CN107625768A - A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof - Google Patents
A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof Download PDFInfo
- Publication number
- CN107625768A CN107625768A CN201710878987.0A CN201710878987A CN107625768A CN 107625768 A CN107625768 A CN 107625768A CN 201710878987 A CN201710878987 A CN 201710878987A CN 107625768 A CN107625768 A CN 107625768A
- Authority
- CN
- China
- Prior art keywords
- sorafenib
- preparation
- albumin nano
- oral administration
- albumin
- 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
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Sorafenib albumin nano preparation of high oral administration biaavailability, belong to field of pharmaceutical preparations, the Sorafenib albumin nano preparation of high oral administration biaavailability, include the component of following mass percent：Sorafenib 0.03~0.07%, carrier material 0.5~2%, organic solvent 0.025~0.05%, crosslinking agent 0.005~0.02%, surplus are physiological saline.The Sorafenib albumin nano preparation of high oral administration biaavailability disclosed by the invention, with particle diameter is small, envelop rate is high, stability is good, low with good targeting, toxic side effect, its oral administration biaavailability is 5.4 times of Sorafenib supensoid agent.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, more particularly to a kind of Sorafenib of high oral administration biaavailability is white
Protein nano preparation and preparation method thereof.
Background technology
Sorafenib (sorafenib, being abbreviated as SRF) is to belong to diaryl urea, clinically be Sorafenib
Toluene fulfonate (trade name Nexavar, Nexavar), entitled 4- (4-3- [4- chloro- 3- (trifluoromethyl) phenyl] the urea groups benzene of chemistry
Epoxide) -2- picoline -2- carboxylic acyl -4- toluene fulfonates, molecular formula C21H16ClF3N4O3·C7H8O3S, molecular weight are
637.03g·mol-1.Its poorly water-soluble, is slightly soluble in ethanol, is dissolved in polyethylene glycols 400 (PEG400).Sorafenib can be with target
To a variety of serine/threonine kinases and receptor tyrosine kinase acted on tumour cell and tumor vessel, play simultaneously
The double action of anti-angiogenesis and anti-tumour cell proliferative：On the one hand Sorafenib can suppress receptor tyrosine kinase KIT
With serine/threonine kinase in FLT-3 and Raf/MEK/ERK approach, hence it is evident that suppress tumor cell proliferation；On the other hand,
Receptor tyrosine kinase VEGFR and PDGFR are suppressed by upstream, and downstream suppresses serine/Soviet Union's ammonia in Raf/MEK/ERK approach
Acid kinase, hence it is evident that suppress Tumor Angiongesis.Because of its good antitumor action, in October, 2007 Drug Administration of European Union
(EMEA), in November, 2007 U.S.'s food and medicine Surveillance Authority (FDA) and in June, 2008 China's food and medicine Surveillance Authority
Etc. (SFDA) have approved in succession Sorafenib be used for treat the hepatocellular carcinoma that can not perform the operation.
The clinical research of SRF treatment hepatocellular carcinomas shows that it can effectively suppress the growth of tumour cell, preventing and treating state of an illness hair
Exhibition deteriorates, and has become a kind of effective medicine.Although SRF toxicity is smaller, tolerance is preferable, and the medicine is still deposited
In the adverse reaction that some need to should draw attention in clinical research and application.In the clinical research of I phase, common adverse reaction
Incidence is：Weak 40%, apocleisis 35%, diarrhoea 34%, fash/husking 27%, HFSR (hand-foot syndrome) 25%；With medication
Related blood pressure rise incidence is 5%~11% (3/4 degree of hypertension is 0~5%).At present, the Sorafenib listed
The general entitled toluenesulfonic acid Sorafenib piece of preparation, after regular dosage form administration, generally only a small amount of medicine can reach liver, kidney target
Tissue.If wanting to improve drug effect, dosage must be increased, but also increase the toxic side effect of medicine simultaneously, reduce patient's
Compliance.Therefore, the targeting of Sorafenib how is improved, the performance drug effect for continuing, concentrating, and improve bioavilability, drop
Low whole body toxic side effect, it is the emphasis that we study.
