CN108096218B - A nanometer granule loaded with saikosaponin a and its preparation method - Google Patents
A nanometer granule loaded with saikosaponin a and its preparation method Download PDFInfo
- Publication number
- CN108096218B CN108096218B CN201810014285.2A CN201810014285A CN108096218B CN 108096218 B CN108096218 B CN 108096218B CN 201810014285 A CN201810014285 A CN 201810014285A CN 108096218 B CN108096218 B CN 108096218B
- Authority
- CN
- China
- Prior art keywords
- saikosaponin
- solution
- ssa
- carrier
- peg
- 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.)
- Expired - Fee Related
Links
Images
Classifications
-
- 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
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K9/5192—Processes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a saikosaponin a-carrying nanoparticle and a preparation method thereof, the saikosaponin a-carrying nanoparticle comprises a carrier and a drug saikosaponin a, wherein the carrier is a segmented copolymer of PCL and PEG. The particle size distribution and the surface charge of the SSa-loaded nano particles obtained by the invention are measured by Dynamic Light Scattering (DLS), and the size and the surface morphology of the nano particles are observed by a Scanning Electron Microscope (SEM), so that the particle size distribution of the SSa-loaded nano particles prepared by the invention is mainly about 100nm, the dispersibility is good, and the requirements of nano preparations are met. The method is simple and easy to implement, low in cost and easy for mass preparation. Adopts a nano drug delivery technology to improve the solubility of the saikosaponin a in water and reduce the hemolytic property, thereby reducing the toxic and side effects of the saikosaponin a.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to saikosaponin a-loaded nanoparticles and a preparation method thereof, in particular to saikosaponin a-loaded nanoparticles taking a segmented copolymer of PCL and PEG as a carrier and a preparation method thereof.
Background
Saikosaponin a (saikosaponin a, SSa) belongs to pentacyclic triterpene saponin component, and its molecular formula is C42H68O13Molecular weight is 780.98; has anti-epileptic, anticonvulsive, cell adhesion resisting, analgesic, antiinflammatory, antibacterial, liver protecting, kidney protecting, anticancer, and antiviral effects. In the research of pharmacokinetic properties, SSa shows the following characteristics that (l) SSa has certain solubility, but is very low; in addition, because of its large molecular weight, it is difficult to permeate biological membranes, and thus, oral bioavailability is very low, below 1%. (2) SSa is composed of pentacyclic tristimulus aglycone and 2 sugar molecules, and is susceptible to intestinal flora after oral administration, and is hydrolyzed to become secondary glycoside or aglycone. The administration route is changed, and the injection administration is the best way for solving the problem of low bioavailability, but the simple injection of SSa can cause serious hemolytic reaction, and has great safety hazard. Therefore, the selection of a suitable drug delivery system, while improving its bioavailability, and reducing its hemolytic toxicity is the key to the study. In the aspect of preparation process, the main research directions at home and abroad are focused on the bupleurum compound or bupleurum total saponin, but the research on the active ingredient SSa is little. The bupleurum injection on the market at present is a sterilized aqueous solution prepared by solubilizing bupleurum volatile oil by tween 80, but the tween-80 has hemolytic effect and can not be injected intravenously, and the bupleurum injection has strong irritation, so that patients feel obvious pain. Some researchers tried to improve the solubility of SSa by using solid dispersion technology and inclusion technology, and the inclusion of hydroxyl-diradical P-CD can significantly increase the solubility but the bioavailability is still very small. Therefore, it is desirable to provide a drug delivery system which can improve the solubility of hydrophobic drug saikosaponin a and improve the biosafety thereof, and has the advantages of biodegradability and good biocompatibility.
Disclosure of Invention
The invention uses PCL-PEG diblock as a carrier to entrap saikosaponin a for the first time, and aims to provide SSa-carried nano-particles, thereby improving SSa water solubility, reducing hemolysis, reducing toxic and side effects on human bodies, improving drug stability, and effectively prolonging half-life period in vivo.
The invention aims to provide the saikosaponin a-loaded nanoparticles.
The invention aims to provide a preparation method of the saikosaponin a-loaded nanoparticles.
The technical scheme adopted by the invention is as follows:
a nanoparticle carrying saikosaponin a contains a medicine saikosaponin a and a carrier, wherein the carrier is a segmented copolymer of polycaprolactone and polyethylene glycol, and the mass ratio of the carrier to the medicine saikosaponin a is (7-25): 1.
furthermore, the average molecular weight of the polyethylene glycol in the carrier is 500-8000, and the average molecular weight of the polycaprolactone is 8000-30000.
A method for preparing nanoparticles loaded with saikosaponin a comprises the following steps:
1) mixing PEG-PCL solution and saikosaponin a solution, and recording as phase A; taking a sodium cholate solution, marking as a phase B, adding the solution into the phase A, and performing ultrasonic treatment to obtain an O/W emulsion;
2) adding a sodium cholate solution into the O/W emulsion, and stirring and solidifying the nano particles; evaporating the organic solvent in the solution by rotary vacuum;
3) filtering, ultrafiltering, centrifuging, concentrating, adding water, ultrafiltering, centrifuging, concentrating to obtain solution with blue opalescence, that is, saikosaponin a-carrying nanoparticles.
Further, in the step 1), the concentration of the PEG-PCL solution is 10-120 mg/mL.
Further, in the step 1), the concentration of the saikosaponin a solution is 5-25 mg/mL.
Further, in the step 1), the mass ratio of the PEG-PCL to the saikosaponin a is (7-25): 1.
further, in the step 1), the concentration of the sodium cholate solution is 0.5-2% w/v.
Further, in the step 1), the volume ratio of the phase A to the phase B is 1-5: 1.
further, in the step 2), the concentration of the sodium cholate solution is 0.1-0.9% w/v.
Further, in the step 2), the volume ratio of the O/W emulsion to the sodium cholate solution is 1: 8 to 25.
The invention has the beneficial effects that:
(1) compared with the prior art, the invention has the following advantages: adopts a nano drug delivery technology to construct SSa-loaded nano particles, improves the problems of SSa such as water solubility, slow release, reduced hemolysis and the like, and further reduces the toxic and side effects of saikosaponin a. The method has the advantages of convenient operation, simple and easy operation, good repeatability, low cost and easy mass preparation.
(2) The particle size distribution and the surface charge of the SSa-loaded nano particles obtained by the invention are measured by Dynamic Light Scattering (DLS), and the size and the surface morphology of the nano particles are observed by a Scanning Electron Microscope (SEM), so that the particle size distribution of the SSa-loaded nano particles prepared by the invention is mainly about 100nm, the dispersibility is good, and the requirements of nano preparations are met.
Drawings
FIG. 1 method for purifying PEG-PCL polymer1H-NMR analysis;
FIG. 2 is a graph showing the particle size distribution of SSa-loaded nanoparticles;
FIG. 3 is a graph of the surface charge of the illustrated SSa-loaded nanoparticle;
FIG. 4 is a scanning electron micrograph of SSa-loaded nanoparticles.
FIG. 5 is a release profile of SSa-loaded nanoparticles
Detailed Description
A nanoparticle carrying saikosaponin a contains a medicine saikosaponin a and a carrier, wherein the carrier is a segmented copolymer of polycaprolactone and polyethylene glycol, and the mass ratio of the carrier to the medicine saikosaponin a is (7-25): 1.
preferably, the average molecular weight of the polyethylene glycol in the carrier is 500-8000, and the average molecular weight of the polycaprolactone is 8000-30000.
A method for preparing nanoparticles loaded with saikosaponin a comprises the following steps:
1) mixing PEG-PCL solution and saikosaponin a solution, and recording as phase A; taking a sodium cholate solution, marking as a phase B, adding the solution into the phase A, and performing ultrasonic treatment to obtain an O/W emulsion;
2) adding a sodium cholate solution into the O/W emulsion, and stirring and solidifying the nano particles; evaporating the organic solvent in the solution by rotary vacuum;
3) filtering, ultrafiltering, centrifuging, concentrating, adding water, ultrafiltering, centrifuging, concentrating to obtain solution with blue opalescence, that is, saikosaponin a-carrying nanoparticles.
Preferably, in the step 1), the concentration of the PEG-PCL solution is 10-120 mg/mL.
Preferably, in step 1), the solvent of the PEG-PCL solution is at least one selected from dichloromethane and chloroform.
Preferably, in the step 1), the concentration of the saikosaponin a solution is 5-25 mg/mL.
Preferably, in step 1), the solvent of the saikosaponin a solution is at least one selected from ethanol and methanol.
Preferably, in the step 1), the mass ratio of the PEG-PCL to the saikosaponin a is (7-25): 1, more preferably (8-12): 1.
preferably, in the step 1), the concentration of the sodium cholate solution is 0.5-2% w/v.
Preferably, in the step 1), the volume ratio of the phase A to the phase B is 1-5: 1.
preferably, in the step 1), the power of ultrasonic treatment is 150-250 w, and the treatment time is 0.5-15 min.
Preferably, in the step 2), the concentration of the sodium cholate solution is 0.1-0.9% w/v.
Preferably, in the step 2), the volume ratio of the O/W emulsion to the sodium cholate solution is 1: 8 to 25.
Preferably, in the step 2), the stirring time is 4-6 min.
Preferably, in the step 3), the filtration is performed by using a filter membrane with a pore size of 0.18-0.24 μm.
Preferably, in step 3), the molecular weight cut-off of the ultrafiltration centrifugation is 3500 or more.
Preferably, in the step 3), the centrifugal force of the ultrafiltration centrifugation is 4500-5500 g, the centrifugation time is 17-34 min, and the temperature is 2-6 ℃.
Preferably, in step 1), the preparation method of the PEG-PCL comprises: mixing epsilon-caprolactone and Me-PEG, taking stannous octoate as a catalyst, stirring and reacting at 120-140 ℃ for 18-26 hours under the protection of nitrogen, dissolving a product with dichloromethane, adding methanol for precipitation, and drying the precipitation in vacuum to obtain the purified PEG-PCL polymer.
Preferably, the mass ratio of epsilon-caprolactone to Me-PEG is 2-10: 1.
Preferably, the average molecular weight of the polyethylene glycol in the PEG-PCL polymer is 500-8000, and the average molecular weight of the polycaprolactone is 8000-30000.
The present invention will be further described with reference to the following examples.
Example 1: a method for preparing nanoparticles loaded with saikosaponin a
(1) Synthesis of the Carrier PEG-PCL
The carrier synthesis steps are as follows: 24g of epsilon-caprolactone (epsilon-CL) and 4g of Me-PEG are mixed (the mass ratio of the epsilon-CL to the polyethylene glycol PEG is 6:1), stannous octoate accounting for 0.1 percent of the total mass of the reaction system is used as a catalyst, and the mixture is slowly and mechanically stirred under the protection of nitrogen and reacts for 24 hours at 130 ℃ to obtain the brown polymer PEG-PCL. 1.4g of the polymer was weighed, dissolved by adding 2ml of methylene chloride, precipitated by adding a large amount (about 100ml) of methanol, and the precipitate was repeated 3 times to remove unreacted epsilon-caprolactone and the epsilon-caprolactone homopolymer formed. The precipitate is dried in vacuum at 40 ℃ for 48 hours to finally obtain the purified PEG-PCL polymer1H-NMR analysis As shown in FIG. 1, the average molecular weight of polyethylene glycol in the carrier was 2000, and the average molecular weight of polycaprolactone was 13000. The product is yellow-white, dried and stored at low temperature.
