CN107057076A - A kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle - Google Patents
A kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle Download PDFInfo
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- CN107057076A CN107057076A CN201710376627.0A CN201710376627A CN107057076A CN 107057076 A CN107057076 A CN 107057076A CN 201710376627 A CN201710376627 A CN 201710376627A CN 107057076 A CN107057076 A CN 107057076A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
- C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
- C08G81/027—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyester or polycarbonate sequences
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- C08G2230/00—Compositions for preparing biodegradable polymers
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- C08J2387/00—Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
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Abstract
The present invention discloses a kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle, using following methods：1）Polyacrylic acid, hydroxy-end capped polycaprolactone monododecyl ether, hydroxy-end capped PTMC list tridecyl ether, solvent and condensing agent are added in reactor, polyacrylic acid polycaprolactone PTMC dual graft copolymer is reacted to obtain；2）Dual graft copolymer and solvent are added in reactor, copolymer stoste is dissolved to obtain；3）Stoste is added into bag filter, the beaker for filling selective solvent is put into, every displacement in 8 hours once, replaces 3~4 times, is poured into graduated volumetric flask, scale is adjusted to selective solvent, obtain object of the present invention.Preparation technology of the present invention is simple, be easy to grasp, and gained object is a kind of new pharmaceutical carrier.
Description
Technical field
The present invention relates to a kind of system of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
Preparation Method, belongs to biodegradated polymer materal preparing technical field.
Background technology
Polyacrylic acid is a kind of biomaterial with good biocompatibility and biodegradability, with excellent
Hydrophily, in medicine extensive application.Polycaprolactone and PTMC are with excellent biofacies
The biomaterial of capacitive and biodegradability, has preferable hydrophobicity, is widely used in medicine.By polycaprolactone
Segment, PTMC segment be grafted to simultaneously on polyacrylic acid strand obtained by poly acrylic acid-poly caprolactone-
PTMC dual graft copolymer has amphipathic, and micella can be self-assembly of in selective solvent, is one
New pharmaceutical carrier is planted, is had broad application prospects in medicine.
The content of the invention
It is an object of the invention to provide a kind of preferable poly acrylic acid-poly caprolactone of simple to operate and effect-poly- Sanya
The preparation method of methyl carbonic dual graft copolymer micelle.Its technical scheme is：
A kind of preparation method of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle, its feature exists
In：The molecular weight of polyacrylic acid segment is 51000~62000 in copolymer, the molecular weight of polycaprolactone segment for 2200~
2300, the molecular weight of PTMC segment is 2200~2300；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer：Added in dry reactor
Polyacrylic acid, hydroxy-end capped polycaprolactone monododecyl ether, hydroxy-end capped PTMC list tridecyl
Under ether, solvent and condensing agent, inert atmosphere, in 26~33 DEG C of stirring reactions 2~3 days, terminating reaction, by filtering, dialysis, dry
It is dry, obtain object；
2）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste：In dry reactor
Poly acrylic acid-poly caprolactone-PTMC dual graft copolymer and solvent are added, in 47~53 DEG C of stirring and dissolvings 50
~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle：At room temperature, by stoste
Add in bag filter, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 8 hours once, displacement 3~4
Secondary, solution shows blue light in bag filter, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent,
Obtain object.
A kind of preparation side of described poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
Method, step 1）In, the mol ratio of polycaprolactone monododecyl ether and polyacrylic acid is 15~25:1, PTMC
The mol ratio of single tridecyl ether and polyacrylic acid is 15~25:1.
A kind of preparation side of described poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
Method, step 1）In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- DIC or 3- ethyls -1-
（3- dimethylaminopropyls）The mol ratio of carbodiimide, condensing agent and polyacrylic acid is 1.08~1.9:1, solvent is sub- using dimethyl
Sulfone, reactant solution concentration is 5~15 g/100 ml.
A kind of preparation side of described poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
Method, step 2）In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
A kind of preparation side of described poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
Method, step 3）In, bag filter capacity is 5~10 ml, and bag filter molecular cut off is 3500~4500, and selective solvent is used
Distilled water, solution concentration is 0.1~0.3 mg/ml.
Compared with prior art, its advantage is the present invention：
1st, the preparation method of described a kind of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle,
The means being combined using a kind of polymer with the esterification and dialysis that two kinds of different polymeric monomers are carried out simultaneously, operation letter
Singly, it is easy to grasp；
2nd, a kind of described poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle is a kind of new
Pharmaceutical carrier.
Embodiment
Embodiment 1
1）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer
14.6 grams of polyacrylic acid are added in dry reactor（Molecular weight is 51000）, 11.1 grams of hydroxy-end capped polycaprolactones
Monododecyl ether（Molecular weight is 2200）With 11.1 grams of hydroxy-end capped PTMC list tridecyl ethers（Molecule
Measure as 2200）, 368 ml dimethyl sulfoxide (DMSO)s are added, 0.076 gram is addedN,N’Under-dicyclohexylcarbodiimide, inert atmosphere,
In 26 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste
Added in dry reactor 120 milligrams of poly acrylic acid-poly caprolactone-PTMC dual graft copolymers,
100 milliliters of dimethyl sulfoxide (DMSO)s, in 47 DEG C of stirring and dissolvings 50 minutes, obtain object；
3）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste is added 5 milliliters
In the bag filter of capacity（Molecular cut off is 3500）, put it into 500 milliliters of beakers for filling distilled water, every 8 hours
Displacement once, is replaced 3 times, and solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is used
Distilled water is adjusted to scale, obtains object.
Embodiment 2
1）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer
15.3 grams of polyacrylic acid are added in dry reactor（Molecular weight is 55000）, 10.6 grams of hydroxy-end capped polycaprolactones
Monododecyl ether（Molecular weight is 2200）With 10.6 grams of hydroxy-end capped PTMC list tridecyl ethers（Molecule
Measure as 2200）, 365 ml dimethyl sulfoxide (DMSO)s are added, 0.043 gram is addedN,N’Under-DIC, inert atmosphere,
In 30 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste
Added in dry reactor 130 milligrams of poly acrylic acid-poly caprolactone-PTMC dual graft copolymers,
100 milliliters of dimethyl sulfoxide (DMSO)s, in 50 DEG C of stirring and dissolvings 55 minutes, obtain object；
3）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste is added 6 milliliters
In the bag filter of capacity（Molecular cut off is 4000）, put it into 500 milliliters of beakers for filling distilled water, every 8 hours
Displacement once, is replaced 4 times, and solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is used
Distilled water is adjusted to scale, obtains object.
Embodiment 3
1）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer
16.6 grams of polyacrylic acid are added in dry reactor（Molecular weight is 62000）, 11.2 grams of hydroxy-end capped polycaprolactones
Monododecyl ether（Molecular weight is 2300）With 11.2 grams of hydroxy-end capped PTMC list tridecyl ethers（Molecule
Measure as 2300）, 392 ml dimethyl sulfoxide (DMSO)s are added, 0.067 gram of 3- ethyls -1- is added（3- dimethylaminopropyls）Carbodiimide,
Under inert atmosphere, in 33 DEG C of stirring reactions 3 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste
Added in dry reactor 140 milligrams of poly acrylic acid-poly caprolactone-PTMC dual graft copolymers,
100 milliliters of dimethyl sulfoxide (DMSO)s, in 53 DEG C of stirring and dissolvings 60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste is added 7 milliliters
In the bag filter of capacity（Molecular cut off is 4500）, put it into 500 milliliters of beakers for filling distilled water, every 8 hours
Displacement once, is replaced 3 times, and solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is used
Distilled water is adjusted to scale, obtains object.
Claims (5)
1. a kind of preparation method of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle, its feature
It is：The molecular weight of polyacrylic acid segment is 51000~62000 in copolymer, the molecular weight of polycaprolactone segment for 2200~
2300, the molecular weight of PTMC segment is 2200~2300；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer：Added in dry reactor
Polyacrylic acid, hydroxy-end capped polycaprolactone monododecyl ether, hydroxy-end capped PTMC list tridecyl
Under ether, solvent and condensing agent, inert atmosphere, in 26~33 DEG C of stirring reactions 2~3 days, terminating reaction, by filtering, dialysis, dry
It is dry, obtain object；
2）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer stoste：In dry reactor
Poly acrylic acid-poly caprolactone-PTMC dual graft copolymer and solvent are added, in 47~53 DEG C of stirring and dissolvings 50
~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer micelle：At room temperature, by stoste
Add in bag filter, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 8 hours once, displacement 3~4
Secondary, solution shows blue light in bag filter, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent,
Obtain object.
2. a kind of poly acrylic acid-poly caprolactone according to claim 1-PTMC dual graft copolymer glue
The preparation method of beam, it is characterised in that：Step 1）In, the mol ratio of polycaprolactone monododecyl ether and polyacrylic acid for 15~
25:1, the mol ratio of PTMC list tridecyl ether and polyacrylic acid is 15~25:1.
3. a kind of poly acrylic acid-poly caprolactone-PTMC dual graft copolymer according to claim 1
The preparation method of micella, it is characterised in that：Step 1）In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- two is different
Propyl group carbodiimide or 3- ethyls -1-（3- dimethylaminopropyls）The mol ratio of carbodiimide, condensing agent and polyacrylic acid is 1.08
~1.9:1, solvent uses dimethyl sulfoxide (DMSO), and reactant solution concentration is 5~15 g/100 ml.
4. a kind of poly acrylic acid-poly caprolactone according to claim 1-PTMC dual graft copolymer glue
The preparation method of beam, it is characterised in that：Step 2）In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
5. a kind of poly acrylic acid-poly caprolactone according to claim 1-PTMC dual graft copolymer glue
The preparation method of beam, it is characterised in that：Step 3）In, bag filter capacity is 5~10 ml, and bag filter molecular cut off is 3500
~4500, selective solvent uses distilled water, and solution concentration is 0.1~0.3 mg/ml.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376627.0A CN107057076A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle |
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| CN201710376627.0A CN107057076A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle |
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| CN201710376627.0A Withdrawn CN107057076A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polycaprolactone PTMC dual graft copolymer micelle |
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Application publication date: 20170818 |