CN103006751B - Medium and long chain fat emulsion injection and preparation method thereof - Google Patents
Medium and long chain fat emulsion injection and preparation method thereof Download PDFInfo
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- 238000002347 injection Methods 0.000 title claims abstract description 44
- 239000007924 injection Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000002960 lipid emulsion Substances 0.000 title claims abstract description 23
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 79
- 235000011187 glycerol Nutrition 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 16
- 235000010445 lecithin Nutrition 0.000 claims abstract description 16
- 239000000787 lecithin Substances 0.000 claims abstract description 16
- 229940067606 lecithin Drugs 0.000 claims abstract description 16
- 235000012424 soybean oil Nutrition 0.000 claims abstract description 16
- 239000003549 soybean oil Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000003921 oil Substances 0.000 claims description 66
- 235000019198 oils Nutrition 0.000 claims description 66
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 35
- 238000003756 stirring Methods 0.000 claims description 25
- 230000001954 sterilising effect Effects 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 210000003022 colostrum Anatomy 0.000 claims description 19
- 235000021277 colostrum Nutrition 0.000 claims description 19
- 239000000839 emulsion Substances 0.000 claims description 18
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 17
- 239000008215 water for injection Substances 0.000 claims description 15
- 238000001802 infusion Methods 0.000 claims description 8
- 229920005549 butyl rubber Polymers 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 238000004659 sterilization and disinfection Methods 0.000 claims description 7
- 238000003556 assay Methods 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 239000012982 microporous membrane Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 238000007789 sealing Methods 0.000 claims description 5
- 238000005374 membrane filtration Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000012216 screening Methods 0.000 abstract description 2
- 229940057917 medium chain triglycerides Drugs 0.000 abstract 1
- 238000011020 pilot scale process Methods 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 38
- 239000000203 mixture Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 235000004626 essential fatty acids Nutrition 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000000265 homogenisation Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 235000005687 corn oil Nutrition 0.000 description 4
- 238000007493 shaping process Methods 0.000 description 4
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
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- 235000021476 total parenteral nutrition Nutrition 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention aims to provide a medium and long chain fat emulsion injection and a preparation method thereof. Specifically, every 1,000 ml of the medium and long chain fat emulsion injection contains 50 to 100 grams of soybean oil for injection, 50 to 100 grams of medium chain triglycerides for injection, 12 grams of lecithin for injection, 25 grams of glycerin for injection and an appropriate quantity of water. By adopting a large quantity of process screening operations and combining pilot scale production, process conditions for a special prescription are determined to fully guarantee the effectiveness, controllability and stability of a product.
Description
Technical field
The invention belongs to medical art, to be specifically related in one/long chain fat emulsion injection and preparation method thereof.
Background technology
Lipomul (1ipid emulsion, LE) is the important component part of parenteral alimentation, is the product of clinical nutrition development.From Wretlind in 1961 first lipomul is applied to clinical since, existing more than 40 year history, LE there occurs great changes in kind, composition etc., in succession introducing/long chain fat emulsion, structural fatty milk, fish oil fat emulsion injection etc.; Its clinical practice has also widened auxiliary treatment to multiple systems disease and drug manufacture field by single energy, essential fatty acid supply.The appearance of LE embodies high-tech achievement in research, becomes indispensable composition in nutritional preparation, plays a very important role in its application in parenteral nutrition in modern age (PN) and development thereof.
Lipid emulsion infusion is except the energy provided needed for body, also for body provides the polyunsaturated fatty acid needed for biomembrane and bioactive substance metabolism, and can prevent or correct the shortage of body essential fatty acid (EFA), control essential fatty acid lacks syndrome (EFAD).The lipomicron formed after emulsifying in LE and natural chyle fairly similar: have that energy density is large, solution is isotonicity, without diuresis and under stress state metabolic rate do not descend degradation advantage.The physicochemical property good due to lipomul and metabolic characteristic thereof, its clinical practice is quite general, known all cannot or unsuitable oral feeding more than one week person, be the indication of parenteral nutrition.Many critically ill patients in surgical field comprise the critical disease such as Severe Acute Pancreatitis SAP, serious burn, postoperative a large amount of heat energy supplements, the treatment of the essential fatty acid deficiency of long-term total parenteral nutrition (TPN) patient, and for improving amino acid transfusion utilization rate in vivo, all have the indication of application lipomul.
Nearly 40 years of long chain fat emulsion injection clinical practice worldwide, its definite nutritive value is generally acknowledged by common people.But these long chain fat emulsions still also exist the harmful effect such as to immune function of human body and liver function in clinical practice, and fat may in some side effect such as liver savings.Therefore, at present clinically more and more use in/long chain fat emulsion, the i.e. physical mixture of long chain triglyceride (LCT) and medium chain triglyceride (MCT).LCT can provide many unsaturated fatty acids, prevents because of essential fatty acid that to lack institute's biochemistry extremely disorderly, corrects the symptom that essential fatty acid shortage (EFAD) occurs; In carbochain, carbon number is mainly 8 and the MCT of l0 is not deposited in tissue soon, substantially than LCT metabolic rate, little effect lipoprotein metabolism and reticuloendothelial system function etc., is specially adapted to critical patient and hepatic disfunction person.Owing to not containing essential fatty acid (EFA) in MCT, and a large amount of input can produce toxicity, therefore for the clinical equivalent physics mix preparation mostly being LCT and MCT, its feature is that metabolism is fast, utilization rate is high, liver function influence is little, is applicable to critical patient and the premature infant of prolonged application fat milk.
Summary of the invention
To the object of the present invention is to provide in one/long chain fat emulsion injection and preparation method thereof, specifically, in of the present invention/long chain fat emulsion injection contains following composition:
In above-mentioned/and long chain fat emulsion injection, it is preferably containing following composition:
In above-mentioned/and long chain fat emulsion injection, it is preferably containing following composition:
In above-mentioned/and the preparation method of long chain fat emulsion injection, it comprises the following steps:
(1) under nitrogen protection, take recipe quantity soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 ~ 75 DEG C, add lecithin, rapid stirring is to dispersed;
(2) separately get water for injection add the mixing of recipe quantity glycerol and through membrane filtration, be prepared into glycerine water solution, temperature maintains 60 ~ 65 DEG C;
(3) under nitrogen protection and rapid stirring, step (1) gained phosphatide oil solution is slowly added in glycerine water solution and forms colostrum, and by 1mol/L sodium hydroxide solution adjust ph about 9.0;
(4) by the colostrum of preparation through high pressure homogenizer homogenizing, circulation homogenize (about 600 ± 00 bar, 4 ~ 6 times) is to newborn grain is qualified;
(5) after the assay was approved, emulsion is through 1-5 μm of filtering with microporous membrane, and fill, in infusion bottle, passes into nitrogen, adds butyl rubber plug, rolls lid sealing, puts in rotating type sterilization device, 117 DEG C of sterilizing 30min.
In above-mentioned/preparation method of long chain fat emulsion injection in, the aperture of the filter membrane in described step (2) is preferably 0.45 μm or 0.22 μm.
Feature of the present invention is filtered by the aqueous phase of step (2) in preparation method of the present invention, effectively increase the stability of finished product Emulsion, result is investigated according to this, in conjunction with a large amount of craft screenings and scale up test, in finally determining/manufacturing condition of long chain fat emulsion injection, effective for product, controlled and stablely provides abundant guarantee.
Detailed description of the invention
Below in conjunction with embodiment and experimental example, the present invention is further detailed.
the prescription that embodiment uses
| Prescription 1 | Prescription 2 |
| Injection soybean oil 50g | Injection soybean oil 100g |
| Injection median chain triglyceride oil 50g | Injection median chain triglyceride oil 100g |
| Injection lecithin 12g | Injection lecithin 12g |
| Water for injection is appropriate | Water for injection is appropriate |
| Glycerol for injection 25g | Glycerol for injection 25g |
| Make 1000ml | Make 1000ml |
the preparation process that embodiment uses
Preparation process 1:
(1) under nitrogen protection, take recipe quantity soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 ~ 75 DEG C, add lecithin, rapid stirring is to dispersed;
(2) separately get water for injection add the mixing of recipe quantity glycerol and through 0.45 μm of membrane filtration, be prepared into glycerine water solution, temperature maintains 60 ~ 65 DEG C;
(3) under nitrogen protection and rapid stirring, step (1) gained phosphatide oil solution is slowly added in glycerine water solution and forms colostrum, and by 1mol/L sodium hydroxide solution adjust ph about 9.0;
(4) by the colostrum of preparation through high pressure homogenizer homogenizing, circulation homogenize (about 600 ± 50 bar, 4 ~ 6 times) is to newborn grain is qualified;
(5) after the assay was approved, emulsion is through 1-5 μm of filtering with microporous membrane, and fill, in infusion bottle, passes into nitrogen, adds butyl rubber plug, rolls lid sealing, puts in rotating type sterilization device, 117 DEG C of sterilizing 30min.
