A slow-release sodium sarcosinate and its preparation method

Abstract

The present invention relates to the technical field of sodium sarcosinate, and specifically relates to a sustained-release sodium sarcosinate and a preparation method thereof. The sustained-release sodium sarcosinate of the present invention comprises the following raw materials in parts by weight: 70-80 parts of an aqueous sodium sarcosinate solution, 5-10 parts of acrylic acid, 5-10 parts of acrylamide, 3-5 parts of co-solvent monomer A, 0.5-1 part of co-solvent monomer B, 0.05-0.15 part of a cross-linking agent, and 0.05-0.15 part of an initiator. The co-solvent monomer B is a mixture of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride. The sustained-release sodium sarcosinate of the present invention has a high drug loading amount and encapsulation efficiency, and does not exhibit an initial burst release phenomenon. Its action in the body lasts for a relatively long time, thereby better exerting its benefits, reducing the number of intakes, and having broad application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of sodium sarcosinate, and particularly relates to a sustained-release sodium sarcosinate and a preparation method thereof. Background Art

[0002] Sodium sarcosinate, also known as sodium N-methylglycinate or sodium N-methylaminoacetate, is a kind of bioamine amino acid salt substance, which is composed of natural amino acid sarcosine and sodium salt. Its appearance is white trigonal solid crystals, highly soluble in water and slightly soluble in ethanol. Sodium sarcosinate is mainly used in the production of creatine monohydrate, sarcosine, N-acyl sarcosine and its sodium salts. Among them, creatine can effectively improve muscle strength, speed and endurance, enhance physical fitness and training level, and prevent fatigue. N-acyl sarcosine can be used as an active agent in high-grade skin care creams, toothpastes, shampoos, as well as high-grade medicinal soaps and sodium sarcosinate. Sodium sarcosinate can also be used as a mordant for fast dyes, a synthetic lubricant and rust inhibitor, a fiber dyeing agent, an antistatic agent, a softening agent, and a biochemical reagent, etc. It is a bactericidal anionic surfactant and is widely used in the daily chemical industry and other industries.

[0003] Sustained-release sodium sarcosinate refers to introducing sodium sarcosinate into the human body in a slow-release form to extend its action time and reduce the dosing frequency. The functions of sodium sarcosinate in the human body mainly include improving muscle explosive power and endurance, protecting the liver and heart, and being able to relieve physical fatigue, etc. This sustained-release form of sodium sarcosinate is often used in sports nutrition products, rehabilitation medical products, and the treatment of heart diseases and other fields.

[0004] Patent technical literature CN202310820789.4 discloses a sustained-release sodium sarcosinate and a preparation method thereof. This invention significantly improves the yield and purity of the sodium sarcosinate product by means of a modified catalyst, but it still lacks in the sustained release of sodium sarcosinate. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a sustained-release sodium sarcosinate and a preparation method thereof, so as to provide a sodium sarcosinate that can be slowly released to extend its action time.

[0006] Based on the above purpose, the present invention provides a sustained-release sodium sarcosinate, which comprises the following raw materials in parts by weight: 70-80 parts of an aqueous sodium sarcosinate solution, 5-10 parts of acrylic acid, 5-10 parts of acrylamide, 3-5 parts of solubilizing monomer A, 0.5-1 part of solubilizing monomer B, 0.05-0.15 part of crosslinking agent, and 0.05-0.15 part of initiator;

[0007] The preparation steps of the solubilizing monomer A are as follows:

[0008] S1: Under an ice bath, diethylenetriamine, methyl acrylate, and methanol are mixed evenly. Subsequently, it is stirred at room temperature for 4 h, evaporated under vacuum, and reacted at 150 - 160 °C for 3 - 5 h to obtain a crude product;

[0009] S2: The crude product, 1,2 - epoxy - 5 - hexene, and deionized water are mixed and stirred evenly, reacted at 50 - 60 °C for 15 - 30 min, purified, dried, and a solubilizing monomer A is obtained.

