WO2022099471A1 - 海藻酸壳聚糖可塑性支架材料的制备方法 - Google Patents
海藻酸壳聚糖可塑性支架材料的制备方法 Download PDFInfo
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- 229920001661 Chitosan Polymers 0.000 title claims abstract description 31
- 239000000463 material Substances 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 239000004005 microsphere Substances 0.000 claims abstract description 67
- 238000003756 stirring Methods 0.000 claims abstract description 40
- 239000011258 core-shell material Substances 0.000 claims abstract description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- 238000000967 suction filtration Methods 0.000 claims abstract description 21
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims abstract description 19
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 19
- 239000000661 sodium alginate Substances 0.000 claims abstract description 19
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 12
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 12
- 238000005406 washing Methods 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 229960000583 acetic acid Drugs 0.000 claims abstract description 6
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 6
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims abstract description 5
- 235000010410 calcium alginate Nutrition 0.000 claims abstract description 3
- 239000000648 calcium alginate Substances 0.000 claims abstract description 3
- 229960002681 calcium alginate Drugs 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 239000008223 sterile water Substances 0.000 claims description 19
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 7
- 229940072056 alginate Drugs 0.000 claims description 7
- 235000010443 alginic acid Nutrition 0.000 claims description 7
- 229920000615 alginic acid Polymers 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims 2
- 230000008014 freezing Effects 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 238000013268 sustained release Methods 0.000 abstract description 16
- 239000012730 sustained-release form Substances 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 5
- 238000004108 freeze drying Methods 0.000 abstract description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract description 3
- 239000011734 sodium Substances 0.000 abstract description 3
- 229910052708 sodium Inorganic materials 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000004140 cleaning Methods 0.000 abstract 1
- 238000002791 soaking Methods 0.000 abstract 1
- 210000000988 bone and bone Anatomy 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 241001474374 Blennius Species 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000003181 biological factor Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 206010056559 Graft infection Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
Definitions
- the present invention relates to a preparation method of alginate chitosan plastic scaffold material.
- the scaffold material with sustained-release system can carry a variety of drugs (or biological factors), providing seed cells with a growth environment that is closer to natural cell osteogenesis.
- drugs or biological factors
- the seed cells can be artificially regulated
- slow-release drugs such as selectively carrying slow-release antibiotics to prevent tissue engineering. Bone infection, carrying VEGF to promote cell osteogenesis and ingrowth of surrounding small blood vessels, etc.
- the sustained-release system With the addition of the sustained-release system, the structure of the new scaffold material will become more complex, and the physicochemical properties will change accordingly. Therefore, exploring the organic combination of sustained-release system and scaffold material provides a new idea for the reconstruction of scaffold material structure and the improvement of scaffold material performance.
- the purpose of the present invention is to provide a preparation method of alginate chitosan plastic scaffold material.
- a preparation method of alginate chitosan plastic scaffold material comprising the steps of: extracting 10-20 parts of sodium alginate solution with a mass fraction of 4% with a syringe, using a 5-gauge needle, at 25-35 DEG C, at 50 Drop into 35-45 parts of calcium chloride solution with a mass fraction of 15% at a constant rate of drop/min, the needle is 11-13cm away from the liquid surface, stir at a speed of 350r/min for 35-45min, remove the residual liquid by suction filtration, and use no After washing with bacteria water, collect the microspheres to obtain calcium alginate CA core spheres; under stirring conditions, add CA core spheres into 30-40 parts of chitosan solution with a mass fraction of 1%, and stir at a speed of 500r/min 15-25min, remove the residual liquid by suction filtration, wash the microspheres with sterile water, and collect the microspheres to obtain the CA-CS double-layer core-shell structure microspheres; under stirring conditions, the
- the needle is 12 cm away from the liquid surface.
- stirring is performed at a speed of 350r/min for 40min.
- the pH is adjusted to 4.2.
- a NaOH solution with a concentration of 1 mol/L is added dropwise to adjust the pH value to 5.2.
- the method for synthesizing a new sustained-release microsphere-type scaffold is feasible, and it is also a combination of the sustained-release system and the existing porous scaffold material.
- the idea of organically combining the preparation of new scaffold materials provides an example.
- a preparation method of alginate chitosan plastic scaffold material comprising the steps of: extracting 15 parts of sodium alginate solution with a mass fraction of 4% with a syringe, using a 5-gauge needle, at 30 DEG C, at a concentration of 50 drops/min Drop into 40 parts of calcium chloride solution with a mass fraction of 15% at a constant speed, the needle is 12cm away from the liquid surface, stir at a speed of 350r/min for 40min, remove the residual liquid by suction filtration, wash with sterile water and collect the microspheres to obtain seaweed Calcium acid CA core balls; under stirring conditions, add CA core balls into 35 parts of chitosan solution with a mass fraction of 1%, stir at 500r/min for 20min, remove the residual liquid by suction filtration, use sterile water After washing, the microspheres were collected to obtain CA-CS double-layer core-shell structure microspheres; under stirring conditions, CA-CS double-layer core-shell structure microspheres were added to 35 parts of 1% sodium
- sustained-release microspheres After the sustained-release microspheres are evenly distributed, freeze at -20 °C for 48 hours, freeze-dry at -80 °C, and then soak in calcium chloride solution with a mass fraction of 3% for 2.5 hours.
- the bacteria were washed 5 times with deionized water, frozen at -20°C for 48 hours, and then freeze-dried at -80°C; each raw material was in parts by weight.
- a preparation method of alginate chitosan plastic scaffold material comprising the steps of: extracting 10 parts of sodium alginate solution with a mass fraction of 4% with a syringe, and using a 5-gauge needle at 25° C. at 50 drops/min.
- a preparation method of alginate chitosan plastic scaffold material comprising the steps of: extracting 20 parts of sodium alginate solution with a mass fraction of 4% with a syringe, and using a 5 gauge needle at 35° C. at 50 drops/min.
- sustained-release microspheres After the sustained-release microspheres are evenly distributed, freeze at -20 °C for 49 hours, freeze-dry at -80 °C, and then soak in calcium chloride solution with a mass fraction of 3% for 3 hours. Washed with deionized water for 6 times, frozen at -20°C for 49 hours, and then freeze-dried at -80°C; all raw materials are in parts by weight.
- the method for synthesizing a new sustained-release microsphere-type scaffold is feasible, and it is also a combination of the sustained-release system and the existing porous scaffold material.
- the idea of organically combining the preparation of new scaffold materials provides an example.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Medicinal Preparation (AREA)
Abstract
公开了一种海藻酸壳聚糖可塑性支架材料的制备方法，步骤如下：用注射器抽取海藻酸钠溶液滴入氯化钙溶液中，抽滤，洗涤，得海藻酸钙CA核心球；将CA核心球加入壳聚糖溶液中，抽滤，洗涤，得双层核壳结构微球；将双层核壳结构微球加入海藻酸钠溶液中，抽滤，洗涤，得三层核壳结构微球；将三层核壳结构微球加入壳聚糖溶液中，抽滤，洗涤，得四层核壳结构微球，冷冻干燥；向海藻酸钠溶液中滴加冰醋酸溶液，加入壳聚糖，溶解后滴加NaOH溶液，搅拌，加入缓释微球，冷冻干燥，然后用氯化钙溶液浸泡，清洗，冷冻干燥即得。将以海藻酸钠-壳聚糖为原料制备的缓释微球结构与多孔海绵状结构相结合，合成缓释微球型支架材料的方法可行。
Description
本发明涉及一种海藻酸壳聚糖可塑性支架材料的制备方法。
寻找理想的人工骨材料用于临床修复一直是骨科研究领域十分活跃的课题。组织工程学通过种子细胞体外扩增并复合于支架材料构建有生物活性的骨移植物，弥补了单纯异体骨无直接成骨活性的不足。同时，在骨移植过程中，新移植的组织工程骨短期内不能与宿主建立良好的血供关系，易发生营养障碍，并且手术存在创口且骨缺损处存在感染或潜在感染几率，血液中的药物很难在缺血局部形成有效的杀菌浓度，潜在的细菌大量繁殖引起移植物的感染，导致移植失败。因此，在构建组织工程骨的研究中，能够搭载药物并具有良好缓释性能的支架材料成为热门的研究方向。壳聚糖和海藻酸钠是近年来在生物医药、组织工程领域得到广泛应用的天然生物高分子材料，具有很好的相容性与可降解性，对人体毒副作用小。
具有缓释系统的支架材料可搭载多种药物(或生物因子)，为种子细胞提供更加接近于自然细胞成骨的生长环境，通过调整搭载的药物(或生物因子)的种类可人为调控种子细胞的成骨过程，针对组织工程骨缺乏血供，血液中药物难以抵达和聚集等问题，也可以通过搭载缓释药物的方式直接作用于组织工程骨内部，如选择性搭载缓释抗生素预防组织工程骨感染，搭载VEGF以促进细胞成骨及周围小血管的长入等。随着缓释系统的加入，新型支架材料的结构也将变得更加复杂，理化性质随之发生变化。因此，探索缓释系统与支架材料的有机结合为支架材料结构的改建及支架材料性能的提升提供了一个新的思路。
发明内容
本发明的目的在于提供一种海藻酸壳聚糖可塑性支架材料的制备方法。
本发明通过下面技术方案实现：
一种海藻酸壳聚糖可塑性支架材料的制备方法，包括如下步骤：用注射器抽取10-20份质量分数为4％的海藻酸钠溶液，用5号针头，在25-35℃下，以50滴/min的速度匀速滴入35-45份质量分数为15％的氯化钙溶液中，针头距液面11-13cm，以350r/min速度搅拌35-45min，抽滤除去残液，用无菌水洗涤后收集微球，得到海藻酸钙CA核心球；在搅拌条件下，将CA核心球逐粒加入30-40份质量分数为1％的壳聚糖溶液中，以500r/min速度搅拌15-25min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS双层核壳结构微球；在搅拌条件下，将CA-CS双层核壳结构微球逐粒加入30-40份质量分数1％的海藻酸钠溶液中，以500r/min速度搅拌3-5min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS-SA三 