CN1488403A - Calcium alginate/poly arginine-chitin glycan composite medicine release -controlled microcap sule and preparing method thereof - Google Patents
Calcium alginate/poly arginine-chitin glycan composite medicine release -controlled microcap sule and preparing method thereof Download PDFInfo
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- CN1488403A CN1488403A CNA03132388XA CN03132388A CN1488403A CN 1488403 A CN1488403 A CN 1488403A CN A03132388X A CNA03132388X A CN A03132388XA CN 03132388 A CN03132388 A CN 03132388A CN 1488403 A CN1488403 A CN 1488403A
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Abstract
The invention refers to calcium alginate/PAA-chitosan compound drug controlled-release microcapsule and making method. The microcapsule is double-component single-layer film compound one or double-component double-layer film compound one. It uses static combination, uses PAA-chitosan as film material, and uses high-pressure static liquid drop generator to make the microcapsule, using sodium alginate to decorate surface, the particle size even and controllable, within 200-1000 mum, and the particle surface glabrous.
Description
Technical field
The invention relates to the calcium alginate and be the glue pearl and be the microcapsule and the method for making of cyst wall, especially belong to the microcapsule and the method for making that are applied to the medicine sustained release with poly arginine-chitosan.
Background technology
The microencapsulation technology is that dispersed solids material grains, drop or gas are encapsulated in a kind of technology that forms spherical microcapsule in the skim fully.Utilize the protection and the control material diffusion function of microcapsule membrane, microcapsule has been widely used in pharmaceutical sector, industry, agricultural and the daily living article, especially in controlled drug delivery system.
Chitosan has excellent biological compatibility, and can be by biodegradation, the catabolite avirulence.Poly arginine and catabolite thereof not only have excellent biological compatibility, avirulence, the effect that improves wound thing immunologic function is arranged, can also improve nitrogen balance, improve the animal dis motility rate, promote the wound healing effect, also can significantly suppress formation, growth and the transfer of many experimental tumors.Chitosan is used for the medicine controlled releasing system, a large amount of reports are all arranged both at home and abroad.But, poly arginine and chitosan be there is no report both at home and abroad in conjunction with the article and the patent that are applied to the microcapsule control delivery.
Summary of the invention
The object of the present invention is to provide a kind of calcium alginate/poly arginine-chitosan combination drug released microcapsule and method for making, carry out film forming shortcoming to have overcome one matter, and promote the Nutrition of product and pharmacological effect and make it possess the interventional therapy function.
Calcium alginate/poly arginine of the present invention-chitosan combination drug released microcapsule is the compound microcapsule membrane of bi-component monofilm that the surface of calcium alginate gel beads forms the alginate/poly arginine-chitosan of one deck.
Its method for making is:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: poly arginine, the chitosan mixed solution of getting finite concentration and proportioning, add calcium alginate gel beads and be carried out to film reaction, make the surface of calcium alginate gel beads form one deck alginate/poly arginine-compound microcapsule membrane of chitosan, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
Calcium alginate/poly arginine of the present invention-chitosan combination drug released microcapsule also can be the surface formation one deck alginate/poly arginine of calcium alginate gel beads and the compound microcapsule membrane of bi-component duplicature of one deck alginate/chitosan.
Its method for making is:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: get certain density poly arginine solution, add calcium alginate gel beads and be carried out to film reaction, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back, the certain density chitosan of reuse carries out two-step film forming, make the surface of calcium alginate gel beads form one deck alginate/poly arginine and the compound microcapsule membrane of one deck alginate/chitosan, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
Calcium alginate/poly arginine of the present invention-chitosan combination drug released microcapsule also can be the surface formation one deck alginate/chitosan of calcium alginate gel beads and the compound microcapsule membrane of bi-component duplicature of one deck alginate/poly arginine.
Its method for making is:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: get certain density chitosan solution, add calcium alginate gel beads and be carried out to film reaction, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back, the certain density poly arginine of reuse carries out two-step film forming, make the surface of calcium alginate gel beads form one deck alginate/chitosan and the compound microcapsule membrane of one deck alginate/poly arginine, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
Calcium alginate/poly arginine of the present invention-chitosan combination drug released microcapsule, the size scope is controlled in 200-1000 μ m, any surface finish.
Like this, the present invention utilizes the static combined techniques to prepare microcapsule by the high-pressure electrostatic drop generating device, the polyamino acid material is preferably poly arginine and chitosan combination, is used for the preparation of calcium alginate/poly arginine-compound microcapsule of chitosan simultaneously.The microcapsule of the present invention preparation especially belongs to the microcapsule of medicine sustained release, and capsule core material is albumen, polypeptide drug.The compound microcapsule of sodium alginate/poly arginine-chitosan has overcome one matter on the one hand and has carried out film forming shortcoming, and on the other hand, because the Nutrition and the pharmacological effect of poly arginine and catabolite thereof, the microcapsule of preparing has the interventional therapy effect.This pharmaceutical carrier can keep excellent biological compatibility, macromolecular drug affinity, medicine sustained release performance, and catabolite also can absorb and its inherent nutrition and pharmacological function make it possess the interventional therapy function.The present invention can be used for embedding medicinal or cell is used for medicine and bioengineering field.
The specific embodiment
Be the concrete implementation step (is the example that is represented as of albumen, polypeptide drug with the bovine hemoglobin) of example with bi-component monofilm composite micro-capsule for the present invention below:
The first, with 1.8% sodium alginate soln after 0.8 μ m, 0.45 μ m, 0.22 μ m filter, it is 1mg/mL that the adding bovine hemoglobin makes its content, mixing, ultrasound wave is got in the 4mL immigration syringe after removing bubble, splash in the calcium chloride solution of the 200mL1.5% (w/v) that contains 0.2% Tween80 dispersant through the static drop generating device, gelation reaction takes place, and forms the calcium alginate gel beads with certain size.
The second, the calcium alginate plastic beads that makes is immersed in the bovine hemoglobin solution of 20mL5mg/mL standing adsorption more than 12 hours.
Three, the glue pearl after will adsorbing with the quick washed twice of normal saline after, add the mixed liquor 20mL that contains chitosan 0.6%, poly arginine 0.08% and carried out film forming 10 minutes, after the normal saline washing, sodium alginate soln with 0.15% (w/v) is modified surface of microcapsule, last reuse normal saline washing.
Four, by above-mentioned method, it is even to make size, and size scope 200-1000 μ m is controlled, the compound microcapsule of the calcium alginate/poly arginine of any surface finish-chitosan.
Claims (7)
1, calcium alginate/poly arginine-chitosan combination drug released microcapsule is characterized in that: the compound microcapsule membrane of bi-component monofilm that forms the alginate/poly arginine-chitosan of one deck for the surface of calcium alginate gel beads.
2, the method for making of calcium alginate/poly arginine-chitosan combination drug released microcapsule is according to claim 1:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: poly arginine, the chitosan mixed solution of getting finite concentration and proportioning, add calcium alginate gel beads and be carried out to film reaction, make the surface of calcium alginate gel beads form one deck alginate/poly arginine-compound microcapsule membrane of chitosan, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
3, calcium alginate/poly arginine-chitosan combination drug released microcapsule is characterized in that: the compound microcapsule membrane of bi-component duplicature that forms one deck alginate/poly arginine and one deck alginate/chitosan for the surface of calcium alginate gel beads.
4, the method for making as calcium alginate/poly arginine-chitosan combination drug released microcapsule as described in the claim 3 is:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: get certain density poly arginine solution, add calcium alginate gel beads and be carried out to film reaction, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back, the certain density chitosan of reuse carries out two-step film forming, make the surface of calcium alginate gel beads form one deck alginate/poly arginine and the compound microcapsule membrane of one deck alginate/chitosan, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
5, calcium alginate/poly arginine-chitosan combination drug released microcapsule is characterized in that: the compound microcapsule membrane of bi-component duplicature that forms one deck alginate/chitosan and one deck alginate/poly arginine for the surface of calcium alginate gel beads.
6, the method for making as calcium alginate/poly arginine-chitosan combination drug released microcapsule as described in the claim 5 is:
The preparation of the first step, calcium alginate gel beads: by the static drop generating device, certain density sodium alginate is splashed in the calcium chloride solution that contains medicinal dispersant, gelation reaction takes place, form calcium alginate gel beads with certain size;
Second step, film formation reaction: get certain density chitosan solution, add calcium alginate gel beads and be carried out to film reaction, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back, the certain density poly arginine of reuse carries out two-step film forming, make the surface of calcium alginate gel beads form one deck alginate/chitosan and the compound microcapsule membrane of one deck alginate/poly arginine, surface of microcapsule is modified with the sodium alginate soln of low concentration in normal saline washing back.
7, as claim 1,3 or 5 described calcium alginate/poly arginines-chitosan combination drug released microcapsule, it is characterized in that: the size scope is controlled in 200-1000 μ m, any surface finish.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03132388XA CN100355456C (en) | 2003-08-15 | 2003-08-15 | Calcium alginate/poly arginine-chitin glycan composite medicine release -controlled microcap sule and preparing method thereof |
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| CNB03132388XA CN100355456C (en) | 2003-08-15 | 2003-08-15 | Calcium alginate/poly arginine-chitin glycan composite medicine release -controlled microcap sule and preparing method thereof |
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| CN1488403A true CN1488403A (en) | 2004-04-14 |
| CN100355456C CN100355456C (en) | 2007-12-19 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1329510C (en) * | 2004-11-17 | 2007-08-01 | 中国科学院沈阳应用生态研究所 | Two-stage micrococcus complex coagulating fix method |
| WO2010124655A1 (en) * | 2009-04-30 | 2010-11-04 | 北京宏医耀科技发展有限公司 | Complex microcapsule comprising epiphyseal plate chondrocytes and preparation method and use thereof |
| CN101947212A (en) * | 2010-09-08 | 2011-01-19 | 华侨大学 | Micro-embedded medicament carrier and preparation method thereof |
| CN101972491A (en) * | 2010-09-25 | 2011-02-16 | 上海交通大学医学院附属瑞金医院 | Grape bunch-shaped micro-capsule system and preparation method thereof |
| CN102286422A (en) * | 2011-06-22 | 2011-12-21 | 南开大学 | Composite microcapsule model for use in in-vitro cell coculture |
| WO2013166681A1 (en) * | 2012-05-10 | 2013-11-14 | 聚和国际股份有限公司 | Composition for producing microcapsules and medicine made thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1167366C (en) * | 2002-04-17 | 2004-09-22 | 苗九昌 | Chitosan collagen and calcium alginate compounded spongy biological dressing and its preparation process |
| CN1383819A (en) * | 2002-05-17 | 2002-12-11 | 天津市园艺工程研究所 | Protocyanidin slow release capsule |
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2003
- 2003-08-15 CN CNB03132388XA patent/CN100355456C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1329510C (en) * | 2004-11-17 | 2007-08-01 | 中国科学院沈阳应用生态研究所 | Two-stage micrococcus complex coagulating fix method |
| WO2010124655A1 (en) * | 2009-04-30 | 2010-11-04 | 北京宏医耀科技发展有限公司 | Complex microcapsule comprising epiphyseal plate chondrocytes and preparation method and use thereof |
| CN101947212A (en) * | 2010-09-08 | 2011-01-19 | 华侨大学 | Micro-embedded medicament carrier and preparation method thereof |
| CN101972491A (en) * | 2010-09-25 | 2011-02-16 | 上海交通大学医学院附属瑞金医院 | Grape bunch-shaped micro-capsule system and preparation method thereof |
| CN101972491B (en) * | 2010-09-25 | 2014-01-08 | 上海交通大学医学院附属瑞金医院 | Grape bunch-shaped micro-capsule system and preparation method thereof |
| CN102286422A (en) * | 2011-06-22 | 2011-12-21 | 南开大学 | Composite microcapsule model for use in in-vitro cell coculture |
| CN102286422B (en) * | 2011-06-22 | 2013-03-27 | 南开大学 | Composite microcapsule model for use in in-vitro cell coculture |
| WO2013166681A1 (en) * | 2012-05-10 | 2013-11-14 | 聚和国际股份有限公司 | Composition for producing microcapsules and medicine made thereof |
| CN104302279A (en) * | 2012-05-10 | 2015-01-21 | 聚和国际股份有限公司 | Composition for producing microcapsules and medicine made thereof |
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| Publication number | Publication date |
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| CN100355456C (en) | 2007-12-19 |
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Granted publication date: 20071219 Termination date: 20110815 |