Microfluidic device and spinning method for bamboo-like structural fibers

Abstract

The present application relates to a microfluidic device and spinning method for bamboo-like structural fibers, and relates to the field of sustained drug release. It includes a liquid inlet unit, a coaxial spinning head connected to the liquid inlet unit, a coagulation bath disposed at the rear end of the coaxial spinning head, a cleaning tank disposed at the rear end of the coagulation bath, and a drafting and winding roller disposed at the rear end of the cleaning tank; wherein the liquid inlet method of the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism both adopts an equidistant intermittent propulsion method, and the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism propel the liquid inlet alternately, while the liquid inlet method of the external phase liquid inlet control mechanism adopts a continuous propulsion method. This achieves effective control of the fiber size, structure, and material composition, and the prepared bamboo-like structural fibers can be used as liquid drug carriers, exerting a sustained release effect after implantation in the body, and significantly improving the utilization efficiency of the drug.

Description

Technical Field

[0001] The present application relates to the technical field of sustained-release drugs, and in particular to a microfluidic device and a spinning method for bamboo-like structural fibers. Background Art

[0002] In recent years, microscale fibers with high surface area and ordered structure have attracted widespread attention. Microfluidic spinning technology can effectively control the size, structure and material composition of fibers, and has become a new method for manufacturing functional fibers with complex structures. Traditional spinning methods such as melt spinning, dry spinning, wet spinning and electrospinning need to consider the effects of extreme processes such as high pressure, high shear and high temperature on the materials. At the same time, these traditional spinning processes limit the choice of fiber raw materials and cannot produce fibers with special structures. Microfluidic spinning technology can prepare fibers with controllable composition and complex structure under mild conditions, providing a powerful platform and broad opportunities for the manufacture of advanced structural fibers with a wide range of applications.

[0003] Drug sustained-release technology is to encapsulate drugs in microspheres, microcapsules or graft and mix them in fibers, which can slowly release drug ingredients after reaching the human body, thereby improving the utilization rate and efficacy of drugs and effectively reducing drug side effects. In current drug delivery systems, drug sustained-release technology mainly involves encapsulating or mixing drug particles in carriers in various ways, and then feeding or implanting the carriers into the body to slowly release the drugs. However, when the drug is in liquid form, it can only be administered by other routes such as injection, and the injection method can cause the rapid release of the drug, which cannot meet the requirements of sustained-release drugs. Encapsulating liquid drugs as the internal phase in core-shell structure fibers can effectively solve the problem that liquid drugs are difficult to encapsulate, and the sustained-release rate required for the drug can be controlled by changing the wall thickness of the core-shell structure fibers, so that the drug can maintain a constant blood drug concentration after being input into the body, preventing the drug from being metabolically ineffective due to the first-pass effect. Summary of the Invention

[0004] The purpose of this application is to provide a microfluidic device and spinning method for bamboo-like structural fibers to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above objectives, the technical solutions adopted in this application are:

[0006] In a first aspect, the present application provides a microfluidic device for imitating bamboo structural fibers, comprising a liquid inlet unit, a coaxial spinning head connected to the liquid inlet unit, a coagulation bath disposed at the rear end of the coaxial spinning head, a cleaning tank disposed at the rear end of the coagulation bath, and a drafting and winding roller disposed at the rear end of the cleaning tank;

[0007] The liquid inlet unit includes a first internal phase liquid inlet control mechanism, two groups of second internal phase liquid inlet control mechanisms and two groups of external phase liquid inlet control mechanisms. The top of the coaxial spinning head is provided with a first internal phase liquid inlet, and the side wall of the coaxial spinning head is provided with two groups of second internal phase liquid inlets and two groups of external phase liquid inlets. The first internal phase liquid inlet is connected to the first internal phase liquid inlet control mechanism, the two groups of second internal phase liquid inlets are respectively connected to the two groups of second internal phase liquid inlet control mechanisms, and the two groups of external phase liquid inlets are respectively connected to the two groups of external phase liquid inlet control mechanisms.

[0008] Among them, the liquid inlet method of the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism both adopts an equidistant intermittent propulsion method, and the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism are alternately advanced, and the liquid inlet method of the external phase liquid inlet control mechanism adopts a continuous propulsion method.

[0009] In a possible implementation, the advancement time of the first internal phase liquid inlet control mechanism is greater than the advancement time of the second internal phase liquid inlet control mechanism.

[0010] In a possible implementation, the external phase spinning solution entering from the external phase liquid inlet is the same as the internal phase spinning solution entering from the second internal phase liquid inlet.

[0011] In a possible implementation, the external phase spinning solution is one of a sodium alginate solution, a sodium alginate-sodium polyacrylate mixed solution, a sodium alginate-gelatin mixed solution, and a sodium alginate-gelatin-sodium polyacrylate mixed solution.

[0012] In a possible implementation, the internal phase spinning solution entering from the first internal phase liquid inlet is a drug solution for sustained drug release.

[0013] In a possible implementation, the coagulation bath tank contains a fiber coagulation bath, and the fiber coagulation bath is an ion solution or a salt solution;

[0014] The cleaning tank contains anhydrous ethanol, which is used to clean the coagulation bath liquid remaining on the fiber.

[0015] In one possible implementation, the first internal phase liquid inlet control mechanism includes a first internal phase liquid inlet propeller and a first internal phase liquid inlet spinning syringe connected to each other, the first internal phase liquid inlet propeller is connected to the liquid inlet end of the first internal phase liquid inlet spinning syringe, and the liquid outlet end of the first internal phase liquid inlet spinning syringe is connected to the first internal phase liquid inlet;

[0016] The second internal phase liquid inlet control mechanism includes a second internal phase liquid inlet propeller and a second internal phase liquid inlet spinning syringe connected to each other, the second internal phase liquid inlet propeller is connected to the liquid inlet end of the second internal phase liquid inlet spinning syringe, and the liquid outlet end of the second internal phase liquid inlet spinning syringe is connected to the second internal phase liquid inlet;

[0017] The external phase liquid inlet control mechanism includes an external phase liquid inlet propeller and an external phase liquid inlet spinning syringe connected to each other, the external phase liquid inlet propeller is connected to the liquid inlet end of the external phase liquid inlet spinning syringe, and the liquid outlet end of the external phase liquid inlet spinning syringe is connected to the external phase liquid inlet.

[0018] In a possible implementation, the liquid inlet unit further includes:

[0019] a single-channel internal phase liquid inlet controller connected to the first internal phase liquid inlet control mechanism;

[0020] a dual-channel internal phase liquid inlet controller connected to two sets of the second internal phase liquid inlet control mechanisms; and

[0021] A dual-channel external phase liquid inlet controller connected to the two sets of external phase liquid inlet control mechanisms.

[0022] In a possible implementation, a first guide roller is provided in the coagulation bath, a second guide roller is provided between the coagulation bath and the cleaning bath, a third guide roller is provided in the cleaning bath, and a fourth guide roller is provided between the cleaning bath and the drafting and winding roller.

[0023] In a second aspect, the present application provides a spinning method for bamboo-like structural fibers, which is applicable to any of the above-described microfluidic devices for bamboo-like structural fibers, and comprises:

[0024] S1. A single-channel internal phase liquid inlet controller controls the operation of a first internal phase liquid inlet control mechanism. A first internal phase liquid inlet propeller in the first internal phase liquid inlet control mechanism is responsible for equidistant intermittent propulsion. A first internal phase liquid inlet spinning syringe in the first internal phase liquid inlet control mechanism is responsible for packaging and feeding a first internal phase spinning solution from a first internal phase liquid inlet port into a coaxial spinning head. The first internal phase spinning solution is a drug solution for sustained drug release.

[0025] S2. At the same time, the dual-channel internal phase liquid inlet controller controls the operation of two sets of second internal phase liquid inlet control mechanisms. The second internal phase liquid inlet propellers of the second internal phase liquid inlet control mechanisms are responsible for equidistant intermittent propulsion. The second internal phase liquid inlet spinning syringes of the second internal phase liquid inlet control mechanisms are responsible for packaging and inputting the second internal phase spinning solution from the second internal phase liquid inlet port into the coaxial spinning head.

[0026] S3. At the same time, the dual-channel external phase liquid inlet controller controls the operation of two sets of external phase liquid inlet control mechanisms. The external phase liquid inlet propellers of the external phase liquid inlet control mechanisms are responsible for continuous propulsion, and the external phase liquid inlet spinning syringes of the external phase liquid inlet control mechanisms are responsible for packaging, and the external phase spinning solution is input into the coaxial spinning head from the external phase liquid inlet port.

[0027] S4, fibers are formed and extruded from the fiber outlet at the lower end of the coaxial spinning head, the extruded fibers are coagulated in a coagulation bath, and are guided by a first guide roller and a second guide roller into a cleaning tank to clean off the coagulation bath liquid remaining on the fiber surface, and then the fibers are guided by a third guide roller and a fourth guide roller to a drafting and winding roller for collection, thereby obtaining primary fibers with a bamboo-like structure;

[0028] S5. Post-processing the bamboo-like structural primary fibers to finally obtain bamboo-like structural fibers.

[0029] In a possible implementation, in step S5, post-processing the bamboo-like structural primary fibers to obtain the bamboo-like structural fibers includes:

[0030] S51, fixing both ends of the primary bamboo-like structure fibers and placing them on a glass plate, and drying or air-drying the primary bamboo-like structure fibers;

[0031] S52. During the post-processing process, the moisture in the first internal phase spinning liquid-drug liquid is discharged from the imitation bamboo structure primary fibers through the small holes formed by the incomplete gelation of the external phase spinning liquid, thereby causing the diameter of the drug liquid part to shrink to form a bamboo structure imitation cavity part, while the diameter of the second internal phase spinning liquid-non-drug liquid part remains unchanged to form a bamboo structure imitation bamboo node part, and the external phase spinning liquid forms the bamboo structure imitation surface part, and finally the bamboo structure imitation fibers are obtained.

