CN118615259A - Preparation technology and application of brittle capsule based on ultraviolet light curing and wrapping water-soluble carrying object - Google Patents
Preparation technology and application of brittle capsule based on ultraviolet light curing and wrapping water-soluble carrying object Download PDFInfo
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- CN118615259A CN118615259A CN202311784082.9A CN202311784082A CN118615259A CN 118615259 A CN118615259 A CN 118615259A CN 202311784082 A CN202311784082 A CN 202311784082A CN 118615259 A CN118615259 A CN 118615259A
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Landscapes
- Manufacturing Of Micro-Capsules (AREA)
Abstract
The invention relates to a preparation technology of a brittle capsule based on ultraviolet light curing and wrapping a water-soluble carrying object and application thereof, belongs to the field of bioengineering, and relates to a preparation method of a water/alcohol core brittle capsule based on a sharp hole forming method. The invention adopts small molecule photo-curable hydrophobic material as brittle capsule wall material. After capsule liquid drops are formed by using an orifice forming method, the capsule liquid drops directly fall into a curing pool, stirring is immediately applied, and ultraviolet irradiation is performed to induce the wall material to crosslink and cure. And curing and soaking the prepared brittle capsules, airing at a low temperature and high humidity until the surfaces of the brittle capsules are dried, and refrigerating the brittle capsules to obtain finished products of the brittle capsules. The production method of the brittle capsule capable of realizing long-term encapsulation and preservation of the water/alcohol core can realize long-term carrying encapsulation of water/alcohol soluble micromolecules, medicaments and bioactive substances, realize mechanical controlled release and have great significance in pharmacy and substrate repair.
Description
Technical Field
The invention belongs to the technical field of bioengineering, and particularly relates to a manufacturing method and application of an ultraviolet light curing brittle capsule for wrapping water-soluble molecules, medicines and bioactive substances.
Background
Carrier development with trigger release characteristics is an important challenge in the field of materials, controlled drug release. Capsules with stimulus-responsiveness can be used as effective carriers of the above substances, and have been widely used for packaging various valuable goods, including nanomaterials, water-soluble molecules, drugs, bioactive substances, etc., so as to realize the storage and transportation of carried goods. It is also important that when the capsule responds to external stimuli, the encapsulated cargo should be released to perform its function, carrying a controlled release of the drug to effect a site-directed therapy, etc. Various external stimuli, including temperature, pH, light, magnetic fields, etc., can be used to effect triggered release of the cargo by chemical or physical changes in the shell material. Although these special functions have a good effect in the controlled release of the cargo, they directly change the shell structure or define the preconditions of the shell material, which affects the strength and stability of the shell itself to a great extent, and thus affects the storage time of the loaded cargo. In addition, complex synthesis or manufacturing procedures are often required to achieve versatility of the shell material, which time or cost of synthesis is even higher than the value of the carried cargo itself. The mechanical response is a simple and easy strategy to circumvent this limitation, when the shell material undergoes a physical change, such as a pressure induced shell melting, a porosity change or a direct rupture, the release can be triggered by mechanical cracking or breaking of the shell wall. Meanwhile, the mechanical controlled release capsule is required to have certain structural strength so as to realize stable carrying before carrying goods is triggered, and a foundation is provided for long-term storage of the carried goods.
The conventional brittle capsules are composed of two parts, namely a wall material and a core material, wherein the wall material plays a role in sealing, and the structural strength of the wall material directly influences the storage environment requirement and the storage time of finished capsules; the core material is a liquid or suspension which has no solubility to the wall material. Conventional mechanical stimulation disruption methods typically involve external force extrusion to cause the shell to break. In order to realize accurate control of mechanical stimulation, the hardness and uniformity of the shell layer are very important control parameters. The soft shell layer can generate larger deformation, and extremely fine cracks are easy to generate in the deformation process, so that the core material is leaked; among the uneven shell layers, the weak part shell layer is easy to break firstly under smaller mechanical stimulation, so that the mechanical controlled release accuracy and controllability are affected, and the storage capacity of the capsule is also affected to a certain extent. Therefore, shell uniformity control during the production process becomes very important.
Among the existing preparation methods of brittle capsules, the methods of dropping and interfacial polymerization have been mainly used in industrialization. The preparation method meets the requirements of thin wall material, narrow crushing pressure range and biocompatibility, and can realize the brittle capsules which are embedded by water-soluble and alcohol-soluble carrying objects and stored for a long time, and currently, no successful products and research and development schemes exist at home and abroad. In the prior proposal, a series of problems such as immature processing technology, unstable quality of finished products, unqualified breaking strength of capsules, difficult mass production and the like are still the main obstacle for mass production and application of the product. For example, in the existing production process for producing brittle capsules (patent CN 105536656A, CN101564667A, CN102824887 a), aqueous polymer is generally used as a wall material, a embryonic capsule is produced by using orifice forming, then the wall material is solidified by ion polymerization, and the brittle capsule is produced after drying, and the hydrophilic wall material is generally used for preparing brittle capsules containing oil-soluble essence and drug core materials. For water-soluble flavors/drugs, the existing method is usually carried in an ester solvent (CN 106215818A) which is miscible with water/alcohol, so that the carrying capacity is usually low, and the product quality is seriously affected.
The orifice forming method is a droplet emulsifying mode realized by comprehensively utilizing the force applied during the formation of hanging drops based on a droplet microfluidic system. The existing orifice forming method is used for the production process of brittle capsules, and generally only an oily solvent which is not easy to volatilize can be used as a core material, so that various oil-soluble essence and other substances are carried. For the core material, an ion crosslinking or low-temperature curing temperature sensitive material is used as a wall material, and further the core material is packaged. The wall material for encapsulation generally has soft and flexible characteristics, so that the obtained shell layer has no strong mechanical stability and is easy to leak liquid due to compression deformation. In addition, there is currently no mature solution for packaging aqueous phase core materials and achieving long-term storage of internal active materials in conventional storage environments.
Disclosure of Invention
In order to solve the problems, the invention provides a preparation technology of ultraviolet light solidified brittle capsules which are prepared by using a sharp hole forming method and are coated with water-soluble molecules, medicines and bioactive substances based on a microfluidic droplet technology and application thereof.
According to the invention, a class of hydrophobic wall material capable of being rapidly photo-cured is used, a short stable time window after the water-in-oil capsule is formed is utilized, local disturbance is applied to homogenize the thickness of the shell layer, meanwhile, ultraviolet light irradiation is applied to realize rapid cross-linking and curing of the wall material, so that a capsule shell layer with sufficient mechanical strength and controllable and adjustable crushing strength is formed, and complete release of carried goods after crushing is realized.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a preparation method of a brittle capsule wrapping a water-soluble carrier comprises the following steps:
(1) Preparing a wall material stock solution and a core material stock solution:
Dissolving a photoinitiator in a wall material to obtain a wall material stock solution, and dissolving a water-soluble carrying object in a core material solution containing a surfactant to obtain a core material stock solution; the wall material is a photo-curable hydrophobic organic material;
(2) Preparing microcapsules by a sharp hole method: mixing the wall material stock solution and the core material stock solution, and obtaining the rudiment vesicle by a sharp hole method;
(3) Curing: the embryonic vesicles are soaked in the curing liquid, and the ultraviolet light source irradiates the embryonic vesicles to complete the curing of the wall material, so that the brittle capsules are obtained.
In the above technical scheme, further, the ultraviolet light source has a wavelength range of 254-450nm and an illumination intensity of 0.2-20w/cm 2, and the flow ratio of the core material stock solution to the wall material stock solution is 1:1-6:1.
In the above technical scheme, further, when the ultraviolet light source in the step (3) irradiates the rudiment vesicle, disturbance is applied to the curing liquid at the same time, and the disturbance frequency is 100-200rpm.
In the above technical scheme, further, the main chain of the photocurable hydrophobic organic material is ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, polylactic acid, polyethylene, glycerol or polyglycerol; the photocrosslinking group is propenyl, methylpropenyl or norbornenyl; the photocuring hydrophobic organic material is selected from any combination of the main chain and the photocrosslinking group;
in the above technical scheme, the photoinitiator is one or more of photoinitiator 659, photoinitiator 379, photoinitiator 369, photoinitiator 819, photoinitiator 1173, photoinitiator 2959, benzoin dimethyl ether, phenyl-2, 4, 6-trimethylbenzoyl lithium phosphonate; the addition concentration of the photoinitiator is 0.05-3%.
When the wall material is dissolved in a solvent, the solvent is selected from one or more of liquid paraffin, dichloromethane, chloroform, carbon tetrachloride, simethicone, vegetable oil, tetrahydrofuran, toluene, benzene, xylene, cyclohexane and cyclopentane.
