A preparation method and application of sustained-release sodium sarcosinate

Abstract

The invention discloses a preparation method and application of a sustained-release sodium sarcosinate, which belongs to the technical field of chemical synthesis, including the synthesis of methylaminoacetonitrile: gradually adding hydroxyacetonitrile to a monomethylamine aqueous solution by a peristaltic pump, mixing and reacting at room temperature to generate methylaminoacetonitrile; primary embedding: purifying methylaminoacetonitrile by vacuum distillation and adding it to an embedding agent 1, stirring and mixing to obtain primary embedded methylaminoacetonitrile; synthesis of sodium sarcosinate: gradually adding the primary embedded methylaminoacetonitrile to an alcohol sodium aqueous solution by a peristaltic pump to generate a crude sodium sarcosinate product; secondary embedding: gradually adding embedding agent 2 to the crude sodium sarcosinate product, stirring and mixing to obtain secondary embedded sodium sarcosinate; washing and impurity removal: filtering the secondary embedded sodium sarcosinate, washing and impurity removal to obtain sustained-release sodium sarcosinate. The present application not only realizes the purification of sustained-release sodium sarcosinate, but also improves stability and sustained release.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a preparation method of sustained-release sodium sarcosinate and application thereof. Background Art

[0002] As an important chemical raw material, sodium sarcosinate is widely used in many fields such as medicine, cosmetics, and food. In particular, its non-irritating and easily biodegradable products are inseparable from daily life, so the market demand is large. For example, as a dyeing aid for fast dyes, it can improve the coloring effect and stability of dyes; it is used to make advanced medicated soaps, cosmetics, etc., as an active agent or additive to improve product performance and user experience. In the prior art, there are three main methods for preparing sodium sarcosinate, one is the chloroacetic acid method, that is, chloroacetic acid and monomethylamine react under the action of sodium hydroxide to generate sodium sarcosinate; another method is the hydroxyacetonitrile method, which can also be called the hydrocyanic acid method; and another is the methyl monoethanolamine method. Among them, the hydroxyacetonitrile method for preparing sodium sarcosinate is a common method in the field.

[0003] However, the traditional preparation method of sodium sarcosinate often has problems such as poor product stability and too fast release rate, which limits its application in specific fields. Therefore, it is particularly important to develop a method for preparing sodium sarcosinate with good stability and sustained release effect. Summary of the invention

[0004] To this end, the present invention provides a preparation method of sustained-release sodium sarcosinate and application thereof to solve the related technical problems existing in the prior art.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] According to a first aspect of the present invention, there is provided a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0007] (1) Synthesis of methylaminoacetonitrile: Hydroxyacetonitrile is gradually added to a monomethylamine aqueous solution by a peristaltic pump, and mixed and reacted at room temperature to generate methylaminoacetonitrile;

[0008] (2) Primary embedding: purify methylaminoacetonitrile by vacuum distillation and add it to embedding agent 1, stir and mix, and obtain primary embedded methylaminoacetonitrile;

[0009] (3) Synthesis of sodium sarcosinate: The primary embedded methylaminoacetonitrile is gradually added into the sodium alcohol aqueous solution through a peristaltic pump to generate a crude sodium sarcosinate product;

[0010] (4) Secondary embedding: gradually add embedding agent 2 to the crude sodium sarcosinate product, stir and mix, and obtain secondary embedded sodium sarcosinate;

[0011] (5) Washing and removing impurities: Filter the secondary embedded sodium sarcosinate, wash and remove impurities to obtain sustained-release sodium sarcosinate.

[0012] Furthermore, in step (1), the reaction temperature of hydroxyacetonitrile and monomethylamine is 15-25°C.

[0013] Furthermore, in step (3), the reaction temperature of methylaminoacetonitrile and sodium alkoxide is 42-53°C.

[0014] Furthermore, in step (2), the preparation method of embedding agent 1 comprises:

[0015] The single-walled carbon nanotube powder is dispersed in deionized water, and sodium dodecylbenzene sulfonate as a dispersant is added, wherein the mass ratio of the single-walled carbon nanotube to the sodium dodecylbenzene sulfonate is 1:(3-6), and ultrasonically crushed in an ultrasonic crusher, and then centrifuged in a centrifuge and the supernatant is collected to prepare a single-walled carbon nanotube dispersion;

[0016] The single-walled carbon nanotube dispersion and the graphene oxide solution were mixed in a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0017] Furthermore, in step (2), the volume ratio of methylaminoacetonitrile to embedding agent 1 is 1:(2-5), the stirring speed is 150-250 rpm, the mixing temperature is 10-15°C, the mixing pH is 2-3, and the mixing time is 12-18h.

