to improve the stability of fat emulsions, thereby addressing the problem of further impacting the stability of fat emulsions.

[0025] To achieve the above objectives, this application adopts the following technical solution.

[0026] A method for adding alkali to affect the stability of fat emulsion involves adding sodium hydroxide during the preparation of the oil phase, then mixing and stirring the prepared oil phase with the aqueous phase to form a primary emulsion, and then performing post-treatment on the primary emulsion to obtain the finished fat emulsion injection solution.

[0027] Includes the following steps:

[0028] (1) Preparation of oil phase: Heat the oily substance to 60℃-90℃, stir and disperse it, add sodium hydroxide while stirring, and stir evenly to obtain the oil phase;

[0029] (2) Aqueous phase preparation;

[0030] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and then homogenize to obtain the colostrum.

[0031] The oily substance is one or more of soybean oil, olive oil, medium-chain triglycerides, structured triglycerides, and fish oil.

[0032] Take an oily substance, add egg yolk lecithin to it, heat it to 60℃-90℃, stir and disperse it, then add sodium hydroxide while stirring, and stir evenly to obtain the oil phase.

[0033] Take an oily substance, add a fat-soluble drug to the oily substance, heat to 60℃-90℃, stir to disperse, add sodium hydroxide while stirring, and stir evenly to obtain the oil phase.

[0034] The lipid-soluble drug is one or more of propofol, alprostadil, flurbiprofen ester, and chlorpropamide.

[0035] In step (1), the oil is heated to 60℃-90℃, stirred and dispersed, and sodium hydroxide is added while stirring. The flow rate of sodium hydroxide is controlled to avoid boiling due to excessive dilution, and to avoid temperature changes affecting the stability of the oil phase. After stirring evenly, the oil phase is obtained.

[0036] In step (2) of the aqueous phase preparation, sodium hydroxide is not added.

[0037] The process of preparing the aqueous phase in step (2) is as follows: Take glycerol and water-soluble substances in the prescription (i.e., water-soluble substances; the components in the prescription will affect the isotonic and isotonic properties of the fat emulsion. Based on the isotonic and isotonic requirements of the final fat emulsion, determine whether to add and what kind of water-soluble substances to add), add them to water for injection, stir to dissolve, and heat to 60℃~90℃ to obtain the aqueous phase.

[0038] In step (3), the oil phase prepared in step (1) is mixed and stirred with the aqueous phase prepared in step (2), and then water for injection is added to the prepared amount. After homogenization by a high-pressure homogenizer, the colostrum is obtained.

[0039] In step (3), the colostrum is post-processed to obtain the fat emulsion injection product. The post-processing process is as follows: the colostrum is filled into a bottle, nitrogen is then added to the bottle, and the bottle is capped, sealed, and sterilized to obtain the fat emulsion injection product.

[0040] In step (3), the oil phase prepared in step (1) is mixed and stirred with the aqueous phase prepared in step (2), and then water for injection is added to the prepared amount. After homogenization, sodium hydroxide is added to adjust the pH value according to the pH value requirements to obtain the colostrum.

[0041] The total mass of sodium hydroxide used to prepare the fat emulsion injection is denoted as M0. The sodium hydroxide is divided into two parts: one part is used for the preparation of the oil phase in step (1), and the mass of sodium hydroxide used for the preparation of the oil phase is 10%-90% of the total mass of sodium hydroxide M0; the remaining part is used to adjust the pH value after homogenization in step (3), and the mass of sodium hydroxide used to adjust the pH value after homogenization in step (3) is 10%-90% of the total mass of sodium hydroxide M0.

[0042] In step (1), sodium hydroxide aqueous solution or sodium hydroxide solid is added while stirring.

[0043] In step (1), the mass of sodium hydroxide added to each liter of oil phase is ≤0.06g;

[0044] Alternatively, in step (1), an aqueous solution of sodium hydroxide is added while stirring. The concentration of the aqueous solution of sodium hydroxide is 0.3-1.2 mol / L, and the amount of sodium hydroxide added per liter of oil phase is ≤0.0015 mol.

[0045] The aforementioned alkali addition method was applied to affect the stability of fat emulsions.

[0046] To address the aforementioned problems, this invention provides a method for adding alkali to improve the stability of fat emulsions and its application. One objective of this application is to provide a method for adding alkali to improve the stability of fat emulsions. This method involves adding sodium hydroxide during the oil phase preparation process to prepare an oil phase, then mixing the oil phase with an aqueous phase and performing post-processing to obtain the finished fat emulsion injection solution. This application has identified a new production process for fat emulsions through improved process flow and experimental verification. Preferably, this application can also add egg yolk lecithin to the oily substances, then heat the mixture, and then add sodium hydroxide to prepare the corresponding oil phase; the finished fat emulsion injection solution is then prepared based on the prepared oil phase.

[0047] Furthermore, this invention divides the sodium hydroxide used in preparing the fat emulsion injection into two parts: one part is used for the oil phase preparation in step (1), and the remaining part is used for adjusting the pH value after homogenization in step (3). The maximum amount of sodium hydroxide added per liter of oil phase is 0.06 g; taking a 1 mol / L sodium hydroxide aqueous solution as an example, the maximum amount added per liter of oil phase is 1.5 ml of sodium hydroxide. This method facilitates the balance between PDI and non-bleaching oil, meeting the corresponding application requirements.

[0048] The second objective of this application is to claim protection for the application of the aforementioned alkali addition method, which is used to affect the stability of fat emulsions, thereby meeting the needs of practical applications. Attached Figure Description

[0049] The present invention will be described by way of example and with reference to the accompanying drawings, wherein:

[0050] Figure 1 This is a schematic diagram of the overall structure of the preparation device in Example 1.

[0051] The diagram is labeled as follows: 1. Glycerin tank, 2. First chemical pump, 3. Filter tank, 4. Second chemical pump, 5. Oil tank, 6. Third chemical pump, 7. Colostrum tank, 8. Homogenizer, 9. Fourth chemical pump, 10. Homogenizer, 11. Filling tank, 12. Filling equipment. Detailed Implementation

[0052] All features disclosed in this specification, or steps in all methods or processes disclosed herein, may be combined in any way, except for mutually exclusive features and / or steps.

[0053] Any feature disclosed in this specification, unless otherwise stated, may be replaced by other equivalent or similar features. That is, unless otherwise stated, each feature is merely one example of a series of equivalent or similar features.

[0054] In this embodiment of the invention, the sodium hydroxide added during oil phase preparation can be either solid sodium hydroxide or an aqueous solution of sodium hydroxide. When adding an aqueous solution of sodium hydroxide, the concentration of the aqueous solution is 0.3-1.2 mol / L, and the upper limit of sodium hydroxide added per liter of oil phase is 0.0015 mol. When adding the aqueous solution of sodium hydroxide in step (1) of oil phase preparation, the aqueous solution of sodium hydroxide should be added under stirring, and the flow rate of the aqueous solution of sodium hydroxide should be controlled to avoid excessive dilution leading to boiling, and at the same time to avoid temperature changes affecting the stability of the oil phase.

