Synthesis method of high-purity pharmaceutical adjuvant sodium caprate

Abstract

The invention discloses a synthesis method of high-purity pharmaceutical adjuvant sodium caprate, and relates to the technical field of pharmaceutical adjuvant synthesis, and the synthesis method comprises the following steps: S1, preparing raw materials; s2, synthesizing sodium caprate; s3, performing pretreatment; s4, separation and purification; s5, elution and collection; and S6, carrying out post-treatment. According to the synthesis method of the high-purity pharmaceutical adjuvant sodium decanoate, in the separation and purification link, an ion exchange resin technology is utilized, and ion impurities including inorganic ions and other organic impurities in a sodium decanoate solution can be efficiently removed, so that the purity of the product is improved, and the production cost is reduced. And the ion exchange resin can selectively remove or retain some ions according to needs, so that the accurate control of the sodium caprate solution is realized, and the content and purity of sodium caprate in a final product can be ensured to meet the requirements of pharmaceutic adjuvants.

Description

Technical Field

[0001] The present invention relates to the technical field of synthesis of pharmaceutical excipients, and particularly to a method for synthesizing sodium caprate as a high-purity pharmaceutical excipient. Background Art

[0002] Sodium caprate is a chemical compound with the chemical formula C9H19COONa (which can also be written as C10H19NaO2). It is usually a colorless to light yellow crystal or powder under normal temperature and pressure, soluble in water and certain organic solvents such as ethanol, but insoluble in ether. Sodium caprate has a wide range of uses, including but not limited to being used as a surfactant, emulsifier, preservative, etc., and has extensive applications in the fields of chemistry, industry, food, and medicine. For example, sodium caprate can be used as a surfactant in the manufacture of personal care products such as detergents, shampoos, and soaps, as it can reduce the surface tension of liquids and help enhance the cleaning effect. In the industrial field, it can be used as a lubricant, rust inhibitor, and metal corrosion inhibitor. In the food industry, sodium caprate can be used as a food additive, such as an emulsifier and stabilizer.

[0003] In addition, sodium caprate can be used as a pharmaceutical excipient, especially as an absorption enhancer / intestinal permeability enhancer. Sodium caprate can increase the permeability of the intestinal mucosa, thereby promoting the absorption of drug molecules, which helps to improve the bioavailability of drugs. In some pharmaceutical preparations, sodium caprate can be used alone or in combination with surfactants to effectively improve the oral bioavailability of poorly permeable oral macromolecular drugs and certain small molecule drugs.

[0004] It should be noted that sodium caprate as a pharmaceutical excipient must meet strict purity requirements. However, in the actual synthesis process, the purity of sodium caprate is easily affected by reasons such as raw material impurities, incomplete reactions, and poor separation and purification effects, resulting in low purity of the prepared sodium caprate. Especially in the separation and purification step, if the separation and purification technology used is improper or the operating conditions are not well controlled, impurities will not be effectively removed, thereby reducing the purity of sodium caprate.

[0005] Therefore, it is urgent to improve this shortcoming. The present invention is to research and improve the existing technology and deficiencies, and provides a method for synthesizing sodium caprate as a high-purity pharmaceutical excipient. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for synthesizing sodium caprate as a high-purity pharmaceutical excipient to solve the problems raised in the above background art.

[0007] To achieve the above purpose, the present invention provides the following technical solution: A method for synthesizing sodium caprate as a high-purity pharmaceutical excipient, comprising the following steps:

[0008] S1. Prepare raw materials: According to the preparation requirements, prepare the main raw materials for synthesizing sodium caprate and other auxiliary materials (for subsequent purification operations). The main raw materials include capric acid and sodium hydroxide, and the auxiliary materials include, but are not limited to, deionized water and ethanol;

[0009] S2. Synthesize sodium caprate: Dissolve capric acid in water, and then slowly add sodium hydroxide solution for neutralization reaction to generate sodium caprate solution;

[0010] S3. Pretreatment: Pretreat the generated sodium caprate solution to remove some insoluble impurities and adjust the solution properties to improve the efficiency and product quality of subsequent steps;

[0011] S4. Separation and purification: Pump the pretreated sodium caprate solution into an ion exchange resin column. Use the ion exchange resin in the resin column to adsorb and remove ionic impurities in the solution, and sodium caprate passes through the resin column smoothly to achieve separation and purification;

[0012] S5. Elution and collection: Use an eluent to elute the ion exchange resin, elute the sodium caprate adsorbed on the resin, and collect it;

[0013] S6. Post-treatment: Perform post-treatment on the collected sodium caprate solution, including concentration, crystallization, and drying operations to obtain a high-purity sodium caprate product.

[0014] Further, the specific operation of step S2: Add capric acid and an appropriate amount of water to the reaction kettle, heat to 40 - 50 °C (since the melting point of capric acid is about 31.5 °C, setting the heating temperature within a range slightly higher than this value can ensure that capric acid can be completely dissolved in water), then start to slowly drip sodium hydroxide solution, and at the same time turn on the stirrer for stirring until the reaction is complete.

[0015] Further, the stirring operation uses a planetary stirrer to ensure that capric acid and sodium hydroxide can be evenly mixed and react. The self-rotation speed of the planetary stirrer is 300 ± 5 r / min, and the revolution speed is 90 ± 5 r / min. The stirring speed is moderate, which not only ensures the uniform progress of the reaction but also avoids the generation of excessive foam or shear force that may have an adverse impact on the reaction.

[0016] Further, in step S3, the pretreatment specifically includes the following operations:

[0017] Adjust the pH value: Use a pH meter to measure the pH value of the sodium caprate solution, and add an appropriate amount of acid (such as hydrochloric acid, sulfuric acid, etc.) or base (such as sodium hydroxide, potassium hydroxide, etc.) for adjustment as needed until the pH value range is 7.0 - 9.0. The purpose of this step is to make the sodium caprate solution reach a suitable acidity and alkalinity for subsequent separation and purification steps;

[0018] Filtration: Filter the solution through a filter to remove insoluble impurities such as particulate matter and precipitates, thereby improving the clarity and purity of the solution. The filter includes filter paper (suitable for removing larger particulate matter and precipitates, with a high interception efficiency, but not effective for very fine impurities) and a microporous membrane (suitable for removing fine particulate matter and microorganisms. The microporous membrane has a smaller pore size and can intercept finer impurities. According to different pore sizes, the microporous membrane can be divided into different specifications, such as 0.22 μm, 0.45 μm, etc.), and the filtration is first through the filter paper and then through the microporous membrane.

[0019] Furthermore, in the step S4, the types of impurities present in the pre-treated sodium caprate solution include inorganic ions (such as sodium ions, chloride ions, etc.), organic impurities, microorganisms, etc. Different types of impurities have different selectivities for ion exchange resins. When selecting an ion exchange resin, it must be selected according to the properties of sodium caprate and the types of impurities. Specifically: for the removal of inorganic ions, select a resin with the corresponding ion exchange function; for the removal of organic impurities, select a resin with special adsorption properties.

[0020] Furthermore, in the step S4, the separation and purification can be improved by increasing the number of times passing through the resin column, and the resin must be regenerated regularly to restore its exchange capacity.

[0021] Furthermore, in the step S4, the eluent is selected as deionized water or an appropriate salt solution (such as NaCl solution), and elution is carried out through the resin column. During the elution process, the flow rate of the eluent is controlled within the range of 5 - 8 milliliters per hour per square centimeter of the cross-sectional area of the chromatography column, and the elution time is controlled within 15 - 45 minutes to ensure the complete elution of sodium caprate.

[0022] Furthermore, in the step S4, the post-treatment specifically includes the following operations:

[0023] Concentration: Remove excess water, reduce the volume of the sodium caprate solution, and increase the concentration of sodium caprate to prepare for subsequent crystallization operations;

[0024] Crystallization: Crystallize sodium caprate from the solution to further purify sodium caprate;

[0025] Drying: Evaporate the water in the sodium caprate crystals by heating, remove the water or other solvents in the sodium caprate crystals, and obtain a dry sodium caprate product. When heating and drying, the temperature should be controlled to avoid the decomposition or deterioration of sodium caprate.

[0026] Further, the concentration is carried out by evaporation or distillation. Evaporation is to evaporate the solvent in the solution by heating, so as to concentrate the solution. Distillation utilizes the different boiling points of the components in the solution. By heating, the low-boiling components (mainly the solvent) are evaporated and then condensed and collected to achieve the purpose of concentration.

[0027] Further, the crystallization is carried out by cooling crystallization, evaporation crystallization or salting-out crystallization. Cooling crystallization is to reduce the temperature of the solution to lower the solubility of sodium caprate and precipitate crystals. Evaporation crystallization is to evaporate the solvent to make the solution reach a supersaturated state and precipitate crystals. Salting-out crystallization is to add a salting-out agent to the solution to reduce the solubility of sodium caprate in the solvent, thereby precipitating crystals.

[0028] The present invention provides a method for synthesizing high-purity pharmaceutical excipient sodium caprate, which has the following beneficial effects:

[0029] 1. In the separation and purification step of the present invention, the ion exchange resin technology is utilized, which can efficiently remove ionic impurities in the sodium caprate solution, including inorganic ions and other organic impurities, thereby improving the purity of the product. The ion exchange resin can selectively remove or retain certain ions according to needs, so as to achieve precise control of the sodium caprate solution, which helps to ensure that the sodium caprate content and purity in the final product meet the requirements of pharmaceutical excipients.

[0030] 2. The process of the present invention is simple and easy to operate. Using ion exchange resin for separation and purification usually does not require complex equipment and steps, and the operation is relatively simple, which helps to reduce production costs and improve production efficiency. And the ion exchange resin does not produce harmful substances during use, is environmentally friendly; the resin can be reused through regeneration treatment, which reduces waste generation and is conducive to further reducing the synthesis cost of sodium caprate. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is a schematic flow chart of the steps of a method for synthesizing high-purity pharmaceutical excipient sodium caprate of the present invention;

[0032] Figure 2 is a schematic diagram of the post-treatment of a method for synthesizing high-purity pharmaceutical excipient sodium caprate of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0033] The following further describes in detail the embodiments of the present invention in conjunction with the drawings and examples. The following examples are used to illustrate the present invention, but cannot be used to limit the scope of the present invention.

[0034] As Figure 1 - Figure 2 shown, a method for synthesizing high-purity pharmaceutical excipient sodium caprate includes the following steps:

[0035] S1. Prepare raw materials: According to the preparation requirements, prepare the main raw materials and other auxiliary materials (for subsequent purification operations) required for synthesizing sodium caprate. The main raw materials include capric acid and sodium hydroxide, and the auxiliary materials include, but are not limited to, deionized water and ethanol.

[0036] S2. Synthesize sodium caprate: Dissolve capric acid in water, and then slowly add sodium hydroxide solution for neutralization reaction to generate sodium caprate solution.

[0037] In this embodiment, the specific operation of this step is as follows: Add capric acid and an appropriate amount of water into the reaction kettle, heat it to 40 - 50 °C (since the melting point of capric acid is about 31.5 °C, setting the heating temperature within a range slightly higher than this value can ensure that capric acid can be completely dissolved in water), then start to slowly dropwise add sodium hydroxide solution, and at the same time turn on the stirrer for stirring until the reaction is complete. The stirring operation uses a planetary stirrer to ensure that capric acid and sodium hydroxide can be evenly mixed and react. The self-rotation speed of the planetary stirrer is 300 ± 5 r / min, and the revolution speed is 90 ± 5 r / min. The stirring speed is moderate, which not only ensures the uniform progress of the reaction but also avoids the adverse effects caused by excessive foam or shear force on the reaction.

[0038] S3. Pretreatment: Pretreat the generated sodium caprate solution to remove some insoluble impurities and adjust the solution properties to improve the efficiency and product quality of the subsequent steps.

[0039] In this embodiment, the pretreatment specifically includes the following operations:

[0040] Adjust the pH value: Use a pH meter to measure the pH value of the sodium caprate solution, and add an appropriate amount of acid (such as hydrochloric acid, sulfuric acid, etc.) or base (such as sodium hydroxide, potassium hydroxide, etc.) for adjustment as needed until the pH value range is 7.0 - 9.0. The purpose of this step is to make the sodium caprate solution reach a suitable acidity and alkalinity for subsequent separation and purification steps.

[0041] Filtration: Filter the solution through a filter to remove insoluble impurities such as particulate matter and precipitates, thereby improving the clarity and purity of the solution. The filter includes filter paper (suitable for removing larger particulate matter and precipitates, with a high interception efficiency, but not very effective for very fine impurities) and microporous membranes (suitable for removing fine particulate matter and microorganisms. The microporous membrane has a smaller pore size and can intercept finer impurities. According to different pore sizes, the microporous membrane can be divided into different specifications, such as 0.22 μm, 0.45 μm, etc.), and first filter with filter paper and then with a microporous membrane.

[0042] S4. Separation and purification: The pretreated sodium caprate solution is pumped into an ion exchange resin column. The ion exchange resin in the resin column is used to adsorb and remove ionic impurities in the solution, while sodium caprate passes through the resin column smoothly, achieving separation and purification.

[0043] In this embodiment, the types of impurities present in the pretreated sodium caprate solution include inorganic ions (such as sodium ions, chloride ions, etc.), organic impurities, microorganisms, etc. Different types of impurities have different selectivities for ion exchange resins. When selecting an ion exchange resin, it must be selected according to the properties of sodium caprate and the types of impurities. Specifically: for the removal of inorganic ions, a resin with corresponding ion exchange functions is selected; for the removal of organic impurities, a resin with special adsorption properties is selected;

[0044] At the same time, the separation and purification can be improved by increasing the number of times passing through the resin column, and the resin must be regenerated regularly to restore its exchange capacity.

[0045] S5. Elution and collection: An eluent is used to elute the ion exchange resin, eluting the sodium caprate adsorbed on the resin and collecting it.

[0046] In this embodiment, deionized water or a NaCl solution is selected as the eluent, and elution is carried out through the resin column. During the elution process, the flow rate of the eluent is controlled within the range of 5 - 8 milliliters per square centimeter of the cross-sectional area of the chromatography column per hour, and the elution time is controlled within 15 - 45 minutes to ensure the complete elution of sodium caprate;

[0047] S6. Post-treatment: The collected sodium caprate solution is post-treated, including concentration, crystallization, and drying operations to obtain a high-purity sodium caprate product;

[0048] In this embodiment, the post-treatment specifically includes the following operations:

[0049] Concentration: Evaporation or distillation methods are used to remove excess water, reduce the volume of the sodium caprate solution, and increase the concentration of sodium caprate to prepare for the subsequent crystallization operation; among them, evaporation evaporates the solvent in the solution by heating to concentrate the solution, and distillation utilizes the different boiling points of the components in the solution. By heating, the low-boiling components (mainly the solvent) are evaporated and then condensed and collected to achieve the purpose of concentration.

[0050] Crystallization: Cooling crystallization, evaporation crystallization, or salting-out crystallization methods are used to crystallize sodium caprate from the solution to further purify sodium caprate; among them, cooling crystallization reduces the temperature of the solution to lower the solubility of sodium caprate and precipitate crystals, evaporation crystallization evaporates the solvent to make the solution reach a supersaturated state and precipitate crystals, and salting-out crystallization is to add a salting-out agent to the solution to reduce the solubility of sodium caprate in the solvent, thereby precipitating crystals.

[0051] Drying: Evaporate the moisture in the sodium caprate crystals by heating to remove the moisture or other solvents in the sodium caprate crystals, and obtain a dried sodium caprate product. When heating and drying, the temperature should be controlled to avoid decomposition or deterioration of sodium caprate.

[0052] The embodiments of the present invention are given for purposes of illustration and description, and are not exhaustive or limit the invention to the disclosed forms. Many modifications and variations are obvious to those of ordinary skill in the art. The embodiments are chosen and described in order to better illustrate the principles of the invention and its practical applications, and to enable those of ordinary skill in the art to understand the invention and design various embodiments with various modifications suitable for specific purposes.

Claims

1. A method for synthesizing high-purity pharmaceutical excipient sodium caprate, characterized in that: The following steps are involved: S1. Prepare raw materials: prepare the main raw materials and other auxiliary materials required for synthesizing sodium caprate according to the preparation requirements, wherein the main raw materials include capric acid and sodium hydroxide, and the auxiliary materials include but are not limited to deionized water and ethanol; S2, synthesizing sodium decanoate: dissolving decanoic acid in water, and then slowly adding sodium hydroxide solution for neutralization reaction to generate sodium decanoate solution; S3, pretreatment: pretreating the generated sodium decanoate solution to remove some insoluble impurities and adjust the properties of the solution; S4, separation and purification: the pretreated sodium decanoate solution is pumped into an ion exchange resin column, and the ion exchange resin in the resin column is used to adsorb and remove ionic impurities in the solution; S5, eluting and collecting: using an eluent to elute the ion exchange resin, eluting the sodium decanoate adsorbed on the resin, and collecting it; S6. Post-processing: The collected sodium decanoate solution is post-processed, including concentration, crystallization, and drying operations, to obtain a high-purity sodium decanoate product.

2. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: The specific operation of step S2 is as follows: adding capric acid and water into a reaction kettle, heating to 40-50° C., and then slowly adding sodium hydroxide solution dropwise, while turning on a stirrer to stir until the reaction is complete.

3. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 2, characterized in that: The stirring operation uses a planetary mixer to ensure that the capric acid and sodium hydroxide can be evenly mixed and reacted, and the stirring rotation speed of the planetary mixer is 300±5r / min and the revolution speed is 90±5r / min.

4. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: In step S3, the preprocessing specifically includes the following operations: Adjusting pH: Use a pH meter to measure the pH of the sodium decanoate solution, and add an appropriate amount of acid or base as needed to adjust the pH value to a range of 7.0 to 9.0; Filtration: Filter the solution through a filter to remove insoluble impurities. The filter includes filter paper and a microporous membrane, and the filter paper is filtered first and then the microporous membrane is filtered.

5. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: In step S4, the impurity types present in the pretreated sodium decanoate solution include inorganic ions, organic impurities, and microorganisms, and different types of impurities have different selectivities for ion exchange resins. When selecting ion exchange resins, it is necessary to select according to the properties of sodium decanoate and the types of impurities. Specifically, for the removal of inorganic ions, select a resin with corresponding ion exchange function; for the removal of organic impurities, select a resin with special adsorption properties.

6. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: In step S4, separation and purification can be performed by increasing the number of times the resin column is passed to improve the purification effect, and the resin must be regenerated regularly to restore its exchange capacity.

7. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: In step S4, deionized water or saline solution is selected as the eluent, and eluted through the resin column. During the elution process, the flow rate of the eluent is controlled within the range of 5 to 8 ml per square centimeter of the cross-sectional area of ​​the chromatography column per hour, and the elution time is controlled within 15 to 45 minutes to ensure complete elution of sodium decanoate.

8. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 1, characterized in that: In step S4, post-processing specifically includes the following operations: Concentration: remove excess water, reduce the volume of sodium decanoate solution, and increase the concentration of sodium decanoate; Crystallization: Crystallize sodium decanoate from the solution to further purify the sodium decanoate; Drying: The water in the sodium decanoate crystals is evaporated by heating, and the water or other solvent in the sodium decanoate crystals is removed to obtain a dry sodium decanoate product.

9. The method for synthesizing a high-purity pharmaceutical excipient sodium caprate according to claim 8, characterized in that: The concentration is carried out by evaporation or distillation. The evaporation evaporates the solvent in the solution by heating, thereby concentrating the solution. The distillation utilizes the different boiling points of the components in the solution, evaporates the low-boiling-point component by heating, and then condenses and collects it to achieve the purpose of concentration.

10. The method for synthesizing high-purity pharmaceutical excipient sodium caprate according to claim 8, characterized in that: The crystallization adopts cooling crystallization, evaporation crystallization or salting-out crystallization. The cooling crystallization reduces the solubility of sodium decanoate by lowering the temperature of the solution to precipitate crystals. The evaporation crystallization evaporates the solvent to make the solution reach a supersaturated state to precipitate crystals. The salting-out crystallization adds a salting-out agent to the solution to reduce the solubility of sodium decanoate in the solvent, thereby precipitating crystals.

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