CN107049951A - It is a kind of to carry hollow Jenner's grain of rice and the thermal sensitive liposome preparation of tumor therapeutic agent and three integral applications altogether - Google Patents
It is a kind of to carry hollow Jenner's grain of rice and the thermal sensitive liposome preparation of tumor therapeutic agent and three integral applications altogether Download PDFInfo
- Publication number
- CN107049951A CN107049951A CN201710273592.8A CN201710273592A CN107049951A CN 107049951 A CN107049951 A CN 107049951A CN 201710273592 A CN201710273592 A CN 201710273592A CN 107049951 A CN107049951 A CN 107049951A
- Authority
- CN
- China
- Prior art keywords
- grain
- jenner
- rice
- hollow
- thermal sensitive
- 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.)
- Granted
Links
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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Prepared and " three integrations " application the present invention relates to a kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether.Said preparation is mainly made up of DPPC (DPPC), hollow Jenner's grain of rice and therapeutic agent, and thermal sensitive liposome is prepared by a conventional method, hollow Jenner's grain of rice is contained using extruded film method, then contains this preparation is obtained after therapeutic agent.This preparation had both reduced the toxic side effect of systemic drug treatment, and drug therapy, " three integrations " therapeutic effect of hyperthermia combined radiation are can reach again, the lethal effect to tumour is improved.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of temperature-sensitive lipid for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether
Body, the antitumor application thereof of its preparation method and its " three integration ".
Background technology
Thermal sensitive liposome (thermosensitive liposomes) is also known as temperature sensitive liposome, is that one kind can be in temperature
The liposome of medicine is discharged under heat condition.Under the heating-up temperature higher than phase change temperature of liposome, liposome membrane is by " glue crystalline state "
Liquid crystal structure is converted to, permeability increase, its medicine carried is released to rapidly heating position and produces Thermal targeting effect.It has
Effect make use of the double dominant of liposome and thermotherapy, further increases the targeting of liposome, reduces reticuloendothelial system
Intake to liposome, improves therapeutic effect, reduces toxicity.
Thermotherapy (hyperthermia, HT) is to improve tissue temperature to treat one kind side of tumour by artificial method
Method, the mechanism of thermotherapy treatment tumour mainly has following three kinds：1. there is selectively acting to tumor tissues, tumor group of being equally heated
The thermal response knitted is sensitive, and temperature correction often organizes rise, and 2. easily selectively killed has direct killing effect to tumour cell, temperature
Degree is denatured tumor cell proteins more than 40 DEG C, so as to cause death of neoplastic cells 3. to stimulate tumour cell to produce heat shock protein
In vain, the tumour cell for expressing heat shock protein is especially sensitive to NK, dissolved destruction can occurs.Although thermotherapy is not
Operation, radiotherapy or chemotherapy can be replaced as a kind of independent cancer immunotherapies, but it is controlled tumours such as chemotherapy, radiotherapy and operations
Treatment means have obvious synergy and supplementary function.
Radiotherapy (Radiation Therapy) is to cause biological cell to produce damage by the ionization of ray
Process, be one of the three big important means for treating malignant tumour.About 60%-70% malignant tumor patient needs to receive
Radiotherapy.According to the biological behaviour of tumour, the treatment of some tumours is reachable based on radiotherapy to effect a radical cure purpose.To unsuitable
Perform the operation, lose operative chance, Post operation and have residual tumor or suspected tumor residual person, it is tumor by local control to receive radiotherapy
Important selection.At present, increase tumor target radiological dose, improve local control rate, reduce tumour normal surrounding tissue
Exposure dose, preserves important organ normal function, improves the life quality of patient, the Main Trends of The Development as radiotherapy.
Hollow Jenner's grain of rice belongs to one kind of gold nano grain, by the big absorption cross-section that its cavity structure is formed, therefore
There is higher photothermal deformation effect compared with solid gold nanoparticle, and possess low toxicity, small size (diameter 30-60nm), spherical shape
The characteristics such as shape, tunable (550-950nm) absorption band, therefore on photo-thermal therapy, hollow Jenner's grain of rice can be substituted effectively
Solid gold nanoparticle.In addition, the photo-thermal therapy of gold nano-material is than chemotherapy and radiation side reaction much less, do not damage normal substantially
Tissue, is a kind of new tumor thermotherapy technology, is had a wide range of applications in biomedical sector.On the other hand, gold nano
Particle produces strong photoelectric absorption effect and secondary electron, accelerates DNA fracture, therefore after X-ray or gamma-rays irradiation
The new radiosensitizer of a class in radiotherapy field can be used as.
It is contemplated that tumor therapeutic agent is combined with hollow Jenner's grain of rice, prepares and possess photosensitivity and temperature is quick
The preparation of perception, effectively Cocktail treatment, thermotherapy and this " three integrations " treatment means of radiotherapy, are improved to tumor target
Tropism therapeutic effect and the toxic side effect for reducing single means treatment.
The content of the invention
An object of the present invention is a kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether of offer,
Said preparation can be such that medicine is efficiently discharged in tumor locus, and combine thermotherapy as good antineoplastic drug carrier by NIR
With radiotherapy effect, therapeutic effect is improved.
The second object of the present invention is to provide a kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether
The preparation method of preparation.
The third object of the present invention is to provide a kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether
Application of the preparation in oncotherapy.
The present invention provides following technical scheme
A kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether, it is characterised in that the preparation be by
Thermal sensitive liposome contains hollow Jenner's grain of rice by extruded film method, then contains tumor therapeutic agent and be prepared from, the phase of the liposome
Temperature is 39.0 DEG C~45.0 DEG C, and the liposome includes DPPC (DPPC).
Further, described thermal sensitive liposome preparation, it is characterised in that：Hollow Jenner's grain of rice and two palmityl lecithins
The weight ratio of fat (DPPC) is 1~4: 60, and the particle diameter of liposome is 150-250nm, and current potential is -15~-30mV.
Further, described thermal sensitive liposome preparation, it is characterised in that hollow Jenner's grain of rice particle diameter is 30-
60nm, maximum absorption wavelength is in 650-850nm.
Further, described thermal sensitive liposome preparation, it is characterised in that the tumor therapeutic agent is selected from small-molecule chemical
Medicine, biological protein medicament or gene therapy related drugs.
Further, described thermal sensitive liposome preparation, it is characterised in that the small-molecule chemical medicine is selected from purple
China fir alcohol, doxorubicin hydrochloride, mitoxantrone, 5 FU 5 fluorouracil, cis-platinum, daunorubicin, hormone medicine or traditional Chinese medicine monomer；The life
Thing protein drug is selected from Rituximab, Avastin or Herceptin；The genomic medicine is selected from containing reporter gene, resisted
The DNA that oncogene, cytokine gene can be recombinantly expressed in eukaryotic, oligonucleotide or siRNA.
Further, described thermal sensitive liposome preparation, it is characterised in that：The Liposomal formulation prescription is：
It is prepared via a method which to obtain：DPPC, DSPE-PEG2000 are weighed according to recipe quantity, is added after uniform mixing
Organic solvent dissolves, and is placed in removing organic solvent film forming on Rotary Evaporators, adds hollow Jenner's grain of rice solution water of concentration
Afterwards, 60 DEG C of mistakes, 0.2 μm of filter membrane ten several times, prepares the thermal sensitive liposome for containing hollow Jenner's grain of rice；Add recipe quantity adriamycin
Powder, dissolves at 60 DEG C and stirs incubation 4 hours, and dialysis removes the adriamycin of unentrapped after letting cool, and obtains containing adriamycin
With the thermal sensitive liposome preparation of hollow Jenner's grain of rice.
