CN100558408C - Calcium alginate gel beads with porous calcium carbonate microspheres as shell and preparation method thereof - Google Patents
Calcium alginate gel beads with porous calcium carbonate microspheres as shell and preparation method thereof Download PDFInfo
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- CN100558408C CN100558408C CNB2006101242037A CN200610124203A CN100558408C CN 100558408 C CN100558408 C CN 100558408C CN B2006101242037 A CNB2006101242037 A CN B2006101242037A CN 200610124203 A CN200610124203 A CN 200610124203A CN 100558408 C CN100558408 C CN 100558408C
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- calcium carbonate
- carbonate microspheres
- porous calcium
- gel beads
- sodium alginate
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Abstract
本发明涉及一种多孔碳酸钙微球为壳层的海藻酸钙凝胶珠的制备方法，是将海藻酸钠水相分散到含有多孔碳酸钙微球的油相，经乳化形成油包水乳液；多孔碳酸钙微球吸附到乳滴表面，形成壳层，稳定乳滴；加入葡萄糖酸内脂水溶液进行海藻酸钠凝胶化反应。本发明能够简单、大量制备以多孔碳酸钙微球为壳以海藻酸钙凝胶为核的微珠。The invention relates to a method for preparing calcium alginate gel beads with porous calcium carbonate microspheres as the shell layer. The aqueous phase of sodium alginate is dispersed into the oil phase containing porous calcium carbonate microspheres, and then emulsified to form a water-in-oil emulsion. ; Porous calcium carbonate microspheres are adsorbed to the surface of the emulsion droplet to form a shell to stabilize the emulsion droplet; add gluconolactone aqueous solution to carry out gelation reaction of sodium alginate. The invention can simply and massively prepare microbeads with porous calcium carbonate microspheres as the shell and calcium alginate gel as the core.
Description
Technical Field
The invention relates to a controlled release carrier in the field of biomedicine, in particular to a calcium alginate gel bead with porous calcium carbonate microspheres as shell layers and a preparation method thereof.
Background
The calcium alginate gel beads are commonly used cell and protein immobilization materials at present, particularly microcapsules coated with high polymer material films (such as polylysine and chitosan) are used as an immune isolation tool for cell transplantation and a controlled release carrier of bioactive substances of proteins and polypeptides, and have great application prospects in the field of biomedicine. The calcium alginate gel beads are prepared by crosslinking calcium ion with sodium alginate. Among the methods for preparing calcium alginate gel beads reported so far, the electrostatic method (Canadian patent No.1241598) is to extrude a sodium alginate solution through a needle and drop the sodium alginate solution into a calcium chloride solution under the action of an electric field to form calcium alginate gel beads; the emulsification method (Drug J. Microencapsulation, 1992, 9: 309-316) is to prepare calcium alginate gel beads by secondary emulsification of sodium alginate and calcium chloride solution in an organic solvent; the emulsification/internal gelation method (method approach appl. Microbiol. Biotechnol., 1992, 38: 39-45; Physichemistry appl. Microbiol. Biotechnol., 1995, 43: 644-650; Chinese patent 01104365.2; Chinese patent 01109449.4) is to prepare calcium alginate gel beads by using an insoluble calcium salt instead of a calcium chloride solution. The calcium alginate gel beads prepared by the method have the common defects that the surface strength of the gel beads is not high, the gel beads are easy to crack, and the actual using effect of the gel beads is influenced.
Disclosure of Invention
The invention aims to provide a preparation method of calcium alginate gel beads with porous calcium carbonate microspheres as shell layers aiming at the defects of the prior art, and the obtained calcium alginate gel beads have good surface strength and can be well applied to the field of biomedicine.
The invention also aims to provide calcium alginate gel beads taking the porous calcium carbonate microspheres prepared by the method as shell layers.
The invention relates to a preparation method of calcium alginate gel beads with porous calcium carbonate microspheres as shell layers, which comprises the following steps:
(1) dispersing a sodium alginate aqueous phase into an oil phase containing porous calcium carbonate microspheres, and emulsifying to form a water-in-oil emulsion;
(2) adding aqueous solution of gluconolactone to carry out gelation reaction of sodium alginate.
In the step (1), the concentration of the sodium alginate aqueous phase is 0.5-3% by mass; the oil phase is liquid paraffin, hexane, isooctane, decane or sunflower seed oil; the particle size of the porous calcium carbonate microspheres is 1-10 microns.
Wherein the weight ratio of the porous calcium carbonate microspheres to the sodium alginate aqueous solution is 1: 20-35.
The volume ratio of the water phase to the oil phase is 1: 2-8.
In the step (2), the concentration of the aqueous solution of the gluconolactone is 0.1-0.3 g/ml, and the weight ratio of the aqueous solution of the gluconolactone to the aqueous solution of the sodium alginate is 1: 10-40.
For better emulsification, in the step (1), stirring is carried out at 50-300 rpm for 1-30 minutes during emulsification.
In order to complete the reaction, in step (2), the reaction is carried out while stirring.
Compared with the prior art, the invention has the following differences and advantages:
the method of the invention is similar to the existing emulsification/internal gelation method in that insoluble calcium salt is adopted to replace calcium chloride solution to prepare calcium alginate gel beads.
Except that an emulsifier is required to be added in the emulsification process in the emulsification/internal gelation method; the insoluble calcium salt is dispersed in the water phase, and calcium ions are completely dissociated to initiate the gelation reaction of the sodium alginate, so that pure calcium alginate gel beads are formed. According to the invention, a large amount of porous calcium carbonate microspheres are used as insoluble calcium salt and dispersed in an oil phase, and meanwhile, the porous calcium carbonate microspheres are also used as an emulsifier in an emulsification process and adsorbed on the surface of emulsion droplets to form a shell layer to stabilize the emulsion droplets, and the emulsifier is not required to be added in the emulsification process; only a very small amount of porous calcium carbonate microspheres dissociate calcium ions to initiate the gelation reaction of sodium alginate, and a large amount of porous calcium carbonate microspheres are still on the surface of gel beads to form microbeads with the porous calcium carbonate microspheres as shells and the calcium alginate gel as cores.
The surface of the obtained calcium alginate gel bead is provided with a layer of porous calcium carbonate microspheres, so that the surface strength is improved; meanwhile, the porous calcium carbonate microspheres have good active substance adsorption performance and can endow the calcium alginate gel beads with new drug loading and releasing performance.
Drawings
FIG. 1 is a scanning electron microscope picture of porous calcium carbonate microspheres with different magnifications; wherein,
FIG. 1-1 is an overall view thereof;
FIGS. 1-2 are a schematic of a microsphere thereof;
FIGS. 1-3 are partial views thereof;
FIG. 2 is an optical microscope image of calcium alginate gel beads with different magnifications, wherein the porous calcium carbonate microspheres prepared by the method are taken as shells; wherein,
FIG. 2-1 is an overall view thereof;
FIGS. 1-2 are a gel bead diagram thereof;
fig. 1-3 are partial views thereof.
Detailed Description
Preparation of calcium alginate gel bead with porous calcium carbonate microsphere as shell
Example 1
Uniformly dispersing 40g of 5 μm porous calcium carbonate microspheres (see figure 1) into 4L sunflower seed oil, adding 1L of 1% sodium alginate water solution dropwise into the mixture of porous calcium carbonate microspheres and sunflower seed oil, and stirring at 150rpm for 10min to form emulsion. 100mL of 200g/L of gluconolactone aqueous solution is dropwise added into the emulsion, and the mixture is continuously stirred for 10 minutes to prepare calcium alginate gel beads, wherein the surface of the calcium alginate gel beads is provided with a layer of porous calcium carbonate microspheres (shown in figure 2), the appearance is regular, the sphericity is high, and the particle size is 100-1000 microns.
Example 2
Uniformly dispersing 30g of 5-micron porous calcium carbonate microspheres into 4L of sunflower seed oil, then dripping 1L of 1% sodium alginate aqueous solution into the mixed solution of the porous calcium carbonate microspheres and the liquid paraffin, and stirring at the rotating speed of 150rpm for 10min to form emulsion. 100mL of 200g/L of gluconolactone aqueous solution is dropwise added into the emulsion, and the mixture is continuously stirred for 10 minutes to prepare calcium alginate gel beads, wherein the surface of the calcium alginate gel beads is provided with a layer of porous calcium carbonate microspheres, the appearance is regular, the sphericity is high, and the particle size is 100-1000 microns.
Example 3
50g of 1-micron porous calcium carbonate microspheres are uniformly dispersed into 4L of sunflower seed oil, then 1L of 1% sodium alginate aqueous solution is dropwise added into a mixed solution of the porous calcium carbonate microspheres and decane, and the mixture is stirred for 10min at the rotating speed of 150rpm to form emulsion. 100mL of 200g/L of gluconolactone aqueous solution is dropwise added into the emulsion, and the mixture is continuously stirred for 10 minutes to prepare calcium alginate gel beads, wherein the surface of the calcium alginate gel beads is provided with a layer of porous calcium carbonate microspheres, the appearance is regular, the sphericity is high, and the particle size is 10-1000 microns.
In the embodiment, the coverage rate of the porous calcium carbonate microspheres on the surface shell layer of the prepared calcium alginate gel beads is regulated and controlled by the weight ratio of the porous calcium carbonate microspheres to the sodium alginate aqueous solution, so that the gel beads with different surface strengths and permeation speeds can be prepared according to the requirements of the embedded objects.
According to the invention, the surface of the prepared calcium alginate gel bead is provided with the layer of porous calcium carbonate microspheres, so that the surface strength of the gel bead can be improved, and the stability of the gel bead can be improved. The porous calcium carbonate microspheres can endow the calcium alginate gel beads with new drug loading and release properties. In addition, the technology of the invention adopts materials with good biocompatibility, has no toxicity or irritation, has no harm to the activity of immobilized substances, and is suitable for the pharmaceutical industry, the food industry and other biotechnology fields.
Claims (4)
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| CNB2006101242037A CN100558408C (en) | 2006-12-13 | 2006-12-13 | Calcium alginate gel beads with porous calcium carbonate microspheres as shell and preparation method thereof |
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| CNB2006101242037A CN100558408C (en) | 2006-12-13 | 2006-12-13 | Calcium alginate gel beads with porous calcium carbonate microspheres as shell and preparation method thereof |
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| CN1985995A CN1985995A (en) | 2007-06-27 |
| CN100558408C true CN100558408C (en) | 2009-11-11 |
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9327061B2 (en) * | 2008-09-23 | 2016-05-03 | Senorx, Inc. | Porous bioabsorbable implant |
| CN102226012B (en) * | 2011-04-29 | 2012-10-17 | 山东大学 | Preparation method of macroporous cross-linked sodium alginate gel ball |
| CN102698667B (en) * | 2012-06-19 | 2014-05-28 | 重庆大学 | Spherical pore foaming agent with nuclear shell structure and three-dimensional cytoskeleton prepared by same |
| CN102703417B (en) * | 2012-06-26 | 2014-10-08 | 东南大学 | Preparation method of cell-loaded biological microcapsules |
| CN102772825B (en) * | 2012-07-06 | 2014-06-11 | 华南理工大学 | Polylactic-co-glycolic acid (PLGA)/calcium carbonate compound microsphere with porous shell and preparation method for compound microsphere |
| CN106674555B (en) * | 2016-12-28 | 2019-03-01 | 西南交通大学 | A kind of calcium alginate compounded microballoon and preparation method thereof for stablizing water-in-oil type pickering emulsion |
| CN109549928A (en) * | 2017-09-26 | 2019-04-02 | 清华大学深圳研究生院 | A kind of compound microballoon of Chitosan-Thiolated Polymers/calcium carbonate and preparation method thereof |
| CN114762661B (en) * | 2021-01-12 | 2024-02-02 | 万华化学集团股份有限公司 | A low-temperature stable core-shell structure soft bead and its preparation method |
| CN113171354B (en) * | 2021-04-13 | 2022-12-16 | 华南理工大学 | A kind of ropivacaine hydrochloride multivesicular liposome microsphere modified by sodium alginate and its preparation method and application |
| CN119838569B (en) * | 2025-03-20 | 2025-06-17 | 南昌航空大学 | Double-shell calcium carbonate/calcium sulfide loaded biochar adsorbent and preparation and application thereof |
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2006
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Non-Patent Citations (1)
| Title |
|---|
| Size control of calcium alginate beads containing living cellsusing micro-nozzli array. Shinji Sugiura. et al.Biomaterial,Vol.26. 2005 * |
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