Low-aluminum-element egg yolk lecithin and preparation method thereof

Abstract

The invention discloses low-aluminum-element egg yolk lecithin and a preparation method thereof, and relates to the technical field of pharmacy. Comprising the following steps: adding yolk powder into ethanol and extracting to obtain an extracting solution; adding a material containing an aluminum element into the extracting solution for refining, stirring for reaction, and filtering to obtain filtrate; adding cationic resin into the filtrate, stirring for reaction, and filtering to obtain filtrate; and carrying out rotary evaporation concentration on the filtrate, adding acetone for crystallization, and drying the crystallized product to obtain the low-aluminum-element egg yolk lecithin. According to the preparation method disclosed by the invention, after refining treatment, the aluminum element in the egg yolk lecithin is further removed by using cationic resin, so that the level of the aluminum element in the prepared egg yolk lecithin is obviously reduced, and finally, the content of the aluminum element in a fat emulsion product prepared from the low-aluminum egg yolk lecithin is obviously reduced; therefore, the risk of ultrahigh aluminum element level in fat emulsion and other preparation products prepared from the egg yolk lecithin is reduced.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to low-aluminum egg yolk lecithin and a preparation method thereof. Background Art

[0002] Aluminum is a common additive for parenteral nutrition solutions, which is used to provide nutrients needed by the human body. However, excessive aluminum intake may be harmful to human health, especially long-term high-dose intake. According to international regulations and standards, the control limit of aluminum in parenteral nutrition solutions is generally no more than 25 micrograms per liter of liquid. This limit is based on research on the toxicity of aluminum intake and clinical experience. High-dose aluminum intake may lead to health problems such as osteoporosis, anemia, and nervous system damage. In addition, long-term high-dose aluminum intake is also associated with an increased incidence of diseases such as kidney disease and aluminum bone disease. In order to ensure the safety and effectiveness of parenteral nutrition solutions, clinicians should carefully control the amount of aluminum added to ensure that nutrition is provided within a safe range. At the same time, for patients who need long-term parenteral nutrition treatment, aluminum levels should be monitored regularly, and close attention should be paid to the possible risk of aluminum poisoning. It should be noted that the control limit of aluminum in parenteral nutrition solutions only applies to the use of parenteral nutrition solutions, and does not apply to the intake limit of aluminum in oral nutritional supplements or other food sources. Therefore, when determining personal aluminum intake limits, it is also necessary to consider other sources of aluminum intake and make judgments based on personal circumstances.

[0003] In recent years, with the gradual disclosure of some major drug-related incidents, the public has become increasingly concerned about the quality of injections. Drug regulatory authorities have also introduced a series of measures to improve the safety control standards of injections. There have been reports of aluminum toxicity (central nervous system or bone) in patients with renal dysfunction using TbrN preparations abroad. The appendix of the Japanese Pharmacopoeia contains the content of the determination method of trace aluminum in central venous parenteral nutrition infusion (Totalbrarenteral Nutrition, TbrN). Since July 2004, the FDA has required manufacturers to quantify aluminum in most parenteral nutrition solutions. Large-volume injection solutions, such as glucose, amino acids, fat emulsions, and distilled water for injection, require aluminum content to be less than 25μg / L, but there is no upper limit on aluminum content for injection solutions with small solvents, such as electrolytes, vitamins, and trace elements. Aluminum in parenteral nutrition solutions There is no requirement to add aluminum to parenteral nutrition solutions, and the aluminum present in them is a type of drug pollution.

[0004] Egg yolk lecithin is an important pharmaceutical excipient and is often used as an emulsifier in the pharmaceutical industry in related dosage forms such as fat emulsion injections, including drug-loaded emulsions such as propofol medium and long-chain fat emulsion injection, flurbiprofen axetil injection, etc.; parenteral nutrition emulsions such as fat emulsion injection, fat emulsion amino acid (17) glucose (11%) injection, etc. Egg yolk lecithin is defined in the Chinese Pharmacopoeia 2020 Edition as: This product is a phospholipid mixture obtained by extracting and refining with an appropriate solvent using egg yolk or egg yolk powder as the raw material. Calculated on the anhydrous basis, the nitrogen (N) content should be 1.75% - 1.95%, the phosphorus (P) content should be 3.5% - 4.1%, phosphatidylcholine should not be less than 68%, phosphatidylethanolamine should not exceed 20%, and the total amount of phosphatidylcholine and phosphatidylethanolamine should not be less than 80%.

[0005] Thus, the pharmacopoeia controls multiple indicators of egg yolk lecithin. Therefore, in the process of preparing and extracting egg yolk lecithin, various refining / purification processes are often required, such as using aluminum oxide, silica gel, activated clay for refining / purification treatment, and these refining / purification processes may have a certain impact on the aluminum element content of egg yolk lecithin, resulting in a relatively high aluminum element content in the finally prepared egg yolk lecithin. And egg yolk lecithin, as a raw and auxiliary material, ultimately also affects the aluminum element level in the fat emulsion preparation, making the finally prepared fat emulsion-related products at risk of having a relatively high aluminum element content. Summary of the Invention

[0006] The present invention is to solve the technical problem that in the process of preparing and extracting egg yolk lecithin, materials containing aluminum are often used, resulting in a relatively high aluminum element content in the finally prepared egg yolk lecithin, which in turn affects the aluminum element level in the fat emulsion preparation and leads to a relatively high aluminum element content in the finally prepared fat emulsion-related products. The purpose is to provide a low-aluminum-element egg yolk lecithin and its preparation method, which can effectively reduce the aluminum element level in egg yolk lecithin, thereby reducing the risk of excessive aluminum element level in the preparation products such as fat emulsion prepared using such egg yolk lecithin.

[0007] The present invention is achieved by the following technical solutions:

[0008] The first object of the present invention is to provide a preparation method of low-aluminum-element egg yolk lecithin, including the following steps:

[0009] Add egg yolk powder to ethanol for extraction to obtain an extract;

[0010] Add materials containing aluminum elements to the extract for refining, stir and react, and filter to obtain a filtrate;

[0011] Add cation exchange resin to the filtrate, stir and react, and filter to obtain a filtrate;

[0012] The filtrate is concentrated by rotary evaporation, acetone is added for crystallization, and the crystallization product is dried to obtain low-aluminum-element egg yolk lecithin.

[0013] As a further technical solution of the present invention, the egg yolk powder is defatted egg yolk powder.

[0014] As a further technical solution of the present invention, the preparation steps of the defatted egg yolk powder are: adding acetone to the egg yolk powder and stirring, repeating at least three times to obtain defatted egg yolk powder.

[0015] As a further technical solution of the present invention, the mass ratio of the egg yolk powder to the material containing aluminum element is 50:(2 - 3).

[0016] As a further technical solution of the present invention, the material containing aluminum element is aluminum trioxide or activated clay.

[0017] As a further technical solution of the present invention, the mass ratio of the egg yolk powder to the cationic resin is 1000:(5 - 12).

[0018] As a further technical solution of the present invention, the cationic resin is a strong acid cation exchange resin or a weak acid cation exchange resin.

[0019] As a further technical solution of the present invention, the cationic resin is 732 strong acid styrene cation exchange resin or Zhengguang ZGCMB50 strong acid cation exchange resin.

[0020] As a further technical solution of the present invention, the reaction temperature for adding the material containing aluminum element and adding the cationic resin is 50 - 60 °C.

[0021] The second object of the present invention is to provide a low-aluminum-element egg yolk lecithin prepared by the foregoing method.

[0022] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0023] Since materials containing aluminum element such as aluminum trioxide and activated clay are usually used for refining treatment during the preparation of egg yolk lecithin, a relatively large amount of aluminum element is introduced. After the refining treatment in the present invention, a cationic resin is further used to remove the aluminum element in the egg yolk lecithin. The aluminum element level in the prepared egg yolk lecithin is significantly decreased. Finally, the aluminum element content in the fat emulsion product prepared with the low-aluminum egg yolk lecithin is significantly reduced, thereby reducing the risk of excessive aluminum element level in the preparation products such as fat emulsion prepared with such egg yolk lecithin. Description of the Drawings

[0024] To more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the accompanying drawings required in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings. In the drawings:

[0025] Figure 1 is the process flow chart of the present invention; Specific embodiments

[0026] To make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments and the accompanying drawings. Obviously, the illustrative embodiments and explanations of the present invention are only used to explain the present invention and do not serve as a limitation to the present invention.

[0027] The following will appropriately refer to the accompanying drawings to detail the embodiments of a low-aluminum element egg yolk lecithin and its preparation method of the present invention. However, there will be cases where unnecessary detailed descriptions are omitted. For example, there are cases of omitting detailed descriptions of well-known matters and repeated descriptions. This is to avoid the following descriptions from becoming unnecessarily lengthy and to facilitate the understanding of those skilled in the art.

[0028] The "range" disclosed in this application is defined in the form of a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundary of a specific range. The ranges defined in this way can include the end values or not include the end values, and can be combined arbitrarily, that is, any lower limit can be combined with any upper limit to form a range.

[0029] If there is no special description, all embodiments and optional embodiments of this application can be combined with each other to form new technical solutions.

[0030] If there is no special description, all technical features and optional technical features of this application can be combined with each other to form new technical solutions.

[0031] If there is no special description, the "including" and "comprising" mentioned in this application mean open-ended or can also be closed-ended. For example, the "including" and "comprising" can mean that other substances not listed can also be included or comprised, or only the substances listed can be included or comprised.

[0032] Unless otherwise specified, all steps of this application can be carried out sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), which means that the method may include steps (a) and (b) carried out sequentially, or may also include steps (b) and (a) carried out sequentially. For example, when it is mentioned that the method may further include step (c), it means that step (c) can be added to the method in any order. For example, the method may include steps (a), (b) and (c), or may also include steps (a), (c) and (b), or may also include steps (c), (a) and (b), etc.

[0033] In order to solve the technical problem that in the preparation and extraction process of egg yolk lecithin, materials containing aluminum are often used, resulting in a relatively high aluminum element content in the finally prepared egg yolk lecithin, which in turn affects the aluminum element level in the fat emulsion preparation and leads to a relatively high aluminum element content in the finally prepared fat emulsion-related products, the present invention provides a method for preparing low-aluminum egg yolk lecithin, comprising the following steps:

[0034] (1) Add egg yolk powder to ethanol for extraction to obtain an extract;

[0035] (2) Add materials containing aluminum elements to the extract for refining, stir and react, and filter to obtain a filtrate;

[0036] (3) Add cation exchange resin to the filtrate, stir and react, and filter to obtain a filtrate;

[0037] (4) Rotate and evaporate the filtrate for concentration, add acetone for crystallization, and dry the crystallization product to obtain low-aluminum egg yolk lecithin.

[0038] Since materials containing aluminum elements such as aluminum oxide and activated clay are usually used for refining in the process of preparing egg yolk lecithin, introducing a relatively large amount of aluminum elements, the present invention further uses cation exchange resin to remove aluminum elements in egg yolk lecithin after refining. The aluminum element level in the prepared egg yolk lecithin is significantly decreased, and the aluminum element content in the fat emulsion products finally prepared with low-aluminum egg yolk lecithin is significantly reduced, thus reducing the risk of excessive aluminum element level in the preparation of fat emulsion and other preparation products using such egg yolk lecithin.

[0039] As a further technical solution of the present invention, the egg yolk powder is defatted egg yolk powder. The egg yolk powder can be ordinary egg yolk powder or can be defatted. The preparation steps of the defatted egg yolk powder are: add acetone to the egg yolk powder and stir, repeat at least three times, and defatted egg yolk powder can be obtained.

[0040] As a further technical solution of the present invention, the mass ratio of the egg yolk powder to the materials containing aluminum elements is 50:(2 - 3).

[0041] As a further technical solution of the present invention, the material containing aluminum element is aluminum oxide or activated clay.

[0042] As a further technical solution of the present invention, the mass ratio of the egg yolk powder to the cationic resin is 1000:(5 - 12).

[0043] As a further technical solution of the present invention, the cationic resin is a strongly acidic cation exchange resin or a weakly acidic cation exchange resin.

[0044] Specifically, the cationic resin is 732 strong acid styrene cation exchange resin or Zhengguang ZGCMB50 strongly acidic cation exchange resin.

[0045] As a further technical solution of the present invention, the reaction temperature for adding the material containing aluminum element and adding the cationic resin is 50 - 60°C.

[0046] The technical solution of the present invention will be further described in detail below in conjunction with the embodiments.

[0047] It should be noted that the experimental methods used in the embodiments are all conventional methods unless otherwise specified. The materials, reagents, methods and instruments used are all conventional materials, reagents, methods and instruments in the art, and those skilled in the art can obtain them through commercial channels without special instructions.

[0048] Example 1

[0049] A preparation method of low - aluminum - element egg yolk lecithin includes the following steps:

[0050] Take 1 kg of egg yolk powder, add 5 L of 95% ethanol, stir and extract at 29°C for 30 min, then let it stand and filter to obtain an extract; take 3850 mL of the above - mentioned extract, add 54 g of aluminum oxide, stir and react at 50°C for 30 min, then let it stand and filter to obtain a filtrate; then take 600 mL of the above - mentioned filtrate, add 5 g of Zhengguang ZGCMB50 cation exchange resin, stir at 50°C for 1 h, then filter, and then successively carry out rotary evaporation concentration, add acetone for crystallization, and dry the crystallization product to finally obtain low - aluminum - element egg yolk lecithin.

[0051] Example 2

[0052] A preparation method of low - aluminum - element egg yolk lecithin includes the following steps:

[0053] Take 1kg of egg yolk powder, add 5L of 95% ethanol, stir and extract at 29°C for 30min, then stand and filter to obtain an extract; take 3850mL of the above extract, add 54g of aluminum oxide, stir and react at 50°C for 30min, then stand and filter to obtain a filtrate; take 600mL of the above filtrate, add 12g of Zhengguang ZGCMB50 cation exchange resin, stir at 50°C for 1h, then filter, and then concentrate by rotary evaporation, add acetone to crystallize, and dry the crystalline product to finally obtain low-aluminum egg yolk lecithin.

[0054] Example 3

[0055] A method for preparing low-aluminum egg yolk lecithin comprises the following steps:

[0056] Take 1kg of egg yolk powder, add 5L of 95% ethanol, stir and extract at 29°C for 30min, then stand and filter to obtain an extract; take 3850mL of the above extract, add 54g of aluminum oxide, stir and react at 50°C for 30min, then stand and filter to obtain a filtrate; take 600mL of the above filtrate, add 5g of 732 type cation exchange resin, stir at 50°C for 1h, then filter, then concentrate by rotary evaporation, add acetone to crystallize, and dry the crystallized product to finally obtain low-aluminum egg yolk lecithin.

[0057] Example 4

[0058] A method for preparing low-aluminum egg yolk lecithin comprises the following steps:

[0059] Take 1kg of egg yolk powder, add 5L of 95% ethanol, stir and extract at 29°C for 30min, then stand and filter to obtain an extract; take 3850mL of the above extract, add 54g of aluminum oxide, stir and react at 50°C for 30min, then stand and filter to obtain a filtrate; take 600mL of the above filtrate, add 12g of 732 type cation exchange resin, stir at 50°C for 1h, then filter, then concentrate by rotary evaporation, add acetone for crystallization, and dry the crystallized product to finally obtain low-aluminum egg yolk lecithin.

[0060] Example 5

[0061] A method for preparing low-aluminum egg yolk lecithin comprises the following steps:

[0062] Take 1 kg of egg yolk powder, add 3 L of acetone, stir at room temperature for 30 min, then filter the residue. Add 3 L of acetone again to stir and remove oil, repeat 3 times, and then dry the egg yolk powder after acetone deoiling treatment under a fume hood; add 5 L of 95% ethanol to the deoiled egg yolk powder after acetone deoiling, stir and extract at 29 °C for 30 min, then let it stand and filter to obtain an extract; take 3850 mL of the above extract, add 54 g of aluminum oxide, stir and react at 50 °C for 30 min, then let it stand and filter to obtain a filtrate; take 600 mL of the above filtrate, add 5 g of ZhengGuang ZGCMB50 cation exchange resin, stir at 50 °C for 1 h, then filter, and then successively perform rotary evaporation concentration, add acetone for crystallization, and dry the crystallization product to finally obtain low-aluminum-element egg yolk lecithin.

[0063] Example 6

[0064] A preparation method of low-aluminum-element egg yolk lecithin includes the following steps:

[0065] Take 1 kg of egg yolk powder, add 3 L of acetone, stir at room temperature for 30 min, then filter the residue. Add 3 L of acetone again to stir and remove oil, repeat 3 times, and then dry the egg yolk powder after acetone deoiling treatment under a fume hood; add 5 L of 95% ethanol to the deoiled egg yolk powder after acetone deoiling, stir and extract at 29 °C for 30 min, then let it stand and filter to obtain an extract; take 3850 mL of the above extract, add 54 g of aluminum oxide, stir and react at 50 °C for 30 min, then let it stand and filter to obtain a filtrate; take 600 mL of the above filtrate, add 12 g of ZhengGuang ZGCMB50 cation exchange resin, stir at 50 °C for 1 h, then filter, and then successively perform rotary evaporation concentration, add acetone for crystallization, and dry the crystallization product to finally obtain low-aluminum-element egg yolk lecithin.

[0066] Determine the aluminum element content of the products before and after cation exchange treatment in the above Examples 1-6, and the results are shown in Table 1.

[0067] Table 1. Data of aluminum element content determination of products before and after cation exchange treatment in Examples 1-6

[0068]

[0069] It can be seen from the data in Table 1 that within a certain range, the more the cation dosage, the better the aluminum removal effect. Compared with the product without cation resin treatment, the aluminum element content of the egg yolk lecithin prepared by the present invention is significantly reduced; at the same time, it also shows that there may be differences in the aluminum removal effects of cation resins from different manufacturers; in addition, it can be seen that the aluminum element content of egg yolk lecithin prepared with deoiled egg yolk powder under the same conditions will be lower.

[0070] The above has proven that the aluminum element level of the egg yolk lecithin prepared after adopting the aluminum element removal process provided by the present invention can be significantly reduced. Therefore, after using such low-aluminum egg yolk lecithin in the production of preparations such as fat emulsion, the aluminum element level of its products will also be significantly reduced, thereby reducing the risk of high aluminum element levels in preparations such as fat emulsion.

[0071] Finally, it should be noted that: the above specific embodiments are only used to elaborate in detail the purpose, technical solution and beneficial effects of the present invention. It should be understood that the above is only the specific implementation manner of the present invention and is not used to limit the protection scope of the present invention; although the present invention has been described in detail with reference to the foregoing specific embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements or improvements on some or all of the technical features; and these modifications, equivalent replacements and improvements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered by the scope of the claims and the description of the present invention.

Claims

1. A method for preparing low-aluminum egg yolk lecithin, characterized in that: The following steps are involved: The egg yolk powder is added to ethanol for extraction to obtain an extract; Adding materials containing aluminum element to the extract for refining, stirring for reaction, and filtering to obtain filtrate; Add cationic resin to the filtrate, stir to react, and filter to obtain the filtrate; The filtrate is concentrated by rotary evaporation, acetone is added for crystallization, and the crystal product is dried to obtain low-aluminum egg yolk lecithin.

2. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The egg yolk powder is deoiled egg yolk powder.

3. The method for preparing low-aluminum egg yolk lecithin according to claim 2, characterized in that: The deoiled egg yolk powder is prepared by adding acetone to the egg yolk powder and stirring, and repeating the process at least three times to obtain the deoiled egg yolk powder.

4. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The mass ratio of the egg yolk powder to the material containing aluminum element is 50:(2-3).

5. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The material containing aluminum element is aluminum oxide or activated clay.

6. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The mass ratio of the egg yolk powder to the cationic resin is 1000:(5-12).

7. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The cationic resin is a strongly acidic cation exchange resin or a weakly acidic cation exchange resin.

8. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The cationic resin is 732 strong acid styrene cationic exchange resin or Zhengguang ZGCMB50 strong acid cationic exchange resin.

9. The method for preparing low-aluminum egg yolk lecithin according to claim 1, characterized in that: The reaction temperature for adding materials containing aluminum elements and cationic resin is 50-60°C.

10. A low-aluminum egg yolk lecithin, characterized in that: The method is prepared by any one of claims 1 to 9.

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