CN105418909A - Polyethylene-glycol-modification water-solubility tryptanthrin polymer derivative, preparing method thereof and application thereof - Google Patents
Polyethylene-glycol-modification water-solubility tryptanthrin polymer derivative, preparing method thereof and application thereof Download PDFInfo
- Publication number
- CN105418909A CN105418909A CN201510815603.1A CN201510815603A CN105418909A CN 105418909 A CN105418909 A CN 105418909A CN 201510815603 A CN201510815603 A CN 201510815603A CN 105418909 A CN105418909 A CN 105418909A
- Authority
- CN
- China
- Prior art keywords
- couroupitine
- soluble
- modified water
- polymer derivant
- polyethyleneglycol modified
- 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
- 0 C*(CCO*)C(OCCNN=C(c(cccc1)c1N12)C1=Nc(cccc1)c1C2=O)=O Chemical compound C*(CCO*)C(OCCNN=C(c(cccc1)c1N12)C1=Nc(cccc1)c1C2=O)=O 0.000 description 2
- KFLRMERNDLPGLI-QGOAFFKASA-N N/N=C(\c(cccc1)c1N12)/C1=Nc(cccc1)c1C2=O Chemical compound N/N=C(\c(cccc1)c1N12)/C1=Nc(cccc1)c1C2=O KFLRMERNDLPGLI-QGOAFFKASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
- C08G65/33396—Polymers modified by chemical after-treatment with organic compounds containing nitrogen having oxygen in addition to nitrogen
Landscapes
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Polyethers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a polyethylene-glycol-modification water-solubility tryptanthrin polymer derivative, a preparing method thereof and an application thereof, and belongs to the technical field of drug preparing. The polyethylene-glycol-modification water-solubility tryptanthrin polymer derivative is prepared after tryptanthrin and modified polyethylene glycol are reacted or prepared after modified tryptanthrin and polyethylene glycol are reacted. By means of the prepared water-solubility tryptanthrin polymer derivative (a water-solubility tryptanthrin prodrug), the solubility of the tryptanthrin can be increased by 200-3,000 times; the content of the tryptanthrin in the prodrug is 1%-90%, the acid sensitivity (acid sensitivity hydrazone bond rupturing) characteristic is achieved, the tryptanthrin can be dissociated in the weak acid environment at the tumor portion and the inflammation portion, and therefore drug activity is developed; nano-micelle can be prepared from the tryptanthrin polymer derivative with a mixed solvent dialysis method, and nano-micelle can be formed after the tryptanthrin and PEG are dissolved into water in a certain proportion.
Description
Technical field
The invention belongs to field of medicine preparing technology, be specifically related to a kind of polyethyleneglycol modified water-soluble couroupitine A polymer derivant and its preparation method and application.
Background technology
Natural Product Tryptanthrin (Tryptanthrin; TRYP) the acanthaceous indigo platymisciums such as indigo are derived from; it is reported that it has stronger toxicity to mammary cancer MCF-7, lung cancer NCI-H460, central nervous system cancer SF-268 clone; to liver cell, there is provide protection; allergic dermatitis can be improved, effectively disease such as treatment intestinal disorder and inflammation etc.Namely couroupitine A and some derivatives thereof have as antibacterial, anti-inflammatory, the pharmacologically active such as antitumor, anti-oxidant.
Although the pharmacological action of couroupitine A is very strong, pharmaceutical use is very large, but be insoluble in water and limit its absorption in vivo, cause bioavailability extremely low, its solubleness in phosphate buffer soln is 5.4 μm of ol/L (1.339 μ g/mL), and the solubleness of compound in water absorbs lower than limiting it during 100 μ g/mL.
The method of current insoluble drug solubilising is divided into physical method and modifying for chemical structure, and wherein physical method comprises and adds solubilizing agent, solubility promoter, makes soluble salt, cyclodextrin encapsulated, makes liposome etc.Although add the solubleness that solubilizing agent, solubility promoter etc. effectively can increase medicine, some auxiliary agent add the absorption, physiologically active, toxicity etc. that membership affects Liquid drug preparation; And the method making soluble salt is only applicable to slightly acidic or weakly alkaline medicine; During physical encapsulation, drug delivery amount is on the low side, and its stability is relevant with wrapped up pharmaceutical properties.Some scholar to propose with medicine at the logarithm logP of Octanol/water Partition Coefficients for index, and the fat-soluble medicine of logP>4.5 could form stable medicinal liposome, and couroupitine A logP=2.37, therefore liposomal encapsulated also inadvisable.
Also do not have at present and improve the water miscible report of couroupitine A by chemical process.
Summary of the invention
In order to overcome the defect that above-mentioned prior art exists, the object of the present invention is to provide a kind of polyethyleneglycol modified water-soluble couroupitine A polymer derivant and its preparation method and application, this polyethyleneglycol modified water-soluble couroupitine A polymer derivant solvability is good, preparation method is simple, easy to operate.
The present invention is achieved through the following technical solutions:
The invention discloses a kind of polyethyleneglycol modified water-soluble couroupitine A polymer derivant, described polyethyleneglycol modified water-soluble couroupitine A polymer derivant is connected by couroupitine A obtained with polyoxyethylene glycol by chemical bond.
Described derivative is obtained after couroupitine A and the polyoxyethylene glycol after modifying being reacted, or the couroupitine A after modification and polyoxyethylene glycol is reacted rear obtained.
The structural formula of polyethyleneglycol modified water-soluble couroupitine A polymer derivant is as follows:
Or:
Or:
Wherein, n be more than or equal to 2 integer, R is methoxyl group, polypeptide, DNA fragmentation, RNA fragment, taxol, camptothecine or Zorubicin.
The invention also discloses the preparation method of above-mentioned polyethyleneglycol modified water-soluble couroupitine A polymer derivant, the intermediate reaction of couroupitine A and the series of the polyethyleneglycol derivative " R-PEG-Z " after modifying is obtained; Or, intermediate serial for the couroupitine A derivative " TRYP-NH-Y " after modifying and polyoxyethylene glycol are reacted obtained.
By the intermediate reaction of the polyethyleneglycol derivative R-PEG-Z series after couroupitine A and modification, concrete operations are: polyoxyethylene glycol is carried out end group modification, obtained " R-PEG-Z " scaffold intermediate, and then with 6 carbonyl reactions of couroupitine A, obtained polyethyleneglycol modified water-soluble couroupitine A polymer derivant;
Intermediate serial for couroupitine A derivative " TRYP-NH-Y " after modifying and polyoxyethylene glycol are reacted, concrete operations are: by couroupitine A and hydrazine reaction, 6 of couroupitine A carbonyl reactions are made to become hydrazone key, obtained " TRYP-NH-Y " scaffold intermediate, and then react with polyoxyethylene glycol, obtained polyethyleneglycol modified water-soluble couroupitine A polymer derivant.
The intermediate of " R-PEG-Z " series, Z is N
2h
3-, Boc-NH-, Fmoc-NH-or-OCH
2cH
2nHNH
2; The intermediate of " TRYP-NH-Y " series, Y is H ,-NH
2,-CH
2cH
2oH, C
5h
10o
2n-or PEG-R.
The molecular weight of polyoxyethylene glycol is 500 ~ 10000; When the molar ratio of couroupitine A and PEG is between 1:4 ~ 4:1, water-solublely nano-micelle can be formed.
The invention also discloses by the obtained Pegylation couroupitine A micellar solution of above-mentioned polyethyleneglycol modified water-soluble couroupitine A polymer derivant, polyethyleneglycol modified water-soluble couroupitine A polymer derivant is dissolved in the mixed solvent be made up of poor solvent and good solvent, is self-assembled into polyoxyethylene glycol couroupitine A micellar solution; Wherein, the volume ratio of poor solvent and good solvent is 0.1:1 ~ 500:1.
Described poor solvent is water; Described good solvent is dimethyl sulfoxide (DMSO), dimethyl formamide, acetone, tetrahydrofuran (THF) or acetonitrile.
The invention also discloses the application of above-mentioned polyethyleneglycol modified water-soluble couroupitine A polymer derivant in preparation anti-inflammatory or antitumor drug.
Compared with prior art, the present invention has following useful technique effect:
Polyethyleneglycol modified water-soluble couroupitine A polymer derivant disclosed by the invention, according to couroupitine A C
6there is the feature of carbonyl, and consider the slightly acidic (pH6.5-6.8) of tumor tissues and inflammatory microenvironment, therefore on 6 carbonyls, introduce the responsive hydrazone key of pH, and by this intermediate product, hydrophilic flexibility chain polyalkylene glycol (PEG) is introduced couroupitine A, improve it water-soluble, and then improve its bioavailability.The solubleness of couroupitine A can be improved 200 ~ 3000 times by obtained water-soluble couroupitine A polymer derivant (water-soluble couroupitine A prodrug), in prodrug, the content of couroupitine A is 1% ~ 90%, and there is the characteristic of acid-sensitive (acid-sensitive hydrazone bond rupture), couroupitine A can be dissociateed under the weakly acidic condition of tumour and inflammation part, thus play its antitumor action.
The invention also discloses the synthetic method of polyethyleneglycol modified water-soluble couroupitine A polymer derivant, intermediate serial for couroupitine A-couroupitine A derivative (TRYP-NH-Y) after modifying and PEG are reacted, or the intermediate reaction of couroupitine A and the series of the PEG-PEG derivative (R-PEG-Z) after modifying is obtained.The method is reasonable in design, simple to operate.
The invention also discloses the Pegylation couroupitine A micellar solution prepared by above-mentioned polyethyleneglycol modified water-soluble couroupitine A polymer derivant, the nanoscale structures of micellar solution has the effect extending circulation time in vivo and target tumor tissue, and preparation micellar solution is simple to operation, can adopt the methods such as dialysis method, solvent evaporation method, emulsion process.
Confirm through experiment, the polyethyleneglycol modified water-soluble couroupitine A polymer derivant that the present invention obtains, as prodrug, has obvious restraining effect to MCF-7 cell, thus has broad application prospects in the preparation of antitumor drug.
Accompanying drawing explanation
Fig. 1 is the TRYP-NNHCH that the present invention obtains
2cH
2oCO-PEG synthetic route chart;
Fig. 2 is the TRYP-NNHCH that the present invention obtains
2cH
2the proton nmr spectra of OCO-PEG;
Fig. 3 is the TRYP-NNHCH that the present invention obtains
2cH
2oH is HPLC figure in different pH solution; Wherein, (a) is pH7.4, t=15min; B () is pH5.0, t=3min; C () is pH5.0, t=30min;
Fig. 4 is TRYP-NNHCH
2cH
2oCO-PEG accumulation release amount of medicine (pH5.5,7.4, n=3);
Fig. 5 is under different pH, TRYP, TRYP-NNHCH
2cH
2oCO-PEG is to MCF-7 cytotoxicity;
Fig. 6 is TRYP-NNHCH
2cH
2the transmission electron microscope picture of the OCO-PEG aqueous solution.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, and the explanation of the invention is not limited.
Building-up process of the present invention be couroupitine A with modify after PEG react, or the couroupitine A after PEG and modification reacts, and generates some intermediate.
Be specifically as follows couroupitine A and contain " Y-NH
2" the compound reaction of structure, formed and there is the hydrazone key of acid-sensitive feature-couroupitine A derivative (TRYP-NH-Y) series, and by this key, introduce hydrophilic PEG chain, synthesis PEGization couroupitine A.Also can be that PEG chain end group is modified, form some intermediate-PEG derivative (R-PEG-Z) series.Then react with couroupitine A, obtain PEGization couroupitine A.
The present invention obtains PEGization couroupitine A polymer derivant.Its structural formula can be:
Or:
Or:
The present invention is by some intermediate, and PEG chain is introduced couroupitine A.Concrete grammar is, intermediate serial for the couroupitine A-couroupitine A derivative (TRYP-NH-Y) after modifying and PEG is reacted, or is obtained by the intermediate reaction of couroupitine A and the series of the PEG-PEG derivative (R-PEG-Z) after modifying.
By couroupitine A and hydrazine reaction, 6 carbonyl reactions are become hydrazone key, obtain " TRYP-NH-Y " scaffold intermediate, then react with PEG, polyethyleneglycol modified couroupitine A derivative can be obtained---PEGization couroupitine A.
PEG is carried out end group modification, " R-PEG-Z " structure, then with 6 carbonyl reactions of couroupitine A, also can obtain PEGization couroupitine A.
Embodiment 1
Synthetic route is shown in accompanying drawing 1, and 0.248g couroupitine A is dissolved in 20mL tetrahydrofuran (THF), and 0.328g hydroxyethylhydrazine is dissolved in 2mL ethanolic soln, vacuumizes 20min, nitrogen protection, stirring at room temperature reaction 12h.After reaction terminates, column chromatography purification, collects object product-TRYP-NNHCH
2cH
2oH.The fracture qualitative characterization of its hydrazone key sees accompanying drawing 3, and wherein, (a) is pH7.4, t=15min; B () is pH5.0, t=3min; C () is pH5.0, t=30min.
By 41.5mgmPEG
2000-COOH and 12mgDCC, 6mgDMAP are dissolved in appropriate anhydrous methylene chloride, ice-water bath reaction 24h.Appropriate intermediate is added to mPEG
2000in the solution of-COOH, add 2mL pyridine simultaneously, continue to keep ice-water bath 24h, after reaction terminates, removal of solvent under reduced pressure, adds saturated sodium bicarbonate solution, filters, adds extraction into ethyl acetate three times, collect organic phase, decompression removing ethyl acetate, obtains light yellow class oily solid-TRYP-NNHCH
2cH
2oCO-PEG.Obtained TRYP-NNHCH
2cH
2the proton nmr spectra of OCO-PEG is shown in accompanying drawing 2.Its content discharging couroupitine A under the condition of pH7.4 and 5.5 is shown in Fig. 4.
Use human breast cancer cell line MCF-7, MTT detects couroupitine A and TRYP-NNHCH
2cH
2the cytotoxicity of OCO-PEG, under condition of different pH, it sees Fig. 5 to the restraining effect of MCF-7 cell.As can be seen from Figure 5, under pH7.4 condition, TRYP-NNHCH
2cH
2oCO-PEG has significant concn dependency, and itself and couroupitine A have similar anti-tumor activity.And under pH5.5 condition, due to TRYP-NNHCH
2cH
2oCO-PEG is macromole, can form nano-micelle in aqueous, therefore can better enter born of the same parents, and under sour environment, hydrazone bond rupture, discharges couroupitine A, shows the effect of killing tumor cells more better than couroupitine A.
Embodiment 2
Be dissolved in 15mL tetrahydrofuran (THF) by 0.248g couroupitine A, add 1.5mL hydrazine hydrate, 50 DEG C of oil baths, reaction 10h, column chromatography purification, obtains object product-TRYP-NNH
2.63.4mgMPEG-COOH, 18.3mgDDC, 20.6mgNHS are dissolved in anhydrous methylene chloride, and ice bath reaction 24h, obtains the activation products of mPEG-COOH.The activation products of intermediate and mPEG-COOH are dissolved in anhydrous methylene chloride, room temperature reaction 24h.Rotary evaporation, saturated NaHCO
3solution washes three times, extraction into ethyl acetate, collects product-TRYP-NNHCO-PEG.
Embodiment 3
Take 100mgmPEG-OH, 13.1mg carbonyl dimidazoles (CDI) and be placed in 25mL eggplant type bottle, add 5mL anhydrous methylene chloride, room temperature, stirring reaction 24h, after completion of the reaction, solvent removed by evaporation at reduced pressure, remainder adds excessive anhydrous diethyl ether, collect white precipitate, vacuum-drying, obtains mPEG-CDI36.7mg.This product and hydrazine hydrate, triethylamine are dissolved in 5mL methylene dichloride.The same step of experiment aftertreatment, obtains mPEG-NHNH
2.Itself and equivalent couroupitine A react, and obtain TRYP-NNH-mPEG.
Embodiment 4
Intermediate-1 or intermediate-2, with case 1 or case 2, during end product synthesis, are dissolved in 10mLDMSO with PEG by the preparation of intermediate, and stirring at room temperature reaction 24h, dialyses at 4 DEG C, obtain PEGization couroupitine A micellar solution.
Case study on implementation 5
Get the TRYP-NNHCH prepared
2cH
2oCO-PEG4.5mg, directly water-soluble, ultrasonic vibration 1min, nano micellar solution.Its transmission electron microscope picture is shown in Fig. 6.
Case study on implementation 6
Get the TRYP-NNHCH prepared
2cH
2oCO-PEG4.5mg, is dissolved in 2mLDMSO solution, and under magnetic agitation, constant voltage titration funnel drips 4mL deionized water, stirs 4h, dialysis 12h, to collect in dialysis tubing solution nano micellar solution.
In sum, polyethyleneglycol modified water-soluble couroupitine A polymer derivant of the present invention is obtained after couroupitine A and the polyoxyethylene glycol after modifying being reacted, or the couroupitine A after modification and polyoxyethylene glycol is reacted rear obtained.The solubleness of couroupitine A can be improved 200 ~ 3000 times by obtained water-soluble couroupitine A polymer derivant (water-soluble couroupitine A prodrug), in prodrug, the content of couroupitine A is 1% ~ 90%, and there is the characteristic of acid-sensitive (acid-sensitive hydrazone bond rupture), couroupitine A can be dissociateed under the weakly acidic condition of tumour and inflammation part, thus play pharmaceutical activity; This couroupitine A polymer derivant prepares nano-micelle by mixed solvent dialysis method, and water-solublely when couroupitine A and PEG certain proportion can form nano-micelle.
Claims (10)
1. polyethyleneglycol modified water-soluble couroupitine A polymer derivant, is characterized in that, described polyethyleneglycol modified water-soluble couroupitine A polymer derivant is connected by couroupitine A obtained with polyoxyethylene glycol by chemical bond.
2. polyethyleneglycol modified water-soluble couroupitine A polymer derivant according to claim 1, it is characterized in that, described derivative is obtained after couroupitine A and the polyoxyethylene glycol after modifying being reacted, or the couroupitine A after modification and polyoxyethylene glycol is reacted rear obtained.
3. polyethyleneglycol modified water-soluble couroupitine A polymer derivant according to claim 1, it is characterized in that, its structural formula is as follows:
Wherein, n be more than or equal to 2 integer, R is methoxyl group, polypeptide, DNA fragmentation, RNA fragment, taxol, camptothecine or Zorubicin.
4. the preparation method of polyethyleneglycol modified water-soluble couroupitine A polymer derivant, is characterized in that, is obtained by the intermediate reaction of couroupitine A and the series of the polyethyleneglycol derivative " R-PEG-Z " after modifying; Or, intermediate serial for the couroupitine A derivative " TRYP-NH-Y " after modifying and polyoxyethylene glycol are reacted obtained.
5. the preparation method of polyethyleneglycol modified water-soluble couroupitine A polymer derivant according to claim 4, it is characterized in that, by the intermediate reaction of the polyethyleneglycol derivative R-PEG-Z series after couroupitine A and modification, concrete operations are: polyoxyethylene glycol is carried out end group modification, obtained " R-PEG-Z " scaffold intermediate, and then with 6 carbonyl reactions of couroupitine A, obtained polyethyleneglycol modified water-soluble couroupitine A polymer derivant;
Intermediate serial for couroupitine A derivative " TRYP-NH-Y " after modifying and polyoxyethylene glycol are reacted, concrete operations are: by couroupitine A and hydrazine reaction, 6 of couroupitine A carbonyl reactions are made to become hydrazone key, obtained " TRYP-NH-Y " scaffold intermediate, and then react with polyoxyethylene glycol, obtained polyethyleneglycol modified water-soluble couroupitine A polymer derivant.
6. the preparation method of polyethyleneglycol modified water-soluble couroupitine A polymer derivant according to claim 4, is characterized in that, the intermediate of " R-PEG-Z " series, Z is N
2h
3-, Boc-NH-, Fmoc-NH-or-OCH
2cH
2nHNH
2; The intermediate of " TRYP-NH-Y " series, Y is H ,-NH
2,-CH
2cH
2oH, C
5h
10o
2n-or PEG-R.
7. the preparation method of polyethyleneglycol modified water-soluble couroupitine A polymer derivant according to claim 4, is characterized in that, the molecular weight of polyoxyethylene glycol is 500 ~ 10000; When the molar ratio of couroupitine A and PEG is between 1:4 ~ 4:1, water-solublely nano-micelle can be formed.
8. by the Pegylation couroupitine A micellar solution that the polyethyleneglycol modified water-soluble couroupitine A polymer derivant in claims 1 to 3 described in any one is obtained, it is characterized in that, polyethyleneglycol modified water-soluble couroupitine A polymer derivant is dissolved in the mixed solvent be made up of poor solvent and good solvent, is self-assembled into polyoxyethylene glycol couroupitine A micellar solution; Wherein, the volume ratio of poor solvent and good solvent is 0.1:1 ~ 500:1.
9. Pegylation couroupitine A micellar solution according to claim 9, is characterized in that, described poor solvent is water; Described good solvent is dimethyl sulfoxide (DMSO), dimethyl formamide, acetone, tetrahydrofuran (THF) or acetonitrile.
10. the application of the polyethyleneglycol modified water-soluble couroupitine A polymer derivant in claims 1 to 3 described in any one in preparation anti-inflammatory or antitumor drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510815603.1A CN105418909B (en) | 2015-11-20 | 2015-11-20 | Polyethyleneglycol modified water-soluble couroupitine A polymer derivant and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510815603.1A CN105418909B (en) | 2015-11-20 | 2015-11-20 | Polyethyleneglycol modified water-soluble couroupitine A polymer derivant and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105418909A true CN105418909A (en) | 2016-03-23 |
| CN105418909B CN105418909B (en) | 2017-11-24 |
Family
ID=55497484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510815603.1A Active CN105418909B (en) | 2015-11-20 | 2015-11-20 | Polyethyleneglycol modified water-soluble couroupitine A polymer derivant and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105418909B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106139159A (en) * | 2016-08-30 | 2016-11-23 | 四川大学 | The polyethyleneglycol derivative small-molecule drug conjugate polymer micelle sensitive for pH purposes in inflammation targeted delivery system |
| RU2694058C1 (en) * | 2019-04-08 | 2019-07-09 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Water-soluble derivative of tryptane-trin, having anti-tumor, anti-inflammatory and antimicrobial activity, and increasing therapeutic activity of anti-tumor antibiotics |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010248086A (en) * | 2009-04-10 | 2010-11-04 | Hirosaki Univ | Tryptanthrin derivative |
| CN102250342A (en) * | 2011-05-26 | 2011-11-23 | 河北科技大学 | PEG/mPEG (Polyethylene Glycol) multi-carboxyl chemical modifying agent connected with citric acid, preparation method and application thereof in modification of toluylene compound |
| CN103656652A (en) * | 2013-12-10 | 2014-03-26 | 深圳先进技术研究院 | Dual-sensing response type polymer nano-micelle as well as preparation method and application thereof |
| CN102603555B (en) * | 2012-03-22 | 2014-04-16 | 浙江大学 | All-trans retinoic acid amide derivative and preparation method and application thereof |
| CN104072624A (en) * | 2014-05-15 | 2014-10-01 | 温州医科大学 | Polyamine modified polymer drug as well as preparation method and application thereof as anti-tumor drug |
-
2015
- 2015-11-20 CN CN201510815603.1A patent/CN105418909B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010248086A (en) * | 2009-04-10 | 2010-11-04 | Hirosaki Univ | Tryptanthrin derivative |
| CN102250342A (en) * | 2011-05-26 | 2011-11-23 | 河北科技大学 | PEG/mPEG (Polyethylene Glycol) multi-carboxyl chemical modifying agent connected with citric acid, preparation method and application thereof in modification of toluylene compound |
| CN102603555B (en) * | 2012-03-22 | 2014-04-16 | 浙江大学 | All-trans retinoic acid amide derivative and preparation method and application thereof |
| CN103656652A (en) * | 2013-12-10 | 2014-03-26 | 深圳先进技术研究院 | Dual-sensing response type polymer nano-micelle as well as preparation method and application thereof |
| CN104072624A (en) * | 2014-05-15 | 2014-10-01 | 温州医科大学 | Polyamine modified polymer drug as well as preparation method and application thereof as anti-tumor drug |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106139159A (en) * | 2016-08-30 | 2016-11-23 | 四川大学 | The polyethyleneglycol derivative small-molecule drug conjugate polymer micelle sensitive for pH purposes in inflammation targeted delivery system |
| RU2694058C1 (en) * | 2019-04-08 | 2019-07-09 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Water-soluble derivative of tryptane-trin, having anti-tumor, anti-inflammatory and antimicrobial activity, and increasing therapeutic activity of anti-tumor antibiotics |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105418909B (en) | 2017-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Qu et al. | Anisamide-functionalized pH-responsive amphiphilic chitosan-based paclitaxel micelles for sigma-1 receptor targeted prostate cancer treatment | |
| CN102060991B (en) | Amphiphilic prodrug of 7- ethyl-10-hydroxycamptothecin and preparation method thereof | |
| Cao et al. | Polymeric prodrugs conjugated with reduction-sensitive dextran–camptothecin and pH-responsive dextran–doxorubicin: an effective combinatorial drug delivery platform for cancer therapy | |
| EP2287230A1 (en) | Docetaxel polymer derivative, method for producing same and use of same | |
| CN108066770A (en) | Amphipathic nature polyalcohol prodrug of reduction response release active compound and preparation method thereof | |
| CN107669626A (en) | A kind of preparation method and applications of the drug delivery system of the reduction sensitivity of high drug load | |
| EP3118244B1 (en) | Novel cationic polyphosphazene compound, polyphosphazenes-drug conjugate compound and method for preparing same | |
| JP7506444B2 (en) | Preparation method and use of novel abiraterone derivative for injection | |
| CN105131182B (en) | Poly- (β amino esters) polymer of pluronic and its synthesis and methods for using them | |
| JP2010528105A (en) | Anticancer drugs that simultaneously perform diagnosis and treatment of cancer | |
| Lu et al. | Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles | |
| CN103893769B (en) | Containing poly (glycolide-lactide) targeting polymer drug carrier and preparation method thereof | |
| CN105418909A (en) | Polyethylene-glycol-modification water-solubility tryptanthrin polymer derivative, preparing method thereof and application thereof | |
| CN102174187B (en) | Synthetic method of targeted pegylated lipid medicinal material | |
| Li et al. | Tailored Trojan horse nanocarriers for enhanced redox-responsive drug delivery | |
| CN105504293B (en) | A kind of preparation and application of fluorescence star block copolymer | |
| CN107090082B (en) | A kind of Salanesol derivative, preparation method and application with tumor tissues reduction-sensitive | |
| CN111793147B (en) | Modified chitosan, double-response nano-carrier drug, and preparation method and application thereof | |
| CN103055321A (en) | Methoxy polyethylene glycol-polyphosphate diblock copolymer and adriamycin bonding medicine thereof | |
| CN104974353B (en) | PH response three block linear polymers and micellar system based on poly- β amidos ester | |
| CN103656669A (en) | Compound micelle-based nano-vector, and preparation method and application thereof | |
| WO2012159197A1 (en) | Drug delivery agents comprising cyclodextrin covalently linked to a gemini surfactant, and pharmaceutical compositions comprising the same | |
| Sreekanth et al. | Self-assembled supramolecular nanomicelles from a bile acid–docetaxel conjugate are highly tolerable with improved therapeutic efficacy | |
| CN107266677B (en) | A kind of PEGylated matrix material of oxidation responsiveness, preparation method and its application | |
| BR112012012539B1 (en) | CROWN ETHERS ORTHOESTER DERIVATIVES AND PHARMACEUTICAL OR DIAGNOSTIC COMPOSITION INCLUDING THEM |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |