Preparation process method of hydrophilic diglyceride oil microcapsule powder
Through emulsification crosslinking method and electrostatic adsorption principle, diglycerides are coated in microcapsules of chitosan and sodium alginate, which solves the problems of unstable and difficult to control the release of diglycerides, and achieves stable packaging and efficient release of diglycerides.
Patent Information
- Application Number
- CN202510220657.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-27
- Publication Date
- 2025-05-13
AI Technical Summary
In the prior art, diglycerides have problems such as unstable, volatile and insoluble in water, which are difficult to store and use. At the same time, there is a lack of a method of controlling the release effect with diglyceride microcapsules as the research object.
Diglyceride microcapsules were prepared by emulsifying cross-linking method. Diglycerides were coated in microcapsules using chitosan and sodium alginate through the principle of electrostatic adsorption, and the release effect was controlled by surfactant and pH sensitivity.
The stable packaging of diglycerides was achieved, and a hydrophilic diglyceride microcapsule powder with uniform particle size, good spherical shape, high encapsulation rate and drug loading rate was obtained. It has the characteristics of ecologically friendly, hydrophilic surface, stable structure and easy storage, and a wide range of use.
Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing a modified structure of an oil-phase hydrophilic microcapsule, in particular to a method for preparing hydrophilic diglyceride oil microcapsule powder. Background Art
[0002] Diacylcerol is natural, low-cost, safe, widely applicable, and has good application prospects. However, liquid diacylglycerol has problems such as instability, volatility, and insolubility in water, making it inconvenient to store and use.
[0003] In the prior art, no research has been conducted on diglycerol microcapsules to study the controlled release effects of microcapsules under different environments, in order to provide new ideas for nature-friendly diglycerol packaging materials. Among similar technologies in the prior art, the current mainstream method has not applied the emulsification cross-linking method for preparing microcapsules to diglycerol microcapsules.
[0004] Therefore, there is a need for a preparation process for hydrophilic diglyceride oil microcapsule powder which is eco-friendly, has a hydrophilic surface, is stable in structure, is easy to preserve, and has a wide range of uses. Summary of the invention
[0005] The invention aims to provide a preparation process of hydrophilic diglyceride oil microcapsule powder which is eco-friendly, surface hydrophilic, stable in structure, easy to preserve and has a wide range of applications.
[0006] In order to achieve the above object, the present invention adopts the following technical scheme: a preparation process of hydrophilic diglycerol oil microcapsule powder, the process comprising the following stages: S1: Raw material preparation ① Raw material preparation: prepare sufficient amount of diglyceride, sufficient amount of Northeastern crayfish shell, protease, chitosan glycosaminoglycans, deacetylase, prepare sodium alginate aqueous solution with a solute mass fraction of 2%, sufficient amount of acetic acid aqueous solution with a volume ratio of acetic acid to water (10-20):100, sufficient amount of dilute acetic acid aqueous solution with a volume ratio of acetic acid to water (0.8-1.2):100, surfactant, and calcium chloride aqueous solution with a solute mass fraction of 5%; wherein the surfactant is a surfactant of polyoxyethylene hydrogenated castor oil / n-butene system, and the surfactant K m The value is 5 / 2~2 / 1; ② Preparation of tools and equipment: prepare constant flow pump, magnetic stirring device, ultrasonic generator, quartz reaction container with heating device, mechanical powder making device, centrifugal device; S2: Preparation of water-soluble chitosan ① After cleaning the Northeastern crayfish shells prepared in step ① of stage S1, the shells are crushed into powder using the mechanical powder making device prepared in step ② of stage S1 to obtain shell powder; ② Soak the shell powder obtained in step ① in pure water, then add the lysin prepared in step ① of stage S1 into the water, inject it into the quartz reaction container prepared in step ② of stage S1, heat it to 35°C~38°C, maintain it for 8h~10h, then filter out the liquid to obtain solid crude chitin; ③ The solid crude chitosan obtained in step ② is cleaned with pure water and then immersed in pure water, and then the chitosan aminoacidase and deacetylase prepared in step ① of stage S1 are added into the water, and the temperature is raised to 35°C to 38°C, and maintained for 8h to 10h to obtain a chitosanase water mixed solution; ④ heating the chitosanase water mixed solution obtained