(2) Preparation of SSa-loaded nanoparticles
Weighing 90mg of carrier material PCL-PEG, adding 1mL of solvent dichloromethane to fully dissolve the carrier material PCL-PEG, adding 1mL of SSa anhydrous ethanol solution of 10mg/mL, and uniformly mixing to obtain phase A; then, 1% (w/v) sodium cholate solution (phase B) was slowly added to the above solution, wherein the volume ratio of phase A to phase B was 2: 1; the resulting O/W emulsion was further diluted to 15 volumes of 0.5% W/v sodium cholate solution, and then stirred at room temperature for 5 minutes with a magnetic stirrer to solidify the nanoparticles. After this time, the added organic solvents (dichloromethane and absolute ethanol) were evaporated by rotary vacuum. Filtering the solution through a 0.22-micron microporous filter membrane, performing ultrafiltration centrifugal concentration by using a Millipore ultrafiltration centrifugal tube, centrifuging for 30min at 5000g and 4 ℃, taking the concentrated solution, adding deionized water for washing, and repeating the ultrafiltration and centrifugation twice to obtain a solution with blue opalescence, namely SSa-loaded nanoparticles.
The effect of SSa-loaded nanoparticles prepared according to the present invention was further examined below.
Dynamic light Scattering test (DLS)
The particle size distribution and the apparent charge of the SSa-loaded nanoparticles prepared according to the present invention were measured by Dynamic Light Scattering (DLS) method, and the results are shown in fig. 2 and 3. As can be seen from FIG. 2, the particle size distribution of the carrier prepared by the invention is mainly about 100nm, the dispersibility is better, and the carrier meets the requirements of nano preparations. As can be seen from FIG. 3, the SSa-loaded nanoparticles prepared by the method have a surface potential of-25.77 mV, and can be stably present in a suspension.
Second, scanning electron microscope detection
The size and surface morphology of the nanoparticles of the invention were observed by Scanning Electron Microscopy (SEM). As shown in fig. 4, further demonstrating the results of fig. 2, the under-lens nanoparticles are round, uniform in size, and well dispersed.
Third, detection of hemolysis rate
The method comprises the following steps: the in vitro hemolysis experiment is carried out by adopting sterile defibrinated goat blood, 2% sheep red blood cell solution is prepared by normal saline, SSa with different concentration or SSa-carried nano particles of the invention are incubated for 1 hour at 37 ℃, centrifugation is carried out for 15min at 4 ℃ under 800g, supernatant is collected, and hemolysis rate is measured and calculated at 540nm by an ultraviolet spectrophotometer.
As a result: as shown in Table 1, the SSa-loaded nanoparticles of the present invention showed very low hemolysis rates in the concentration range of 10-100 μ g/ml, which are 0.78 + -0.13% and 3.26 + -0.17%. The invention can improve SSa water solubility, reduce its hemolytic property, reduce its toxic and side effects to human body, improve medicine stability, and effectively prolong half life period in vivo.
TABLE 1 results of determination of hemolysis rate of SSa-loaded nanoparticles of the present invention
IV, in vitro Release detection
The method comprises the following steps: the in vitro release behavior of SSa-loaded nanoparticles was examined by dialysis. The release medium was PBS (0.01mol/L, pH7.4) containing 5% Tween-20, and the release test was designed to ensure that drug release was performed in a sink-drain condition. lmL drug-loaded nanoparticle solution was added into a pre-swollen dialysis bag (MWCO ═ 3500Da), the bag mouth was tightened, and the bag was placed in a container containing 40mL of release medium, and the release experiment was performed at 37 ℃ with shaking at 100 rpm. The SSa concentration in the released samples was determined by sampling 1mL for 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96,120h, respectively, while supplementing an equivalent amount of 37 ℃ blank release medium. The cumulative percent release was calculated SSa. SSa as a control group.
As a result: the detection results are shown in fig. 5, the cumulative release rates of ssa (free ssa) and the inventive supported SSa nanoparticle (MePEG-PCL @ SSa) are 85.0 ± 2.95% and 19.6 ± 1.94% respectively within 24 hours, and after 120 hours, the cumulative release rate of the inventive supported SSa nanoparticle reaches 75.7 ± 4.8%, which indicates that the inventive supported SSa nanoparticle can continuously and slowly release SSa without burst release.