Further, the preparation method of the thermal sensitive liposome preparation of the hollow Jenner's grain of rice of described common load and tumor therapeutic agent
Comprise the following steps：
(1) 100 milliliter of ultra-pure water, adds 0.5-1mL 0.05M sodium citrate solutions and 100 μ L 0.4M cobalt chloride solutions,
Nitrogen is protected；0.5-1mL 0.1M sodium borohydride solutions are added, 15-30min is stirred, the gold chlorides of 200-500 μ L 1% is added, leads to
Air stirring 30min, obtains hollow Jenner's grain of rice；
(2) DPPC 30-60mg, DSPE-mPEG 6-15mg are weighed respectively, are dissolved in chloroform 5-10mL, 30-40 DEG C of rotation
Turn evaporating organic solvent and immobilized artificial membrane is made；
(3) by obtained hollow Jenner's grain of rice in step (1) according to recipe quantity, supernatant is removed after high speed centrifugation, is used
Ultra-pure water disperses obtained immobilized artificial membrane, 0.2 μm of filter membrane ten of 50-60 DEG C of mistake in hollow Jenner's grain of rice of precipitation, hydration step (2) again
Several times；Add tumor therapeutic agent and dissolve, 50-60 DEG C of stirring 2-6h, the tumour for dialysing or being centrifuged off unentrapped after letting cool is controlled
Agent is treated, the common thermal sensitive liposome preparation for carrying hollow Jenner's grain of rice and tumor therapeutic agent is obtained.
Further, prepared by the described hollow Jenner's grain of rice of common load of present invention offer and tumor therapeutic agent thermal sensitive liposome
Application in terms of antitumor carrier.The method of administration of the antitumor carrier is injection, oral or mucosal drug delivery, applied to tumour
Drug therapy, " three integration " synergistic treatment of hyperthermia combined radiation.
Further, the present invention provides a kind of thermal sensitive liposome for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether " three
Application in connection integration " treatment, gives after preparation, with 1-5w/cm2NIR irradiation tumor locus, irradiation time is 2-
15min, repeats 2-4 wheels；With the radiation exposure tumor locus of 2-12Gy power, irradiation time is 3-15min.
The features of the present invention
The advantage of the invention is that by thermal sensitive liposome and possessing in preferable photothermal conversion ability and radio therapy sensitization effect
Empty Jenner's grain of rice is combined, at 37 DEG C of normal body temperature, only no more than 20% insoluble drug release, and irradiates tumour portion by NIR
Position, hollow Jenner's grain of rice photothermal conversion makes lipid temperature exceed phase transition point rapidly, medicine killing is discharged quick and completely swollen
Oncocyte, and thermotherapy purpose is reached by the heat production of hollow Jenner's grain of rice.Hollow Jenner's grain of rice is inhaled to the strong photoelectricity of X-ray simultaneously
Produce effects the sensitiveness that should strengthen tumour to radiotherapy, realize the synergistic treatment strategy of " three integrations ", improve oncotherapy effect.
What the present invention was prepared contains the thermal sensitive liposome of hollow Jenner's grain of rice, can be in tumor locus by NIR irradiations
Release medicine reaches Targeting Effect, the toxic side effect of drug therapy is reduced, further through thermotherapy and the further killing energy of radiotherapy
Power, improves therapeutic effect, and this therapeutic alliance mode is one of main trend of future tumors treatment.
Brief description of the drawings
Fig. 1 is the transmission electron microscope picture of hollow Jenner's grain of rice in the present invention.
Fig. 2 is the ultraviolet full wavelength scanner figure of hollow Jenner's grain of rice in the present invention.
Fig. 3 is the heating curve of several gold nano-material photothermal conversions.
Fig. 4 is contains the transmission electron microscope picture of hollow Jenner's grain of rice thermal sensitive liposome in the present invention.
Fig. 5 is contains the grain size distribution of hollow Jenner's grain of rice thermal sensitive liposome in the present invention.
Fig. 6 is the photo-thermal heating curve for containing hollow Jenner's grain of rice and solid gold nanoparticle thermal sensitive liposome.
Fig. 7 is bent to contain release in vitro of the hollow Jenner's grain of rice thermal sensitive liposome at a temperature of 37 DEG C and 42 DEG C in the present invention
Line.
Fig. 8 contains solid gold nanoparticle thermal sensitive liposome to contain hollow Jenner's grain of rice thermal sensitive liposome in the present invention, wraps
Carry the cell survival rate of adriamycin thermal sensitive liposome and free adriamycin in MCF-7 cells.
Hollow Jenner's grain of rice thermal sensitive liposome is contained in Fig. 9 present invention, solid gold nanoparticle thermal sensitive liposome is contained, contains
The survival rate of adriamycin thermal sensitive liposome and free adriamycin the MCF-7 cells after laser treatment.
Hollow Jenner's grain of rice thermal sensitive liposome is contained in Figure 10 present invention, solid gold nanoparticle thermal sensitive liposome is contained through X
Cell survival rate after radiation exposure.
Embodiment
It is the embodiment of this patent below, but following embodiments are not intended to limit the interest field of this patent.
Embodiment 1：
The synthesis of hollow Jenner's grain of rice and sign
100 milliliters of ultra-pure waters, add 1mL 0.05M sodium citrate solutions and 100 μ L 0.4M cobalt chloride solutions, and nitrogen is protected
Shield；1mL 0.1M sodium borohydride solutions are added, 15min is stirred, the gold chlorides of 200 μ L 1% are added, blowing air stirs 30min,
15000 leave heart 15min, and ultra-pure water disperses precipitation, obtains hollow Jenner's grain of rice again；Use transmission electron microscope and ultraviolet all-wave length
Scanner is detected to product, as a result such as Fig. 1 and Fig. 2.
Embodiment 2：
The comparison of several gold nano-material photothermal conversion abilities
Solid gold nanoparticle, gold nano star and hollow Jenner's grain of rice are prepared according to pertinent literature method, passes through centrifugation
Concentration, adjustment makes its gold content identical；Take 1mL in silica dish from above-mentioned solution respectively, 808nm laser is with 3w/cm2Irradiation
10min, infrared temperature-measuring gun detects a temperature every 1min, and using physiological saline as control, as a result such as Fig. 3.
Embodiment 3：
DPPC, DSPE-PEG2000 are weighed according to recipe quantity, organic solvent dissolving is added after uniform mixing, rotation is placed in and steams
Send out and organic solvent film forming is removed on instrument, after the hollow Jenner's grain of rice solution water for adding concentration, 60 DEG C of mistakes, 0.2 μm of filter membrane more than ten
It is secondary, prepare the thermal sensitive liposome for containing hollow Jenner's grain of rice；Recipe quantity adriamycin powder is added, dissolves and stirs at 60 DEG C
It is incubated 4 hours, dialysis removes the adriamycin of unentrapped after letting cool, and obtains containing the temperature-sensitive fat of adriamycin and hollow Jenner's grain of rice
Liposome preparation.
Embodiment 4：
DPPC, MPPC are weighed according to recipe quantity, organic solvent dissolving is added after uniform mixing, is placed on Rotary Evaporators and removes
Organic solvent film forming is gone, after the hollow Jenner's grain of rice solution water for adding concentration, 50 DEG C of mistakes, 0.2 μm of filter membrane ten several times, is prepared
Contain the thermal sensitive liposome of hollow Jenner's grain of rice；Recipe quantity cis-platinum powder is added, is dissolved at 50 DEG C and stirs incubation 3 hours,
Dialysis removes the cis-platinum of unentrapped after letting cool, and obtains containing the thermal sensitive liposome preparation of cis-platinum and hollow Jenner's grain of rice.
Embodiment 5
DPPC, DSPE-PEG2000 are weighed according to recipe quantity, organic solvent dissolving is added after uniform mixing, rotation is placed in and steams
Send out and organic solvent film forming is removed on instrument, after PBS solution (0.5-2mg/mL) aquation for adding Rituximab, add in concentration
Empty Jenner's grain of rice, 50 DEG C of mistakes, 0.2 μm of filter membrane ten several times, prepares the temperature-sensitive lipid for containing Rituximab and hollow Jenner's grain of rice
Body preparation.
Embodiment 6：Contain transmission electron microscope detection and the particle size distribution measuring of hollow Jenner's grain of rice thermal sensitive liposome：Pass through
JEM transmission electron microscopes detect the form of thermal sensitive liposome, as a result such as Fig. 4；Lipid is determined by Malvern laser particle analyzer
The particle diameter distribution of body, liposome average grain diameter is 200nm, and grain size distribution is shown in Fig. 5.
Embodiment 7：The photothermal conversion ability that hollow Jenner's grain of rice is contained with solid gold nanoparticle thermal sensitive liposome is compared
The thermal sensitive liposome for containing hollow Jenner's grain of rice and solid gold nanoparticle is prepared according to above-mentioned technique, adjustment concentration makes
Its gold content is identical；Take 1mL in silica dish from above-mentioned solution respectively, 808nm laser is with 3w/cm2Irradiate 10min, infrared survey
Warm rifle detects a temperature every 1min, and using PBS (7.4) as control, as a result such as Fig. 6.
Embodiment 8：The release in vitro evaluation of the thermal sensitive liposome of hollow Jenner's grain of rice and adriamycin is carried altogether
Take the preparation 2mL for containing adriamycin in bag filter (molecular cut off=7000Da), two ends are tightened with cotton thread, are put
In 50mL iodine flask, dissolution medium (pH7.4) 20mL is respectively added, is respectively placed in 37 DEG C and 42 DEG C of thermostatic control oscillator vibrations,
Rotating speed is 100r/min, and respectively at 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 24h mends Isothermal release medium per sub-sampling 1mL
1mL, sample is detected in sepectrophotofluorometer, calculates release amount of medicine, as a result such as Fig. 7.
Embodiment 9：The thermal sensitive liposome anti tumor activity in vitro evaluation of hollow Jenner's grain of rice and tumor therapeutic agent is carried altogether
(1) single Chemotherapy
MCF-7 cells are inoculated in 96 orifice plates with 5000/hole, is incubated after 24h, preparation diluent is added into various concentrations
Enter in 96 orifice plates, while with free Doxorubicin solution as a control group.It is incubated after 48h, takes 20 μ L Methyl thiazoly tetrazolium assays
(MTT, 5mg/mL) is added in each hole, is continued to be incubated 4h, is discarded liquid in hole, adds DMSO150 μ L, and shaking 10min makes crystallization
Fully dissolving, determines the light absorption value (ODsample) of each sample under 570nm wavelength with ELIASA, while determining blank group OD
It is worth (ODcontrol), and calculates cell survival rate, as a result sees Fig. 8.
(2) chemotherapy combined heat-therapeutic action
MCF-7 cells are inoculated in 96 orifice plates with 5000/hole, is incubated after 24h, preparation diluent is added into various concentrations
Enter in 96 orifice plates, while with free Doxorubicin solution as a control group.It is incubated after 6h, with 808nm laser 2w/cm2, irradiation
5min, is handled 4 times in 2h, is continued to be incubated 42h, is taken 20 μ L Methyl thiazoly tetrazolium assays (MTT, 5mg/mL) to add in each hole, after
It is continuous to be incubated 4h, liquid in hole is discarded, DMSO150 μ L are added, shaking 10min makes crystallization fully dissolve, used under 570nm wavelength
ELIASA determines the light absorption value (ODsample) of each sample, while determining blank group OD values (ODcontrol), and calculates cell and deposits
Motility rate, is as a result shown in Fig. 9.
(3) Apoptosis
MCF-7 cells are inoculated in 96 orifice plates with 5000/hole, are incubated after 24h, the preparation of unentrapped therapeutic agent is dilute
It is interpreted into various concentrations (with Au content meters) to add in 96 orifice plates, while with PBS solution as a control group.It is incubated after 6h, with 6Gay
Radioactive ray irradiate 5min, continue to be incubated 42h, take 20 μ L Methyl thiazoly tetrazolium assays (MTT, 5mg/mL) to add in each hole, continue to incubate
4h is educated, liquid in hole is discarded, DMSO150 μ L are added, shaking 10min makes crystallization fully dissolve, enzyme mark is used under 570nm wavelength
Instrument determines the light absorption value (ODsample) of each sample, while determining blank group OD values (ODcontrol), and calculates cell survival
Rate, is as a result shown in Figure 10.
Claims (10)
1. a kind of thermal sensitive liposome preparation for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether, it is characterised in that the preparation is
Hollow Jenner's grain of rice is contained by extruded film method by thermal sensitive liposome, then contains tumor therapeutic agent and is prepared from, the liposome
Phase transition temperature is 39.0 DEG C~45.0 DEG C, and the liposome includes DPPC (DPPC).
2. thermal sensitive liposome preparation according to claim 1, it is characterised in that：Hollow Jenner's grain of rice and two palmityl ovum
The weight ratio of phosphatide (DPPC) is 1~4: 60, and the particle diameter of liposome is 150-250nm, and current potential is -15~-30mV.
3. thermal sensitive liposome preparation according to claim 1, it is characterised in that in photo-thermal therapy, NIR irradiation powers are
1-5w/cm2, irradiation time is 2-15min；Radiation power is 2-12gay in radiotherapy, and irradiation time is 3-15min.
4. thermal sensitive liposome preparation according to claim 1, it is characterised in that hollow Jenner's grain of rice particle diameter is 30-
60nm, maximum absorption wavelength is in 650-850nm.
5. thermal sensitive liposome preparation according to claim 1, it is characterised in that the tumor therapeutic agent is selected from small molecule
Learn medicine, biological protein medicament or gene therapy related drugs.
6. thermal sensitive liposome preparation according to claim 5, it is characterised in that the small-molecule chemical medicine is selected from
Taxol, doxorubicin hydrochloride, mitoxantrone, 5 FU 5 fluorouracil, cis-platinum, daunorubicin, hormone medicine or traditional Chinese medicine monomer；It is described
Biological protein medicament is selected from Rituximab, Avastin or Herceptin；The genomic medicine be selected from containing reporter gene,
The DNA that antioncogene, cytokine gene can be recombinantly expressed in eukaryotic, oligonucleotide or siRNA.
7. thermal sensitive liposome preparation according to claim 1, it is characterised in that：The Liposomal formulation prescription is：
It is prepared via a method which to obtain：DPPC, DSPE-PEG2000 are weighed according to recipe quantity, is added after uniform mixing organic
Solvent dissolves, and is placed in after removing organic solvent film forming on Rotary Evaporators, the hollow Jenner's grain of rice solution water for adding concentration, 60
DEG C 0.2 μm of filter membrane ten of mistake several times, prepares the thermal sensitive liposome for containing hollow Jenner's grain of rice；Recipe quantity adriamycin powder is added,
Dissolved at 60 DEG C and stir incubation 4 hours, dialysis removes the adriamycin of unentrapped after letting cool, obtain containing adriamycin with it is hollow
The thermal sensitive liposome preparation of Jenner's grain of rice.
8. the preparation side of the thermal sensitive liposome preparation according to claim 1 for carrying hollow Jenner's grain of rice and tumor therapeutic agent altogether
Method, it is characterised in that comprise the following steps：
(1) 100 milliliter of ultra-pure water, adds 0.5-1mL 0.05M sodium citrate solutions and 100 μ L 0.4M cobalt chloride solutions, nitrogen
Protection；0.5-1mL 0.1M sodium borohydride solutions are added, 15-30min is stirred, the gold chlorides of 200-500 μ L 1%, blowing air is added
30min is stirred, hollow Jenner's grain of rice is obtained；
(2) DPPC 30-60mg, DSPE-mPEG 6-15mg are weighed respectively, is dissolved in chloroform 5-10mL, and 30-40 DEG C of rotation is steamed
Hair removes organic solvent and immobilized artificial membrane is made；
(3) by obtained hollow Jenner's grain of rice in step (1) according to recipe quantity, supernatant is removed after high speed centrifugation, using ultrapure
Water disperses obtained immobilized artificial membrane, 0.2 μm of filter membrane more than ten of 50-60 DEG C of mistake in hollow Jenner's grain of rice of precipitation, hydration step (2) again
It is secondary；Add tumor therapeutic agent and dissolve, 50-60 DEG C of stirring 2-6h dialyses or be centrifuged off the oncotherapy of unentrapped after letting cool
Agent, obtains the common thermal sensitive liposome preparation for carrying hollow Jenner's grain of rice and tumor therapeutic agent.
9. hollow Jenner's grain of rice and the tumor therapeutic agent thermal sensitive liposome according to claim 1 of carrying altogether is preparing antitumor carry
Application in terms of body.
10. application according to claim 10, it is characterised in that the method for administration of the antitumor carrier is injection, mouth
Clothes or mucosal drug delivery, " three integrations " synergistic treatment of drug therapy, hyperthermia combined radiation applied to tumour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710273592.8A CN107049951B (en) | 2017-04-19 | 2017-04-19 | Preparation and triple integrated application of thermosensitive liposome carrying hollow gold nanoparticles and tumor therapeutic agent together |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710273592.8A CN107049951B (en) | 2017-04-19 | 2017-04-19 | Preparation and triple integrated application of thermosensitive liposome carrying hollow gold nanoparticles and tumor therapeutic agent together |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107049951A true CN107049951A (en) | 2017-08-18 |
| CN107049951B CN107049951B (en) | 2021-06-29 |
Family
ID=59604182
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710273592.8A Active CN107049951B (en) | 2017-04-19 | 2017-04-19 | Preparation and triple integrated application of thermosensitive liposome carrying hollow gold nanoparticles and tumor therapeutic agent together |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107049951B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108721790A (en) * | 2018-05-31 | 2018-11-02 | 中国工程物理研究院化工材料研究所 | A kind of cell bomb of laser initiation explosion |
| CN110090203A (en) * | 2019-04-29 | 2019-08-06 | 南京锐利施生物技术有限公司 | A kind of degradable microsphere preparation of the load Pramipexole of near-infrared response type |
| CN114288247A (en) * | 2021-12-20 | 2022-04-08 | 合肥工业大学 | Controllable assembled liposome nano motor and preparation method thereof |
| WO2023207931A1 (en) * | 2022-04-26 | 2023-11-02 | 石药集团中奇制药技术（石家庄）有限公司 | Use of mitoxantrone liposome in combination with anti-angiogenic targeted drug for treating ovarian cancer |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103284951A (en) * | 2013-04-27 | 2013-09-11 | 浙江大学 | Photosensitive liposome with encapsulated water-soluble medicament |
| CN103768600A (en) * | 2014-01-25 | 2014-05-07 | 郑州大学 | Magnetic thermosensitive liposome nano-gold comopound, preparation method and application |
| CN106389332A (en) * | 2016-11-29 | 2017-02-15 | 四川大学 | New long-circulating oxylycorine organic acid complex preparation |
-
2017
- 2017-04-19 CN CN201710273592.8A patent/CN107049951B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103284951A (en) * | 2013-04-27 | 2013-09-11 | 浙江大学 | Photosensitive liposome with encapsulated water-soluble medicament |
| CN103768600A (en) * | 2014-01-25 | 2014-05-07 | 郑州大学 | Magnetic thermosensitive liposome nano-gold comopound, preparation method and application |
| CN106389332A (en) * | 2016-11-29 | 2017-02-15 | 四川大学 | New long-circulating oxylycorine organic acid complex preparation |
Non-Patent Citations (1)
| Title |
|---|
| 陆彬主编: "《药剂学》", 31 January 2003 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108721790A (en) * | 2018-05-31 | 2018-11-02 | 中国工程物理研究院化工材料研究所 | A kind of cell bomb of laser initiation explosion |
| CN110090203A (en) * | 2019-04-29 | 2019-08-06 | 南京锐利施生物技术有限公司 | A kind of degradable microsphere preparation of the load Pramipexole of near-infrared response type |
| CN114288247A (en) * | 2021-12-20 | 2022-04-08 | 合肥工业大学 | Controllable assembled liposome nano motor and preparation method thereof |
| WO2023207931A1 (en) * | 2022-04-26 | 2023-11-02 | 石药集团中奇制药技术（石家庄）有限公司 | Use of mitoxantrone liposome in combination with anti-angiogenic targeted drug for treating ovarian cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107049951B (en) | 2021-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lin et al. | Multimodal imaging guided cancer phototherapy by versatile biomimetic theranostics with UV and γ irradiation protection | |
| Ji et al. | Ros‐mediated apoptosis and anticancer effect achieved by artesunate and auxiliary fe (ii) released from ferriferous oxide‐containing recombinant apoferritin | |
| CN107049951A (en) | It is a kind of to carry hollow Jenner's grain of rice and the thermal sensitive liposome preparation of tumor therapeutic agent and three integral applications altogether | |
| Tang et al. | Thermochromism-induced temperature self-regulation and alternating photothermal nanohelix clusters for synergistic tumor chemo/photothermal therapy | |
| Huang et al. | Enhanced tumor targeting and radiotherapy by quercetin loaded biomimetic nanoparticles | |
| Cao et al. | Recent advances in phase change material based nanoplatforms for cancer therapy | |
| CN106620696A (en) | Nano-mesoporous granular drug carrier with photothermal effect and preparation method of nano-mesoporous granular drug carrier | |
| CN106421784A (en) | Nano drug carrier having photothermal effect and preparation method and application thereof | |
| Zhang et al. | Near-infrared triggered injectable ferrimagnetic chitosan thermosensitive hydrogel for photo hyperthermia and precisely controlled drug release in tumor ablation | |
| CN108354913A (en) | A kind of application of nano drug-carrying nanosystems in preparing the drug for treating intractable thyroid cancer | |
| He et al. | Nano-drug system based on hierarchical drug release for deep localized/systematic cascade tumor therapy stimulating antitumor immune responses | |
| CN108295257A (en) | A kind of graphite alkene nanometer sheet Quito function medicine-carried system and its preparation method and application | |
| Lin et al. | Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate | |
| CN109999197A (en) | Nano-complex, preparation method and its application in the tumour that sound power mediates precisely is treated of cancer target | |
| CN108030922A (en) | Temperature sensitive gold nanometer cage and preparation method and application, carry the temperature sensitive gold nanometer cage of medicine and preparation method | |
| CN102603912A (en) | Natural pullulan nano drug carrier and method for preparing same | |
| Zhong et al. | Recent Advances of Platinum‐Based Anticancer Complexes in Combinational Multimodal Therapy | |
| Ouyang et al. | Efficient improvement in chemo/photothermal synergistic therapy against lung cancer using Bi@ Au nano-acanthospheres | |
| CN109846857A (en) | A kind of preparation method and applications of the natural supermolecule photosensitizer of activity | |
| Tian et al. | Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer | |
| CN106729733A (en) | A kind of cysteine/ferroso-ferric oxide/copper sulfide/bovine serum albumin(BSA) nano-complex particle and its preparation and application | |
| CN109224063A (en) | The nano combined carrier and its preparation and application of dual load peptides and chemotherapeutics | |
| CN112546025A (en) | Preparation method of Ce6@ CMCS-DSP-IPI549 antitumor nano-delivery system | |
| CN106606783B (en) | A kind of targeting is passed altogether to be released the drug of photosensitizer and chemotherapeutics and passs release system | |
| Zhu et al. | Gold nanorod-loaded thermosensitive liposomes facilitate the targeted release of ruthenium (II) polypyridyl complexes with anti-tumor activity |
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 |