in step ③ to 75°C~80°C and maintaining it for 1.5h~2h to obtain an inactivated chitosan solution; filtering out the solidified material and drying it to obtain water-soluble chitosan; S3: Microcapsule preparation ① Mix the diglyceride prepared in step ① of stage S1 with the surfactant in a mass ratio of (8.5-9):1 and stir evenly to obtain an emulsion; ② The water-soluble chitosan obtained in step ④ of stage S2 is completely dissolved in the acetic acid aqueous solution prepared in step ① of stage S1, and the proportion of the water-soluble chitosan and the acetic acid aqueous solution is such that the water-soluble chitosan is just completely dissolved to form a saturated chitosan acetic acid aqueous solution; ③ The sodium alginate aqueous solution prepared in step ① of stage S1 and the emulsion obtained in step ① are uniformly mixed according to the mass ratio of sodium alginate to diglyceride (3-3.5): (14-16); then the magnetic stirring device and ultrasonic generating device prepared in step ② of stage S1 are used for magnetic stirring and ultrasonic dispersion to prepare a dispersed emulsion; ④ The calcium chloride aqueous solution prepared in step ① of stage S1 is evenly added dropwise to the dispersed emulsion and stirred for 2.5h~3h until the reaction is complete; the reaction system is centrifuged at a rate of 8500rpm~9000rpm using the centrifugal device prepared in step ② of stage S1, and the product is alternately washed with ether and water after removing the upper oil phase, and the centrifugation, oil phase removal and washing are repeated 3~4 times to obtain gel microspheres encapsulating diglyceride; ⑤ The gel microspheres obtained in step ④ are put into the saturated chitosan acetic acid aqueous solution obtained in step ②, heated to 38°C~43°C, stirred by a magnetic stirring device, and reacted for 75min~90min until the surface of the gel microspheres is fully complexed with chitosan to obtain a microcapsule turbid liquid; the microcapsule turbid liquid is centrifuged at a rate of 6200rpm~6500rpm using the centrifugal device prepared in step ② of stage S1, and the surface is cleaned using the dilute acetic acid aqueous solution prepared in step ① of stage S1, and the centrifugal separation and surface cleaning steps are repeated 2~3 times to obtain prefabricated microcapsules; ⑥ Freeze-dry the prefabricated microcapsules obtained in step ⑤ for 1 day to 1.5 days to obtain the desired hydrophilic diglyceride oil microcapsule powder.
[0007] Compared with the prior art, the present invention has the following advantages due to the adoption of the above technical solution: (1) The method of the present invention utilizes the electrostatic adsorption principle of chitosan and sodium alginate, controls oil and water, adds a surfactant of a polyoxyethylene hydrogenated castor oil / n-butene system, pre-encapsulates by reaction of sodium alginate and calcium chloride, and then encapsulates diglycerol in sodium alginate chitosan microcapsules by the electrostatic adsorption principle of chitosan and sodium alginate, thereby obtaining diglycerol microcapsules with uniform particle size, good sphericity, high encapsulation rate and drug loading rate.
[0008] (2) The applicant of the present invention has finally determined the release rate law of the drug in microcapsules in different sustained-release media through a large number of production practices and replacement of raw materials. In particular, in the present invention, the selection of three raw materials is the best selection obtained after a large number of material comparisons and screenings. One is the type of surfactant, which is a surfactant of the polyoxyethylene hydrogenated castor oil / n-butene system and a limited K m The first is that it is the most suitable material for natural affinity and hydrophilic effect modification and core-shell system construction; the second is that the source of chitosan is the shell of Northeast Crayfish, which is the best choice for the hydrophilic effect and source of finished chitosan, the best choice for low-cost technology, stability and economic effect; the third is that in the process of preparing chitosan, the combination of protease, chitosan aminoacidase and deacetylase and supporting process parameters are the best combination of yield, stability and hydrophilic effect. No other raw materials or methods with better technical effects have been found in the prior art.
[0009] (3) The present invention loads fat-soluble substances into pH-sensitive sodium alginate chitosan microcapsules in the form of microemulsions, which, on the one hand, achieves a higher drug loading rate and encapsulation rate; secondly, it also obtains hydrophilicity that is unattainable by fat-soluble substances; finally, it also obtains that the product can achieve different controlled-release effects under different environmental conditions by adjusting the pH value, and has a wide range of applications.
