Preparation method of fat emulsion

Abstract

The embodiment of the invention discloses a fat emulsion preparation method, which comprises: (1) oil phase preparation: taking grease, and heating to obtain an oil phase; (2) preparing a water phase, namely heating water for injection, glycerol and a part of sodium hydroxide in the prescription to obtain the water phase; (3) preparing primary emulsion: mixing and shearing the oil phase and the water phase in proportion to obtain an oil-water mixed phase, circularly shearing uniformly, and filtering to obtain relatively stable primary emulsion; (4) front low-pressure homogenization: homogenizing the primary emulsion to obtain stable primary emulsion; (5) high-pressure homogenization: homogenizing the stable primary emulsion to obtain stable finished emulsion; (6) post-low-pressure homogenization: homogenizing the finished milk to obtain final milk; and (7) adding the residual sodium hydroxide in the prescription: adding the residual sodium hydroxide in the prescription into the final emulsion, and uniformly stirring to obtain the full-prescription fat emulsion.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a method for preparing a fat emulsion. Background Technology

[0002] Fat emulsion injections have been used clinically since the 1960s. They are one of the body's energy sources during parenteral nutrition and provide essential fatty acids. Fat emulsion injections include various types, such as structured fat emulsions (C...). 6～24 ), medium / long chain fat emulsion injection, fat emulsion injection (C 14～24 ), multiple oil fat emulsion injection (C 6～24 ), long-chain fat emulsion injection (OO) and ω-3 fish oil fat emulsion injection.

[0003] To meet the quality requirements of fat emulsions, sodium oleate is typically added as a co-emulsifier in addition to emulsifiers during the preparation process. Sodium oleate, as a sodium salt of fatty acids, is an anionic surfactant that plays a co-emulsifying role in fat emulsion preparation, promoting particle size uniformity. Furthermore, sodium oleate also acts as a potential regulator, helping fat emulsion particles maintain a high potential charge during long-term storage, making it less prone to droplet aggregation. This overcomes the problems of poor emulsification and excessive large droplets in fat emulsion injections.

[0004] However, adding sodium oleate to fat emulsion injections can easily lead to potential safety risks, such as hemolysis and venous inflammation. If sodium oleate is not added to the formulation, the emulsification effect will be reduced, resulting in surface oil floating and large, substandard emulsion particles in the finished product. Increasing the amount of sodium hydroxide to raise the pH of the fat emulsion can improve its stability to some extent and reduce oil floating in the finished product. However, if the method or amount of sodium hydroxide addition is inappropriate, it can lead to a higher level of free fatty acids in the product, bringing new potential risks. Furthermore, when the percentage of fat globules greater than five micrometers (PFAT5) exceeds 0.05% of the oil phase volume of the fat emulsion, fat embolism is easily caused after intravenous infusion. Summary of the Invention

[0005] In view of this, the object of the present invention is to provide a method for preparing a fat emulsion. A first aspect of the present invention provides a method for preparing a fat emulsion without adding the co-emulsifier sodium oleate. By adjusting the method of separately adding NaOH, and the filtration and homogenization conditions, the phenomena of oil floating on the surface of the fat emulsion and large, unqualified emulsion particles can be avoided, while simultaneously reducing the free fat emulsion content. A second aspect of the present invention provides a method for preparing a fat emulsion that is applicable to the preparation of different types of fat emulsions.

[0006] This invention provides a method for preparing a fat emulsion, which includes the following steps:

[0007] (1) Preparation of oil phase: Take oil and heat it to obtain oil phase;

[0008] (2) Preparation of aqueous phase: Take water for injection, glycerol and a portion of sodium hydroxide from the prescription, heat them to obtain the aqueous phase;

[0009] (3) Preparation of primary emulsion: The oil phase and the water phase are mixed and sheared in a certain proportion to obtain an oil-water mixed phase. After uniform shearing by circulation, a relatively stable primary emulsion is obtained by filtration.

[0010] (4) Low-pressure homogenization: Homogenize the colostrum to obtain a stable colostrum;

[0011] (5) High-pressure homogenization: Homogenize the stable colostrum to obtain a stable emulsion;

[0012] (6) Post-low pressure homogenization: Homogenize the emulsion to obtain the final emulsion;

[0013] (7) Add the remaining sodium hydroxide in the prescription: Add the remaining sodium hydroxide in the prescription to the final emulsion, stir well, and obtain the fat emulsion of the full prescription.

[0014] In some embodiments, the oil may be selected from structured triglycerides or soybean oil.

[0015] In some embodiments, the amount of sodium hydroxide used in step (2) is 50%-90%, 55%-85%, 60%-80%, 65%-75%, 70%-80%, 70%-90% of the total amount of sodium hydroxide in the formulation, or any single value or subrange thereof.

[0016] In some embodiments, the amount of sodium hydroxide in the remaining portion of step (7) is 10%-50%, 15%-45%, 20%-40%, 25%-35%, 30%-40%, 40%-50%, or any single value or subrange thereof, of the total amount of sodium hydroxide in the formulation.

[0017] The total amount of sodium hydroxide in the formulation can be determined based on the amount of fat emulsion prepared. In some embodiments, the total amount of sodium hydroxide in the formulation may be 0.75-1.5 mmol of sodium hydroxide per 1 L of preparation. In some embodiments, the total amount of sodium hydroxide in the formulation may be 0.8-1.4 mmol of sodium hydroxide per 1 L of preparation. In some embodiments, the total amount of sodium hydroxide in the formulation may be 0.9-1.3 mmol of sodium hydroxide per 1 L of preparation. In some embodiments, the total amount of sodium hydroxide in the formulation may be 1.0-1.2 mmol of sodium hydroxide per 1 L of preparation. In some embodiments, the total amount of sodium hydroxide in the formulation may be 1.1-1.3 mmol of sodium hydroxide per 1 L of preparation.

[0018] In some embodiments, the preparation method further includes adding lecithin in step (1). In some embodiments, the preparation method further includes adding lecithin in step (2).

[0019] In some embodiments, the mass ratio of oil to water in step (3) is 1:(2-4), 1:(2.5-4), 1:(2.5-3.5), 1:(3-4), 1:(3.5-4), or any single value or subrange thereof.

[0020] In some embodiments, the pore size of the filter used in step (3) is 1-5 μm, 2-5 μm, 3-5 μm, 4-5 μm, 2-4 μm, or any single value or subrange thereof. In some embodiments, the filter is made of polypropylene or polyethersulfone.