[0032] In a possible implementation, the second inner phase spinning solution and the outer phase spinning solution are the same, and are both one of a sodium alginate solution, a sodium alginate-sodium polyacrylate mixed solution, a sodium alginate-gelatin mixed solution, and a sodium alginate-gelatin-sodium polyacrylate mixed solution;

[0033] The spinning solution concentrations of the second inner phase spinning solution and the outer phase spinning solution are both 1% to 5%;

[0034] The propulsion speeds of the first inner phase liquid inlet propeller and the second inner phase liquid inlet propeller are both 0.05 to 2 ml / min, and the propulsion speed of the outer phase liquid inlet propeller is 2 to 5 ml / min;

[0035] The single-channel internal phase liquid inlet controller and the dual-channel internal phase liquid inlet controller alternately control the propulsion;

[0036] The coagulation bath contains a calcium chloride solution with a concentration of 20% to 50%, and the calcium ions in the calcium chloride solution cross-link with the outer phase spinning solution, so that the outer phase of the fiber is rapidly solidified to form a shell-core structure;

[0037] The cleaning tank contains anhydrous ethanol, which is used to clean the calcium chloride solution remaining on the fiber surface.

[0038] The beneficial effects of the technical solution provided by this application include at least:

[0039] The microfluidic device for producing bamboo-like structural fibers provided in this application is equipped with two internal phase liquid inlets. By controlling the alternating time of the liquid inlets, primary fibers with bamboo-like structural morphology can be produced. The microfluidic spinning technology can effectively control the size, structure, and material composition of the fibers, and is a new method for producing functional fibers with complex structures.

[0040] The bamboo-like structured fibers prepared by the microfluidic device and spinning method of the bamboo-like structured fibers provided in the present application include a bamboo-like node structure, a bamboo-like cavity structure, and a bamboo-like surface structure. The bamboo-like cavity structure and the bamboo-like surface structure act as carriers for encapsulating the liquid medicine. The bamboo-like node structure separates the encapsulated liquid medicine into several closed layers, thereby preventing the loss of liquid medicine after fiber breakage.

[0041] The bamboo-like structural fibers prepared by the microfluidic device and spinning method of the bamboo-like structural fibers provided in this application can not only encapsulate liquid drugs as the internal phase in the fibers, effectively solving the problem of difficult encapsulation of liquid drugs, but also control the required sustained-release rate of the drugs by changing the wall thickness of the core-shell structural fibers, so that the blood drug concentration can be maintained at a constant level after the drugs are injected into the body, thereby preventing the drugs from being metabolically ineffective due to the first-pass effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] The accompanying drawings are used to provide a further understanding of the present application and constitute a part of the specification. Together with the embodiments of the present application, they are used to explain the present application and do not constitute a limitation of the present application. In the accompanying drawings:

[0043] Figure 1 A schematic structural diagram of a microfluidic device of bamboo-like structural fibers provided by an exemplary embodiment of the present application is shown;

[0044] Figure 2 A schematic structural diagram of a coaxial spinning head of a microfluidic device for bamboo-like structural fibers provided by an exemplary embodiment of the present application is shown;

[0045] Figure 3 A schematic diagram of a spinning method of bamboo-like structural fibers provided by an exemplary embodiment of the present application is shown;

[0046] Figure 4Schematic diagrams showing the structures of bamboo-like structural fibers before and after post-processing provided by an exemplary embodiment of the present application are shown;

[0047] In the picture:

[0048] 1. Liquid inlet unit; 2. Coaxial spinning head; 3. Coagulation bath; 4. Cleaning tank; 5. First guide roller; 6. Second guide roller; 7. Third guide roller; 8. Fourth guide roller; 9. Drafting and winding roller;

[0049] 11. First internal phase liquid inlet control mechanism; 12. Second internal phase liquid inlet control mechanism; 13. External phase liquid inlet control mechanism; 14. Single-channel internal phase liquid inlet controller; 15. Dual-channel internal phase liquid inlet controller; 16. Dual-channel external phase liquid inlet controller;

[0050] 111, first internal phase liquid inlet propeller; 112, first internal phase liquid inlet spinning syringe; 121, second internal phase liquid inlet propeller; 122, second internal phase liquid inlet spinning syringe; 131, external phase liquid inlet propeller; 132, external phase liquid inlet spinning syringe;

[0051] 21. First internal phase liquid inlet; 22. Second internal phase liquid inlet; 23. External phase liquid inlet; 24. Fiber outlet;

[0052] 100. First inner phase spinning solution; 200. Second inner phase spinning solution; 300. External phase spinning solution; 400. Bamboo-like structure cavity; 500. Bamboo-like structure nodes; 600. Bamboo-like structure surface. DETAILED DESCRIPTION

[0053] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0054] Among them, the same parts are represented by the same figure marks. It should be noted that the words "front", "rear", "left", "right", "up" and "down" used in the following description refer to the directions in the drawings of the present application specification, and the words "bottom" and "top", "inside" and "outside" refer to directions toward or away from specific parts, respectively. In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present application specification, the meaning of "multiple" is two or more.

