CN100391540C - Prepn process of nanometer carboxymethyl chitosan particle as medicine carrier - Google Patents
Prepn process of nanometer carboxymethyl chitosan particle as medicine carrier Download PDFInfo
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- CN100391540C CN100391540C CNB2006100183506A CN200610018350A CN100391540C CN 100391540 C CN100391540 C CN 100391540C CN B2006100183506 A CNB2006100183506 A CN B2006100183506A CN 200610018350 A CN200610018350 A CN 200610018350A CN 100391540 C CN100391540 C CN 100391540C
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Abstract
The present invention relates to a preparation method for a medicine carrier, namely carboxymethyl chitosan nanometer particles. The present invention relates to the preparation method of the medicine carrier, namely the carboxymethyl chitosan nanometer particles, which is characterized in that the preparation method comprises the following steps: the carboxymethyl chitosan is dissolved in water at the room temperature, and the carboxymethyl chitosan water solution with the concentration of 0.5 to 2.0 mg/mL is made; the mixture is prepared by one of the following two methods; the mixture obtained by one of the two methods is stirred until complete crosslinking, and the medicine carrier, namely the carboxymethyl chitosan nanometer particles are obtained through centrifugal separation at high speed and freeze drying, wherein the particle diameter is from 90 nm to 220 nm. The preparation condition of the nanometer particle is mild, the side effect of organic solvent is avoided, and the preparation method of the present invention is particularly suitable for the carryover of sensitive macromolecules, such as protein medicine. The result of experiments taking bovine serum albumin as model medicine indicates that the encapsulation efficiency can reach 40%, and the slow-release time reaches more than six days.
Description
Technical field
The present invention relates to a kind of pharmaceutical carrier---the preparation method of nanometer carboxymethyl chitosan particle.
Background technology
Chitosan is owing to its adhesiveness height, good biocompatibility, and the application aspect pharmaceutical carrier and medical auxiliary material has more report.Chitosan is water insoluble more than 6 at pH value, causes it to be not suitable for adion under neutrallty condition; And after carboxy methylation, the amino and the hydroxyl that have suppressed chitosan generate hydrogen bond, thereby have improved water solublity, make it have good water-solubility under acid, alkali condition.Carboxymethyl chitosan has many viscosity, can strengthen the permeability and the absorbability of mucomembranous cell.
The preparation method of existing nanometer carboxymethyl chitosan particle adopts solvent evaporation and emulsifying-solvent diffusion method, has adopted organic solvent, and organic solvent has side effect, and institute's energy requirement is big.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of the nanometer carboxymethyl chitosan particle as medicine carrier that has no side effect.
Technical scheme of the present invention is: a kind of preparation method of nanometer carboxymethyl chitosan particle as medicine carrier is characterized in that it comprises the steps:
1). with in the carboxymethyl chitosan water-soluble (distilled water), making concentration is the carboxymethyl chitosan sugar aqueous solution of 0.5-2.0mg/mL under room temperature;
2). the sodium hydroxide adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 6-9, under stirring condition, adding concentration is the 0.3-1.8mg/mL calcium chloride water, press the carboxymethyl chitosan sugar aqueous solution: the volume ratio of calcium chloride water=1: 1.5-2.5, add calcium chloride water, get mixture;
3). with said mixture be stirred to crosslinked fully after, high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle as medicine carrier that particle diameter is 90-220nm.
During entrapped drug, in step 2) in, after adjusting the carboxymethyl chitosan pH value of water solution, will be that the medicine of 20-40% is dissolved in the carboxymethyl chitosan sugar aqueous solution, be loaded with the nanometer carboxymethyl chitosan particle of medicine again according to said method (all the other steps are constant) preparation with the carboxymethyl chitosan mass ratio.With the bovine serum albumin is the model drug test, and envelop rate can reach 30, and slow release reached more than six days.
Nanometer carboxymethyl chitosan particle as medicine carrier provided by the invention is applicable to sealing various medicines, the preparation of this nanometer carboxymethyl chitosan particle as medicine carrier has been avoided with an organic solvent, avoid the side effect of organic solvent, promptly have no side effect, institute's energy requirement greatly reduces than common preparation method (solvent evaporation and emulsifying-solvent diffusion method), is very suitable for the delivery of responsive macromole such as protein drug.Preparation method process safety provided by the invention, simple effective, compliance with environmental protection requirements.
The specific embodiment
In order to understand the present invention better, further illustrate content of the present invention below in conjunction with embodiment, but content of the present invention not only is confined to the following examples.
Embodiment 1:
A kind of preparation method of nanometer carboxymethyl chitosan particle as medicine carrier, it comprises the steps:
1). under room temperature carboxymethyl chitosan is dissolved in the distilled water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 0.5mg/mL; 2). the hydrochloric acid adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 1, under stirring condition, adding concentration is 0.3mg/mL tripolyphosphate sodium water solution, press the carboxymethyl chitosan sugar aqueous solution: sodium tripolyphosphate volume aqueous solution is than=1: 1.5, add the tripolyphosphate sodium water solution, get mixture; 3). the mixture that obtains be stirred to crosslinked fully after, high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle as medicine carrier that particle diameter is 90-220nm.
During entrapped drug, in step 2) in, adjust the carboxymethyl chitosan pH value of water solution after, will be that 20% medicine is dissolved in the carboxymethyl chitosan sugar aqueous solution with the carboxymethyl chitosan mass ratio, be loaded with the nanometer carboxymethyl chitosan particle of medicine again according to method for preparing.
Embodiment 2:
A kind of preparation method of nanometer carboxymethyl chitosan particle as medicine carrier, it comprises the steps:
1). under room temperature carboxymethyl chitosan is dissolved in the distilled water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 2.0mg/mL; 2). the sodium hydroxide adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 6, under stirring condition, adding concentration is the 1.8mg/mL calcium chloride water, press the carboxymethyl chitosan sugar aqueous solution: the volume ratio of calcium chloride water=1: 2.5, add calcium chloride water, get mixture; 3). the mixture that obtains be stirred to crosslinked fully after, high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle as medicine carrier that particle diameter is 90-220nm.
During entrapped drug, in step 2) in, adjust the carboxymethyl chitosan pH value of water solution after, will be that 40% medicine is dissolved in the carboxymethyl chitosan sugar aqueous solution with the carboxymethyl chitosan mass ratio, be loaded with the nanometer carboxymethyl chitosan particle of medicine again according to method for preparing.
Embodiment 3:
A kind of preparation method that is loaded with the nanometer carboxymethyl chitosan particle of medicine is dissolved in the 40mg carboxymethyl chitosan in the 20mL distilled water under room temperature, and making concentration is the carboxymethyl chitosan sugar aqueous solution of 2.0mg/mL; The hydrochloric acid adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 2, model drug bovine serum albumin 10mg is dissolved in the carboxymethyl chitosan sugar juice again, and bovine serum albumin concentration is 0.5mg/mL; 1.4mg/mL tripolyphosphate sodium water solution with 4mL joins in the carboxymethyl chitosan sugar juice of 2mL then, gets mixture; The mixture stirring at room to crosslinked fully after, the 12000rmp high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle that is loaded with medicine that particle diameter is 90-220nm.Prepared nanoparticle is the sphere of rule.Nanometer carboxymethyl chitosan particle as medicine carrier reaches 35.2%, six day accumulation slow release to the envelop rate of bovine serum albumin and reaches 92%.
Embodiment 4:
A kind of preparation method that is loaded with the nanometer carboxymethyl chitosan particle of medicine is dissolved in the 36mg carboxymethyl chitosan in the 20mL distilled water under room temperature, and making concentration is the carboxymethyl chitosan sugar aqueous solution of 1.8mg/mL; The hydrochloric acid adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 2, model drug bovine serum albumin 10mg is dissolved in the carboxymethyl chitosan sugar juice again, and bovine serum albumin concentration is 0.5mg/mL; 1.6mg/mL tripolyphosphate sodium water solution with 4mL joins in the carboxymethyl chitosan sugar juice of 2mL then, gets mixture; The mixture stirring at room to crosslinked fully after, the 12000rmp high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle that is loaded with medicine that particle diameter is 90-220nm.The prepared nanometer carboxymethyl chitosan particle that is loaded with medicine is the sphere of rule.Nanometer carboxymethyl chitosan particle as medicine carrier reaches 32.6%, six day accumulation slow release to the envelop rate of bovine serum albumin and reaches 94%.
Embodiment 5:
A kind of preparation method that is loaded with the nanometer carboxymethyl chitosan particle of medicine, under room temperature, the 40mg carboxymethyl chitosan is dissolved in the 20mL distilled water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 2.0mg/mL, and the sodium hydroxide adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 7; Model drug bovine serum albumin 12mg is dissolved in the carboxymethyl chitosan sugar juice, wherein bovine serum albumin concentration is 0.6mg/mL again; Aqueous solution with the calcium chloride 1.4mg/mL of 4mL joins in the carboxymethyl chitosan sugar juice of 2mL then, mixture; The mixture stirring at room to crosslinked fully after, the 12000rmp high speed centrifugation separates, lyophilization obtain particle diameter be 90-220nm be loaded with the medicine nanometer carboxymethyl chitosan particle.The prepared nanometer carboxymethyl chitosan particle that is loaded with medicine is the sphere of rule.Nanometer carboxymethyl chitosan particle as medicine carrier reaches 37.3%, six day accumulation slow release to the envelop rate of bovine serum albumin and reaches 90%.
Embodiment 6:
A kind of preparation method that is loaded with the nanometer carboxymethyl chitosan particle of medicine, under room temperature, the 40mg carboxymethyl chitosan is dissolved in the 20mL distilled water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 2.0mg/mL, and the sodium hydroxide adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 8; Model drug bovine serum albumin 10mg is dissolved in the carboxymethyl chitosan sugar juice, wherein bovine serum albumin concentration is 0.5mg/mL again; Aqueous solution with the calcium chloride 1.6mg/mL of 4mL joins in the carboxymethyl chitosan sugar juice of 2mL then, mixture; The mixture stirring at room to crosslinked fully after, the 12000rmp high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle that is loaded with medicine that particle diameter is 90-220nm.The prepared nanometer carboxymethyl chitosan particle that is loaded with medicine is the sphere of rule.Nanometer carboxymethyl chitosan particle as medicine carrier reaches 32.0%, six day accumulation slow release to the envelop rate of bovine serum albumin and reaches 97%.
Claims (2)
1. the preparation method of a nanometer carboxymethyl chitosan particle as medicine carrier is characterized in that it comprises the steps:
1). under room temperature that carboxymethyl chitosan is soluble in water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 0.5-2.0mg/mL;
2). the sodium hydroxide adjustment carboxymethyl chitosan pH value of water solution that drips 0.1M to the carboxymethyl chitosan sugar aqueous solution is 6-9, under stirring condition, adding concentration is the 0.3-1.8mg/mL calcium chloride water, press the carboxymethyl chitosan sugar aqueous solution: the volume ratio of calcium chloride water=1: 1.5-2.5, add calcium chloride water, get mixture;
3). with said mixture be stirred to crosslinked fully after, high speed centrifugation separates, lyophilization obtains the nanometer carboxymethyl chitosan particle as medicine carrier that particle diameter is 90-220nm.
2. the preparation method of a kind of nanometer carboxymethyl chitosan particle as medicine carrier according to claim 1, it is characterized in that in step 2) in, after adjusting the carboxymethyl chitosan pH value of water solution, to be that the medicine of 20-40% is dissolved in the carboxymethyl chitosan sugar aqueous solution with the carboxymethyl chitosan mass ratio, must be loaded with the nanometer carboxymethyl chitosan particle of medicine again according to method for preparing.
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Families Citing this family (11)
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| CN100446756C (en) * | 2007-01-18 | 2008-12-31 | 广州中医药大学第二附属医院 | Preparation of composite drug-loaded nanoparticles of carboxyl-chitosan and chitosan modified by glycyrrhizanates |
| US7943597B2 (en) | 2008-04-08 | 2011-05-17 | Cypress Pharmaceutical, Inc. | Phosphate-binding chitosan and uses thereof |
| CN101805452B (en) * | 2010-03-11 | 2012-04-04 | 南昌航空大学 | Preparation method of crosslinked carboxymethyl chitosan nano particle |
| CN101856432B (en) * | 2010-05-19 | 2012-01-11 | 南京农业大学 | Preparation method of chitosan nanoparticles encapsulated tea polyphenol |
| CN102274192B (en) * | 2011-08-09 | 2013-08-28 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
| CN102407089B (en) * | 2011-10-19 | 2014-07-23 | 中国海洋大学 | Method for preparing chitosan compound nano/micron capsule with core-shell structure |
| CN105168120B (en) * | 2015-08-13 | 2018-08-10 | 贵州扬生医用器材有限公司 | A kind of calcification carboxyl chitosan nano-solution and preparation method thereof |
| CN107083057A (en) * | 2017-04-29 | 2017-08-22 | 成都博美实润科技有限公司 | A kind of preparation method for having electroactive carboxyl chitosan based composites |
| CN107281109B (en) * | 2017-05-11 | 2019-11-26 | 王智森 | A kind of cordycepin/O-CMC nanoparticle and preparation method thereof |
| CN108498484A (en) * | 2018-06-11 | 2018-09-07 | 荆楚理工学院 | With carbon dioxide and the sour chitin nanometer of response and its preparation method of aqueous dispersions |
| CN110575534B (en) * | 2019-10-18 | 2023-10-27 | 南通大学 | Endu synthetic medicine and preparation method and application thereof |
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