• 专利附录
  • 专利说明
  • 权利要求
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    • 专利摘要:
    A golf ball-type degradable microsphere having a micro-topological structure and a method of preparing the same. The microsphere is composed of PCL and other components of polymeric material, the diameter of the microsphere ranging from 1 µm to 600 µm having a concave or crumpled appearance on the inside with a micro-topological structure of spherical shape.
    公开号:BE1027169B1
    申请号:E20195723
    申请日:2019-10-18
    公开日:2020-10-27
    发明作者:Daixu Wei
    申请人:Shanghai Moyang Biotechnology Co Ltd；
    IPC主号:
    专利说明:

    Description A golf ball-type degradable microsphere exhibiting a microtopological structure and its preparation process Technical Field The invention relates to the field of polymeric materials, in particular a golf ball-type degradable microsphere exhibiting a microtopological structure and its preparation. preparation process.
    Background Art Degradable microspheres are in the form of degradable spherical or ellipsoidal polymeric supports having a particle size of 1 to 600 µm prepared by degradable polymer biomaterials. Degradable microspheres are commonly used as carriers for drugs and cells due to their small size, large specific surface area and degradable characteristics, with a wide range of applications in medicine, medical beauty, agriculture. and environmental protection.
    Biopolyester is a type of biodegradable polymer with an ester bond as the primary chemical bond. It has the following advantages: biodegradable absorption, high strength, good plasticity and ease of processing. It is widely used in medical tissue engineering and in controlled release drug delivery systems. Polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), and polycaprolactone (PCL) are the three most typical types of biopolyester materials. Polylactic acid and PLGA can be quickly broken down by enzymes in the body to form carbon dioxide and water. The degradation cycle is shorter than that of other biodegradable biopolyester materials, typically 2 to 12 months. Too rapid degradation can often lead to non-bacterial (acidic) inflammation of the tissues surrounding the implant. Due to its more conservative structure, polycaprolactone has a slower degradation rate, usually 6 to 36 months, but the material is soft and the bearing capacity is poor. The structure of most of the degradable microspheres that have been described is a smooth surface similar to a two dimensional smooth plane.
    Recent studies have shown that substrates with a micro-topological structure can promote cell adhesion and growth, and even induce differentiation and functional expression. For example, if a circular micro-topological structure with five holes is realized, the three-dimensional growth of stem cell aggregates is achieved by using the features that the neural stem cells can be detached from the micro-topological concave surface and have a growth in suspension in the micro-topological structure.
    At present, the microspheres prepared from the aforementioned materials are mostly smooth and there is little research and product reports on the micro-topological structure of the microspheres; moreover, most of the microspheres described exhibiting a surface micro-topology are prepared by chemical etching, synthesis and grafting, thus with the risks of residual catalysts and toxic chemicals.
    General Description The object of the present invention is to provide a degradable golf ball-type microsphere (also referred to as a golf-type microsphere) having a micro-topological structure and a method of preparation thereof.
    This object is achieved by a microsphere according to claim 1, and a method according to claim 5. The microsphere being comprised of medium and low molecular weight PCL and other components of polymeric material.
    The microsphere has a diameter between 1 µm and 600 µm and a spherical structure with a typical internal hollow or wrinkle.
    The microsphere has a micro-topological structure in the shape of a golf ball, allowing cell adhesion and growth.
    Since the medium and low molecular weight PCL material in component B degrades rapidly in vivo and ex vivo, as a preferred embodiment of the present invention, control of the rate of size and size degradation overall appearance of the microsphere can be achieved by separately adjusting the mass ratio and molecular weight of component B in total components, or by adjusting the mass ratio and molecular weight of component A (other polymeric materials except PCL) in the total of the components.
    The residual rate of degradation over three months is between 85% and 98%; its residual rate of degradation over six months, between 8% and 95%; its residual rate of degradation over 9 months, between 0% and 90%; its residual rate of degradation over 12 months, between 0% and 80%; its residual rate of degradation over 24 months, between 0% and 60%, and its residual rate of degradation over 36 months, ranging from 0% to 7%. To achieve the above object, the present invention is specifically achieved by the following measures: Step 1: Arrange component A and component B (PCL) in a mass ratio of 99: 1 to 50:50 and dissolve them in the organic solvent component C to form a mixed solution component D; Step 2: Add component D to stabilizer solution component E and mix by stirring to form emulsion component F; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized, to form component G.
    Step 4: Wash component G with water or swab as needed to remove residue and get golf ball type microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder.
    As a preferred embodiment of the present invention, Component A in step 1 is a mixture of one or more of PLA and PLGA. Its molecular weight is 100 KD to 500 KD, other degradable polymeric materials are also suitable, such as polyhydroxy acid PHA.
    In step 1, component B is a medium and low molecular weight PCL of 10 KD to 60 KD, which is the key to adjusting the size, morphology and degradation time of the microsphere.
    In step 1, component C is a mixture of one or more of dichloromethane, chloroform and acetone.
    In step 2, the concentration of the total material in component D is Swt% to 20wt%.
    As a preferred embodiment of the present invention, the stabilizer solution component E in step 2 is a mixture of one or more of PVA and PEG, and its total concentration is from 0.02wt% to 3wt. %. It can be other stabilizer solutions or active agents such as chitosan or Tween 80.
    As a preferred embodiment of the present invention, the stirring and mixing modes in steps 2 and 3 are carried out with a homogenate using a magnetic stirrer, mechanical stirrer or other similar means for mixing the compounds. oil and water phases.
    As a preferred embodiment of the present invention, the buffer described in step 4 is phosphate buffered saline (PBS), physiological saline, or a similar buffer as that which can be used for cell research. , human and medical.
    In step 5, the sterilization treatment comprises soaking in a 75% ethanol solution, irradiation with cobalt-60 and treatment with ethylene oxide.
    When the invention is used as a cell adhesion vector in the field of bioengineering, the particular shape of the microsphere is more favorable to cell adhesion, cell growth and the growth of metabolites than smooth microspheres.
    When the present invention is used as a medical load, it is combined with a porous sponge-like scaffold which can be repaired by injection stacking. The invention can be used alone as a filling material and can also be used as a cell carrier to deliver, transport and release cells for cell therapy auxiliaries. In addition, the invention also makes it possible to adjust the mass proportion of the components and the molecular weight of the component materials to define the size, the morphology and the degradation time of the microspheres in order to meet different needs, such as the promotion of cell adhesion, growth and stimulation of metabolites.
    When the invention is used as a sustained release drug carrier, the golf ball type microspheres can define the degradation time and the slow release curve of the golf ball type microsphere by adjusting the mass ratio of the microspheres. components and molecular weight of the constituent materials, and can be used in case of long-term sluggishness.
    The release effect solves the problem that the current drug release is too fast.
    The invention has the advantage that all materials are FDA or CFDA approved, that there is no chemical reaction in the preparation process, that chemical by-products and catalyst residues are avoided. , that the preparation process is simpler, the cost is lower, and the micro-topological structure of its surface can promote cell adhesion and growth.
    It is conducive to promoting antibody production, three-dimensional cell culture, tissue repair and other fields Description of the Drawings Fig. 1 is a scanning electron microscopy image of golf-type microsphere.
    Fig. 2 is a graph showing the golf-type microsphere degradation curve.
    Detailed Description of Preferred Embodiments Example 1. Examination of the Effect of Component B PCL Ratio on the Preparation of Golf Ball-Type Microspheres
    Step 1: Arrange polylactic acid component A (molecular weight 100KD) and polycaprolactone component B (molecular weight 40KD), with a total weight of 1g, in a mass ratio according to 99: 1, 90:10, 80:20, 70:30, 60:40, 50:50, and dissolving them in the 20 ml dichloromethane component C to form a mixed solution biological component D of 5% concentration; Step 2: Add component D to 200ml 0.1% PVA stabilizer solution E component and stir by stirring to form emulsion component F; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder. The prepared microspheres have the appearance of a golf ball obtained by scanning electron microscopy. However, when the composition ratio of PCL is 1%, the microspheres are smooth spherical indicating that PCL is a key component in the preparation of golf ball type microspheres. The particle size of the prepared microspheres is shown in Table 1 by the particle size analyzer. Table 1 shows that decreasing the proportion of PCL can increase the particle size of the microspheres, ranging from 1 µm to 410 µm.
    Table 1. Effect of PCL ratio on the preparation of golf-type microspheres Compo Composa No. Ratio Ratio Diameter Sample shape | sant nt de A de B (um) microsphere on AB (%) (%) S1-1 PLA PCL 99 1 2-410 Smooth ball S1-2 PLA PCL 90 10 4-390 Golf ball S1-3 PLA PCL 80 20 4-380 Golf ball S1-4 PLA PCL 70 30 2-379 Golf ball S1-5 PLA PCL 60 40 3-350 Golf ball S1-6 PLA PCL 50 50 1311 Golf ball S1-7 PLA PCL 40 60 1-314 Golf ball S1-8 PLA PCL 30 70 1-305 Golf ball S1-9 PLA PCL 20 80 - In pieces without ball shape S1-10 PLA PCL 10 90 - In pieces without ball shape Example 2. Examination on the effect of the molecular weight ratio of materials on the preparation of golf ball type microspheres Step 1: Arrange the polylactic acid component A (molecular weight 100KD, 150KD, 200KD) and the polycaprolactone component B (molecular weight 20KD, 40KD, 60KD, 100KD), with a total weight of 1g, in a mass ratio of 50:50, and dissolve them in the dichloromethane component C of 20 ml to form a biological component of mixed solution D with a concentration of 5%; Step 2: Add component D to 200 ml 0.1% PVA stabilizer solution E component and mix by stirring to form emulsion component F;
    Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder. Observed by scanning electron microscopy, when the molecular weight of component λ PLA is less than 200 KD, the prepared microspheres have a golf ball shape. The particle size of the prepared microspheres is shown in Table 2 by the particle size analyzer. Table 2 shows that the molecular weights of components A and B can change the particle size of the microspheres in the range of 2-760 µm.
    Table 2. Effect of the Molecular Weight Ratio of Materials on the Preparation of Golf Ball-Type Microspheres Component No. Component Weight Weight Diameter Sample Shape | ant molecular molecular (um) microsph on AB of A (KD) area of B era (KD) S2-1 PLA PCL 100 20 2-340 Golf ball s2-2 PLA PCL 100 40 3-380 Golf ball S2- 3 PLA PCL 100 60 2-390 Golf ball s2-4 PLA PCL 100 100 4-410 Golf ball s2-5 PLA PCL 150 20 4-350 Golf ball S2-6 PLA PCL 150 40 4-360 Golf ball s2-7 PLA PCL 150 60 3-390 Golf ball S2-8 PLA PCL 150 100 2-400 Smooth ball S2-9 PLA PCL 200 20 3-370 Smooth ball S2-10 PLA PCL 200 40 3-200 Smooth ball S2 -11 PLA PCL 200 60 3-610 Extended spheroid S2-12 PLA PCL 200 100 4-760 Extended spheroid Example 3. Examination of the effect of the type and proportion of component A on the preparation of golf ball type microspheres Step 1: Arrange component A of different types (including PLA, PLGA and a mixture of different proportions of the above two materials) and component polycaprolactone B (molecular weight 40KD), with a total weight of 1g, in a mass ratio of 50:50, and dissolve them in the com applying 20 ml of dichloromethane C to form a biological component of mixed solution D at a concentration of 5%; Step 2: Add component D to 200 ml 0.1% PVA stabilizer solution E component and mix by stirring to form emulsion component F;
    Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder. Observed by scanning electron microscopy, when component A is a mixture of PLA, and PLGA in different ratios, the prepared microspheres have a golf ball shape. The particle size of the prepared microspheres is shown in Table 2 by the particle size analyzer. Table 2 shows that the change of each component λ has little effect on the particle size of the microspheres and is in the range of 2 µm to 470 µm.
    Table 3. Effect of the types and proportions of component λ on the preparation of golf ball-like microspheres. Component No. Component Report Report Diameter Sample Shape | A ant different rtdeB re microsph lon B materials (%) (um) era (%) S3-1 PLLA PCL 70 30 3-340 Golf ball S3-2 PLLA PCL 50 50 5-310 Golf ball S3-3 PLLA PCL 30 70 3-300 Golf ball
    S3-4 PLGA (LA: GA = 7 PCL 70 30 2-385 Ball of 5:25) golf S3-5 PLGA (LA: GA = 5 PCL 50 50 4-390 Ball of 0:50) golf S3-6 PLGA (LA: GA = 2 PCL 30 70 4-400 Ball of 5:75) golf S3-7 PLA: PLGA (LA: PCL 50:20 30 6-450 Ball of GA = 50: 50) golf S3-8 PLA: PLGA (LA: PCL 33:33 33 4-480 Ball of GA = 50: 50) golf S3-9 PLA: PLGA (LA: PCL 20:50 30 2-440 Ball of GA = 50: 50) golf Example 4. Examination on the effect of the organic solvent species of component C on the preparation of golf ball-type microspheres Step 1: Arrange the polylactic acid component A (molecular weight 150KD) and the polycaprolactone component B (molecular weight 60KD), with a total weight of 1g, are arranged in a mass ratio of 50:50, and dissolve them in the dichloromethane component C of 20 ml to form a biological component of mixed solution D with a concentration of 5%; Step 2: Add component D to 200 ml 0.1% PVA stabilizer solution E component and mix by stirring to form emulsion component F; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder.
