Method for preparing Brucea javanica oil emulsion injection and its application

Abstract

The present invention provides a method for preparing Brucea javanica oil composition and its application. The Brucea javanica oil composition includes refined soybean phospholipid and Brucea javanica oil. Among them, the iodine value of the refined soybean phospholipid is not less than 90 and not more than 100. When the Brucea javanica oil composition prepared by the method is clinically applied within 18 months, the risk of hemolysis is significantly reduced, and the quality stability and product safety are significantly improved.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technologies, and specifically, to a method for preparing Brucea javanica oil composition and its applications. Background Art

[0002] Hemolysis refers to the rupture of red blood cells, and the escape of hemoglobin is called red blood cell lysis, simply referred to as hemolysis. The isotonic solution of human plasma is 0.9% NaCl solution. Red blood cells will rupture and hemoglobin will escape due to the infiltration of water when placed in an NaCl solution below 0.45%. In the human body, hemolysis can be caused by hemolytic bacteria or certain snake venoms invading, antigen-antibody reactions (such as transfusing incompatible blood), various mechanical damages, intrinsic (membrane, enzyme) defects of red blood cells, and certain drugs.

[0003] For some traditional Chinese medicine injections, due to the presence of hemolytic components (such as saponins) or physical, chemical, and biological reasons, they can produce hemolytic effects after being directly injected into the blood vessels; there are also some injections that contain impurities and other components, which can cause swelling and pain when injected locally, and can cause adverse reactions such as blood cell aggregation and blood circulation dysfunction after being injected into the blood vessels; in addition, due to the complex composition of traditional Chinese medicine preparations, there is also immune hemolysis caused by immune reactions.

[0004] Brucea javanica, also known as "Brucea fruit" or "Sophora flavescens fruit", is the mature fruit of Brucea javanica (L.) Merr. of the Simaroubaceae family, which is grayish-black, oblong or oval. When the fruit of Brucea javanica turns purple or purplish-black, it is harvested, and after harvesting, it is washed 1 - 2 times with clean water. The washed fruits are placed on a drying yard for drying. After several days of turning and drying, when the fruits and pulp shrink and the humidity is lower than 10% - 13%, they are packaged and stored in a cool and ventilated place.

[0005] Brucea javanica oil emulsion injection is prepared from the Brucea javanica oil obtained by extracting Brucea javanica with petroleum ether, soybean phospholipids, glycerol, and a certain mass of injection water. The specific preparation method refers to the preparation method of Brucea javanica oil emulsion injection recorded in "The Fourteenth Volume of Traditional Chinese Medicine Formulas and Preparations WS3 - B - 2739 - 97": that is, 15 g of refined soybean phospholipids and 25 mL of warm glycerol are mixed with a certain mass of injection water, transferred to a high-speed tissue homogenizer, and stirred twice at 8000 revolutions per minute, the first time for 5 minutes and the second time for 2 minutes to make them disperse evenly. 100 mL of warm refined Brucea javanica oil is added and stirred 3 times, each time for 2 minutes, to form a primary emulsion. Injection water is added to 1000 mL, and then transferred to a high-pressure homogenizer (40 MPa) for homogenization three times, filtered, the filtrate is taken, filled and sealed, and sterilized to obtain the product.

[0006] Brucea oil is a mixed composition directly derived from plant seeds. It has a complex composition, and both the effective and toxic components are difficult to accurately control. Among them, the acid value of Brucea oil has a very large impact on the participation of Brucea oil in the pharmaceutical process. Modern research has found that during the production and storage process, both Brucea oil and refined soybean lecithin may be hydrolyzed to produce free fatty acids, resulting in a decrease in the pH value of the fat emulsion. The decrease in pH can significantly reduce the degree of ionization of various components in phospholipids, thereby causing a decrease in zeta potential, resulting in instability of the fat emulsion and prone to hemolysis.

[0007] During the preparation process, in order to avoid hemolysis of Brucea javanica oil emulsion injection during clinical use as much as possible, a hemolysis test is carried out in the product quality control. By formulating corresponding indicators, the hemolysis experimental data is judged, thereby indicating to the manufacturer whether this batch of products has a hemolysis risk in future clinical use. If the hemolysis results do not meet the standard requirements, the corresponding products will not be allowed to enter the market, thereby reducing the safety risks of Brucea javanica oil emulsion injection in clinical use.

[0008] This method is used to control the safety risks of clinical use of javanica oil emulsion injection. It is a monitoring of product quality rather than an improvement in the quality of the product itself. Therefore, the hemolysis that easily occurs during production and storage of javanica oil emulsion preparations has not been fundamentally improved.

[0009] In order to solve this problem, the most basic idea is to solve the hemolysis risk of javanica oil emulsion injection by improving certain processes or production parameters that affect its hemolysis risk in the production of javanica oil emulsion injection.

[0010] For ordinary fat emulsions, some additives can be added to prevent oxidation of fat emulsions or protect the stability of fat emulsions, such as pH regulators and isotonic regulators for adjusting pH value and osmotic pressure, antioxidants or reducing agents added to prevent oxidation, and interfacial membrane stabilizers, etc. pH regulators are usually hydrochloric acid, citric acid or sodium hydroxide solution, to meet the physiological pH value and minimize the hydrolysis of the drugs and phospholipids contained; glycerol is the most commonly used isotonic regulator; antioxidants or reducing agents are often vitamin E, ascorbic acid, sodium sulfite or L-cysteine, etc.; more commonly used interfacial membrane stabilizers are oleic acid or its salts, bile acid or its salts, which can increase the strength of the interfacial membrane, increase the zeta-potential, increase the repulsive force between emulsion droplets, prevent emulsion droplet aggregation, and thus improve the stability of fat emulsions.

[0011] In the process of preparing Brucea javanica oil emulsion injection, some people use NaOH to react with free fatty acids to undergo saponification, which is beneficial to the formation and stability of the emulsion system, and use it as a pH regulator for Brucea javanica oil emulsion injection. However, Brucea javanica oil is a mixture of various fat-soluble and non-fat-soluble components. Its active ingredients are unclear for its main indication for treatment, anti-tumor treatment. The rash use of chemical agents is very likely to react with the components of Brucea javanica oil while reducing free fatty acids, thereby bringing relatively large safety risks and reduced efficacy risks to Brucea javanica oil emulsion injection.