Example 2: a method for preparing nanoparticles loaded with saikosaponin a
(1) Synthesis of the Carrier PEG-PCL
The carrier synthesis steps are as follows: mixing epsilon-caprolactone (epsilon-CL) and Me-PEG (the mass ratio of the epsilon-CL to the polyethylene glycol PEG is 10:1), taking stannous octoate accounting for 0.1 percent of the total mass of a reaction system as a catalyst, slowly and mechanically stirring under the protection of nitrogen, and reacting for 18 hours at 120 ℃ to obtain the brown polymer PEG-PCL. 1.4g of the brown polymer was weighed, dissolved by adding 2ml of methylene chloride, precipitated by adding a large amount (about 100ml) of methanol, and the precipitate was repeated 3 times to remove unreacted epsilon-caprolactone and the epsilon-caprolactone homopolymer formed. And (3) drying the precipitate at 40 ℃ for 48 hours in vacuum to finally obtain a purified PEG-PCL polymer carrier, wherein the average molecular weight of the polyethylene glycol in the carrier is 8000, and the average molecular weight of the polycaprolactone is 30000. The product is yellow-white, dried and stored at low temperature.
(2) Preparation of SSa-loaded nanoparticles
Weighing 120mg of carrier material PCL-PEG, adding 1mL of solvent dichloromethane to fully dissolve the PCL-PEG, adding 0.5mL of SSa anhydrous ethanol solution of 25mg/mL, and mixing uniformly to obtain phase A; then, 0.5% (w/v) sodium cholate solution (phase B) was slowly added to the above solution, wherein the volume ratio of phase A to phase B was 5: 1; the resulting O/W emulsion was further diluted to 25 volumes of 0.1% W/v sodium cholate solution and then stirred at room temperature for 4 minutes with a magnetic stirrer to solidify the nanoparticles, which was then sonicated at 200W for 15 minutes to form an O/W milky white emulsion. After this time, the added organic solvents (dichloromethane and absolute ethanol) were evaporated by rotary vacuum. Filtering the solution with a 0.22um microporous filter membrane, performing ultrafiltration centrifugal concentration (molecular weight cutoff is 3500) by using a Millipore ultrafiltration centrifugal tube, centrifuging for 17min at 5500g and 6 ℃, taking the concentrated solution, washing with deionized water, and repeating the ultrafiltration and centrifugation for two times to obtain a solution with blue opalescence, namely SSa-loaded nano-particles.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Example 3: a method for preparing nanoparticles loaded with saikosaponin a
(1) Synthesis of the Carrier PEG-PCL
The carrier synthesis steps are as follows: mixing epsilon-caprolactone (epsilon-CL) and Me-PEG (the mass ratio of the epsilon-CL to the polyethylene glycol PEG is 2:1), taking stannous octoate accounting for 0.1 percent of the total mass of a reaction system as a catalyst, slowly and mechanically stirring under the protection of nitrogen, and reacting for 26 hours at 140 ℃ to obtain the brown polymer PEG-PCL. 1.4g of the brown polymer was weighed, dissolved by adding 2ml of methylene chloride, precipitated by adding a large amount (about 100ml) of methanol, and the precipitate was repeated 3 times to remove unreacted epsilon-caprolactone and the epsilon-caprolactone homopolymer formed. And (3) drying the precipitate at 40 ℃ for 48 hours in vacuum to finally obtain a purified PEG-PCL polymer carrier, wherein the average molecular weight of the polyethylene glycol in the carrier is 500, and the average molecular weight of the polycaprolactone is 8000. The product is yellow-white, dried and stored at low temperature.
