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Alginate-epsilon-polylysine microcapsules and preparation and application thereof

A polylysine microcapsule, alginate gel technology, applied in microcapsule preparation, microsphere preparation, microcapsule and other directions, can solve the limitation of sodium alginate/α-polylysine microcapsule application, biological Poor compatibility, high price and other problems, to achieve the effect of superior membrane strength, low cost, and good biocompatibility

Inactive Publication Date: 2011-06-22
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the many biological microcapsules, sodium alginate / polylysine microcapsules are used more, and the microcapsule membrane material is chemically synthesized α-polylysine (the amide bond between lysine residues is made of α-amino and α-carboxyl condensation), but due to the high price of α-polylysine (300-400US$ / g), and the inherent poor biocompatibility of the material, it has certain toxicity, which greatly limits the use of algae. The clinical application of sodium lysate / α-polylysine microcapsules [Strand B L, Ryan TL, Veld P I, et al. Cell Transplant., 2001, 10: 263-275]

Method used

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  • Alginate-epsilon-polylysine microcapsules and preparation and application thereof
  • Alginate-epsilon-polylysine microcapsules and preparation and application thereof
  • Alginate-epsilon-polylysine microcapsules and preparation and application thereof

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Effect test

Embodiment 1

[0038] 1) Using high-voltage electrostatic method [Qu Beibei, Yu Weiting, Liu Xiudong, etc., preparation of monodisperse calcium alginate microgel beads by high-voltage electrostatic method, Acta Chemical Industry, 2005, 56(8): 1547] to prepare embedding Calcium alginate gel microspheres with CHO cells, the initial cell seeding density was 1×10 6 / mL sodium alginate solution.

[0039] 2) Immerse the calcium alginate gel microspheres prepared above into 0.01% (w / v), pH5.5, ε-polylysine / normal saline solution, CHO / calcium alginate gel microspheres and ε - The volume ratio of PLL solution was 1:40, reacted for 60 minutes to prepare ε-AP microcapsules, and then washed 3 times with physiological saline.

[0040] 3) Immerse the ε-AP microcapsules prepared above in a sodium alginate / 0.9% (w / v) NaCl solution with a concentration of 0.05% (w / v), CHO / ε-AP microcapsules and sodium alginate solution The volume ratio was 1:40, and the reaction was carried out for 10 minutes to obtain ε-A...

Embodiment 2

[0045] 1) Calcium alginate gel microspheres embedded with hepatocytes were prepared, and the initial cell seeding density was 1×10 6 / mL sodium alginate solution.

[0046] 2) Immerse the above-mentioned calcium alginate gel microspheres into 0.1% (w / v), pH6.5, ε-polylysine / normal saline solution, and hepatocytes / calcium alginate gel microspheres and The volume ratio of ε-PLL solution was 1:20, and reacted for 15 minutes to prepare ε-AP microcapsules, which were then washed 3 times with normal saline.

[0047] 3) The ε-AP microcapsules prepared above were immersed in the sodium alginate / 0.9% (w / v) NaCl solution with a concentration of 0.1% (w / v), and the liver cells / ε-AP microcapsules and sodium alginate The volume ratio of the solution was 1:20, and the reaction was carried out for 15 minutes to obtain ε-APA microcapsules, which were washed with physiological saline for 3 times.

[0048] 4) Immerse the above-prepared ε-APA microcapsules in 55 mmol / L sodium citrate solution, ...

Embodiment 3

[0052] 1) Prepare calcium alginate gel microspheres embedded with embryonic stem cells (ES), and the initial cell seeding density is 1×10 7 / mL sodium alginate solution.

[0053] 2) Immerse the calcium alginate gel microspheres prepared above into 0.2% (w / v), pH7.4, ε-polylysine / normal saline solution, ES / calcium alginate gel microspheres and ε - The volume ratio of the PLL solution was 1:5, reacted for 15 minutes to prepare ε-AP microcapsules, and then washed 3 times with physiological saline.

[0054] 3) Immerse the ε-AP microcapsules prepared above in a sodium alginate / 0.9% (w / v) NaCl solution with a concentration of 0.2% (w / v), ES / ε-AP microcapsules and sodium alginate solution The volume ratio was 1:5, and the reaction was carried out for 10 minutes to obtain ε-APA microcapsules, which were washed with normal saline for 3 times.

[0055] 4) Immerse the above-prepared ε-APA microcapsules in 55 mmol / L sodium citrate solution, the volume ratio of ES / ε-APA microcapsules to ...

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Abstract

The invention relates to a bioactive substance included alginate microcapsule product. The invention is characterized in that: the microcapsule product is a spherical microcapsule with diameter of 100 to 1,000 microns, and the structure of the microcapsule product comprises a microcapsule film and a core, wherein the microcapsule film is a polyelectrolyte composite hydrogel film formed by electrostatic complexing reaction of two macromolecular materials, namely alginate and epsilon-polylysine; and the core is a liquid or hydrogel environment containing a bioactive substance. The microcapsule product is mainly applied to cell transplantation, cell culture and included carriers of bioactive substances such as protein, polypeptide, enzyme, nucleic acid and the like.

Description

technical field [0001] The invention relates to a microcapsule product, in particular to an alginate-ε-polylysine microcapsule product used for embedding biologically active substances. Background technique [0002] In the 1960s, Chang reported semipermeable membrane microcapsules, pointing out that bioactive substances and cells such as proteins and enzymes could be embedded in them, which could maintain the activity of biological substances [Chang TMS.Semipermeable microcapsules, Science, 1964, 146: 524-525 ]. In the early 1980s, Lim and Sun successfully prepared sodium alginate / α-polylysine (alginate / α-polylysine) semipermeable membrane microcapsules (referred to as α -APA microcapsules), encapsulated Wistar rat islet cells and transplanted into diabetic WistarLewis rats, secreted and released insulin to regulate blood sugar [Lim F, Sun A M. Microencapsulated islets bioartificial endocrine pancreas, Science, 1980, 210: 908 -910]. This has promoted the rapid development...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J13/02A61K9/50A61K9/52A61K47/36
CPCA61K9/5036A61K2035/128A61K9/5052B01J13/10
Inventor 马小军马颖张英于炜婷朱静谢红国
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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