Nanoparticle is the focus of Modern Pharmaceutics research, and medicine is disperseed, encapsulated, is adsorbed on polymer particle, passed through
Cyst wall leaching, infiltration and dispersal events come out, and can also be released the drug by the corrosion of matrix in itself.With targeting, slow release, change
The method of administration of medicine, the absorption for increasing medicine and bioavilability, the solubility for increasing insoluble drug, improve drug substance stable
Property and reduce adverse reaction the advantages that.Have researcher both at home and abroad at present to grind Sorafenib nano-particle technology
Study carefully：1) glucan-polylactic-co-glycolic acid block copolymer Sorafenib nanoparticle is prepared using nanoprecipitation dialysis, ground
Study carefully result and show that the nanoparticle has good slow releasing function, growth of tumour cell can be suppressed；2) high-pressure homogenising method is utilized
Taxol-Sorafenib protein nano particulate is prepared, while growth of cancer cells is suppressed, relative to taxol and Sorafenib
Monomer medicine, its toxic side effect significantly reduce；3) it is micro- to develop poly glycol monomethyl ether-poly-dl-lactide block copolymer nano
Grain, the nanoparticle have cell and molecular level dual-target and good slow-releasing and controlled-releasing action；4) silica 350 is used respectively
And the obtained Sorafenib nanoparticles of acrylic resin s100 that pH is sensitive, mouse experiment in vivo show and Sorafenib supensoid agent
Compare, Sorafenib nanoparticle can substantially increase bioavilability, made from acrylic resin s100 sensitive wherein pH
Sorafenib nanoparticle bioavilability is higher than the bioavilability of nanoparticle made from silica 350.
Albumin is frequently as targetable drug carriers to improve the targeting of medicine in vivo.Selection albumin is given as targeting
It is endogenous material that drug carrier, which is based primarily upon it, will not produce toxicity or immune response；In addition, the amino acid in albumin is with peptide
Key is connected, and is twisted into bulk, has reticulated void, advantage is created to inlay carrying medicine, with liposome and emulsion
It is preferable with bin stability compared to inside albumin nano granular.
In consideration of it, preparing Sorafenib albumin nano granular using the method for simple possible has great potential market valency
Value, and also have important theory significance to researching and developing new Sorafenib targeting preparation.
The content of the invention
The defects of in order to overcome prior art, the technical problems to be solved by the invention are to propose a kind of high oral bio
The Sorafenib albumin nano preparation of availability, it is set, with good targeting, to improve Sorafenib when treating liver cancer
Bioavilability, reduce toxic side effect.
To use following technical scheme up to this purpose, the present invention：
The invention provides a kind of Sorafenib albumin nano preparation of high oral administration biaavailability, including following quality
The component of percentage：Sorafenib 0.03~0.07%, carrier material 0.5~2%, organic solvent 0.025~0.05%, crosslinking
Agent 0.005~0.02%, surplus are physiological saline.
In preferably technical scheme of the invention, the carrier material is animal serum albumin.
In preferably technical scheme of the invention, the organic solvent is absolute ethyl alcohol or isopropanol.
In preferably technical scheme of the invention, the crosslinking agent is glutaraldehyde or polyethylene glycol；Volume fraction is 0.1
~1.0%.
In preferably technical scheme of the invention, the system of the Sorafenib albumin nano preparation of high oral administration biaavailability
Preparation Method, it is characterised in that comprise the following steps：
(1) carrier material is dissolved in physiological saline and carrier solution is made；
(2) 0.2molL is used-1NaOH adjusts the carrier solution pH value to 8~9, obtains alkalescence carrier solution；
(3) Sorafenib is dissolved in the organic solvent and oil phase is made；
(4) at normal temperatures, by the oil phase under 500rpm/min stirring conditions, it is slowly added to the alkalescence carrier
In solution, crosslinking agent solidification more than the 3h is then instilled, obtains Sorafenib albumin nano granular suspension.
(5) into the Sorafenib albumin nano granular suspension, freeze drying protectant freeze-drying, get Suo Lafei are added
Buddhist nun's albumin nano (SRF-BSA NPs) preparation.
In preferably technical scheme of the invention, step (1) carrier material and step (3) the Sorafenib quality
Than for 10~40:1.
In preferably technical scheme of the invention, the carrier solution is 17~40 with the oil phase volume ratio:1.
In preferably technical scheme of the invention, in the step (4), the dosage of the crosslinking agent is every gram of carrier
2~6mL of material.
In preferably technical scheme of the invention, in the step (4), the Sorafenib albumin nano granular suspension
In Sorafenib albumin nano granular average grain diameter be 109.4~149.4nm, average envelop rate is 80.1~90.1%, is put down
Equal drugloading rate is 7.41~9.61%.
In preferably technical scheme of the invention, the freeze drying protectant is mannitol or trehalose, mass fraction 1
~8%.
Beneficial effects of the present invention are：
Sorafenib albumin nano preparation of high oral administration biaavailability provided by the invention and preparation method thereof, passes through
The mass concentration of control vector solution, the pH of carrier solution, oil phase and the volume ratio of carrier solution, the dosage of crosslinking agent and friendship
Join the key factors such as the time of solidification, the Sorafenib albumin nano granular of high oral administration biaavailability is prepared, when pH=9 matter
The carrier solution that concentration is 0.5% is measured, mass concentration is 1.2% oil phase, and the volume ratio of oil phase and carrier solution is 1:24,
0.5% glutaraldehyde dosage is 4mL/g carriers, the Sorafenib albumin nano granular average grain diameter prepared by crosslinking curing 3 hours
For 129.4nm, PDI (dispersion index) is that 0.2, zeta current potentials are -16.4mv, envelop rate 85.1%, drugloading rate 8.51%,
Quality evaluation is good, and its when treating liver cancer with good targeting, Sorafenib bioavilability highest, oral bio
Availability is 5.4 times of Sorafenib supensoid agent, and toxic side effect is low.
Brief description of the drawings
The Sorafenib standard items liquid phase figure for the high oral administration biaavailability that Fig. 1 specific embodiment of the invention provides；
The Sorafenib albumin nano granular middle reaches for the high oral administration biaavailability that Fig. 2 specific embodiment of the invention provides
From the liquid phase figure of medicine；
In the Sorafenib albumin nano preparation for the high oral administration biaavailability that Fig. 3 specific embodiment of the invention provides
The grain size distribution of Sorafenib albumin nano granular；
In the Sorafenib albumin nano preparation for the high oral administration biaavailability that Fig. 4 specific embodiment of the invention provides
The potential diagram of Sorafenib albumin nano granular；
In the Sorafenib albumin nano preparation for the high oral administration biaavailability that Fig. 5 specific embodiment of the invention provides
Sorafenib albumin nano granular transmission electron microscope picture (50nm)；
In the Sorafenib albumin nano preparation for the high oral administration biaavailability that Fig. 6 specific embodiment of the invention provides
Sorafenib albumin nano granular transmission electron microscope picture (0.5 μm)；
In the Sorafenib albumin nano preparation for the high oral administration biaavailability that Fig. 7 specific embodiment of the invention provides
Sorafenib albumin nano granular (SRF-BSA NPs) and with concentration Sorafenib suspension (Suspension) in rat body
Drug-time curve comparison diagram.
Embodiment
Further illustrate technical scheme below in conjunction with the accompanying drawings and by embodiment.
Embodiment 1
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 50mg bovine serum albumin(BSA)s and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL-1NaOH
Adjust the PH to 9 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L absolute ethyl alcohols and 100 μ L PEG400, ultrasound
Dissolving is made into oil phase；417 μ L oil phases are slowly added dropwise in carrier solution under normal temperature 500rpm/min stirring conditions；Stir
After mixing 1 hour, it is slowly added dropwise 200 μ L0.5% glutaraldehydes and solidifies 3 hours, finally give Sorafenib albumin nano granular
Suspension.