[0055] The present application will be further described below with reference to the accompanying drawings and embodiments.

[0056] Example 1:

[0057] Figure 1 A structural schematic diagram of a microfluidic device for imitating bamboo structural fibers provided by an exemplary embodiment of the present application is shown. According to the front and back end descriptions of the process steps, the microfluidic device for imitating bamboo structural fibers includes a liquid inlet unit 1, a coaxial spinning head 2 connected to the liquid inlet unit 1 through a conduit, a coagulation bath 3 arranged at the rear end of the coaxial spinning head 2, a cleaning tank 4 arranged at the rear end of the coagulation bath 3, and a stretching winding roller 9 arranged at the rear end of the cleaning tank 4; the liquid inlet unit 1 includes a first internal phase liquid inlet control mechanism 11, two groups of second internal phase liquid inlet control mechanisms 12, and two groups of external phase liquid inlet control mechanisms 13.

[0058] In the embodiment of the present application, the material of the drafting and winding roller 9 is aluminum alloy, and the drafting and winding speed is 40 cm / min.

[0059] See also Figure 1 and Figure 2 The top of the coaxial spinning head 2 has a first internal phase liquid inlet 21, and the side wall of the coaxial spinning head 2 has two groups of second internal phase liquid inlets 22 and two groups of external phase liquid inlets 23. The first internal phase liquid inlet 21 is connected to the first internal phase liquid inlet control mechanism 11 through a conduit, and the two groups of second internal phase liquid inlet 22 are respectively connected to the two groups of second internal phase liquid inlet control mechanisms 12 through conduits, and the two groups of external phase liquid inlets 23 are respectively connected to the two groups of external phase liquid inlet control mechanisms 13 through conduits; wherein, the liquid inlet mode of the first internal phase liquid inlet control mechanism 11 and the second internal phase liquid inlet control mechanism 12 both adopts an equidistant intermittent propulsion mode, and the first internal phase liquid inlet control mechanism 11 and the second internal phase liquid inlet control mechanism 12 are alternately propulsed, and the liquid inlet mode of the external phase liquid inlet control mechanism 13 adopts a continuous propulsion mode.

[0060] In order to realize the control of the first inner phase liquid inlet control mechanism 11, the two sets of second inner phase liquid inlet control mechanisms 12 and the two sets of outer phase liquid inlet control mechanisms 13, please refer to Figure 1 The liquid inlet unit 1 also includes a single-channel internal phase liquid inlet controller 14 connected to the first internal phase liquid inlet control mechanism 11, a dual-channel internal phase liquid inlet controller 15 connected to the two groups of second internal phase liquid inlet control mechanisms 12, and a dual-channel external phase liquid inlet controller 16 connected to the two groups of external phase liquid inlet control mechanisms 13.

[0061] In the embodiment of the present application, the first internal phase inlet 21, the second internal phase inlet 22, and the external phase inlet 23 are all circular. Optionally, the diameter of the external phase inlet 23 is 0.5 to 3 mm, and the diameters of the first internal phase inlet 21 and the second internal phase inlet 22 are 0.2 to 2 mm. Preferably, the diameter of the external phase inlet 23 is 1 mm, and the diameters of the first internal phase inlet 21 and the second internal phase inlet 22 are 0.4 mm.

[0062] In the embodiment of the present application, the drafting winding roller 9 plays the role of drafting and collecting fibers.

[0063] In an embodiment of the present application, the preparation of bamboo-like structural fibers is based on microfluidic equipment, and the external phase spinning liquid and the internal phase spinning liquid are respectively introduced into corresponding ducts, and the liquid inlet is controlled by the corresponding propeller, and the fibers converge at the fiber outlet 24 of the coaxial spinning head 2 to form bamboo-like structural primary fibers. After the bamboo-like structural primary fibers pass through the coagulation bath 3, the external phase spinning liquid is rapidly cross-linked and solidified to obtain fibers with a core-shell structure. By controlling the liquid inlet method and time by the internal phase liquid inlet controller, an internal phase non-uniform continuous structure can be obtained, that is, the bamboo-like structural primary fibers are initially formed.

[0064] Further, see Figure 1 and Figure 2 , the external phase spinning solution entering from the external phase liquid inlet 23 is the same as the internal phase spinning solution entering from the first internal phase liquid inlet 21 or the second internal phase liquid inlet 22. In an embodiment of the present application, the external phase spinning solution entering from the external phase liquid inlet 23 is the same as the internal phase spinning solution entering from the second internal phase liquid inlet 22. Optionally, the external phase spinning solution is one of a sodium alginate solution, a sodium alginate-sodium polyacrylate mixed solution, a sodium alginate-gelatin mixed solution, and a sodium alginate-gelatin-sodium polyacrylate mixed solution. Preferably, the external phase spinning solution is a sodium alginate solution. Optionally, the concentration of the external phase spinning solution is 1% to 5%. Preferably, the concentration of the external phase spinning solution is 3%.