[0018] Furthermore, in step (4), the embedding agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:(1-3).

[0019] Furthermore, in step (4), the secondary embedding step is:

[0020] The gallic catechin gallate is added into the crude sodium sarcosinate product, stirred and mixed with the single-walled carbon nanotubes in the crude sodium sarcosinate product by a non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary-embedded sodium sarcosinate.

[0021] Furthermore, in step (4), the stirring speed is 180-350 rpm, the mixing temperature is 15-20° C., the mixing pH is 5-7, and the mixing time is 21-36 h.

[0022] According to a second aspect of the present invention, provided is the use of the sustained-release sodium sarcosinate prepared by the preparation method described above in the preparation of cosmetics.

[0023] The present invention has the following advantages:

[0024] The present application improves the traditional hydroxyacetonitrile method, introduces an embedding agent to embed the produced sodium sarcosinate, and in particular, primary embedding of the intermediate product methylaminoacetonitrile by embedding agent 1, so that methylaminoacetonitrile can be attached to embedding agent 1, improving the reaction screening of the intermediate product methylaminoacetonitrile, and further embedding agent 2 and embedding agent 1 are non-covalently grafted to embed the final product and filter and remove impurities, thereby achieving screening and purification to obtain sustained-release sodium sarcosinate. The present application not only achieves the purification of sustained-release sodium sarcosinate, but also improves stability and sustained-release. DETAILED DESCRIPTION

[0025] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] In order to solve the problems of poor stability and too fast release rate of sodium sarcosinate products in the prior art, which limit its application in specific fields, this patent application is based on the applicant's prior research and improves the process of synthesizing sodium sarcosinate by the traditional hydroxyacetonitrile method, in order to add an embedding agent to perform two-stage embedding of the intermediate product and the final product of the reaction process, thereby improving the stability of the sodium sarcosinate product and achieving a sustained release effect when it is used as a cosmetic additive.

[0027] In the first aspect of the present invention, the present application provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0028] (1) Synthesis of methylaminoacetonitrile: Hydroxyacetonitrile is gradually added to a monomethylamine aqueous solution by a peristaltic pump, and mixed and reacted at room temperature to generate methylaminoacetonitrile. This step is the synthesis step of the intermediate product methylaminoacetonitrile, wherein the reaction temperature of hydroxyacetonitrile and monomethylamine is 15-25°C, and other parameters are set and reacted according to the prior art.

[0029] (2) Primary embedding: methylaminoacetonitrile is purified by vacuum distillation and added to embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, and the pressure of the vacuum distillation instrument is controlled at 70-100 mmHg and the temperature is controlled at 38-55°C. After distillation, the temperature is first cooled to room temperature for standby use. After the distillation is completed, methylaminoacetonitrile is added to embedding agent 1.

[0030] In this step, the embedding agent 1 is first prepared, specifically:

[0031] The single-walled carbon nanotube powder is dispersed in deionized water, and sodium dodecylbenzene sulfonate as a dispersant is added, wherein the mass ratio of the single-walled carbon nanotube to the sodium dodecylbenzene sulfonate is 1:(3-6), and ultrasonically crushed in an ultrasonic crusher, and then centrifuged in a centrifuge and the supernatant is collected to prepare a single-walled carbon nanotube dispersion; the single-walled carbon nanotube dispersion and the graphene oxide solution are mixed in a volume ratio of 1:1, and the mixed solution is ultrasonically crushed in an ultrasonic crusher to obtain an embedding agent 1.

[0032] Wherein, in step (2), the volume ratio of methylaminoacetonitrile to embedding agent 1 is 1:(2-5), the stirring speed is 150-250 rpm, the mixing temperature is 10-15°C, the mixing pH is 2-3, and the mixing time is 12-18h.

[0033] (3) Synthesis of sodium sarcosinate: The primary embedded methylaminoacetonitrile is gradually added to the sodium alkoxide aqueous solution through a peristaltic pump to generate a crude sodium sarcosinate product. In this step, the reaction temperature of methylaminoacetonitrile and sodium alkoxide is 42-53°C, and other parameters are set and reacted according to the prior art.

[0034] (4) Secondary embedding: embedding agent 2 is gradually added to the crude product of sodium sarcosinate, stirred and mixed, and sodium sarcosinate with secondary embedding is obtained. In this step, embedding agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotube is 1: (1-3). Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotube in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary embedded sodium sarcosinate.

[0035] In the above steps, the stirring speed is 180-350 rpm, the mixing temperature is 15-20° C., the mixing pH is 5-7, and the mixing time is 21-36 h.

[0036] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, the sodium sarcosinate is filtered through an ultrafiltration membrane and washed with water for multiple times to remove impurities.

[0037] According to a second aspect of the present invention, provided is the use of the sustained-release sodium sarcosinate prepared by the above method for preparing sustained-release sodium sarcosinate in the preparation of cosmetics.

[0038] The technical effects of the present invention are described below through embodiments.

[0039] Example 1

[0040] This embodiment 1 provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0041] (1) Synthesis of methylaminoacetonitrile:

[0042] Prepare 30 mL of hydroxyacetonitrile for use, and gradually add hydroxyacetonitrile to a 40% monomethylamine aqueous solution through a peristaltic pump, the total volume of the monomethylamine aqueous solution is 360 mL. The reaction conditions are: stirring while adding dropwise, the stirring speed is 90 rpm, the reaction temperature of hydroxyacetonitrile and monomethylamine is 20°C, and after the addition is completed, continue stirring the reaction for 0.5 h and then stop to generate methylaminoacetonitrile.

[0043] After the reaction is completed, the mixture is allowed to stand for 2 h and then heated to the distillation temperature.

[0044] (2) Primary embedding:

[0045] In this step, the embedding agent 1 is first prepared, specifically:

[0046] 10 g of single-walled carbon nanotube powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of single-walled carbon nanotubes to sodium dodecylbenzene sulfonate was 1:3, dispersant sodium dodecylbenzene sulfonate was added, and ultrasonic crushing was carried out in an ultrasonic crusher, the ultrasonic time was 45 min, the ultrasonic power was 250 W, the stirring speed of the magnetic stirrer was 300 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a single-walled carbon nanotube dispersion.

[0047] Similarly, 10 g of graphene oxide powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of graphene oxide to sodium dodecylbenzene sulfonate was 1:3, dispersant sodium dodecylbenzene sulfonate was added, and ultrasonic crushing was performed in an ultrasonic crusher, the ultrasonic time was 45 min, the ultrasonic power was 250 W, the stirring speed of the magnetic stirrer was 300 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a graphene oxide dispersion.

[0048] Then, the single-walled carbon nanotube dispersion and the graphene oxide solution were mixed at a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0049] Finally, methylaminoacetonitrile is purified by vacuum distillation and added to the embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, the pressure of the vacuum distillation instrument is controlled at 80 mmHg, and the temperature is controlled at 40°C. After distillation, self-cooling is first performed to cool to room temperature for standby use. After distillation, methylaminoacetonitrile is added to the embedding agent 1.

[0050] Specifically, in step (2), the distilled concentrated methylaminoacetonitrile and the embedding agent 1 are mixed in a volume ratio of 1:4, the stirring speed is maintained at 180 rpm, the mixing temperature is adjusted to 15° C., the mixed pH is adjusted to 2.1 with a hydrochloric acid solution, and the mixing time is 15 h.

[0051] (3) Synthesis of sodium sarcosinate:

[0052] Prepare 100 mL of primary embedding methylaminoacetonitrile solution, gradually add it into the prepared 200 mL sodium ethoxide aqueous solution through a peristaltic pump, add dropwise while stirring, the stirring speed is 120 rpm, the reaction temperature of methylaminoacetonitrile and sodium ethoxide is 45 ° C. After the addition is completed, continue stirring the reaction for 3 hours and then stop to generate a crude sodium sarcosinate product.

[0053] (4) Secondary encapsulation: gradually add encapsulating agent 2 to the crude product of sodium sarcosinate, stir and mix, and obtain secondary encapsulated sodium sarcosinate. In this step, encapsulating agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:2. Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotubes in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary encapsulated sodium sarcosinate. In this step, the stirring speed is 320 rpm, the mixing temperature is 15°C, the mixing pH is 5, and the mixing time is 25 h.

[0054] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, filtration is performed through an ultrafiltration membrane and impurities are removed multiple times through a 50% ethanol aqueous solution.

[0055] The content of sustained-release sodium sarcosinate was detected to be 51.7%, and the yield of sustained-release sodium sarcosinate in this example was 95.3%.

[0056] Example 2

[0057] This embodiment 2 provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0058] (1) Synthesis of methylaminoacetonitrile:

[0059] Prepare 30 mL of hydroxyacetonitrile for use, and gradually add hydroxyacetonitrile to a 40% aqueous monomethylamine solution through a peristaltic pump, the total volume of the monomethylamine solution is 360 mL. The reaction conditions are: stirring while adding dropwise, the stirring speed is 80 rpm, the reaction temperature of hydroxyacetonitrile and monomethylamine is 25 ° C, and after the addition is completed, continue stirring the reaction for 0.5 hours and then stop to generate methylaminoacetonitrile.

[0060] After the reaction is completed, the mixture is allowed to stand for 2 h and then heated to the distillation temperature.

[0061] (2) Primary embedding:

[0062] In this step, the embedding agent 1 is first prepared, specifically:

[0063] 10 g of single-walled carbon nanotube powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of single-walled carbon nanotubes to sodium dodecylbenzene sulfonate was 1:5, and dispersant sodium dodecylbenzene sulfonate was added, and ultrasonic crushing was carried out in an ultrasonic crusher, the ultrasonic time was 50 min, the ultrasonic power was 300 W, and the stirring speed of the magnetic stirrer was 400 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a single-walled carbon nanotube dispersion.

[0064] Similarly, 10 g of graphene oxide powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of graphene oxide to sodium dodecylbenzene sulfonate was 1:5, sodium dodecylbenzene sulfonate was added as a dispersant, and ultrasonic crushing was performed in an ultrasonic crusher, the ultrasonic time was 50 min, the ultrasonic power was 300 W, and the stirring speed of the magnetic stirrer was 400 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a graphene oxide dispersion.

[0065] Then, the single-walled carbon nanotube dispersion and the graphene oxide solution were mixed at a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0066] Finally, methylaminoacetonitrile is purified by vacuum distillation and added to the embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, the pressure of the vacuum distillation instrument is controlled at 90 mmHg, and the temperature is controlled at 50°C. After distillation, self-cooling is first performed to cool to room temperature for standby use. After distillation, methylaminoacetonitrile is added to the embedding agent 1.

[0067] Specifically, in step (2), the distilled concentrated methylaminoacetonitrile and the embedding agent 1 are mixed in a volume ratio of 1:3, the stirring speed is maintained at 200 rpm, the mixing temperature is adjusted to 12° C., the mixed pH is adjusted to 2.5 with a hydrochloric acid solution, and the mixing time is 18 h.

[0068] (3) Synthesis of sodium sarcosinate:

[0069] Prepare 100 mL of primary embedding methylaminoacetonitrile solution, gradually add it into the prepared 200 mL sodium ethoxide aqueous solution through a peristaltic pump, add dropwise while stirring, the stirring speed is 140 rpm, the reaction temperature of methylaminoacetonitrile and sodium ethoxide is 50°C, after the addition is completed, continue stirring the reaction for 2 hours and then stop to generate a crude sodium sarcosinate product.

[0070] (4) Secondary encapsulation: gradually add encapsulating agent 2 to the crude product of sodium sarcosinate, stir and mix, and obtain secondary encapsulated sodium sarcosinate. In this step, encapsulating agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:3. Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotubes in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary encapsulated sodium sarcosinate. In this step, the stirring speed is 350 rpm, the mixing temperature is 20°C, the mixing pH is 6, and the mixing time is 30 hours.

[0071] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, filtration is performed through an ultrafiltration membrane and impurities are removed multiple times through a 50% ethanol aqueous solution.

[0072] The content of sustained-release sodium sarcosinate was detected to be 52.5%, and the yield of sustained-release sodium sarcosinate in this example was 94.6%.

[0073] Example 3

[0074] This embodiment 3 provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0075] (1) Synthesis of methylaminoacetonitrile:

[0076] Prepare 30 mL of hydroxyacetonitrile for use, and gradually add hydroxyacetonitrile to a 40% monomethylamine aqueous solution through a peristaltic pump, the total volume of the monomethylamine aqueous solution is 360 mL. The reaction conditions are: stirring while adding dropwise, the stirring speed is 100 rpm, the reaction temperature of hydroxyacetonitrile and monomethylamine is 15°C, and after the addition is completed, continue stirring the reaction for 0.5 h and then stop to generate methylaminoacetonitrile.

[0077] After the reaction was completed, the mixture was allowed to stand for 1.5 h and then heated to the distillation temperature.

[0078] (2) Primary embedding:

[0079] In this step, the embedding agent 1 is first prepared, specifically:

[0080] 10 g of single-walled carbon nanotube powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of single-walled carbon nanotubes to sodium dodecylbenzene sulfonate was 1:6, and dispersant sodium dodecylbenzene sulfonate was added, and ultrasonic crushing was carried out in an ultrasonic crusher, the ultrasonic time was 35 min, the ultrasonic power was 210 W, and the stirring speed of the magnetic stirrer was 500 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a single-walled carbon nanotube dispersion.

[0081] Similarly, 10 g of graphene oxide powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of graphene oxide to sodium dodecylbenzene sulfonate was 1:6, sodium dodecylbenzene sulfonate was added as a dispersant, and ultrasonic crushing was performed in an ultrasonic crusher, the ultrasonic time was 35 min, the ultrasonic power was 210 W, the stirring speed of the magnetic stirrer was 500 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a graphene oxide dispersion.

[0082] Then, the single-walled carbon nanotube dispersion and the graphene oxide solution were mixed at a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0083] Finally, methylaminoacetonitrile is purified by vacuum distillation and added to the embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, the pressure of the vacuum distillation instrument is controlled at 95 mmHg, and the temperature is controlled at 55°C. After distillation, self-cooling is first performed to cool to room temperature for standby use. After distillation, methylaminoacetonitrile is added to the embedding agent 1.

[0084] Specifically, in step (2), the distilled concentrated methylaminoacetonitrile and the embedding agent 1 are mixed at a volume ratio of 1:5, the stirring speed is maintained at 250 rpm, the mixing temperature is adjusted to 10° C., the mixing pH is adjusted to 3 with a hydrochloric acid solution, and the mixing time is 18 h.

[0085] (3) Synthesis of sodium sarcosinate:

[0086] Prepare 100 mL of primary embedding methylaminoacetonitrile solution, gradually add it into the prepared 200 mL sodium ethoxide aqueous solution through a peristaltic pump, add dropwise while stirring, the stirring speed is 150 rpm, the reaction temperature of methylaminoacetonitrile and sodium ethoxide is 53 ° C. After the addition is completed, continue stirring the reaction for 2 hours and then stop to generate a crude sodium sarcosinate product.

[0087] (4) Secondary encapsulation: gradually add encapsulating agent 2 to the crude product of sodium sarcosinate, stir and mix, and obtain secondary encapsulated sodium sarcosinate. In this step, encapsulating agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:1.5. Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotubes in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary encapsulated sodium sarcosinate. In this step, the stirring speed is 200 rpm, the mixing temperature is 18°C, the mixing pH is 7, and the mixing time is 36 hours.

[0088] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, filtration is performed through an ultrafiltration membrane and impurities are removed multiple times through a 50% ethanol aqueous solution.

[0089] The content of sustained-release sodium sarcosinate was detected to be 53.8%, and the yield of sustained-release sodium sarcosinate in this example was 94.5%.

[0090] Example 4

[0091] This embodiment 4 provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0092] (1) Synthesis of methylaminoacetonitrile:

[0093] Prepare 30 mL of hydroxyacetonitrile for use, and gradually add hydroxyacetonitrile to a 40% aqueous monomethylamine solution through a peristaltic pump, the total volume of the monomethylamine solution is 360 mL. The reaction conditions are: stirring while adding dropwise, the stirring speed is 100 rpm, the reaction temperature of hydroxyacetonitrile and monomethylamine is 22°C, and after the addition is completed, continue stirring the reaction for 0.5 h and then stop to generate methylaminoacetonitrile.

[0094] After the reaction was completed, the mixture was allowed to stand for 1 hour and then heated to the distillation temperature.

[0095] (2) Primary embedding:

[0096] In this step, the embedding agent 1 is first prepared, specifically:

[0097] 10 g of single-walled carbon nanotube powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of single-walled carbon nanotubes to sodium dodecylbenzene sulfonate was 1:4, and dispersant sodium dodecylbenzene sulfonate was added, and ultrasonic crushing was carried out in an ultrasonic crusher, the ultrasonic time was 60 min, the ultrasonic power was 350 W, and the stirring speed of the magnetic stirrer was 450 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a single-walled carbon nanotube dispersion.