Embodiment 2
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 50mg dog serum albumin and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL-1NaOH
Adjust the PH to 9 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L isopropanols and 100 μ L PEG400, and ultrasound is molten
Solution is made into oil phase；250 μ L oil phases are slowly added dropwise in carrier solution under normal temperature 500rpm/min stirring conditions；Stirring
After 1 hour, it is slowly added dropwise 200 μ L0.1% polyethylene glycol and solidifies 3 hours, finally give Sorafenib albumin nano granular
Suspension.
Embodiment 3
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 100mg bovine serum albumin(BSA)s and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL- 1NaOH adjusts the PH to 9 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L absolute ethyl alcohols and 100 μ L
PEG400, ultrasonic dissolution are made into oil phase；417 μ L oil phases are slowly added dropwise load under normal temperature 500rpm/min stirring conditions
In liquid solution；After stirring 1 hour, it is slowly added dropwise the glutaraldehydes of 200 μ L 0.1% and solidifies 3 hours, finally give Sorafenib
Albumin nano granular suspension.
Embodiment 4
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 50mg dog serum albumin and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL-1NaOH
Adjust the PH to 9 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L isopropanols and 100 μ L PEG400, and ultrasound is molten
Solution is made into oil phase；417 μ L oil phases are slowly added dropwise in carrier solution under normal temperature 500rpm/min stirring conditions；Stirring
After 1 hour, it is slowly added dropwise 200 μ L1.0% glutaraldehydes and solidifies 1 hour, finally give Sorafenib albumin nano granular and mix
Suspension.
Embodiment 5
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 50mg bovine serum albumin(BSA)s and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL-1NaOH
Adjust the PH to 7.5 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L absolute ethyl alcohols and 100 μ L PEG400, surpasses
Sound dissolving is made into oil phase；417 μ L oil phases are slowly added dropwise in carrier solution under normal temperature 500rpm/min stirring conditions；
After stirring 1 hour, it is slowly added dropwise the glutaraldehydes of 200 μ L 1.0% and solidifies 3 hours, finally give Sorafenib albumin nano
Grain suspension.
Embodiment 6
The preparation of Sorafenib albumin nano granular：
Precision, which weighs 50mg bovine serum albumin(BSA)s and is dissolved in 10mL physiological saline, is made carrier solution, uses 0.2molL-1NaOH
Adjust the PH to 9 of carrier solution；Precision weighs 12mg Sorafenibs, adds 900 μ L absolute ethyl alcohols and 100 μ L PEG400, ultrasound
Dissolving is made into oil phase；417 μ L oil phases are slowly added dropwise in carrier solution under normal temperature 500rpm/min stirring conditions；Stir
After mixing 1 hour, it is slowly added dropwise 100 μ L0.5% glutaraldehydes and solidifies 3 hours, finally give Sorafenib albumin nano granular
Suspension.
Sorafenib albumin nano granular property determines：
1st, the measure of Sorafenib albumin nano granular envelop rate and drugloading rate
The present invention uses high effective liquid chromatography for measuring Sorafenib concentration.
1.1 its HPLC-UV chromatographic condition are：Chromatographic column is Venusil AA C18 chromatographic columns (5 μm, 250*4.6mm)；Stream
Dynamic is mutually second eyeball:0.1% methanol (60:40)；Detection wavelength 265nm；Flow velocity 0.8mL/min；38 DEG C of column temperature；Sample size is 20 μ
L。
1.2 standard curve and Method validation
It is standby to prepare 1mg/mL Sorafenibs 80% methanol solution of reference substance.Sorafenib reference substance storing solution is drawn to add
0.1,0.5,1,3,6,10,20,50,100,250,500 μ g/mL reference substance solution is made in 80% methanol, injects liquid chromatogram
Instrument, using peak area as ordinate, Sorafenib concentration is abscissa, draws standard curve.As a result it is y to show calibration curve equation
=131.8x-41.113, R2=0.9999.Sorafenib reference substance HPLC collection of illustrative plates is as depicted in figs. 1 and 2.