(2) Preparation of SSa-loaded nanoparticles
Weighing 10mg of carrier material PCL-PEG, adding 1mL of solvent dichloromethane to fully dissolve the carrier material PCL-PEG, adding 0.2mL of SSa anhydrous ethanol solution of 5mg/mL, and uniformly mixing to obtain phase A; next, 2% (w/v) sodium cholate solution (phase B) was slowly added to the above solution, wherein the volume ratio of phase a to phase B was 1: 1; the resulting O/W emulsion was further diluted to 8 volumes of 0.9% W/v sodium cholate solution, and then stirred at room temperature for 6 minutes with a magnetic stirrer to solidify the nanoparticles, after which it was sonicated at 250W for 0.5 minutes to form an O/W type milky white emulsion. After this time, the added organic solvents (dichloromethane and absolute ethanol) were evaporated by rotary vacuum. Filtering the solution with 0.24um microporous membrane, performing ultrafiltration centrifugal concentration (molecular weight cutoff is 3500) by a Millipore ultrafiltration centrifugal tube, centrifuging at 4500g 2 ℃ for 34min, taking the concentrated solution, washing with deionized water, and repeating the ultrafiltration and centrifugation twice to obtain solution with blue opalescence, namely SSa-loaded nanoparticles.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (9)
1. The nanoparticle carrying the saikosaponin a is characterized by comprising a medicine saikosaponin a and a carrier, wherein the carrier is a block copolymer of polycaprolactone and polyethylene glycol, and the mass ratio of the carrier to the medicine saikosaponin a is (7-25): 1; the average molecular weight of the polyethylene glycol in the carrier is 500-8000, and the average molecular weight of the polycaprolactone is 8000-30000.
2. A method for preparing the saikosaponin a-loaded nanoparticles as claimed in claim 1, comprising the steps of:
1) mixing PEG-PCL solution and saikosaponin a solution, and recording as phase A; taking a sodium cholate solution, marking as a phase B, adding the solution into the phase A, and performing ultrasonic treatment to obtain an O/W emulsion;
2) adding a sodium cholate solution into the O/W emulsion, and stirring and solidifying the nano particles; evaporating the organic solvent in the solution by rotary vacuum;
3) filtering, ultrafiltering, centrifuging, concentrating, adding water, ultrafiltering, centrifuging, concentrating to obtain solution with blue opalescence, that is, saikosaponin a-carrying nanoparticles.
3. The method according to claim 2, wherein in step 1), the concentration of the PEG-PCL solution is 10-120 mg/mL.
4. The method as claimed in claim 2, wherein in the step 1), the concentration of the saikosaponin a solution is 5-25 mg/mL.
5. The method according to claim 2, wherein in step 1), the mass ratio of PEG-PCL to saikosaponin a is (7-25): 1.
6. the method as claimed in claim 2, wherein the concentration of the sodium cholate solution in step 1) is 0.5-2% w/v.
7. The method according to claim 2, wherein in the step 1), the volume ratio of the phase A to the phase B is 1-5: 1.
8. the method as claimed in claim 2, wherein the concentration of the sodium cholate solution in step 2) is 0.1-0.9% w/v.
