CN101831000A - Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof - Google Patents
Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof Download PDFInfo
- Publication number
- CN101831000A CN101831000A CN 201010179030 CN201010179030A CN101831000A CN 101831000 A CN101831000 A CN 101831000A CN 201010179030 CN201010179030 CN 201010179030 CN 201010179030 A CN201010179030 A CN 201010179030A CN 101831000 A CN101831000 A CN 101831000A
- Authority
- CN
- China
- Prior art keywords
- pullulan polysaccharide
- acetyl
- acetyl pullulan
- folic acid
- polysaccharide
- 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.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a purification method of acetyl pullulan polysaccharide folate conjugate and a preparation method of nanometer particles thereof. Folate, acetyl pullulan polysaccharide solution, 4-dimethylaminopyridine (DMAP) and a carbodiimide dehydrating agent are mixed for reaction for 5 to 7 days at the temperature of 25 to 28 DEG C, excessive absolute ethyl alcohol is dropwise added into filter liquor for sedimentation, and centrifugation is carried out, the sediment is collected, is dialyzed for 24 to 48 hours by sodium carbonate buffer solution and is dialyzed for 24 to 48 hours in deionized water, and a material is obtained through freezing-drying or vacuum drying. The material is dissolved in dimethyl sulfoxide (DMSO) or other organic solvents, and a dialysis method is adopted for preparing the nanometer particles. The invention has less steps, simple operation and good repeatability and dose not need other stabilizing agents and emulsifiers, and the nanometer particles are in ball shapes, have uniform grain sizes, low absolute potential, and good stability, and do not have significant toxicity for single mainline to mice.
Description
Technical field:
The present invention relates to a kind of acetyl pullulan polysaccharide folate conjugate (Folate-conjugated pullulan acetate, FPA) purifying and nanoparticle thereof (Folate-conjugated pullulan acetate nanoparticles, preparation method FPAN).
Background technology:
Nano-medicament carrier is meant that can change medicine enters the mode of human body and distribution in vivo, the release rate of control medicine also conducts drugs to the system of the Nano grade of target organs, the ideal drug conveying carrier has following feature (Wim H DeJong, et al., Int J Nanomedicine.2008,3 (2): 133-149; S.M.Moghimi, et al., FASEB J.2005,19 (3): 311-330; Karina R, et al., Adv Drug Deliv Rev.2008,60 (8): 929-938): can seal and release well, Stability Analysis of Structures, good biocompatibility, hypotoxicity and have bio distribution and target ability and effect to medicine, in addition, also need to carry behind the medicine well biological degradability.The pharmaceutical carrier research of target becomes the focus of Recent study, the molecular targeted treatment of tumour is meant on the basis of tumour molecular cytobiology, utilize specificity (or special relatively) structural molecule that tumor tissues or cell have as target spot, use some can reach a class therapy of direct treatment or targeted therapy purpose with the antibody of these target molecule specific combination, part etc.This methods of treatment has lower untoward reaction and good efficacy, can obviously improve patient's quality of life, is the breakthrough and revolutionary development in present oncotherapy field, has represented the present the latest development direction of tumor biotherapy.Folic acid is a kind of rope of supporting one's family of small molecular weight, and its acceptor is a kind of glycoprotein, at human cancer, comprises the malignant tumour of ovary, brain, kidney, breast, cord cell and lung etc., and folacin receptor is higher than normal level; And in most healthy tissuess, express hardly.Utilize the high affinity of folic acid, can be used for medicine or solid support material and folacin coupled are delivered to tumour with drug targeting folacin receptor.With folic acid (or its analogue) is part, all can combine from the small molecules radiological imaging agent to the htrb gene medicine with folic acid is efficient, and being entered cell by transhipment, the solid support material that folic acid connects also has tangible targeting to the tumour cell of folacin receptor high expression level.
The material of preparation nano-medicament carrier can be divided into synthetic materials and natural materials, wherein, polysaccharide extensively is present in nature, it is the important natural materials of a class that becomes more readily available, (OH), carboxyl (COOH) and amino (hydrophilic radical such as NH2) to contain hydroxyl, but reactive group is more, be easy to be modified and modification, generate a variety of derivatives, be widely used in research (the Zonghua Liu of Nano medication and nano-medicament carrier, et al., Adv Drug Deliv Rev.2008,60 (15): 1650-1662).Pulullan polysaccharide (Pullulan) is owing to have good resistance to acids and bases, plasticity-is strong, good film-forming property, ventilation property is low, no hygroscopicity, solution viscosity is starkly lower than other polysaccharide soln, in recent years, the scientific research personnel recognizes the nontoxic of pulullan polysaccharide gradually, no mutagenesis, good biocompatibility and biodegradable, can be used as a kind of good biomaterial and be used in field (R RM et al. such as medicine, gene delivery and organizational project, Trends Biomater Artif Organs, 2007,20 (2): 116-121; Leathers TD, et al., Appl Microbiol Biotechnol.2003,62 (5-6): 468-473; Shingel KI, et al., Carbohydr Res.2004,339 (3): 447-460).As far back as 1986; Motozato (Motozato Y, et al., JChromatogra.1986; 55:434-437) find that water-soluble pulullan polysaccharide can generate hydrophobic acetyl pullulan polysaccharide through the acetylize modification, this material is made microballoon by solvent evaporation method easily.2003, (Jung SW such as Jung, et al., Int J Pharm, 2003,254 (2): 109-121) charging capacity of discovery change aceticanhydride and pyridine can be prepared the acetyl pullulan polysaccharide of different degree of substitution, can prepare the nanoparticle of different-grain diameter with dialysis process, the fluorescent probe method studies have shown that nanoparticle is to form by self-assembling method, and micelle-forming concentration increases with the acetyl substitution value and reduces, and this nanoparticle bag carries the release that can delay medicine behind the hydrophobic drug.Acetyl pullulan polysaccharide is connected with White streptocide coupling (PA/SDM) can forms pH susceptibility nanogel particle (NaK, et al., J Control Release.2003,87 (1-3): 3-13), in addition, this testing laboratory also adopts solvent diffusion method to prepare nanoparticle acetyl pullulan polysaccharide, and it has been carried out studying (Zhang H.Z as the antitumor drug carrier, et al., Colloid SurfB.2009,71 (1): 19-26), external employing mtt assay has been investigated its toxicity to normal fibroblast and Hela cancer cells.Remaining hydroxyl can also combine with part and form the targeting vector material in the acetyl pullulan polysaccharide structure, as introduce vitamin H and make vitamin H receptor target nano-carrier (Na K, et al., Eur J Pharm Sci.2003,18 (2): 165-173), vitamin H acceptor high expression tumour cell is had the special target effect, and the amount of cellular uptake nanoparticle increases with the increase of vitamin H substitution value; Our early-stage Study (Hui-zhu Zhang, et al., Drug Delivery, 2010; 17 (1): 48-57) also successfully synthesized folic acid acetyl pullulan polysaccharide conjugate; and the solvent-applied diffusion process has prepared nanoparticle; test-results shows that the medicine-carried nano particles behind the connection folic acid enters cell mainly by the folacin receptor approach; point out folacin coupled nanoparticle to enter cell by the folacin receptor approach; can increase selectivity to tumor tissues; strengthen antitumor curative effect; thereby be a rising antitumor drug carrier; but; this material synthetic has two steps; it is most important how reaction product to be carried out separation and purification; in addition; when synthetic material degree of substitution with acetyl group lower; when the folic acid substitution value is higher; adopt solvent diffusion method to prepare nanoparticle; the syringe needle that injects dispersion liquid can have a small amount of floss; prepared nano-solution opalescence is not strong; visible suspended particle is arranged in the nanometer suspension; (20000 rev/mins of high speed centrifugations; 4 ℃; 15min); solution has still had strong yellow, collected nanoparticle seldom, most of material adopts this method all can not become nanoparticle.CN200810052708.6 discloses the preparation of folacin receptor mediated targeted acetyl pullulan polysaccharide nano granule.The present invention uses conventional reagent dehydrated alcohol with product and precipitates on the early-stage Study basis, sodium carbonate buffer is dialysed and is separated and purifying, in addition, by dialysis method with this material preparation nanoparticle as pharmaceutical carrier, more than research there is no any document or patent report.
Summary of the invention:
The purification process and the nanometer particle process method thereof that the purpose of this invention is to provide a kind of acetyl pullulan polysaccharide folate conjugate.Adopting dehydrated alcohol is that precipitation reagent and precipitation reagent methyl alcohol compare, and toxic side effect obviously reduces.For the higher acetyl pullulan polysaccharide folate conjugate of folic acid substitution value, adopt to prepare the productive rate that nanoparticle significantly improves nanoparticle with dialysis method, the form rule, particle diameter is even, and nanoparticle surface institute is electrically charged low, good stability.Step is few, and is simple to operate, need not to add reagent such as stablizer, emulsifying agent.This material has excellent biological compatibility, degradability and non-immunogenicity.
The step that the purifying of a kind of acetyl pullulan polysaccharide folate conjugate provided by the invention and nanometer particle process method thereof comprise:
1) folic acid and acetyl pullulan polysaccharide solution are reacted under catalyzer 4-Dimethylamino pyridine (DMAP) and carbodiimide (1-(3-dimethylaminopropyl)-3-ethyl carbodiimide) class dewatering agent effect, temperature of reaction is 25～28 ℃, reaction times is 5～7 days (substitution value of synthetic product is selected as required), makes to be condensed into folic acid-acetyl pullulan polysaccharide conjugate; Described pulullan polysaccharide molecular weight ranges is 4,000～200,000Da.
2) generate in will reacting 1,3-dicyclohexylurea (DCU) (DCU) sedimentation and filtration is removed, filtrate is added dropwise to precipitation in the excessive dehydrated alcohol (volume ratio is 1: 50～150), centrifugal (speed is 3000～8000 rev/mins, and the time is 5～20 minutes and 4 ℃) collecting precipitation;
3) dialyse 24～48h to eliminate free folic acid with sodium carbonate buffer, deionized water dialysis 24-48h removes other small molecules.Described dialysis tubing is that molecular weight cut-off is the dialysis tubing of 8000-14000.
4) vacuum-drying or freeze-drying get yellow powder.
Described acetyl pullulan polysaccharide solution is for being dissolved in the solution in the dimethyl sulfoxide (DMSO) (DMSO).
Described acetyl pullulan polysaccharide: folic acid: DCC: DMAP=1: 0.3～5: 0.36～1.5: 0.17～0.6 (mol ratio).
The sub-preparation method of a kind of folacin receptor mediated targeted acetyl pullulan polysaccharide nano granule provided by the invention: acetyl pullulan polysaccharide folate conjugate be dissolved in fully with the miscible organic solvent of water in (organic phase), lysate is transferred in the dialysis tubing dialyses.Organic solvent is the solvent that sough (DMSO) in dimethyl formamide (DMF), dimethyl Asia or other organic solvents and organic solvent and water dilute according to a certain percentage.Described dialysis time is 24～48h, and water is changed in beginning at interval 1～2h 1 time, change 4 times after at interval 4～6h change water one time.Behind dialysis 24～48h, can directly obtain the nanoparticle suspension.
A kind of folacin receptor mediated targeted acetyl pullulan polysaccharide bag medicine carrying thing nanoparticle (Epirubicinloaded FPAN provided by the invention, EPI-FPAN) preparation method is to be carrier with the acetyl pullulan polysaccharide folate conjugate, embedding antitumor drug, particle diameter are 250～500nm.
Described bag medicine carrying thing nanometer particle process method is: medicine and material are dissolved in respectively in the organic solvent, and medicine and material mix according to certain ratio, fully are transferred in the dialysis tubing behind the mixing and dialyse.The mass ratio of described cancer therapy drug and folacin coupled acetyl pullulan polysaccharide nano granule is 1: 10～50.Described organic solvent is the solvent that sough (DMSO) in dimethyl formamide (DMF) or dimethyl Asia or other organic solvents and organic solvent and water dilute according to a certain percentage.Described dialysis tubing is that molecular weight cut-off is the dialysis tubing of 8000-14000Da.Used dialyzate is deionized water or redistilled water.Described dialysis time is 24～48h, and water is changed in beginning at interval 1～2h 1 time, change 4 times after at interval 4～6h change water one time.
Described bag medicine carrying thing is: pidorubicin, Zorubicin, daunorubicin, all-trans-retinoic acid, taxol, methotrexate, camptothecine etc.
The sub-form of folacin coupled acetyl pullulan polysaccharide nano granule of the present invention is spherical in shape, particle size distribution range is little, the current potential absolute value is little, and nanoparticle and medicine-carried nano particles structure are more stable, and the nanoparticle intravenous injection gives not see obviously in the body behind the animal and has no side effect.This material has excellent biological compatibility, degradability and non-immunogenicity, and various raw material is cheap and easy to get, and preparation technology is simple, and preparation condition is controlled, is a kind of solid support material that has cancer target preferably.
Description of drawings:
Fig. 1 is FPAN size distribution figure.
Fig. 2 is that the Zeta potential of FPAN is measured figure.
Fig. 3 is EPI-FPAN size distribution figure.
Fig. 4 is that the Zeta potential of EPI-FPAN is measured figure.
Fig. 5 is the FPAN transmission electron microscope photo.
Fig. 6 is the EPI-FPAN transmission electron microscope photo.
Fig. 7 is the HE dyeing histopathologic slide photo of mouse main organs.
Embodiment:
Embodiment 1: the precipitation and the purification process of folic acid acetyl pullulan polysaccharide conjugate:
1g (2.27mmol) folic acid is dissolved with 15ml dimethyl sulfoxide (DMSO) (DMSO), Dropwise 5 drips triethylamine, stirring makes dissolving fully, add 0.9g (4.4mmol) N, N '-dicyclohexylcarbodiimide (DCC), 0.25g (2.05mmol) 4-Dimethylamino pyridine (DMAP) adds the 0.615g acetyl pullulan polysaccharide that is dissolved among the 6.15ml DMSO behind the stirring reaction 1h, the lucifuge reaction is 5 days under the induction stirring.Remove by filter the DCU precipitation, filtrate is added dropwise in the 250ml ethanol solution, centrifugal (8000 rev/mins, 4 ℃, centrifugal 15min) collect yellow mercury oxide, 24h dialyses in the sodium carbonate buffer, 48h dialyses in the deionized water, freeze-drying or vacuum-drying get yellow powder, are folacin coupled acetyl pullulan polysaccharide derivative.
The proton magneto-optic spectrum of the folacin coupled acetyl pullulan polysaccharide derivative of gained (
1H-NMR) and this laboratory synthetic product basically identical (CN200810052708.6) in early stage.At FPA
1The characteristic peak of folic acid appears in δ 6.75-8.77ppm place among the H-NMR, illustrates that folic acid and acetyl pullulan polysaccharide are by chemical bond link (figure slightly).
The preparation of embodiment 2:FPA nanoparticle
Accurately taking by weighing the 48mg acetyl pullulan polysaccharide folate conjugate is dissolved in the 4.8ml dimethyl sulfoxide (DMSO), concentration is 10mg/ml, lysate is transferred to dialysis tubing dialyses, the dialysis tubing molecular weight cut-off is 14000Da, dialyzate is a deionized water, water is changed in beginning at interval 1～2h 1 time, change 4 times after at interval 4～6h change water one time, 48h altogether dialyses.Final solution is with in the graduated centrifuge tube for being with yellow opalescent solution, being transferred to, and 100W is final nanoparticle suspension after ultrasonic 3 minutes, and ultimate density is volume (12ml) ratio of the material (48mg) that added and final nano-particle solution, is 4mg/ml.Can be diluted to purpose concentration according to experiment needs water or other solution, perhaps high speed centrifugation (18000 rev/mins, 4 ℃, centrifugal 15min) is collected nanoparticle, adds entry or other solution is dispersed to purpose concentration again.
Embodiment 3: bag carries the preparation of the FPA nanoparticle of pidorubicin
Accurately take by weighing acetyl pullulan polysaccharide folate conjugate 40mg, be dissolved in the 3.2ml dimethyl sulfoxide (DMSO), making concentration is 12.5mg/ml.Pidorubicin 10mg is dissolved in the 2ml dimethyl sulfoxide (DMSO), and concentration is 5mg/ml, adds 4.9 μ l triethylamines (2 times of molar weights), and lucifuge stirs 12h and makes pidorubicin desalination acid under the room temperature condition.Medicine/material solution is mixed by 4: 1 volume ratios, lysate is transferred to dialysis tubing dialyses, the dialysis tubing molecular weight cut-off is 10000Da, dialyzate is a deionized water, water is changed in beginning at interval 1～2h 1 time, change 4 times after at interval 4～6h change water one time, 48h altogether dialyses.Final solution is the opalescent solution of band orange, be transferred to and be with in the graduated centrifuge tube, 100W is final nanoparticle suspension after ultrasonic 3 minutes, ultimate density is volume (7ml) ratio of the material (40mg) that added and final nano-particle solution, is 5.7mg/ml.Can be diluted to purpose concentration according to experiment needs water or other solution, perhaps high speed centrifugation (18000 rev/mins, 4 ℃, centrifugal 15min) is collected nanoparticle, adds entry or other solution is dispersed to purpose concentration again.
Embodiment 4: nano particle diameter distribution, Zeta potential and morphology observation
Adopting laser particle size analyzer to measure nano particle diameter distributes and Zeta potential.The nanometer suspension is diluted to proper concn (1mg/ml) puts into cuvette, cuvette is put into the particle size analyzer sample pool test, each sample test 3 times.The nanometer suspension is dropped on the carbon supporting film, and with 2% phospho-wolframic acid (pH6.0) negative staining, dry back is observed under transmission electron microscope after the seasoning.The nanoparticle suspension is dropped on the silicon chip, carried out discontinuous metal spraying after the seasoning 3 minutes, under scanning electron microscope, observe.
The investigation of embodiment 5:FPAN and EPI-FPAN stability
Nano-particle solution is kept in Dark Place at 2-8 ℃, and every certain interval of time adopts laser particle size analyzer to measure nano particle diameter distribution and Zeta potential.The results are shown in Table 1 and table 2.
The size distribution of table 1FPAN nanoparticle and Zeta potential (
N=3)
The size distribution of table 2EPI-FPAN nanoparticle and Zeta potential (
N=3)
Embodiment 6:FPAN toxicity in vivo is investigated
With 20 of ICR mouse, in age in 4-6 week, body weight 17-22g is divided into two groups, every group 10, male and female half and half, difference tail vein injection FPA nano-solution 125mg/kg and 0.9% sodium chloride injection, the general physical signs of observing animal after the administration, appetite and body weight, observed 14 days continuously, experiment finishes animal is cutd open inspection, if there is the visible pathology of naked eyes to do pathologic finding.The results are shown in Table 3 and table 4.
Table 3FPAN single intravenous injection 125mg/kg is to the influence of mouse body weight
Table 4FPAN single intravenous injection 125mg/kg is to the influence of mouse appetite
Claims (5)
1. the purifying of an acetyl pullulan polysaccharide folate conjugate and nanometer particle process method thereof is characterized in that the step that it comprises:
1) folic acid and acetyl pullulan polysaccharide solution are reacted under catalyzer 4-Dimethylamino pyridine (DMAP) and the effect of carbodiimide dewatering agent, temperature of reaction is 25～28 ℃, and the reaction times is 5～7 days, makes to be condensed into folic acid-acetyl pullulan polysaccharide conjugate;
2) generate in will reacting 1,3-dicyclohexylurea (DCU) (DCU) sedimentation and filtration is removed, it is to precipitate in 1: 50～150 the dehydrated alcohol that filtrate is added dropwise to volume ratio, under 4 ℃, 3000～8000 rev/mins are centrifugal, the time is 5～20min, collecting precipitation;
3) dialyse 24～48h to eliminate free folic acid with sodium carbonate buffer, deionized water dialysis 24-48h removes other small molecules.
4) vacuum-drying or freeze-drying get yellow powder.
2. preparation according to claim 1 and purification process is characterized in that described acetyl pullulan polysaccharide: folic acid: DCC: the mol ratio of DMAP=1: 0.3～5: 0.36～1.5: 0.17～0.6.
3. preparation according to claim 1 and purification process is characterized in that described acetyl pullulan polysaccharide solution is the solution that is dissolved in the dimethyl sulfoxide (DMSO).
4. preparation according to claim 1 and purification process is characterized in that described pulullan polysaccharide molecular weight ranges is 4,000～200,000.
5. preparation according to claim 1 and purification process is characterized in that described dialysis tubing is that molecular weight cut-off is the dialysis tubing of 8000-14000Da.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010179030 CN101831000A (en) | 2010-05-21 | 2010-05-21 | Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010179030 CN101831000A (en) | 2010-05-21 | 2010-05-21 | Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101831000A true CN101831000A (en) | 2010-09-15 |
Family
ID=42715236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010179030 Pending CN101831000A (en) | 2010-05-21 | 2010-05-21 | Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101831000A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106390127A (en) * | 2015-08-03 | 2017-02-15 | 首都医科大学附属北京妇产医院 | Novel combined inhibitor for phagocytosis of nano-drug particles by liver Kuppfer cells and application of combined inhibitor |
| CN106727423A (en) * | 2016-10-13 | 2017-05-31 | 中国药科大学 | Core crosslinking pullulan polysaccharide nano granule and the preparation method of a kind of Redox-sensitive with double targetings |
| CN108264578A (en) * | 2018-02-12 | 2018-07-10 | 华中科技大学 | Polysaccharide graft folic acid copolymer and its nanoparticle preparation method |
| CN110478318A (en) * | 2019-09-17 | 2019-11-22 | 齐鲁工业大学 | A kind of Fenton reagent and adriamycin cotransport targeted nano carrier and preparation method thereof |
| US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
| CN114392271A (en) * | 2022-02-09 | 2022-04-26 | 黑龙江八一农垦大学 | Preparation method of sulfated polysaccharide-folic acid conjugate |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
| CN116370645A (en) * | 2023-03-03 | 2023-07-04 | 齐鲁工业大学(山东省科学院) | Endoplasmic reticulum targeted fluorescent nano-carrier, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101036788A (en) * | 2007-04-20 | 2007-09-19 | 中国医学科学院生物医学工程研究所 | Pulullan polysaccharide carrier material having the function of targeting therapy of cancer and the preparation method |
| CN101254309A (en) * | 2008-04-11 | 2008-09-03 | 中国医学科学院生物医学工程研究所 | Folacin receptor mediated targeted acetyl pullulan polysaccharide nano granule and preparation thereof |
-
2010
- 2010-05-21 CN CN 201010179030 patent/CN101831000A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101036788A (en) * | 2007-04-20 | 2007-09-19 | 中国医学科学院生物医学工程研究所 | Pulullan polysaccharide carrier material having the function of targeting therapy of cancer and the preparation method |
| CN101254309A (en) * | 2008-04-11 | 2008-09-03 | 中国医学科学院生物医学工程研究所 | Folacin receptor mediated targeted acetyl pullulan polysaccharide nano granule and preparation thereof |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
| CN106390127A (en) * | 2015-08-03 | 2017-02-15 | 首都医科大学附属北京妇产医院 | Novel combined inhibitor for phagocytosis of nano-drug particles by liver Kuppfer cells and application of combined inhibitor |
| CN106390127B (en) * | 2015-08-03 | 2019-10-01 | 首都医科大学附属北京妇产医院 | A kind of New Liver Kupffer's cells swallows composite restrainer and its application of Nano medication particle |
| CN106727423A (en) * | 2016-10-13 | 2017-05-31 | 中国药科大学 | Core crosslinking pullulan polysaccharide nano granule and the preparation method of a kind of Redox-sensitive with double targetings |
| US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
| US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
| US11878079B2 (en) | 2017-04-14 | 2024-01-23 | Capsugel Belgium Nv | Pullulan capsules |
| CN108264578A (en) * | 2018-02-12 | 2018-07-10 | 华中科技大学 | Polysaccharide graft folic acid copolymer and its nanoparticle preparation method |
| CN110478318A (en) * | 2019-09-17 | 2019-11-22 | 齐鲁工业大学 | A kind of Fenton reagent and adriamycin cotransport targeted nano carrier and preparation method thereof |
| CN110478318B (en) * | 2019-09-17 | 2021-07-30 | 齐鲁工业大学 | Fenton reagent and adriamycin co-transport targeting nano-carrier and preparation method thereof |
| CN114392271A (en) * | 2022-02-09 | 2022-04-26 | 黑龙江八一农垦大学 | Preparation method of sulfated polysaccharide-folic acid conjugate |
| CN116370645A (en) * | 2023-03-03 | 2023-07-04 | 齐鲁工业大学(山东省科学院) | Endoplasmic reticulum targeted fluorescent nano-carrier, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101831000A (en) | Purification method of acetyl pullulan polysaccharide folate conjugate and preparation method of nanometer particles thereof | |
| CN107661504B (en) | Dendritic macromolecule modified gold nanoparticle and preparation method and application thereof | |
| CN101254309A (en) | Folacin receptor mediated targeted acetyl pullulan polysaccharide nano granule and preparation thereof | |
| CN109010846A (en) | Polyethylene glycol-chitosan-curcumin polymer and its medicine-carried nano particles and preparation method | |
| CN110408047B (en) | Nano coordination polymer and preparation method and application thereof | |
| CN107417752B (en) | Compound with anticancer activity and preparation method and application thereof | |
| CN109678909B (en) | Preparation method and application of platinum derivative and platinum-containing nano particle | |
| CN102863557A (en) | Preparation method and application of fatty acid-trimethyl chitosan polymer modified by lactobionic acid | |
| CN101531800B (en) | Method for preparing poly(amidoamine)/carbon nanometer tube composite material for cancer cell targeting diagnosis | |
| CN111494411A (en) | In-situ self-assembled tetravalent platinum drug and preparation method and application thereof | |
| CN107266384B (en) | N- carboxyl inner-acid anhydride monomer and polyaminoacid based on 2- aminohexadecanoic acid and preparation method thereof | |
| CN105860057A (en) | Hydrophobic functional micromolecule-hydrophilic polyamino acid based biodegradable polymer and preparation method and application thereof | |
| CN104784700B (en) | A kind of medicine carries the preparation method of compound, micella and micella altogether | |
| CN107929261B (en) | pH-sensitive targeted nanoparticle preparation loaded with chemotherapeutic drugs and preparation method thereof | |
| Chen et al. | Branched polyethyleneimine modified with hyaluronic acid via a PEG spacer for targeted anticancer drug delivery | |
| CN107007550B (en) | Redox-responsive amphiphilic copolymer and preparation method and application thereof | |
| CN103127524B (en) | Preparation method of polyamide-amine dendrimer-loaded alpha-Tos | |
| CN103083682B (en) | Folic acid modified chitosan quaternary ammonium salt-taxol polymer medicine, as well as preparation method and application thereof | |
| EP3215545A1 (en) | A process for preparing water-dispersible single-chain polymeric nanoparticles | |
| Guo et al. | Ethylene glycol oligomer modified-sodium alginate for efficiently improving the drug loading and the tumor therapeutic effect | |
| Gao et al. | Hydrotropic polymer-based paclitaxel-loaded self-assembled nanoparticles: preparation and biological evaluation | |
| Hu et al. | A two-photon fluorophore labeled multi-functional drug carrier for targeting cancer therapy, inflammation restraint and AIE active bioimaging | |
| CN108997575A (en) | Polyethylene glycol-b- polytyrosine-lipoic acid copolymer, poly- polypeptide micella and the preparation method and application thereof | |
| CN113278092B (en) | Polymer carrier material, preparation and application thereof | |
| CN112843244B (en) | Intelligent drug-loaded nanocluster system with variable size and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100915 |