CN103386134B - Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method - Google Patents
Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method Download PDFInfo
- Publication number
- CN103386134B CN103386134B CN201310306880.0A CN201310306880A CN103386134B CN 103386134 B CN103386134 B CN 103386134B CN 201310306880 A CN201310306880 A CN 201310306880A CN 103386134 B CN103386134 B CN 103386134B
- Authority
- CN
- China
- Prior art keywords
- chitosan
- solution
- acetic acid
- preparation
- microspheres
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method for a medicinal preparation, and particularly relates to a preparation method for chitosan drug-carrying microspheres by an ionic cross-linking method. Chitosan solid is weighed and dissolved in an acetic acid solution, and impurities in the chitosan are removed by suction filtration through a circulating water vacuum pump. A NaOH solution is added dropwise into the chitosan acetic acid solution. Under conditions that the mole ratio of positive charges to negative charges is 20:1-60:1, the cross-linking time is 5-25 min and the rotate speed is 300-700 rpm, the parameters are set up in a microwave reactor and a sodium pyrophosphate solution is added into the prepared chitosan acetic acid solution, and a chitosan microsphere solution is prepared. After the reaction is finished, the prepared chitosan microsphere solution is subjected to steps of centrifuging by using an automatic low-speed table-type centrifuge, removing supernatant liquid, washing with purified water, and finally freeze-drying products to obtain chitosan blank microspheres. The chitosan microspheres can be used for preparing lung-targeted medicament carriers. The chitosan microspheres are environmental friendly and non-toxic. The chitosan microspheres have a simple preparation technology and a low cost.
Description
Technical field
The present invention relates to a kind of preparation method of pharmaceutical preparation, particularly relate to a kind of method that ionic cross-linking prepares chitosan drug-loading microsphere.
Background technology
Using biodegradable macromolecular material as the medicine carrying microballoons of pharmaceutical carrier, have broad application prospects in medical science and drug world.In recent years, along with the development of pharmaceutical preparation, the pharmaceutical carrier with nontoxic, biodegradable, good histocompatibility has become the focus of research.Chitosan is a kind of positively charged natural polysaccharide, it has nontoxic, nonirritant, without sensitization, without mutagenic action, without haemolysis effect, the effect of good biocompatibility, biological degradability, bioadhesive and promotion drug absorption, makes it in pharmaceutical carrier, have unique advantage.
Microwave irradiation is a kind of efficient, environmental protection, high selectivity, the synthetic technology of high yield.The fast several times of heating means that organic reaction speed under microwave radiation is more traditional, decades of times, even thousands of times, and have easy to operate, the high and easy purification of products of productive rate etc. feature.
Ionic cross-linking refers under ion crosslinking agent effect, is tied between the macromolecular chain in raw material by chemical bond, forms method that is netted or body structure macromolecular material.The advantage of ionic cross-linking be in preparation process not with an organic solvent, the activity of medicine can be kept when being applied to medicine, also may be used for mucosal drug delivery.Ionic cross-linking is also physical crosslinking method usually, because this preparation method is very simple, and the chitosan microball of preparation avoids most of chemical cross-linking agent if glutaraldehyde cross-linking agent is to the harm of human body, is in this way widely used.Chitosan in acid condition can be protonated, makes its amino with positive charge.And mostly ion crosslinking agent is polyanionic compound, the cation generation Electrostatic Absorption of its anion produced in the solution and the protonated rear amino of chitosan is reacted, and is linked together by intermolecular force.Affect chitosan and polyanionic compound because of have following some: the molecular structure of anion, charge density and concentration, the pH value of chitosan solution and and deacetylation (DDA) etc.Conventional ion crosslinking agent is the tripolyphosphate, four Quadrafos, pyrophosphate, molybdate etc. of low relative molecular amount.
Summary of the invention
A kind of ionic cross-linking is the object of the present invention is to provide to prepare the method for chitosan drug-loading microsphere, the chitosan microball that the method obtains is as preparation treatment Lung targeting pharmaceutical carrier (7-12um), environment-protecting asepsis, its preparation technology is easy, with low cost, simultaneously the method can Reaction time shorten, raise the efficiency and product quality.
The object of the invention is to be achieved through the following technical solutions:
Ionic cross-linking prepares the method for chitosan drug-loading microsphere, and described method comprises following process:
Taking quantitative chitosan solid, to be dissolved in 50-100ml volume fraction be in the acetum of 2-3%, the chitosan-acetic acid solution of obtained 1-2% w/v, then with the impurity in circulating water type vacuum pump sucking filtration removing chitosan; At room temperature, NaOH solution 1.0mol/L is dripped in chitosan-acetic acid solution, regulate the pH of chitosan solution at pH=4-7 with pH meter, and with under the condition of fixing temperature room temperature-100 DEG C, positive and negative charge mol ratio 20:1-60:1, crosslinking time 5-25min, rotating speed 300-700rpm, set in microwave reactor parameter sodium pyrophosphate solution 0.5-0.8 g/L is added drop-wise to prepare chitosan-acetic acid solution in, and obtain chitosan microball solution; After reaction terminates, by the centrifugal 2-5min of chitosan microball solution table-type low-speed automatic centrifuge, the 3000-4000rpm that prepare, go the supernatant, then with pure water washing 3 to 5 times, finally by product under the condition of-30-45 DEG C after lyophilizing 12-24 hr, namely the blank microsphere of chitosan is obtained, for the preparation for the treatment of Lung targeting pharmaceutical carrier, particle size range 7-12um.
Described ionic cross-linking prepares the method for chitosan drug-loading microsphere, and described tetrasodium pyrophosphate is as cross-linking agent, and the anion-content of tetrasodium pyrophosphate is 9.402 × 10-4mol/g.
Advantage of the present invention and effect are:
The chitosan microball that the method obtains is as preparation treatment Lung targeting pharmaceutical carrier (particle size range 7-12um), and environment-protecting asepsis, preparation technology is easy, with low cost.
Accompanying drawing explanation
Fig. 1 is the influence curve figure of revolution to the blank microspherulite diameter of chitosan;
A, b, c microsphere ball-type of Fig. 2 under differential responses condition and distribution photo;
The infrared spectrum spectrogram of Fig. 3 chitosan and chitosan microball;
The scanning electron microscope (SEM) photograph of the blank microsphere of Fig. 4;
Fig. 5 chitosan microball surface topography.
Note: Fig. 1-Fig. 5 of the present invention is analysis schematic diagram or the photo (only for reference) of product state, word or the unintelligible understanding do not affected technical solution of the present invention of image in figure.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in detail.
Taking quantitative chitosan solid, to be dissolved in 50-100ml volume fraction be in the acetum of 2-3%, the chitosan-acetic acid solution of obtained 1-2% (w/v), then with the impurity in circulating water type vacuum pump sucking filtration removing chitosan.At room temperature, NaOH solution (1.0mol/L) is dripped in chitosan-acetic acid solution, the pH (pH=4-7) in certain scope of chitosan solution is regulated with pH meter, and with under the condition of fixing temperature (room temperature-100 DEG C), positive and negative charge mol ratio (20:1-60:1), crosslinking time (5-25min), rotating speed (300-700rpm), set in microwave reactor parameter sodium pyrophosphate solution (0.5-0.8 g/L) is added drop-wise to prepare chitosan-acetic acid solution in, and obtain chitosan microball solution.After reaction terminates, centrifugal 2-5min(3000-the 4000rpm of chitosan microball solution table-type low-speed automatic centrifuge by preparing), go the supernatant, then with pure water washing 3 to 5 times, finally product after lyophilizing 12-24 hr, is namely obtained the blank microsphere of chitosan under the condition of-30-45 DEG C.
Because tetrasodium pyrophosphate itself is nontoxic, so tetrasodium pyrophosphate can be used as humectant metaphosphate, quality improver, pH regulator, metal-chelator etc. in the food industry.The anion-content of tetrasodium pyrophosphate is 9.402 × 10-4mol/g, the anion-content of the cross-linking agent sodium tripolyphosphate that ratio is conventional is 5.437 × 10-4mol/g, the content for 2.724 × 10-4mol/g of sodium hexameta phosphate all wants many, so use tetrasodium pyrophosphate can save certain production cost as ion crosslinking agent.
1. illustrate, the particle diameter of chitosan medicine carrying microballoons and microsphere pattern and distribution under different revolution.
As Fig. 1 can find out the increase along with revolution, curve has a declining tendency, show the increase along with revolution, the particle diameter of the blank microsphere of chitosan is little gradually. and the particle diameter of revolution microsphere when 300rpm is maximum, due to revolution, to cause microspherulite diameter compared with minimicrosphere generating portion aggregation phenomenon maximum, when revolution is at 400rpm-600rpm, curve more steadily shows that the impact of revolution on microspherulite diameter is little within the scope of this, when revolution is 700rpm, the particle diameter of microsphere is minimum, because revolution very senior general's chitosan microball is smashed, cause microspherulite diameter minimum.
Fig. 2 is that rotating speed is respectively 300rpm, and the chitosan microball solution prepared by 400rpm, 500rpm amplifies the image of 400 times under the microscope.As shown in the figure, when rotating speed is 300rpm and 400rpm, microsphere ball-type is regular, and overall distribution is even.When rotating speed is more than 500rpm, microsphere quantity obviously reduces, this is because rotating speed increases, the microsphere just formed may be smashed, causes microsphere balling-up amount to decline.
3. the IR of chitosan drug-loading microsphere analyzes
By comparing the infrared spectrum of chitosan and tetrasodium pyrophosphate crosslinked chitosan microsphere, can be clearly seen that 3425cm-1 place is absworption peak that is amino on chitosan and hydroxyl, compared with Fig. 3 a b 3359cm-1 place narrow this is because a part of amino be protonated after with the result of anion Electrostatic Absorption.In Fig. 3 b, the absworption peak at 1115cm-1 place and 1069cm-1 place is tetrasodium pyrophosphate-P=O functional group, and this shows in crosslinked microsphere containing tetrasodium pyrophosphate.
3. the SEM morphology analysis of chitosan drug-loading microsphere
As shown in Figure 4, crosslinked microsphere better spherical in shape, particle diameter is at 7 μm ~ 8 μm, and surface is more smooth, has layer structure.Can see that microsphere surface is uneven by Fig. 5, layer structure is obvious, has a little aperture, is conducive to load and the release of medicine.
Claims (1)
1. ionic cross-linking prepares the method for chitosan drug-loading microsphere, it is characterized in that, described method comprises following process:
Taking quantitative chitosan solid, to be dissolved in 50-100ml volume fraction be in the acetum of 2-3%, the chitosan-acetic acid solution of obtained 1-2% w/v, then with the impurity in circulating water type vacuum pump sucking filtration removing chitosan; At room temperature, NaOH solution 1.0mol/L is dripped in chitosan-acetic acid solution, regulate the pH of chitosan solution at pH=4-7 with pH meter, and with under the condition of fixing temperature room temperature-100 DEG C, positive and negative charge mol ratio 20:1-60:1, crosslinking time 5-25min, rotating speed 300-700rpm, set in microwave reactor parameter sodium pyrophosphate solution 0.5-0.8 g/L is added drop-wise to prepare chitosan-acetic acid solution in, and obtain chitosan microball solution; After reaction terminates, by the centrifugal 2-5min of chitosan microball solution table-type low-speed automatic centrifuge, the 3000-4000rpm that prepare, go the supernatant, then with pure water washing 3 to 5 times, finally by product under the condition of-30-45 DEG C after lyophilizing 12-24 hr, namely the blank microsphere of chitosan is obtained, for the preparation for the treatment of Lung targeting pharmaceutical carrier, particle size range 7-12um;
Described tetrasodium pyrophosphate is as cross-linking agent, and the anion-content of tetrasodium pyrophosphate is 9.402 × 10-4mol/g.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310306880.0A CN103386134B (en) | 2013-07-22 | 2013-07-22 | Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310306880.0A CN103386134B (en) | 2013-07-22 | 2013-07-22 | Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103386134A CN103386134A (en) | 2013-11-13 |
| CN103386134B true CN103386134B (en) | 2015-05-20 |
Family
ID=49530667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310306880.0A Active CN103386134B (en) | 2013-07-22 | 2013-07-22 | Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103386134B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110025581A (en) * | 2019-04-19 | 2019-07-19 | 武汉大学 | The preparation method and applications of rhodioside chitosan microball |
| CN111697234B (en) * | 2020-06-19 | 2022-09-02 | 中国地质大学（武汉） | Water-based crosslinking binder for lithium ion battery and preparation method and application thereof |
| CN112106770A (en) * | 2020-09-06 | 2020-12-22 | 惠州市银农科技股份有限公司 | Methylamino abamectin benzoate nano capsule and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1290524A (en) * | 1999-09-30 | 2001-04-11 | 浙江大学 | Ion crosslinking process of preparing medicinal slow-releasing chitosan microball |
| CN1485362A (en) * | 2002-09-29 | 2004-03-31 | 中国科学院过程工程研究所 | Ion cross-linked chitosan microballoon, its preparing process and use |
| CN101214228A (en) * | 2008-01-14 | 2008-07-09 | 四川大学 | Water-solubility chitosan microsphere for carrying medicament and preparation thereof |
| CN102274192A (en) * | 2011-08-09 | 2011-12-14 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
| CN102293752A (en) * | 2011-08-26 | 2011-12-28 | 广东药学院 | Preparation method of chitosan-carried capsaicin microsphere as well as microsphere and application of microsphere to weight reduction and sugar reduction |
-
2013
- 2013-07-22 CN CN201310306880.0A patent/CN103386134B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1290524A (en) * | 1999-09-30 | 2001-04-11 | 浙江大学 | Ion crosslinking process of preparing medicinal slow-releasing chitosan microball |
| CN1485362A (en) * | 2002-09-29 | 2004-03-31 | 中国科学院过程工程研究所 | Ion cross-linked chitosan microballoon, its preparing process and use |
| CN101214228A (en) * | 2008-01-14 | 2008-07-09 | 四川大学 | Water-solubility chitosan microsphere for carrying medicament and preparation thereof |
| CN102274192A (en) * | 2011-08-09 | 2011-12-14 | 山西医科大学第一医院 | Carboxymethyl chitosan medicament-carrying microspheres and preparation method thereof |
| CN102293752A (en) * | 2011-08-26 | 2011-12-28 | 广东药学院 | Preparation method of chitosan-carried capsaicin microsphere as well as microsphere and application of microsphere to weight reduction and sugar reduction |
Non-Patent Citations (1)
| Title |
|---|
| 《姜黄素壳聚糖微球的制备及其在体内外释放度的研究》;孙颖倩等;《现代生物医药进展》;20121031;第12卷(第29期);第5652页右栏，第5655页左栏 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103386134A (en) | 2013-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102161729B (en) | Preparation method of water-soluble polysaccharide/hydrophobic monomer formed nanoparticles | |
| CN104001178B (en) | A kind of PLGA nano-medicament carrier and its preparation method and application | |
| CN101766820B (en) | Novel method for preparation of chitosan nano carrier and functionalization thereof | |
| CN110623918B (en) | Carboxymethyl chitosan/sodium alginate nano hydrogel and preparation method and application thereof | |
| CN110384684B (en) | Monocarboxyl chitosan/alkannin composite nano-particles and preparation method thereof | |
| CN103386134B (en) | Preparation method for chitosan drug-carrying microspheres by ionic cross-linking method | |
| CN103159962B (en) | Preparation method of photosensitive cyclodextrin gel | |
| CN103385856B (en) | Method for preparing nanometer particles of 5-ALA or 5-ALA derivatives | |
| CN110292041B (en) | Nano pesticide preparation and preparation method thereof | |
| Ioelovich | Nanoparticles of amorphous cellulose and their properties | |
| CN113751079B (en) | Perovskite-titanium dioxide nano composite photocatalyst loaded by biological material and construction method and application thereof | |
| CN104785179A (en) | Preparation method for starch nanospheres | |
| CN102407089A (en) | Method for preparing chitosan compound nano/micron capsule with core-shell structure | |
| CN104906073A (en) | Preparation method of chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors | |
| CN102614133A (en) | Andrographolide ground suspending liquid, preparation method thereof, and application of pharmaceutical preparation | |
| CN104352442B (en) | A kind of mifepristone chitosan sustained-release microsphere preparation and preparation method thereof | |
| CN103191441B (en) | Method for preparing stimuli-response type esterified nano cellulose prodrug sustained-release material | |
| CN103520135A (en) | Resveratrol-supporting poly(lactic-co-glycolic acid) micro-nano particles and preparation method thereof | |
| CN103961319A (en) | Preparation method of chitosan and montmorillonite compound drug carrying microsphere | |
| CN104367551A (en) | Aprepitant compound and its preparation method | |
| Raj et al. | Formulation and evaluation of chitosan prazosin beads by ionotropic gelation method | |
| CN110522740B (en) | double-pH-sensitive drug carrier system and preparation method thereof | |
| CN102697731B (en) | 5-aminolevulinic acid nano particle as well as preparation method and device thereof | |
| CN106466300B (en) | A kind of recombination chitosan nano particle preparations and its preparation method and application loading insoluble drug | |
| CN101696278A (en) | Preparation method of water soluble self-assembly chitosan nano-particles and application of chitosan nano-particles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Xuegui Inventor after: Gao Pinyi Inventor after: Song Lin Inventor after: Nian Zhongfeng Inventor after: Zhang Zhenxue Inventor before: Song Tianyang Inventor before: Zhang Jinlu Inventor before: Liu Xuegui Inventor before: Nian Zhongfeng Inventor before: Gao Pinyi Inventor before: Zhang Zhenxue |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: SONG TIANYANG ZHANG JINLU LIU XUEGUI NIAN ZHONGFENG GAO PINYI ZHANG ZHENXUE TO: LIU XUEGUI GAO PINYI SONG LIN NIAN ZHONGFENG ZHANG ZHENXUE |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information |
Inventor after: Gao Pinyi Inventor after: Liu Xuegui Inventor after: Zhang Zhenxue Inventor before: Liu Xuegui Inventor before: Gao Pinyi Inventor before: Song Lin Inventor before: Nian Zhongfeng Inventor before: Zhang Zhenxue |
|
| CB03 | Change of inventor or designer information |