层核壳结构微球；在搅拌条件下，将CA-CS-SA三层核壳结构微球逐粒加入30-40份质量分数1％的壳聚糖溶液中，以500r/min速度搅拌15-25min，抽滤除去残液，用无菌水洗涤后收集微球，即得CA-CS-SA-CS四层核壳结构微球，于-80℃冷冻干燥；向60-70份质量分数为2％的海藻酸钠溶液中滴加体积分数为1％的冰醋酸溶液，调节pH为4.1-4.3，加入35-45份壳聚糖，充分溶解后，滴加浓度为1mol/L的NaOH溶液调pH值至5.1-5.3，以1000r/min速度搅拌35-45min，加入20-30份冻干后的缓释微球，以300r/min速度搅拌15-25min待缓释微球分布均匀后，于-20℃冷冻47-49h后于-80℃冷冻干燥，然后用质量分数为3％的氯化钙溶液浸泡2-3h，取出后用等量无菌去离子水清洗4-6次，-20℃冷冻47-49h后于-80℃冷冻干燥即得；各原料均为重量份。
优选地，所述的制备方法中，针头距液面12cm。
优选地，所述的制备方法中，以350r/min速度搅拌40min。
优选地，所述的制备方法中，调节pH为4.2。
优选地，所述的制备方法中，滴加浓度为1mol/L的NaOH溶液调pH值至5.2。
优选地，所述的制备方法中，于-20℃冷冻48h。
本发明技术效果：
将以海藻酸钠-壳聚糖为原料制备的缓释微球结构与多孔海绵状结构相结合，合成新型缓释微球型支架材料的方法可行，也为缓释系统与现有多孔支架材料有机结合制备新型支架材料的思路提供了一个实例。
下面结合实施例具体介绍本发明的实质性内容。
实施例1
一种海藻酸壳聚糖可塑性支架材料的制备方法，包括如下步骤：用注射器抽取15份质量分数为4％的海藻酸钠溶液，用5号针头，在30℃下，以50滴/min的速度匀速滴入40份质量分数为15％的氯化钙溶液中，针头距液面12cm，以350r/min速度搅拌40min，抽滤除去残液，用无菌水洗涤后收集微球，得到海藻酸钙CA核心球；在搅拌条件下，将CA核心球逐粒加入35份质量分数为1％的壳聚糖溶液中，以500r/min速度搅拌20min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS双层核壳结构微球；在搅拌条件下，将CA-CS双层核壳结构微球逐粒加入35份质量分数1％的海藻酸钠溶液中，以500r/min速度搅拌4min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS-SA三层核壳结构微球；在搅拌条件下，将CA-CS-SA三层核壳结构微球逐粒加入35份质量分数1％的壳聚糖溶液中，以500r/min速度搅拌20min，抽滤除去残液，用无菌水洗涤后收集微球，即得CA-CS-SA-CS四层核壳结构 微球，于-80℃冷冻干燥；向65份质量分数为2％的海藻酸钠溶液中滴加体积分数为1％的冰醋酸溶液，调节pH为4.2，加入40份壳聚糖，充分溶解后，滴加浓度为1mol/L的NaOH溶液调pH值至5.2，以1000r/min速度搅拌40min，加入25份冻干后的缓释微球，以300r/min速度搅拌20min待缓释微球分布均匀后，于-20℃冷冻48h后于-80℃冷冻干燥，然后用质量分数为3％的氯化钙溶液浸泡2.5h，取出后用等量无菌去离子水清洗5次，-20℃冷冻48h后于-80℃冷冻干燥即得；各原料均为重量份。
实施例2
一种海藻酸壳聚糖可塑性支架材料的制备方法，包括如下步骤：用注射器抽取10份质量分数为4％的海藻酸钠溶液，用5号针头，在25℃下，以50滴/min的速度匀速滴入35份质量分数为15％的氯化钙溶液中，针头距液面11cm，以350r/min速度搅拌35min，抽滤除去残液，用无菌水洗涤后收集微球，得到海藻酸钙CA核心球；在搅拌条件下，将CA核心球逐粒加入30份质量分数为1％的壳聚糖溶液中，以500r/min速度搅拌15min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS双层核壳结构微球；在搅拌条件下，将CA-CS双层核壳结构微球逐粒加入30份质量分数1％的海藻酸钠溶液中，以500r/min速度搅拌3min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS-SA三层核壳结构微球；在搅拌条件下，将CA-CS-SA三层核壳结构微球逐粒加入30份质量分数1％的壳聚糖溶液中，以500r/min速度搅拌15min，抽滤除去残液，用无菌水洗涤后收集微球，即得CA-CS-SA-CS四层核壳结构微球，于-80℃冷冻干燥；向60份质量分数为2％的海藻酸钠溶液中滴加体积分数为1％的冰醋酸溶液，调节pH为4.1，加入35份壳聚糖，充分溶解后，滴加浓度为1mol/L的NaOH溶液调pH值至5.1，以1000r/min速度搅拌35min，加入20份冻干后的缓释微球，以300r/min速度搅拌15min待缓释微球分布均匀后，于-20℃冷冻47h后于-80℃冷冻干燥，然后用质量分数为3％的氯化钙溶液浸泡2h，取出后用等量无菌去离子水清洗4次，-20℃冷冻47h后于-80℃冷冻干燥即得；各原料均为重量份。
实施例3
一种海藻酸壳聚糖可塑性支架材料的制备方法，包括如下步骤：用注射器抽取20份质量分数为4％的海藻酸钠溶液，用5号针头，在35℃下，以50滴/min的速度匀速滴入45份质量分数为15％的氯化钙溶液中，针头距液面13cm，以350r/min速度搅拌45min，抽滤除去残液，用无菌水洗涤后收集微球，得到海藻酸钙CA核心球；在搅拌条件下，将CA核心球逐粒加入40份质量分数为1％的壳聚糖溶液中，以500r/min速度搅拌25min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS双层核壳结构微球；在搅拌条件下，将CA-CS双层核壳结构微球逐粒加入40份质量分数1％的海藻酸钠溶液中，以500r/min速度搅拌5min，抽 滤除去残液，用无菌水洗涤后收集微球，得到CA-CS-SA三层核壳结构微球；在搅拌条件下，将CA-CS-SA三层核壳结构微球逐粒加入40份质量分数1％的壳聚糖溶液中，以500r/min速度搅拌25min，抽滤除去残液，用无菌水洗涤后收集微球，即得CA-CS-SA-CS四层核壳结构微球，于-80℃冷冻干燥；向70份质量分数为2％的海藻酸钠溶液中滴加体积分数为1％的冰醋酸溶液，调节pH为4.3，加入45份壳聚糖，充分溶解后，滴加浓度为1mol/L的NaOH溶液调pH值至5.3，以1000r/min速度搅拌45min，加入30份冻干后的缓释微球，以300r/min速度搅拌25min待缓释微球分布均匀后，于-20℃冷冻49h后于-80℃冷冻干燥，然后用质量分数为3％的氯化钙溶液浸泡3h，取出后用等量无菌去离子水清洗6次，-20℃冷冻49h后于-80℃冷冻干燥即得；各原料均为重量份。
将以海藻酸钠-壳聚糖为原料制备的缓释微球结构与多孔海绵状结构相结合，合成新型缓释微球型支架材料的方法可行，也为缓释系统与现有多孔支架材料有机结合制备新型支架材料的思路提供了一个实例。
Claims (6)
- 一种海藻酸壳聚糖可塑性支架材料的制备方法，其特征在于包括如下步骤：用注射器抽取10-20份质量分数为4％的海藻酸钠溶液，用5号针头，在25-35℃下，以50滴/min的速度匀速滴入35-45份质量分数为15％的氯化钙溶液中，针头距液面11-13cm，以350r/min速度搅拌35-45min，抽滤除去残液，用无菌水洗涤后收集微球，得到海藻酸钙CA核心球；在搅拌条件下，将CA核心球逐粒加入30-40份质量分数为1％的壳聚糖溶液中，以500r/min速度搅拌15-25min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS双层核壳结构微球；在搅拌条件下，将CA-CS双层核壳结构微球逐粒加入30-40份质量分数1％的海藻酸钠溶液中，以500r/min速度搅拌3-5min，抽滤除去残液，用无菌水洗涤后收集微球，得到CA-CS-SA三层核壳结构微球；在搅拌条件下，将CA-CS-SA三层核壳结构微球逐粒加入30-40份质量分数1％的壳聚糖溶液中，以500r/min速度搅拌15-25min，抽滤除去残液，用无菌水洗涤后收集微球，即得CA-CS-SA-CS四层核壳结构微球，于-80℃冷冻干燥；向60-70份质量分数为2％的海藻酸钠溶液中滴加体积分数为1％的冰醋酸溶液，调节pH为4.1-4.3，加入35-45份壳聚糖，充分溶解后，滴加浓度为1mol/L的NaOH溶液调pH值至5.1-5.3，以1000r/min速度搅拌35-45min，加入20-30份冻干后的缓释微球，以300r/min速度搅拌15-25min待缓释微球分布均匀后，于-20℃冷冻47-49h后于-80℃冷冻干燥，然后用质量分数为3％的氯化钙溶液浸泡2-3h，取出后用等量无菌去离子水清洗4-6次，-20℃冷冻47-49h后于-80℃冷冻干燥即得；各原料均为重量份。
- 根据权利要求1所述的制备方法，其特征在于：针头距液面12cm。
- 根据权利要求1所述的制备方法，其特征在于：以350r/min速度搅拌40min。
- 根据权利要求1所述的制备方法，其特征在于：调节pH为4.2。
- 根据权利要求1所述的制备方法，其特征在于：滴加浓度为1mol/L的NaOH溶液调pH值至5.2。
- 根据权利要求1所述的制备方法，其特征在于：于-20℃冷冻48h。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115430372A (zh) * | 2022-08-18 | 2022-12-06 | 中国地质大学（武汉） | 一种三维多孔凹凸棒石微球及其制备方法和应用 |
| CN115869228A (zh) * | 2022-12-07 | 2023-03-31 | 苏州猫尔科技有限公司 | 一种纳米缓释微囊及其制备方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150224221A1 (en) * | 2012-08-31 | 2015-08-13 | Chung-Ang University Industry-Academic Cooperation Foundation | Method for preparing microspheres for emboli, and method for preparing microspheres to which drug-containing carrier is bound |
| CN107050509A (zh) * | 2017-05-08 | 2017-08-18 | 吉林大学 | 一种具有搭载多种药物功能的可塑性缓释微球型支架材料及其制备方法 |
| CN107753934A (zh) * | 2016-08-18 | 2018-03-06 | 温州医科大学 | 包载SA‑mGM‑CSF或/和SA‑hTNFα的生物素化壳聚糖‑海藻酸钙微球的制备 |
| CN108451925A (zh) * | 2018-04-16 | 2018-08-28 | 中南大学 | 一种用于载药的空心缓释微球及其制备方法 |
| US10569253B1 (en) * | 2017-08-21 | 2020-02-25 | University Of Puerto Rico | Synthesis of biocomposite alginate-chitosan-magnetite nanoparticle beads for removal of organic persistent contaminants from water systems |
| CN111346263A (zh) * | 2020-04-22 | 2020-06-30 | 吉林大学 | 一种具有抗感染及骨形成双功能的无菌骨支架材料及其制备方法 |
-
2020
- 2020-11-10 WO PCT/CN2020/127851 patent/WO2022099471A1/zh active Application Filing
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150224221A1 (en) * | 2012-08-31 | 2015-08-13 | Chung-Ang University Industry-Academic Cooperation Foundation | Method for preparing microspheres for emboli, and method for preparing microspheres to which drug-containing carrier is bound |
| CN107753934A (zh) * | 2016-08-18 | 2018-03-06 | 温州医科大学 | 包载SA‑mGM‑CSF或/和SA‑hTNFα的生物素化壳聚糖‑海藻酸钙微球的制备 |
| CN107050509A (zh) * | 2017-05-08 | 2017-08-18 | 吉林大学 | 一种具有搭载多种药物功能的可塑性缓释微球型支架材料及其制备方法 |
| US10569253B1 (en) * | 2017-08-21 | 2020-02-25 | University Of Puerto Rico | Synthesis of biocomposite alginate-chitosan-magnetite nanoparticle beads for removal of organic persistent contaminants from water systems |
| CN108451925A (zh) * | 2018-04-16 | 2018-08-28 | 中南大学 | 一种用于载药的空心缓释微球及其制备方法 |
| CN111346263A (zh) * | 2020-04-22 | 2020-06-30 | 吉林大学 | 一种具有抗感染及骨形成双功能的无菌骨支架材料及其制备方法 |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115430372A (zh) * | 2022-08-18 | 2022-12-06 | 中国地质大学（武汉） | 一种三维多孔凹凸棒石微球及其制备方法和应用 |
| CN115430372B (zh) * | 2022-08-18 | 2023-08-04 | 中国地质大学（武汉） | 一种三维多孔凹凸棒石微球及其制备方法和应用 |
| CN115869228A (zh) * | 2022-12-07 | 2023-03-31 | 苏州猫尔科技有限公司 | 一种纳米缓释微囊及其制备方法 |
| CN115869228B (zh) * | 2022-12-07 | 2023-11-21 | 苏州猫尔科技有限公司 | 一种纳米缓释微囊及其制备方法 |
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