[0065] In addition, one of the internal phase spinning solutions entering through the first internal phase liquid inlet 21 or the second internal phase liquid inlet 22 is a drug solution for sustained drug release. In the embodiment of the present application, the internal phase spinning solution entering through the first internal phase liquid inlet 21 is a 25% curcumin solution. Preferably, 3% to 10% deionized water is added to the 25% curcumin solution.

[0066] It is worth noting that see Figure 1 The advancement time of the first internal phase liquid inlet control mechanism 11 is greater than the advancement time of the second internal phase liquid inlet control mechanism 12 to ensure the formation of primary fibers similar to the bamboo structure.

[0067] Specifically, see Figure 1Coagulation bath 3 contains a fiber coagulation bath, which is an ionic or salt solution. Its primary purpose is to allow the external spinning solution to rapidly crosslink with the ions in the fiber coagulation bath upon entry, resulting in instant solidification and thus successfully encapsulating the internal spinning solution (the chemical solution). In this embodiment, the fiber coagulation bath uses a 25% calcium chloride solution. Cleaning tank 4 contains anhydrous ethanol, which is used to clean residual calcium chloride solution from the fibers.

[0068] For more details, see Figure 1 and Figure 2 The first internal phase liquid inlet control mechanism 11 includes a first internal phase liquid inlet propeller 111 and a first internal phase liquid inlet spinning syringe 112 that are connected to each other, the first internal phase liquid inlet propeller 111 is connected to the liquid inlet end of the first internal phase liquid inlet spinning syringe 112, and the liquid outlet end of the first internal phase liquid inlet spinning syringe 112 is connected to the first internal phase liquid inlet 21; the second internal phase liquid inlet control mechanism 12 includes a second internal phase liquid inlet propeller 121 and a second internal phase liquid inlet spinning syringe 122 that are connected to each other, The second internal phase liquid inlet propeller 121 is connected to the liquid inlet end of the second internal phase liquid inlet spinning syringe 122, and the liquid outlet end of the second internal phase liquid inlet spinning syringe 122 is connected to the second internal phase liquid inlet port 22; the external phase liquid inlet control mechanism 13 includes an external phase liquid inlet propeller 131 and an external phase liquid inlet spinning syringe 132 that are interconnected, the external phase liquid inlet propeller 131 is connected to the liquid inlet end of the external phase liquid inlet spinning syringe 132, and the liquid outlet end of the external phase liquid inlet spinning syringe 132 is connected to the external phase liquid inlet port 23.

[0069] Optionally, the propulsion speeds of the first inner phase liquid inlet propeller 111 and the second inner phase liquid inlet propeller 121 are both 0.05 to 2 ml / min, and the propulsion speed of the outer phase liquid inlet propeller 131 is 2 to 5 ml / min. Preferably, the propulsion speed of the outer phase liquid inlet propeller 131 is 3.6 ml / min, and the propulsion speeds of the first inner phase liquid inlet propeller 111 and the second inner phase liquid inlet propeller 121 are both 1.2 ml / min.

[0070] In the embodiment of the present application, the specifications of the first internal phase liquid-inlet spinning syringe 112, the second internal phase liquid-inlet spinning syringe 122 and the external phase liquid-inlet spinning syringe 132 are 5 to 100 ml.

[0071] To achieve the effect of guiding the fiber direction, see Figure 1 There is a first guide roller 5 in the coagulation bath 3, a second guide roller 6 between the coagulation bath 3 and the cleaning tank 4, a third guide roller 7 in the cleaning tank 4, and a fourth guide roller 8 between the cleaning tank 4 and the drafting winding roller 9.

[0072] In the embodiment of the present application, the first guide roller 5 , the second guide roller 6 , the third guide roller 7 and the fourth guide roller 8 are all made of aluminum alloy, and their outer diameters are all 30 mm.

[0073] Example 2:

[0074] Figure 3 A schematic diagram of a spinning method of bamboo-like structural fibers provided by an exemplary embodiment of the present application is shown. Figure 1 and Figure 2 From the perspective of the present invention, the method is applicable to the microfluidic device of the bamboo-like structural fiber provided in the above embodiment 1, and the method comprises:

[0075] Step S1: The single-channel internal phase liquid inlet controller 14 controls the operation of the first internal phase liquid inlet control mechanism 11. The first internal phase liquid inlet propeller 111 in the first internal phase liquid inlet control mechanism 11 is responsible for equidistant intermittent propulsion. The first internal phase liquid inlet spinning syringe 112 in the first internal phase liquid inlet control mechanism 11 is responsible for packaging. The first internal phase spinning solution is input from the first internal phase liquid inlet port 21 into the coaxial spinning head 2. The first internal phase spinning solution is a drug solution for sustained drug release.