2nd, envelop rate and drugloading rate measure
The Sorafenib albumin nano granular suspension 1mL of Example 1 is placed in centrifuge tube, is centrifuged under 15000rpm
30min.Supernatant is taken, the content of free drug is determined using HPLC-UV.According to the following formula calculate nanoparticle envelop rate and
Drugloading rate, its measurement result show that the average envelop rate of obtained Sorafenib albumin nano granular is 85.1%, and drugloading rate is
8.51%.
Envelop rate=(WAlwaysOne WIt is free)/WAlways× 100%；
Drugloading rate=(WAlwaysOne WIt is free)/WCarrier× 100%；
Wherein, WAlwaysIt is the gross weight of medicine, WIt is freeIt is not wrap the weight into the medicine in nanoparticle, WCarrierIt is to be carried in nanoparticle
The weight of body.
3rd, the measure of the particle diameter of Sorafenib albumin nano granular and current potential
The particle diameter and current potential of prepared Sorafenib albumin nano granular determine by Institute of Analysis of University Of Nanchang.
The Sorafenib albumin nano granular particle diameter (a) of embodiment 1 and the measurement result of current potential (b) are as shown in Figures 2 and 3.
4th, the investigation of Sorafenib albumin nano granular stability
4.1 evaluation index
1) outward appearance：The nanoparticle sample of different sample points is visually observed, is evaluated by following standard：
A. it is translucent, there are light blue opalescence, no precipitation
B. it is translucent, there is light blue opalescence, there is a little flocculation, slightly shake resilient
C. it is muddy, there is irreversible precipitation
2) envelop rate：Envelop rate is the important indicator for evaluating nanoparticle quality, while in nanoparticle storage process easily
Generation seepage, therefore the monitoring of envelop rate is very necessary.
3) particle diameter：The surface free energy of nano-particle is big, and in storage process, particle has spontaneous aggregation tendency, makes particle diameter
Increase, test result are shown in Fig. 5 and Fig. 6.
4.2 Accelerated stability test
The Sorafenib albumin nano granular suspension of brand-new is placed in ampoule bottle, preserved under the conditions of 25 DEG C of lucifuges,
Respectively at 0,0.5,1,1.5,2 month timing sampling, investigate project by aforementioned stable and be measured.As a result show, Sorafenib
Albumin nano granular suspension has declined with the extension of standing time, envelop rate, and particle diameter is without significant change, bottom after 45 days
Start to occur to precipitate a little, after two months basic precipitation.
5th, pharmacokinetic of the Sorafenib albumin nano granular in rat body
5.1 zoopery
Healthy female SD rats 10 are chosen, two groups is equally divided into, rope is orally given with 7.5mg/kg single doses respectively
La Feini albumin nano granulars and Sorafenib suspension.Gavage after time point 0.5,1,2,4,6,8,10,12,14,24,
34th, 48,58,72h, respectively eyeground take blood 0.5mL to be placed in centrifuge tube, after standing half an hour, 13000rpm centrifugation 5min, take out
Supernatant blood plasma is standby in -20 DEG C.
5.2 blood sample treatments
Taking-up freezes standby plasma sample, after being thawed under natural temperature, takes 200 μ L blood to add 100 μ L in centrifuge tube
Internal standard, 1.0mL80% methanol, ultrasonic extraction, 13000rpm centrifugation 5min, after taking-up supernatant 1mL is evaporated, with the first of 150 μ L 80%
Alcohol ultrasound is redissolved, and 13000rpm centrifuges 5min, takes supernatant sample introduction again.Each time point rope is determined using Agilent 1260HPLC
La Feini contents.
