CN113318089A - Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof - Google Patents
Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof Download PDFInfo
- Publication number
- CN113318089A CN113318089A CN202110518445.9A CN202110518445A CN113318089A CN 113318089 A CN113318089 A CN 113318089A CN 202110518445 A CN202110518445 A CN 202110518445A CN 113318089 A CN113318089 A CN 113318089A
- Authority
- CN
- China
- Prior art keywords
- sorafenib
- aza
- infrared
- preparation
- pyrrolopyrrole
- 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
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 title claims abstract description 68
- 239000005511 L01XE05 - Sorafenib Substances 0.000 title claims abstract description 68
- 229960003787 sorafenib Drugs 0.000 title claims abstract description 68
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 30
- RQGPLDBZHMVWCH-UHFFFAOYSA-N pyrrolo[3,2-b]pyrrole Chemical compound C1=NC2=CC=NC2=C1 RQGPLDBZHMVWCH-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229920001400 block copolymer Polymers 0.000 claims abstract description 17
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 10
- 150000004936 Sorafenib derivatives Chemical class 0.000 claims abstract description 5
- 239000008367 deionised water Substances 0.000 claims abstract description 5
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 5
- 239000002245 particle Substances 0.000 claims abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 239000012528 membrane Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000011248 coating agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 17
- 229940079593 drug Drugs 0.000 abstract description 12
- 238000012544 monitoring process Methods 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 2
- 238000009513 drug distribution Methods 0.000 abstract 1
- 238000005374 membrane filtration Methods 0.000 abstract 1
- 230000037353 metabolic pathway Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 24
- 230000000694 effects Effects 0.000 description 13
- 238000000502 dialysis Methods 0.000 description 12
- 238000011282 treatment Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 239000000693 micelle Substances 0.000 description 5
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 4
- 238000000799 fluorescence microscopy Methods 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 229910021642 ultra pure water Inorganic materials 0.000 description 4
- 239000012498 ultrapure water Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 229960004657 indocyanine green Drugs 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- -1 polyoxyethylene chain Polymers 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002047 solid lipid nanoparticle Substances 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Optics & Photonics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a nano particle loaded with near-infrared emission fluorescent molecules/sorafenib and a preparation method thereof. The average hydrated particle size of the obtained nanoparticles is 90-150 nm, so that the water solubility, stability and water dispersibility of the sorafenib are improved, and a fluorescence monitoring means is provided for researches on pharmacokinetics, drug distribution, drug metabolic pathways and the like. The preparation method comprises the steps of respectively preparing polyoxyethylene polyoxypropylene ether block copolymer, pyrrolopyrrole aza-fluoroboron compound and sorafenib salt into solutions, mixing, adding deionized water, fully stirring, dialyzing and performing membrane filtration to obtain the product.
Description
Technical Field
The invention relates to the field of application of medicines and nanotechnology, in particular to a nano particle loaded with near-infrared emission fluorescent molecules/sorafenib.
Background
Sorafenib is an oral multi-target molecule targeting preparation and can prolong the life of patients with late-stage cellular liver cancer. In 2007, the united states food and drug administration approved it as a first-line drug for standard therapy of advanced liver cancer. Although sorafenib has a good curative effect on clinical treatment, the toxic and side effects and drug resistance of sorafenib are not negligible, including: (1) sorafenib has poor water solubility, low bioavailability and is susceptible to diet; (2) sorafenib is very cytotoxic, and drug molecules can be distributed in the whole body, so that a series of serious side effects are caused, such as diarrhea, dysentery, weight loss, hypertension, anorexia, noise change, nausea and vomiting and the like; (3) tumor cells are extremely easy to generate strong drug resistance to sorafenib, the volume of the tumor of a patient treated by sorafenib cannot be obviously reduced, and the average life of the patient is prolonged by three months compared with that of placebo treatment. (4) After the sorafenib enters the human body, the sorafenib often enters a black box just like a black box, and the medicament cannot be monitored in real time and the treatment effect of the medicament cannot be fed back in time. Therefore, the development of a sorafenib preparation with low toxicity and capable of monitoring the curative effect of the medicament in real time is a problem to be solved urgently.
Patent CN 107349432A discloses sorafenib/si RNA-loaded mesoporous silica-lactobionic acid targeted nanoparticles, which can realize targeted drug delivery of sorafenib and reduce toxic and side effects on normal cells; patent CN 110302153A discloses a preparation method of sorafenib nano-micelle, which can improve the drug concentration of tumor parts and reduce the toxicity of drugs to normal tissues; patent CN 109091672A discloses sorafenib solid lipid nanoparticles and a preparation method and application thereof, sorafenib and indocyanine green are loaded into a phospholipid membrane nano-carrier together, so that the toxicity and solubility of the sorafenib are improved, and simultaneously the light resistance and tumor aggregation performance of the indocyanine green can be enhanced. The currently published and reported sorafenib nano preparation (such as nano micelle, liposome, polymer nano particle, inorganic nano particle and the like) improves the water solubility of sorafenib on a uniform degree, thereby improving the treatment effect of sorafenib. However, these nano preparations cannot monitor a series of processes such as absorption, distribution, metabolism, transport and excretion of the drug, physiological reactions of the body, therapeutic effects of the drug, toxic and side effects, and the like by an effective means.
The near infrared fluorescence imaging provides an effective research means for in-vivo monitoring of disease processes, in-vivo tracing of gene therapy, in-vivo activity rule of functional molecules, in-vivo efficacy evaluation of drugs and the like, and has the advantages of non-invasiveness, real-time performance, high sensitivity, strong tissue penetration capacity, low fluorescence background and the like. Especially, the organic combination of the fluorescence imaging reagent and the therapeutic drug can provide important information such as important pathology, individual difference between tumors and patients and the like, realize the tracking of the treatment effect, contribute to the formulation of treatment strategies (treatment time, drug selection, dosage and the like) by doctors, and have important significance for synergy and attenuation and realization of personalized treatment. At present, no document or patent report exists on the sorafenib nano-preparation, and the nano-particle loaded with the near-infrared emission fluorescent molecule/sorafenib is disclosed by the invention.
Disclosure of Invention
In order to solve the problems of poor water solubility, low bioavailability, no effective means for monitoring the curative effect of the medicament and the like of sorafenib, the invention provides a nanoparticle loaded with near-infrared emission fluorescent molecules/sorafenib, wherein the components of the nanoparticle are sorafenib, a near-infrared fluorescent molecule pyrrolopyrrole aza-fluoroboron compound and a medicament carrier polyoxyethylene polyoxypropylene ether block copolymer.
The invention has the beneficial effects that: the invention adopts biomedical material polyoxyethylene polyoxypropylene ether block copolymer with good biocompatibility approved by FDA as a drug carrier, and has the advantage of high biological safety. The preparation method is simple, mild in condition and easy to operate, and the prepared finished product sorafenib nano-micelle is easy to dissolve in water and has good dispersibility in water. The sorafenib and pyrrolopyrrole aza-borofluoride compound is a lipophilic compound, the amphiphilic polyoxyethylene polyoxypropylene ether block copolymer is used as a drug carrier, the sorafenib and pyrrolopyrrole aza-borofluoride compound can enter a hydrophobic core of a micelle under the action of hydrophobic force, so that the solubility of the sorafenib and the photostability of the pyrrolopyrrole aza-borofluoride compound are improved, and the pyrrolopyrrole aza-borofluoride compound has the characteristic of near-infrared fluorescence imaging and can provide exact information for the cancer treatment effect of the sorafenib through a fluorescence imaging means. The polyoxyethylene chain segment in the drug carrier is used as the hydrophilic end of the micelle, so that the nonspecific uptake of macrophages in vivo can be reduced, and the circulation time of the drug in vivo can be prolonged. The average hydrated particle size of the prepared near-infrared emission fluorescent molecule/sorafenib-loaded nanoparticle is 90-150 nm, the nanoparticle has good stability, and the particle size of the nanoparticle is not obviously changed when the nanoparticle is stored for one week at 4 ℃ and 37 ℃. The invention improves the water solubility of the sorafenib and provides a near-infrared fluorescence monitoring means for researching the distribution, metabolism, curative effect and the like of the sorafenib in the body.
The chemical structural formula of the sorafenib is as follows:
the chemical structural formula of the pyrrolopyrrole aza-fluoroboron compound is as follows:
the chemical structural formula of the polyoxyethylene polyoxypropylene ether block copolymer is as follows:
HO(CH2CH2O)a(CH2CH2CH2O)b(CH2CH2)cH(a，c＝10-110，b＝20-60)
in addition, the invention provides a preparation method of the nanoparticle loaded with the near-infrared emission fluorescent molecule/sorafenib, sorafenib salt, a pyrrolopyrrole aza-fluoroboron compound, a polyoxyethylene polyoxypropylene ether block copolymer, tetrahydrofuran and deionized water are used as preparation raw materials, and a finished product is prepared by adopting five steps in total, wherein the preparation method comprises the following steps of (1) dissolving the polyoxyethylene polyoxypropylene ether block copolymer in the tetrahydrofuran, and uniformly stirring to form a clear and transparent solution A; (2) dissolving sorafenib salt in tetrahydrofuran, and uniformly mixing to form a solution B; (3) dissolving a pyrrolopyrrole aza-fluoroboron compound in tetrahydrofuran, and uniformly mixing to form a solution C; (4) uniformly mixing the solution A, B and C, and injecting the mixture into deionized water by using an injector under the ultrasonic condition; (5) and (3) dialyzing to remove tetrahydrofuran, and filtering by using a 0.22 mu m filter membrane to remove free sorafenib and pyrrolopyrrole aza-fluoroboron compounds to obtain a finished product of the nano particle loaded with the near-infrared emission fluorescent molecule/sorafenib.
Drawings
FIG. 1 is a dynamic light scattering diagram of nano-particles loaded with near-infrared emission fluorescent molecules/sorafenib
FIG. 2 is an ultraviolet absorption diagram of nanoparticles loaded with near-infrared emission fluorescent molecules/sorafenib
FIG. 3 is a fluorescence emission diagram of nanoparticles loaded with near-infrared emission fluorescent molecules/sorafenib
Detailed Description
The present invention is described below by way of specific examples, which are provided only for the purpose of further illustrating the present invention and do not represent the scope of the present invention, and other insubstantial modifications and adaptations made in accordance with the present invention would still fall within the scope of the present invention.
Example 1
Weighing 10mg of polyoxyethylene polyoxypropylene ether block copolymer with the molecular weight of 5000, 1mg of sorafenib toluenesulfonic acid and 1mg of pyrrolo-pyrrole aza-fluorine boron compound, respectively adding the mixture into 3 sample bottles, respectively adding 2mL of tetrahydrofuran, and fully stirring and dissolving to obtain a solution A, a solution B and a solution C. Under the condition of continuous stirring, evenly mixing the solution A, B, C, dropwise adding 20mL of ultrapure water into the mixed solution under the ultrasonic condition, transferring the obtained solution into a dialysis bag with the molecular weight cutoff (Mw) ═ 3500 Da) for dialysis, changing water every 3 hours, dialyzing for 48 hours, and filtering through a filter membrane of 0.22 mu m after the dialysis is finished so as to remove the unencapsulated sorafenib and pyrrolopyrrole aza-fluoroboron compounds, thus obtaining the nano particles loaded with the near-infrared emission fluorescent molecules/sorafenib. Dynamic light scattering, ultraviolet and fluorescence emission analysis are carried out on the product, and corresponding spectrograms are respectively shown in figure 1, figure 2 and figure 3.
Example 2
100mg of polyoxyethylene polyoxypropylene ether block copolymer with the molecular weight of 9000, 10mg of sorafenib toluenesulfonic acid and 10mg of pyrrolopyrrole aza-fluoroboron compound are weighed and respectively added into 3 sample bottles, 5mL of tetrahydrofuran is respectively added, and the mixture is fully stirred and dissolved to obtain a solution A, a solution B and a solution C. Under the condition of continuous stirring, evenly mixing the solution A, B, C, dropwise adding 50mL of ultrapure water into the mixed solution under the ultrasonic condition, transferring the obtained solution into a dialysis bag with the molecular weight cutoff (Mw) ═ 3500 Da) for dialysis, changing water every 3 hours, dialyzing for 48 hours, and filtering through a filter membrane of 0.22 mu m after the dialysis is finished so as to remove the unencapsulated sorafenib and pyrrolopyrrole aza-fluoroboron compounds, thus obtaining the nano particles loaded with the near-infrared emission fluorescent molecules/sorafenib.
Example 3
Weighing 1000mg of polyoxyethylene polyoxypropylene ether block copolymer with the molecular weight of 4000, 10mg of sorafenib toluenesulfonic acid and 10mg of pyrrolopyrrole aza-fluoroboron compound, respectively adding the weighed materials into 3 sample bottles, respectively adding 10mL of tetrahydrofuran, and fully stirring and dissolving to obtain a solution A, a solution B and a solution C. Under the condition of continuous stirring, evenly mixing the solution A, B, C, dropwise adding 200mL of ultrapure water into the mixed solution under the ultrasonic condition, transferring the obtained solution into a dialysis bag with the molecular weight cutoff (Mw) ═ 3500 Da) for dialysis, changing water every 3 hours, dialyzing for 48 hours, and filtering through a filter membrane of 0.22 mu m after the dialysis is finished so as to remove the unencapsulated sorafenib and pyrrolopyrrole aza-fluoroboron compounds, thus obtaining the nano particles loaded with the near-infrared emission fluorescent molecules/sorafenib.
Example 4
Weighing 5mg of polyoxyethylene polyoxypropylene ether block copolymer with molecular weight of 6000, 5mg of sorafenib toluenesulfonic acid and 5mg of pyrrolo-pyrrole aza-fluorine boron compound, respectively adding the mixture into 3 sample bottles, respectively adding 3mL of tetrahydrofuran, and fully stirring and dissolving to obtain a solution A, a solution B and a solution C. Under the condition of continuous stirring, evenly mixing the solution A, B, C, dropwise adding 30mL of ultrapure water into the mixed solution under the ultrasonic condition, transferring the obtained solution into a dialysis bag with the molecular weight cutoff (Mw) ═ 3500 Da) for dialysis, changing water every 3 hours, dialyzing for 48 hours, and filtering through a filter membrane of 0.22 mu m after the dialysis is finished so as to remove the unencapsulated sorafenib and pyrrolopyrrole aza-fluoroboron compounds, thus obtaining the nano particles loaded with the near-infrared emission fluorescent molecules/sorafenib.
Claims (7)
1. A near-infrared emission fluorescent molecule/sorafenib-loaded nanoparticle comprises a polymer wrapping agent, a near-infrared emission fluorescent molecule and sorafenib. The average hydrated particle size of the nanoparticles is 90-150 nm, the polymer coating agent is a polyoxyethylene polyoxypropylene ether block copolymer, and the near-infrared emission fluorescent molecules are pyrrole and pyrrole aza-fluorine boron compounds.
2. The near-infrared-emitting fluorescent molecule/sorafenib-loaded nanoparticle according to claim 1, wherein the structural formula of the pyrrolopyrrole aza-borofluoride compound is as follows:
3. the preparation method of the near-infrared-emission-fluorescent-molecule/sorafenib-loaded nanoparticle according to claim 1, wherein sorafenib salt, a pyrrolopyrrole aza-fluoroboron compound, a polyoxyethylene polyoxypropylene ether block copolymer, tetrahydrofuran and deionized water are used as preparation raw materials, and a finished product is prepared by adopting five steps in total, wherein the steps comprise (1) dissolving the polyoxyethylene polyoxypropylene ether block copolymer in tetrahydrofuran, and uniformly stirring to form a clear and transparent solution A; (2) dissolving sorafenib salt in tetrahydrofuran, and uniformly mixing to form a solution B; (3) dissolving a pyrrolopyrrole aza-fluoroboron compound in tetrahydrofuran, and uniformly mixing to form a solution C; (4) uniformly mixing the solution A, B and C, and injecting the mixture into deionized water by using an injector under the ultrasonic condition; (5) and (3) dialyzing to remove tetrahydrofuran, and filtering by using a filter membrane to remove free sorafenib and pyrrolopyrrole aza-fluoroboron compounds to obtain a finished product of the nano-particle loaded with the near-infrared emission fluorescent molecule/sorafenib.
4. The preparation method of the near-infrared-emission-fluorescent-molecule/sorafenib-loaded nanoparticle according to claim 3, wherein the mass ratio of the pyrrolopyrrole aza-fluoroboron compound to the polyoxyethylene polyoxypropylene block copolymer is 1-100: 1-1000.
5. The preparation method of the near-infrared-emission-fluorescent-molecule/sorafenib-loaded nanoparticle according to claim 3, wherein the mass ratio of sorafenib to polyoxyethylene polyoxypropylene ether block copolymer is 1-100: 1-100.
6. The preparation method of the near-infrared-emitting fluorescent molecule/sorafenib-loaded nanoparticle according to claim 3, wherein the mass ratio of the pyrrolopyrrole aza-fluoroboron compound to the sorafenib is 1-10: 1-10.
7. The method for preparing the near-infrared-emitting fluorescent molecule/sorafenib-loaded nanoparticle as claimed in claim 3, wherein the molecular weight of the polyoxyethylene polyoxypropylene block copolymer is 1000-9000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110518445.9A CN113318089A (en) | 2021-05-12 | 2021-05-12 | Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110518445.9A CN113318089A (en) | 2021-05-12 | 2021-05-12 | Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113318089A true CN113318089A (en) | 2021-08-31 |
Family
ID=77415362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110518445.9A Pending CN113318089A (en) | 2021-05-12 | 2021-05-12 | Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113318089A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200820991A (en) * | 2006-07-10 | 2008-05-16 | Elan Pharma Int Ltd | Nanoparticulate sorafenib formulations |
| CN103301072A (en) * | 2013-06-04 | 2013-09-18 | 上海中医药大学附属普陀医院 | Preparation method of sorafenib nanoparticles |
| CN106166141A (en) * | 2016-09-11 | 2016-11-30 | 复旦大学 | A kind of Multifunctional composite nanometer medicine for tumor imaging and treatment and preparation method thereof |
| CN109970774A (en) * | 2019-04-19 | 2019-07-05 | 华南理工大学 | It is a kind of it is highly sensitive, can open hole detection organic primary amine fluorescent chemicals PPAB and its application |
| CN110218300A (en) * | 2019-06-25 | 2019-09-10 | 苏州大学 | Alkanone containing pyrrolopyrrole and the fluorescence conjugated macromolecule of fluorenes construction unit, preparation method and application |
| CN112175956A (en) * | 2020-09-15 | 2021-01-05 | 上海健康医学院 | DNA aptamer modified water-soluble aza-BODIPY fluorescent molecular probe and preparation method and application thereof |
-
2021
- 2021-05-12 CN CN202110518445.9A patent/CN113318089A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200820991A (en) * | 2006-07-10 | 2008-05-16 | Elan Pharma Int Ltd | Nanoparticulate sorafenib formulations |
| CN103301072A (en) * | 2013-06-04 | 2013-09-18 | 上海中医药大学附属普陀医院 | Preparation method of sorafenib nanoparticles |
| CN106166141A (en) * | 2016-09-11 | 2016-11-30 | 复旦大学 | A kind of Multifunctional composite nanometer medicine for tumor imaging and treatment and preparation method thereof |
| CN109970774A (en) * | 2019-04-19 | 2019-07-05 | 华南理工大学 | It is a kind of it is highly sensitive, can open hole detection organic primary amine fluorescent chemicals PPAB and its application |
| CN110218300A (en) * | 2019-06-25 | 2019-09-10 | 苏州大学 | Alkanone containing pyrrolopyrrole and the fluorescence conjugated macromolecule of fluorenes construction unit, preparation method and application |
| CN112175956A (en) * | 2020-09-15 | 2021-01-05 | 上海健康医学院 | DNA aptamer modified water-soluble aza-BODIPY fluorescent molecular probe and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 李兰清: "新型氟硼二吡咯类反应型荧光探针的设计、合成及应用", 《中国优秀博硕士学位论文全文数据库(博士)工程科技Ⅰ辑》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Renal-clearable ultrasmall covalent organic framework nanodots as photodynamic agents for effective cancer therapy | |
| US11331387B2 (en) | Self-assembled drug-loading system and preparation method therefor | |
| Sahu et al. | Prussian blue/serum albumin/indocyanine green as a multifunctional nanotheranostic agent for bimodal imaging guided laser mediated combinatorial phototherapy | |
| Pan et al. | In-situ drug generation and controllable loading: rational design of copper-based nanosystems for chemo-photothermal cancer therapy | |
| US10874609B2 (en) | ß-cyclodextrin-based star-shaped polymer, a preparation method therefor and an integrated unimolecular micelle system for diagnosis and treatment thereof | |
| Chen et al. | Dual activated NIR-II fluorescence and photoacoustic imaging-guided cancer chemo-radiotherapy using hybrid plasmonic-fluorescent assemblies | |
| CN111617246B (en) | Self-assembled nanoparticles of pure photosensitizer and preparation and application thereof | |
| CN108409756B (en) | Camptothecin-based heterodimer multifunctional prodrug and preparation method and application thereof | |
| WO2012040513A1 (en) | Compositions and methods for the delivery of beta lapachone | |
| CN105030795A (en) | Nanometer drug-loading system as well as preparation method and application thereof | |
| CN112999153B (en) | Nano micelle carrying chemotherapeutic drug/photosensitizer and preparation method and application thereof | |
| CN104013968B (en) | A kind of modified with folic acid cholesterol hydrophobically modified sodium alginate self-assembled nanometer grain and its preparation method and application | |
| CN113952463B (en) | Nanometer diagnosis and treatment agent and preparation method and application thereof | |
| CN111012918A (en) | Cholesterol biguanide conjugate with anti-tumor and carrier effects and application of salt thereof in microparticle administration preparation | |
| CN105126102A (en) | Hypocrellin B nanoparticle and preparation method thereof | |
| Shahabi et al. | Doxorubicin loaded liposomal nanoparticles containing quantum dot for treatment of breast cancer | |
| EP1672025B1 (en) | Finely particulate composite containing carbon compound encapsulated therein | |
| CN113318089A (en) | Nano particle loaded with near-infrared emission fluorescent molecule/sorafenib and preparation method thereof | |
| JP2013540785A (en) | Liposomal drug compositions containing polymeric guanidine derivatives | |
| CN111671917B (en) | Lycorine nanoparticle, and preparation method and application thereof | |
| CN110354099B (en) | Proton-triggered nano-drug system with hydrophilic-hydrophobic-size double conversion characteristics and preparation method and application thereof | |
| CN103919738B (en) | A kind of methotrexate prodrug and micellar preparation thereof and preparation method | |
| CN107115297B (en) | Double-drug-loaded hybrid prodrug nano composition and preparation method and application thereof | |
| CN114425085B (en) | 7-Ethyl-10-hydroxycamptothecin and curcumin coordination polymer nano-drug and preparation method thereof | |
| CN115475254B (en) | Self-sensitization type nano assembly for enhancing photodynamic therapy and preparation method and application 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 |