Preparation process 2:
(1) under nitrogen protection, take recipe quantity soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 ~ 75 DEG C, add lecithin, rapid stirring is to dispersed;
(2) separately get water for injection add the mixing of recipe quantity glycerol and through 0.22 μm of membrane filtration, be prepared into glycerine water solution, temperature maintains 60 ~ 65 DEG C;
(3) under nitrogen protection and rapid stirring, step (1) gained phosphatide oil solution is slowly added in glycerine water solution and forms colostrum, and by 1mol/L sodium hydroxide solution adjust ph about 9.0;
(4) by the colostrum of preparation through high pressure homogenizer homogenizing, circulation homogenize (about 600 ± 50 bar, 4 ~ 6 times) is to newborn grain is qualified;
(5) after the assay was approved, emulsion is through 1-5 μm of filtering with microporous membrane, and fill, in infusion bottle, passes into nitrogen, adds butyl rubber plug, rolls lid sealing, puts in rotating type sterilization device, 117 DEG C of sterilizing 30min.
Comparative formulation technique:
(1) under nitrogen protection, take recipe quantity soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 ~ 75 DEG C, add lecithin, rapid stirring is to dispersed;
(2) separately get water for injection and add the mixing of recipe quantity glycerol, be prepared into glycerine water solution, temperature maintains 60 ~ 65 DEG C;
(3) under nitrogen protection and rapid stirring, step (1) gained phosphatide oil solution is slowly added in glycerine water solution and forms colostrum, and by 1mol/L sodium hydroxide solution adjust ph about 9.0;
(4) by the colostrum of preparation through high pressure homogenizer homogenizing, circulation homogenize (about 600 ± 50 bar, 4 ~ 6 times) is to newborn grain is qualified;
(5) after the assay was approved, emulsion is through 1-5 μm of filtering with microporous membrane, and fill, in infusion bottle, passes into nitrogen, adds butyl rubber plug, rolls lid sealing, puts in rotating type sterilization device, 117 DEG C of sterilizing 30min.
the prescription of embodiment 1-6 and preparation process
| Embodiment | Prescription | Preparation process |
| Embodiment 1 | Prescription 1 | Preparation process 1 |
| Embodiment 2 | Prescription 2 | Preparation process 1 |
| Embodiment 3 | Prescription 1 | Preparation process 2 |
| Embodiment 4 | Prescription 2 | Preparation process 2 |
| Embodiment 5 | Prescription 1 | Comparative formulation technique |
| Embodiment 6 | Prescription 2 | Comparative formulation technique |
the selection of colostrum temperature in experimental example 1-the present invention
Take soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 60 DEG C, 70 DEG C, 80 DEG C respectively, add lecithin, rapid stirring is to even.Separately get water for injection and add glycerol, stir, be heated to 60 DEG C, 70 DEG C, 80 DEG C respectively, phosphatide oil solution is slowly added in glycerine water solution form colostrum under fast stirring, perusal face shaping after high pressure homogenizer (700bar) homogenizing 6 times.The results are shown in Table 1, table 2.
Selection result-the embodiment 1 of table 1 colostrum temperature
| Oil phase temperature (DEG C) | Aqueous phase temperature (DEG C) | Face shaping |
| 60 | 60 | Liquid level has > 10 oil droplets |
| 70 | 70 | Evenly milky white, liquid level is without oil droplet |
| 80 | 80 | Liquid level has < 10 oil droplets |
As shown in Table 1: raised temperature (70 DEG C) forms facilitation to embodiment 1, but too high temperature affects the stable of whole system on the contrary.
Selection result-the embodiment 2 of table 2 colostrum temperature
| Oil phase temperature (DEG C) | Aqueous phase temperature (DEG C) | Face shaping |
| 60 | 60 | Liquid level has > 10 oil droplets |
| 70 | 70 | Evenly milky white, liquid level is without oil droplet |
| 80 | 80 | Liquid level has < 10 oil droplets |
As known from Table 2: the result of embodiment 2 is identical with embodiment 1, therefore when preparation embodiment 1 and the colostrum of embodiment 2, temperature should control phosphatide oil solution 70 DEG C, glycerine water solution 70 DEG C.
the selection of experimental example 2-high pressure homogenize pressure
Take soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 DEG C, add lecithin, rapid stirring is to even.Separately get water for injection and add glycerol, stir, be heated to 70 DEG C, phosphatide oil solution is slowly added in glycerine water solution form colostrum under fast stirring, through high pressure homogenizer with after different pressures (500bar, 600bar, 700bar) homogenizing 5 times, get emulsion particle size analyzer determination particle diameter.The results are shown in Table 3, table 4.
Selection result-the embodiment 1 of table 3 homogenization pressure
As shown in Table 3: when pressure is increased to 600 bar, the mean diameter of embodiment 1 is at below 300nm, but mean diameter under 600 bar process conditions and 700 bar are more or less the same, and its 90% particle diameter, maximum particle diameter are also in the allowed band of particle size distribution.
Selection result-the embodiment 2 of table 4 homogenization pressure
As shown in Table 4: the result of embodiment 2 is similar to embodiment 1, although the particle size distribution of 700 bar is better, considers large equipment cost problem of producing, think that 600 bar are more suitable.Examine or check result more than comprehensive, embodiment 1, embodiment 2 pressure when high pressure homogenize should control at 600 bar.
the selection of experimental example 3-high pressure homogenize number of times
Take soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 DEG C, add lecithin, rapid stirring is to even.Separately get water for injection and add glycerol, stir, be heated to 70 DEG C, phosphatide oil solution is slowly added in glycerine water solution form colostrum under fast stirring, after high pressure homogenizer (600bar) difference homogenizing 4 times, 6 times, 8 times, get emulsion particle size analyzer determination particle diameter.The results are shown in Table 5, table 6.
Selection result-the embodiment 1 of table 5 homogenization cycles
As shown in Table 5: homogenizing 4 particle diameters just can reach suitable scope, and mean diameter reduces with the increase of homogenization cycles, but the operating time of homogenizing 8 times longer.
Selection result-the embodiment 2 of table 6 homogenization cycles
As shown in Table 6, the result of the test of embodiment 2 is similar to embodiment 1, therefore when embodiment 1 and embodiment 2 high pressure homogenize, number of times should control at 4 ~ 6 times.
the control of experimental example 4-pH value
Take soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 DEG C, add lecithin, under nitrogen protection, rapid stirring is to even.Separately get water for injection and add glycerol; stir; be heated to 70 DEG C, under nitrogen protection, rapid stirring, phosphatide oil solution slowly added in glycerine water solution and form colostrum, after high pressure homogenizer (600bar) homogenizing 6 times; by sodium hydroxide solution adjust ph to 7.5,8.0,8.5; with 5 μm of filtering with microporous membranes, fill, in infusion bottle, passes into nitrogen; add butyl rubber plug, aluminium lid seals.The pH value of emulsion is surveyed after rotating sterilizing 30min in 117 DEG C.The results are shown in Table 7, table 8.
Result of variations-the embodiment 1 of pH value before and after table 7 sterilizing
| PH value before sterilizing | PH value after sterilizing |
| 7.51 | 6.83 |
| 8.02 | 7.22 |
| 8.51 | 7.94 |
Result of variations-the embodiment 2 of pH value before and after table 8 sterilizing
| PH value before sterilizing | PH value after sterilizing |
| 7.52 | 6.91 |
| 8.01 | 7.34 |
| 8.53 | 7.82 |
From table 7,8 result: after sterilizing, the pH value of sample all has reduction, consider sample in put procedure pH value also have reduce may, before sterilizing, the pH value of embodiment 1 and embodiment 2 should control 9.0 better.
the checking of experimental example 5-sterilization process
Take soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 DEG C, add lecithin, under nitrogen protection, rapid stirring is even.Separately get water for injection and add glycerol; stir; be heated to 70 DEG C, under nitrogen protection, rapid stirring, phosphatide oil solution slowly added in glycerine water solution and form colostrum, after high pressure homogenizer (600bar) homogenizing 6 times; by sodium hydroxide solution adjust ph to 8.5; with 5 μm of filtering with microporous membranes, fill, in infusion bottle, passes into nitrogen; add butyl rubber plug, aluminium lid seals.Observe face shaping after rotating sterilizing 30min in 117 DEG C, survey granularity, the content of emulsion.The results are shown in Table 9.
The result of table 9 sterilization process
As shown in Table 9: after embodiment 1 and embodiment 2 rotate sterilizing 30min through 117 DEG C, indices all conforms to quality requirements, and before and after sterilizing, change is little.
experimental example 6-aqueous phase filters the checking of technique
Get each 50 bottles of the sample of embodiments of the invention 1-6, respectively 25 DEG C, keep sample under the condition of relative humidity 45%, measure the stability of Emulsion, investigate different process to the impact of preparation stability.The results are shown in Table 10.
Table 10 different process is on the impact of preparation stability
| Standing time | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 |
| 1 month | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet |
| 3 months | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet |
| 6 months | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet |
| 9 months | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet |
| 12 months | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | 3 bottles of sample generation breakdowns of emulsion, layering | 5 bottles of sample generation breakdowns of emulsion, layering |
| 18 months | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | Evenly milky white, liquid level is without oil droplet | 5 bottles of sample generation breakdowns of emulsion, layering | 9 bottles of sample generation breakdowns of emulsion, layering |
As shown in Table 10, the aqueous phase in step (2) filters the stability that technique effectively increases finished product Emulsion.
The present invention according to above examination result and in scale up test determines/process conditions of long chain fat emulsion injection, effective for product, controlled and stablely provides abundant guarantee.
Claims (5)
1. in/and a long chain fat emulsion injection, it is characterized in that supplementary material is:
And adopt following methods preparation:
(1) under nitrogen protection, take recipe quantity soybean oil and median chain triglyceride oil, be uniformly mixed, be heated to 70 ~ 75 DEG C, add lecithin, rapid stirring is to dispersed;
(2) separately get water for injection add the mixing of recipe quantity glycerol and through membrane filtration, be prepared into glycerine water solution, temperature maintains 60 ~ 65 DEG C;
(3) under nitrogen protection and rapid stirring, step (1) gained phosphatide oil solution is slowly added in glycerine water solution and forms colostrum, and by 1mol/L sodium hydroxide solution adjust ph about 9.0;
(4) by preparation colostrum through high pressure homogenizer homogenizing, 600 ± 00bar circulated under pressure homogenize 4 ~ 6 times, to newborn grain is qualified;
(5) after the assay was approved, emulsion is through 1-5 μm of filtering with microporous membrane, and fill, in infusion bottle, passes into nitrogen, adds butyl rubber plug, rolls lid sealing, puts in rotating type sterilization device, 117 DEG C of sterilizing 30min.
2. according to claim 1/and long chain fat emulsion injection, it is characterized in that supplementary material is:
3. according to claim 1/and long chain fat emulsion injection, it is characterized in that supplementary material is:
4. according to claim 1-3 arbitrary described in/long chain fat emulsion injection, it is characterized in that the aperture of filter membrane in described step (2) is 0.45 μm.
5. according to claim 1-3 arbitrary described in/long chain fat emulsion injection, it is characterized in that the aperture of filter membrane in described step (2) is 0.22 μm.
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| CN103301062A (en) * | 2013-06-03 | 2013-09-18 | 四川百利药业有限责任公司 | Medium and long-chain lipid emulsion injection preparation method |
| CN103330734B (en) * | 2013-06-21 | 2015-02-04 | 辽宁海思科制药有限公司 | Medium/long-chain fat emulsion injection pharmaceutical composition and preparation method thereof |
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