[0010] Therefore, the invention has the characteristics of being eco-friendly, having a hydrophilic surface, having a stable structure, being easy to store, and having a wide range of uses. DETAILED DESCRIPTION Example 1
[0011] A preparation process of hydrophilic diglyceride oil microcapsule powder, the process comprising the following stages: S1: Raw material preparation ① Raw material preparation: prepare sufficient amount of diglyceride, sufficient amount of Northeastern crayfish shell, protease, chitosan glycosaminoglycans, deacetylase, prepare sodium alginate aqueous solution with a solute mass fraction of 2%, sufficient amount of acetic acid aqueous solution with a volume ratio of acetic acid to water (10-20):100, sufficient amount of dilute acetic acid aqueous solution with a volume ratio of acetic acid to water (0.8-1.2):100, surfactant, and calcium chloride aqueous solution with a solute mass fraction of 5%; wherein the surfactant is a surfactant of polyoxyethylene hydrogenated castor oil / n-butene system, and the surfactant K m The value is 5 / 2~2 / 1; ② Preparation of tools and equipment: prepare constant flow pump, magnetic stirring device, ultrasonic generator, quartz reaction container with heating device, mechanical powder making device, centrifugal device; S2: Preparation of water-soluble chitosan ① After cleaning the Northeastern crayfish shells prepared in step ① of stage S1, the shells are crushed into powder using the mechanical powder making device prepared in step ② of stage S1 to obtain shell powder; ② Soak the shell powder obtained in step ① in pure water, then add the lysin prepared in step ① of stage S1 into the water, inject it into the quartz reaction container prepared in step ② of stage S1, heat it to 35°C~38°C, maintain it for 8h~10h, then filter out the liquid to obtain solid crude chitin; ③ The solid crude chitosan obtained in step ② is cleaned with pure water and then immersed in pure water, and then the chitosan aminoacidase and deacetylase prepared in step ① of stage S1 are added into the water, and the temperature is raised to 35°C to 38°C, and maintained for 8h to 10h to obtain a chitosanase water mixed solution; ④ heating the chitosanase water mixed solution obtained in step ③ to 75°C~80°C and maintaining it for 1.5h~2h to obtain an inactivated chitosan solution; filtering out the solidified material and drying it to obtain water-soluble chitosan; S3: Microcapsule preparation ① Mix the diglyceride prepared in step ① of stage S1 with the surfactant in a mass ratio of (8.5-9):1 and stir evenly to obtain an emulsion; ② The water-soluble chitosan obtained in step ④ of stage S2 is completely dissolved in the acetic acid aqueous solution prepared in step ① of stage S1, and the proportion of the water-soluble chitosan and the acetic acid aqueous solution is such that the water-soluble chitosan is just completely dissolved to form a saturated chitosan acetic acid aqueous solution; ③ The sodium alginate aqueous solution prepared in step ① of stage S1 and the emulsion obtained in step ① are uniformly mixed according to the mass ratio of sodium alginate to diglyceride (3-3.5): (14-16); then the magnetic stirring device and ultrasonic generating device prepared in step ② of stage S1 are used for magnetic stirring and ultrasonic dispersion to prepare a dispersed emulsion; ④ The calcium chloride aqueous solution prepared in step ① of stage S1 is evenly added dropwise to the dispersed emulsion and stirred for 2.5h~3h until the reaction is complete; the reaction system is centrifuged at a rate of 8500rpm~9000rpm using the centrifugal device prepared in step ② of stage S1, and the product is alternately washed with ether and water after removing the upper oil phase, and the centrifugation, oil phase removal and washing are repeated 3~4 times to obtain gel microspheres encapsulating diglyceride; ⑤ The gel microspheres obtained in step ④ are put into the saturated chitosan acetic acid aqueous solution obtained in step ②, heated to 38°C~43°C, stirred by a magnetic stirring device, and reacted for 75min~90min until the surface of the gel microspheres is fully complexed with chitosan to obtain a microcapsule turbid liquid; the microcapsule turbid liquid is centrifuged at a rate of 6200rpm~6500rpm using the centrifugal device prepared in step ② of stage S1, and the surface is cleaned using the dilute acetic acid aqueous solution prepared in step ① of stage S1, and the centrifugal separation and surface cleaning steps are repeated 2~3 times to obtain prefabricated microcapsules; ⑥ Freeze-dry the prefabricated microcapsules obtained in step ⑤ for 1 day to 1.5 days to obtain the desired hydrophilic diglyceride oil microcapsule powder.
[0012] The hydrophilic diglyceride oil microcapsule powder obtained according to this embodiment has the characteristics of being eco-friendly, having a hydrophilic surface, being stable in structure, being easy to store, and having a wide range of uses.
