Process for the preparation of sodium oleate of vegetable origin

Abstract

The present application relates to the field of medicine manufacturing, and relates to a preparation method of sodium oleate of plant origin, which comprises the following steps: crushing fresh plant raw materials, sufficiently stirring and kneading the fresh plant raw materials with a proper amount of solid alkali and adsorbent, adding solvent 1, filtering out pomace and adsorbent after a period of stirring and extraction reaction, and then filtering again after cooling the filtrate, adding solvent 2 to recrystallize and refine the obtained filter cake, and obtaining the final product sodium oleate after drying under reduced pressure, wherein the content of oleic acid is 45% to 80%. The present application solves the problem that the content of oleic acid in the product cannot be flexibly controlled without other changes in the prior art.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical manufacturing, and specifically to a method for preparing sodium oleate from plant sources. Background Technology

[0002] Sodium oleate, also known as sodium octadecenoate or oleic acid soap, is a mixture of sodium salts of fatty acids, primarily oleic acid. It is an anionic surfactant used as an emulsifying stabilizer in fat emulsions. It is widely used as a raw material and excipient in the production of pharmaceuticals, food, and health products. In pharmaceuticals, it serves as an emulsifier, solubilizer, transdermal penetration enhancer, and base for creams and ointments. As a food additive, it has a particularly wide range of applications as an emulsifier and coating agent.

[0003] Sodium oleate is an anionic surfactant used as an emulsion stabilizer in fat emulsions. It is used in many fat emulsion products, such as Clinox long-chain fat emulsion injection, propofol injection, Ivelipix injection, Liposuction, Liposuction injection, ω-3 fish oil fat emulsion, and Liposuction intravenous injection. The required oleic acid content in sodium oleate varies depending on the formulation process and requirements of different preparations. The oleic acid content in sodium oleate has a certain impact on indicators such as emulsion particle count, pH, peroxide value, acid value, and methoxyaniline value in the preparation.

[0004] Current sodium oleate preparation processes use oleic acid as a raw material through saponification. However, oleic acid is typically obtained through high-temperature distillation of fatty acids, a process that is energy-intensive, environmentally challenging, and poorly adaptable to industrial applications. Furthermore, oleic acid is prone to heat-sensitive reactions at high temperatures, producing trans fatty acids that negatively impact product quality. Therefore, it is necessary to address the sourcing and processing issues of oleic acid. In addition, current market specifications for sodium oleate include sodium oleate containing oleic acid, sodium oleate (for injection), sodium oleate (45-55% oleic acid), sodium oleate (containing more than 80% oleic acid), and sodium oleate (low-alkali). Different oleic acid contents are used in different formulations; however, because the oleic acid content in sodium oleate produced by existing processes is relatively fixed, forcibly changing the oleic acid content can cause adverse changes in indicators such as peroxide value and trans fatty acids, making it unsuitable for pharmaceutical use.

[0005] Many oilseed plants have oleic acid content in their oils that falls within this range. How to make full use of oilseed plant resources and ensure that the oleic acid content of the obtained product is flexible and controllable without causing other changes is a problem worth considering in the sodium oleate preparation process. Summary of the Invention

[0006] The purpose of this invention is to provide a method for preparing sodium oleate from plant sources, so as to solve the problem that existing technologies are unable to flexibly control the oleic acid content of the product without causing other changes.

[0007] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0008] A method for preparing sodium oleate from plant sources includes the following steps:

[0009] S1. Crush the plant material and mix it with solid alkali and adsorbent to obtain a mixture;

[0010] S2. Take the mixture, add mixed solvent 1, stir and react, and then separate the solid and liquid while hot to obtain the filtrate;

[0011] S3. Cool the filtrate overnight, filter it again, and obtain a filter cake;

[0012] S4. Dissolve the filter cake in mixed solvent 2, recrystallize it, and dry it to obtain sodium oleate product.

[0013] In step S2, centrifugation or filtration while hot can remove fruit residue and adsorbent.

[0014] Preferably, in step S2, the plant raw materials include one or more of olive, camellia seed, almond, high-oleic rapeseed, high-oleic peanut, and tiger nut; in step S4, the oleic acid content of the sodium oleate product is 45% to 80%.

[0015] Preferably, in step S2, the mixed solvent 1 includes alcohols and water; in step S4, the mixed solvent 2 includes alcohols and water.

[0016] In step S2, if only alcohol is used in mixed solvent 1 without adding water, sodium hydroxide is difficult to dissolve. If only water is used without adding alcohol, sodium oleate has a high solubility in water, which will make it difficult for sodium oleate to precipitate after the reaction.

[0017] In step S4, sodium oleate is difficult to dissolve using only alcohol, and sodium oleate is difficult to precipitate using only water. Only by adding a certain proportion of water to the alcohol can sodium oleate be dissolved and successfully recrystallized for purification.

[0018] Preferably, in step S2, the alcohols in the mixed solvent 1 include one or more of methanol, ethanol, isopropanol, and butanol; in step S4, the alcohols in the mixed solvent 2 include one or more of methanol and ethanol.

[0019] Preferably, in step S2, the volume fraction of water in the mixed solvent 1 is 5-10%; in step S4, the volume fraction of water in the mixed solvent 2 is 2-10%.

[0020] Preferably, in step S1, the mass of the solid alkali is 3% to 6% of the mass of the plant raw material; in step S2, the volume-to-mass ratio of the mixed solvent 1 to the mixture is 2 to 8 ml; in step S4, the volume-to-mass ratio of the mixed solvent 2 to the filter cake is 5 to 15 mL: 1 g.

[0021] Preferably, in step S1, the mass of the adsorbent is 1% to 5% of the mass of the plant raw material; in step S2, the reaction temperature is 40 to 60°C and the time is 1 to 5 hours; in step S3, the temperature at which the filtrate is cooled overnight is -10 to 10°C; in step S4, the recrystallization is performed 1 to 3 times, and the drying includes vacuum drying.

[0022] Preferably, in step S1, the adsorbent includes one or more of diatomaceous earth, kaolin, γ-alumina, and activated carbon; in step S2, the solid-liquid separation includes one or more of centrifugation and filtration; and in step S4, the drying temperature is 30–50°C.

[0023] Preferably, in step S1, the solid alkali includes one or more of sodium hydroxide, sodium methoxide, and sodium ethoxide; in step S4, the drying temperature is 35-45°C.

[0024] A sodium oleate product obtained by the method described above for preparing sodium oleate from plant sources.

[0025] Compared with the prior art, implementing the present invention has the following beneficial effects:

[0026] This invention proposes a method for preparing sodium oleate from plant sources. The raw materials are widely available and inexpensive. The hydrolysis of oils into fatty acids and the saponification of fatty acids occur simultaneously, significantly shortening the steps of existing sodium oleate preparation processes and making it highly suitable for industrial production. The resulting sodium oleate product has an oleic acid content between 45% and 80%, and sodium oleate products meeting different formulation specifications can be prepared based on the oleic acid levels in different plants. The process does not require oleic acid enrichment and avoids prolonged high temperatures, thus preventing the formation of trans fatty acids. Some oxidation indicators, such as peroxide value, are also far below the limits. Detailed Implementation

[0027] Example 1

[0028] Weigh 100g of tiger nuts, crush them, and mix them thoroughly with 5g of sodium hydroxide and 2.5g of activated carbon. Add solvent 1, which consists of 550ml of methanol and 50ml of water. Stir and react at 40℃ for 4 hours. Filter while hot to remove fruit residue and adsorbent. Cool the filtrate at -3℃ overnight and filter again. Add solvent 2, which consists of 200ml of ethanol and 10ml of water, to the filter cake for recrystallization and purification. Dry under reduced pressure at 38℃ for 30 hours to obtain the final product, sodium oleate. The key indicators are as follows:

[0029] index Product measured values The Chinese Pharmacopoeia specifies the limits. peroxide 0.17 No more than 10 Trans fatty acids 0 / Oleic acid 54.7 Greater than 50

[0030] Example 2

[0031] Weigh 500g of almonds, crush them, and mix them thoroughly with 18g of sodium ethoxide and 5g of kaolin. Add solvent 1, which consists of 500ml of methanol, 500ml of ethanol, and 60ml of water. Stir and react at 55℃ for 2 hours. Centrifuge while hot to remove fruit residue and adsorbent. Cool the filtrate at 5℃ overnight and filter again. Add solvent 2, which consists of 800ml of methanol and 20ml of water, to the filter cake for recrystallization and purification. Dry under reduced pressure at 35℃ for 38 hours to obtain the final product, sodium oleate. The key indicators are as follows:

[0032] index Actual product value The Chinese Pharmacopoeia specifies the limits. peroxide 0.31 No more than 10 Trans fatty acids 0 / Oleic acid 51.3 Greater than 50

[0033] Example 3

[0034] Weigh 200g of almonds and 300g of camellia seeds, crush them, and mix them thoroughly with 30g of sodium hydroxide and 25g of diatomaceous earth. Add solvent 1, which consists of 1.5L of ethanol, 1.5L of isopropanol, and 300ml of water. Stir and react at 60℃ for 1.5h. Filter while hot to remove fruit residue and adsorbent. Cool the filtrate at -5℃ overnight and filter again. Add solvent 2, which consists of 1120ml of ethanol and 100ml of water, to the filter cake for recrystallization and purification. Dry under reduced pressure at 48℃ for 16h to obtain the final product, sodium oleate. The key indicators are as follows:

[0035]

[0036]

[0037] Example 4

[0038] 2 kg of high-oleic peanuts were crushed and thoroughly mixed with 100 g of sodium methoxide and 70 g of alumina. Solvent 1, consisting of 5 L of methanol, 4.2 L of butanol, and 800 mL of water, was added. The mixture was stirred and reacted at 45 °C for 3 hours. While still hot, the mixture was filtered to remove the peanut residue and adsorbent. The filtrate was cooled to -10 °C overnight and then filtered again. The resulting filter cake was recrystallized and purified using solvent 2, consisting of 7.6 L of ethanol and 400 mL of water. The purified product, sodium oleate, was dried under reduced pressure at 42 °C for 22 hours. The key indicators were tested as follows:

[0039] index Actual product value The Chinese Pharmacopoeia specifies the limits. peroxide 0.32 No more than 10 Trans fatty acids 0 / Oleic acid 78.6 Greater than 50

[0040] Example 5

[0041] Weigh 5 kg of high-oleic rapeseed and 5 kg of high-oleic peanuts, crush them, and mix them thoroughly with 300 g of sodium hydroxide, 200 g of sodium ethoxide, and 250 g of alumina. Add solvent 1, which consists of 25 L of ethanol, 11 L of isopropanol, and 3 L of water. Stir and react at 58 °C for 1.5 h. Centrifuge while hot to remove fruit residue and adsorbent. Cool the filtrate at -3 °C overnight and filter again. Add solvent 2, which consists of 14 L of methanol, 9 L of ethanol, and 2 L of water, to the filter cake for recrystallization and purification. Dry under reduced pressure at 50 °C for 15 h to obtain the final product, sodium oleate. The key indicators are as follows:

[0042]

[0043]

[0044] Example 6

[0045] 50 kg of high-oleic rapeseed was crushed and thoroughly mixed with 2 kg of sodium hydroxide, 0.2 kg of sodium methoxide, and 1 kg of diatomaceous earth. Solvent 1, consisting of 105 L of ethanol, 125 L of methanol, and 20 L of water, was added. The mixture was stirred and reacted at 55 °C for 2 hours. While still hot, the mixture was filtered to remove the pomace and adsorbent. The filtrate was cooled at -8 °C overnight and then filtered again. The resulting filter cake was recrystallized and purified using solvent 2, consisting of 114 L of methanol and 6 L of water. The final product, sodium oleate, was obtained after drying under reduced pressure at 40 °C for 28 hours. The key indicators were tested as follows:

[0046] index Product measured values The Chinese Pharmacopoeia specifies the limits. peroxide 0.18 No more than 10 Trans fatty acids 0 / Oleic acid 63.6 Greater than 50

[0047] The above-disclosed embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of the present invention. Therefore, any equivalent variations made in accordance with the claims of the present invention are still within the scope of the present invention.

Claims

1. A process for the preparation of sodium oleate of vegetable origin, characterized in that, The method comprises the following steps: S1, crushing the plant raw material, stirring and kneading with solid alkali and adsorbent to obtain a mixture; S2, taking the mixture, adding mixed solvent 1, stirring and reacting, then separating the solid and the liquid while hot to obtain a filtrate; S3, cooling the filtrate overnight, filtering again to obtain a filter cake; S4, dissolving the filter cake in mixed solvent 2, recrystallizing, and drying to obtain a sodium oleate product; In step S2, the plant raw material comprises one or more of the following: olive, oil tea seed, almond, high-oleic rapeseed, high-oleic peanut, and yam bean; the mixed solvent 1 comprises alcohol and water; the alcohol in the mixed solvent 1 comprises one or more of the following: methanol, ethanol, isopropyl alcohol, and butanol; the volume fraction of water in the mixed solvent 1 is 5-10%; In step S4, the oleic acid content of the sodium oleate product is 45-80%; the mixed solvent 2 comprises alcohol and water; the alcohol in the mixed solvent 2 comprises one or more of the following: methanol and ethanol; the volume fraction of water in the mixed solvent 2 is 2-10%.

2. The process for the preparation of sodium oleate of plant origin as claimed in claim 1, wherein, In step S1, the mass of the solid alkali is 3-6% of the mass of the plant raw material; in step S2, the volume-mass ratio of the mixed solvent 1 to the mixture is 2-8 ml; in step S4, the volume-mass ratio of the mixed solvent 2 to the filter cake is 5-15 mL:1 g.

3. The process for the preparation of sodium oleate of plant origin as claimed in claim 1, wherein, In step S1, the mass of the adsorbent is 1-5% of the mass of the plant raw material; in step S2, the reaction temperature is 40-60℃, and the reaction time is 1-5 h; in step S3, the temperature for cooling the filtrate overnight is-10-10℃; in step S4, the recrystallization is performed 1-3 times, and the drying comprises reduced-pressure drying.

4. The process for the preparation of sodium oleate of plant origin as claimed in claim 1, wherein, In step S1, the adsorbent comprises one or more of the following: diatomite, white clay, γ-alumina, and activated carbon; in step S2, the solid-liquid separation comprises one or more of the following: centrifugation and filtration; in step S4, the drying temperature is 30-50℃.

5. The process as claimed in claim 1, wherein the sodium oleate is prepared from plant sources. In step S1, the solid alkali comprises one or more of the following: sodium hydroxide, sodium methoxide, and sodium ethoxide; in step S4, the drying temperature is 35-45℃.

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