CN104739783A - Preparation method and product of biodegradable polylactic acid-hydroxyacetic acid copolymer/chitosan drug carrying microsphere - Google Patents
Preparation method and product of biodegradable polylactic acid-hydroxyacetic acid copolymer/chitosan drug carrying microsphere Download PDFInfo
- Publication number
- CN104739783A CN104739783A CN201510176581.9A CN201510176581A CN104739783A CN 104739783 A CN104739783 A CN 104739783A CN 201510176581 A CN201510176581 A CN 201510176581A CN 104739783 A CN104739783 A CN 104739783A
- Authority
- CN
- China
- Prior art keywords
- plga
- microsphere
- concentration
- chitosan
- solution
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
The invention relates to a preparation method for a biodegradable polylactic acid-hydroxyacetic acid copolymer/chitosan drug carrying microsphere. The preparation method is used for preparing a PLGA-CS composite microsphere which entraps hydrophilic protein drugs through an improved physical process. Surface hydrolysis-modification is firstly performed on PLGA, so that the carboxyl group content is increased and the quantity of electric charge is increased. In order to further increase a drug loading ratio and prolong the sustained-release time, the multi-layer composite PLGA-CS drug-loading composite microsphere is prepared by adopting a layer-layer self-assembly technology.
Description
Technical field
The present invention relates to the preparation method of the Poly(D,L-lactide-co-glycolide composite drug carried microsphere of a kind of degradable medicaments carrier material, particularly a kind of surface modification.
The invention still further relates to the composite drug carried microsphere that said method obtains.
Background technology
In recent years, along with the development of genetic engineering recombinant technique and protein science, the application clinically of polypeptide and protein medicaments is increasingly extensive, deeply.Due to such medicine poor stability in vivo and in vitro, the half-life is short, is subject to the impact of intestines and stomach pH environment and enzyme and inactivation, needs frequent, heavy dose of and long-time administration, cause the generation of toxic and side effects and toleration, had a strong impact on its Clinical practice effect.Therefore, significant to the research of the protection of polypeptide, protein-based biologically active drug.
Poly(D,L-lactide-co-glycolide (being called for short PLGA) is biodegradable functional polymer organic compound, not only have nontoxic, degradable, the advantages such as good biocompatibility, and be used for human body by food and drug administration (FDA) approval, have huge application prospect at pharmaceutical field.Because its degradation rate changes along with the difference of two kinds of Composition ratio of compound examples, the poly lactic-co-glycolic acid therefore different proportion can being selected to be combined into according to the character of medicine and purposes, is prepared into the microball preparation with given efficacy.But PLGA also also exists deficiency as drug carrier material: (1) exists obvious burst effect at drug release process, adds side effects of pharmaceutical drugs, also may cause drug waste and microsphere cannot be discharged for a long time; (2) PLGA microsphere and body cell lack specific combination, and cellular uptake is indifferent, drug absorption poor effect.
Chitosan (CS) is a kind of alkaline polysaccharide, high containing hydroxyl, amino, positive charge density in its structure, is conducive to the adhesion of cell, and cheap and easy to get, nonpoisonous and tasteless, and degradation in vivo is that glucosamine can be absorbed; Simultaneously chitosan has the function such as expression of activated macrophage, induction of immunity regulatory factor, has excellent biocompatibility and adsorptivity.
In recent years, the bag that PLGA medicine carrying microcapsule based on chitin modified modification has been used to various medicine carries and on slow release, the method of modifying and decorating mainly contains Physical and chemical method two kinds, so-called chemical method mainly prepares copolymer with chitosan and PLGA covalent cross-linking, then self assembly obtains medicine carrying microcapsule, discloses the preparation method of the chitosan-PLGA composite nano particle of a kind of year hydrophilic medicament as Chinese patent CN103006567A.Physical is simple compared with chemical method process, mainly be composited based on the electrostatic attraction between two kinds of oppositely charged polymer, prepared by most employing emulsified solvent volatilization technology, Chinese patent CN104001178A discloses the PLGA nano-medicament carrier that a kind of PLGA Nano microsphere kernel of being prepared by mon-galacta method and vanillin cross-linked chitosan shell are formed, and is applied to bag and carries a hydrophobicity tumour medicine.Its major defect is that the drug encapsulation rate of this complex carrier is lower, causes wastage of material and cannot reach the object of long-term sustained release.The present invention adopts improvement Physical preparation bag to carry the PLGA-CS complex microsphere of hydrophilic protein class medicine, first the present invention carries out surface hydrolysis modified to PLGA, thus increase its carboxyl-content, improve its quantity of electric charge, in order to improve carrying drug ratio further, extend slow-release time, layer-by-layer is adopted to prepare MULTILAYER COMPOSITE PLGA-CS medicine carrying complex microsphere.