[0010] Preferably, the weight ratio of diethylenetriamine, methyl acrylate, and methanol in step S1 is 50 - 55:40 - 45:100 - 120.

[0011] Preferably, the weight ratio of the crude product, 1,2 - epoxy - 5 - hexene, and deionized water in step S2 is 10:5 - 50:50 - 100.

[0012] Preferably, the specific purification steps in step S2 are to pour it into acetone after vacuum evaporation, let it stand for layering, pour out the acetone, dissolve the residue in ethanol, and precipitate the obtained solution in acetone.

[0013] Preferably, the drying in step S2 is vacuum drying at 40 °C.

[0014] Preferably, the solubilizing monomer B is a mixture of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride.

[0015] Preferably, the cross - linker is one of glycidyl methacrylate, propyl methacrylate, and ethylene glycol dimethacrylate.

[0016] Preferably, the initiator is one of potassium persulfate, ammonium persulfate, and sodium dodecyl propanesulfonate.

[0017] Preferably, the weight ratio of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride is 2:1.

[0018] Furthermore, the present invention also provides a preparation method of slow - release sodium sarcosinate, which is characterized in that the specific preparation steps are as follows:

[0019] (1) Add the solubilizing monomer A to 30 - 40 parts of an aqueous sodium sarcosinate solution, stir evenly to obtain a mixed solution;

[0020] (2) Prepare aqueous solutions of acrylic acid and acrylamide respectively to obtain an aqueous acrylic acid solution and an aqueous acrylamide solution. Subsequently, under a nitrogen atmosphere, mix the remaining aqueous sodium sarcosinate solution, aqueous acrylic acid solution, aqueous acrylamide solution, co-solvent monomer B, mixed solution, and cross-linking agent, stir evenly, add an initiator, and react at 60 - 80 °C for 2 - 3 h. Then, centrifuge, wash, and dry to obtain slow-release sodium sarcosinate.

[0021] Preferably, in step (2), the concentration of the aqueous acrylic acid solution is 45 - 55%, and the concentration of the aqueous acrylamide solution is 40 - 50%.

[0022] Advantages of the present invention:

[0023] The slow-release sodium sarcosinate of the present invention can form hydrogen bonds and other interactions with sodium sarcosinate molecules by adding co-solvent monomer A, which is beneficial to the adsorption and loading of sodium sarcosinate, improving the drug loading amount and encapsulation efficiency, and at the same time preventing the burst release of sodium sarcosinate.

[0024] The slow-release sodium sarcosinate of the present invention can make the sodium sarcosinate molecules better compatible with the carrier by adding co-solvent monomer B, and at the same time can further adsorb a part of the sodium sarcosinate molecules, improving the drug loading amount and encapsulation efficiency, and achieving the result of slow release.

[0025] The slow-release sodium sarcosinate of the present invention can have a synergistic effect by adding co-solvent monomer A and co-solvent monomer B, increasing the binding strength between sodium sarcosinate and the carrier material, helping to stabilize the loading state, and achieving the result of slow release. Detailed implementation manners

[0026] To make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the following further elaborates on the present invention in conjunction with specific embodiments.

[0027] Example 1: A preparation method of slow-release sodium sarcosinate, and the specific preparation steps are as follows:

[0028] (1) Under an ice bath, mix 50 g of diethylenetriamine, 40 g of methyl acrylate, and 100 g of methanol evenly, then stir at room temperature for 4 h, perform vacuum evaporation, and react at 150 °C for 3 h to obtain a primary product;

[0029] (2) Mix 10 g of the primary product, 5 g of 1,2-epoxy-5-hexene, and 50 g of deionized water, stir evenly, react at 50 °C for 15 min, perform vacuum evaporation, then pour it into acetone, let it stand for layer separation, pour out the acetone, dissolve the residue in ethanol, precipitate the obtained solution in acetone, and perform vacuum drying at 40 °C to obtain co-solvent monomer A;

[0030] (3) Mix 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride to obtain cosolvent monomer B;

[0031] (4) Add 3 g of cosolvent monomer A to 30 g of an aqueous solution of sodium sarcosinate, stir evenly to obtain a mixed solution;

[0032] (5) Prepare 5 g of acrylic acid and 5 g of acrylamide into an aqueous acrylic acid solution with a concentration of 45% and an aqueous acrylamide solution with a concentration of 40% respectively. Subsequently, under a nitrogen atmosphere, mix the remaining aqueous sodium sarcosinate solution, aqueous acrylic acid solution, aqueous acrylamide solution, 0.5 g of cosolvent monomer B, the mixed solution and 0.05 g of propyl methacrylate, stir evenly, add 0.05 g of ammonium persulfate, and react at 60 °C for 2 h. Then, centrifuge, wash, dry to obtain slow-release sodium sarcosinate.

[0033] Example 2: A method for preparing slow-release sodium sarcosinate, and the specific preparation steps are as follows:

[0034] (1) Under an ice bath, mix 53 g of diethylenetriamine, 43 g of methyl acrylate, and 110 g of methanol evenly. Then, stir at room temperature for 4 h, evaporate under vacuum, and react at 155 °C for 4 h to obtain a crude product;

[0035] (2) Mix 10 g of the crude product, 30 g of 1,2-epoxy-5-hexene, and 80 g of deionized water, stir evenly, react at 55 °C for 20 min, evaporate under vacuum, pour the product into acetone, let it stand for layer separation, pour out the acetone, dissolve the residue in ethanol, precipitate the obtained solution in acetone, and perform vacuum drying at 40 °C to obtain cosolvent monomer A;

[0036] (3) Mix 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride to obtain cosolvent monomer B;

[0037] (4) Add 4 g of cosolvent monomer A to 35 g of an aqueous solution of sodium sarcosinate, stir evenly to obtain a mixed solution;

[0038] (5) Prepare 7.5 g of acrylic acid and 7.5 g of acrylamide into an aqueous acrylic acid solution with a concentration of 50% and an aqueous acrylamide solution with a concentration of 45% respectively. Subsequently, under a nitrogen atmosphere, mix the remaining aqueous sodium sarcosinate solution, aqueous acrylic acid solution, aqueous acrylamide solution, 0.75 g of cosolvent monomer B, the mixed solution and 0.1 g of propyl methacrylate, stir evenly, add 0.1 g of ammonium persulfate, and react at 70 °C for 3 h. Then, centrifuge, wash, dry to obtain slow-release sodium sarcosinate.

[0039] Example 3: A method for preparing slow-release sodium sarcosinate, and the specific preparation steps are as follows:

[0040] (1) Under an ice bath, 55 g of diethylenetriamine, 45 g of methyl acrylate, and 100 g of methanol were mixed evenly. Subsequently, it was stirred at room temperature for 4 h, evaporated under vacuum, and reacted at 160 °C for 5 h to obtain a crude product;

[0041] (2) 10 g of the crude product, 40 g of 1,2-epoxy-5-hexene, and 90 g of deionized water were mixed and stirred evenly. It was reacted at 60 °C for 30 min, evaporated under vacuum, then poured into acetone, allowed to stand for layer separation, the acetone was poured out, the residue was dissolved in ethanol, the resulting solution was precipitated in acetone, and vacuum dried at 40 °C to obtain solubilizing monomer A;

[0042] (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain solubilizing monomer B;

[0043] (4) 4 g of solubilizing monomer A was added to 35 g of an aqueous solution of sodium sarcosinate and stirred evenly to obtain a mixed solution;

[0044] (5) 10 g of acrylic acid and 5 g of acrylamide were respectively prepared into an aqueous acrylic acid solution with a concentration of 55% and an aqueous acrylamide solution with a concentration of 40%. Subsequently, under a nitrogen atmosphere, the remaining aqueous sodium sarcosinate solution, aqueous acrylic acid solution, aqueous acrylamide solution, 0.8 g of solubilizing monomer B, the mixed solution, and 0.12 g of propyl methacrylate were mixed and stirred evenly. 0.15 g of ammonium persulfate was added, and the reaction was carried out at 80 °C for 3 h. After centrifugation, washing, and drying, slow-release sodium sarcosinate was obtained.

[0045] Example 4: A preparation method of slow-release sodium sarcosinate, and the specific preparation steps are as follows:

[0046] (1) Under an ice bath, 55 g of diethylenetriamine, 45 g of methyl acrylate, and 100 g of methanol were mixed evenly. Subsequently, it was stirred at room temperature for 4 h, evaporated under vacuum, and reacted at 160 °C for 3 h to obtain a crude product;

[0047] (2) 10 g of the crude product, 50 g of 1,2-epoxy-5-hexene, and 100 g of deionized water were mixed and stirred evenly. It was reacted at 60 °C for 30 min, evaporated under vacuum, then poured into acetone, allowed to stand for layer separation, the acetone was poured out, the residue was dissolved in ethanol, the resulting solution was precipitated in acetone, and vacuum dried at 40 °C to obtain solubilizing monomer A;

[0048] (3) 4 g of diallyldimethylammonium chloride and 2 g of methacryloyloxyethyltrimethylammonium chloride were mixed to obtain solubilizing monomer B;

[0049] (4) 5 g of solubilizing monomer A was added to 40 g of an aqueous solution of sodium sarcosinate and stirred evenly to obtain a mixed solution;

[0050] (5) Dissolve 10 g of acrylic acid and 10 g of acrylamide into aqueous solutions with a concentration of 55% and 50% respectively. Subsequently, under a nitrogen atmosphere, mix the remaining aqueous sarcosinate solution, aqueous acrylic acid solution, aqueous acrylamide solution, 1 g of solubilizing monomer B, the mixed solution, and 0.15 g of propyl methacrylate, stir evenly, add 0.15 g of ammonium persulfate, and react at 80 °C for 3 h. Then, centrifuge, wash, and dry to obtain sustained-release sarcosinate sodium.

[0051] Comparative Example 1: A method for preparing sustained-release sarcosinate sodium, the specific preparation steps are as follows:

[0052] The difference from Example 2 is that solubilizing monomer A is not added.

[0053] Comparative Example 2: A method for preparing sustained-release sarcosinate sodium, the specific preparation steps are as follows:

[0054] The difference from Example 2 is that solubilizing monomer B is not added.

[0055] Comparative Example 3: A method for preparing sustained-release sarcosinate sodium, the specific preparation steps are as follows:

[0056] The difference from the Example is that neither solubilizing monomer A nor solubilizing monomer B is added.

[0057] Performance test

[0058] Drug loading and encapsulation efficiency test: The drug loading and encapsulation efficiency of the samples obtained in the Examples and Comparative Examples were tested according to the HPLC method. The calculation formulas are as follows, and the test results are shown in Table 1

[0059] In vitro release test:

[0060] Weigh a certain amount of the samples obtained in the Examples and Comparative Examples and put them into a release bottle. Add 1 mL of acetic acid buffer solution with a pH of 4.5 (containing 0.02% Tween 80 and 0.02% sodium azide), place it in a 37 °C air bath shaker with a rotation speed of 100 rpm, and sample regularly every day. When sampling, take out all the liquid and supplement an equal amount of fresh acetic acid buffer solution with a pH of 4.5 (containing 0.02% Tween 80 and 0.02% sodium azide). The samples are detected by HPLC, and the test results are shown in Table 1.

[0061] Table 1 Performance test results

[0062]

[0063] Table 2 In vitro release test

[0064]

[0065] Data analysis shows that, as can be seen from the examples in Tables 1 and 2, the sustained-release sodium sarcosinate of the present invention has a high encapsulation efficiency and drug loading, and can continuously release for more than 200 hours, releasing slowly continuously, thus achieving the effect of continuous action.