[0012] Another way to reduce the risk of hemolysis is to control the production and processing of Brucea brucea, such as controlling gray Brucea brucea with high acidity or removing the shells of Brucea brucea with impurities and high acidity. These two methods can effectively reduce the acidity of Brucea brucea oil, making it more stable when participating in preparations while retaining its various components. However, this method requires increasing the production cost of Brucea brucea and processing equipment, so other methods need to be explored. Summary of the invention

[0013] This application is based on the inventor's discovery and understanding of the following problems:

[0014] The existence of refined soybean lecithin on the quality stability of Brucea brucea oil emulsion injection, refined soybean lecithin refers to soybean lecithin suitable for injection after processing, and like soybean lecithin, its main component is phosphatidylcholine (PC), and it also contains a small amount of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI) and hemolytic phosphatidyl, etc., and hemolytic phosphatidyl is the main degradation product of phosphatidylcholine, which has the effect of hemolysis or dissolving cell membrane. After a large number of experimental studies, the inventor found that when the PC content in refined soybean lecithin is increased to 80% or even higher, the results of in vitro hemolysis test show that Brucea brucea oil emulsion injection has the risk of hemolysis. The inventor unexpectedly found that after the iodine value of refined soybean lecithin is controlled, the risk of hemolysis is alleviated. On this basis, the PC content and LPC content in soybean lecithin are further controlled, and the stability of the Brucea brucea oil emulsion injection obtained within 18 months is significantly improved, and the risk of hemolysis in clinical application is significantly reduced.

[0015] Therefore, in the first aspect of the present invention, the present invention proposes a Brucea javanica oil composition. According to an embodiment of the present invention, it comprises: refined soybean lecithin and Brucea javanica oil, wherein the iodine value of the refined soybean lecithin is not less than 90 and not more than 100. The stability of the Brucea javanica oil composition according to the embodiment of the present invention is significantly improved during storage, and the risk of hemolysis or other side effects in clinical applications is significantly reduced.

[0016] According to an embodiment of the present invention, the iodine value is determined according to the iodine value determination method described in the "Fourth Volume of Chinese Pharmacopoeia 2020 Edition", Method for the Determination of Fats and Fixed Oils 0713.

[0017] According to an embodiment of the present invention, the Brucea javanica oil composition may further include at least one of the following additional technical features:

[0018] According to an embodiment of the present invention, the PC content of the refined soybean phospholipid is not less than 80% and not more than 95%. According to a specific embodiment of the present invention, on the basis of controlling the iodine value of the refined soybean phospholipid to be not less than 90 and not more than 100, further controlling the PC content significantly improves the stability of the Brucea javanica oil composition.

[0019] According to an embodiment of the present invention, the LPC content of the refined soybean phospholipid is not more than 3%. According to a specific embodiment of the present invention, on the basis of controlling the iodine value of the refined soybean phospholipid to be not less than 90 and not more than 100, and the PC content to be not less than 80% and not more than 95%, further controlling the LPC content maximally improves the stability of the Brucea javanica oil composition.

[0020] According to an embodiment of the present invention, the Brucea javanica oil complies with the Brucea javanica oil standard in "The Fourteenth Volume of Chinese Traditional Patent Medicine Formulas WS3-B-2739-97". The Brucea javanica oil contained in the Brucea javanica oil composition according to the embodiment of the present invention is not particularly limited, and any Brucea javanica oil that complies with the standard of "The Fourteenth Volume of Chinese Traditional Patent Medicine Formulas WS3-B-2739-97" can be used.

[0021] According to an embodiment of the present invention, the mass-volume ratio of the refined soybean phospholipid to the Brucea javanica oil is 3 g:20 mL.

[0022] According to an embodiment of the present invention, the Brucea javanica oil composition is Brucea javanica oil emulsion injection.

[0023] According to an embodiment of the present invention, it further includes glycerol.

[0024] According to an embodiment of the present invention, the volume ratio of the glycerol to the Brucea javanica oil is 1:4.

[0025] According to an embodiment of the present invention, the iodine value of the refined soybean phospholipid in the Brucea javanica oil emulsion injection is not less than 90 and not more than 100, the PC content is not less than 80% and not more than 95%, and the LPC content is not more than 3%.

[0026] According to an embodiment of the present invention, the oleic acid content in the Brucea javanica oil emulsion injection is 9%-12%. The Brucea javanica oil emulsion injection according to the embodiment of the present invention complies with the standard of Brucea javanica oil emulsion injection in "The Fourteenth Volume of Chinese Traditional Patent Medicine Formulas WS3-B-2739-97".

[0027] In the second aspect of the present invention, the present invention provides a method for preparing the Brucea javanica oil composition described in the first aspect. According to an embodiment of the present invention, it includes: mixing refined soybean phospholipid with an iodine value of not less than 90 and not more than 100 with Brucea javanica oil. The risk of hemolysis and other side effects during clinical application of the Brucea javanica oil emulsion injection composition prepared by the method according to the embodiment of the present invention is significantly reduced within 18 months, and the stability of the Brucea javanica oil composition is significantly increased.

[0028] According to an embodiment of the present invention, the above method may further include at least one of the following additional technical features:

[0029] According to an embodiment of the present invention, the PC content of the refined soybean phospholipid is not less than 80% and not more than 95%. According to a specific embodiment of the present invention, the stability of the Brucea javanica oil composition obtained by further controlling the PC content on the basis of controlling the iodine value of the refined soybean phospholipid to be not less than 90 and not more than 100 is extremely significantly improved.

[0030] According to an embodiment of the present invention, the LPC content of the refined soybean phospholipid is not more than 3%. According to a specific embodiment of the present invention, on the basis of controlling the iodine value of the refined soybean phospholipid to be not less than 90 and not more than 95%, and the PC content to be not less than 80% and not more than 95%, further controlling the LPC content, the stability of the obtained Brucea javanica oil composition is maximally improved.

[0031] According to an embodiment of the present invention, the mass-to-volume ratio of the refined soybean phospholipid to the Brucea javanica oil is 3 g: 20 mL.

[0032] According to an embodiment of the present invention, the Brucea javanica oil complies with the regulations on Brucea javanica oil in "The Fourteenth Volume of Chinese Patent Formulations WS3-B-2739-97".

[0033] According to an embodiment of the present invention, it further includes mixing with glycerol.

[0034] According to an embodiment of the present invention, the refined soybean phospholipid, glycerol, and Brucea javanica oil with an iodine value of not less than 90 and not more than 100 are mixed at a ratio of 3 g: 5 mL: 20 mL. The inventors found that by controlling the iodine value of the refined soybean phospholipid within the range of not less than 90 and not more than 100, and mixing the refined soybean phospholipid, glycerol, and Brucea javanica oil at a ratio of 3 g: 5 mL: 20 mL, the stability of the obtained Brucea javanica oil composition is significantly improved, and the risk of side effects after clinical application is significantly reduced.

[0035] The inventors conducted a large number of experiments to optimize the iodine value, PC content, and LPC content of refined soybean phospholipids. According to specific embodiments of the present invention, when the iodine value of the refined soybean phospholipids is not less than 90 and not more than 100, the PC content is not less than 80% and not more than 95%, and the LPC content is not more than 3%, the stability of the Brucea javanica oil composition obtained by mixing it with glycerol and Brucea javanica oil in the above-mentioned ratio is extremely significantly improved, and the risk of side effects after clinical application is extremely significantly reduced.

[0036] In the third aspect of the present invention, the present invention provides a Brucea javanica oil composition. According to embodiments of the present invention, the Brucea javanica oil composition is obtained by using the method described in the second aspect. The stability of the Brucea javanica oil composition according to embodiments of the present invention is significantly improved within 18 months, and the risk of hemolysis or other side effects during clinical application is significantly reduced.

[0037] In the fourth aspect of the present invention, the present invention provides a pharmaceutical composition. According to embodiments of the present invention, the pharmaceutical composition comprises the Brucea javanica oil composition described in the first aspect or the third aspect. The risk of hemolysis and other side effects during clinical application of the pharmaceutical composition according to embodiments of the present invention is significantly reduced, and the stability is significantly improved.

[0038] According to embodiments of the present invention, the pharmaceutical composition further comprises: a pharmaceutically acceptable adjuvant.

[0039] According to embodiments of the present invention, the pharmaceutically acceptable adjuvant includes at least one of a stabilizer, a wetting agent, an emulsifier, a binder, and an isotonic agent.

[0040] According to embodiments of the present invention, the pharmaceutical composition is in at least one of the forms of tablets, granules, powders, capsules, solutions, suspensions, and freeze-dried preparations.

[0041] Additional aspects and advantages of the present invention will be given in part in the following description, become apparent in part from the following description, or be learned through the practice of the present invention. Detailed Description of the Embodiments

[0042] The embodiments of the present invention will be described in detail below. The embodiments are intended to explain the present invention and should not be construed as limiting the present invention.

[0043] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one of these features. In the description of the present invention, "a plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0044] The main components of soybean phospholipids are phosphatidylcholine (PC), and also contain a small amount of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), etc. PC and PE are prone to hydrolysis during purification and storage, each losing one molecule of fatty acid to form lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Therefore, the risk of hemolysis is significantly increased after using Brucea javanica oil emulsion injection containing a large amount of LPC and LPE in clinical applications.

[0045] In the records of the prior art, it has been reported that the emulsifying effects and comprehensive quality indexes of different lecithin products with PC mass fractions of 98%, 80%, and 30% were compared, and it was found that lecithin with extremely high purity and extremely low purity was not conducive to the formation and stability of fat emulsion. Only the fat emulsion prepared from lecithin with a PC content of 80% (Lipoid E80, a product of Lipoid Company) was the most stable. In addition to containing 80% PC by mass fraction, Lipoid E80 also contains a small amount of acidic lipids. These acidic lipids can form a relatively high surface negative charge at pH = 7, preventing the aggregation between emulsion droplets and making the fat emulsion have excellent stability. In the purified lecithin, the content of phosphatidylcholine or phosphatidylethanolamine is as high as 95% - 100% by mass fraction, and there is almost no acidic lipid present. The surface charge between emulsion droplets decreases and the stability is poor, so it is not an ideal emulsifier. For Brucea javanica oil emulsion injection, since the lecithin with 80% content (Lipoid E80 of German Lipoid Company) has relatively stable properties, using Lipoid E80 as an emulsifier and adding antioxidant vitamin E can significantly improve the hemolysis situation of Brucea javanica oil emulsion injection (The influence of different emulsifiers on the hemolysis results of Brucea javanica oil emulsion injection, Gao Shan, Ma Junfa, Chinese Journal of Modern Applied Pharmacy, February 2011, 28(2)). Among them, Lipoid E80 is egg yolk lecithin with a PC content of 80% by mass fraction.

[0046] It can be seen that by replacing the refined soybean phospholipid involved in the preparation of Brucea javanica oil emulsion injection with egg yolk lecithin with a PC mass fraction of 80%, the stability of Brucea javanica oil emulsion injection will be improved and the hemolytic problem will be alleviated.

[0047] However, the composition gap between egg yolk phospholipid and soybean phospholipid is relatively large. Without clarifying the active ingredients of Brucea javanica oil emulsion injection, simple replacement is not advisable. This study was conducted based on the condition of not changing the phospholipid type of Brucea javanica oil emulsion injection.

[0048] Refined soybean phospholipid, as an emulsifier for Brucea javanica oil emulsion injection, will affect the quality of Brucea javanica oil emulsion injection. However, there are many factors affecting the properties of soybean phospholipid, such as the content of the main components of refined soybean phospholipid, the number of free fatty acids in refined soybean phospholipid, the number of unsaturated double bonds in refined soybean phospholipid, and so on. It still has practical significance to determine which factors in soybean phospholipid affect the hemolysis phenomenon in the preparation of Brucea javanica oil emulsion injection prepared with it, and adjust these factors so as to reduce its impact on the hemolysis of Brucea javanica oil emulsion injection without affecting other emulsifying properties of soybean phospholipid.

[0049] The refined soybean phospholipid used in Brucea javanica oil emulsion injection is the soybean phospholipid processed to be suitable for injection. According to the regulations of soybean phospholipid (for injection) in the fourth part of the Chinese Pharmacopoeia 2020 Edition, the PC content shall not be less than 45.0%, the PE shall not exceed 30.0%, and the total amount of PC and PE shall not be less than 70%. The content of LPE shall not exceed 1%, the content of LPC shall not exceed 3.5%, the total amount of LPE and LPC shall not exceed 4.0%, and the content of PI shall not exceed 5.0%. In the production of Brucea javanica oil emulsion injection, with the gradual optimization of the production process of refined soybean phospholipid, the PC content of the refined soybean phospholipid currently used in the production of Brucea javanica oil emulsion injection is between 50% and 70%.

[0050] According to the inspiration of the existing technology, the hemolysis situation of Brucea javanica oil emulsion injection will be alleviated when using egg yolk lecithin with a PC content of 80%.