[0055] The device used in this embodiment is as follows: Figure 1 As shown, the apparatus includes a glycerin tank, a first chemical pump, a filtration tank, a second chemical pump, an oil tank, a third chemical pump, a colostrum tank, a homogenizing tank, a fourth chemical pump, a homogenizer, a filling tank, and filling equipment. The glycerin tank is used for stirring and heating glycerin and water-soluble substances; the oil tank is used for stirring and heating oily substances; the colostrum tank is used to temporarily store the prepared colostrum; the homogenizing tank is used to temporarily store the material processed by the homogenizer; the filling tank is used to temporarily store the material to be filled; and the filling equipment is used to fill the material in the filling tank. The glycerin tank is connected to the colostrum tank via a pipeline, and a first chemical pump is installed on the pipeline connecting the glycerin tank and the colostrum tank. The filtration tank is connected to the oil tank via a pipeline, and a second chemical pump is installed on the pipeline connecting the filtration tank and the oil tank. The oil tank is connected to the colostrum tank via a pipeline, and a third chemical pump is installed on the pipeline connecting the oil tank and the colostrum tank. The colostrum tank is connected to the homogenizing tank via a pipeline, and the material in the colostrum tank can flow between the colostrum tank and the homogenizing tank. The homogenizing tank and the homogenizer form a circulation loop via pipelines, and a fourth chemical pump is installed on the pipeline connecting the homogenizing tank and the homogenizer. The material in the homogenizing tank can be pumped into the homogenizer for homogenization and then returned to the homogenizing tank. The colostrum tank is connected to the filling tank via a pipeline, and the filling tank is connected to the filling equipment via a pipeline.

[0056] The process of preparing fat emulsion using this device is as follows: (1) The oil (i.e., oily substances) is filtered by a vacuum filter tank and then sent to an oil tank; (2) In the oil tank, the oil is stirred and heated, and then egg yolk lecithin and sodium hydroxide are added to form an oil phase; (3) Glycerin and water-soluble substances in the prescription are added to a glycerin tank, and stirred and heated in the glycerin tank, and then filtered and sent to a colostrum tank, and a portion of water for injection is added to the colostrum tank to form an aqueous phase; then, the oil phase is sent to the colostrum tank to form a colostrum; then, the colostrum is homogenized several times between the colostrum tank and the homogenizing tank (homogenization pressure 800 bar-80 bar), and finally sent to a filling tank; when the fat emulsion particles and pH adjustment in the filling tank are qualified, it is filled by the filling equipment.

[0057] Example 1

[0058] This embodiment provides a nutritional fat emulsion, the preparation process of which is as follows.

[0059] (1) Preparation of oil phase: Take 10g soybean oil and 10g fish oil, mix them, heat to 60℃, add 1.2g egg yolk lecithin, stir to disperse, add 0.8mL 1.0ml sodium hydroxide while stirring, stir evenly to obtain the oil phase.

[0060] (2) Preparation of aqueous phase: Take 2.5g of glycerol, add it to 20mL of water for injection, stir to dissolve, and heat to 60℃ to obtain the aqueous phase.

[0061] (3) Mixing and homogenization: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize. Adjust the pH value to 8.5 with 1.0 mL / L sodium hydroxide to obtain the colostrum. Fill the colostrum into bottles, fill the bottles with nitrogen, stopper, cap, and sterilize to obtain the finished fat emulsion injection solution.

[0062] Example 2

[0063] This embodiment provides a nutritional fat emulsion, the preparation process of which is as follows.

[0064] (1) Preparation of oil phase: Take 10g soybean oil and 10g medium chain triglycerides, mix them, heat to 60℃, add 1.2g egg yolk lecithin, stir and disperse, add 1.0mL 1.0ml sodium hydroxide while stirring, stir evenly to obtain the oil phase.

[0065] (2) Preparation of aqueous phase: Take 2.5g of glycerol, add it to 20mL of water for injection, stir to dissolve, and heat to 60℃ to obtain the aqueous phase.

[0066] (3) Mixing and homogenization: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize. Adjust the pH value to 7.5 with 1.0 mL / L sodium hydroxide to obtain the colostrum. Fill the colostrum into bottles, fill the bottles with nitrogen, stopper, cap, and sterilize to obtain the finished fat emulsion injection solution.

[0067] Example 3

[0068] This embodiment provides a drug-loaded fat emulsion, the preparation process of which is as follows.

[0069] (1) Preparation of oil phase: Take 5g soybean oil, 5g medium chain triglycerides and 1g propofol, mix them, heat to 60℃, then add 1.2g egg yolk lecithin, stir and disperse, then add 1mL 1.0ml sodium hydroxide while stirring, stir evenly and the oil phase is obtained.

[0070] (2) Preparation of aqueous phase: Take 2g of glycerol, add it to 20mL of water for injection, stir to dissolve, and heat to 60℃ to obtain the aqueous phase.

[0071] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize to obtain the colostrum. Fill the colostrum into a bottle, fill the bottle with nitrogen, stopper, cap, and sterilize to obtain the fat emulsion injection product.

[0072] Example 4

[0073] This embodiment provides a drug-loaded fat emulsion, the preparation process of which is as follows.

[0074] (1) Preparation of oil phase: Take 5g soybean oil, 5g olive oil and 0.73g aprepitant and mix them. Heat to 60℃ and then add 1.95g egg yolk lecithin. After stirring and dispersing, add 0.8mL of 1.0mL sodium hydroxide while stirring. After stirring evenly, the oil phase is obtained.

[0075] (2) Preparation of aqueous phase: Take 1g of glycerol and 5.4g of sucrose, add them to 30mL of water for injection, stir to dissolve, and heat to 70℃ to obtain the aqueous phase.

[0076] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize to obtain the colostrum. Fill the colostrum into a bottle, fill the bottle with nitrogen, stopper, cap, and sterilize to obtain the fat emulsion injection product.

[0077] Example 5

[0078] To determine the visual oil-shedding properties of the prepared fat emulsion, the following comparative experiment was conducted.

[0079] (1) Preparation of oil phase: Take 5g soybean oil and 5g medium chain triglycerides, mix them, heat to 60℃, stir and disperse, add the set amount of 1mol / L sodium hydroxide aqueous solution under stirring (the set amount is shown in Table 1 below), stir evenly and the oil phase is obtained.

[0080] (2) Preparation of aqueous phase: Take 2g of glycerol, add it to 25mL of water for injection, stir to dissolve, and heat to 65℃ to obtain the aqueous phase.

[0081] (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize to obtain the colostrum. Fill the colostrum into a bottle, fill the bottle with nitrogen, stopper, cap, and sterilize to obtain the fat emulsion injection product.

[0082] Each batch consisted of 242 bottles, and the experimental results are shown in Table 1 below.

[0083] Experimental results show that adding sodium hydroxide to the oil phase in this invention can improve the appearance of fat emulsions by visually removing excess oil, thereby improving the stability of the fat emulsion.

[0084] Table 1. Set values ​​and measurement results for Example 5

[0085]

[0086] Example 6

[0087] In this embodiment, the sodium hydroxide used to prepare the fat emulsion injection solution is divided into two parts. One part is used for the preparation of the oil phase in step (1), and the remaining part is used to adjust the pH value after homogenization in step (3). The proportions are shown in Table 2, and the specific preparation process is as follows. In this embodiment, 1 mol / L sodium hydroxide is used, and the total amount is 1 mL.

[0088] (1) Preparation of oil phase: Take 5g of soybean oil and 5g of medium chain triglycerides, mix them, heat to 60℃, stir and disperse, add the set amount of 1mol / L sodium hydroxide aqueous solution under stirring (the set amount is shown in Table 2 below), stir evenly and the oil phase is obtained.

[0089] (2) Preparation of aqueous phase: Take 2g of glycerol, add it to 25mL of water for injection, stir to dissolve, and heat to 65℃ to obtain the aqueous phase.

[0090] (3) Mixing and homogenization: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to 100 mL, and then homogenize. Add sodium hydroxide to adjust the pH value (the amount of sodium hydroxide added is shown in Table 2) to obtain the colostrum. Fill the colostrum into bottles, fill the bottles with nitrogen, stopper, cap, and sterilize to obtain the finished fat emulsion injection solution.