[0013] The above description of the disclosed embodiments is intended only to enable those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A process for preparing hydrophilic diglyceride oil microcapsule powder, characterized in that: The process The following phases are included: S1: Raw material preparation ① Raw material preparation: prepare sufficient amount of diglyceride, sufficient amount of Northeastern crayfish shell, protease, chitosan glycosaminoglycans, deacetylase, prepare sodium alginate aqueous solution with a solute mass fraction of 2%, sufficient amount of acetic acid aqueous solution with a volume ratio of acetic acid to water (10-20):100, sufficient amount of dilute acetic acid aqueous solution with a volume ratio of acetic acid to water (0.8-1.2):100, surfactant, and calcium chloride aqueous solution with a solute mass fraction of 5%; wherein the surfactant is a surfactant of polyoxyethylene hydrogenated castor oil / n-butene system, and the surfactant K m The value is 5 / 2~2 / 1; ② Preparation of tools and equipment: prepare constant flow pump, magnetic stirring device, ultrasonic generator, quartz reaction container with heating device, mechanical powder making device, centrifugal device; S2: Preparation of water-soluble chitosan ① After cleaning the Northeastern crayfish shells prepared in step ① of stage S1, the shells are crushed into powder using the mechanical powder making device prepared in step ② of stage S1 to obtain shell powder; ② Soak the shell powder obtained in step ① in pure water, then add the lysin prepared in step ① of stage S1 into the water, inject it into the quartz reaction container prepared in step ② of stage S1, heat it to 35°C~38°C, maintain it for 8h~10h, then filter out the liquid to obtain solid crude chitin; ③ The solid crude chitosan obtained in step ② is cleaned with pure water and then immersed in pure water, and then the chitosan aminoacidase and deacetylase prepared in step ① of stage S1 are added into the water, and the temperature is raised to 35°C to 38°C, and maintained for 8h to 10h to obtain a chitosanase water mixed solution; ④ heating the chitosanase water mixed solution obtained in step ③ to 75°C~80°C and maintaining it for 1.5h~2h to obtain an inactivated chitosan solution; filtering out the solidified material and drying it to obtain water-soluble chitosan; S3: Microcapsule preparation ① Mix the diglyceride prepared in step ① of stage S1 with the surfactant in a mass ratio of (8.5-9):1 and stir evenly to obtain an emulsion; ② The water-soluble chitosan obtained in step ④ of stage S2 is completely dissolved in the acetic acid aqueous solution prepared in step ① of stage S1, and the proportion of the water-soluble chitosan and the acetic acid aqueous solution is such that the water-soluble chitosan is just completely dissolved to form a saturated chitosan acetic acid aqueous solution; ③ The sodium alginate aqueous solution prepared in step ① of stage S1 and the emulsion obtained in step ① are uniformly mixed according to the mass ratio of sodium alginate to diglyceride (3-3.5): (14-16); then the magnetic stirring device and ultrasonic generating device prepared in step ② of stage S1 are used for magnetic stirring and ultrasonic dispersion to prepare a dispersed emulsion; ④ The calcium chloride aqueous solution prepared in step ① of stage S1 is evenly added dropwise to the dispersed emulsion and stirred for 2.5h~3h until the reaction is complete; the reaction system is centrifuged at a rate of 8500rpm~9000rpm using the centrifugal device prepared in step ② of stage S1, and the product is alternately washed with ether and water after removing the upper oil phase, and the centrifugation, oil phase removal and washing are repeated 3~4 times to obtain gel microspheres encapsulating diglyceride; ⑤ The gel microspheres obtained in step ④ are put into the saturated chitosan acetic acid aqueous solution obtained in step ②, heated to 38°C~43°C, stirred by a magnetic stirring device, and reacted for 75min~90min until the surface of the gel microspheres is fully complexed with chitosan to obtain a microcapsule turbid liquid; the microcapsule turbid liquid is centrifuged at a rate of 6200rpm~6500rpm using the centrifugal device prepared in step ② of stage S1, and the surface is cleaned using the dilute acetic acid aqueous solution prepared in step ① of stage S1, and the centrifugal separation and surface cleaning steps are repeated 2~3 times to obtain prefabricated microcapsules; ⑥ Freeze-dry the prefabricated microcapsules obtained in step ⑤ for 1 day to 1.5 days to obtain the desired hydrophilic diglyceride oil microcapsule powder.