In the above technical scheme, further, the polymerization degree of the polyethylene glycol is 1-10, the polymerization degree of the polypropylene glycol is 1-10, the polymerization degree of the polylactic acid is 1-22000, the polymerization degree of the polyethylene is 1-34000, and the polymerization degree of the polyglycerol is 1-12000; preferably, the polymerization degree of the polylactic acid is 2-200, the polymerization degree of the polyethylene is 3-510, and the polymerization degree of the polyglycerol is 1-150.
In the above technical scheme, further, the surfactant is selected from one or a combination of several of polyvinyl alcohol, sodium dodecyl benzene sulfonate, sodium dodecyl sulfate, span 80, span 60, span 40, span 20, tween 80, tween 60, tween 40 and tween 20, and the mass concentration is 1-20%;
the solvent used in the core material solution is one or more of water, ethanol, glycerol, ethylene glycol, propylene glycol, isopropanol and 1-butanol;
The water-soluble carrier is water solution of soluble salt, water-soluble functional micromolecule, water-soluble medicine or water-soluble bioactive substance.
In the above technical solution, further, the soluble salt is one or more of soluble salts of Ca 2+、Fe3+、Fe2+、Cu2+、Zn2+、Ba2+;
The water-soluble functional micromolecules are selected from one or more of photoinitiator, cross-linking agent, light absorber, fluorescent agent, catalyst, preservative, anesthetic, stimulant, detergent, ion exchanger and precipitant; preferably, the organic light-emitting device is selected from one or more of a photoinitiator, a cross-linking agent, a fluorescent agent, a preservative and a precipitant;
The water-soluble medicine is one or more selected from Chinese medicinal materials, chinese medicinal decoction pieces, chinese patent medicines, chinese and western patent medicines, chemical raw medicines and preparations thereof, antibiotics, biochemical medicines, radioactive medicines, serum, vaccines, blood products and diagnostic medicines;
the water-soluble bioactive substances are selected from one or more of living cells, nucleic acid, protein, perfume, nano particles and quantum dots;
the mass concentration of the water-soluble carrier in the core material stock solution is 0.05-3%.
In the above technical scheme, further, the curing solution is a soluble salt solution containing one or more of Ca 2+、Fe3+、Fe2+、Cu2+、Zn2+、Ba2+, and the mass concentration of the soluble salt is 2-20%.
In the technical scheme, further, the brittle capsules obtained in the step (3) are soaked and dried; preferably, the soaking liquid used for soaking is one or more of tannic acid, glycerol, ethanol, glycol, tetrol and polyvinyl alcohol, and the mass concentration of the soaking liquid is 1-60%.
The use of the foregoing friable capsules in self-healing frame materials, drug storage and delivery capsules or bioactive substance encapsulation materials.
The invention adopts small molecule photo-curable hydrophobic material as wall material, forms water-in-oil capsule by orifice forming method, then falls into curing pool directly, immediately applies disturbance and ultraviolet light to induce wall material to crosslink and cure. Based on the hanging drop type orifice forming spray head, the particle size of the capsule liquid drops formed under quasi-static conditions is controlled only by gravity, interface force, spray head size and flow relation of capsule wall materials and core materials borne by the embryonic capsule, and is irrelevant to liquid phase flow velocity, so that the capsule liquid drops with the same particle size can be produced regardless of the input flow velocity under the condition that the input flow rate of the wall/core materials is controlled to be smaller than the threshold flow rate. The prepared capsule is put into the soaking solution for soaking for 72 hours, then is fished out, dried at low temperature and high humidity until the surface is dried, and then is refrigerated.
Compared with the prior art, the invention has the beneficial effects that:
1) Compared with the traditional production process system of carrying capsules by using small molecules, medicines and bioactive substances of water-based polymer wall materials, the invention creatively selects a class of photo-curable hydrophobic materials as the wall materials, and the high hydrophobicity of the photo-curable hydrophobic materials can isolate core materials from air environment, so that the quality loss of the carried materials in the water-based core materials caused by long-term storage is greatly reduced, the long-term and high-efficiency encapsulation of the water-soluble and alcohol-soluble carried materials is realized, and the bottleneck problem that the hydrophilic carried materials in industry cannot realize long-term encapsulation is solved;
2) Compared with the traditional capsule production process, the microfluidic technology-based capsule production process provided by the invention can ensure the uniformity of the thickness of the wall material while stably producing the microcapsule with complete structure, greatly improve the integral structural strength of the capsule, reduce the crushing strength range, ensure that the capsule has accurate mechanical controlled release performance, and further can be applied to application environments of various mechanical responses.
3) Compared with the traditional brittle capsules, the photocuring process utilized by the process has attractive appearance, high yield and controllable particle size and rupture strength of the produced products, greatly simplifies the production flow and realizes the one-step continuous production of the products;
4) Compared with the traditional brittle capsule production process, the brittle capsule production device provided by the invention can be used for preparing water-in-oil brittle capsules, is also suitable for producing traditional water-based wall material capsules, maintains the quality of capsules similar to the traditional production process, greatly widens the selection range of brittle capsule core materials, and improves the diversity of products;
5) Compared with the traditional brittle capsule production process, the brittle capsule production process provided by the invention effectively solves the problems of poor mechanical stability and insufficient structural strength of the existing capsule wall material system, can greatly improve the uniformity of the thickness of the capsule shell, obviously improves the shell strength, and effectively solves the problems of insufficient strength, fragility and the like of the existing brittle capsule.
Drawings
FIG. 1 is a schematic diagram of an orifice forming apparatus used, wherein a1 orifice forming nozzle, a2 curing tank, a 1-1 orifice outlet, a 1-2 wall material input channel, a 1-3 core material input channel, a 2-1 stirring paddle, and a 2-2 ultraviolet lamp are used.
FIG. 2 is a pictorial view of a friable capsule; a is the product diagram of example 1 and b is the product diagram of example 4.
FIG. 3 is a schematic view of a tannic acid-containing brittle capsule in example 5.
Fig. 4, a schematic representation of a friable capsule: fig. 4a is a product diagram of example 3, and fig. 4b is a product diagram of example 2.
Detailed Description
The invention is further illustrated below in connection with specific examples, but is not limited in any way.
The invention uses the improved orifice forming device to prepare (figure 1), the used device includes the orifice forming spray head (1) and solidifying groove (2), the said orifice forming spray head is fixed over solidifying groove in a upside down manner, the orifice forming spray head is at least two layers of orifice structure, including orifice outlet (1-1), outer wall material input channel (1-2), inner core material input channel (1-3), orifice outlet downward, the capsule formed falls into solidifying groove directly, the said solidifying groove is placed under orifice forming spray head, the solidifying groove bottom has stirring paddle (2-1), solidifying liquid is placed in solidifying groove, solidifying liquid immersing area applies ultraviolet light irradiation by ultraviolet lamp (2-2); the wall surface of the solidifying groove in front of the ultraviolet lamp is set to be a transparent wall surface.
Example 1
A method for producing a friable capsule, which comprises the following steps, using an orifice forming apparatus as shown in FIG. 1.
1) Preparing a stock solution: respectively mixing according to the following formula to prepare core material stock solution, wall material stock solution, UV curing solution and soaking solution;
The formula of the core material is as follows:
the formula of the wall material is as follows:
the formula of the UV curing liquid is as follows:
The formula of the soaking solution is as follows:
2) And (3) dripping: the core material stock solution and the wall material stock solution are respectively input into a wall material input channel (1-2) and an inner core material input channel (1-3) of the orifice forming spray head, capsule liquid drops are prepared through a dropping method, and the flow ratio of the core material to the wall material is controlled to be 4:1, capsule liquid drops are formed and grown at the outlet of the orifice until the capsule drops naturally drop off, the dropped capsule drops into a curing groove, and UV curing liquid is injected into the groove. Simultaneously, using 365nm ultraviolet light with the light intensity of 800mW/cm 2 to irradiate the whole curing pool, applying uniform stirring at 120rpm, immediately initiating a crosslinking curing reaction by ultraviolet light irradiation, and collecting the prepared brittle capsules by sinking at the bottom of the curing tank;
3) Soaking: collecting the brittle capsules, transferring into a soaking tank, soaking at low temperature (4deg.C) for 48 hr, taking out, drying at low temperature and high humidity (4deg.C, 60%), and storing at 4deg.C to obtain brittle capsules, wherein the product is shown in figure 2 a;
Example 2
A method for manufacturing a friable capsule carrying a water-soluble small molecule fluorescent agent eosin Y, which uses the procedure described in example 1 to prepare the friable capsule, is different from example 1 in the formulation of each material, and the finished product is shown in FIG. 4 b. The formulation of this example is as follows:
The formula of the core material is as follows:
the formula of the wall material is as follows:
the formula of the UV curing liquid is as follows:
The formula of the soaking solution is as follows:
Example 3
A method for producing a friable capsule carrying a water-soluble protein (green fluorescent protein) by using the procedure described in example 1, which differs from example 1 in the formulation of each material, and the finished product is shown in FIG. 4 a. The formulation of this example is as follows:
The formula of the core material is as follows:
the formula of the wall material is as follows:
the formula of the UV curing liquid is as follows:
The formula of the soaking solution is as follows:
Example 4
A method for manufacturing a friable capsule carrying a water-soluble drug, which uses the procedure described in example 1 to prepare a friable capsule, the product is shown in FIG. 2b, and differs from example 1 in the formulation of the materials as follows:
The formula of the core material is as follows:
the formula of the wall material is as follows:
the formula of the UV curing liquid is as follows:
The formula of the soaking solution is as follows:
Example 5
A method for preparing brittle capsules containing water-soluble cross-linking agent tannic acid, the product of which is shown in figure 4, comprises preparing brittle capsules by using an orifice forming device shown in figure 1 according to the following steps.
1) Preparing a stock solution: respectively mixing according to the following formula to prepare core material stock solution, wall material stock solution, UV curing solution and soaking solution;
The formula of the core material is as follows:
the formula of the wall material is as follows:
the formula of the UV curing liquid is as follows:
The formula of the soaking solution is as follows:
2) And (3) dripping: the core material stock solution and the wall material stock solution are respectively input into a wall material input channel (1-2) and an inner core material input channel (1-3) of the orifice forming spray head, and the flow ratio of the core material stock solution to the wall material stock solution is controlled to be 6:1, preparing a rudiment capsule by a dripping method, dripping the rudiment capsule into a curing groove, and injecting UV curing liquid into the groove. Simultaneously, using 365nm ultraviolet light with the light intensity of 800mW/cm 2 to irradiate the whole curing pool, applying uniform stirring at 120rpm, and depositing the prepared brittle capsules at the bottom of the curing tank and collecting;
3) Soaking: collecting the brittle capsules, transferring into a soaking tank, soaking for 48h at low temperature, taking out, drying at low temperature and high humidity (4 ℃ and 60%), and storing at 4 ℃ to obtain brittle capsules;
Experimental example 1
The friable capsules obtained in example 1, as well as some commercially available friable capsule products, were placed on a mechanical tester, and a compression procedure was performed to determine the breaking strength.
Table 1 different capsule burst strength test
The results in table 1 show that the brittle capsules produced in example 1 perform well in terms of both structural rigidity and crushing strength compared to commercial products, and are significantly better than existing commercial products, achieving coating of aqueous vehicles.
Experimental example 2
Using an orifice forming apparatus having orifice forming heads of different diameters, a friable capsule was prepared according to the preparation scheme described in example 1 to examine its size control ability
Table 2 particle size distribution of capsule products prepared from different size spray heads
The results in Table 2 show that in a certain size range, the size of the brittle capsule product prepared by the orifice forming spray head of the invention is positively correlated with the size of the spray head, and the particle size is uniform, which shows that the invention has the size control capability on the brittle capsule product.
Experimental example 3
The friable capsules obtained in examples 2 and 3 were stored at 4℃and the change in fluorescence intensity at different time points was examined to examine their storage capacity for the loaded goods. After 7 days of storage, the friable capsules carrying eosin Y and green fluorescent protein were subjected to fluorescent intensity detection, which indicated that the green fluorescent intensity of the liquid phase in the capsules after 7 days was 97.3±1.1% of the first day. Since the fluorescence intensity of green fluorescent protein is directly related to the protein activity, it has been demonstrated that the friable capsule can store water-soluble protein active substances for a long period of time and maintain the functionality thereof. After 31 days of storage, the friable capsules carrying eosin Y were tested for fluorescence intensity, which was 96.6±1.5% of the first day, demonstrating the storage capacity and activity retention capacity of the friable capsules for water-soluble small molecule substances.
Experimental example 4
Mixing the brittle capsules obtained in the example 5 with gelatin nanoparticle hydrogel (CN 201710600536.0) for shaping to obtain a cylindrical gel model, wherein the mass of the brittle capsules is 2% of that of the gelatin nanoparticles; mixing with bone cement to obtain long-strip bone cement model, drying and shaping, wherein the mass of brittle capsule is 1% of that of bone cement.
And taking the gel model, and placing the gel model in a rheometer for rotary shearing test. As a result, the gel shear modulus was significantly reduced in the initial stage of rotational shear; after 5 minutes of continued shear, the gel shear modulus rose back and eventually was higher than the initial shear modulus. Indicating that during the rotary shearing process, the brittle capsules in the gel break, releasing tannic acid, promoting rapid adhesion of the gel and restoring structural strength.
And (3) taking the bone cement model, breaking the model from the middle position of the strip, and then immediately jointing the two parts of the model along the section and fixing. After 20 minutes of fixation, the bone cement model was lifted from one side, and it was seen that the whole bone cement model was lifted completely, and the fracture did not separate. It was shown that tannic acid in the capsules was released after breaking and penetrated into the whole section after mold joining, participating in section adhesion. The two experimental results show that the brittle capsule can be used for emergency repair of various module materials and has important significance in substrate repair.
Experimental example 5
A friable capsule was prepared according to the preparation scheme described in example 3 using an orifice forming apparatus with orifice forming spray head size of 3.5mm, wherein different formulations of UV curing liquid were used for particle production to verify the effect of the curing liquid formulation on the particle size distribution and strength of the capsule particle product.
TABLE 3 influence of different curing liquid formulations on particle size distribution and Strength of Capsule particle products
The results in Table 3 show that the introduction of ionic salt in the curing liquid can significantly improve the minimum shell thickness of the brittle capsule without changing the particle size, improve the uniformity of the shell and significantly improve the crushing strength.
Experimental example 6
A friable capsule was prepared according to the preparation scheme described in example 4 using an orifice forming apparatus with a nozzle size of 3.5mm, wherein different wall stock solutions, core stock solution flow ratios were used to input the liquid phase to optimize production parameters.
TABLE 4 influence of different wall Material and core flow ratios on the strength of Capsule particle products
The results in table 4 show that in a certain range, when the flow ratio of the wall material stock solution to the core material stock solution is gradually increased, the crushing strength of the brittle capsule product is obviously improved under the condition that the crushing strength distribution is kept similar; when the ratio exceeds a certain range, the crushing strength is improved, but the distribution range of the crushing strength is obviously enlarged, and the defective rate is obviously improved. Therefore, the strength of the brittle capsule product can be controlled by the flow ratio of the wall material stock solution and the core material stock solution within a certain range.
Experimental example 7
A friable capsule was prepared according to the preparation protocol described in example 1 using an orifice forming apparatus with orifice forming nozzle size of 4mm, wherein different stirring rates were used to optimize production parameters.
TABLE 5 influence of different stirring rates on the strength of the capsule particle products
The results in Table 5 show that, in a certain range, when the stirring rotation speed is gradually increased, the crushing strength distribution range of the brittle capsule product is obviously reduced under the condition that the crushing strength distribution is kept similar; when the ratio exceeds a certain range, the distribution range of the crushing strength is obviously enlarged, and the defective rate is obviously improved. Therefore, the invention can control the strength of the brittle capsule product by the stirring rotation speed within a certain range.
Many possible variations and modifications of the disclosed technology can be made by anyone skilled in the art without departing from the scope of the technology, or the technology can be modified to be equivalent. Therefore, any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention shall still fall within the scope of the technical solution of the present invention.
Claims (10)
1. A method for preparing a friable capsule coated with a water-soluble carrier, comprising the steps of:
(1) Preparing a wall material stock solution and a core material stock solution:
Dissolving a photoinitiator in a wall material to obtain a wall material stock solution, and dissolving a water-soluble carrying object in a core material solution containing a surfactant to obtain a core material stock solution; the wall material is a photo-curable hydrophobic organic material;
(2) Preparing microcapsules by a sharp hole method: mixing the wall material stock solution and the core material stock solution, and obtaining the rudiment vesicle by a sharp hole method;
(3) Curing: the embryonic vesicles are soaked in the curing liquid, and the ultraviolet light source irradiates the embryonic vesicles to complete the curing of the wall material, so that the brittle capsules are obtained.
2. The method for producing a brittle capsule coated with a water-soluble carrier according to claim 1, characterized in that,
The wavelength range of the ultraviolet light source is 254-450nm, the illumination intensity is 0.2-20w/cm 2, and the flow ratio of the core material stock solution to the wall material stock solution is 1:1-6:1.
3. The method of claim 1, wherein the ultraviolet light source irradiates the rudiment vesicles and simultaneously applies a disturbance to the solidifying liquid, and the disturbance frequency is 100-200rpm.
4. The method for preparing a friable capsule for encapsulating a water-soluble carrier according to claim 1, wherein the main chain of the photocurable hydrophobic organic material is ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, polylactic acid, polyethylene, glycerin or polyglycerol; the photocrosslinking group is propenyl, methylpropenyl or norbornenyl; the photocuring hydrophobic organic material is selected from any combination of the main chain and the photocrosslinking group;
The photoinitiator is one or more of photoinitiator 659, photoinitiator 379, photoinitiator 369, photoinitiator 819, photoinitiator 1173, photoinitiator 2959, benzoin dimethyl ether and phenyl-2, 4, 6-trimethyl benzoyl lithium phosphonate; the addition concentration of the photoinitiator is 0.05-3%.
When the wall material is dissolved in a solvent, the solvent is selected from one or more of liquid paraffin, dichloromethane, chloroform, carbon tetrachloride, simethicone, vegetable oil, tetrahydrofuran, toluene, benzene, xylene, cyclohexane and cyclopentane.
5. The method according to claim 4, wherein the polyethylene glycol has a polymerization degree of 1 to 10, the polypropylene glycol has a polymerization degree of 1 to 10, the polylactic acid has a polymerization degree of 1 to 22000, the polyethylene has a polymerization degree of 1 to 34000, and the polyglycerol has a polymerization degree of 1 to 12000; preferably, the polymerization degree of the polylactic acid is 2-200, the polymerization degree of the polyethylene is 3-510, and the polymerization degree of the polyglycerol is 1-150.
6. The method for producing a brittle capsule coated with a water-soluble carrier according to claim 1, characterized in that,
The surfactant is selected from one or more of polyvinyl alcohol, sodium dodecyl benzene sulfonate, sodium dodecyl sulfate, span 80, span 60, span 40, span 20, tween 80, tween 60, tween 40 and tween 20, and the mass concentration is 1-20%;
the solvent used in the core material solution is one or more of water, ethanol, glycerol, ethylene glycol, propylene glycol, isopropanol and 1-butanol;
The water-soluble carrier is water solution of soluble salt, water-soluble functional micromolecule, water-soluble medicine or water-soluble bioactive substance.
7. The method for producing a brittle capsule coated with a water-soluble carrier according to claim 6, characterized in that,
The soluble salt is one or more of soluble salts of Ca 2+、Fe3+、Fe2+、Cu2+、Zn2+、Ba2+;
The water-soluble functional micromolecules are selected from one or more of photoinitiator, cross-linking agent, light absorber, fluorescent agent, catalyst, preservative, anesthetic, stimulant, detergent, ion exchanger and precipitant; preferably, the organic light-emitting device is selected from one or more of a photoinitiator, a cross-linking agent, a fluorescent agent, a preservative and a precipitant;
The water-soluble medicine is one or more selected from Chinese medicinal materials, chinese medicinal decoction pieces, chinese patent medicines, chinese and western patent medicines, chemical raw medicines and preparations thereof, antibiotics, biochemical medicines, radioactive medicines, serum, vaccines, blood products and diagnostic medicines;
the water-soluble bioactive substances are selected from one or more of living cells, nucleic acid, protein, perfume, nano particles and quantum dots;
the mass concentration of the water-soluble carrier in the core material stock solution is 0.05-3%.
8. The method for producing a brittle capsule coated with a water-soluble carrier according to claim 1, characterized in that,
The curing liquid is a soluble salt solution containing one or more of Ca 2+、Fe3+、Fe2+、Cu2+、Zn2+、Ba2+, and the mass concentration of the soluble salt is 2-20%.
9. The method for producing a brittle capsule coated with a water-soluble carrier according to claim 1, characterized in that,
Soaking and drying the brittle capsules obtained in the step (3); preferably, the soaking liquid used for soaking is one or more of tannic acid, glycerol, ethanol, glycol, tetrol and polyvinyl alcohol, and the mass concentration of the soaking liquid is 1-60%.
10. Use of a friable capsule prepared according to any one of claims 1 to 7 in a self-healing frame material, a drug storage and delivery capsule or a bioactive substance encapsulation material.
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