CN108653242A - A kind of targeted nano pharmaceutical carrier and its preparation method and application - Google Patents
A kind of targeted nano pharmaceutical carrier and its preparation method and application Download PDFInfo
- Publication number
- CN108653242A CN108653242A CN201810716206.2A CN201810716206A CN108653242A CN 108653242 A CN108653242 A CN 108653242A CN 201810716206 A CN201810716206 A CN 201810716206A CN 108653242 A CN108653242 A CN 108653242A
- Authority
- CN
- China
- Prior art keywords
- polypeptide probe
- pharmaceutical carrier
- targeted nano
- peg
- pamam
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K9/5169—Proteins, e.g. albumin, gelatin
-
- 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention provides a kind of targeted nano pharmaceutical carriers and its preparation method and application.The targeted nano pharmaceutical carrier includes：Daiamid type dendritic macromole, polyethylene glycol and polypeptide probe；Some or all of daiamid type dendritic macromole periphery amino connects a peg molecule, and the other end of the polyethylene glycol connects the polypeptide probe；The polypeptide probe can express lung carcinoma cell with EGFR high or cancerous lung tissue targeting combines.The targeted drug nano-carrier of the present invention is apparent to the targeting of tumor markers EGFR albumen, selectivity is strong, there is high drug encapsulation efficiency simultaneously, and almost without toxicity, the safety for greatly improving pharmaceutical carrier, the diagnosing and treating for lung cancer and other EGFR positive tumors provide new selection.
Description
Technical field
The present invention relates to Nano medication technical fields, more particularly to a kind of targeted nano pharmaceutical carrier and preparation method thereof
And application.
Background technology
Lung cancer is current morbidity and the highest cancer of lethality, although the early diagnosis and treatment of lung cancer recent years are
It has made some progress, but still there is also many open questions.The antitumor drug clinically applied at present is main
It is cell toxicant based chemotherapy drug, such drug selectivity is poor, and toxic side effect is big, easily causes adverse reaction.And the albumen such as antibody
Although class drug specificity is high, toxic side effect is small, due to its molecular mass it is big, it is complicated, easily cause immune response and
Drug resistance etc. is generated, and its preparation process complexity is so that price is more expensive, it is difficult to which patient bears by Common tumors.
How to treat lung cancer and has become people's problem in the urgent need to address.
Invention content
A kind of targeted nano pharmaceutical carrier of present invention offer and its preparation method and application, to solve to treat in the prior art
Toxic side effect is big during lung cancer, easily cause immune response and generates drug resistance or the more expensive problem of price.
To solve the above-mentioned problems, the invention discloses a kind of targeted nano pharmaceutical carriers, including：Polyamidoamine tree
Dendritic macromolecules, polyethylene glycol and polypeptide probe；Some or all of polyamidoamine dendritic macromole periphery amino
A peg molecule is connected, the other end of the polyethylene glycol connects the polypeptide probe；The polypeptide probe can be with
EGFR high expresses lung carcinoma cell or cancerous lung tissue targeting combines.
Preferably, the molar ratio of the polypeptide probe and the polyamidoamine dendritic macromole is 1:4, it is described poly-
The molar ratio of ethylene glycol and the polyamidoamine dendritic macromole is 1:30；
Preferably, the polypeptide probe includes：Tyrosine, glutamic acid, arginine, valine, phenylalanine, phenylalanine
Unit；
Preferably, putting in order for each propylhomoserin is followed successively by tyrosine, glutamic acid, arginine, figured silk fabrics ammonia in the polypeptide probe
Acid, phenylalanine, phenylalanine unit.
Preferably, the other end of the polyethylene glycol is keyed with the polypeptide probe chemistry.
Preferably, the polyamidoamine dendritic macromole is 3-6 polyamide-amine type dendritic macromoles.
The embodiment of the invention also discloses a kind of preparation methods, are applied to targeted nano drug described in any one of the above embodiments and carry
Body, including：Synthesize PAMAM-PEG；Wherein, PAMAM is polyamidoamine dendritic macromole, and PEG is polyethylene glycol；Synthesis
Polypeptide probe；The PAMAM-PEG is activated using maleic amide, and is matched at room temperature by the first setting with the polypeptide probe
Reaction, to obtain the targeted nano pharmaceutical carrier.
Preferably, the step of synthesis PAMAM-PEG, including：In the in the mixed solvent of methanol and dimethyl sulfoxide (DMSO), institute
It states PAMAM to react at room temperature by the second setting proportioning with the PEG activated through n-hydroxysuccinimide, purify, with
To the PAMAM-PEG.
Preferably, the step of synthesis polypeptide probe, including：1) resin is soaked in molten in dimethyl formamide solution
The dimethyl formamide solution is discharged after swollen several minutes；2) resin after swelling is positioned over hexahydropyridine accounting
Several minutes are reacted in 20% dimethyl formamide solution, to remove the blocking group of amino acid, expose free amino；3)
The resin after step 2) reaction is alternately cleaned using dichloromethane solution and dimethyl formamide solution respectively several times；4)
Will be disengaged from the amino acid and benzotriazole-N, N, N of blocking group ', N '-tetramethylureas hexafluorophosphate (HBTU) equimolar ratio
Mixing, and activating reagent is added in mixed solution and reacts at room temperature several points through the resin of the step 3) after over cleaning
Clock；5) using dichloromethane solution and dimethyl formamide solution, alternately the resin of the cleaning after step 4) reaction is each several
It is secondary；6) above-mentioned steps 2 are repeated)~step 5), until obtaining the polypeptide probe.
Present invention implementation also discloses targeted nano pharmaceutical carrier or described in any one of the above embodiments described in any one of the above embodiments
Application of the preparation method in preparing treatment lung-cancer medicament radiation targeting marker.
Compared with prior art, the present invention includes following advantages：
An embodiment of the present invention provides a kind of targeted nano pharmaceutical carrier and its preparation method and application, targeted nano drugs
Carrier includes polyamidoamine dendritic macromole, polyethylene glycol and polypeptide probe, outside polyamidoamine dendritic macromole
Some or all of enclose NH2Base respectively connects a peg molecule, the other end connecting peptides probe of part polyethylene glycol,
The molar ratio of polypeptide probe and polyamidoamine dendritic macromole is 1:4, polyethylene glycol and polyamidoamine dendroid are big
The molar ratio of molecule is 1:30, polypeptide probe is can to target the more of combination with EGFR high expression lung carcinoma cells or cancerous lung tissue
Peptide.The targeted nano pharmaceutical carrier of the embodiment of the present invention has the function of targeting EGFR height expression lung carcinoma cell or cancerous lung tissue,
The content in pharmaceutical carrier such as nano material, liposome EGFR high expression lung carcinoma cells can be increased as target head, then added
Novel more effective targeted anticancer medicine is made in chemically acceptable auxiliary material or adjuvant.And the targeting of the embodiment of the present invention is received
Rice pharmaceutical carrier may be used chemically synthesized method and be prepared, and purity is high, and molecular weight is small, high specificity, and original shape is immunized in nothing,
Securely and reliably.The targeted drug nano-carrier of the present invention is apparent to the targeting of tumor markers EGFR albumen, and selectivity is strong,
There is high drug encapsulation efficiency simultaneously, and almost without toxicity, greatly improve the safety of pharmaceutical carrier, be lung cancer
New selection is provided with the diagnosing and treating of other EGFR positive tumors.
Description of the drawings
Fig. 1 shows a kind of structural schematic diagram of targeted drug nano-carrier provided in an embodiment of the present invention；
Fig. 2 shows a kind of step flow charts of preparation method provided in an embodiment of the present invention；
Fig. 3 shows a kind of test result schematic diagram provided in an embodiment of the present invention；
Fig. 4 shows a kind of test result schematic diagram provided in an embodiment of the present invention；
Fig. 5 shows the inspection of a kind of targeted drug nano-carrier and EGFR protein binding capacities provided in an embodiment of the present invention
Survey result schematic diagram.
Specific implementation mode
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, below in conjunction with the accompanying drawings and specific real
Applying mode, the present invention is described in further detail.
Embodiment one
Referring to Fig.1, a kind of structural schematic diagram of targeted drug nano-carrier provided in an embodiment of the present invention, the target are shown
May include to medicament nano carrier：Polyamidoamine dendritic macromole 3 (PAMAM), polyethylene glycol 2 (PEG) and polypeptide are visited
Needle 1, wherein some or all of peripheries PAMAM amino respectively connects a PEG molecule, the other end connecting peptides of part PEG
Probe.
The molar ratio of polypeptide probe 1 and PAMAM3 is 1 in the targeted drug nano-carrier:4, PEG2 and PAMAM3's rubs
You are than being 1:30.
Polypeptide probe 1 is the polypeptide that lung carcinoma cell or cancerous lung tissue targeting combination can be expressed with EGFR high, passes through polypeptide
Probe 1 and EGFR high expression lung carcinoma cell or cancerous lung tissue targeting combine, so as to using the targeted drug nano-carrier as
Target head increases the content in pharmaceutical carrier such as nano material, liposome EGFR high expression lung carcinoma cells, then adds and chemically may be used
Novel more effective targeted anticancer medicine is made in the auxiliary material or adjuvant of receiving.
In a kind of preferred embodiment of the embodiment of the present invention, polypeptide probe 1 may include tyrosine, glutamic acid, smart ammonia
Acid, valine, phenylalanine, phenylalanine unit, and putting in order for above-mentioned each propylhomoserin is followed successively by tyrosine, glutamic acid, essence
Propylhomoserin, valine, phenylalanine, phenylalanine unit put in order by the way that each propylhomoserin of setting is for example above-mentioned, so as to realize
1 targeting EGFR albumen of polypeptide probe, so as to play the targeting of lung carcinoma cell or cancerous lung tissue.
In a kind of preferred embodiment of the embodiment of the present invention, targeted drug nano-carrier can also include detection agent, inspection
It may include any one in excipient, diluent, carrier, flavoring agent, adhesive and filler to survey agent, or arbitrary
A variety of combinations, the embodiment of the present invention do not limit this.
Excipient, diluent, carrier, flavoring agent, adhesive and filler can be as auxiliary materials pharmaceutically, with targeting medicine
Object nano-carrier collectively constitutes novel more effective targeted anticancer medicine.
In another preferred embodiment of the embodiment of the present invention, the other end of PEG2 can be with the chemistry of polypeptide probe 1
Key connection, PAMAM3 can be 3-6 for PAMAM, preferably the 4th generation PAMAM.
Targeted nano pharmaceutical carrier provided in an embodiment of the present invention has targeting EGFR height expression lung carcinoma cell or lung cancer group
The effect knitted can increase containing in pharmaceutical carrier such as nano material, liposome EGFR high expression lung carcinoma cells as target head
Amount, then add chemically acceptable auxiliary material or novel more effective targeted anticancer medicine is made in adjuvant, to tumor markers
The targeting of EGFR albumen is apparent, and selectivity is strong, while having high drug encapsulation efficiency, and almost without toxicity, pole
The big safety for improving pharmaceutical carrier, the diagnosing and treating for lung cancer and other EGFR positive tumors provide new choosing
It selects.
Embodiment two
With reference to Fig. 2, a kind of step flow chart of preparation method provided in an embodiment of the present invention is shown, which can
Applied to the targeted drug nano-carrier described in any one of above-described embodiment one, can specifically include following steps：
Step 201：Synthesize PAMAM-PEG；Wherein, PAMAM is polyamidoamine dendritic macromole, and PEG is poly- second two
Alcohol.
In embodiments of the present invention, divergent method is used with forth generation polyamidoamine (G4PAMAM) dendritic macromole
It is synthesized with methacrylate by repeating michael reaction addition amino, is carried out secondly by 1H-NMR spectroscopic methodologies after dialysis
The Structural Identification of PAMAMG4.
In methanol (MeOH) and dimethyl sulfoxide (DMSO) (DMSO) (1:1) in solvent mixture, PAMAM dendritics
Peripheral amino group and the settings of PEG second proportioning of n-hydroxysuccinimide (NHS) activation synthesize for 15 minutes in room temperature reaction
PAMAM-PEG.Sephadex G-50 column purifications are used in combination to remove unreacted PEG.
It is to be appreciated that the second setting proportioning can be 1:64, synthesis PAMAM-PEG, the present invention need to be only reacted according to the ratio
Embodiment is not limited the occurrence of the second setting proportioning.
And then execute step 202.
Step 202：Synthesis polypeptide probe.
In inventive embodiments, it is synthesized by the following polypeptide probe：
1) resin is soaked in dimethylformamide (DMF) solution and is fully swollen several minutes (embodiment of the present invention is excellent
Select 15 minutes) DMF solution is discharged afterwards；
2) resin after swelling is positioned in the DMF solution of hexahydropyridine accounting 20% and is reacted 10 minutes, to remove ammonia
The blocking group of base acid, exposes free amino；
3) dichloromethane (DCM) solution and DMF solution is used alternately to clean the resin after step 2) reaction respectively several times
(embodiment of the present invention preferably 3 times)；
4) amino acid and benzotriazole-N, N, N of blocking group be will be disengaged from ', N '-tetramethylurea hexafluorophosphates
(HBTU) equimolar is than mixing, and activating reagent and the resin room through step 3) after over cleaning are added in mixed solution
Temperature reacts several minutes (embodiment of the present invention preferably 50 minutes)；
5) using DCM solution and DMF amine aqueous solutions, alternately respectively (present invention is real several times for resin of the cleaning after step 4) reaction
Apply example preferably 3 times)；
6) above-mentioned steps 2 are repeated)-step 5), until synthesis polypeptide probe.
After to be synthesized, side chain protecting group is removed, and is used in combination 95% trifluoroacetic acid, 2.5% ultra-pure water, and 2.5% 3
Polypeptide is cleaved from resin spare by isopropyl base silane, and executes step 203.
Step 203：The PAMAM-PEG is activated using maleic amide, and is matched by the first setting with the polypeptide probe
It reacts at room temperature, to obtain the targeted nano pharmaceutical carrier.
In order to synthesize targeted drug nano-carrier, PAMAM-PEG, and and polypeptide probe are activated by maleic amide (Mal)
Lower reaction 30 hours is continuously stirred at room temperature by setting the first setting proportioning, and reaction mixture is dialysed and is lyophilized, target is obtained
It is white solid to medicament nano carrier dendritic.
It is to be appreciated that the first setting proportioning can be 1:16, synthesis targeted drug nano-carrier need to be only reacted according to the ratio
, the embodiment of the present invention for first setting proportioning occurrence be not limited.
The test process of targeted drug nano-carrier is as follows：
With reference to Fig. 3 and 4, a kind of test result schematic diagram provided in an embodiment of the present invention is shown, by controlling environment pH
The drug release ability for adjusting the nano-carrier with polypeptide probe, is as follows：
1) it uses SEM and dynamic light scattering to characterize respectively the PAMAM for having modified polypeptide probe, ensures its dimensional structure；
2) nano-carrier for having contained broad-spectrum medicinal DOX is immersed respectively in the buffer solution that pH value is 5.5 and pH value is 7.4
24h；
3) burst size of DOX, and statistic curve are measured, the drug release ability under two kinds of environment is compared.
Test result can be as shown in Figure 3, Figure 4, and in acid condition, targeted drug nanometer carries targeted drug nano-carrier
The DOX rates of release contained on body are obviously that 7.4 faster, pH value may be positively charged DOX molecules in PAMAM branches than pH value
In acidic environment, DOX is accelerated to improve drug effect from the release of hydrophobic dendritic macromole by protonating to repel.
With reference to Fig. 5, a kind of targeted drug nano-carrier provided in an embodiment of the present invention and EGFR protein binding energy are shown
The testing result schematic diagram of power carries the targeted drug nanometer of polypeptide probe using surface plasma resonance image-forming technical testing
Binding ability is as follows between carrier and EGFR albumen：
A) nano-carrier is dissolved into ddH2O, a concentration of 1-1000 μM；
B) by sample spot on a 3D chip surface, each sample repeats 3 points and uses 10X after 4 DEG C are incubated 12 hours
PBS, 1X PBS, ultra-pure water cleaning.Then chip 1M Monoethanolaminium chlorides are closed 30 minutes, then cleans 5 with ultra-pure water
It is secondary, finally dried up with clean nitrogen；
C) chip is mounted on SPRi instruments, measures the angles SPRi and is adjusted to best optical position, selected in detection zone
It is 2 μ L/s to take coherent detection point, including sample spot and blank spot, setting experimental flow rate；
D) select PBS be passed through after flow cell to baseline stability for buffer solution pass sequentially through a concentration of 55.6nM, 22.8nM,
The EGFR albumen of 11.4nM, 5.70nM and 2.85nM are detected, and binding time is 300 seconds, and Dissociation time is 300 seconds, each
Phosphoric acid is passed through between concentration to live again.
Testing result as shown in figure 5, targeted drug nano-carrier SPRi signals with Human epidermal growth factor receptor albumen concentration increase
It gradually increases, equilibrium dissociation constant KDIt is 7.48 × 10-10Mol/L illustrates the targeted drug nano-carrier of the embodiment of the present invention
It is strong binding ability to EGFR albumen, can be applied for relevant research as the pharmaceutical carrier of targeting EGFR tumour.
Preparation method provided in an embodiment of the present invention, targeted nano pharmaceutical carrier may be used chemically synthesized method and prepare
It obtains, purity is high, and molecular weight is small, high specificity, without original shape is immunized, securely and reliably.
For each method embodiment above-mentioned, for simple description, therefore it is all expressed as a series of combination of actions, but
Be those skilled in the art should understand that, the present invention is not limited by the described action sequence because according to the present invention, certain
A little steps can be performed in other orders or simultaneously.Secondly, it those skilled in the art should also know that, is retouched in specification
The embodiment stated belongs to preferred embodiment, and involved action and module are not necessarily essential to the invention.
Each embodiment in this specification is described in a progressive manner, the highlights of each of the examples are with
The difference of other embodiment, the same or similar parts between the embodiments can be referred to each other.
Finally, it is to be noted that, herein, relational terms such as first and second and the like be used merely to by
One entity or operation are distinguished with another entity or operation, without necessarily requiring or implying these entities or operation
Between there are any actual relationship or orders.Moreover, the terms "include", "comprise" or its any other variant meaning
Covering non-exclusive inclusion, so that process, method, commodity or equipment including a series of elements include not only that
A little elements, but also include other elements that are not explicitly listed, or further include for this process, method, commodity or
The intrinsic element of equipment.In the absence of more restrictions, the element limited by sentence "including a ...", is not arranged
Except there is also other identical elements in process, method, commodity or the equipment including the element.
A kind of targeted nano pharmaceutical carrier provided by the present invention, a kind of preparation method and a kind of targeting are received above
Rice pharmaceutical carrier application, is described in detail, specific case used herein to the principle of the present invention and embodiment into
Elaboration is gone, the explanation of above example is only intended to facilitate the understanding of the method and its core concept of the invention；Meanwhile for this
The those skilled in the art in field, according to the thought of the present invention, there will be changes in the specific implementation manner and application range,
In conclusion the content of the present specification should not be construed as limiting the invention.
Claims (10)
1. a kind of targeted nano pharmaceutical carrier, which is characterized in that including polyamidoamine dendritic macromole, polyethylene glycol and
Polypeptide probe；
Some or all of polyamidoamine dendritic macromole periphery amino connects a peg molecule, described
The other end of polyethylene glycol connects the polypeptide probe；
The polypeptide probe can express lung carcinoma cell with EGFR high or cancerous lung tissue targeting combines.
2. targeted nano pharmaceutical carrier according to claim 1, which is characterized in that the polypeptide probe and the polyamides
The molar ratio of amine-amine type dendritic macromole is 1:4, the polyethylene glycol and the polyamidoamine dendritic macromole
Molar ratio is 1:30.
3. targeted nano pharmaceutical carrier according to claim 1, which is characterized in that the polypeptide probe includes：Tyrosine,
Glutamic acid, arginine, valine, phenylalanine, phenylalanine unit.
4. targeted nano pharmaceutical carrier according to claim 3, which is characterized in that the row of each propylhomoserin in the polypeptide probe
Row sequence is followed successively by tyrosine, glutamic acid, arginine, valine, phenylalanine, phenylalanine unit.
5. targeted nano pharmaceutical carrier according to claim 1, which is characterized in that the other end of the polyethylene glycol and institute
State polypeptide probe chemistry key connection.
6. targeted nano pharmaceutical carrier according to claim 1, which is characterized in that the polyamidoamine dendroid is big
Molecule is 3-6 polyamide-amine type dendritic macromoles.
7. a kind of preparation method, is applied to the targeted nano pharmaceutical carrier described in any one of claim 1-6, feature exists
In, including：
Synthesize PAMAM-PEG；Wherein, PAMAM is polyamidoamine dendritic macromole, and PEG is polyethylene glycol；
Synthesis polypeptide probe；
The PAMAM-PEG is activated using maleic amide, and is reacted at room temperature by the first setting proportioning with the polypeptide probe,
To obtain the targeted nano pharmaceutical carrier.
8. the method according to the description of claim 7 is characterized in that the step of synthesis PAMAM-PEG, including：
In the in the mixed solvent of methanol and dimethyl sulfoxide (DMSO), the PAMAM and PEG activated through n-hydroxysuccinimide
It reacts, purifies, to obtain the PAMAM-PEG at room temperature by the second setting proportioning.
9. the method according to the description of claim 7 is characterized in that the step of synthesis polypeptide probe, including：
1) resin is soaked in dimethyl formamide solution to be swollen after several minutes and the dimethyl formamide solution is discharged；
2) resin after swelling is positioned in the dimethyl formamide solution of hexahydropyridine accounting 20% and reacts several points
Clock exposes free amino to remove the blocking group of amino acid；
If 3) using dichloromethane solution and dimethyl formamide solution, alternately the resin of the cleaning after step 2) reaction is each
Dry time；
4) amino acid and benzotriazole-N, N, N of blocking group be will be disengaged from ', N '-tetramethylureas hexafluorophosphate (HBTU) etc.
Molar ratio mixes, and if activating reagent and the resin room temperature reaction through step 3) after over cleaning are added in mixed solution
Dry minute；
If 5) using dichloromethane solution and dimethyl formamide solution, alternately the resin of the cleaning after step 4) reaction is each
Dry time；
6) above-mentioned steps 2 are repeated)~step 5), until obtaining the polypeptide probe.
10. the preparation described in any one of claim 1-6 any one of them targeted nano pharmaceutical carriers or claim 7-9
Application of the method in preparing treatment lung-cancer medicament radiation targeting marker.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810716206.2A CN108653242A (en) | 2018-07-03 | 2018-07-03 | A kind of targeted nano pharmaceutical carrier and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810716206.2A CN108653242A (en) | 2018-07-03 | 2018-07-03 | A kind of targeted nano pharmaceutical carrier and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108653242A true CN108653242A (en) | 2018-10-16 |
Family
ID=63772730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810716206.2A Pending CN108653242A (en) | 2018-07-03 | 2018-07-03 | A kind of targeted nano pharmaceutical carrier and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108653242A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111868072A (en) * | 2019-01-03 | 2020-10-30 | 京东方科技集团股份有限公司 | Peptoid compound, preparation method thereof, nano-carrier and pharmaceutical composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213468A (en) * | 2017-04-14 | 2017-09-29 | 国家纳米科学中心 | A kind of targeted nano pharmaceutical carrier and its preparation method and application |
-
2018
- 2018-07-03 CN CN201810716206.2A patent/CN108653242A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107213468A (en) * | 2017-04-14 | 2017-09-29 | 国家纳米科学中心 | A kind of targeted nano pharmaceutical carrier and its preparation method and application |
Non-Patent Citations (5)
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111868072A (en) * | 2019-01-03 | 2020-10-30 | 京东方科技集团股份有限公司 | Peptoid compound, preparation method thereof, nano-carrier and pharmaceutical composition |
| US11352390B2 (en) | 2019-01-03 | 2022-06-07 | Beijing Boe Technology Development Co., Ltd. | Peptoid compound and preparation method, carrier, and pharmaceutical composition thereof |
| CN111868072B (en) * | 2019-01-03 | 2023-08-29 | 京东方科技集团股份有限公司 | Peptoid compound, preparation method thereof, nano carrier and pharmaceutical composition |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1107998B1 (en) | Method for the preparation of polyamide chains of precise length, their conjugates with proteins | |
| Roy et al. | Glycodendrimers: novel glycotope isosteres unmasking sugar coding. Case study with T-antigen markers from breast cancer MUC1 glycoprotein | |
| Lee et al. | Cross-linked nanoassemblies from poly (ethylene glycol)-poly (aspartate) block copolymers as stable supramolecular templates for particulate drug delivery | |
| Obeid et al. | Synthesis and self-assembly of well-defined poly (amino acid) end-capped poly (ethylene glycol) and poly (2-methyl-2-oxazoline) | |
| Mihov et al. | Polyphenylene dendrimers as scaffolds for shape-persistent multiple peptide conjugates | |
| CN106750376B (en) | A kind of preparation method of the turnover reduction sensitivity reversible crosslink nano-micelle of charge | |
| US11865508B2 (en) | Conditioned surfaces for in situ molecular array synthesis | |
| CN107141488A (en) | Multiple stimulation response shell-crosslinked polymeric micelles and preparation method thereof | |
| CN102105191A (en) | Biodegradable metal-chelating polymers and vaccines | |
| CN113292635B (en) | Polypeptide targeting CD47 and application thereof | |
| CN105085631B (en) | A kind of polypeptide of special target HER2 albumen and its application | |
| CN107556438A (en) | Multiple response sexual intercourse linked polymer and medicament-carried nano micelle and their preparation method | |
| CN110078934A (en) | A kind of preparation method and its utilization of PDA supermolecular gel | |
| JP2018509623A5 (en) | ||
| CN107213468A (en) | A kind of targeted nano pharmaceutical carrier and its preparation method and application | |
| CN107137724A (en) | A kind of intracellular material for constructing temperature-responsive aggregation and its preparation method and application | |
| CN108586579A (en) | One type peptide and its derivative, salt, preparation method and purposes | |
| CN108653242A (en) | A kind of targeted nano pharmaceutical carrier and its preparation method and application | |
| Peluso et al. | Solid-Phase Strategies for the Assembly of Template-Based Protein Mimetics1 | |
| Fuchs et al. | Enzyme cleavable nanoparticles from peptide based triblock copolymers | |
| Studenovsky et al. | Polymer carriers for anticancer drugs targeted to EGF receptor | |
| Bi et al. | Synthesis, characterization and stability of a luteinizing hormone-releasing hormone (LHRH)-functionalized poly (amidoamine) dendrimer conjugate | |
| Whitton et al. | Arborescent micelles: Dendritic poly (γ‐benzyl l‐glutamate) cores grafted with hydrophilic chain segments | |
| CN105085632A (en) | Specific EGFR (epidermal growth factor receptor)-protein-targeted polypeptide and application thereof | |
| Bulmuş et al. | Conjugates of poly (N‐isopropyl acrylamide‐co‐acrylic acid) with alanine monopeptide, dipeptide, and tripeptide |
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: 20181016 |