[0098] Similarly, 10 g of graphene oxide powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of graphene oxide to sodium dodecylbenzene sulfonate was 1:4, sodium dodecylbenzene sulfonate was added as a dispersant, and ultrasonic crushing was performed in an ultrasonic crusher, the ultrasonic time was 60 min, the ultrasonic power was 350 W, and the stirring speed of the magnetic stirrer was 450 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a graphene oxide dispersion.

[0099] Then, the single-walled carbon nanotube dispersion and the graphene oxide solution were mixed at a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0100] Finally, methylaminoacetonitrile is purified by vacuum distillation and added to the embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, the pressure of the vacuum distillation instrument is controlled at 100 mmHg, and the temperature is controlled at 38°C. After distillation, it is first cooled to room temperature for standby use. After distillation, methylaminoacetonitrile is added to the embedding agent 1.

[0101] Specifically, in step (2), the distilled concentrated methylaminoacetonitrile and embedding agent 1 are mixed at a volume ratio of 1:2, the stirring speed is maintained at 235 rpm, the mixing temperature is adjusted to 13° C., the mixing pH is adjusted to 2.5 with a hydrochloric acid solution, and the mixing time is 13 h.

[0102] (3) Synthesis of sodium sarcosinate:

[0103] Prepare 100 mL of primary embedding methylaminoacetonitrile solution, gradually add it into the prepared 200 mL sodium ethoxide aqueous solution through a peristaltic pump, add dropwise while stirring, the stirring speed is 130 rpm, the reaction temperature of methylaminoacetonitrile and sodium ethoxide is 50°C, after the addition is completed, continue stirring the reaction for 4 hours and then stop to generate a crude sodium sarcosine product.

[0104] (4) Secondary encapsulation: gradually add encapsulating agent 2 to the crude product of sodium sarcosinate, stir and mix, and obtain secondary encapsulated sodium sarcosinate. In this step, encapsulating agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:2.5. Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotubes in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary encapsulated sodium sarcosinate. In this step, the stirring speed is 300 rpm, the mixing temperature is 16°C, the mixing pH is 5.5, and the mixing time is 34 hours.

[0105] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, filtration is performed through an ultrafiltration membrane and impurities are removed multiple times through a 50% ethanol aqueous solution.

[0106] The content of sustained-release sodium sarcosinate was detected to be 58.1%, and the yield of sustained-release sodium sarcosinate in this example was 97.2%.

[0107] Example 5

[0108] This embodiment 5 provides a method for preparing sustained-release sodium sarcosinate, comprising the following steps:

[0109] (1) Synthesis of methylaminoacetonitrile:

[0110] Prepare 30 mL of hydroxyacetonitrile for use, and gradually add hydroxyacetonitrile to a 40% monomethylamine aqueous solution through a peristaltic pump, the total volume of the monomethylamine aqueous solution is 360 mL. The reaction conditions are: stirring while adding dropwise, the stirring speed is 85 rpm, the reaction temperature of hydroxyacetonitrile and monomethylamine is 18°C, and after the addition is completed, continue stirring the reaction for 0.5 h and then stop to generate methylaminoacetonitrile.

[0111] After the reaction was completed, the mixture was allowed to stand for 1.5 h and then heated to the distillation temperature.

[0112] (2) Primary embedding:

[0113] In this step, the embedding agent 1 is first prepared, specifically:

[0114] 10 g of single-walled carbon nanotube powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of single-walled carbon nanotube to sodium dodecylbenzene sulfonate was 1:4.5, and sodium dodecylbenzene sulfonate was added as a dispersant. The mixture was ultrasonically crushed in an ultrasonic crusher, the ultrasonic time was 40 min, the ultrasonic power was 280 W, and the stirring speed of the magnetic stirrer was 350 rpm until uniform mixing. The mixture was then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a single-walled carbon nanotube dispersion.

[0115] Similarly, 10 g of graphene oxide powder was weighed and dispersed in 100 mL of deionized water, wherein the mass ratio of graphene oxide to sodium dodecylbenzene sulfonate was 1:4.5, and sodium dodecylbenzene sulfonate was added as a dispersant, and ultrasonic crushing was performed in an ultrasonic crusher, the ultrasonic time was 40 min, the ultrasonic power was 280 W, and the stirring speed of the magnetic stirrer was 350 rpm until uniform mixing, and then placed in a centrifuge for centrifugation and the supernatant was collected to prepare a graphene oxide dispersion.

[0116] Then, the single-walled carbon nanotube dispersion and the graphene oxide solution were mixed at a volume ratio of 1:1, and the mixed solution was placed in an ultrasonic crusher for ultrasonication to obtain an embedding agent 1.

[0117] Finally, methylaminoacetonitrile is purified by vacuum distillation and added to the embedding agent 1, and stirred to obtain primary embedded methylaminoacetonitrile. In this step, vacuum distillation is performed based on the reaction system, the pressure of the vacuum distillation instrument is controlled at 78 mmHg, and the temperature is controlled at 52°C. After distillation, self-cooling is first performed to cool to room temperature for standby use. After distillation, methylaminoacetonitrile is added to the embedding agent 1.

[0118] Specifically, in step (2), the distilled concentrated methylaminoacetonitrile and the embedding agent 1 are mixed at a volume ratio of 1:3.5, the stirring speed is maintained at 200 rpm, the mixing temperature is adjusted to 12° C., the mixing pH is adjusted to 3 with a hydrochloric acid solution, and the mixing time is 15 h.

[0119] (3) Synthesis of sodium sarcosinate:

[0120] Prepare 100 mL of primary embedding methylaminoacetonitrile solution, gradually add it into the prepared 200 mL sodium ethoxide aqueous solution through a peristaltic pump, add dropwise while stirring, the stirring speed is 100 rpm, the reaction temperature of methylaminoacetonitrile and sodium ethoxide is 53 ° C. After the addition is completed, continue stirring the reaction for 3 hours and then stop to generate a crude sodium sarcosinate product.

[0121] (4) Secondary encapsulation: gradually add encapsulating agent 2 to the crude product of sodium sarcosinate, stir and mix, and obtain secondary encapsulated sodium sarcosinate. In this step, encapsulating agent 2 is epigallocatechin gallate, and the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:2.8. Epigallocatechin gallate is added to the crude product of sodium sarcosinate, stirred and mixed with the single-walled carbon nanotubes in the crude product of sodium sarcosinate by non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary encapsulated sodium sarcosinate. In this step, the stirring speed is 180 rpm, the mixing temperature is 20°C, the mixing pH is 6.5, and the mixing time is 30 hours.

[0122] (5) Washing and removing impurities: The secondary embedded sodium sarcosinate is filtered, washed and removed to obtain sustained-release sodium sarcosinate. Specifically, in this step, filtration is performed through an ultrafiltration membrane and impurities are removed multiple times through a 50% ethanol aqueous solution.

[0123] The content of sustained-release sodium sarcosinate was detected to be 57.4%, and the yield of sustained-release sodium sarcosinate in this example was 96.7%.

[0124] Comparative Example

[0125] The processing steps of sodium sarcosinate in this comparative example are the same as those in Example 4, but embedding agent 1 and embedding agent 2 are not added. The content of sodium sarcosinate is 34.4% by detection, and the yield of sodium sarcosinate in this comparative example is 83.2%.

[0126] In summary, in the preparation of sustained-release sodium sarcosinate, the addition of embedding agent 1 and embedding agent 2 improves the yield of sodium sarcosinate relative to the prior art. In particular, as in the above-mentioned embodiment 4, when single-walled carbon nanotubes and graphene oxide are mixed to prepare embedding agent 1 in a ratio of 1:4, a higher embedding effect can be achieved. At the same time, as in embodiment 4 and embodiment 5, when single-walled carbon nanotubes and epigallocatechin gallate are added in a ratio of 1:2.5, the best embedding effect can be obtained, and the yield can also reach more than 97%. Compared with the comparative example, it can be seen that when embedding agent is not added, its content and yield are significantly reduced. Therefore, by the use of embedding agent, the yield of sustained-release sodium sarcosinate can be significantly improved.

[0127] Test Case

[0128] Preparation of soothing gel mask: 5g hyaluronic acid, 10g glycerol, 2g 4-tert-butyl cyclohexanol, 75g water and 5g auxiliary ingredients such as preservatives and fragrances. Add 3g of the sustained-release sodium sarcosinate prepared in Example 4 to prepare an experimental example; add 3g of the sodium sarcosinate prepared in the comparative example to prepare a control example.

[0129] The prepared examples and control examples were spread in culture dishes, with a thickness of 2-3 mm, and were placed in an oven at 95° C., and the content of sodium sarcosinate was detected by high performance liquid chromatography every 8 hours. The experimental results show that when the control example was detected for 42 hours, the detection signal was weak and almost completely volatilized, while the sodium sarcosinate component was still detectable in the experimental example at 72 hours (when the experiment was terminated), indicating that by using the method of Example 4, sodium sarcosinate can be embedded under the conditions of adding embedding agent 1 and embedding agent 2, and can maintain stability for a long time under heating conditions, so it can be foreseen that the sustained release effect can be achieved by adding it to cosmetics, and the shelf life of cosmetics can also be extended.

[0130] The present application improves the traditional hydroxyacetonitrile method, introduces an embedding agent to embed the produced sodium sarcosinate, and in particular, primary embedding of the intermediate product methylaminoacetonitrile by embedding agent 1, so that methylaminoacetonitrile can be attached to embedding agent 1, improving the reaction screening of the intermediate product methylaminoacetonitrile, and further embedding agent 2 and embedding agent 1 are non-covalently grafted to embed the final product and filter and remove impurities, thereby achieving screening and purification to obtain sustained-release sodium sarcosinate. The present application not only achieves the purification of sustained-release sodium sarcosinate, but also improves stability and sustained-release.

[0131] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A method for preparing sustained-release sodium sarcosinate, characterized in that: The steps include: (1) Synthesis of methylaminoacetonitrile: Hydroxyacetonitrile is gradually added to a monomethylamine aqueous solution by a peristaltic pump, and mixed and reacted at room temperature to generate methylaminoacetonitrile; (2) Primary embedding: purifying methylaminoacetonitrile by vacuum distillation and adding it to embedding agent 1, stirring and mixing, to obtain primary embedded methylaminoacetonitrile; wherein the preparation method of embedding agent 1 comprises: The single-walled carbon nanotube powder is dispersed in deionized water, and sodium dodecylbenzene sulfonate as a dispersant is added, wherein the mass ratio of the single-walled carbon nanotube to the sodium dodecylbenzene sulfonate is 1:(3-6), and ultrasonically crushed in an ultrasonic crusher, and then centrifuged in a centrifuge and the supernatant is collected to prepare a single-walled carbon nanotube dispersion; the single-walled carbon nanotube dispersion and the graphene oxide solution are mixed in a volume ratio of 1:1, and the mixed solution is ultrasonically crushed in an ultrasonic crusher to obtain an embedding agent 1; (3) Synthesis of sodium sarcosinate: The primary embedded methylaminoacetonitrile is gradually added into the sodium alcohol aqueous solution through a peristaltic pump to generate a crude sodium sarcosinate product; (4) Secondary embedding: gradually adding embedding agent 2 to the crude product of sodium sarcosinate, stirring and mixing, to obtain secondary embedded sodium sarcosinate; wherein embedding agent 2 is epigallocatechin gallate; (5) Washing and removing impurities: Filter the secondary embedded sodium sarcosinate, wash and remove impurities to obtain sustained-release sodium sarcosinate.

2. The method for preparing sustained-release sodium sarcosinate according to claim 1, characterized in that: in, In step (1), the reaction temperature of hydroxyacetonitrile and monomethylamine is 15-25°C.

3. The method for preparing sustained-release sodium sarcosinate according to claim 1, characterized in that: in, In step (3), the reaction temperature of methylaminoacetonitrile and sodium alcoholate is 42-53°C.

4. The method for preparing sustained-release sodium sarcosinate according to claim 1, characterized in that: in, In step (2), the volume ratio of methylaminoacetonitrile to embedding agent 1 is 1:(2-5), the stirring speed is 150-250 rpm, the mixing temperature is 10-15°C, the mixing pH is 2-3, and the mixing time is 12-18 hours.

5. The method for preparing sustained-release sodium sarcosinate according to claim 4, characterized in that: in, In step (4), the mass ratio of epigallocatechin gallate to single-walled carbon nanotubes is 1:(1-3).

6. The method for preparing sustained-release sodium sarcosinate according to claim 5, characterized in that: in, In step (4), the secondary embedding step is: The gallic catechin gallate is added into the crude sodium sarcosinate product, stirred and mixed with the single-walled carbon nanotubes in the crude sodium sarcosinate product by a non-covalent grafting method, and ultrasonically dispersed to obtain uniform secondary-embedded sodium sarcosinate.

7. The method for preparing sustained-release sodium sarcosinate according to claim 6, characterized in that: in, In step (4), the stirring speed is 180-350 rpm, the mixing temperature is 15-20° C., the mixing pH is 5-7, and the mixing time is 21-36 h.

8. Use of the sustained-release sodium sarcosinate prepared by the preparation method according to any one of claims 1 to 7 in the preparation of cosmetics.