[0051] However, when only increasing the PC content of refined soybean phospholipid to more than 80%, the hemolysis situation of Brucea javanica oil emulsion injection has not been alleviated. Of course, when the pH value of the refined soybean phospholipid is increased to 7 at this time, the hemolysis situation of Brucea javanica oil emulsion injection is alleviated to some extent, but the pH value of Brucea javanica oil emulsion injection is between 6.5 and 6.8 at this time, exceeding the national standard range of 4.0 - 6.0 for Brucea javanica oil emulsion injection.

[0052] LPC is lysophosphatidylcholine. In the existing technology, the key factor affecting the hemolysis risk of the preparation with refined soybean phospholipid is the LPC contained in soybean phospholipid. LPC is a by - product of the main component PC of refined soybean phospholipid, and LPC is helpful for the emulsification of refined soybean phospholipid. Therefore, it is not practical to simply remove LPC to reduce the hemolysis risk of Brucea javanica oil emulsion injection.

[0053] In view of the fact that the actual influencing factors of the stability of different emulsions are different, the inventor carried out the research on the preparation of Brucea javanica oil emulsion injection with refined soybean phospholipid with low LPC. However, the experimental results show that simply reducing the refined soybean phospholipid with low LPC cannot completely solve the hemolysis risk problem of Brucea javanica oil emulsion injection. On the contrary, it increases other risks of unstable quality of Brucea javanica oil emulsion injection, such as the stratification phenomenon between the aqueous phase and the oil phase.

[0054] The inventors also carried out the preparation of Brucea javanica oil emulsion injection with soybean phospholipids having a high PC content and a low LPC content. In the research, the inventors learned from existing reports that LPC has the characteristics of an emulsifier and can play a positive role in the stability of the emulsifier. By reducing the LPC content of refined soybean phospholipids to less than 2.5% and increasing the PC content to more than 80%, it was found that the hemolysis problem of Brucea javanica oil emulsion injection was controlled to a certain extent, and the stability problem was also solved.

[0055] During the process of the inventors' research on the component ratios of refined soybean phospholipids, it was very unexpectedly found that when the iodine value of the refined soybean phospholipids exceeded 90 and was not higher than 100, the Brucea javanica oil emulsion injection prepared with the refined soybean phospholipids had a low hemolysis risk, while when the iodine value was less than 90, the Brucea javanica oil emulsion injection prepared with the refined soybean phospholipids had a high hemolysis risk.

[0056] In the prior art, the iodine value of oils and fats is an index reflecting the degree of unsaturation of refined soybean phospholipids. Refined soybean phospholipids with a high iodine value contain more unsaturated double bonds and are prone to oxidation during storage and in the preparation of preparations, thereby generating volatile small-molecule substances such as aldehydes and ketones, being prone to oxidation, which limits the performance of refined soybean phospholipids and makes the Brucea javanica oil emulsion injection unstable.

[0057] In the present invention, the refined soybean phospholipids used in the Brucea javanica oil emulsion injection should first comply with the regulations in "Soybean Phospholipids (for Injection)" in the Fourth Part of the Chinese Pharmacopoeia (2020 Edition), that is, the range of the iodine value should not be less than 75. However, in the standard of the Fourteenth Volume of the Chinese Medicine Formulation Preparations (WS3-B-2739-97) of the Ministry of Health Drug Standards, it is stipulated that the iodine value of refined soybean phospholipids should be 80 - 100. In the prior art, in order to ensure that refined soybean phospholipids do not oxidize during use and storage, attention is usually paid to not making the iodine value too large. However, according to the research of the present invention, when the iodine value is greater than 90 for the preparation of Brucea javanica oil emulsion injection with refined soybean phospholipids and their PC and LPC are within a certain range, the stability of the obtained Brucea javanica oil emulsion injection is significantly improved.

[0058] The following describes the present invention with reference to specific embodiments. It should be noted that these embodiments are only descriptive and do not limit the present invention in any way.

[0059] Example 1 Preparation of refined soybean phospholipids with different PC contents, LPC contents, and iodine values

[0060] 1. Crude extraction of soybean phospholipids

[0061] The inventor controls the iodine value of refined soybean phospholipids by screening soybean concentrated phospholipids with an iodine value greater than 90 or less than 90. The screened soybean concentrated phospholipids are mixed with acetone at a mass-to-volume ratio of 1:2 to 1:10, stirred and mixed evenly, and after suction filtration to remove the supernatant, the precipitate is dried to obtain acetone-insoluble matter. 95% ethanol with a mass-to-volume ratio of 1:10 to 1:50 with respect to the soybean concentrated phospholipids is added to the acetone-insoluble matter, stirred and mixed evenly, then suction filtered to obtain an ethanol solution and ethanol-insoluble matter. The ethanol solution is collected, and then the same amount of ethanol as the first addition is added to the ethanol-insoluble matter, stirred and mixed evenly, followed by suction filtration. The ethanol solution obtained is collected again, and 95% ethanol with a volume half that of the first addition is added to the ethanol-insoluble matter, mechanically stirred and mixed evenly, and then suction filtered. The ethanol solution obtained is collected. The ethanol solutions obtained from the above three suction filtrations are combined to obtain a soybean phospholipid extract.

[0062] 2. Refined soybean phospholipids

[0063] The soybean phospholipid extract obtained in step 1 is added to a silica gel column chromatography, and eluted with a mixed solvent of petroleum ether:ethanol:water (about 1:1:0.2 to 1:1:1) as the eluent. The PC values of each soybean phospholipid fraction are monitored, and all soybean phospholipid fractions with a pH value meeting the requirements are collected and combined to form a combined solution of qualified soybean phospholipid fractions. The pH value of the combined solution is adjusted, and after evaporating the solvent of the combined solution, it is directly purified through an aluminum oxide column. The PC content in the soybean phospholipids is controlled by adjusting the filling amount of neutral aluminum oxide in the neutral aluminum oxide column, and then eluted with 95% industrial ethanol as the eluent. The LPC content in the soybean phospholipids is controlled by adjusting the concentration of the ethanol solvent participating in the elution. After collecting the eluent, the solvent is evaporated to obtain refined soybean phospholipids meeting the experimental requirements.

[0064] 3. Determination of the quality of refined soybean phospholipids

[0065] The iodine value, PC content, LPC content, and pH value of the refined soybean phospholipids obtained in step 2 are detected to screen out soybean phospholipids meeting the requirements. The detection methods for each quality index are as follows:

[0066] (1) Iodine value content

[0067] The iodine value refers to the amount of iodine (g) required when 100 g of the test sample is fully halogenated.

[0068] Unless otherwise specified, take an appropriate amount of the test sample [its weight (g) is approximately equivalent to 25 divided by the maximum iodine value of the test sample], weigh accurately, place it in a dry iodine flask of 250 mL, add 10 mL of chloroform, dissolve it, accurately add 25 mL of iodine bromide solution, stopper tightly, shake well, and place it in the dark for 30 minutes. Add 10 mL of freshly prepared potassium iodide test solution and 100 mL of water, shake well, titrate the remaining iodine with sodium thiosulfate titrant (0.1 mol / L), pay attention to shaking well during titration. When the brown color of the mixed solution turns light yellow, add 1 mL of starch indicator solution, and continue titrating until the blue color disappears; at the same time, conduct a blank test. Let the volume (mL) of sodium thiosulfate titrant (0.1 mol / L) consumed by the test sample be A, the volume (mL) consumed by the blank test be B, and the weight (g) of the test sample be W. Calculate the iodine value according to the following formula: Iodine value of the test sample = ((B - A) × 1.269) / W.

[0069] (2) PC content

[0070] Determine the PC content of the refined soybean phospholipid obtained in Step 2 according to the high performance liquid chromatography method (General Principles 0512) in Part IV of the Chinese Pharmacopoeia (2020 Edition), and the specific operation is as follows:

[0071] Use silica gel as the filler (chromatographic column: Alltima Sillica, 250 mm × 4.6 mm, 5 μm or a chromatographic column with equivalent efficiency), column temperature is 40 °C; use methanol - water - glacial acetic acid - triethylamine (85∶15∶0.45∶0.05) as mobile phase A, and use n - hexane - isopropanol - mobile phase A (20∶48∶32)

[0072] as mobile phase B; flow rate is 1 mL per minute; perform gradient elution according to the parameters shown in Table 1; the detector is an evaporative light scattering detector (reference conditions: drift tube temperature is 72 °C; carrier gas flow rate is 2.0 L per minute).

[0073] Table 1:

[0074] Time (min) Mobile Phase A (%) Mobile Phase B (%) 0 10 90 20 30 70 35 95 5 36 10 90 41 10 90

[0075] Take appropriate amounts of phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylethanolamine, phosphatidylcholine, and lysophosphatidylcholine reference substances, dissolve and dilute them with chloroform - methanol (2∶1) to prepare a mixed solution containing 50 μg, 100 μg, 100 μg, 200 μg, and 200 μg of the above reference substances respectively in each 1 mL. Take 20 μL and inject it into the liquid chromatograph. Each component is eluted in the above order, and the resolution of each component should meet the requirements. The number of theoretical plates calculated based on the peaks of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol is not less than 1500.

[0076] Weigh appropriate amounts of phosphatidylethanolamine and soy phosphatidylcholine reference substances accurately, dissolve them with chloroform-methanol (2:1), and quantitatively dilute to prepare solutions containing 50 μg, 100 μg, 150 μg, 200 μg, 300 μg, 400 μg of soy phosphatidylcholine and 5 μg, 10 μg, 15 μg, 20 μg, 30 μg, 40 μg of phosphatidylethanolamine per 1 mL as reference substance solutions. Precisely measure 20 μL of each of the above reference substance solutions and inject them into the liquid chromatograph, record the chromatogram, and calculate the regression equation using the logarithm of the reference substance solution concentration and the logarithm of the corresponding peak area; separately, accurately weigh about 15 mg of this product, place it in a 50 mL volumetric flask, dissolve it with chloroform-methanol (2:1), dilute to the mark, shake well, and use it as the test substance solution. Precisely measure 20 μL of the test substance solution and inject it into the liquid chromatograph, record the chromatogram. Calculate the contents of phosphatidylcholine and phosphatidylethanolamine from the regression equation.

[0077] (3) Content of LPC

[0078] Accurately weigh about 125 mg of the refined soybean phospholipid obtained in step 2, place it in a 25 mL volumetric flask, dissolve it with chloroform-methanol (2:1), dilute to the mark, shake well, and use it as the test substance solution; separately, weigh appropriate amounts of lysophosphatidylethanolamine, lysophosphatidylcholine, and phosphatidylinositol reference substances accurately, dissolve them with chloroform-methanol (2:1), and quantitatively dilute to prepare solutions containing 10 μg, 20 μg, 40 μg, 60 μg, 80 μg, 100 μg of lysophosphatidylethanolamine, 50 μg, 100 μg, 200 μg, 300 μg, 400 μg, 500 μg of lysophosphatidylcholine, and 5 μg, 10 μg, 15 μg, 20 μg, 30 μg, 40 μg of phosphatidylinositol per 1 mL as reference substance solutions. According to the chromatographic conditions under the determination of the contents of phosphatidylcholine and phosphatidylethanolamine, precisely measure 20 μL of each reference substance solution and inject it into the liquid chromatograph, calculate the regression equation with the logarithm of the reference substance solution concentration as the abscissa and the logarithm of the peak area as the ordinate. Precisely measure 20 μL of the test substance solution and inject it into the liquid chromatograph, record the peak area, and calculate the contents of lysophosphatidylethanolamine, lysophosphatidylcholine, and phosphatidylinositol from the regression equation. The content of lysophosphatidylethanolamine shall not exceed 1%, the content of lysophosphatidylcholine shall not exceed 3.5%, the total content of lysophosphatidylethanolamine and lysophosphatidylcholine shall not exceed 4.0%, the content of phosphatidylinositol shall not exceed 5.0%, and the total related substances shall not exceed 8.0%.

[0079] (4) pH value

[0080] It is processed according to the quality standard of refined soybean phospholipid specified in "The Fourteenth Volume of Traditional Chinese Medicine Prepared Patent Formulas WS3-B-2739-97". Take 1 g of the refined soybean phospholipid obtained in Example 2, grind it evenly (about 10 minutes), and determine it according to the pH value determination method in General Principles 0631 of the Fourth Part of the Chinese Pharmacopoeia 2020 Edition. The pH meter (acidimeter) should be periodically calibrated and meet the relevant national regulations. Before determination, the instrument should be calibrated with a standard buffer solution. When measuring the pH value, operate according to the instrument's operating instructions.

[0081] 4. Preparation of Brucea javanica Oil Emulsion Injection

[0082] The same batch of Brucea javanica oil obtained by extracting Brucea javanica with petroleum ether and the same batch number of glycerol are evenly divided into 2 groups, with 36 portions in each group, for a total of 72 portions. Each group is respectively mixed with the qualified refined soybean phospholipid obtained in Step 1 and a certain mass of injection water to prepare the Brucea javanica oil emulsion injection. The specific preparation method refers to the preparation method of Brucea javanica oil emulsion injection recorded in "The Fourteenth Volume of Traditional Chinese Medicine Prepared Patent Formulas WS3-B-2739-97": Take refined soybean phospholipid and warm glycerol, mix them with a certain mass of injection water, transfer them into a high-speed tissue homogenizer, stir at 8000 revolutions per minute twice, the first time for 5 minutes and the second time for 2 minutes to make them evenly dispersed. Add warm refined Brucea javanica oil. Among them, the ratio of soybean phospholipid: glycerol: Brucea javanica oil is 3 g: 5 mL: 20 mL, stir 3 times, 2 minutes each time, to form a primary emulsion. Add injection water until the ratio of Brucea javanica oil to the total amount is 1 g: 10 mL, then transfer it into a high-pressure homogenizer (40 MPa) for homogenization three times, filter, take the filtrate, fill and seal, and sterilize to obtain Brucea javanica oil injection. Each batch of Brucea javanica oil emulsion injection corresponding to the refined soybean phospholipid is produced in parallel for 3 batches, and each quality control point of the obtained batches of Brucea javanica oil emulsion injection meets "The Fourteenth Volume of Traditional Chinese Medicine Prepared Patent Formulas WS3-B-2739-97".

[0083] 5. Long-term stability experiment of Brucea javanica oil emulsion injection

[0084] For each batch of Brucea javanica oil emulsion injection, long-term hemolysis and aggregation experiments are carried out on the test samples at 0 months, 6 months, 12 months, 15 months, and 18 months, and the appearance of each batch of Brucea javanica oil emulsion injection is observed with the naked eye.

[0085] The determination of hemolysis and aggregation is carried out according to the in vitro method recorded in General Principles 1148 of the Fourth Part of the Chinese Pharmacopoeia 2020 Edition. The specific experimental operation is as follows:

[0086] (1) Preparation of 2% red blood cell suspension

[0087] Take the blood of healthy rabbits, put it into a conical flask containing glass beads, shake for 10 minutes, or stir the blood with a glass rod to remove fibrinogen and make it defibrinated blood. Add about 10 times the amount of 0.9% sodium chloride solution, shake well, centrifuge at 1000 - 1500 revolutions per minute for 15 minutes, remove the supernatant, and wash the precipitated red blood cells with 0.9% sodium chloride solution 2 - 3 times by the above method until the supernatant is no longer red. Make the obtained red blood cells into a 2% suspension with 0.9% sodium chloride solution for the test.

[0088] (2) Preparation of the test article (Brucea javanica oil emulsion injection)

[0089] Take 5 clean glass test tubes, number them. Tubes 1 and 2 are the test tubes for the test article, tube 3 is the negative control tube, tube 4 is the positive control tube, and tube 5 is the test article control tube. Add 2% red blood cell suspension, 0.9% sodium chloride solution, and purified water successively as shown in Table 2. After mixing evenly, immediately place it in a constant temperature incubator at 37°C ± 0.5°C for incubation; observe the hemolysis reaction after 3 hours.

[0090] Table 2:

[0091]

[0092] If the solution in the test tube is clearly red, there is no cell residue or only a small amount of red blood cell residue at the bottom of the tube, it indicates that hemolysis has occurred; if all the red blood cells sink, the supernatant is colorless and clear, or although the supernatant is colored and clear, there is no obvious difference between tubes 1, 2 and tube 5 observed with the naked eye, it indicates that no hemolysis has occurred. If hemolysis occurs in one of tubes 1 or 2, the experiment will be repeated for this batch number.

[0093] (3) Result judgment

[0094] When there is no hemolysis in the negative control tube and hemolysis occurs in the positive control tube, if the solutions in the 2 test tubes for the test article do not show hemolysis within 3 hours, it is determined that the test article meets the requirements; if the solution in 1 test tube for the test article shows hemolysis within 3 hours, 4 test tubes for the test article should be set up for retest, and the solutions in the test tubes for the test article shall not show hemolysis within 3 hours, otherwise it is determined that the test article does not meet the requirements.

[0095] Example 2 Preparation of Brucea javanica oil emulsion injection with refined soybean phospholipids of different PC contents

[0096] 1. Preparation of refined soybean phospholipids with different PC contents

[0097] According to the preparation method described in Example 1, and adjusting the filling amount of neutral alumina in the neutral alumina column, the refined soybean phospholipids with different PC contents shown in Table 3 were prepared. The pH values of batch numbers 100004 and 100006 were controlled at about 7. In addition to meeting the requirements of Table 3, the quality control points of each batch of the prepared refined soybean phospholipids must comply with the provisions of the Fourth Part of the Chinese Pharmacopoeia (2020 Edition) and the Regulations of the Fourteenth Volume of Traditional Chinese Medicine Formulas (WS3-B-2739-97).

[0098] Table 3: Setting of PC Content of Each Batch of Soybean Phospholipids

[0099] Batch Numbers of Each Lot of Soybean Lecithin Setting of PC Content Setting of pH Value 100001 Not Controlled Not Controlled 100002 70% < PC Content < 80% Not Controlled 100003 80% ≤ PC Content < 90% Not Controlled 100004 80% ≤ PC Content < 90% pH Value = 7.0 100005 90% ≤ PC Content Not Controlled 100006 90% ≤ PC Content pH Value = 7.0

[0100] Each batch of refined soybean phospholipids was detected according to the method described in Example 1, and the obtained key quality control points are shown in Table 4. The same batch of Brucea javanica oil and the same batch of glycerol were divided into 6 parallel portions, and Brucea javanica oil emulsion injection was prepared with each batch of refined soybean phospholipids numbered 100001 - 100006 according to the method described in Example 1. For each batch of refined soybean phospholipids, 3 batches of Brucea javanica oil emulsion injection were produced in parallel, as shown in Table 5. The quality control points of each batch of Brucea javanica oil emulsion injection met the standards in the Fourteenth Volume of Traditional Chinese Medicine Formulas (WS3-B-2739-97).

[0101] Each batch of Brucea javanica oil emulsion injection was subjected to relevant research on in vitro hemolysis and aggregation experiments and long-term hemolysis and aggregation experiments as described in Example 3. At the same time, the appearance of each batch of Brucea javanica oil emulsion injection was observed with the naked eye, and the results are shown in Table 5.

[0102] Table 4: Measured Values of Key Quality Control Points of Each Batch of Refined Soybean Phospholipids

[0103]

[0104]

[0105] Table 5: Brucea javanica Oil Emulsion Injection Corresponding to Each Batch of Refined Soybean Phospholipids and Each Experimental Result

[0106]

[0107] Experimental Results: According to the experimental data of this example, only increasing the PC content of refined soybean phospholipids, for example, when the PC content exceeds 80%, the hemolysis situation of Brucea javanica oil emulsion injection has not been effectively improved.

[0108] Example 3 Preparation of Brucea javanica Oil Emulsion Injection with Different LPC Contents

[0109] 1. Preparation of Refined Soybean Phospholipids with Different LPC Contents

[0110] Preparation of refined soybean phospholipids with different LPC contents: According to the preparation methods described in Example 1 and Example 2 respectively, further adjust the concentration of the ethanol solvent involved in elution to control, and prepare batches of refined soybean phospholipids with LPC and PC contents as shown in Table 6, Table 9, Table 12, and Table 15. Except for meeting the requirements of Table 6, Table 9, Table 12, and Table 15 respectively, other quality control points of each batch of soybean phospholipids prepared must comply with the provisions of "Volume IV of Chinese Pharmacopoeia 2020 Edition" and "WS3-B-2739-97, Fourteenth Volume of Chinese Patent Formulary".

[0111] Detect each batch of refined soybean phospholipids according to the method described in Example 1, and the measured values of the key quality control points are shown in Table 7, Table 10, Table 13, and Table 16. Take the same batch of Brucea javanica oil and the same batch of glycerol, divide them into 4 groups in parallel, with 12 portions in each group, a total of 48 portions. Each group is respectively prepared into Brucea javanica oil emulsion injection with each batch of refined soybean phospholipids as shown in Table 6, Table 9, Table 12, and Table 15 according to the method described in Example 1. For each batch of soybean phospholipids, the Brucea javanica oil emulsion injection is produced in parallel for 3 batches. The batch numbers of soybean phospholipids and Brucea javanica oil emulsion injection are shown in Table 8, Table 11, Table 14, and Table 17. Each quality control point of each batch of Brucea javanica oil emulsion injection meets the standards of "WS3-B-2739-97, Fourteenth Volume of Chinese Patent Formulary".

[0112] Conduct relevant research on each batch of Brucea javanica oil emulsion injection according to the in vitro hemolysis and long-term hemolysis experiments described in Example 1. At the same time, visually observe the appearance of each batch of Brucea javanica oil emulsion injection, and the results are shown in Table 8, Table 11, Table 14, and Table 17.

[0113] Table 6: Setting of relevant parameters of each batch of refined soybean phospholipids when 3% < LPC content ≤ 3.5%

[0114] Batch Numbers of Each Lot of Refined Soybean Lecithin Setting of PC Content 200001 Not Controlled (about 60%) 200002 70% < PC Content < 80% 200003 80% ≤ PC Content < 90% 200004 90% ≤ PC Content

[0115] Table 7: Situation of key quality control points of each batch of refined soybean phospholipids when 3% < LPC content ≤ 3.5%

[0116] Batch Numbers of Each Lot of Refined Soybean Lecithin PC Content LPC Content pH Value Iodine Value 200001 61％ 3.5％ 5.6 86 200002 77％ 3.2％ 5.4 91 200003 85％ 3.1％ 5.5 94 200004 91％ 3.1％ 5.6 90

[0117] Table 8: Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids and each experimental result when 3% < LPC content ≤ 3.5%

[0118]

[0119]

[0120] Note: "Qualified" in the appearance means meeting the requirement of the character of Brucea javanica oil emulsion injection in "WS3-B-2739-97, Fourteenth Volume of Chinese Patent Formulary": "This product is a milky white homogeneous emulsion liquid".

[0121] Table 9: Settings of relevant parameters for each batch of refined soybean phospholipids when 2.5% < LPC content ≤ 3%

[0122] Batch Numbers of Each Lot of Refined Soybean Lecithin Setting of PC Content 300001 Not Controlled 300002 70% < PC Content < 80% 300003 80% ≤ PC Content < 90% 300004 90% ≤ PC Content

[0123] Table 10: Key property control point situations for each batch of refined soybean phospholipids when 2.5% < LPC content ≤ 3%

[0124] Batch Numbers of Each Lot of Refined Soybean Lecithin PC Content LPC Content pH Value Iodine Value 300001 68％ 2.7％ 5.8 91 300002 74％ 2.6％ 5.8 89 300003 86％ 2.8％ 5.2 86 300004 90％ 2.7％ 5.1 87

[0125] Table 11: Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids and each experimental result when 2.5% < LPC content ≤ 3%

[0126]

[0127] Table 12: Settings of relevant parameters for each batch of refined soybean phospholipids when 1.5% < LPC content ≤ 2.5%

[0128]

[0129]

[0130] Table 13: Key property control point situations for each batch of refined soybean phospholipids when 1.5% < LPC content ≤ 2.5%

[0131] Batch Numbers of Each Lot of Refined Soybean Lecithin PC Content LPC Content pH Value Iodine Value 400001 68％ 1.8％ 5.1 89 400002 76％ 2.2％ 5.6 91 400003 84％ 1.7％ 5.4 86 400004 92％ 1.7％ 5.3 86

[0132] Table 14: Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids and each experimental result when 1.5% < LPC content ≤ 2.5%

[0133]

[0134] Table 15: Settings of relevant parameters for each batch of refined soybean phospholipids when "not detected" < LPC content ≤ 1.5%

[0135] Batch Numbers of Each Lot of Refined Soybean Lecithin Setting of PC Content 500001 Not Controlled 500002 70% < PC Content < 80% 500003 80% ≤ PC Content < 90% 500004 90% ≤ PC Content

[0136] Table 16: Key property control point situations for each batch of refined soybean phospholipids when "not detected" < LPC content ≤ 1.5%

[0137]

[0138]

[0139] Table 17: Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids and each experimental result when "not detected" < LPC content ≤ 1.5%

[0140]

[0141] From the experimental results shown in Table 8, Table 11, Table 14, and Table 17, it can be seen that when the LPC content is ≤ 2.5% and the PC content is ≥ 80%, the Brucea javanica oil emulsion injection prepared has a relatively low risk of hemolysis.

[0142] Example 4 Preparation of Brucea javanica oil emulsion injection with different iodine values

[0143] 1. Preparation of refined soybean phospholipids with different iodine values

[0144] According to the preparation methods described in Examples 1 - 3 respectively, refined soybean phospholipids with different iodine values, PC, and LPC values were prepared according to the values shown in Table 18 and Table 19. Each batch of selected refined soybean phospholipids was detected according to the method described in Example 1. Except for the numerical requirements shown in Table 18 and Table 19, other quality control points of the prepared refined soybean phospholipids complied with the provisions of "Volume IV of the Chinese Pharmacopoeia 2020 Edition" and "The Fourteenth Volume of Chinese Patent Medicines WS3 - B - 2739 - 97". The measured values of the key indicators of each batch of refined soybean phospholipids are shown in Table 20 and Table 21.

[0145] Table 18: Parameter settings of refined soybean phospholipids when the iodine value is less than 90

[0146]

[0147]

[0148] Table 19: Parameter settings of refined soybean phospholipids when the iodine value is not less than 90

[0149]

[0150] Table 20: Measured values of each parameter of refined soybean phospholipids when the iodine value is less than 90

[0151]

[0152]

[0153] Table 21: Measured values of each parameter of soybean phospholipids when the iodine value is not less than 90

[0154] Batch Numbers of Each Lot of Refined Soybean Lecithin PC Content LPC Content pH Value Iodine Value 700001 76％ 3.4％ 5.5 94 700002 74％ 2.6％ 5.6 91 700003 78％ 2.1％ 5.5 99 700004 75％ 1.3％ 5.4 95 700005 88％ 3.2％ 5.5 91 700006 82％ 2.6％ 5.6 97 700007 83％ 1.7％ 5.5 90 700008 86％ 0.1％ 5.6 93 700009 91％ 3.4％ 5.5 92 700010 92％ 2.6％ 5.6 98 700011 90％ 2.0％ 5.5 96 700012 92％ 1.5％ 5.6 94

[0155] When the iodine value is less than 90, the results of the long-term hemolysis test of Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids are shown in Table 22. Among them, the Brucea javanica oil emulsion injection prepared with refined soybean phospholipids with batch numbers 600007, 600008, 600011, and 600012 has a lower risk of causing hemolysis within 18 months. When the iodine value is not less than 90, the results of the long-term hemolysis test of Brucea javanica oil emulsion injection corresponding to each batch of refined soybean phospholipids are shown in Table 23. Among them, the Brucea javanica oil emulsion injection prepared with refined soybean phospholipids with batch numbers 700006 - 700012 has a lower risk of causing hemolysis within 18 months. When the iodine value of the refined soybean phospholipid is not less than 90, the risk of hemolysis of the Brucea javanica oil emulsion injection is lower than that of the Brucea javanica oil emulsion injection prepared with refined soybean phospholipids with an iodine value less than 90.

[0156] Table 22: Results of the long-term hemolysis test of Brucea javanica oil emulsion injection with an iodine value less than 90

[0157]

[0158]

[0159] Table 23: Results of the long-term hemolysis test of Brucea javanica oil emulsion injection with an iodine value not less than 90

[0160]

[0161]

[0162] It can be seen from the data shown in Table 22 that when the iodine value < 90 and the LPC content is ≤ 2.5% and the PC content ≥ 80%, the prepared Brucea javanica oil emulsion injection has a lower risk of hemolysis. It can be seen from the data shown in Table 23 that when the iodine value is controlled not less than 90 and not higher than 100, the LPC content of the Brucea javanica oil emulsion injection can be appropriately increased. When the iodine value of the refined soybean phospholipid used in the Brucea javanica oil emulsion injection is not less than 90 and not higher than 100, the LPC content ≤ 3%, and 80% ≤ PC content ≤ 95%, the risk of hemolysis of the prepared Brucea javanica oil emulsion injection is almost zero. At this time, the risk of hemolysis of the Brucea javanica oil emulsion injection can be more effectively controlled.

[0163] In the description of this specification, the description referring to terms such as "one embodiment", "some embodiments", "examples", "specific examples", or "some examples", etc. means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0164] Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention.

Claims

1. A Brucea javanica oil composition, characterized in that, Comprising: Refined soya lecithin, Brucea javanica oil and glycerol, wherein the iodine value of the refined soya lecithin is not less than 90 and not more than 100, the PC content of the refined soya lecithin is not less than 80% and not more than 95%, the LPC content of the refined soya lecithin is not more than 3%, the mass-to-volume ratio of the refined soya lecithin to the Brucea javanica oil is 3 g:20 mL, and the volume ratio of the glycerol to the Brucea javanica oil is 1:

4.

2. The Brucea javanica oil composition according to claim 1, characterized in that, The Brucea javanica oil composition is Brucea javanica oil emulsion injection.

3. The Brucea javanica oil composition according to claim 2, characterized in that, In the Brucea javanica oil emulsion injection, the iodine value of the refined soya lecithin is not less than 90 and not more than 100, the PC content is not less than 80% and not more than 95%, and the LPC content is not more than 3%.

4. The Brucea javanica oil composition according to claim 2, characterized in that, The oleic acid content in the Brucea javanica oil emulsion injection is 9% - 12%.

5. A method for preparing the Brucea javanica oil composition according to any one of claims 1 to 4, characterized in that, Comprising: Mixing refined soya lecithin with an iodine value not less than 90 and not more than 100, glycerol, and Brucea javanica oil in a ratio of 3 g:5 mL:20 mL, wherein the PC content of the refined soya lecithin is not less than 80% and not more than 95%, and the LPC content of the refined soya lecithin is not more than 3%.

6. A Brucea javanica oil composition, characterized in that, The Brucea javanica oil composition is obtained by the method described in claim 5.

7. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises the Brucea javanica oil composition described in claim 1 - 4 or claim 6.

8. The pharmaceutical composition according to claim 7, characterized in that, The pharmaceutical composition further comprises: a pharmaceutically acceptable adjuvant, and the pharmaceutically acceptable adjuvant includes at least one of a stabilizer, a wetting agent, an emulsifier, a binder, and an isotonic agent.

9. The pharmaceutical composition according to claim 7, characterized in that, The pharmaceutical composition is in at least one of a solution form and a suspension form.

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