[0091] The experimental results are shown in Table 2. Among them, PDI is a dimensionless value reflecting the particle size distribution width, ranging from 0 to 1. The smaller the value, the more uniform the particle size, the more concentrated the particle size distribution, and the more stable the emulsion.

[0092] According to Table 2, it can be seen that in step (3), adding sodium hydroxide after homogenization can improve the consistency of emulsion particles (PDI) level, making D10, D50 and D95 ​​more similar, which can improve the stability of fat emulsion.

[0093] Table 2. Set values ​​and measurement results for Example 6

[0094]

[0095] This invention is not limited to the specific embodiments described above. The invention extends to any new feature or combination disclosed in this specification, as well as any new method or process step or combination disclosed herein.

Claims

1. A method for adding alkali that affects the stability of fat emulsions, characterized in that, Sodium hydroxide is added during the preparation of the oil phase. The prepared oil phase is then mixed and stirred with the aqueous phase to form a primary emulsion. The primary emulsion is then post-treated to obtain the finished fat emulsion injection solution.

2. The method for adding alkali to affect the stability of fat emulsion according to claim 1, characterized in that, Includes the following steps: (1) Preparation of oil phase: Heat the oily substance to 60℃-90℃, stir and disperse it, add sodium hydroxide while stirring, and stir evenly to obtain the oil phase; (2) Aqueous phase preparation; (3) Mixing and homogenizing: After mixing and stirring the oil phase prepared in step (1) and the aqueous phase prepared in step (2), add water for injection to the prepared amount, and then homogenize to obtain the colostrum.

3. The method for adding alkali to affect the stability of fat emulsion according to claim 2, characterized in that, The oily substance is one or more of soybean oil, olive oil, medium-chain triglycerides, structured triglycerides, and fish oil.

4. The method for adding alkali to affect the stability of fat emulsion according to claim 2, characterized in that, Take an oily substance, add egg yolk lecithin to it, heat it to 60℃-90℃, stir and disperse it, then add sodium hydroxide while stirring, and stir evenly to obtain the oil phase.

5. The method for adding alkali to affect the stability of fat emulsion according to claim 2, characterized in that, Take an oily substance, add a fat-soluble drug to the oily substance, heat to 60℃-90℃, stir to disperse, add sodium hydroxide while stirring, and stir evenly to obtain the oil phase.

6. The method for adding alkali to affect the stability of fat emulsion according to any one of claims 2-5, characterized in that, In step (3), the oil phase prepared in step (1) is mixed and stirred with the aqueous phase prepared in step (2), and then water for injection is added to the prepared amount. After homogenization, sodium hydroxide is added to adjust the pH value according to the pH value requirements to obtain the colostrum.

7. The method for adding alkali to affect the stability of fat emulsion according to claim 6, characterized in that, The total mass of sodium hydroxide used to prepare the fat emulsion injection is denoted as M0. The sodium hydroxide is divided into two parts: one part is used for the preparation of the oil phase in step (1), and the mass of sodium hydroxide used for the preparation of the oil phase is 10%-90% of the total mass of sodium hydroxide M0; the remaining part is used to adjust the pH value after homogenization in step (3), and the mass of sodium hydroxide used to adjust the pH value after homogenization in step (3) is 10%-90% of the total mass of sodium hydroxide M0.

8. The method for adding alkali to affect the stability of fat emulsion according to claim 2, characterized in that, In step (1), the mass of sodium hydroxide added to each liter of oil phase is ≤0.06g; Alternatively, in step (1), an aqueous solution of sodium hydroxide is added while stirring. The concentration of the aqueous solution of sodium hydroxide is 0.3-1.2 mol / L, and the amount of sodium hydroxide added per liter of oil phase is ≤0.0015 mol.

9. The application of the alkali addition method according to any one of claims 1-8, characterized in that, This method was used to influence the stability of fat emulsions.

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