9. The method as claimed in claim 2, wherein in step 2), the volume ratio of the O/W emulsion to the sodium cholate solution is 1: 8 to 25.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810014285.2A CN108096218B (en) | 2018-01-08 | 2018-01-08 | A nanometer granule loaded with saikosaponin a and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810014285.2A CN108096218B (en) | 2018-01-08 | 2018-01-08 | A nanometer granule loaded with saikosaponin a and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108096218A CN108096218A (en) | 2018-06-01 |
| CN108096218B true CN108096218B (en) | 2021-03-16 |
Family
ID=62219909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810014285.2A Expired - Fee Related CN108096218B (en) | 2018-01-08 | 2018-01-08 | A nanometer granule loaded with saikosaponin a and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108096218B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117327262B (en) * | 2023-09-06 | 2024-06-14 | 中山大学附属第三医院 | Responsive nano-drug carrier and preparation and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107242998A (en) * | 2016-06-28 | 2017-10-13 | 同济大学 | A kind of sodium taurocholate polymer nanocomposite combination drug carrier |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110020478A1 (en) * | 2009-07-24 | 2011-01-27 | Henrich Cheng | Method for treating neural injuries |
| CN105358220A (en) * | 2014-06-03 | 2016-02-24 | 高雄医学大学 | Composition prepared from saikosaponin, the use and the preparation method thereof |
-
2018
- 2018-01-08 CN CN201810014285.2A patent/CN108096218B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107242998A (en) * | 2016-06-28 | 2017-10-13 | 同济大学 | A kind of sodium taurocholate polymer nanocomposite combination drug carrier |
Non-Patent Citations (1)
| Title |
|---|
| 靶向星形细胞的柴胡皂苷a、柴胡皂苷d复方脂质体制备工艺研究及体内外评价;张国松;《中国博士学位论文全文数据库 医药卫生科技辑》;20151015(第10期);第E057-5 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108096218A (en) | 2018-06-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109010846B (en) | Polyethylene glycol-chitosan-curcumin polymer, drug-loaded nanoparticles thereof and preparation method | |
| Adeli et al. | Anticancer drug delivery systems based on noncovalent interactions between carbon nanotubes and linear–dendritic copolymers | |
| Wang et al. | Preparation of tacrolimus loaded micelles based on poly (ɛ-caprolactone)–poly (ethylene glycol)–poly (ɛ-caprolactone) | |
| US20060013885A1 (en) | Water soluble chitosan nanoparticle for delivering an anticancer agent and preparing method thereof | |
| CN108186605B (en) | Medicine-carrying nano-particles based on tannic acid and preparation method and application thereof | |
| Mady et al. | Cyclodextrin-based nanosponge for improvement of solubility and oral bioavailability of Ellagic acid. | |
| CN102198117A (en) | Thermosensitive polymeric microcapsules and preparation method and use thereof | |
| US20190328880A1 (en) | Amphiphilic block copolymer composition having enhanced micelle stability, and pharmaceutical composition comprising same | |
| Vineeth et al. | Influence of organic solvents on nanoparticle formation and surfactants on release behaviour in-vitro using costunolide as model anticancer agent | |
| CN108096218B (en) | A nanometer granule loaded with saikosaponin a and its preparation method | |
| CN101984958A (en) | Nanoscale albendazole micropowder and preparation method thereof | |
| CN112089838B (en) | Black phosphorus nanogel medicine for tumor microenvironment response and preparation method and application thereof | |
| CN113307970A (en) | Preparation method of ultra-small poly-dopamine/poly-dopamine cysteine nano-particles | |
| CN112006986A (en) | Vitamin E succinate polyethylene glycol nano micelle and preparation method and application thereof | |
| CN114642652B (en) | Preparation and application of fucoidin self-assembled drug-loaded nanoparticle | |
| CN111297829A (en) | Modified glucan-coated core-shell composite nanoparticle and preparation method thereof | |
| CN113332453B (en) | Preparation method of water-soluble propolis nanoparticles | |
| CN105879051A (en) | Preparation and application of self-assembled nano-drug of core-shell structure | |
| CN108524942A (en) | A kind of pH responsive type medicine-carried nano particles and preparation method thereof based on ganoderma lucidum polysaccharide-histidine conjugate | |
| CN106389385B (en) | Annonacin nanoparticle based on cyclodextrin and lecithin as carriers and preparation method and application thereof | |
| EP2167031B1 (en) | Hyperbranched polymers based on cyclodextrins and poly(amidoamines) for the controlled release of insoluble drugs | |
| CN109276545B (en) | Preparation method of tanshinone IIA/chitosan pH sensitive solid dispersion | |
| WO2007029898A1 (en) | Water soluble chitosan nanoparticle for delivering an anticancer agent and preparing method thereof | |
| CN108451931B (en) | PAH/F polyelectrolyte compound nano-carrier and preparation method thereof | |
| CN112807443A (en) | Multiple synergistic antibacterial nano prodrug |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210316 Termination date: 20220108 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |