CN105168184A - Calcium alginate/polylysine medicine controlled release microcapsule and preparation method and application thereof - Google Patents

Calcium alginate/polylysine medicine controlled release microcapsule and preparation method and application thereof Download PDF

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Publication number
CN105168184A
CN105168184A CN201510610106.8A CN201510610106A CN105168184A CN 105168184 A CN105168184 A CN 105168184A CN 201510610106 A CN201510610106 A CN 201510610106A CN 105168184 A CN105168184 A CN 105168184A
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Prior art keywords
polylysine
calcium alginate
microcapsule
medicine controlled
preparation
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CN201510610106.8A
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洪立芝
姚卫蓉
李宗波
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ZHANGSHU LIONKING BIOLOGICAL TECHNOLOGY Co Ltd
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ZHANGSHU LIONKING BIOLOGICAL TECHNOLOGY Co Ltd
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Abstract

The invention relates to a preparation method of a medicine controlled release microcapsule used for the field of medicine and bioengineering. Calcium alginate serves as gel beads. Polylysine serves as the capsule wall. The microcapsule is prepared through a static combination method. Meanwhile, polylysine is used as a film formation material used for preparing the calcium alginate/polylysine medicine controlled release microcapsule, and the calcium alginate/polylysine medicine controlled release microcapsule which is uniform in particle size, allows the particle size to be controlled within the range of 300-900 micrometers and is smooth in surface can be prepared with the help of a high voltage static drop generation device and through calcium alginate external gelatinization and polylysine film formation. Due to the fact that polylysine and degraded products of polylysine have pharmacology functions, a drug carrier with an interventional therapy effect can be obtained, and the calcium alginate/polylysine medicine controlled release microcapsule is used for embedding medicine or cells and used for the field of food and bioengineering.

Description

Calcium alginate/polylysine medicine controlled releasing microcapsule and its preparation method and application
Technical field
The invention belongs to microcapsule technology field, be specifically related to a kind of with calcium alginate be glue pearl and with polylysine be cyst wall can be used for food and bioengineering field, be particularly useful for the microcapsule of drug controlled release.The invention still further relates to the preparation method of this microcapsule.
Background technology
Microcapsule is a kind of slow releasing preparation, can be used as artery embolization for treatment malignant tumor, in order to the extended treatment time on pharmaceutics, improve the drug level of target organ, and reduce systemic blood levels, improve curative effect, lower the effectiveness such as toxicity, can be applicable in controlled drug delivery system.Polylysine has good biocompatibility, energy biodegradation, and product is nontoxic, and has the pharmacological effects such as treatment hepatitis virus.Yet there are no report polylysine being prepared microcapsule as membrane material both at home and abroad at present.
Summary of the invention
The object of the present invention is to provide a kind of method for making with the calcium alginate/polylysine medicine controlled releasing microcapsule of interventional therapeutic effect, to be applied to medicine and bioengineering field.
The present invention solves the problems of the technologies described above by the following technical programs:
Calcium alginate/polylysine medicine controlled releasing microcapsule, is made up of calcium alginate and polylysine, it is characterized in that, described calcium alginate is gel beads, and its surface has the form compact and stable polylysine microcapsule membrane of one deck.
The invention still further relates to the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule, the steps include:
(1) preparation of calcium alginate gel beads: by electrostatic drop generating device, voltage 2.0-3.1 × 10 4kV, syringe pump fltting speed 30-50mm/h, by 2-10mL1.5-1.8%(w/v) sodium alginate soln instillation 100-300mL1.2-1.5%(w/v) calcium chloride solution in, there is gelation reaction, form calcium alginate gel beads of uniform size;
(2) film formation reaction: get 10-15mL1.0%-1.5%(w/v) polylysin solution, add in calcium alginate gel beads solution prepared by 10-15mL step (1) and carry out magnetic agitation, time 10-20min, makes the surface of calcium alginate gel beads form the form compact and stable polylysine microcapsule membrane of one deck.
As preferably, in step (1), described sodium alginate soln is successively through 0.8 μm, 0.45 μm, 0.22 μm filtration;
As preferably, in step (1), the injection needle diameter of described electrostatic drop generating device is 100-600 μm;
As preferably, in step (1), described calcium alginate gel beads particle diameter is 200-800 μm;
As preferably, in step (2), the polylysine microcapsule membrane thickness 50-100 μm on described calcium alginate gel beads surface;
As preferably, in step (2), the calcium alginate/polylysine medicine controlled releasing Microcapsules Size 300-900 μm of preparation.
The invention still further relates to the application of calcium alginate/polylysine medicine controlled releasing microcapsule, it is characterized in that, as sustained-release drug carrier.
Calcium alginate of the present invention/polylysine medicine controlled releasing microcapsule, by controlling calcium alginate concentration, the diameter spraying syringe needle and polylysine concentration, make the size of calcium alginate/polylysine medicine controlled releasing microcapsule at 300-900 μm of range-controllable, size is even, any surface finish, good sphericity, wherein the thickness of the polylysine microcapsule membrane of calcium alginate gel bead surface is at 50-100 μm.
Like this, the present invention utilizes electrostatic method in conjunction with electrostatic drop generating device to prepare microcapsule.Introduced in microcapsule preparation as membrane material by polylysine, due to the pharmacological effect of polylysine and catabolite thereof, when making polylysine for calcium alginate/polylysine medicine controlled releasing microcapsule, the microcapsule prepared has interventional therapeutic effect.This pharmaceutical carrier can keep good biocompatibility, macromolecular drug affinity, and the pharmacological function that its catabolite is intrinsic simultaneously makes it possess interventional therapy function.The present invention can be used for delivery and is released in medicine and the effective material of bioengineering field.
Detailed description of the invention
Below in conjunction with embodiment, explain content of the present invention in detail further.
Embodiment 1
Calcium alginate/polylysine medicine controlled releasing microcapsule, is made up of calcium alginate and polylysine, it is characterized in that, described calcium alginate is gel beads, and its surface has the form compact and stable polylysine microcapsule membrane of one deck.
Embodiment 2
Calcium alginate described in embodiment 1/polylysine medicine controlled releasing microcapsule is prepared by the following method,
(1) by 1.8%(w/v) sodium alginate soln filter through 0.8 μm, 0.45 μm, 0.22 μm after, get 4mL and move in syringe, through electrostatic drop generating device instillation 200mL1.5%(w/v) calcium chloride solution in, voltage 3.1 × 10 4, there is gelation reaction in kV, syringe pump fltting speed 50mm/h, forms the calcium alginate gel beads with particle diameter 200-800 μm; Described electrostatic drop generating device purchased from Dalian Physical and Chemical Inst. of the Chinese Academy of Sciences, model JDF; The injection needle diameter of described electrostatic drop generating device is 100 μm;
(2) 10mL calcium alginate gel beads is added 10mL0.08%(w/v) carry out film forming 10min in polylysin solution, make the surface of calcium alginate gel beads form one deck form compact and stable alginate/polylysine microcapsule membrane.
(3) by above-mentioned method, size can be obtained even, size scope 300-900 μm controlled, the polylysine microcapsule membrane average thickness 50 μm on calcium alginate gel beads surface, any surface finish and the calcium alginate of good sphericity/polylysine medicine controlled releasing microcapsule.
Embodiment 3
Calcium alginate described in embodiment 1/polylysine medicine controlled releasing microcapsule is prepared by the following method,
(1) by 1.5%(w/v) sodium alginate soln filter through 0.8 μm, 0.45 μm, 0.22 μm after, get 2mL and move in syringe, through electrostatic drop generating device instillation 100mL1.2%(w/v) calcium chloride solution in, voltage 2.0 × 10 4, there is gelation reaction in kV, syringe pump fltting speed 30mm/h, forms the calcium alginate gel beads with particle diameter 200-800 μm; Described electrostatic drop generating device purchased from Dalian Physical and Chemical Inst. of the Chinese Academy of Sciences, model JDF; The injection needle diameter of described electrostatic drop generating device is 600 μm;
(2) 15mL calcium alginate gel beads is added 15mL1.0%(w/v) carry out film forming 20min in polylysin solution, make the surface of calcium alginate gel beads form one deck form compact and stable alginate/polylysine microcapsule membrane.
(3) by above-mentioned method, size can be obtained even, size scope 300-900 μm controlled, the polylysine microcapsule membrane average thickness 100 μm on calcium alginate gel beads surface, any surface finish and the calcium alginate of good sphericity/polylysine medicine controlled releasing microcapsule.
Embodiment 4
Calcium alginate described in embodiment 1/polylysine medicine controlled releasing microcapsule is prepared by the following method,
(1) by 1.6%(w/v) sodium alginate soln filter through 0.8 μm, 0.45 μm, 0.22 μm after, get 10mL and move in syringe, through electrostatic drop generating device instillation 300mL1.3%(w/v) calcium chloride solution in, voltage 2.4 × 10 4, there is gelation reaction in kV, syringe pump fltting speed 40mm/h, forms the calcium alginate gel beads with particle diameter 200-800 μm; Described electrostatic drop generating device purchased from Dalian Physical and Chemical Inst. of the Chinese Academy of Sciences, model JDF; The injection needle diameter of described electrostatic drop generating device is 300 μm;
(2) 12mL calcium alginate gel beads is added 14mL1.2%(w/v) carry out film forming 13min in polylysin solution, make the surface of calcium alginate gel beads form one deck form compact and stable alginate/polylysine microcapsule membrane.
(3) by above-mentioned method, size can be obtained even, size scope 300-900 μm controlled, the polylysine microcapsule membrane average thickness 80 μm on calcium alginate gel beads surface, any surface finish and the calcium alginate of good sphericity/polylysine medicine controlled releasing microcapsule.
Embodiment 5
Calcium alginate described in embodiment 1/polylysine medicine controlled releasing microcapsule is prepared by the following method,
(1) by 1.7%(w/v) sodium alginate soln filter through 0.8 μm, 0.45 μm, 0.22 μm after, get 7mL and move in syringe, through electrostatic drop generating device instillation 150mL1.4%(w/v) calcium chloride solution in, voltage 2.8 × 10 4, there is gelation reaction in kV, syringe pump fltting speed 45mm/h, forms the calcium alginate gel beads with particle diameter 200-800 μm; Described electrostatic drop generating device purchased from Dalian Physical and Chemical Inst. of the Chinese Academy of Sciences, model JDF; The injection needle diameter of described electrostatic drop generating device is 500 μm;
(2) 13mL calcium alginate gel beads is added 11mL1.3%(w/v) carry out film forming 17min in polylysin solution, make the surface of calcium alginate gel beads form one deck form compact and stable alginate/polylysine microcapsule membrane.
(3) by above-mentioned method, size can be obtained even, size scope 300-900 μm controlled, the polylysine microcapsule membrane average thickness 60 μm on calcium alginate gel beads surface, any surface finish and the calcium alginate of good sphericity/polylysine medicine controlled releasing microcapsule.
Embodiment 6
By the calcium alginate of arbitrary for embodiment 2-5 preparation/polylysine medicine controlled releasing microcapsule, wrap up need slow release discharge medicine, by control calcium alginate/polylysine medicine controlled releasing microcapsule particle size range 300-900 μm and control calcium alginate gel beads surface polylysine microcapsule membrane thickness at 50-100 μm; Make medicine 1-24h release after taking.

Claims (8)

1. calcium alginate/polylysine medicine controlled releasing microcapsule, is made up of calcium alginate and polylysine, it is characterized in that, described calcium alginate is gel beads, and its surface has the form compact and stable polylysine microcapsule membrane of one deck.
2. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as claimed in claim 1, the steps include:
(1) preparation of calcium alginate gel beads: by electrostatic drop generating device, voltage 2.0-3.1 × 10 4kV, syringe pump fltting speed 30-50mm/h, by 2-10mL1.5-1.8%(w/v) sodium alginate soln instillation 100-300mL1.2-1.5%(w/v) calcium chloride solution in, there is gelation reaction, form calcium alginate gel beads of uniform size;
(2) film formation reaction: get 10-15mL1.0%-1.5%(w/v) polylysin solution, add in calcium alginate gel beads solution prepared by 10-15mL step (1) and carry out magnetic agitation, time 10-20min, makes the surface of calcium alginate gel beads form the form compact and stable polylysine microcapsule membrane of one deck.
3. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as claimed in claim 2, it is characterized in that, in step (1), described sodium alginate soln is successively through 0.8 μm, 0.45 μm, 0.22 μm filtration.
4. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as described in Claims 2 or 3, it is characterized in that, in step (1), the injection needle diameter of described electrostatic drop generating device is 100-600 μm.
5. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as described in Claims 2 or 3, it is characterized in that, in step (1), described calcium alginate gel beads particle diameter is 200-800 μm.
6. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as described in Claims 2 or 3, is characterized in that, in step (2), and the polylysine microcapsule membrane thickness 50-100 μm on described calcium alginate gel beads surface.
7. the preparation method of calcium alginate/polylysine medicine controlled releasing microcapsule as described in Claims 2 or 3, is characterized in that, in step (2), and the calcium alginate/polylysine medicine controlled releasing Microcapsules Size 300-900 μm of preparation.
8. the application of calcium alginate/polylysine medicine controlled releasing microcapsule as claimed in claim 1, is characterized in that, as the carrier of slow releasing pharmaceutical.
CN201510610106.8A 2015-09-23 2015-09-23 Calcium alginate/polylysine medicine controlled release microcapsule and preparation method and application thereof Pending CN105168184A (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107252108A (en) * 2017-06-27 2017-10-17 福建农林大学 A kind of lactase microcapsules and preparation method thereof
CN107802602A (en) * 2017-12-09 2018-03-16 任冉 The preparation method of gossypol acetate calcium alginate gel bead
CN109504082A (en) * 2018-10-08 2019-03-22 中原工学院 A kind of preparation method of albumen self-assembled nanometer aperture film
WO2020103918A1 (en) * 2018-11-22 2020-05-28 深圳先进技术研究院 Paste for 3d printing, 3d struct, preparation method therefor and application thereof
CN112897673A (en) * 2019-12-04 2021-06-04 怀化鑫崀峰钙业有限公司 Sewage treatment material with slow release effect
CN114190363A (en) * 2021-12-24 2022-03-18 大连大学 Epsilon-polylysine microsphere carrier and application thereof in cryopreservation of a small amount of sperms

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107252108A (en) * 2017-06-27 2017-10-17 福建农林大学 A kind of lactase microcapsules and preparation method thereof
CN107802602A (en) * 2017-12-09 2018-03-16 任冉 The preparation method of gossypol acetate calcium alginate gel bead
CN107802602B (en) * 2017-12-09 2020-10-16 任冉 Preparation method of gossypol acetate calcium alginate gel microspheres
CN109504082A (en) * 2018-10-08 2019-03-22 中原工学院 A kind of preparation method of albumen self-assembled nanometer aperture film
CN109504082B (en) * 2018-10-08 2021-03-16 中原工学院 Preparation method of protein self-assembly nano-aperture membrane
WO2020103918A1 (en) * 2018-11-22 2020-05-28 深圳先进技术研究院 Paste for 3d printing, 3d struct, preparation method therefor and application thereof
CN112897673A (en) * 2019-12-04 2021-06-04 怀化鑫崀峰钙业有限公司 Sewage treatment material with slow release effect
CN112897673B (en) * 2019-12-04 2024-05-24 湖南绿骏新材料有限公司 Sewage treatment material with slow release effect
CN114190363A (en) * 2021-12-24 2022-03-18 大连大学 Epsilon-polylysine microsphere carrier and application thereof in cryopreservation of a small amount of sperms

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Application publication date: 20151223