[0021] In some embodiments, the homogenization temperature of the pre-low-pressure homogenization in step (4) includes 50-70°C, 55-70°C, 60-70°C, 55-65°C, or any single value or sub-range thereof. In some embodiments, the number of homogenization cycles for the pre-low-pressure homogenization includes 1-2 cycles. In some embodiments, the homogenization pressure for the pre-low-pressure homogenization is 50-200 bar for the primary valve and 20-50 bar for the secondary valve. In some embodiments, the homogenization pressure for the pre-low-pressure homogenization is 100-150 bar for the primary valve and 20-40 bar for the secondary valve. In some embodiments, the homogenization pressure for the pre-low-pressure homogenization is 150-200 bar for the primary valve and 30-50 bar for the secondary valve.

[0022] In some embodiments, the homogenization temperature in step (5) includes 50-70°C, 55-70°C, 60-70°C, 55-65°C, or any single value or sub-range thereof. In some embodiments, the number of homogenization cycles in the high-pressure homogenization includes 3-6 cycles, 4-6 cycles, 5-6 cycles, 3-5 cycles, or any single value or sub-range thereof. In some embodiments, the homogenization pressure in the high-pressure homogenization is 300-600 bar for the primary valve and 30-70 bar for the secondary valve. In some embodiments, the homogenization pressure in the high-pressure homogenization is 350-550 bar for the primary valve and 40-60 bar for the secondary valve. In some embodiments, the homogenization pressure in the high-pressure homogenization is 400-500 bar for the primary valve and 40-50 bar for the secondary valve. In some embodiments, the homogenization pressure in the high-pressure homogenization is 400-600 bar for the primary valve and 40-70 bar for the secondary valve.

[0023] In some embodiments, the homogenization temperature of the post-low-pressure homogenization in step (6) includes 50-70°C, 55-70°C, 60-70°C, 55-65°C, or any single value or sub-range thereof. In some embodiments, the number of homogenization cycles of the post-low-pressure homogenization includes 1-3 cycles, 1-2 cycles, 2-3 cycles, or any single value or sub-range thereof. In some embodiments, the homogenization pressure of the post-low-pressure homogenization is 80-300 bar for the primary valve and 10-40 bar for the secondary valve. In some embodiments, the homogenization pressure of the post-low-pressure homogenization is 100-250 bar for the primary valve and 20-40 bar for the secondary valve. In some embodiments, the homogenization pressure of the post-low-pressure homogenization is 150-250 bar for the primary valve and 30-40 bar for the secondary valve. In some embodiments, the homogenization pressure of the post-low-pressure homogenization is 100-200 bar for the primary valve and 10-30 bar for the secondary valve.

[0024] In some embodiments, the amount of sodium hydroxide used in the remaining portion of step (7) is 10%-50%, 15%-45%, 20%-40%, 25%-35%, 30%-40%, 30%-50%, or any single value or subrange thereof, of the total amount of sodium hydroxide in the formulation.

[0025] Furthermore, embodiments of the present invention provide a method for preparing a fat emulsion, the method comprising the following steps:

[0026] (1) Preparation of oil phase: Take oil and heat it to obtain oil phase;

[0027] (2) Preparation of aqueous phase: Take water for injection, glycerol and 50%-90% of sodium hydroxide in the prescription, heat to obtain aqueous phase;

[0028] (3) Preparation of primary emulsion: The oil phase and the water phase are mixed and sheared in a certain proportion to obtain an oil-water mixed phase. After uniform shearing by circulation, a relatively stable primary emulsion is obtained by filtration.

[0029] (4) Low-pressure homogenization: Homogenize the colostrum to obtain a stable colostrum;

[0030] (5) High-pressure homogenization: Homogenize the stable colostrum to obtain a stable emulsion;

[0031] (6) Post-low pressure homogenization: Homogenize the emulsion to obtain the final emulsion;

[0032] (7) Add the remaining sodium hydroxide in the formula: Add 10%-50% of the remaining sodium hydroxide in the formula to the final emulsion, stir well, and obtain the fat emulsion of the whole formula.

[0033] Furthermore, embodiments of the present invention provide a method for preparing a fat emulsion, the method comprising the following steps:

[0034] (1) Preparation of oil phase: Take oil and heat it to obtain oil phase;

[0035] (2) Preparation of aqueous phase: Take water for injection, glycerol and 50%-90% of sodium hydroxide in the prescription, heat to obtain aqueous phase;

[0036] (3) Preparation of primary emulsion: The oil phase and the water phase are mixed and sheared at a mass ratio of 1:(2-4) to obtain an oil-water mixed phase. After uniform shearing, the mixture is filtered to obtain a relatively stable primary emulsion.

[0037] (4) Low-pressure homogenization: Homogenize the colostrum to obtain a stable colostrum;

[0038] (5) High-pressure homogenization: Homogenize the stable colostrum to obtain a stable emulsion;

[0039] (6) Post-low pressure homogenization: Homogenize the emulsion to obtain the final emulsion;

[0040] (7) Add the remaining sodium hydroxide in the formula: Add 10%-50% of the remaining sodium hydroxide in the formula to the final emulsion, stir well, and obtain the fat emulsion of the whole formula.

[0041] Furthermore, embodiments of the present invention provide a method for preparing a fat emulsion, the method comprising the following steps:

[0042] (1) Preparation of oil phase: Take oil and heat it to obtain oil phase;

[0043] (2) Preparation of aqueous phase: Take water for injection, glycerol and 50%-90% of sodium hydroxide in the prescription, heat to obtain aqueous phase;

[0044] (3) Preparation of primary emulsion: The oil phase and the water phase are mixed and sheared at a mass ratio of 1:(2-4) to obtain an oil-water mixed phase. After uniform shearing by circulation, the primary emulsion is obtained by filtration. The pore size of the filter is 1-5μm, and the material of the filter is polypropylene or polyethersulfone.

[0045] (4) Low-pressure homogenization: Homogenize the colostrum to obtain a stable colostrum;

[0046] (5) High-pressure homogenization: Homogenize the stable colostrum to obtain a stable emulsion;

[0047] (6) Post-low pressure homogenization: Homogenize the emulsion to obtain the final emulsion;

[0048] (7) Add the remaining sodium hydroxide in the formula: Add 10%-50% of the remaining sodium hydroxide in the formula to the final emulsion, stir well, and obtain the fat emulsion of the whole formula.

[0049] Furthermore, embodiments of the present invention provide a method for preparing a fat emulsion, the method comprising the following steps:

[0050] (1) Preparation of oil phase: Take oil and heat it to obtain oil phase;

[0051] (2) Preparation of aqueous phase: Take water for injection, glycerol and 50%-90% of sodium hydroxide in the prescription, heat to obtain aqueous phase;

[0052] (3) Preparation of primary emulsion: The oil phase and the water phase are mixed and sheared at a mass ratio of 1:(2-4) to obtain an oil-water mixed phase. After uniform shearing by circulation, the primary emulsion is obtained by filtration. The pore size of the filter is 1-5μm, and the material of the filter is polypropylene or polyethersulfone.

[0053] (4) Low-pressure homogenization: Homogenize the colostrum to obtain a stable colostrum; the homogenization temperature of low-pressure homogenization includes 50-70℃, the number of homogenizations includes 1-2 times, and the homogenization pressure is 50-200 bar for the first-stage valve and 20-50 bar for the second-stage valve.

[0054] (5) High-pressure homogenization: The stable colostrum is homogenized to obtain a stable emulsion; the homogenization temperature of high-pressure homogenization includes 50-70℃, the number of homogenization times includes 3-6 times, and the homogenization pressure is 300-600 bar for the first-stage valve and 30-70 bar for the second-stage valve.

[0055] (6) Post-low pressure homogenization: Homogenize the emulsion to obtain the final emulsion; the homogenization temperature of post-low pressure homogenization includes 50-70℃, the number of homogenizations includes 1-3 times, and the homogenization pressure is 80-300 bar for the first-stage valve and 10-40 bar for the second-stage valve.

[0056] (7) Add the remaining sodium hydroxide in the formula: Add 10%-50% of the remaining sodium hydroxide in the formula to the final emulsion, stir well, and obtain the fat emulsion of the whole formula.

[0057] In some embodiments, no oil scumming occurred in the full-formula fat emulsion.

[0058] In some embodiments, the percentage of large milk particles in the full-formulation fat emulsion is no more than 0.02%, no more than 0.018%, no more than 0.016%, or no more than 0.015%.

[0059] In some embodiments, the concentration of free fatty acids in the full-formulation fat emulsion does not exceed 1.5 mmol / L, 1.45 mmol / L, 1.40 mmol / L, 1.35 mmol / L, or 1.3 mmol / L.

[0060] In some embodiments, the full-formulation fat emulsion may be further processed (e.g., filled, nitrogen-filled and capped, crimped and sterilized) to obtain a fat emulsion injection.

[0061] This invention provides a method for preparing fat emulsions, which has the following beneficial effects:

[0062] (1) By adopting the technical solution of the present invention, under the premise of controlling the total amount of sodium hydroxide, a portion of the sodium hydroxide in the prescription is added to the aqueous phase and the remaining portion is added to the final emulsion, the mixing ratio of the oil phase and the aqueous phase is controlled, a filtration process is added in the preparation of the primary emulsion, a homogenization operation of low pressure before high pressure after low pressure is adopted, and the process parameters are controlled within a suitable range, the phenomenon of oil floating in the prepared fat emulsion can be avoided, the percentage of large emulsion particles and the content of free fatty acids can be reduced, and the stability and safety of fat emulsion injection can be improved.

[0063] (2) The fat emulsion preparation method and process parameters provided by the present invention are applicable to the preparation of various types of fat emulsions and fat emulsion injections. The process is simple and stable, has good repeatability, and the quality is controllable, making it suitable for industrial production. Detailed Implementation

[0064] To more clearly illustrate the technical solution of the present invention, embodiments will be used to describe the technical solution of the present invention below. It should be understood that the description of the embodiments is only for the purpose of facilitating understanding of the technical solution, and is not intended to limit the present invention to the specific embodiments shown. The headings in this invention are provided for convenience only and should not be construed as limiting the invention in any way. Embodiments shown under any heading can be combined with embodiments shown under any other heading.

[0065] This specification uses process steps to illustrate the operations performed according to the technical solutions of the present invention. It should be understood that the preceding or subsequent operations are not necessarily performed precisely in sequence. In some embodiments, the steps may be processed in reverse order or simultaneously. In some embodiments, other operations may be added to these processes, or one or more operations may be removed from these processes.

[0066] The "%" mentioned in this invention refers to weight percentage, which is one of the ways of characterizing content that is understood in the art. The "first-stage valve" pressure mentioned in this invention refers to the pressure value of the first-stage valve, not the total pressure; the "second-stage valve" pressure refers to the pressure value of the second-stage valve, not the total pressure.

[0067] Methods for detecting the percentage of large milk particles:

[0068] Fat emulsion products were analyzed using an optical particle size analyzer based on single-particle optical sensing technology (detector threshold set to 1.8 μm, upper limit 50 μm). A calibration curve was established using a series of standard particles to correlate particle size with intensity signal magnitude. The optical particle size analyzer measured the signal generated by emulsion particles passing through the photosensitive area in the sample, and the particle size and weighted volume of the emulsion particles were calculated based on the calibration curve. The percentage of the total weighted volume of emulsion particles larger than 5 μm in the oil phase volume was calculated using the following formula:

[0069] Limit: The weighted total volume of emulsion particles larger than 5 μm shall not exceed 0.05% of the volume of the oil phase of the fat emulsion.

[0070] The percentage of large milk particles is a safety indicator. In the process of fat emulsion preparation, the lower the percentage of large milk particles, the higher the safety. Therefore, although the limit requirement is that the percentage of large milk particles should not exceed 0.05%, in order to ensure safety, it is actually controlled to not exceed 0.02%.

[0071] Methods for detecting the content of free fatty acids:

[0072] Accurately measure 15 ml of the fat emulsion product into a beaker, add 60 ml of anhydrous ethanol, 30 ml of water, and 1 ml of 0.05 mol / L hydrochloric acid solution, and mix well to prepare the test solution. Separately, accurately weigh approximately 28.5 mg of stearic acid reference standard, place it in a 100 ml volumetric flask, dissolve and dilute to the mark with anhydrous ethanol, and mix well. Accurately measure 15 ml of this solution, add 45 ml of anhydrous ethanol, 30 ml of water, and 1 ml of 0.05 mol / L hydrochloric acid solution, and mix well to prepare the blank solution. Titrate with sodium hydroxide titrant (0.1 mol / L) according to the potentiometric titration procedure. Calculate using the following formula: In the formula: B represents the result of free fatty acids in the blank solution, in mmol / L; C is the concentration of sodium hydroxide titrant (0.1 mol / L), in mmol / L; V 1b The volume of sodium hydroxide titrant consumed when the blank solution is titrated to the first equivalence point, in ml; V 2b The volume of sodium hydroxide titrant consumed when the blank solution is titrated to the second equivalence point, in ml; X represents the concentration of the reference solution, in mmol / L; V 1S The volume of sodium hydroxide titrant consumed when the test solution is titrated to the first equivalence point, in ml; V 2S This is the volume of sodium hydroxide titrant consumed when the test solution is titrated to the second equivalence point, in ml.

[0073] Limits: The concentration of free fatty acids should not exceed 5 mmol / L during the shelf life. During the stability study, an increasing trend in the content of free fatty acids was observed. It was found that the level on day 0 should be controlled at no more than 1.5 mmol / L to ensure that it does not exceed 5 mmol / L at the end of the shelf life.

[0074] Methods for detecting floating oil:

[0075] Take a fat emulsion product, add about 0.8 mg of Sudan Red to the surface of the emulsion, shake the bottle carefully, and let it stand for 5 minutes. No staining rings should appear, and no more than 5 drops of red emulsion should be visible to the naked eye.

[0076] To address the issues of oil bleed and large milk particles in fat emulsions that do not meet standards without the addition of sodium oleate, the applicant conducted extensive trials and experiments using various methods. During the fat emulsion preparation process, adjustments were made to the method of adding NaOH, including but not limited to adding the full prescription amount of NaOH to the aqueous phase, adding the full prescription amount of NaOH to the colostrum, adding the full prescription amount of NaOH to the final emulsion, and adding the prescription amount of NaOH separately in different steps. Ultimately, it was found that only by adding the prescription amount of NaOH separately in different steps could the oil bleed and the percentage of large milk particles caused by oil bleed be significantly reduced, while simultaneously reducing the content of free fatty acids.

[0077] To further explore the optimal way to add the prescribed amount of NaOH separately in different steps, the applicant has designed the following comparative examples and embodiments. Comparative Example 1

[0078] Take 200g of the structured triglyceride, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Add the remaining 30% of the sodium hydroxide in the formula. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, homogenize using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second valve, 100 bar for the first valve, homogenization temperature of 60℃, and one homogenization cycle to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 50 bar for the second valve, 500 bar for the first valve, homogenization temperature of 55℃, and five homogenization cycles. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the second-stage valve and 150 bar for the first-stage valve; homogenization temperature of 55℃; and homogenization was performed once. The resulting fat emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 2

[0079] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 65℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, add the remaining 30% of the sodium hydroxide in the formula, and then homogenize using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second-stage valve, 120 bar for the first-stage valve, homogenization temperature of 60℃, and homogenization times of 1. A stable primary emulsion is obtained. The primary emulsion is then subjected to high-pressure homogenization under the following conditions: homogenization pressure of 50 bar for the second-stage valve, 450 bar for the first-stage valve, homogenization temperature of 55℃, and homogenization times of 5. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the secondary valve and 100 bar for the primary valve; homogenization temperature of 55℃; and homogenization was performed once. The resulting fat emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 3

[0080] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and add it to 700ml of water for injection (total sodium hydroxide: 1.3mmol). Stir to dissolve and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Add 70% of the sodium hydroxide from the formulation to the oil-water mixture and circulate and shear for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, homogenize using a homogenizer under the following conditions: homogenization pressure: 50bar for the second-stage valve, 100bar for the first-stage valve; homogenization temperature: 60℃; homogenization cycle: 1. Stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure: 50bar for the second-stage valve, 500bar for the first-stage valve; homogenization temperature: 55℃; homogenization cycle: 5. After high-pressure homogenization, 30% sodium hydroxide from the prescription was added, followed by low-pressure homogenization. The homogenization conditions were: 20 bar for the second-stage valve and 150 bar for the first-stage valve; 55°C; and one homogenization cycle. The resulting fat emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized at 121°C for 12 minutes in a rotary sterilizer to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 4

[0081] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and add it to 700ml of water for injection (total sodium hydroxide: 1.3mmol). Stir to dissolve and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Add 70% of the sodium hydroxide from the formulation to the oil-water mixture and circulate and shear for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, homogenize using a homogenizer under the following conditions: homogenization pressure: 50bar for the second-stage valve, 150bar for the first-stage valve; homogenization temperature: 60℃; homogenization cycle: 1 time. A stable primary emulsion is obtained. The primary emulsion is then subjected to high-pressure homogenization under the following conditions: homogenization pressure: 50bar for the second-stage valve, 550bar for the first-stage valve; homogenization temperature: 55℃; homogenization cycle: 5 times. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the secondary valve and 150 bar for the primary valve; homogenization temperature of 55℃; and homogenization was performed once. After homogenization, the remaining 30% of sodium hydroxide was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 5

[0082] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 40% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Add 30% of the sodium hydroxide in the formula to the oil-water mixture and circulate and shear for 10min to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, homogenize using a homogenizer under the following conditions: homogenization pressure of 50bar for the second valve and 100bar for the first valve, homogenization temperature of 60℃, and one homogenization cycle to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 50bar for the second valve and 500bar for the first valve, homogenization temperature of 55℃, and five homogenization cycles. After high-pressure homogenization, 30% sodium hydroxide from the prescription was added, followed by low-pressure homogenization. The homogenization conditions were: 20 bar for the second-stage valve and 80 bar for the first-stage valve; 55°C for the first-stage valve; and one homogenization cycle. The resulting fat emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized at 121°C for 12 minutes in a rotary sterilizer to obtain the structured fat emulsion injection (C). 6～24 ). Example 1

[0083] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter. After filtration, homogenize using a homogenizer under the following conditions: homogenization pressure of 40 bar for the second valve and 150 bar for the first valve; homogenization temperature of 60℃; and homogenization once to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 50 bar for the second valve and 500 bar for the first valve; homogenization temperature of 55℃; and homogenization five times. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the second-stage valve and 150 bar for the first-stage valve; homogenization temperature of 55℃; and homogenization was performed once. After homogenization, the remaining 30% of sodium hydroxide in the formulation was added to obtain the complete fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ).

[0084] Comparative Examples 1-5 and Example 1: Structural fat emulsion injection (C) 6～24 The quality indicators were tested, and the results are shown in Table 1.

[0085] The experimental results in Table 1 show that, compared with the method of adding NaOH in the preparation methods of Comparative Examples 1-5, the method of preparing fat emulsion by adding NaOH to the aqueous phase and the final emulsion respectively according to Example 1 can significantly avoid oil floating in the product, further avoid the excessive percentage of large emulsion particles, and reduce the content of free fatty acids, thereby ensuring the stability and safety of the fat emulsion.

[0086] Based on the fact that the way NaOH is added in the above preparation method affects the percentage of oil floating, large milk particles and free fatty acid content in fat emulsion, the applicant speculates that other steps in the fat emulsion preparation process may also affect the quality indicators of the product. Therefore, the applicant further investigated the effects of homogenization and filtration methods and designed the following comparative examples and embodiments.

[0087] Comparative Examples 6-8 and Example 1 illustrate the effects of different homogenization methods on the quality indicators of fat emulsions. Comparative Example 6

[0088] Take 200g of the structured triglyceride, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:2 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it in a homogenizer under high pressure. The homogenization conditions are: homogenization pressure of 50 bar for the second valve and 450 bar for the first valve, homogenization temperature of 55℃, and homogenization times of 5 times. Then, perform low-pressure homogenization again under the following conditions: homogenization pressure of 20 bar for the second valve and 100 bar for the first valve, homogenization temperature of 55℃, and homogenization times of 1 time. After homogenization, the remaining 30% of sodium hydroxide in the prescription was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121°C for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 7

[0089] Take 200g of structured triglycerides, add 12g of lecithin and heat to 65℃, shear to disperse the lecithin in the oil phase; take 22g of glycerol and 70% of the sodium hydroxide in the formula and add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve and heat to 60℃; mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture, add water for injection to a volume of 1000ml, circulate the oil-water mixture and shear for 10min to obtain a uniform primary emulsion, filter the primary emulsion through a 5μm polypropylene filter and then homogenize it in a homogenizer under low pressure. The homogenization conditions are: homogenization pressure of 60bar for the second valve and 150bar for the first valve, homogenization temperature of 60℃, and homogenization times of 1 time to obtain a stable primary emulsion. The colostrum was further homogenized under high pressure under the following conditions: homogenization pressure of 50 bar for the second-stage valve and 500 bar for the first-stage valve; homogenization temperature of 55°C; and homogenization cycles of 5 times. After homogenization, the remaining 30% of sodium hydroxide in the formulation was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121°C for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 8

[0090] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it under high pressure. The homogenization conditions are: homogenization pressure of 40 bar for the second valve and 550 bar for the first valve, homogenization temperature of 60℃, and one homogenization cycle to obtain a stable primary emulsion. Continue to homogenize the primary emulsion under low pressure. The homogenization conditions are: homogenization pressure of 20 bar for the second valve and 100 bar for the first valve, homogenization temperature of 55℃, and one homogenization cycle. The solution was then subjected to high-pressure homogenization again under the following conditions: homogenization pressure of 60 bar for the second-stage valve and 550 bar for the first-stage valve; homogenization temperature of 55°C; and homogenization was performed four times. After homogenization, the remaining 30% of sodium hydroxide in the formulation was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121°C for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ).

[0091] Comparative Examples 6-8: Structural fat emulsion injection (C) 6～24 The quality indicators were tested, and the results are shown in Table 2. Table 2 Quality indicators of structured fat emulsions prepared by different homogenization methods

[0092] The experimental results in Table 1 show that, compared with the homogenization method in the preparation methods of Comparative Examples 6-8, the preparation method in Example 1, by performing pre-low pressure-high pressure-post-low pressure homogenization on the relatively stable colostrum, can significantly avoid oil drift in the product while controlling the free fatty acid content of the precursor, and at the same time reduce the percentage of large milk particles, thereby ensuring the stability and safety of the fat emulsion.

[0093] Comparative Example 9 and Examples 1-2 illustrate the effects of different filtration and homogenization methods on the quality indicators of fat emulsions. Comparative Example 9

[0094] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. The primary emulsion is homogenized under the following conditions: homogenization pressure of 40 bar for the second valve and 150 bar for the first valve, homogenization temperature of 60℃, and homogenization times of 1 time to obtain a stable primary emulsion. The primary emulsion is then subjected to high-pressure homogenization under the following conditions: homogenization pressure of 50 bar for the second valve and 500 bar for the first valve, homogenization temperature of 55℃, and homogenization times of 5 times. Low-pressure homogenization was performed again under the following conditions: homogenization pressure of 20 bar for the secondary valve and 150 bar for the primary valve; homogenization temperature of 55°C; and homogenization was performed once. After homogenization, the remaining 30% of sodium hydroxide in the formulation was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121°C for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Example 2

[0095] Take 200g of the structured triglyceride, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polyethersulfone filter, and then homogenize it using a homogenizer. Homogenization conditions: homogenization pressure of 40 bar for the second valve, 100 bar for the first valve, homogenization temperature of 60℃, and homogenization times of 1 time to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 50 bar for the second valve, 400 bar for the first valve, homogenization temperature of 55℃, and homogenization times of 5 times. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the second-stage valve and 150 bar for the first-stage valve; homogenization temperature of 55℃; and homogenization was performed once. After homogenization, the remaining 30% of sodium hydroxide in the prescription was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ).

[0096] Comparative Example 9 and Example 2 structural fat emulsion injection (C 6～24 The quality indicators were tested, and the results are shown in Table 3. Table 3 Quality indicators of structured fat emulsions prepared by different filtration methods

[0097] The experimental results in Table 3 show that, compared with Comparative Example 9, by filtering the colostrum after cyclic shearing according to the preparation method in Examples 1-2, and controlling the content of free fatty acids in the precursor, oil drift in the product can be significantly avoided, while reducing the percentage of large milk particles, thereby ensuring the stability and safety of the fat emulsion.

[0098] Existing technologies disclose processes for preparing fat emulsions without sodium oil. The applicant further investigated whether these preparation methods were suitable for preparing structured fat emulsions. The applicant prepared structured fat emulsions according to the preparation methods of Examples 3-5 of CN106265507A and Example 2 of CN103381195A, and compared their quality indicators with those of the preferred structured fat emulsions of Examples 1-2 of the present invention. Comparative Example 10: Preparation method according to Example 3 of CN106265507A.

[0099] Oil phase preparation: Take 200g of structured triglyceride, heat to 60℃, add 12g of lecithin, stir and disperse to obtain the oil phase.

[0100] Aqueous phase preparation: Add 22g of glycerol to about 300ml of water for injection, add sodium hydroxide to adjust the pH to 11.0, stir to dissolve, and heat to 65℃ to obtain the aqueous phase.

[0101] After mixing and stirring the oil and aqueous phases, add water for injection to 600 ml (60% of the prepared volume), stir well, and then homogenize twice using a homogenizer at a pressure of 600 bar for the first valve and 200 bar for the second valve. The homogenization temperature is 65℃. Add sodium hydroxide solution to the homogenized emulsion to adjust the pH to 9.5. Add water for injection to 1000 ml, mix well, and homogenize once more at a pressure of 160 bar for the first valve to obtain a homogeneous emulsion. Fill the emulsion into infusion bottles, purge with nitrogen, stopper, cap, and incubate at 121℃ for 12 minutes in a rotary sterilizer to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 11: Preparation method according to Example 4 of CN106265507A

[0102] Oil phase preparation: Take 200g of structured triglyceride, heat to 90℃, stir and disperse to obtain the oil phase.

[0103] Aqueous phase preparation: Add 22g of glycerol to about 300ml of water for injection, add sodium hydroxide to adjust the pH to 11.5, stir to dissolve, heat to 90℃, add 12g of lecithin to obtain the aqueous phase.

[0104] After mixing and stirring the oil and aqueous phases, sodium hydroxide solution was added to adjust the pH to 8.5. Water for injection was added to a final volume of 600 ml (60% of the prepared volume). The mixture was then homogenized once at a pressure of 800 bar for the first valve and 200 bar for the second valve, at a temperature of 65°C. Water for injection was then added to a final volume of 1000 ml, mixed thoroughly, and homogenized again at a pressure of 160 bar for the first valve and 120 bar for the second valve, resulting in a homogeneous emulsion. The emulsion was filled into infusion bottles, purged with nitrogen, capped, and incubated at 121°C for 12 minutes in a rotary sterilizer to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 12: Preparation method according to Example 5 of CN106265507A

[0105] Oil phase preparation: Take 200g of structured triglyceride, heat to 50℃, add 12g of lecithin, stir and disperse to obtain the oil phase.

[0106] Aqueous phase preparation: Add 22g of glycerol to about 150ml of water for injection, add sodium hydroxide to adjust the pH to 9.0, stir to dissolve, heat to 50℃, add 12g of lecithin to obtain the aqueous phase.

[0107] After mixing and stirring the oil and aqueous phases, sodium hydroxide solution was added to adjust the pH to 8.5. Water for injection was added to a final volume of 400 ml (40% of the prepared volume). The mixture was then homogenized three times at a pressure of 700 bar for the first valve and 80 bar for the second valve. The homogenization temperature was 55°C. Sodium hydroxide solution was added again to adjust the pH to 8.5. Water for injection was added to a final volume of 1000 ml. The mixture was then homogenized once more at a pressure of 200 bar for the first valve and 100 bar for the second valve, resulting in a homogeneous emulsion. The emulsion was filled into infusion bottles, purged with nitrogen, capped, and incubated at 121°C for 12 minutes in a rotary sterilizer to obtain the structured fat emulsion injection (C). 6～24 ). Comparative Example 13: Preparation method according to Example 2 of CN103381195A

[0108] Add an appropriate amount of water for injection to a mixing tank, add 22g of the prescribed amount of glycerol, stir to dissolve, add an appropriate amount of 1mol / L sodium hydroxide solution, filter through a 0.2μm filter membrane, heat to 50℃, add 12g of lecithin, and stir to disperse evenly. Add 200g of structured triglycerides, filter through a 0.45μm filter membrane, heat to 50℃, mix and stir the structured triglycerides and lecithin to form a primary emulsion, add water for injection to a volume of 1000ml, stir well, filter through a 40μm filter membrane, emulsify 6-7 times using a high-pressure homogenizer, and then release the emulsion into a dilution tank. After adjusting the pH value, check the semi-finished product, filter through a 10μm filter membrane, rinse with nitrogen, fill, and cap. Sterilize the infusion bottles containing the emulsion in a rotary autoclave at 121℃ for 15 minutes, inspect by light, and package to obtain the structured fat emulsion injection (C). 6～24 ).

[0109] Comparative Examples 10-13: Structural fat emulsion injection (C) 6～24 The quality indicators were tested, and the results are shown in Table 4. Table 4 Quality indicators of structured fat emulsions prepared using different processes

[0110] Table 4 shows the experimental results: Structured fat emulsions prepared using existing techniques exhibit high levels of floating oil and free fatty acids, or high levels of free fatty acids, or high percentages of large milk particles and free fatty acids, or both floating oil and high percentages of large milk particles and free fatty acids. This indicates that existing preparation methods are unsuitable for producing the structured fat emulsion of this invention. Therefore, the preparation method in Example 1 of this invention is suitable for preparing structured fat emulsions with no floating oil and low percentages of large milk particles and free fatty acids.

[0111] Based on the preparation methods determined in Examples 1-2 of the present invention, the applicant further investigated the influence of different process parameters on the quality of fat emulsion products. Specifically, fat emulsions were prepared by adding different proportions of sodium hydroxide to the aqueous phase and the final emulsion, under different homogenization parameters, and using filter cartridges of different sizes. The oil content, percentage of large emulsion particles, and content of free fatty acids in the fat emulsions were then measured to analyze the influence of different process parameters on the fat emulsion products. Example 3

[0112] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 30% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second valve and 100 bar for the first valve, homogenization temperature of 60℃, and one homogenization cycle to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 60 bar for the second valve and 550 bar for the first valve, homogenization temperature of 55℃, and four homogenization cycles. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the secondary valve and 100 bar for the primary valve; homogenization temperature of 55℃; and homogenization was performed once. After homogenization, the remaining 70% of the sodium hydroxide in the prescription was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Example 4

[0113] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 50% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second valve and 150 bar for the first valve, homogenization temperature of 55℃, and homogenization times of 2 times to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 60 bar for the second valve and 600 bar for the first valve, homogenization temperature of 65℃, and homogenization times of 3 times. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: 30 bar for the second-stage valve and 150 bar for the first-stage valve; 50°C for the homogenization temperature; and two homogenization cycles. After homogenization, the remaining 50% of the sodium hydroxide in the formulation was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, stoppered, capped, and sterilized in a rotary sterilizer at 121°C for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Example 5

[0114] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 90% of the sodium hydroxide in the formula, add to 700ml of water for injection (total sodium hydroxide 1.3mmol), stir to dissolve, and heat to 65℃. Mix the oil phase and water phase at a mass ratio of 1:2 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second valve and 50 bar for the first valve, homogenization temperature of 60℃, and one homogenization cycle to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 50 bar for the second valve and 400 bar for the first valve, homogenization temperature of 50℃, and six homogenization cycles. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the second-stage valve and 200 bar for the first-stage valve; homogenization temperature of 65℃; and homogenization was performed once. After homogenization, the remaining 10% of sodium hydroxide in the formulation was added to obtain a fat emulsion. The emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ). Example 6

[0115] Take 200g of structured triglycerides, add 12g of lecithin, and heat to 65℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 100% sodium hydroxide from the formulation, add to 700ml of water for injection (total sodium hydroxide is 1.3mmol), stir to dissolve, and heat to 60℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Filter the primary emulsion through a 5μm polypropylene filter and then homogenize it using a homogenizer. Homogenization conditions: homogenization pressure of 50 bar for the second valve and 100 bar for the first valve, homogenization temperature of 50℃, and one homogenization cycle to obtain a stable primary emulsion. Continue high-pressure homogenization of the primary emulsion under the following conditions: homogenization pressure of 60 bar for the second valve and 600 bar for the first valve, homogenization temperature of 55℃, and four homogenization cycles. After high-pressure homogenization, low-pressure homogenization was performed again. The homogenization conditions were: homogenization pressure of 20 bar for the secondary valve and 100 bar for the primary valve; homogenization temperature of 55℃; and homogenization was performed once. The resulting fat emulsion was filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the structured fat emulsion injection (C). 6～24 ).

[0116] For the structural fat emulsion injections of Examples 3-6 (C) 6～24 The quality indicators were tested, and the results are shown in Table 5. Table 5 Quality indicators of structured fat emulsions prepared with different process parameters

[0117] The experimental results in Table 5 show that when the amount of sodium hydroxide added to the aqueous phase accounts for 50%-90% of the total sodium hydroxide in the formulation, the percentage of fat emulsion without floating oil, large droplets, and the content of free fatty acids are all low. However, when the amount of sodium hydroxide added to the aqueous phase accounts for more than 90% of the total sodium hydroxide in the formulation (e.g., 95% in Example 6), the amount of sodium hydroxide added to the aqueous phase is relatively large, which increases the ionic strength of the emulsion, increases the repulsive force between droplets, and improves the stability of the emulsion, thus reducing the formation of floating oil and large droplets. However, due to the large sodium hydroxide content, the fat emulsion (triglycerides) is hydrolyzed, resulting in a higher level of free fatty acids in the product, affecting the safety of product use. When the amount of sodium hydroxide added to the aqueous phase accounts for less than 50% of the total sodium hydroxide in the formulation (e.g., 30% in Example 3), the amount of sodium hydroxide added is relatively small. Although it can avoid the hydrolysis of fat emulsion (triglycerides) and reduce the content of free fatty acids in the product, it cannot completely avoid the formation of floating oil and large droplets in the product, affecting the stability and safety of product use. In summary, the products prepared through Examples 2, 4, and 5 of the present invention can avoid oil drift, reduce the percentage of large emulsion particles and the content of free fatty acids, improve the stability and safety of fat emulsion injections, and improve product quality.

[0118] Based on the preparation method and process parameters determined above, the applicant further investigated the applicability of the above preparation method and process parameters to the preparation of different types of fat emulsions, and found that the preparation method and process parameters of the present invention are also applicable to the preparation of fat emulsion injections (C). 14～24 ). Example 7

[0119] Take 200g of soybean oil, add 12g of lecithin, and heat to 70℃. Shear to disperse the lecithin in the oil phase. Take 22g of glycerol and 70% of the sodium hydroxide in the prescription, add to 700ml of water for injection (total sodium hydroxide is 1mmol), stir to dissolve, and heat to 65℃. Mix the oil phase and water phase at a mass ratio of 1:3 and shear to form an oil-water mixture. Add water for injection to a final volume of 1000ml. Circulate and shear the oil-water mixture for 10 minutes to obtain a homogeneous primary emulsion. Pass the primary emulsion through a 5μm polypropylene filter and then homogenize it under low pressure using a homogenizer. The homogenization conditions are: homogenization pressure 100 bar for the first valve, 50 bar for the second valve, homogenization temperature 65℃, and homogenization times 1. After homogenization, continue high-pressure homogenization under the following conditions: homogenization pressure 500 bar for the first valve, 50 bar for the second valve, homogenization temperature 55℃, and homogenization times 5. After high-pressure homogenization, low-pressure homogenization was performed under the following conditions: homogenization pressure of 100 bar for the first valve and 20 bar for the second valve; homogenization temperature of 55℃; and homogenization was performed once. After low-pressure homogenization, the remaining 30% of sodium hydroxide in the formulation was added to the emulsion to adjust the pH to 8.0-9.0, resulting in a homogeneous emulsion. The emulsion was then filled into glass infusion bottles, filled with nitrogen, capped, and sterilized in a rotary sterilizer at 121℃ for 12 minutes to obtain the fat emulsion injection (C). 14～24 ).

[0120] The fat emulsion of Example 7 was tested for quality indicators. The results of Examples 1 and 7 are shown in Table 6. Table 6 Quality Indicators of Different Types of Fat Emulsions Example Example 7 Example 1 Types of oils soybean oil structural triglycerides Oil drift Unbleached oil Unbleached oil Percentage of large milk particles 0.001％ 0.002％ Free fatty acids 0.8 mmol / L 0.8 mmol / L

[0121] Table 6 shows the experimental results: the fat emulsion injection (C) prepared by the method of the present invention... 14～24 The product contained no floating oil, and the percentage of large emulsion particles and the content of free fat emulsion were very low. This preparation method is suitable for preparing fat emulsion injections (C). 14～24 ).

[0122] The basic concepts have been described above. Obviously, for those skilled in the art, the detailed disclosure above is merely illustrative and does not constitute a limitation of the present invention. Without inventive effort, those skilled in the art may make various modifications, improvements, and corrections to the present invention. Such modifications, improvements, and corrections still fall within the spirit and scope of the exemplary embodiments described herein. All methods described herein can be performed in any suitable order unless otherwise stated herein or clearly contradicted by the context.

[0123] In some embodiments, numbers describing the quantity of components and attributes are used. It should be understood that such numbers used in the description of embodiments are modified in some examples by the terms "about," "approximately," "approximately," or "generally." Unless otherwise stated, "about," "approximately," "approximately," or "generally" indicates that the numbers are allowed to vary by ±20%. Accordingly, in some embodiments, numerical parameters used in the specification and claims may be approximate values, which may be changed according to the characteristics required by individual embodiments. In some embodiments, numerical parameters should take into account specified significant digits and employ a general method of digit reservation. Although the numerical fields and parameters used to confirm their breadth of range in some embodiments of this specification are approximate values, in specific embodiments, such numerical values ​​are set as precisely as practicable. Unless otherwise stated herein, the enumeration of ranges of values ​​herein is intended only as a shorthand method for individually referring to each individual value falling within that range, and each individual value incorporated into the specification is equivalent to being individually enumerated herein.

[0124] The use of any and all instances or exemplary language provided herein is intended solely to illustrate certain materials, products, and methods, and does not constitute a limitation on the scope. The language in this specification should not be construed as indicating that any unclaimed element is necessary for practicing the disclosed materials, products, and methods.

[0125] As indicated in this invention and the claims, unless the context clearly indicates otherwise, the words "a," "an," "an," and / or "the" do not specifically refer to the singular and may also include the plural. Generally speaking, the terms "comprising" and "including" only indicate the inclusion of explicitly identified steps and elements, which do not constitute an exclusive list, and the method or composition may also include other steps or elements.

[0126] Furthermore, this specification uses specific terms to describe embodiments thereof. For example, "in some embodiments," "in multiple embodiments," "one embodiment," "an embodiment," and / or "some embodiments" refer to a particular feature, structure, or characteristic associated with at least one embodiment of this specification. Therefore, it should be emphasized and noted that the repeated use of "in some embodiments," "in multiple embodiments," "one embodiment," "an embodiment," and / or "some embodiments" in different locations within this specification does not necessarily refer to the same embodiment. Moreover, certain features, structures, or characteristics in one or more embodiments of this specification can be appropriately combined.

[0127] While the foregoing disclosure has discussed some inventive embodiments that are currently considered useful through various examples, it should be understood that such details are for illustrative purposes only, and the claims are not limited to the disclosed embodiments. Rather, the claims are intended to cover all modifications and equivalent combinations that conform to the substance and scope of the embodiments described herein.

[0128] Similarly, it should be noted that, in order to simplify the descriptions disclosed herein and thus aid in the understanding of one or more embodiments of the invention, multiple features may sometimes be grouped into a single embodiment in the foregoing description of the embodiments. However, this method of disclosure does not imply that the subject matter of this specification requires more features than those mentioned in the claims.

[0129] For each patent, patent application, patent application publication, and other material, such as articles, books, specifications, publications, and documents, referenced in this specification, the entire contents of which are incorporated herein by reference. This excludes historical application documents that are inconsistent with or conflict with the content of this specification, as well as documents that limit the broadest scope of the claims in this specification (currently or subsequently appended to this specification). It should be noted that in the event of any inconsistency or conflict between the descriptions, definitions, and / or terminology used in the supplementary materials to this specification and the content of this specification, the descriptions, definitions, and / or terminology used in this specification shall prevail.

[0130] Finally, it should be understood that the embodiments described in this specification are merely illustrative of the principles of the embodiments described herein. Other variations may also fall within the scope of this specification. Therefore, alternative configurations of the embodiments in this specification are intended to be exemplified rather than limited, and are considered consistent with the teachings of this specification. Accordingly, the embodiments in this specification are not limited to those explicitly described and illustrated herein.

Claims

1. A method for the preparation of a fat emulsion, characterized in that, The preparation method comprises the following steps: (1) Oil phase preparation: take oil and fat, heat, and obtain oil phase; (2) Water phase preparation: take water for injection, glycerol, and part of sodium hydroxide in the prescription, heat, and obtain water phase; (3) Preparation of colostrum: mix and shear the oil phase and the water phase in proportion to obtain oil-water mixed phase, and then filter the uniformly circulated and sheared colostrum to obtain relatively stable colostrum; (4) Pre-low-pressure homogenization: homogenize the colostrum to obtain stable colostrum; (5) High-pressure homogenization: homogenize the stable colostrum to obtain stable emulsion; (6) Post-low-pressure homogenization: homogenize the emulsion to obtain final emulsion; (7) Add the remaining sodium hydroxide in the prescription: add the remaining sodium hydroxide in the prescription to the final emulsion, stir uniformly, and obtain the full-prescription fat emulsion.

2. The production method according to claim 1, characterized by, The oil and fat is selected from structural triglyceride or soybean oil.

3. The production method according to claim 1, characterized by, The amount of sodium hydroxide in step (2) accounts for 50%-90% of the total amount of sodium hydroxide in the prescription.

4. The method of claim 1, wherein, The preparation method further comprises: adding lecithin in step (1) or step (2).

5. The preparation method according to claim 1, characterized in that, The mass ratio of oil to water in step (3) is 1:(2-4).

6. The method of claim 1, wherein, The filter used in step (3) has a pore size of 1-5 μm, and the filter material is polypropylene or polyether sulfone.

7. The preparation method according to claim 1, characterized in that, The homogenization temperature in step (4) includes 50-70℃, the homogenization times include 1-2 times, the homogenization pressure is 50-200 bar for a primary valve and 20-50 bar for a secondary valve.

8. The method of claim 1, wherein, The homogenization temperature in step (5) includes 50-70℃, the homogenization times include 3-6 times, the homogenization pressure is 300-600 bar for a primary valve and 30-70 bar for a secondary valve.

9. The method of claim 1, wherein, The homogenization temperature in step (6) includes 50-70℃, the homogenization times include 1-3 times, the homogenization pressure is 80-300 bar for a primary valve and 10-40 bar for a secondary valve.

10. The method of claim 1, wherein, The quality performance of the full-prescription fat emulsion includes at least one of the following: no oil floating, the percentage of large emulsion particles is not more than 0.02%, and the concentration of free fatty acid is not more than 1.5 mmol / L.

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