5.3 oral administration biaavailabilities contrast
The blood concentration of oral Sorafenib albumin nano granular is above the concentration of oral administration mixed suspension.The two Drug-time curve
Such as Fig. 4.Each pharmacokinetic parameter is calculated using DAS2.0.The bioavilability of Sorafenib suspension is 21.539mg/L*
H, the bioavilability of Sorafenib albumin nano granular is 116.837mg/L*h.As a result illustrate, be suspended with respect to Sorafenib
Liquid, Sorafenib albumin nano granular can greatly improve the blood concentration and bioavilability of Sorafenib in vivo.
6th, the distribution characteristics in rat body of Sorafenib albumin nano granular
Healthy female SD rats 30 are chosen, two groups is equally divided into, rope is orally given with 7.5mg/kg single doses respectively
La Feini albumin nano granulars and Sorafenib suspension.Gavage is after time point 2,6,8,10,24,58h per component other places dead 3
Rat, takes serum, liver standby in -20 DEG C.Determined using Agilent 1260HPLC in each time point blood plasma, hepatic tissue
Sorafenib content.
With selectivity index (DSI) and the targeting of drug targeting index (DTI) evaluation preparation.Calculation formula is as follows：
The medication amount of the medication amount of DSI=T moment target organs/T moment blood non-target organs
DTI=awards T moment target organs after the non-targeted preparation of the medication amount of T moment target organs after targeting preparation/award
Medication amount
Each time point after Sorafenib albumin nano granular and Sorafenib suspension is given by what efficient liquid phase measured
Sorafenib medicament contg substitutes into above formula in hepatic tissue and in blood, calculates in single oral Sorafenib albumin nano
After grain 2,6,10,24,58h, the selectivity index (DSI) in SD rat bodies is respectively 7.94,6.98,4.90,6.67,4.23,
And after single oral is with dosage Sorafenib supensoid agent 2,6,10,24,58h, the selectivity index (DSI) in SD rat bodies is respectively
For 2.4,3.97,1.39,1.5,1.73, supensoid agent group is all higher than in the DSI of same time point nanoparticle group, this is indicated that, should
Nanoparticle has good selectivity to rat liver, and hepatic tissue is with strong points, and effect is simple, and toxic side effect is few.Orally giving
After medicine Sorafenib albumin nano granular and Sorafenib suspension 2,6,10,24,58h, DSI is respectively 20.83,47.85,
11.16th, 21.64,11.81, this shows that Sorafenib albumin nano granular has good targeting, and Suo Lafei for hepatic tissue
The hepatic targeting of Buddhist nun's albumin nano granular is much larger than supensoid agent, as shown in Figure 7.
In a word, each index of distribution characteristics shows that the Sorafenib albumin nano granular can carry significantly in targeting preparation body
High drug bioavailability, while also have good hepatic targeting, so as to realize Targeting delivery, reduce toxic side effect.
The present invention is described with reference to the preferred embodiments, and those skilled in the art know, is not departing from the present invention's
In the case of spirit and scope, various changes or equivalence replacement can be carried out to these features and embodiment.The present invention is not by this
The limitation of specific embodiment disclosed in place, other embodiments fallen into claims hereof belong to protection of the present invention
Scope.
Claims (10)
1. the Sorafenib albumin nano preparation of a kind of high oral administration biaavailability, it is characterised in that including following quality hundred
The component of fraction：Sorafenib 0.03~0.07%, carrier material 0.5~2%, organic solvent 0.025~0.05%, crosslinking agent
0.005~0.02%, surplus is physiological saline.
2. the Sorafenib albumin nano preparation of high oral administration biaavailability according to claim 1, it is characterised in that
The carrier material is animal serum albumin.
3. the Sorafenib albumin nano preparation of high oral administration biaavailability according to claim 1, it is characterised in that
The organic solvent is absolute ethyl alcohol or isopropanol.
4. the Sorafenib albumin nano preparation of high oral administration biaavailability according to claim 1, it is characterised in that
The crosslinking agent is glutaraldehyde or polyethylene glycol；Volume fraction is 0.1~1.0%.
A kind of 5. preparation side of the Sorafenib albumin nano preparation of the high oral administration biaavailability described in Claims 1-4
Method, it is characterised in that comprise the following steps：
(1) carrier material is dissolved in physiological saline and carrier solution is made；
(2) 0.2molL is used-1NaOH adjusts the carrier solution pH value to 8~9, obtains alkalescence carrier solution；
(3) Sorafenib is dissolved in the organic solvent and oil phase is made；
(4) at normal temperatures, by the oil phase under 500rpm/min stirring conditions, it is slowly added to the alkalescence carrier solution
In, crosslinking agent solidification more than the 3h is then instilled, obtains Sorafenib albumin nano granular suspension.
(5) into the Sorafenib albumin nano granular suspension, freeze drying protectant freeze-drying is added, it is white to obtain Sorafenib
Protein nano preparation.
6. preparation method according to claim 5, it is characterised in that step (1) carrier material and step (3) are described
Sorafenib mass ratio is 10~40:1.
7. preparation method according to claim 5, it is characterised in that the carrier solution is 17 with the oil phase volume ratio
~40:1.
8. preparation method according to claim 5, it is characterised in that in the step (4), the dosage of the crosslinking agent is
Every gram of 2~6mL of carrier material.
9. preparation method according to claim 5, it is characterised in that in the step (4), the Sorafenib albumin
Sorafenib albumin nano granular average grain diameter in nanoparticle suspension is 109.4~149.4nm, and average envelop rate is 80.1
~90.1%, drug loading is 7.41~9.61%.
10. preparation method according to claim 5, it is characterised in that the freeze drying protectant is mannitol or marine alga
Sugar, mass fraction are 1~8%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710878987.0A CN107625768A (en) | 2017-09-26 | 2017-09-26 | A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710878987.0A CN107625768A (en) | 2017-09-26 | 2017-09-26 | A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107625768A true CN107625768A (en) | 2018-01-26 |
Family
ID=61101490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710878987.0A Pending CN107625768A (en) | 2017-09-26 | 2017-09-26 | A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107625768A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524951A (en) * | 2018-07-06 | 2018-09-14 | 南昌大学第二附属医院 | A kind of Sorafenib nanometer formulation with liver tumour targeting |
| CN110237049A (en) * | 2019-05-15 | 2019-09-17 | 齐齐哈尔医学院 | A method of preparing drug albumin nano granular |
| CN110403916A (en) * | 2019-07-31 | 2019-11-05 | 深圳大学 | A kind of nanometer of therapeutic agent and the preparation method and application thereof |
| CN113813257A (en) * | 2021-10-22 | 2021-12-21 | 吉林大学 | Application of biimidazole salt and drug-carrying system in serving as anticancer agent and anticancer preparation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105616361A (en) * | 2014-10-30 | 2016-06-01 | 复旦大学 | Preparation method of tinib drug alhumin nano preparation used for injection |
| CN107126564A (en) * | 2017-05-12 | 2017-09-05 | 辽宁大学 | A kind of albumin combination type Sorafenib nanometer formulation and preparation method thereof |
| WO2019050926A1 (en) * | 2017-09-06 | 2019-03-14 | Nantcell, Inc. | Aldoxorubicin combination treatments and methods |
-
2017
- 2017-09-26 CN CN201710878987.0A patent/CN107625768A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105616361A (en) * | 2014-10-30 | 2016-06-01 | 复旦大学 | Preparation method of tinib drug alhumin nano preparation used for injection |
| CN107126564A (en) * | 2017-05-12 | 2017-09-05 | 辽宁大学 | A kind of albumin combination type Sorafenib nanometer formulation and preparation method thereof |