[0066] As can be seen from Examples 2 and the comparative examples in Tables 1 and 2, by adding two solubilizing monomers, the sustained-release sodium sarcosinate of the present invention has a high encapsulation efficiency and drug loading, and can release slowly. The reasons may be as follows: on the one hand, solubilizing monomer A can form a relatively stable encapsulation network with the carrier, making it difficult for sodium sarcosinate to flow out, and the encapsulation network contains hydrophilic groups. Sodium sarcosinate molecules will interact with these hydrophilic regions to form hydrogen bonds and other interactions, which is conducive to the adsorption and loading of sodium sarcosinate; on the other hand, solubilizing monomer B has a water-soluble quaternary ammonium salt molecule, which can further adsorb some sodium sarcosinate molecules that have not been adsorbed by solubilizing monomer A, and has a certain synergistic effect with solubilizing monomer A. This can increase the binding strength between sodium sarcosinate and the carrier material, and help to stabilize the loading state, prevent the occurrence of burst release phenomenon, and achieve the result of slow release.

[0067] Those of ordinary skill in the art should understand that: the discussion of any above embodiment is only exemplary, and is not intended to imply that the scope of the present invention (including the claims) is limited to these examples; under the concept of the present invention, the technical features in the above embodiments or different embodiments can also be combined, and the steps can be implemented in any order, and there are many other variations in different aspects of the present invention as described above, which are not provided in detail for the sake of brevity.

[0068] The present invention aims to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omission, modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A sustained-release sodium sarcosinate, characterized in that: The invention comprises the following raw materials in parts by weight: 70-80 parts of sodium sarcosinate aqueous solution, 5-10 parts of acrylic acid, 5-10 parts of acrylamide, 3-5 parts of solubilizing monomer A, 0.5-1 part of solubilizing monomer B, 0.05-0.15 parts of crosslinking agent, and 0.05-0.15 parts of initiator; the preparation steps of the solubilizing monomer A are as follows: S1: diethylenetriamine, methyl acrylate, and methanol are mixed evenly in an ice bath, and then stirred at room temperature for 4 hours, vacuum evaporated, and reacted at 150-160° C. for 3-5 hours to obtain a primary product; S2: the primary product, 1,2-epoxy-5-hexene, and deionized water are mixed, stirred evenly, reacted at 50-60° C. for 15-30 minutes, purified, and dried to obtain the solubilizing monomer A; The weight ratio of diethylenetriamine, methyl acrylate and methanol in step S1 is 50-55:40-45:100-120; The solubilizing monomer B is a mixture of diallyldimethylammonium chloride and methacryloyloxyethyltrimethylammonium chloride; The weight ratio of the diallyldimethylammonium chloride to methacryloyloxyethyltrimethylammonium chloride is 2:

1.

2. The sustained-release sodium sarcosinate according to claim 1, characterized in that: In step S2, the weight ratio of the initial product, 1,2-epoxy-5-hexene and deionized water is 10:5-50:50-100.

3. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The cross-linking agent is one of glycidyl methacrylate, propyl methacrylate and ethylene glycol dimethacrylate.

4. The sustained-release sodium sarcosinate according to claim 1, characterized in that: The initiator is one of potassium persulfate, ammonium persulfate and sodium dodemethylpropane sulfonate.

5. A method for preparing the sustained-release sodium sarcosinate according to any one of claims 1 to 4, characterized in that: The specific preparation steps are as follows: (1) adding solubilizing monomer A to 30-40 parts of sodium sarcosinate aqueous solution, stirring evenly to obtain a mixed solution; (2) preparing acrylic acid and acrylamide into aqueous solutions respectively, obtaining acrylic acid aqueous solution and acrylamide aqueous solution, and then mixing the remaining sodium sarcosinate aqueous solution, acrylic acid aqueous solution, acrylamide aqueous solution, solubilizing monomer B, the mixed solution and the cross-linking agent under a nitrogen atmosphere, stirring evenly, adding an initiator, reacting at 60-80° C. for 2-3 hours, centrifuging, washing, and drying to obtain sustained-release sodium sarcosinate.

6. The method for preparing sustained-release sodium sarcosinate according to claim 5, characterized in that: In step (2), the concentration of the acrylic acid aqueous solution is 45-55%, and the concentration of the acrylamide aqueous solution is 40-50%.

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