[0076] Step S2: At the same time, the dual-channel internal phase liquid inlet controller 15 controls the two sets of second internal phase liquid inlet control mechanisms 12 to work, the second internal phase liquid inlet propellers 121 of the second internal phase liquid inlet control mechanisms 12 are responsible for equidistant intermittent propulsion, and the second internal phase liquid inlet spinning syringes 122 of the second internal phase liquid inlet control mechanisms 12 are responsible for packaging, and the second internal phase spinning solution is input into the coaxial spinning head 2 from the second internal phase liquid inlet port 22;

[0077] Step S3: At the same time, the dual-channel external phase liquid inlet controller 16 controls the operation of the two sets of external phase liquid inlet control mechanisms 13. The external phase liquid inlet propeller 131 of the external phase liquid inlet control mechanism 13 is responsible for continuous propulsion, and the external phase liquid inlet spinning syringe 132 of the external phase liquid inlet control mechanism 13 is responsible for packaging, and the external phase spinning solution is input into the coaxial spinning head 2 from the external phase liquid inlet port 23;

[0078] Step S4: Fibers are formed and extruded from the fiber outlet 24 at the lower end of the coaxial spinning head 2. The extruded fibers are coagulated in the coagulation bath 3 and guided by the first guide roller 5 and the second guide roller 6 into the cleaning tank 4 to clean the coagulation bath liquid remaining on the fiber surface. The fibers are then guided by the third guide roller 7 and the fourth guide roller 8 to the drafting and winding roller 9 for collection, thereby obtaining primary fibers with a bamboo-like structure.

[0079] Step S5: post-processing the bamboo-like structural primary fibers to finally obtain bamboo-like structural fibers.

[0080] In the embodiment of the present application, the post-processing step is constrained drying.

[0081] In the embodiment of the present application, the second internal phase spinning solution and the external phase spinning solution are the same, both using a 3% sodium alginate solution. The first internal phase spinning solution uses a 25% curcumin solution.

[0082] In the embodiment of the present application, the propulsion speeds of the first inner phase liquid inlet propeller 111 and the second inner phase liquid inlet propeller 121 are both 1.2 ml / min, and the propulsion speed of the outer phase liquid inlet propeller 131 is 3.6 ml / min.

[0083] It should be noted that the single-channel internal phase liquid inlet controller 14 and the dual-channel internal phase liquid inlet controller 15 control the advancement alternately to form primary fibers similar to the bamboo structure.

[0084] In the embodiment of the present application, the coagulation bath 3 contains a calcium chloride solution with a solution concentration of 25%. The calcium ions in the calcium chloride solution cross-link with the external phase spinning solution, so that the external phase of the fiber is rapidly solidified to form a shell-core structure; the cleaning tank 4 contains anhydrous ethanol, which is used to clean the calcium chloride solution remaining on the fiber surface.

[0085] Figure 4 The schematic diagram of the structure of the bamboo-like structural fiber before and after post-processing provided by an exemplary embodiment of the present application is shown. In the above step S5, the bamboo-like structural primary fiber is post-processed to finally obtain the bamboo-like structural fiber, which includes:

[0086] Step S51: fixing both ends of the bamboo-like primary fibers and placing them on a glass plate, and drying or air-drying the bamboo-like primary fibers;

[0087] In step S52, during the post-processing process, the moisture in the first internal phase spinning liquid 100-chemical liquid is discharged from the bamboo-like structure primary fibers through the small holes formed by the incomplete gelation of the external phase spinning liquid 300, thereby causing the diameter of the first internal phase spinning liquid 100-chemical liquid part to shrink to form the bamboo-like structure cavity 400 part, while the diameter of the second internal phase spinning liquid 200-non-chemical liquid part remains unchanged to form the bamboo-like structure bamboo node 500 part, and the external phase spinning liquid 300 forms the bamboo-like structure surface 600 part, and finally the bamboo-like structure fibers are obtained.

[0088] In other words, the two ends of the bamboo-like primary fibers are fixed and placed on a glass plate, and the fibers are dried or air-dried. During the drying or air-drying process, the water in the curcumin solution is discharged from the fibers through the small holes formed by the incomplete gelation of calcium alginate, resulting in a reduction in the diameter of the part encapsulating the curcumin solution, while the diameter of the internal phase sodium alginate part remains unchanged.

[0089] Furthermore, the portion encapsulating the curcumin solution forms a bamboo-like structure cavity portion, the inner phase sodium alginate is cross-linked with calcium ions to form a bamboo-like node portion, and the outer phase sodium alginate is cross-linked with calcium ions to form a bamboo-like structure surface.

[0090] Furthermore, the obtained bamboo-like structural fiber can be used in the field of liquid drug sustained release or liquid encapsulation, and the required sustained release rate of the drug can be controlled by changing the wall thickness of the bamboo-like structural fiber.

[0091] In summary, the microfluidic device for the bamboo-like structural fiber provided by the present application is equipped with two internal phase liquid inlets. By controlling the alternating time of the liquid inlet, primary fibers with a bamboo structure morphology can be prepared. The microfluidic spinning technology can effectively control the size, structure and material composition of the fibers, and is a new method for manufacturing functional fibers with complex structures. The bamboo-like structural fibers prepared by the microfluidic device and spinning method for the bamboo-like structural fibers provided by the present application include a bamboo-like node structure, a bamboo-like cavity structure and a bamboo-like surface structure. The bamboo-like cavity structure and the bamboo-like surface structure act as carriers for encapsulating the drug solution. The bamboo-like node structure separates the encapsulated drug solution into several closed layers, which can prevent the problem of drug solution loss after fiber breakage. The bamboo-like structural fibers prepared by the microfluidic device and spinning method for the bamboo-like structural fibers provided by the present application can not only encapsulate liquid drugs as the internal phase in the fibers, which can effectively solve the problem of difficult encapsulation of liquid drugs, but also can control the sustained release rate required for the drug by changing the wall thickness of the core-shell structure fiber, so that the drug can maintain a constant blood drug concentration after being injected into the body, and prevent the drug from being metabolically ineffective due to the first-pass effect.

[0092] The above is only a preferred embodiment of the present application. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present application. These improvements and modifications should also be regarded as the scope of protection of the present application.

Claims

1. A microfluidic device imitating bamboo structural fiber, characterized in that: It includes a liquid inlet unit, a coaxial spinning head connected to the liquid inlet unit, a coagulation bath arranged at the rear end of the coaxial spinning head, a cleaning tank arranged at the rear end of the coagulation bath, and a drafting and winding roller arranged at the rear end of the cleaning tank; The liquid inlet unit includes a first internal phase liquid inlet control mechanism, two groups of second internal phase liquid inlet control mechanisms and two groups of external phase liquid inlet control mechanisms. The top of the coaxial spinning head is provided with a first internal phase liquid inlet, and the side wall of the coaxial spinning head is provided with two groups of second internal phase liquid inlets and two groups of external phase liquid inlets. The first internal phase liquid inlet is connected to the first internal phase liquid inlet control mechanism, the two groups of second internal phase liquid inlets are respectively connected to the two groups of second internal phase liquid inlet control mechanisms, and the two groups of external phase liquid inlets are respectively connected to the two groups of external phase liquid inlet control mechanisms. Among them, the liquid inlet method of the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism both adopts an equidistant intermittent propulsion method, and the first internal phase liquid inlet control mechanism and the second internal phase liquid inlet control mechanism are alternately advanced, and the liquid inlet method of the external phase liquid inlet control mechanism adopts a continuous propulsion method.

2. The microfluidic device of bamboo-like structural fiber according to claim 1, characterized in that: The advancement time of the first inner phase liquid inlet control mechanism is greater than the advancement time of the second inner phase liquid inlet control mechanism.

3. The microfluidic device of bamboo-like structural fiber according to claim 1, characterized in that: The external phase spinning solution introduced from the external phase liquid inlet is the same as the internal phase spinning solution introduced from the second internal phase liquid inlet.

4. The microfluidic device of bamboo-like structural fiber according to claim 3, characterized in that: The external phase spinning solution is one of sodium alginate solution, sodium alginate-sodium polyacrylate mixed solution, sodium alginate-gelatin mixed solution, and sodium alginate-gelatin-sodium polyacrylate mixed solution.

5. The microfluidic device of imitating bamboo structural fiber according to claim 3, characterized in that: The internal phase spinning solution entering from the first internal phase liquid inlet is a drug solution for sustained drug release.

6. The microfluidic device of imitating bamboo structural fiber according to claim 1, characterized in that: The coagulation bath tank contains a fiber coagulation bath, and the fiber coagulation bath is an ion solution or a salt solution; The cleaning tank contains anhydrous ethanol, which is used to clean the coagulation bath liquid remaining on the fiber.

7. The microfluidic device of imitating bamboo structural fiber according to claim 1, characterized in that: The first internal phase liquid inlet control mechanism includes a first internal phase liquid inlet propeller and a first internal phase liquid inlet spinning syringe connected to each other, the first internal phase liquid inlet propeller is connected to the liquid inlet end of the first internal phase liquid inlet spinning syringe, and the liquid outlet end of the first internal phase liquid inlet spinning syringe is connected to the first internal phase liquid inlet; The second internal phase liquid inlet control mechanism includes a second internal phase liquid inlet propeller and a second internal phase liquid inlet spinning syringe connected to each other, the second internal phase liquid inlet propeller is connected to the liquid inlet end of the second internal phase liquid inlet spinning syringe, and the liquid outlet end of the second internal phase liquid inlet spinning syringe is connected to the second internal phase liquid inlet; The external phase liquid inlet control mechanism includes an external phase liquid inlet propeller and an external phase liquid inlet spinning syringe connected to each other, the external phase liquid inlet propeller is connected to the liquid inlet end of the external phase liquid inlet spinning syringe, and the liquid outlet end of the external phase liquid inlet spinning syringe is connected to the external phase liquid inlet.

8. The microfluidic device of imitating bamboo structural fiber according to claim 1, characterized in that: The liquid inlet unit also includes: a single-channel internal phase liquid inlet controller connected to the first internal phase liquid inlet control mechanism; a dual-channel internal phase liquid inlet controller connected to two sets of the second internal phase liquid inlet control mechanisms; and A dual-channel external phase liquid inlet controller connected to the two sets of external phase liquid inlet control mechanisms.

9. The microfluidic device of imitating bamboo structural fiber according to claim 1, characterized in that: A first guide roller is provided in the coagulation bath tank, a second guide roller is provided between the coagulation bath tank and the cleaning tank, a third guide roller is provided in the cleaning tank, and a fourth guide roller is provided between the cleaning tank and the drafting and winding roller.

10. A spinning method for bamboo-like structural fibers, characterized in that: The method is applicable to the microfluidic device of the bamboo-like structural fiber according to any one of claims 1 to 9, and the method comprises: S1. A single-channel internal phase liquid inlet controller controls the operation of a first internal phase liquid inlet control mechanism. A first internal phase liquid inlet propeller in the first internal phase liquid inlet control mechanism is responsible for equidistant intermittent propulsion. A first internal phase liquid inlet spinning syringe in the first internal phase liquid inlet control mechanism is responsible for packaging and feeding a first internal phase spinning solution from a first internal phase liquid inlet port into a coaxial spinning head. The first internal phase spinning solution is a drug solution for sustained drug release. S2. At the same time, the dual-channel internal phase liquid inlet controller controls the operation of two sets of second internal phase liquid inlet control mechanisms. The second internal phase liquid inlet propellers of the second internal phase liquid inlet control mechanisms are responsible for equidistant intermittent propulsion. The second internal phase liquid inlet spinning syringes of the second internal phase liquid inlet control mechanisms are responsible for packaging and inputting the second internal phase spinning solution from the second internal phase liquid inlet port into the coaxial spinning head. S3. At the same time, the dual-channel external phase liquid inlet controller controls the operation of two sets of external phase liquid inlet control mechanisms. The external phase liquid inlet propellers of the external phase liquid inlet control mechanisms are responsible for continuous propulsion, and the external phase liquid inlet spinning syringes of the external phase liquid inlet control mechanisms are responsible for packaging, and the external phase spinning solution is input into the coaxial spinning head from the external phase liquid inlet port. S4, fibers are formed and extruded from the fiber outlet at the lower end of the coaxial spinning head, the extruded fibers are coagulated in a coagulation bath, and are guided by a first guide roller and a second guide roller into a cleaning tank to clean off the coagulation bath liquid remaining on the fiber surface, and then the fibers are guided by a third guide roller and a fourth guide roller to a drafting and winding roller for collection, thereby obtaining primary fibers with a bamboo-like structure; S5. Post-processing the bamboo-like structural primary fibers to finally obtain bamboo-like structural fibers.

11. The spinning method of the bamboo-like structural fiber according to claim 10, characterized in that: In step S5, the post-processing of the bamboo-like structural primary fibers to obtain the bamboo-like structural fibers comprises: S51, fixing both ends of the primary bamboo-like structure fibers and placing them on a glass plate, and drying or air-drying the primary bamboo-like structure fibers; S52. During the post-processing process, the moisture in the first internal phase spinning liquid-drug liquid is discharged from the imitation bamboo structure primary fibers through the small holes formed by the incomplete gelation of the external phase spinning liquid, thereby causing the diameter of the drug liquid part to shrink to form a bamboo structure imitation cavity part, while the diameter of the second internal phase spinning liquid-non-drug liquid part remains unchanged to form a bamboo structure imitation bamboo node part, and the external phase spinning liquid forms the bamboo structure imitation surface part, and finally the bamboo structure imitation fibers are obtained.

12. The spinning method of the bamboo-like structural fiber according to claim 10, characterized in that: The second inner phase spinning solution is the same as the outer phase spinning solution, and is one of a sodium alginate solution, a sodium alginate-sodium polyacrylate mixed solution, a sodium alginate-gelatin mixed solution, and a sodium alginate-gelatin-sodium polyacrylate mixed solution; The spinning solution concentrations of the second inner phase spinning solution and the outer phase spinning solution are both 1% to 5%; The propulsion speeds of the first inner phase liquid inlet propeller and the second inner phase liquid inlet propeller are both 0.05 to 2 ml / min, and the propulsion speed of the outer phase liquid inlet propeller is 2 to 5 ml / min; The single-channel internal phase liquid inlet controller and the dual-channel internal phase liquid inlet controller alternately control the propulsion; The coagulation bath contains a calcium chloride solution with a concentration of 20% to 50%, and the calcium ions in the calcium chloride solution cross-link with the outer phase spinning solution, so that the outer phase of the fiber is rapidly solidified to form a shell-core structure; The cleaning tank contains anhydrous ethanol, which is used to clean the calcium chloride solution remaining on the fiber surface.

Images