| WO2019050926A1 (en) * | 2017-09-06 | 2019-03-14 | Nantcell, Inc. | Aldoxorubicin combination treatments and methods |
Non-Patent Citations (1)
| Title |
|---|
| 陆彬: "《药物新剂型与新技术》", 31 July 2005, 人民卫生出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524951A (en) * | 2018-07-06 | 2018-09-14 | 南昌大学第二附属医院 | A kind of Sorafenib nanometer formulation with liver tumour targeting |
| CN110237049A (en) * | 2019-05-15 | 2019-09-17 | 齐齐哈尔医学院 | A method of preparing drug albumin nano granular |
| CN110403916A (en) * | 2019-07-31 | 2019-11-05 | 深圳大学 | A kind of nanometer of therapeutic agent and the preparation method and application thereof |
| CN110403916B (en) * | 2019-07-31 | 2021-08-10 | 深圳大学 | Nano therapeutic agent and preparation method and application thereof |
| CN113813257A (en) * | 2021-10-22 | 2021-12-21 | 吉林大学 | Application of biimidazole salt and drug-carrying system in serving as anticancer agent and anticancer preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Hierarchical tumor microenvironment‐responsive nanomedicine for programmed delivery of chemotherapeutics | |
| CN107625768A (en) | A kind of Sorafenib albumin nano preparation of high oral administration biaavailability and preparation method thereof | |
| Poovi et al. | In vitro characterization and in vivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles | |
| Arya et al. | Assessing the viability of microsponges as gastro retentive drug delivery system of curcumin: optimization and pharmacokinetics | |
| Ma et al. | Controlling growth of ultrasmall sub-10 nm fluorescent mesoporous silica nanoparticles | |
| CN104414978B (en) | A kind of enteric-coated micro-pill containing esomeprazole magnesium | |
| Arias et al. | Polymeric nanoparticulate system augmented the anticancer therapeutic efficacy of gemcitabine | |
| CN103656652B (en) | A kind of sensitive response type polymer nano-micelle and its preparation method and application | |
| CN110302175B (en) | Lipoic acid nanocapsule containing hydrophobic cavity and preparation method and application thereof | |
| Rodrigues et al. | Preparation, in vitro characterization and in vivo release of naproxen loaded in poly-caprolactone nanoparticles | |
| CN107149592A (en) | Biological self-assembly nano-crystalline injection and preparation method with lympha targeted function | |
| Xu et al. | Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts | |
| Gupta et al. | Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir | |
| García et al. | Spray drying formulation of albendazole microspheres by experimental design. In vitro–in vivo studies | |
| CN105616385A (en) | Phospholipid protein particle composite microsphere and preparation method thereof | |
| CN104546728A (en) | Nanocrystalline of hydrophobic drug, as well as preparation and application methods of nanocrystalline | |
| Alvi et al. | Enhanced oral bioavailability of epalrestat SBE7-β-CD complex loaded chitosan nanoparticles: preparation, characterization and in-vivo pharmacokinetic evaluation | |
| CN105859990A (en) | Polymer with side chains containing lipoyl, preparation method of polymer, polymer vesica prepared from polymer and application of polymer vesica | |
| CN106361724A (en) | 20(R)-ginsenoside Rg3 slow release nanometer microsphere composition, and preparation method thereof | |
| Gazi et al. | Preparation and characterization of paracetamol loaded Eudragit S100 nanoparticles by salting out technique | |
| CN103585113A (en) | Apigenin polylactic acid sustained release microsphere and preparation method thereof | |
| Soltani et al. | Preparation and characterization of a novel multiparticulate dosage form carrying budesonide-loaded chitosan nanoparticles to enhance the efficiency of pellets in the colon | |
| Zhang et al. | Physical stability and in vivo brain delivery of polymeric ibuprofen nanoparticles fabricated by flash nanoprecipitation | |
| CN106265513B (en) | A kind of effect of nano-paclitaxel and preparation method thereof | |
| CN102552163B (en) | Metoprolol tartrate sustained release pellet and preparation method thereof |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180126 |