    Observation by scanning electron microscopy showed that the type and mixing ratio of the organic solvents of component C did not significantly affect the morphology of the microspheres.
    The particle size of the prepared microspheres is shown in Table 2 by the particle size analyzer.
    Table 2 shows that the change of each component of component λ has little effect on the particle size of the microspheres and is in the range of 3 µm to 470 µm.
    Component No. C Diameter Ratio Sample Shape Component C e (um)… —microsph n (%) era S4-1 Dichloromethane 100 4424 Golf ball S4-2 Trichloromethane 100 4-441 Golf ball S4-3 Acetone 100 4-469 Golf ball S4-4 Dichloromethane: 50: 50: 0 4-378 Chloroform ball: golf acetone S4-5 Dichloromethane: 33:33:33 3-390 Chloroform ball: golf acetone S4-6 Dichloromethane : 0:50: 50 4-342 Chloroform ball: golf acetone Example 5. Examination of the effect of the total material concentration of component D on the preparation of golf ball type microspheres Step 1: Dispose of the polylactic acid component A (molecular weight 100KD) and the polycaprolactone component B (molecular weight 40KD), with a total weight of 1g, in a mass ratio according to 90:10, 80:20, 70:30, 60:40, 50:50, and dissolving them in the 20 ml dichloromethane component C to form a 5% concentration mixed solution biological component D; Step 2: Add component D to 200 ml 0.1% PVA stabilizer solution E component and mix by stirring to form emulsion component F; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in a sterile environment to obtain the golf ball type microspheres in sterile powder form. The prepared microspheres have the appearance of a golf ball obtained by scanning electron microscopy. However, when the composition ratio of PCL is 1%, the microspheres are smooth spherical, indicating that PCL is a key component in the preparation of golf ball type microspheres. The particle size of the prepared microspheres is shown in Table 1 by the particle size analyzer. Table 1 shows that decreasing the proportion of PCL can increase the particle size of the microspheres in the range of 40 to 480 µm.
    Table 5. Effect of Total Material Concentration of Component D on Preparation of Golf Ball-Type Microspheres Diameter Concentration No. Sample Shape | component material (um) microsphere D (%) S5-1 1% - In pieces S5-2 3% 4-310 Golf ball S5-3 5% 4-433 Golf ball S5-4 7% 4-483 Ball S5-5 10% 1-522 Elongated spheroid Example 6. Examination of the effect of the type and concentration of component E of the stabilizer solution on the preparation of golf ball-type microspheres Step 1: Dispose of the polylactic acid component A (molecular weight 150KD) and the polycaprolactone component B (molecular weight 60KD), with a total weight of 1g, in a mass ratio of 50:50, and dissolve them in the dichloromethane component C of 20 ml to form a component biological of mixed solution D with a concentration of 5%; Step 2: Add component D to component E of 200ml 0.1% to 2% PVA, 0.1% to 2% PEG, 0.05% to 2% Tween or 0.1 % to 4% chitosan respectively and mix by stirring to form component F in emulsion; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or buffer as needed, and remove component E from residual stabilizer solution to obtain a golf-like microsphere.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder.
    The type and concentration of component E of the stabilizing solution has little effect on the appearance of golf ball-like microspheres seen under scanning electron microscopy.
    The particle size of the prepared microspheres is shown in Table 6 by the particle size analyzer.
    Table 6 shows that increasing the concentration of the stabilizer causes the particle diameter of the microsphere to shrink, ranging from 2 to 440 µm.
    Table 6. Effect of the type and concentration of component E of the stabilizer solution on the preparation of golf ball type microspheres Component No. of E Concentration Diameter Sample shape (%) (um) microsphere S6-1 PVA 0.10% 5-442 Golf ball S6-2 PVA 1% 2-410 Golf ball S6-3 PVA 2% 2-391 Golf ball S6-4 PEG 0.10% 5-473 Golf ball S6-5 PEG 1 % 4-420 Golf ball S6-6 PEG 2% 3-410 Golf ball S6-7 Tween 80 0.10% 6-472 Golf ball S6-8 Tween 80 1% 4-423 Golf ball S6-9 Tween 80 2% 4—388 Golf ball S6-10 Chitosan 0.10% 5-389 Golf ball S6-11 Chitosan 2% 3-390 Golf ball S6-12 Chitosan 0.04 3-391 Golf ball S6-13 PVA: PEG ( 1: 1) 1% 4-381 Golf ball S6-14 Tween 80: PEG 1% 3-399 Golf ball (1: 1)
    Example 7. Examination on the effect of the stirring and mixing process in step 2 on the preparation of golf ball type microspheres Step 1: Arrange the polylactic acid component A (molecular weight 150KD) and the polycaprolactone component B (molecular weight 60KD), with a total weight of 1g, in a mass ratio of 50:50, and dissolve them in the dichloromethane component C of 20 ml to form a biological component of mixed solution D with a concentration of 5 %; Step 2: Separately add component D to component E of 200 ml at 1% PVA and form component F into an emulsion by magnetic stirring, mechanical stirrer, homogenate mixture; Step 3: Maintain magnetic stirring until the organic solution of component F has completely evaporated to form component G.
    Step 4: Wash component G with water or swab as needed, then remove the residual golf ball.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder.
    Observation by scanning electron microscopy showed that the type and concentration of component E of the stabilizer solution had little effect on the appearance of golf ball-like microspheres. The particle size of the prepared microspheres is shown in Table 5 by the particle size analyzer. Table 5 shows that increasing the concentration of the stabilizer has the effect of reducing the particle diameter of the microsphere, ranging from 1 to 610 µm.
    Table 7. Effect of the stirring and mixing process in step 2 on the preparation of golf ball type microspheres Stirring process number and Diameter Sample shape | mixture (um) microsphere S7-1 Magnetic stirring 4-410 Golf ball S7-2 Mechanical stirring 7-610 Golf ball S7-3 Homogenate mixture 1-5.1 Golf ball Example 8. Examination of the effect of the ratio of PCL molecular weight material (component B) on golf ball-type microsphere degradation Weigh 100 mg of golf-type microsphere samples (S1-1, S1- 2, S1-6, S2-1 and S2-3) having different material ratios and molecular weights in Examples 1 and 2 and immerse them in a 50ml glass jar. Add 10 ml of PBS. Place in a 37 ° C incubator. After some time, collect and centrifuge the sample at 12,000 rpm, lyophilize and weigh. Calculate the residual rate of degradation of the microsphere using the following formula: Residual rate of degradation (%) = total mass of microspheres after degradation / total mass of microspheres before degradation * 100% The release experiment was performed in parallel three times for each sample and the final result was taken as the average of three parallel samples. The results are shown in Figure 2.
    The results show that the higher the proportion of PCL in the microspheres, the faster the rate of degradation of the microspheres; the higher the molecular weight of the PCL, the slower the rate of degradation of the microspheres. Its residual rate of degradation over three months is between 85% and 98%; its residual rate of degradation over six months, between 8% and 95%; its residual rate of degradation over 9 months, between 0% and 90%; its residual rate of degradation over 12 months, between 0% and 80%; its residual rate of degradation over 24 months, between 0% and 60%; its residual rate of degradation over 36 months, between 0% and 7%.
    Example 9. Study of the biocompatibility and cellular behavior of golf ball type microspheres Weigh respectively 10 mg of PCL (component B) of the golf type microsphere samples (samples S1-1 and S1-6) in Example 1 having different ratios of matter and molecular weights for cell-related experiments, respectively. Sterilize the microspheres and place them in a centrifuge tube. To each centrifuge tube, add a 1.0 x 105 number of mouse embryonic fibers (MEFs) from NIH3T3. Grow cells for 1 day, 4 days, and 7 days in a 37 ° C, 5.0% carbon dioxide cell incubator. Perform the cell viability test using the CCK-8 cell viability kit (Tiangen, China). The absorbance at a wavelength of 450 nm reflects the total activity of the cells. The greater the absorbance, the greater the total activity; the smaller the absorbance, the smaller the total activity, the absorbance increases over time, indicating that the cells are proliferating. The results are shown in Table 8: Table 8. Study of the biocompatibility and cellular behaviors of golf ball type microspheres (from the CCK-8 method) Sample | Shape of the day 4th day Te day microsphere S1-1 Smooth ball 0.81 + 0.21 1.01 + 0.21 1.40 + 0.49
    S1-6 Golf ball 1.100.46 1.48 + 0.32 2.01 + 0.55
    From the data of the first day of Table 8, it is known that the MEF NIH3T3 adhered to the golf ball-type microsphere is more developed than that adhered to the smooth spherical microsphere; From day 1 through day 7 data in Table 8, MEF NIH3T3 grows normally on the surface of golf-like microspheres, showing obvious proliferation phenomenon, being more evident than smooth spherical microspheres, indicating that microspheres golf-type have good biocompatibility and a particular structure, which is more conducive to cell adhesion.
    权利要求:
    Claims (9)
    [1]
    1. A golf ball-type degradable microsphere having a micro-topological structure is characterized in that the microsphere is composed of a mixture of component A and component B, and the surface has a concave or wrinkled structure towards the surface. interior spherical or ellipsoidal. It has a ball of particle size between 1 μm and 600 μm; Among them, component B is PCL and component A is other polymeric materials.
    [2]
    2. A golf ball-type degradable microsphere according to claim 1, the golf ball-type degradable microsphere having a micro-topological structure has a three-month residual degradation rate of 85% to 98%; its residual degradation rate over 6 months is between 8% and 95%; its residual rate of degradation over 9 months is between 0% and 90%; its residual rate of degradation over 12 months is between 0% and 80%; its residual degradation rate over 24 months is between 0% and 60% and its residual degradation rate over 36 months, between 0% and 7%.
    [3]
    3. A golf ball-type degradable microsphere according to claim 1, the golf ball-type degradable microsphere having micro-topological structure has good biocompatibility, and cells can adhere and grow on the surface thereof. this.
    [4]
    4. A golf ball-type degradable microsphere according to claim 1, the golf ball-type degradable microsphere having a micro-topological structure in which the PCL has a molecular weight of 20 KD to 100 KD.
    [5]
    5. Process for preparing degradable microsphere of the golf ball type having micro-topological structure, is characterized in that the process comprises the following steps: Step 1: Dissolving component A and component B in the organic solvent component. C to form a component of mixed solution D; Step 2: Add component D to stabilizer solution component E and mix by stirring to form emulsion component F; Step 3: Continue to stir and mix until the organic solution of component F is completely volatilized to form component G.
    Step 4: Wash component G with water or swab as needed, then remove the residual golf ball.
    Step 5: Sterilize and lyophilize the golf ball type microspheres in sterile environment to obtain golf ball type microspheres as sterile powder.
    [6]
    A process for preparing a degradable golf ball type microsphere having a micro-topological structure according to claim 5, wherein the component of the organic solvent component C is one of the following: dichloromethane, chloroform and acetone, or a compound. mixture of two or more.
    [7]
    A process for preparing a degradable golf ball-type microsphere having a micro-topological structure according to claim 5 wherein the mixed solution component D has a total material concentration of 5wt% to 20wt%, and the mass ratio of the material. Component A to Component B is 99: 1 to 50:50.
    [8]
    A process for preparing a degradable golf ball type microsphere having a micro-topological structure according to claim 5, wherein the stabilizer solution component E is PVA, PEG, or a mixture of the above components, with a total concentration of 0.02wt% to 3wt%, or also with other stabilizers or surfactants.
    [9]
    9. A process for preparing a degradable golf ball type microsphere according to claim 5, having a micro-topological structure in which the stirring and mixing in step 2 and step 3 is carried out using a magnetic stirrer. , a mechanical stirrer and a uniform filter: it can to mix the mixture in suspension, it is also possible to choose a similar method to mix the oil and water phases.
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    同族专利:
    公开号 | 公开日
    CN110681323A|2020-01-14|
    CN110681323B|2021-12-21|
    NL2023952B1|2021-05-04|
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    法律状态:
    2020-12-04| FG| Patent granted|Effective date: 20201027 |
    优先权:
    申请号 | 申请日 | 专利标题
    CN201910789298.1A|CN110681323B|2019-08-26|2019-08-26|Golf ball type degradable microsphere with micro-topological structure and preparation method thereof|
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