Method for preparing PHA (polyhydroxyalkanoate) microspheres by using micro-fluidic chip and application of PHA microspheres
Preparation of PHA microspheres through microfluidic chips solves the problems of excessive particles and poor uniformity of traditional subcutaneous filling materials, and achieves uniform microsphere particle size and consistency of distribution after injection.
Patent Information
- Application Number
- CN202411860882.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-17
- Publication Date
- 2025-03-28
AI Technical Summary
Too large particles of traditional subcutaneous filling materials may lead to protrusions or irregular shapes on the skin surface, and poor uniformity will lead to uneven distribution after injection and inconsistent metabolic speed.
PHA microspheres were prepared by using a microfluidic chip. PHA microspheres were grinded with PHA raw materials, dissolved in solvent to form an oil phase, and dissolved with polyvinyl alcohol in the aqueous phase. Stable microspheres were formed through the microfluidic chip. After volatilization, solvent removal and cleaning were obtained to obtain PHA microspheres with uniform particle size.
The uniformity of the particle size of the microsphere is achieved, and the convexity or irregular shape of the skin surface is avoided, ensuring uniformity of distribution after injection and consistency of metabolic speed.
Smart Images
Figure CN119701807A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of material technology, and in particular to a method and application of preparing PHA microspheres by using a microfluidic chip. Background Art
[0002] Microfluidics is a technology that allows fluids to pass through micron-sized channels, which can produce microspheres with uniform size and good dispersion, providing new ideas and methods for microsphere preparation. The microspheres prepared by it have a high degree of uniformity, and the production process can be mechanically controlled to achieve unmanned operation, which has great advantages in factory production.
[0003] With the continuous development of medical technology, more and more people are beginning to pay attention to the combination of beauty and health. As a new type of cosmetic method, subcutaneous microspheres can inject tiny particles under the skin to fill wrinkles and increase the three-dimensional sense of the face. Traditional filling materials have some limitations. For example, if the material particles are too large, they may form bulges or irregular shapes on the skin surface, and they are easily displaced by external forces. For example, poor uniformity of material particles may lead to uneven distribution after injection and inconsistent metabolic rates. The microspheres prepared based on microfluidic chips have uniform particle size and appropriate size, which can solve the above problems and provide new possibilities for the development of cosmetic medicine.
[0004] As a specially designed material, subcutaneous filling microspheres have broad application prospects in the medical and beauty fields. As a subcutaneous filling material, this requires that the material must be non-toxic, non-irritating, non-carcinogenic, and can exist safely in the body. It must also have high biocompatibility and biodegradability to reduce or avoid immune reactions or rejection reactions in the human body. PHA materials have the following advantages: good biocompatibility, good biodegradability, excellent physical properties and high safety, which meet the requirements as a raw material for microspheres.
[0005] Taking into account the requirements of particle size uniformity and safety of the prepared microspheres, the method of preparing microspheres using PHA as raw material and microfluidic chips can perfectly meet the above requirements.
[0006] Therefore, it is necessary to design a practical method and application for preparing PHA microspheres using microfluidic chips. Summary of the invention
[0007] The purpose of the present invention is to provide a method and application of preparing PHA microspheres using a microfluidic chip to solve the problems raised in the above background technology.
[0008] In order to solve the above technical problems, the present invention provides the following technical solutions: a method for preparing PHA microspheres using a microfluidic chip, wherein the microfluidic chip includes a chip itself and a clamping device, and the chip has two inlets and one outlet, which are respectively used to introduce water phase and oil phase raw materials and to receive microsphere liquid, and the water phase channel branches in two directions upward and downward and forms a cross structure with the oil phase channel, and is connected to the outlet;
[0009] The preparation method of PHA microspheres comprises the following steps:
[0010] S1: grinding the PHA raw material to obtain a powder with a particle size of about 3 μm, dissolving the powder in a solvent to obtain an oil phase;
[0011] S2: Dissolve polyvinyl alcohol in deionized water to obtain the water phase. Both the oil phase and the water phase must be filtered through a 22 μm filter membrane before use;
[0012] S3: The oil phase and water phase solutions are connected to the designated channels of the microfluidic chip respectively, and the flow rates of the oil phase and water phase liquids are controlled so that they can continuously form stable microspheres. The obtained microspheres need to be evaporated to remove the solvent and wash off the polyvinyl alcohol, and then dried to obtain PHA microspheres. When the microsphere droplets are collected at the outlet, a small amount of polyvinyl alcohol solution needs to be placed in the container to prevent the microsphere liquid from drying and sticking to the container. The microsphere liquid collected at the sample outlet needs to evaporate the solvent therein, which can be treated in an evaporator at 50°C for 30 minutes, and its diameter is observed under a microscope. If it is the same as the size of the standard microsphere, it proves that the solvent is completely evaporated, otherwise continue to treat in the evaporator.
[0013] According to the above technical solution, the powder obtained by grinding the PHA raw material is ground in a grinding method with a mass ratio of PHA powder to deionized water of 2:3, a grinding time of 8 to 16 minutes, and then freeze-dried.
[0014] According to the above technical solution, the solvent is selected from dichloromethane or chloroform; and both the oil phase and the water phase need to be heated during dissolution.
[0015] According to the above technical solution, the mass percentage of PHA is between 1% and 4%.
[0016] According to the above technical solution, the mass percentage of polyvinyl alcohol is between 1% and 3%.
[0017] According to the above technical solution, step S3 specifically includes using a microfluidic device to connect the liquid and the microfluidic chip, controlling the flow rate of the two phases by the negative pressure of the air pump, and controlling the pressure ratio of the oil phase to the water phase at 1:1, but not exceeding 0.03 MPa to obtain stable and high-yield PHA microspheres.
[0018] According to the above technical solution, step S3 also requires that the PHA microsphere liquid formed by the microfluidic chip needs to be kept stationary for a period of time in deionized water containing 2% polyvinyl alcohol to volatilize the solvent therein, and whether the solvent has been completely evaporated is determined by whether the size of the detected microspheres is the same or similar to the size of completely dried microspheres. After the solvent has evaporated, the polyvinyl alcohol in the microspheres needs to be cleaned and removed.
[0019] A PHA microsphere is used in medical beauty products or filling materials.
[0020] Compared with the prior art, the PHA microspheres prepared by the present invention have uniform particle size, no chemical reaction process, and no residual biological toxic substances. They can be widely used in the preparation of tissue fillers and medical beauty products. At the same time, the preparation method of the present invention is simple, has few operating steps, and can achieve automated operation. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:
[0022] Figure 1 The structure diagram of the microfluidic chip used;
[0023] Figure 2 Process flow chart for microsphere preparation;
[0024] Figure 3 This is a scanning electron microscope image of the PHA microspheres prepared in Example 1;
[0025] Figure 4 This is a scanning electron microscope image of the PHA microspheres prepared in Example 2. DETAILED DESCRIPTION
[0026] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0027] Example 1: A method for preparing PHA microspheres, comprising the following steps:
[0028] S1: using dichloromethane as a solvent, dissolving 4% PHA by mass in dichloromethane to obtain an oil phase;
[0029] S2: Dissolve 2% by mass of polyvinyl alcohol in deionized water to obtain a water phase.
[0030] S3: After filtering with a 22 μm filter membrane, the microspheres are connected to the chip, extruded and volatilized, washed and dried to obtain the microspheres, and their size and morphology are observed. Figure 3 It can be seen that the size of the microspheres meets the requirements, the spherical shape is good, and the number is relatively large.
[0031] Example 2: A method for preparing PHA microspheres, comprising the following steps:
[0032] S1: using dichloromethane as a solvent, dissolving 3% PHA by mass in dichloromethane to obtain an oil phase;
[0033] S2: Dissolve 2% by mass of polyvinyl alcohol in deionized water to obtain a water phase.
[0034] S3: After filtering with a 22 μm filter membrane, the microspheres are connected to the chip, extruded and volatilized, washed and dried to obtain the microspheres, and their size and morphology are observed. Figure 4 It can be seen that the microspheres are small in size, but have good spherical shape and are relatively small in number, as shown in Table 1.
[0035] Example 3: A method for preparing PHA microspheres, comprising the following steps:
[0036] S1: using dichloromethane as a solvent, dissolving 2% PHA by mass in dichloromethane to obtain an oil phase;
[0037] S2: Dissolve 2% by mass of polyvinyl alcohol in deionized water to obtain a water phase.
[0038] S3: After filtering with a 22 μm filter membrane, the microspheres were connected to the chip, extruded and volatilized, washed and dried to obtain the microspheres, and their size and morphology were observed. The microspheres were small in size and small in number, as shown in Table 1.
[0039] Example 4: A method for preparing PHA microspheres, comprising the following steps:
[0040] S1: using dichloromethane as a solvent, dissolving 1% PHA by mass in dichloromethane to obtain an oil phase;
[0041] S2: Dissolve 2% by mass of polyvinyl alcohol in deionized water to obtain a water phase.
[0042] S3: After filtering with a 22 μm filter membrane, the microspheres were connected to the chip, extruded and volatilized, washed and dried to obtain the microspheres, and their size and morphology were observed. The microspheres were small in size and small in number, as shown in Table 1.
[0043]
[0044] Table 1
[0045] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.
[0046] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. A method for preparing PHA microspheres using a microfluidic chip, characterized in that: The microfluidic chip includes a chip itself and a clamping device. The chip has two injection ports and one outlet port, which are used to introduce water phase and oil phase raw materials and to receive microsphere liquid respectively. The water phase channel branches in two directions upward and downward to form a cross structure with the oil phase channel and is connected to the outlet port. Specifically, the water phase injection port extends a channel with a diameter of about 280 μm to the right, and then branches in two directions upward and downward to form channels with a diameter of about 160 μm. The diameters of these two channels gradually decrease to 100 μm and form a cross structure with the oil phase channel. The oil phase injection port extends a channel with a diameter of about 160 μm to the right and gradually decreases to 100 μm and forms a cross structure with the water phase channel. The cross structure extends a small channel with a diameter of 80 μm to the outlet port, followed by a channel with a diameter of 100 μm, and then the pore diameter gradually expands to 300 μm to connect to the outlet port. The preparation method of PHA microspheres comprises the following steps: S1: grinding the PHA raw material to obtain a powder with a particle size of about 3 μm, dissolving the powder in a solvent to obtain an oil phase; S2: Dissolve polyvinyl alcohol in deionized water to obtain the water phase. Both the oil phase and the water phase must be filtered through a 22 μm filter membrane before use; S3: The oil phase and water phase solutions are connected to the designated channels of the microfluidic chip respectively, and the flow rates of the oil phase and water phase liquids are controlled so that they can continuously form stable microspheres. The obtained microspheres need to be evaporated to remove the solvent and wash off the polyvinyl alcohol, and then dried to obtain PHA microspheres. When the microsphere droplets are collected at the outlet, a small amount of polyvinyl alcohol solution needs to be placed in the container to prevent the microsphere liquid from drying and sticking to the container. The microsphere liquid collected at the sample outlet needs to evaporate the solvent therein, which can be treated in an evaporator at 50°C for 30 minutes, and its diameter is observed under a microscope. If it is the same as the size of the standard microsphere, it proves that the solvent is completely evaporated, otherwise continue to treat in the evaporator.
2. The method for preparing PHA microspheres using a microfluidic chip according to claim 1, characterized in that: The powder obtained by grinding the PHA raw material is ground in a manner such that the mass ratio of the PHA powder to deionized water is 2:3, the grinding time is 8 to 16 minutes, and then freeze-dried.
3. A method for preparing PHA microspheres using a microfluidic chip according to claim 2, characterized in that: The solvent is selected from dichloromethane or chloroform; both the oil phase and the water phase need to be heated during dissolution.
4. The method for preparing PHA microspheres using a microfluidic chip according to claim 3, characterized in that: The mass percentage of PHA is between 1% and 4%.
5. The method for preparing PHA microspheres using a microfluidic chip according to claim 4, characterized in that: The mass percentage of polyvinyl alcohol is between 1% and 3%.
6. The method and application of preparing PHA microspheres using a microfluidic chip according to claim 5, characterized in that: Specifically, step S3 uses a microfluidic device to connect the liquid and the microfluidic chip, and controls the flow rate of the two phases by the negative pressure of the air pump. The pressure ratio of the oil phase to the water phase can be controlled at 1:1, but not exceeding 0.03 MPa to obtain stable and high-yield PHA microspheres.
7. A method for preparing PHA microspheres using a microfluidic chip according to claim 6, characterized in that: Step S3 also requires that the PHA microsphere liquid formed by the microfluidic chip needs to be kept stationary in deionized water containing 2% polyvinyl alcohol for a period of time to evaporate the solvent therein. Whether the solvent has evaporated completely is determined by whether the size of the detected microspheres is the same or similar to the size of completely dried microspheres. After the solvent has evaporated, the polyvinyl alcohol in the microspheres needs to be cleaned and removed.
8. A PHA microsphere is used in medical beauty products or filling materials.