CN105687133A - Amphiphilic chitosan derivative drug-loaded nano-micelle and preparation method - Google Patents
Amphiphilic chitosan derivative drug-loaded nano-micelle and preparation method Download PDFInfo
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- CN105687133A CN105687133A CN201610125193.2A CN201610125193A CN105687133A CN 105687133 A CN105687133 A CN 105687133A CN 201610125193 A CN201610125193 A CN 201610125193A CN 105687133 A CN105687133 A CN 105687133A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Abstract
The invention discloses an amphiphilic chitosan derivative drug-loaded nano-micelle and a preparation method and belongs to the field of pharmaceutical preparations. Amphiphilic chitosan derivatives form the micelle by means of self assembling, vitamin E succinate serves as a kernel, and thiolated chitosan serves as a shell; the hydrophobic kernel is used for entrapping a hydrophobic anti-HIV drug, the shell carrying positive charges is used for adsorbing cytomembrane, the loaded drug can be stably released in vivo, the hydrophilic shell is used for enhancing the solubility of the micelle and maintaining the stability of the micelle in a solution, and then the blood circulation time of the micelle after systematic administration is prolonged. The micelle can stably exist in all kinds of body fluid for more than 10 hours after particles are formed, the particle size is smaller than 200 nanometers, and it is beneficial for controlling the micelle particles to enter cells without being removed by macrophages. The delivery system can keep stability under the condition that serums exist, the drug is delivered into the cells, and good biocompatibility is achieved.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of amphiphilic chitosan derivative (chitosan-vitamin e succinate-N-acetyl-L-cysteine) nano-micelle, preparation method and application thereof。
Background technology
Along with the increase day by day of going from bad to worse of global ecological environment, people's rhythm of life and operating pressure, the M & M of acquired immune deficiency syndrome (AIDS) this serious threat human life and healthy major disease increases year by year。China is first big country in Asia, and economy develops rapidly in recent years, and acquired immune deficiency syndrome (AIDS) is attacking this country also silently simultaneously。Present China has become one of fastest-rising country of world's acquired immune deficiency syndrome (AIDS)。
Estimating China survival patients infected hiv and patient (HIV/AIDS) about 740,000 people at present by the end of the year 2009, wherein AIDS patients is 10.5 ten thousand people；Estimate 2009 newly to send out patients infected hiv 4.8 ten thousand people then, dead 2.6 ten thousand people (Ministry of Health of the People's Republic of China: " in low epidemic status, China's AIDS Epidemic totally estimates that this year newly sends out patients infected hiv 4.8 people ", http://www.moh.gov.cn/sofpro/cms/Previewjspfile/wsb/cms_ooooooo ooooooooo207_tpl.jsp？RequestCode=44690&CategoryID=527,2009-11-25)。Expert estimates: 2010, China's AIDS number of the infected was likely to up to 12,000,000 people。Acquired immune deficiency syndrome (AIDS) become the mankind must faced by a worldwide difficult problem。But the special biological property due to acquired immune deficiency syndrome (AIDS) itself, the features such as i.e. inhibition of HIV variation, multidrug resistance, make the very big (Zhang Fujie for the treatment of difficulty of acquired immune deficiency syndrome (AIDS), Wen Yi, Yu Lan, Ma Ye, Pan Jie, Zhao Yan. the antiviral therapy of acquired immune deficiency syndrome (AIDS) and the free treatment present situation [J] of China. scientific and technological Leader, 2005,7 (23))。
At present, all there is the shortcoming in drug effect and application in the most inverases applied clinically:
(1) dissolubility is low, and most medicines are hydrophobicity, in aqueous poor dissolution, easily precipitate, need to add solubilizing agent, cosolvent or cosolvent to improve dissolubility；
(2) toxic and side effects is big, is distributed poor selectivity after administration in vivo。Before arriving target site, oneself, through being distributed in normal structure too much, reduces target site drug level to medicine。Additionally the addition of adjuvant is easily caused by serious side reaction, as caused allergic reaction after administration, nephrotoxicity, neurotoxicity, bone marrow depression etc., had a strong impact on therapeutic effect (Gao Zhixian. Li little Qiang. nano biological medicine [M]. Beijing: Chemical Industry Press, 2007:1-30)；
(3) pharmacokinetic property is poor, eliminates rapidly through liver, spleen after administration, it is necessary to continuous drip or higher dosage；And if by after oral administration of drugs, being not only due to its extremely strong hydrophobicity is difficult to be absorbed, and also drug absorption can be stoped because of the physiological barriers of internal existence；
(4) degradable, before medicine arrives patient part, experience the processes such as protein binding, metabolism, degraded。
Merck is first integrase inhibitor in acquired immune deficiency syndrome (AIDS) antiviral drugs, is approved listing by U.S. FDA in 2007,2008 in European granted listing, for treating 2 years old and the antiviral therapy of above HIV person。The Merck sheet of Merck company is first hiv integrase chain tra nsfer inhibitor (English integrasestrandtransferinhibitors, referred to as integrase inhibitor), also known as MK-0518, human immunodeficiency virus (HIV)-1 can be treated with other antiretroviral drugs drug combination and infect (Li Yanfeng, Bai Qiujiang, Zhao Jun. AntiHIV1 RT activity infects new drug: Rahegravir [J]. difficult disease magazine, 2008,7 (5): 308)。It slows down the HIV-1 generation infected by the hiv integrase needed for suppressing virus replication。Its modal untoward reaction is diarrhoea, feels sick, has a headache。Additionally, blood test shows that some take the abnormal rising of patient's creatase of this product。
Summary of the invention
For solving above-mentioned the deficiencies in the prior art, the preparation method that the invention provides a kind of amphiphilic chitosan derivative medicament-carried nano micelle, the present invention is directed to the shortcomings and deficiencies that prior art exists, it is provided that a kind of have good biocompatibility and biodegradability loading polymer material。In view of Merck etc. has poorly soluble, metabolism is very fast in vivo, the shortcomings such as bioavailability is relatively low, and side effect is big。We utilize nano-micelle that modification of chitosan is fabricated to wrap load Merck, improve the bioavailability of Merck, go to reduce side effect。The method can be used for multiple amphiphilic and builds carrier micelle, and easy and simple to handle, consuming time shorter, and the carrier micelle of gained has good stability, without phenomenon of burst release in simulated body fluid pH solution。
The preparation method that one of technical scheme realizing the object of the invention is to provide a kind of amphiphilic chitosan derivative medicament-carried nano micelle, comprises the following steps:
(1) amphipathic nature polyalcohol chitosan-vitamin e succinate-N-acetyl-L-cysteine is joined in deionized water, magnetic agitation is to forming translucent solution and mix homogeneously, resulting polymers solution is first passed through the Medium speed filter paper that aperture is 30-50 μm, then then through the filter membrane of 0.8 μm, carry out the centrifugal of 3000-5000r/min, then take supernatant and cross 0.45 μm of syringe filter, discard first two, the amphipathic nature polyalcohol solution obtained；
(2) being dissolved in suitable solvents by the hydrophobic drug weighed, stirring makes medicine dissolution uniform；When stirring, the drug solution dissolved joining in amphipathic nature polyalcohol solution dropwise, stir；
(3) the both the above mixed solution being stirred uses rotary evaporator decompression steam the solvent of step (2), stop when starting to occur muddiness, remaining solution is carried out ultrasonic under probe type ultrasonic instrument, preferred ultrasonic 10min, power 150W, work 5s, interval 3s；Gained solution is centrifugal when 3000-5000r/min, takes supernatant and crosses 0.45 μm of needle type filtration film, obtains the amphipathic nature polyalcohol micelle of medicine carrying。
The preparation of step (1) polymer solution, it is preferable that every 5mg chitosan-vitamin e succinate-N-acetyl-L-cysteine correspondence is dissolved in 5mL deionized water。
The drug solution dissolved joining in amphipathic nature polyalcohol solution dropwise in step (2)。
Hydrophobic drug described in step (2) is the one in Merck or camptothecine。
The solvent corresponding with Merck is the one in acetonitrile, methanol；The solvent corresponding with camptothecine is the one in DMSO or methanol and chloroform mixed solution or aqueous alkali。
The present invention is self-assembly of micelle by amphipathic chitose is derivative, and with vitamin e succinate for kernel, thio chitosan is shell；Hydrophobic cores is used for wrapping the hydrophobic inverase of load, carry the shell of positive charge for adherent cell film, can stably discharge the medicine of institute's load in vivo, hydrophilic shell, for strengthening micelle dissolubility and keeping micelle stablizing in the solution, extends its blood circulation time after being administered systemically。Micelle provided by the invention can be stable after granule is formed be present in more than 10 hours in various body fluid, particle diameter is respectively less than 200 nanometers, is conducive to controlling the entrance cell of micelle granule and not removed by macrophage。This delivery system can under serum existent condition remaining stable for property, medicine is sent into cell, and there is good biocompatibility。Micelle provided by the invention can carry hydrophobic inverase in the way of oral and enter human body, overcomes injectivity administration excitatory greatly, and the shortcoming of patient's poor compliance improves the bioavailability of Merck, reduces side effect。
Compared with prior art, the invention have the advantages that
1 present invention is with chitosan for hydrophilic skeleton, and vitamin e succinate is hydrophobic inner core, and N-acetylcystein is surface functional group, has synthesized the chitosan-vitamin e succinate-N-acetyl-L-cysteine copolymer material with sulfydryl。
The functional material of 2 present invention self-chambering can form nano-micelle, and be provided simultaneously with soluble drug, suppress transporter, bioadhesive and promote the functions such as permeability, develops for inverase oral delivery and adjuvant and provides new approaches。
3 with hydrophobic drugs such as Mercks for model, forms stable nano-micelle for carrier material。Compared with conventional formulation, this micelle, while possessing bioadhesive, can effectively utilize surface free sulfhydryl groups to overcome the obstruction of gastrointestinal tract surface mucus layer, change the rheological property of rete malpighii, escape mucinous winding and arrive gastrointestinal tract surface, increase oral absorption。
Accompanying drawing explanation
Fig. 1 adopts the grain-size graph of micelle after the blank micelle of particle size analyzer determination chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer and medicine carrying in the embodiment of the present invention 1；
Fig. 2 is the grain size distribution of the polymer drug-carried rear micelle of chitosan-vitamin e succinate-N-acetyl-L-cysteine adopting particle size analyzer determination in the embodiment of the present invention 1。
Fig. 3 adopts the current potential of micelle after the blank micelle of particle size analyzer determination chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer and medicine carrying in the embodiment of the present invention 1；
Fig. 4 is the potential image that in the embodiment of the present invention 1, chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer is self-assembly of micelle in aqueous；
Fig. 5 is the result figure utilizing particle instrument to measure chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer supported Merck micelle stability experiment in different pH medium in the embodiment of the present invention 1；
Fig. 6 is the transmission electron microscope picture that chitosan-vitamin e succinate in the embodiment of the present invention 1-N-acetyl-L-cysteine modification of chitosan polymer is self-assembly of micelle in aqueous；
Fig. 7 is the embodiment of the present invention 1 chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan polymer supported Merck micelle In-vitro release curves in different buffer。
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further described, but the present invention is not limited to following example。
Embodiment 1
(1) the amphipathic nature polyalcohol micelle that preparation is blank: 5mg amphipathic nature polyalcohol chitosan-vitamin e succinate-N-acetyl-L-cysteine is dissolved in 5ml deionized water, magnetic agitation is to being completely dissolved and mix homogeneously, resulting polymers solution is first passed through the Medium speed filter paper that aperture is 30-50 μm, then then through the filter membrane of 0.8 μm, at the centrifugal 5min of 4000r/min, take supernatant and cross 0.45 μm of syringe filter, discard first two, the solution finally obtained is ultrasonic 10min (power 150W under probe type ultrasonic instrument, work 5s, interval 3s)。Gained solution, at the centrifugal 5min of 3000r/min, takes supernatant and crosses 0.45 μm of needle type filtration film, obtain blank amphipathic nature polyalcohol micelle。
(2) amphiphilic nano-micelle
5mg amphipathic nature polyalcohol chitosan-vitamin e succinate-N-acetyl-L-cysteine is joined in 5ml deionized water, magnetic agitation is to being completely dissolved and mix homogeneously, resulting polymers solution is first passed through the Medium speed filter paper that aperture is 30-50 μm, then then through the filter membrane of 0.8 μm, at the centrifugal 5min of 4000r/min, take supernatant and cross 0.45 μm of syringe filter, discard first two, the amphipathic nature polyalcohol solution obtained。Being dissolved in by the 4mg Merck weighed in the solvent (acetonitrile or methanol) of correspondence, magnetic agitation makes medicine dissolution uniform。Amphipathic nature polyalcohol solution is when stirring, the drug solution dissolved dropwise join in amphipathic nature polyalcohol solution, the both the above mixed solution being stirred use rotary evaporation decompression steam solvent acetonitrile or methanol, stop when starting to occur muddiness, remaining solution ultrasonic 10min (power 150W under probe type ultrasonic instrument, work 5s, interval 3s)。Gained solution, at the centrifugal 5min of 3000r/min, takes supernatant and crosses 0.45 μm of needle type filtration film, obtain the amphipathic nature polyalcohol micelle of medicine carrying。
The particle diameter of micelle is as shown in Figure 1 after blank micelle and medicine carrying for what the present embodiment provided adopt particle size analyzer determination chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan polymer；The mean diameter of blank micelle is 180nm, and carrier micelle mean diameter is 200nm, and after having carried medicine, particle diameter is slightly larger than blank micelle。
The particle size distribution of the polymer drug-carried rear micelle of chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan adopting particle size analyzer determination that the present embodiment provides is as shown in Figure 2；Micelle particle diameter distribution is narrower, all between 100-600nm, is distributed comparatively uniform。
The current potential of micelle is as shown in Figure 3 after blank micelle and medicine carrying for what the present embodiment provided adopt particle size analyzer determination chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan polymer；The current potential of blank micelle is 55mv, and carrier micelle particle diameter is 56mv, and after having carried medicine, potential value is slightly larger than blank micelle。
Chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan the polymer loading Merck that the present embodiment provides is self-assembly of the potential image of micelle as shown in Figure 4 in aqueous；After having carried medicine, potential value is 56mv。
The present embodiment provide utilize particle instrument measure chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer supported Merck micelle stability experiment in different pH medium result figure as shown in Figure 5；Nanoparticle is all have good stability in 7.4FBS in the simulated body fluid that pH is 1.2,6.8,7.4 and at pH, compare with the particle diameter of the micelle particle in neutral solution (blank, pH7.0), micelle particle in other medium solutions is all to start particle diameter change in various degree in half an hour big, but size is always maintained at very stable in the detection of 10 hours later, illustrate that the nano-micelle various body fluid in human body have certain stability。
Chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer that the present embodiment provides is self-assembly of the transmission electron microscope picture of micelle as shown in Figure 6 in aqueous；The micelle that chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer is self-assembly of in aqueous is homodisperse present more regular spherical particle；After drying, transmission electron microscope particle diameter is about 30nm, and micelle particle distribution is narrower。
The polymer supported Merck micelle of chitosan-vitamin e succinate-N-acetyl-L-cysteine that the present embodiment provides In-vitro release curves in different buffer is as shown in Figure 7；Merck solution (Merck-Sol), the release in vitro behavior of chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer medicament carrying micelle is measured by dynamic dialysis method。Assay method: precision measures the Merck solution of 2mL or chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer medicament carrying micelle in bag filter, two ends are tightened, put into 30mL containing in 2% Tween-60 to PBS (pH=1.2,6.8,7.4) solution, in 37 ± 0.5 DEG C, 100r/min jolting, respectively at 4,12,24,36, sampling 2mL after 48h, supplement the fresh dissolution medium (buffer) of identical temperature same volume simultaneously。Sample, through 0.22um filtering with microporous membrane, discards just filtrate, takes subsequent filtrate 2mL. HPLC method and measures Merck content, and calculates cumulative release percent。
Fig. 7 is Merck solution and the release in vitro situation of chitosan-vitamin e succinate-N-acetyl-L-cysteine polymer medicament carrying micelle。The rate of release of Merck solution is very fast, substantially all release in 5h。Compared to Merck solution, the release in vitro of chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan carrier micelle is then relatively slow, in 48h, chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan micelle releases 82.16%, showing that chitosan-vitamin e succinate-N-acetyl-L-cysteine modification of chitosan series carrier micelle has obvious slow releasing function release in vitro behavior is investigate whether medicine-carried nano particles has an important indicator of slow release or controlled-release effect, it it is the important evidence evaluating nanoparticle performance。
The loading form of the release behavior of polymer micelle and micelle Chinese medicine has important relationship。When medicine is loaded into covalent bond form, the release behavior of medicine depends primarily on hydrone to the fracture of chemical bond between the infiltration of micelle inner core, medicine and micellar carrier material and medicine from the outside diffusion of micelle inner core。When medicine is loaded into physically trapping form, the release behavior of medicine depends primarily on the dissolving in media as well of particle surface medicine, and hydrone enters kernel, the molten candle of carrier material or degraded, the diffusion of the outside aqueous phase of medicine through micelle shell。Polymer micelle carries out medicine carrying in physically trapping mode, is respectively provided with good slow release effect。Wherein, the release of micelle is the slowest, this is because the particle diameter of this carrier micelle is minimum, the structure of micelle inner core is the finest and close, the diffusion being unfavorable in outer aqueous phase hydrone to micelle inner core and the diffusion of the outside aqueous phase of micelle inner core Chinese medicine, and the degradation rate that carrier material itself is in vitro is also slow, therefore define release behavior comparatively slowly。
Embodiment 2
5mg amphipathic nature polyalcohol chitosan-vitamin e succinate-N-acetyl-L-cysteine is joined in 5ml deionized water water, magnetic agitation is to being completely dissolved and mix homogeneously, resulting polymers solution is first passed through the Medium speed filter paper that aperture is 30-50 μm, then then through the filter membrane of 0.8 μm, at the centrifugal 5min of 4000r/min, take supernatant and cross 0.45 μm of syringe filter, discard first two, the amphipathic nature polyalcohol solution obtained。Being dissolved in by the 5mg camptothecine weighed in corresponding solvent, magnetic agitation makes camptothecine be uniformly dissolved。When polymer solution stirs, the camptothecine dropwise dissolved joined in amphipathic nature polyalcohol solution, the both the above mixed solution being stirred use rotary evaporator decompression steam solvent, stop when starting to occur muddiness, remaining solution ultrasonic 10min (power 150W under probe type ultrasonic instrument, work 5s, interval 3s)。Gained solution, at the centrifugal 5min of 3000r/min, takes supernatant and crosses 0.45 μm of needle type filtration film, obtain the amphipathic load camptothecin polymeric thing micelle of medicine carrying。
Record and there is the effect that strength 1 is similar simultaneously。
Claims (7)
1. the preparation method of an amphiphilic chitosan derivative medicament-carried nano micelle, it is characterised in that comprise the following steps:
(1) amphipathic nature polyalcohol chitosan-vitamin e succinate-N-acetyl-L-cysteine is joined in deionized water, magnetic agitation is to forming translucent solution and mix homogeneously, resulting polymers solution is first passed through the Medium speed filter paper that aperture is 30-50 μm, then then through the filter membrane of 0.8 μm, carry out the centrifugal of 3000-5000r/min, then take supernatant and cross 0.45 μm of syringe filter, discard first two, the amphipathic nature polyalcohol solution obtained；
(2) being dissolved in suitable solvents by the hydrophobic drug weighed, stirring makes medicine dissolution uniform；When stirring, the drug solution dissolved joining in amphipathic nature polyalcohol solution dropwise, stir；
(3) the both the above mixed solution being stirred use rotary evaporator decompression steam the solvent of step (2), stop when starting to occur muddiness, remaining solution is carried out ultrasonic under probe type ultrasonic instrument, gained solution is centrifugal when 3000-5000r/min, take supernatant and cross 0.45 μm of needle type filtration film, obtain the amphipathic nature polyalcohol micelle of medicine carrying。
2. the preparation method of a kind of amphiphilic chitosan derivative medicament-carried nano micelle described in claim 1, it is characterised in that step (3) ultrasound condition: ultrasonic 10min, power 150W, work 5s, interval 3s。
3. the preparation method of a kind of amphiphilic chitosan derivative medicament-carried nano micelle described in claim 1, it is characterized in that, the preparation of step (1) polymer solution, it is preferable that every 5mg chitosan-vitamin e succinate-N-acetyl-L-cysteine correspondence is dissolved in 5mL deionized water。
4. the preparation method of a kind of amphiphilic chitosan derivative medicament-carried nano micelle described in claim 1, it is characterised in that the drug solution dissolved joining in amphipathic nature polyalcohol solution dropwise in step (2)。
5. the preparation method of a kind of amphiphilic chitosan derivative medicament-carried nano micelle described in claim 1, it is characterised in that the hydrophobic drug described in step (2) is the one in Merck or camptothecine。
6. the preparation method of a kind of amphiphilic chitosan derivative medicament-carried nano micelle described in claim 5, it is characterised in that the solvent corresponding with Merck is the one in acetonitrile, methanol；The solvent corresponding with camptothecine is the one in DMSO or methanol and chloroform mixed solution or aqueous alkali。
7. according to the amphiphilic chitosan derivative medicament-carried nano micelle of claim 1-5 any one method gained。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501440A (en) * | 2017-09-01 | 2017-12-22 | 中国海洋大学 | A kind of new carboxymethyl chitosan derivative and its preparation method and application |
| CN110124044A (en) * | 2019-06-20 | 2019-08-16 | 中国海洋大学 | Amphipathic self-assembled nanometer carrier based on chitosan and its preparation method and application |
| CN114874354A (en) * | 2022-05-10 | 2022-08-09 | 中国热带农业科学院南亚热带作物研究所 | Double-modified chitosan drug-loaded nano micelle, preparation method and application |
-
2016
- 2016-03-04 CN CN201610125193.2A patent/CN105687133A/en active Pending
Non-Patent Citations (3)
| Title |
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| HE LIAN等: "Enhanced Oral Delivery of Paclitaxel Using Acetylcysteine Functionalized Chitosan-Vitamin E Succinate Nanomicelles Based on a Mucus Bioadhesion and Penetration Mechanism", 《MOLECULAR PHARMACEUTICS》 * |
| HE LIAN等: "Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery", 《INTERNATIONAL JOURNAL OF NANOMEDICINE》 * |
| 廉鹤: "功能性巯基化聚合物胶束口服药物传递系统的构建与评价", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501440A (en) * | 2017-09-01 | 2017-12-22 | 中国海洋大学 | A kind of new carboxymethyl chitosan derivative and its preparation method and application |
| CN110124044A (en) * | 2019-06-20 | 2019-08-16 | 中国海洋大学 | Amphipathic self-assembled nanometer carrier based on chitosan and its preparation method and application |
| CN114874354A (en) * | 2022-05-10 | 2022-08-09 | 中国热带农业科学院南亚热带作物研究所 | Double-modified chitosan drug-loaded nano micelle, preparation method and application |
| CN114874354B (en) * | 2022-05-10 | 2023-02-07 | 中国热带农业科学院南亚热带作物研究所 | Double-modified chitosan drug-loaded nano micelle, preparation method and application |
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