Summary of the invention
The present invention completes to solve above-mentioned deficiency of the prior art, the object of this invention is to provide the preparation method of a kind of Biodegradable polylactic acids-hydroxyacetic acid PLGA/ chitosan drug-loading microsphere.
Technical scheme is as follows:
Said method comprising the steps of:
(1) hydrolysis of PLGA
PLGA film is soaked in 30-50 DEG C of concentration in about 2mol/L NaOH solution, take out after 2.0-6.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of vacuum drying 24h, obtain the PLGA be hydrolyzed;
(2) preparation of PLGA-CS medicine carrying microballoons
Taking quantitative chitosan is dissolved in acetic acid solution, be made into concentration be 1% chitosan solution stand-by;
The PLGA got after about 0.5g hydrolysis is dissolved in 20mL dichloromethane, add BSA (bovine serum albumin) aqueous solution of 10mL concentration 5-10wt% again, add 0.2mL Tween 80 ultrasonic emulsification 1min, it is in PVA (polyvinyl alcohol) aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min, the W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, 1g sodium tripolyphosphate (TPP) is dripped after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA, being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA, and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere, being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.
The present invention is Biodegradable polylactic acids-hydroxyacetic acid PLGA/ chitosan drug-loading microsphere of preparing of further claimed said method also.
Accompanying drawing explanation
Fig. 1 is the In-vitro release curves of medicine carrying microballoons of the present invention.
Detailed description of the invention
Below in conjunction with embodiment and comparative example, the present invention is described in detail, and following embodiment is only used for the detailed explanation to description, not as restriction of the present invention.
The PLGA film that the present invention uses adopts following method to prepare:
Taking 2.0gPLGA is dissolved in 20mL dichloromethane, stirs and pours in mould after dissolving completely, and after room temperature volatilization 24h, by its vacuum drying 24h at 35 DEG C, thin film takes out stand-by.
Other reagent of the present invention is all by commercially available.
Detailed description of the invention
Embodiment 1
2.0gPLGA film being soaked in 50mL30 DEG C of concentration is in 2mol/L NaOH solution, take out after 2.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of vacuum drying 24h, obtain the PLGA be hydrolyzed, its surface-bound carboxylic content and surface charge are in table 1.
The PLGA got after 0.5g hydrolysis is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 5%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min.The W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, drips 1gTPP after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA; Being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA (after hydrolysis), and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere; Being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.The mean diameter of products obtained therefrom, electric charge size, carrying drug ratio and envelop rate are in table 1.
Embodiment 2
2.0gPLGA film being soaked in 50mL30 DEG C of concentration is in 2mol/L NaOH solution, take out after 6.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of vacuum drying 24h, obtain the PLGA be hydrolyzed, its surface-bound carboxylic content and surface charge are in table 1.
The PLGA got after 0.5g hydrolysis is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 8%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min.The W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, drips 1gTPP after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA; Being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA (after hydrolysis), and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere; Being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.The mean diameter of products obtained therefrom, electric charge size, carrying drug ratio and envelop rate are in table 1.
Embodiment 3
2.0gPLGA film being soaked in 50mL50 DEG C of concentration is in 2mol/L NaOH solution, take out after 2.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of vacuum drying 24h, obtain the PLGA be hydrolyzed, its surface-bound carboxylic content and surface charge are in table 1.
The PLGA got after 0.5g hydrolysis is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 9%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min.The W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, drips 1gTPP after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA; Being placed on 20mL is dissolved with in the dichloromethane solution of 0.5g PLGA (after hydrolysis), and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere; Being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.The mean diameter of products obtained therefrom, electric charge size, carrying drug ratio and envelop rate are in table 1.
Embodiment 4
2.0gPLGA film being soaked in 50mL50 DEG C of concentration is in 2mol/L NaOH solution, take out after 6.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of vacuum drying 24h, obtain the PLGA be hydrolyzed, its surface-bound carboxylic content and surface charge are in table 1.
The PLGA got after 0.5g hydrolysis is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 10%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min.The W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, drips 1gTPP after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA; Being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA (after hydrolysis), and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere; Being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.The mean diameter of products obtained therefrom, electric charge size, carrying drug ratio and envelop rate are in table 1.
Comparative example 1
Getting 0.5g PLGA is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 5%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, and ultrasonic emulsification 2min forms emulsion W/O/W.Gained emulsion is at room temperature stirred 3h, organic solvent is volatilized completely, microsphere curing molding, collected by centrifugation, with distilled water wash 3 times, obtain PLGA medicine carrying microballoons powder after lyophilization 24h, the carboxyl-content of raw material PLGA and the mean diameter of thus obtained microsphere product, electric charge size, carrying drug ratio and envelop rate are in table 1.
Comparative example 2
Getting 0.5g PLGA is dissolved in 20mL dichloromethane, add 10mLBSA aqueous solution (concentration 5%) again, add ultrasonic emulsification 1min after 0.2mL Tween 80, it is in the PVA aqueous solution of 1% that the Water-In-Oil obtained (W/O) emulsion pours 100mL concentration into, ultrasonic emulsification 2min.The W/O/W emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, drips 1gTPP after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA; Being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA, and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere; Being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.The mean diameter of products obtained therefrom, electric charge size, carrying drug ratio and envelop rate are in table 1.
Comparative example 1 is directly by the result that unhydrolysed PLGA is raw material preparation year BSA microsphere, and comparative example 2 is for carrying out the result of compound layer by layer after raw material preparation year BSA microsphere with chitosan with unhydrolysed PLGA.PLGA impact on performances such as medicine carrying microballoons electric charge, particle diameter, carrying drug ratio and envelop rates after hydrolysis process is contrasted with this.
The product taken in the embodiment 1 of equal in quality, comparative example 1 and comparative example 2 carries out release in vitro test, concrete steps are as follows: accurately take 20mg medicine carrying microballoons and be placed in centrifuge tube, add the buffer solution of 50mL pH7.4 (simulated intestinal fluid), be placed in 37 DEG C of water-bath constant temperature oscillations, timing sampling 5mL measures absorbance in 283nm place, adds the buffer solution of equivalent homogeneity simultaneously.Standard curve according to BSA calculates medicament contg, and draw release profiles, all samples parallel assay 3 times, gets its meansigma methods.
Result as shown in Figure 1.Contrast can be found out, the prominent phenomenon of releasing of product drug release process of the present invention obviously reduces, and can reach better slow release effect.
The performance parameter of table 1PLGA hydrolyzate and medicine carrying microballoons
Applicant also finds whether add the carrying drug ratio that TPP also have impact on product of the present invention in BSA concentration of aqueous solution and complex microsphere preparation simultaneously, applicant carried out comparative example 3, its institute in steps, product consumption is all identical with embodiment 1, and difference does not add TPP after being to add chitosan in composite drug carried microsphere preparation process.Also carried out its difference from Example 1 of comparative example 4,5 simultaneously and be only that the concentration of aqueous solution of BSA is 1%, 15%, its concrete carrying drug ratio numerical value sees the following form 2
Table 2
| Carrying drug ratio | |
| Comparative example 3 | 13.25％ |
| Comparative example 4 (1%) | 17.65％ |
| Comparative example 5 (15%) | 17.10％ |
Add TPP as can be seen from the above data also to produce a very large impact product carrying drug ratio of the present invention when being prepared, the concentration of BSA also have impact on the carrying drug ratio of final products simultaneously, these factors create synergism with adopting the PLGA film be hydrolyzed, and jointly impel final products to obtain excellent performance.
Beneficial effect
As can be seen from Figure 1, PLGA microsphere drug release rate 23.42% in 1h in comparative example 1, in comparative example 2, after chitosan compound, microsphere drug release rate in 1h drops to 16.52%, and in embodiment 1 after PLGA hydrolysis process again the microsphere of recombination chitosan be reduced to 13.11% at the drug release rate of 1h, burst drug release phenomenon obviously reduces, and can reach longer release time.
Above-mentionedly only several specific embodiments in the present invention to be illustrated; but can not as protection scope of the present invention; every according to the change of the equivalence done by design spirit in the present invention or to modify or equal proportion zooms in or out, all should think and fall into protection scope of the present invention.
Claims (2)
1. a preparation method for Biodegradable polylactic acids-co-glycolic acid/chitosan drug-loading microsphere, is characterized in that said method comprising the steps of:
(1) hydrolysis of PLGA
PLGA film is soaked in 30-50 DEG C of concentration in about 2mol/L NaOH solution, take out after 2.0-6.0h, clean with 1mol/L HCl solution, to remove the NaOH of remained on surface, then under Ultrasonic Conditions with ethanol and deionized water wash 2 times, be placed in 30 DEG C of about 24h of vacuum drying, obtain the PLGA be hydrolyzed;
(2) preparation of PLGA-CS medicine carrying microballoons
Taking quantitative chitosan is dissolved in acetic acid solution, be made into concentration be 1% chitosan solution stand-by;
The PLGA got after about 0.5g hydrolysis is dissolved in about 20mL dichloromethane, add BSA (bovine serum albumin) aqueous solution of 10mL concentration 5-10wt% again, add 0.2mL Tween 80 ultrasonic emulsification 1min, it is in PVA (polyvinyl alcohol) aqueous solution of 1% that Water-In-Oil (W/O) emulsion obtained pours 100mL concentration into, ultrasonic emulsification 2min, oil/water/oil (W/O/W) the emulsion at room temperature magnetic agitation of gained, drip 5g concentration is the chitosan solution of 1% simultaneously, 1g sodium tripolyphosphate (TPP) is dripped after 0.5h, continue afterwards to stir 3h, organic solvent is volatilized completely, microsphere curing molding, obtain the two-layer composite drug carried microsphere of positively charged PLGA, being placed on 20mL is dissolved with in the dichloromethane solution of 0.5gPLGA, and at 25 DEG C, centrifugalize cleaning after sonic oscillation 30min, obtains three layers of electronegative composite drug carried microsphere, being added 5g concentration is in the chitosan solution of 1%, drips 1gTPP, centrifugalize after 0.5h after magnetic agitation 0.5h, with distilled water wash 3 times, namely obtains PLGA composite drug carried microsphere powder-product after lyophilization 24h.
2. Biodegradable polylactic acids-co-glycolic acid/chitosan drug-loading microsphere, it is characterized in that what method according to claim 1 prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510176581.9A CN104739783B (en) | 2015-04-14 | 2015-04-14 | Biodegradable polylactic acids co-glycolic acid/chitosan drug-loading method for preparing microsphere and product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510176581.9A CN104739783B (en) | 2015-04-14 | 2015-04-14 | Biodegradable polylactic acids co-glycolic acid/chitosan drug-loading method for preparing microsphere and product |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104739783A true CN104739783A (en) | 2015-07-01 |
| CN104739783B CN104739783B (en) | 2017-09-15 |
Family
ID=53580414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510176581.9A Active CN104739783B (en) | 2015-04-14 | 2015-04-14 | Biodegradable polylactic acids co-glycolic acid/chitosan drug-loading method for preparing microsphere and product |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104739783B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105060508A (en) * | 2015-09-14 | 2015-11-18 | 湖州道场污水处理有限公司 | Biological sewage-treatment complex microbial inoculant and preparation method thereof |
| CN105494430A (en) * | 2015-12-16 | 2016-04-20 | 河北科技大学 | Silver-loaded low-molecular-weight chitosan composite microsphere antibacterial agent and preparation method thereof |
| CN105617389A (en) * | 2016-03-23 | 2016-06-01 | 首都医科大学附属北京朝阳医院 | Positively charged nano microsphere medicine carrier for eye and preparation method of positively charged nano microsphere medicine |
| CN106038512A (en) * | 2016-06-15 | 2016-10-26 | 华侨大学 | Layer-by-layer self-assembly nano-carrier and preparation method thereof |
| CN107375236A (en) * | 2017-08-05 | 2017-11-24 | 重庆科技学院 | A kind of preparation method of the complex microsphere of double-layer circular spherical structure |
| CN109529126A (en) * | 2018-10-22 | 2019-03-29 | 深圳齐康医疗器械有限公司 | A kind of artificial dermis and preparation method thereof |
| CN110090293A (en) * | 2019-05-10 | 2019-08-06 | 南京工业大学 | A method of inhibiting the acylated side reaction of polypeptide drug in PLGA microballoon |
| CN110327310A (en) * | 2019-07-24 | 2019-10-15 | 华中科技大学鄂州工业技术研究院 | A kind of multicore is total to shell composite drug carried microsphere and its preparation method and application |
| CN112790353A (en) * | 2021-01-14 | 2021-05-14 | 蔡宏旦 | Dried vegetable with high vitamin content and preparation method thereof |
| CN115644175A (en) * | 2022-11-14 | 2023-01-31 | 中国农业科学院农产品加工研究所 | Preparation method of nano embedded pesticide and nano embedded pesticide |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557283A (en) * | 2004-01-18 | 2004-12-29 | 浙江大学 | Ternary composite microsphere formulation and its preparation method |
| WO2009075652A1 (en) * | 2007-12-11 | 2009-06-18 | Nanyang Technological University | Hollow multi-layered microspheres for delivery of hydrophilic active compounds |
| CN101889985A (en) * | 2010-07-08 | 2010-11-24 | 东华大学 | Medicament-carrying nano microspheres and preparation method thereof |
| CN104001178A (en) * | 2014-05-19 | 2014-08-27 | 中山大学 | Polylactic acid-hydroxyacetic acid copolymer nano-drug carrier as well as preparation method and application thereof |
-
2015
- 2015-04-14 CN CN201510176581.9A patent/CN104739783B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557283A (en) * | 2004-01-18 | 2004-12-29 | 浙江大学 | Ternary composite microsphere formulation and its preparation method |
| WO2009075652A1 (en) * | 2007-12-11 | 2009-06-18 | Nanyang Technological University | Hollow multi-layered microspheres for delivery of hydrophilic active compounds |
| CN101889985A (en) * | 2010-07-08 | 2010-11-24 | 东华大学 | Medicament-carrying nano microspheres and preparation method thereof |
| CN104001178A (en) * | 2014-05-19 | 2014-08-27 | 中山大学 | Polylactic acid-hydroxyacetic acid copolymer nano-drug carrier as well as preparation method and application thereof |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105060508A (en) * | 2015-09-14 | 2015-11-18 | 湖州道场污水处理有限公司 | Biological sewage-treatment complex microbial inoculant and preparation method thereof |
| CN105494430A (en) * | 2015-12-16 | 2016-04-20 | 河北科技大学 | Silver-loaded low-molecular-weight chitosan composite microsphere antibacterial agent and preparation method thereof |
| CN105494430B (en) * | 2015-12-16 | 2018-03-06 | 河北科技大学 | One kind carries silver-colored low-molecular weight chitoglycan complex microsphere antiseptic and preparation method thereof |
| CN105617389A (en) * | 2016-03-23 | 2016-06-01 | 首都医科大学附属北京朝阳医院 | Positively charged nano microsphere medicine carrier for eye and preparation method of positively charged nano microsphere medicine |
| CN106038512B (en) * | 2016-06-15 | 2019-06-04 | 华侨大学 | A kind of LBL self-assembly nano-carrier and preparation method thereof |
| CN106038512A (en) * | 2016-06-15 | 2016-10-26 | 华侨大学 | Layer-by-layer self-assembly nano-carrier and preparation method thereof |
| CN107375236A (en) * | 2017-08-05 | 2017-11-24 | 重庆科技学院 | A kind of preparation method of the complex microsphere of double-layer circular spherical structure |
| CN109529126A (en) * | 2018-10-22 | 2019-03-29 | 深圳齐康医疗器械有限公司 | A kind of artificial dermis and preparation method thereof |
| CN110090293A (en) * | 2019-05-10 | 2019-08-06 | 南京工业大学 | A method of inhibiting the acylated side reaction of polypeptide drug in PLGA microballoon |
| CN110090293B (en) * | 2019-05-10 | 2023-04-07 | 南京工业大学 | Method for inhibiting side acylation reaction of polypeptide drug in PLGA microsphere |
| CN110327310A (en) * | 2019-07-24 | 2019-10-15 | 华中科技大学鄂州工业技术研究院 | A kind of multicore is total to shell composite drug carried microsphere and its preparation method and application |
| CN110327310B (en) * | 2019-07-24 | 2021-10-22 | 华中科技大学鄂州工业技术研究院 | Multi-core shell-sharing composite drug-loaded microsphere and preparation method and application thereof |
| CN112790353A (en) * | 2021-01-14 | 2021-05-14 | 蔡宏旦 | Dried vegetable with high vitamin content and preparation method thereof |
| CN115644175A (en) * | 2022-11-14 | 2023-01-31 | 中国农业科学院农产品加工研究所 | Preparation method of nano embedded pesticide and nano embedded pesticide |
| CN115644175B (en) * | 2022-11-14 | 2023-11-10 | 中国农业科学院农产品加工研究所 | Preparation method of nano-embedded pesticide and nano-embedded pesticide |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104739783B (en) | 2017-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104739783A (en) | Preparation method and product of biodegradable polylactic acid-hydroxyacetic acid copolymer/chitosan drug carrying microsphere | |
| Panos et al. | New drug delivery systems based on chitosan | |
| Elieh-Ali-Komi et al. | Chitin and chitosan: production and application of versatile biomedical nanomaterials | |
| CN109432048B (en) | Platelet membrane-coated drug-loaded porous nanoparticle and preparation method thereof | |
| WO2015192603A1 (en) | Oil-in-water emulsion containing no surfactant and use thereof | |
| Nair et al. | Application of chitosan microspheres as drug carriers: a review | |
| CN101658497B (en) | Dual drug-loading composite microsphere and preparation method thereof | |
| CN102532580B (en) | Method for preparing multifunctional nano-carrier | |
| CN105106174B (en) | A kind of core-shell structure copolymer bilayer microballoon and preparation method thereof | |
| CN102198117B (en) | Thermosensitive polymeric microcapsules and preparation method and use thereof | |
| CN105997936B (en) | A kind of preparation method of carboxymethyl chitosan nano particle immobilization porous multilayer sodium alginate glueballs | |
| CN101947212A (en) | Micro-embedded medicament carrier and preparation method thereof | |
| CN1557283A (en) | Ternary composite microsphere formulation and its preparation method | |
| CN107890465A (en) | A kind of preparation method for the magnetic Nano carried medicine sustained-release microsphere for wrapping up 5 fluorouracils | |
| Duan et al. | Recent innovations in immobilization of β-galactosidases for industrial and therapeutic applications | |
| Sudareva et al. | Hybrid systems for oral delivery of a therapeutic neuropeptide | |
| CN205903442U (en) | Novel sustained -release microsphere based on 3D printing technique | |
| CN114569582A (en) | Enzyme preparation, preparation method and application thereof | |
| CN101757631B (en) | Composition of biocompatible microparticles of alginic acid for the controlled release of active ingredients by intravenous administration | |
| MX2014001910A (en) | Method for obtaining microspheres for the controlled release of sensitive active ingredients, produced by assembling porous microspheres and nanoparticles. | |
| CN102362861A (en) | Hollow composite nanoparticle with core-shell structure and preparation method thereof | |
| JP2009215220A (en) | Microcapsule and method for producing the same | |
| Nah et al. | Preparation and encapsulation techniques of chitosan microsphere for enhanced bioavailability of natural antioxidants | |
| CN105395520A (en) | Glucosamine microcapsule and preparation method thereof | |
| CN1069827C (en) | Polypeptide protein micro-beads medicine prepn. method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181126 Address after: 311400 No. 26 Dengcheng North Road, Xindeng Town, Fuyang District, Hangzhou City, Zhejiang Province Patentee after: Zhejiang Xinyuan Technology Co., Ltd. Address before: No. 159, dragon pan Road, Nanjing, Jiangsu Patentee before: Nanjing Forestry University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210513 Address after: 311508 No.77, Tantou Road, Tonglu Economic Development Zone, Tonglu County, Hangzhou City, Zhejiang Province Patentee after: Zhejiang Xinyuan Industrial Co.,Ltd. Address before: 311400 No. 26 Dengcheng North Road, Xindeng Town, Fuyang District, Hangzhou City, Zhejiang Province Patentee before: Zhejiang Xinyuan Technology Co.,Ltd. |