CN106832056B - Sulphated hyaluronic acid 2- octyl dodecanol ester - Google Patents
Sulphated hyaluronic acid 2- octyl dodecanol ester Download PDFInfo
- Publication number
- CN106832056B CN106832056B CN201710119592.2A CN201710119592A CN106832056B CN 106832056 B CN106832056 B CN 106832056B CN 201710119592 A CN201710119592 A CN 201710119592A CN 106832056 B CN106832056 B CN 106832056B
- Authority
- CN
- China
- Prior art keywords
- hyaluronic acid
- octyl dodecanol
- sulphated hyaluronic
- dissolved
- sha
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
Abstract
The present invention relates to and provide a kind of new drug carrier sulphated hyaluronic acid 2- octyl dodecanol ester and its preparation method and application.It is that hydrophobic Y type group 2- octyl dodecanol and hydrophilic radical sulfate radical have been grafted on hyaluronic acid skeleton, with amphipathic, it can be self-assembly of non-linear polymer micella in water, compared to linear polymer micella, bigger hydrophobic cavity can be formed, more insoluble drugs are contained.Sulphated hyaluronic acid 2- octyl dodecanol ester itself can inhibit tumour growth, and the nanoparticle of formation has partial size small, and stability is good, and Drug loading capacity is strong, and encapsulation rate is high, the simple feature of preparation process.
Description
Technical field
The present invention relates to polymer carrier field and field of pharmaceutical preparations, and in particular to a kind of sulphated hyaluronic acid
2- octyl dodecanol ester and preparation method thereof and application as pharmaceutical carrier.
Background technique
Hyaluronic acid (Hyaluronan, HA) be one kind by N-ACETYL-D-GLUCOSAMINE and D-Glucose aldehydic acid through β-Isosorbide-5-Nitrae
Natural linear polysaccharide made of glucosides key connection.HA has good water solubility, and good biocompatibility is easy progress chemistry and repairs
Decorations, have been used as a variety of pharmaceutical carriers to be widely used.The HA receptor CD44 of tumor cell surface has an overexpression, hyaluronic acid with
It can be specifically bound between receptor, nanoparticle can be made to be targeted to tumour, while can by the endocytosis that CD44 is mediated
So that drug enters tumour cell, increase the bioavilability of insoluble drug.But the HA of different molecular weight itself is to tumour
The proliferation of cell and the influence of transfer may show as promoting, it is also possible to show as inhibiting, so HA derivant material is to tumour
The influence of cell needs further to be studied.
The discovery sulphated hyaluronic acid such as Anaid Benitez can inhibit prostate gland cancer cell such as LNCaP, LNCaP-
Proliferation, migration and the invasion of Al, DU145, LAPC-4.(Anaid Benitez, et al., Targeting
Hyaluronidase for Cancer Therapy:Antitumor Activity of Sulfated Hyaluronic
Acid in Prostate Cancer Cells, Cancer Research, 2011,71 (12)；4085-95).Stephanie
Deng synthesis sulphated hyaluronic acid, I type herpesviral is acted on, illustrates that it has antiviral activity, and antiviral activity is with sulphur
The raising of acidizing degree and enhance (Stephanie Michaela, et al, Synthesis and Antiherpetic
Activity of Carboxymethylated and Sulfated Hyaluronan
Derivatives.Carbohydrate Polymers, 2012,90 (2012): 608-615).But above-mentioned sulphation is transparent
Matter acid be still it is hydrophilic, be not suitable for encapsulating and the selective transport of insoluble drug.
Amphiphilic polymer micella assembles the kernel formed by its hydrophobic side, contains insoluble drug, enhances fat-soluble medicine
The solubility of object；Water-wet side, which polymerize the shell to be formed, can effectively prevent drug to be swallowed by human body reticuloendothelial cell, make drug
It is smoothly transported to lesions position, improves bioavilability, reduces the toxic side effect of drug normal tissue.Current amphipathic polymerization
Object micellar material mainly linear polymer and non-linear polymer, studies have shown that the hydrophobic chain molecular weight of linear polymer is bigger,
Hydrophobic chain is longer, and nanoparticle is higher by the drugloading rate of hydrophobic effect, but the partial size of micella can also increase with it simultaneously, work as grain
It is easy to be captured by reticuloendothelial system when diameter is excessive, it is also difficult to which the drug release for realizing tumor locus by EPR effect limits
Application of the micella as pharmaceutical carrier.At this time with unique texture non-linear polymer appearance be expected to solve micelle medicine carrying and
The problem of partial size can not get both.Since linear polymer is different from the topological structure of non-linear polymer, when they are with identical
Relative molecular mass when, non-linear polymer assembles the nanometer that the nano-carrier partial size to be formed is formed than linear polymer and carries
Body partial size is much smaller, and may be implemented to carry more hydrophobic drug (Svenson while not increasing nano-carrier partial size
S.Dendrimers as versatile platform in drug delivery applications.Eur J Pharm
Biopharm, 2009,71 (3): 445-462).
The present invention is the hydroxyl on hyaluronic acid to be carried out sulphation, and Y type compound 2- octyl is grafted on HA carboxyl
Lauryl alcohol obtains sulphated hyaluronic acid 2- octyl dodecanol ester.It is amphiphilic polymer nano material, the sulfate radical of introducing
The hydrophily for being conducive to improve material itself, forms hydrophily shell, improves drug to the targeting of cancer cell；Pass through grafting
Y shape group 2- octyl dodecanol, formed non-linear polymer micella, compared to linear polymer micella, be more advantageous to be formed it is thin
Water kernel forms bigger hydrophobic cavity, can wrap up more drugs；Sulphated hyaluronic acid 2- octyl dodecanol ester simultaneously
Be conducive to improve the anti-tumor activity of HA, and nontoxic, good biocompatibility.
At present still not using sulphated hyaluronic acid grafting Y type aliphatic alcohol ester as the report of anti-tumor nano material.
Summary of the invention
The present invention describes and requires a kind of novel sulphated hyaluronic acid 2- octyl dodecanol ester, preparation method and work
For the application of medicament nano carrier；It is the amphipathic polymerization that a kind of safety is good, biodegradable, critical micelle concentration is low
Object can be self-assembly of polymer nanoparticle in water, and as Nano medication transmission system, while material itself has inhibition swollen
The effect of tumor growth.
The purpose of the present invention is to provide a kind of sulphated hyaluronic acid 2- octyl dodecanol esters and preparation method thereof.
The purpose of the present invention is to provide sulphated hyaluronic acid 2- octyl dodecanol ester field of pharmaceutical preparations application.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, it is characterized in that being grafted on hyaluronic acid skeleton
Hydrophobic Y shape group 2- octyldodecanol and hydrophilic radical sulfate radical, make it have it is amphipathic, can self assembly shape in water
Carrier at polymer micelle, as insoluble drug.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, it is characterized in that hydrophobic Y shape group 2- is pungent
Base dodecanol is grafted in hyaluronic acid on the carboxyl of glucuronic acid-N acetylglucosamine repetitive unit by ester bond, parent
Aqueous group sulfate radical replaces the hydroxyl on hyaluronic acid repetitive unit.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, wherein the hydrophobic Y type group 2- octyl being grafted
Total degree of substitution of dodecanol is 1%~30%.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, wherein sulfuric acid rate is 1~13%.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, it is characterised in that the HA molecular weight of selection is 5
×103~5 × 105Da, preferably 5 × 103Da。
Specifically, the present invention provides a kind of preparation methods of sulphated hyaluronic acid 2- octyl dodecanol ester, including with
Lower process:
The preparation of hyaluronic acid tetrabutylammonium salt (HA-TeBA): it weighs appropriate Sodium Hyaluronate (HA-Na) and is dissolved in distilled water
In, magnetic agitation dissolution；It weighs a certain amount of DowexWX8 cation exchange resin (tetrabutylammonium type) to be added in HA-Na, room temperature
Lower magnetic agitation 3h, filtering, vacuum freezedrying for 24 hours, 40 DEG C of vacuum drying 12h to get；
The preparation of sulphated hyaluronic acid (sHA): precision weighs appropriate HA-TeBA and is dissolved in N, N '-dimethyl formamide
(DMF) in, 50 DEG C of magnetic agitation 2h are made it dissolve；Another precision weighs a certain amount of sulfur acidizing reagent (sulfur trioxide N, N '-diformazan
Base formyl amine complex) it is dissolved in DMF, at room temperature after stirring and dissolving, it is added in above-mentioned HA-TeBA solution, nitrogen charging gas shielded, 0
Magnetic agitation 1h under DEG C ice bath；1M NaOH solution adjusts pH to neutrality, and 2-3 times of volume ethanol is added and stands overnight, takes after centrifugation
Precipitating, distilled water dialysis 1d, vacuum freezedrying is for 24 hours；
The preparation of sulphated hyaluronic acid 2- octyl dodecanol ester (sHA-OCD): precision weighs appropriate sHA and is dissolved in formamide
In, the dissolution of room temperature magnetic agitation, then ice bath, adds a certain amount of 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride
Salt (EDC), n-hydroxysuccinimide (NHS) stir 2h under ice bath；The another accurate a certain amount of 2- octyldodecanol of measurement
(OCD) it is dissolved in DMF, is added dropwise in sHA solution, 35 DEG C of magnetic agitations are for 24 hours；Ethanol precipitation centrifugation is added in reaction solution,
Distilled water is dialysed after precipitating is dissolved with water, vacuum freezedrying.
Sulphated hyaluronic acid 2- octyl dodecanol ester of the present invention, can contain insoluble drug (such as Taxotere
Alcohol etc.), drug-carrying polymer micelle is made.
Drug-carrying polymer nanoparticle of the present invention is that sulphated hyaluronic acid 2- octyl dodecanol ester is dissolved in double steamings
Water is self-assembled into the blank micella solution that concentration is 2~8mg/mL, indissoluble or microsolubility drug is dissolved in a small amount of organic solvent
Afterwards, it is added dropwise in above-mentioned blank micella solution, after sonicated, be placed in dialysis in distilled water and remove organic solvent, thoroughly
After analysis liquid is centrifuged, is filtered, the polymer medicament carrying micelle that partial size is 100~300nm is made, drugloading rate is wrapped up to 1%~19%
Envelope rate is 80% or more.
Above-mentioned sulphated hyaluronic acid 2- octyl dodecanol ester has and inhibits tumour growth, easily formation drug-carrying nanometer particle, system
The features such as standby simple process, micella stability is good, and encapsulation rate is high, and administration route is more.
Detailed description of the invention
The IR map of Fig. 1 sulphated hyaluronic acid
Fig. 2 sulphated hyaluronic acid 2- octyl dodecanol ester1H-NMR map
The I of Fig. 3 sulphated hyaluronic acid 2- octyl dodecanol ester371/I382With polymer log concentration relational graph
The cyto-inhibition figure of Fig. 4 sulphated hyaluronic acid
The cyto-inhibition of Fig. 5 sulphated hyaluronic acid 2- octyl dodecanol ester blank nanoparticle and its drug-carrying nanometer particle
Figure
Specific embodiment
Illustrate a specific embodiment of the invention, but protection scope of the present invention by following example, it is not limited to this.
The preparation of 1 hyaluronic acid tetrabutylammonium salt of embodiment
Sodium Hyaluronate (MW5000, HA-Na, 2.0g) is dissolved in 400mL distilled water, at room temperature magnetic stirrer over night；Separately
It weighs 20gDowexWX8 cation exchange resin (tetrabutylammonium type) to be added in HA-Na, at room temperature magnetic stirrer over night, filtering is cold
Freeze vacuum drying, is dried in vacuo at 40 DEG C, obtains hyaluronic acid tetrabutylammonium salt (HA-TeBA).
The preparation of 2 sulphated hyaluronic acid of embodiment (sHA)
Precision weighs the HA-TeBA (MW5000,1000mg) in embodiment 1 and is dissolved in 50mlN, N '-dimethyl formamide
(DMF) in, 50 DEG C of magnetic agitation 2h are made it dissolve；Another precision weighs the sulfating agent sulfur trioxide DMF complex compound of 1540mg
(SO3DMF it) is dissolved in 50mLDMF, stirring is added in HA-TeBA, nitrogen charging gas shielded to after dissolving at room temperature, magnetic after ice bath
Power stirs 1h；1M NaOH solution adjusts pH to neutrality, and addition ethanol precipitation is centrifuged, distilled water dialysis 2d, vacuum freezedrying,
It obtains sulphated hyaluronic acid (sHA).IR map confirms sHA structure (see Fig. 1).Elemental microanalysis method measures degree, and sulphur contains
Measuring (S%) is 4.392%.
The preparation of 3 sulphated hyaluronic acid 2- octyl dodecanol ester (sHA-OCD) of embodiment
Precision weighs the sHA (100mg) in embodiment 2 and is dissolved in 5ml formamide, and room temperature magnetic agitation 20min keeps its molten
Solution, then ice bath, is added 1- ethyl-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDC, 95mg), N- hydroxysuccinimidyl
Acid imide (NHS, 58mg) reacts 2h under ice bath；The another accurate a certain amount of 2- octyldodecanol (OCD) of measurement is dissolved in 9mLDMF
In, it is added dropwise in sHA solution, 35 DEG C of magnetic agitations are for 24 hours；Ethanol precipitation, centrifugation is added in reaction solution, and precipitating is dissolved with water
Distilled water dialysis 2d, vacuum freezedrying obtain sulphated hyaluronic acid 2- octyl dodecanol ester (sHA-OCD) afterwards.1H-NMR map
(see Fig. 2) confirmation sHA-OCD structure, degree of substitution is about 10%.
The measurement of embodiment 4sHA-ODA critical micelle concentration
Precision weighs 10mg sHA-ODA, is scattered in a small amount of distilled water, and for 24 hours, ice-bath ultrasonic 30min is (super for magnetic agitation
Acoustical power 195W, work 2s, interval 3s), it is settled to 10mL, obtains the blank micella solution of 1mg/mL；By the blank glue of 1mg/mL
It is 1 × 10 that beam solution, which is diluted to sHA-OCD concentration (C),-3、2.5×10-3、5×10-3、1×10-2、2.5×10-2、5×10-2、1
×10-1、2.5×10-1、5×10-1The serial micellar solution of mg/mL is separately added into quantitative pyrene (final concentration of 5 × 10-6mol/
L in), mixed liquor ultrasound 30min, 40 DEG C are protected from light water-bath and stay overnight, and utilize the fluorescence intensity of fluorescent spectrophotometer assay pyrene.Excitation
Wavelength is 334nm, launch wavelength I1For 371nm, I3For 382nm, slit width EXFor 5nm, EMFor 5nm.
Fluorescence intensity ratio (the I gone out with 1gC (g/L) and pyrene in 371nm and 382nm371/I382) mapping (see Fig. 3), curve
The corresponding polymer concentration of inflection point be the polymer material critical micelle concentration (CMC).Calculate sHA-OCD CMC
Value is 31.62 μ g/mL.The ratio of the CMC for being indicated above sHA-OCD micella is smaller, illustrates that the carrier micelle of preparation has
Preferable dilution stability.
The preparation of embodiment 5sHA-OCD nanoparticle
It weighs appropriate sHA-OCD by the concentration of 2~8mg/mL to be dissolved in the distilled water of certain volume, sonicated preparation
The blank micella nanoparticle solution (sHA-OCD NPs) for being 100~300nm at partial size.
The preparation of the load medicine sHA-OCD nanoparticle of embodiment 6
16mg sHA-OCD is dissolved in the blank micella solution that concentration 4mg/mL is made in distilled water, by the Taxotere of 2.0mg
Alcohol (DTX) is dissolved in 400 μ L methanol, is added dropwise in above-mentioned blank micella solution, ice-bath ultrasonic 30min (ultrasonic power
195W, work 2s, interval 3s), it is placed in dialysis in distilled water and removes methanol, dialyzate is through being centrifuged, and after filtering, obtained partial size is
The load medicine sHA-OCD micelle nano grain (DTX-sHA-OCD NPs) of 100~300nm.Table 1 is DTX-sHA-OCD nanoparticle and sky
The properties of white nanoparticle.
The property of 1 drug-carrying nanometer particle of table (DTX-sHA-OCD NPs) and blank nanoparticle (sHA-OCD NPs)
The results show that sulphated hyaluronic acid 2- octyl dodecanol ester (sHA-OCD) this amphipathic nature material, it can be in water
Micella is spontaneously formed, and nanoparticle partial size is less than 250nm, entrapment efficiency height (> 80%) has significantly Docetaxel
Solubilization.
Embodiment 7sHA and DTX-sHA-OCD NPs are in vitro to the inhibiting effect of tumour cell
Nanometer formulation group: DTX-sHA-OCD NPs, it is 0.1 μ of μ g/mL~80 g/mL that culture solution, which is diluted to concentration,.
Bulk pharmaceutical chemicals group: Taxotere alcoholic solution (DTX), it is 0.1 μ of μ g/mL~80 g/mL that culture solution, which is diluted to concentration,.
Blank nanoparticle group: sHA-ODA NPs, culture solution are diluted to above-mentioned same concentrations.
Sulphated hyaluronic acid group: sHA, it is 20~320 μ g/mL that culture medium, which is diluted to concentration,.
Hyaluronic acid control group: HA, it is 20~320 μ g/mL that culture medium, which is diluted to concentration,.
The human colon carcinoma RKO cell in good condition in exponential phase of growth is taken, 0.25% tryptic digestive juice is added, disappears
Change makes attached cell fall off, and cell suspension is made in counting；Respectively with 6 × 103~1 × 104The density in a/hole is inoculated in the training of 96 holes
It supports in plate, sets CO2It is cultivated for 24 hours in incubator；Give nanometer formulation group, the bulk pharmaceutical chemicals of required concentration respectively by above-mentioned experimental program
Group, blank nanoparticle solution, sHA group, HA control group, parallel 6 hole of each concentration, continue to cultivate.After 48h, 10 μ are added to every hole
150 μ LDMSO are added to every hole after being put into cell incubator incubation 4h in LMTT liquid, use extinction at microplate reader detection 490nm
Degree.Data are handled, are drawn a diagram (see Fig. 4,5), calculation of half inhibitory concentration IC50Value (is shown in Table 2).
Table 2 is in vitro to the inhibiting effect (IC of human colon carcinoma RKO cell Proliferation50Value)
The results show that sHA and sHA-OCD blank nanoparticle group there is certain inhibition to make the growth of RKO cell
With.The IC of DTX-sHA-OCD NPs preparation group50Less than Docetaxel bulk pharmaceutical chemicals, illustrate that mostly west can be made by carrying medicine sHA-OCD NPs
RKO toxicity is remarkably reinforced in taxol, it may be possible to deliver the medicament to tumour by the receptor-mediated active targeting effect of CD44
Cell improves anti-tumor activity.
Specific embodiments of the present invention are described in detail above, but are intended only as example, the present invention is not intended to limit
In particular embodiments described above.Therefore, made equal transformation and modification without departing from the spirit and scope of the invention,
It all should be contained within the scope of the invention.
Claims (7)
1. sulphated hyaluronic acid 2- octyl dodecanol ester, it is characterized in that being, which is the carboxylic in hyaluronic acid structure
On base grafted hydrophobic Y shape group 2- octyl dodecanol and on hydroxyl be grafted hydrophilic group sulfate radical and form non-linear polymerization
Object, have it is amphipathic, be self-assembly of nanoparticle in water, can be used as the nano-carrier of insoluble drug, it include n weigh
Multiple unit, general structure are (I) as follows:
2. sulphated hyaluronic acid 2- octyl dodecanol ester according to claim 1, wherein the molecular weight of hyaluronic acid is 5
×103~5 × 105Da。
3. sulphated hyaluronic acid 2- octyl dodecanol ester according to claim 1, wherein hydrophobic Y shape group 2- octyl
The degree of substitution of dodecanol is 1%~30%.
4. sulphated hyaluronic acid 2- octyl dodecanol ester according to claim 1, wherein sulfuric acid rate is 1~13%.
5. sulphated hyaluronic acid 2- octyl dodecanol ester according to claim 1, preparation method specifically includes following
Step:
A, the preparation of hyaluronic acid tetrabutylammonium salt (HA-TeBA): weighing appropriate Sodium Hyaluronate (HA-Na) and be dissolved in distilled water,
Magnetic agitation dissolution；It weighs a certain amount of tetrabutylammonium type DowexWX8 cation exchange resin to be added in HA-Na, at room temperature magnetic force
Stir 3h, filtering, vacuum freezedrying for 24 hours, 40 DEG C of vacuum drying 12h to get；
B, the preparation of sulphated hyaluronic acid (sHA): precision weighs appropriate HA-TeBA and is dissolved in N, N '-dimethyl formamide (DMF)
In, 50 DEG C of magnetic agitation 2h make it dissolve；Another precision weighs a certain amount of sulfur trioxide N, and N '-dimethyl formyl amine complex is molten
In DMF, at room temperature after stirring and dissolving, it is added in above-mentioned HA-TeBA solution, nitrogen charging gas shielded, magnetic agitation under 0 DEG C of ice bath
1h；1MNaOH solution adjusts pH to neutrality, and 2-3 times of volume ethanol is added and stands overnight, precipitating, distilled water dialysis are taken after centrifugation
1d, vacuum freezedrying for 24 hours to get；
C, the preparation of sulphated hyaluronic acid 2- octyl dodecanol ester (sHA-OCD): precision weighs appropriate sHA and is dissolved in formamide
In, then the dissolution of room temperature magnetic agitation sets in ice bath, adds a certain amount of 1- ethyl-(3- dimethylaminopropyl) carbodiimide
Hydrochloride (EDC), n-hydroxysuccinimide (NHS) stir 2h under ice bath；The another accurate a certain amount of 2- octyldodecanol of measurement
(OCD) it is dissolved in DMF, is added dropwise in above-mentioned sHA solution, 35 DEG C of magnetic agitations are for 24 hours；Reaction solution be added ethanol precipitation from
The heart, distilled water is dialysed after precipitating is dissolved with water, vacuum freezedrying.
6. a kind of drug-carrying polymer nanoparticle, which is characterized in that sulphated hyaluronic acid 2- octyl ten as described in claim 1
Diol ester contains insoluble drug, and drug-carrying nanometer particle is made.
7. drug-carrying polymer nanoparticle according to claim 6, preparation method includes the following steps: sulphation is saturating
Bright matter acid 2- octyl dodecanol ester is dissolved in distilled water, is self-assembly of the blank nanoparticle solution that concentration is 2~8mg/mL, will be difficult
It after soluble drug is dissolved in a small amount of organic solvent, is added dropwise in above-mentioned blank nanoparticle solution, after sonicated, is placed in double
It steams dialysis in water and removes organic solvent, after dialyzate is centrifuged, is filtered, filtrate is the polymer drug-carried of 100~300nm of partial size
Micella.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710119592.2A CN106832056B (en) | 2017-02-24 | 2017-02-24 | Sulphated hyaluronic acid 2- octyl dodecanol ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710119592.2A CN106832056B (en) | 2017-02-24 | 2017-02-24 | Sulphated hyaluronic acid 2- octyl dodecanol ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106832056A CN106832056A (en) | 2017-06-13 |
| CN106832056B true CN106832056B (en) | 2019-08-06 |
Family
ID=59137254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710119592.2A Active CN106832056B (en) | 2017-02-24 | 2017-02-24 | Sulphated hyaluronic acid 2- octyl dodecanol ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106832056B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101897976A (en) * | 2010-07-16 | 2010-12-01 | 沈阳药科大学 | Medicament solubilization carrier and preparation method and application thereof |
| CN103435718A (en) * | 2013-08-21 | 2013-12-11 | 中国药科大学 | PEG (polyethylene glycol)-modified hyaluronic acid cholesteryl ester |
| CN104024277A (en) * | 2011-12-02 | 2014-09-03 | 实验室维维西公司 | Method for simultaneously substituting and cross-linking a polysaccharide by means of the hydroxyl functions thereof |
| CN105820270A (en) * | 2016-03-30 | 2016-08-03 | 中国药科大学 | Sulfated hyaluronan fatty hydrocarbon amine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3181276B2 (en) * | 1999-08-31 | 2001-07-03 | 科学技術振興事業団 | Amphiphilic compounds with dendritic branch structure |
| WO2007059890A1 (en) * | 2005-11-22 | 2007-05-31 | Centre National De Recherche Scientifique | New derivatives of hyaluronic acid, their preparation process and their uses |
-
2017
- 2017-02-24 CN CN201710119592.2A patent/CN106832056B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101897976A (en) * | 2010-07-16 | 2010-12-01 | 沈阳药科大学 | Medicament solubilization carrier and preparation method and application thereof |
| CN104024277A (en) * | 2011-12-02 | 2014-09-03 | 实验室维维西公司 | Method for simultaneously substituting and cross-linking a polysaccharide by means of the hydroxyl functions thereof |
| CN103435718A (en) * | 2013-08-21 | 2013-12-11 | 中国药科大学 | PEG (polyethylene glycol)-modified hyaluronic acid cholesteryl ester |
| CN105820270A (en) * | 2016-03-30 | 2016-08-03 | 中国药科大学 | Sulfated hyaluronan fatty hydrocarbon amine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106832056A (en) | 2017-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101791411B (en) | Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof | |
| Chen et al. | Core–shell nanocarriers with ZnO quantum dots-conjugated Au nanoparticle for tumor-targeted drug delivery | |
| CN103435718B (en) | The hyaluronic acid cholesteryl ester that PEG modifies | |
| CN102114246B (en) | Amphiphilic polysaccharide derivative vector for specific medicine release in organism focusas well as preparation and application of pharmaceutical composition thereof | |
| CN105727309A (en) | Preparation and application of dual-sensitivity amphiphilic polysaccharide-doxorubicin conjugate and pharmaceutical composition thereof | |
| CN101897976A (en) | Medicament solubilization carrier and preparation method and application thereof | |
| CN103143027A (en) | Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament | |
| CN105175656B (en) | A kind of temperature and oxidant stimuli-responsive Micelle-like Nano-structure of Two preparation method and application | |
| CN109438707B (en) | Poly dithiothreitol nano system for delivering antitumor drugs and preparation method and application thereof | |
| CN101665569B (en) | Hydrophilic polymer the side chain of which is modified by lipoic acid and preparation and application thereof | |
| CN104788670A (en) | Double-responsiveness glucan-polyamino acid block copolymer, preparation method of copolymer and drug-loaded micelle | |
| CN106883404B (en) | Polyethylene glycol vitamin E succinate derivative and its preparation method and application | |
| CN102391517A (en) | Nanometer micelle capable of intelligently releasing medicine as well as preparation method and application thereof | |
| CN111870579B (en) | Tumor-targeted nano micelle, preparation method and application of nano micelle as drug carrier | |
| CN104162169A (en) | Pharmaceutical composition as well as preparation method and use thereof | |
| CN102212146B (en) | Thioctic acid-modified hydrophilic polymer for side chain | |
| CN108245683B (en) | Anti-tumor prodrug with P-glycoprotein inhibition function and preparation method thereof | |
| Xiao et al. | Colloidal hydroxyethyl starch for tumor-targeted platinum delivery | |
| CN100569802C (en) | The synthetic method of subcellular organelle target directional Chitosan oligosaccharide-aliphatic acid grafting matter | |
| CN104398504B (en) | A kind of pharmaceutical composition of deoxypodophyllotoxin class medicine and preparation method thereof and preparation | |
| CN109232875B (en) | PH/reduction double-sensitive carrier material formed by Cys and derivatives thereof and polyester polymer, and preparation method and application thereof | |
| Li et al. | New heparin–indomethacin conjugate with an ester linkage: synthesis, self aggregation and drug delivery behavior | |
| CN105820270A (en) | Sulfated hyaluronan fatty hydrocarbon amine | |
| CN108186607A (en) | A kind of preparation method of the polymer drug-carried composite material of chitosan graft of breast cancer targeting | |
| CN105832668A (en) | Folic acid-targeted acid sensitive core-crosslinked drug-loaded micelles based on polyphosphoester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |