CN107043459A - A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle - Google Patents
A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle Download PDFInfo
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- CN107043459A CN107043459A CN201710376615.8A CN201710376615A CN107043459A CN 107043459 A CN107043459 A CN 107043459A CN 201710376615 A CN201710376615 A CN 201710376615A CN 107043459 A CN107043459 A CN 107043459A
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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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- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
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- C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
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Abstract
The present invention discloses a kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle, using following methods：1）Polyacrylic acid, hydroxy-end capped poly (lactic acid-glycolic acid) monododecyl ether, hydroxy-end capped PTMC list undecyl ether, solvent and condensing agent are added in dry reactor, polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer is reacted to obtain；2）Dual graft copolymer and solvent are added in dry reactor, dissolving obtains copolymer stoste；3）Stoste is added in bag filter, put it into the beaker for filling selective solvent, every displacement in 7 hours once, replaces 3~4 times, is then poured into in 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 poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Preparation method, belong 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.Poly (lactic acid-glycolic acid)（The weight ratio of lactic acid and glycolic is 90/10）With it is poly-
Trimethylene carbonate is the biomaterial with excellent biocompatibility and biodegradability, there is preferable hydrophobicity,
It is widely used in medicine.Poly (lactic acid-glycolic acid) segment, PTMC segment are grafted to poly- third simultaneously
Poly acrylic acid-poly y-PTMC dual graft copolymer obtained by olefin(e) acid strand has two
Parent's property, can be self-assembly of micella in selective solvent, be a kind of new pharmaceutical carrier, have extensively in medicine
Wealthy application prospect.
The content of the invention
It is an object of the invention to provide a kind of preferable poly acrylic acid-poly y of simple to operate and effect-poly-
The preparation method of trimethylene carbonate dual graft copolymer micelle.Its technical scheme is：
A kind of preparation method of poly acrylic acid-poly y-PTMC dual graft copolymer micelle, it is special
Levy and be：The molecular weight of polyacrylic acid segment is 53000~63000 in copolymer, and the molecular weight of poly (lactic acid-glycolic acid) segment is
2200~2400, the molecular weight of PTMC segment is 2200~2400；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer：In dry reactor
Add polyacrylic acid, hydroxy-end capped poly (lactic acid-glycolic acid) monododecyl ether, hydroxy-end capped PTMC list
Under undecyl ether, solvent and condensing agent, inert atmosphere, in 27~34 DEG C of stirring reactions 2~3 days, terminating reaction passed through mistake
Filter, dialyse, dry, obtain object；
2）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer stoste：In dry reaction
Poly acrylic acid-poly y-PTMC dual graft copolymer and solvent are added in device, is stirred in 47~54 DEG C
Mix dissolving 50~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer micelle：At room temperature, will
Stoste is added in bag filter, is put it into 500 milliliters of beakers for filling selective solvent, every displacement in 7 hours once, displacement
3~4 times, in bag filter solution show blue light, be then poured into in graduated volumetric flask, be adjusted to selective solvent carve
Degree, obtains object.
A kind of system of described poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Preparation Method, step 1）In, poly (lactic acid-glycolic acid) monododecyl ether is using poly-（D, Pfansteihl）Glycolic monododecyl ether（Breast
The weight ratio of acid and glycolic is 90/10）, the mol ratio of poly (lactic acid-glycolic acid) monododecyl ether and polyacrylic acid for 15~
25:1, the mol ratio of PTMC list undecyl ether and polyacrylic acid is 15~25:1.
A kind of system of described poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Preparation Method, step 1）In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- DIC or 3- second
Base -1-（3- dimethylaminopropyls）The mol ratio of carbodiimide, condensing agent and polyacrylic acid is 1.07~1.8:1, solvent uses two
Methyl sulfoxide, reactant solution concentration is 5~15 g/100 ml.
A kind of system of described poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Preparation Method, step 2）In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
A kind of system of described poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Preparation Method, step 3）In, bag filter capacity is 5~10 ml, and bag filter molecular cut off is 3500~4500, selective solvent
Using distilled water, solution concentration is 0.1~0.4 mg/ml.
Compared with prior art, its advantage is the present invention：
1st, the preparation of described a kind of poly acrylic acid-poly y-PTMC dual graft copolymer micelle
Method, 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, behaviour
Work is simple, be easy to grasp；
2nd, a kind of described poly acrylic acid-poly y-PTMC dual graft copolymer micelle is a kind of
New pharmaceutical carrier.
Embodiment
Embodiment 1
1）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer
15.2 grams of polyacrylic acid are added in dry reactor（Molecular weight is 53000）, 11.7 grams of hydroxy-end capped PLA second
Alkyd monododecyl ether（Molecular weight is 2200）With 11.7 grams of hydroxy-end capped PTMC list undecyl ethers
（Molecular weight is 2200）, 386 ml dimethyl sulfoxide (DMSO)s are added, 0.075 gram is addedN,N’- dicyclohexylcarbodiimide, indifferent gas
Under atmosphere, in 27 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer stoste
130 milligrams of poly acrylic acid-poly y-PTMC dual graft copolymerization are added in dry reactor
Thing, 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 y-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly y-PTMC dual graft copolymer stoste is added 6
In the bag filter of milliliter capacity（Molecular cut off is 3500）, put it into 500 milliliters of beakers for filling distilled water, every 7
Hour displacement once, is replaced 3 times, and solution shows blue light in bag filter, is then poured into graduated 10 milliliters of volumetric flasks
In, scale is adjusted to distilled water, object is obtained.
Embodiment 2
1）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer
15.4 grams of polyacrylic acid are added in dry reactor（Molecular weight is 55000）, 12.2 grams of hydroxy-end capped PLA second
Alkyd monododecyl ether（Molecular weight is 2300）With 12.2 grams of hydroxy-end capped PTMC list undecyl ethers
（Molecular weight is 2300）, 398 ml dimethyl sulfoxide (DMSO)s are added, 0.044 gram is addedN,N’- DIC, indifferent gas
Under 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 y-PTMC dual graft copolymer stoste
135 milligrams of poly acrylic acid-poly y-PTMC dual graft copolymerization are added in dry reactor
Thing, 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 y-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly y-PTMC dual graft copolymer stoste is added 7
In the bag filter of milliliter capacity（Molecular cut off is 4000）, put it into 500 milliliters of beakers for filling distilled water, every 7
Hour displacement once, is replaced 4 times, and solution shows blue light in bag filter, is then poured into graduated 10 milliliters of volumetric flasks
In, scale is adjusted to distilled water, object is obtained.
Embodiment 3
1）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer
17.5 grams of polyacrylic acid are added in dry reactor（Molecular weight is 63000）, 12.6 grams of hydroxy-end capped PLA second
Alkyd monododecyl ether（Molecular weight is 2400）With 12.6 grams of hydroxy-end capped PTMC list undecyl ethers
（Molecular weight is 2400）, 427 ml dimethyl sulfoxide (DMSO)s are added, 0.066 gram of 3- ethyls -1- is added（3- dimethylaminopropyls）Carbon two
Under imines, inert atmosphere, in 34 DEG C of stirring reactions 3 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer stoste
140 milligrams of poly acrylic acid-poly y-PTMC dual graft copolymerization are added in dry reactor
Thing, 100 milliliters of dimethyl sulfoxide (DMSO)s, in 54 DEG C of stirring and dissolvings 60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly y-PTMC dual graft copolymer stoste is added 8
In the bag filter of milliliter capacity（Molecular cut off is 4500）, put it into 500 milliliters of beakers for filling distilled water, every 7
Hour displacement once, is replaced 3 times, and solution shows blue light in bag filter, is then poured into graduated 10 milliliters of volumetric flasks
In, scale is adjusted to distilled water, object is obtained.
Claims (5)
1. a kind of preparation method of poly acrylic acid-poly y-PTMC dual graft copolymer micelle, its
It is characterised by：The molecular weight of polyacrylic acid segment is 53000~63000, the molecular weight of poly (lactic acid-glycolic acid) segment in copolymer
For 2200~2400, the molecular weight of PTMC segment is 2200~2400；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer：In dry reactor
Add polyacrylic acid, hydroxy-end capped poly (lactic acid-glycolic acid) monododecyl ether, hydroxy-end capped PTMC list
Under undecyl ether, solvent and condensing agent, inert atmosphere, in 27~34 DEG C of stirring reactions 2~3 days, terminating reaction passed through mistake
Filter, dialyse, dry, obtain object；
2）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer stoste：In dry reaction
Poly acrylic acid-poly y-PTMC dual graft copolymer and solvent are added in device, is stirred in 47~54 DEG C
Mix dissolving 50~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly y-PTMC dual graft copolymer micelle：At room temperature, will
Stoste is added in bag filter, is put it into 500 milliliters of beakers for filling selective solvent, every displacement in 7 hours once, displacement
3~4 times, in bag filter solution show blue light, be then poured into in graduated volumetric flask, be adjusted to selective solvent carve
Degree, obtains object.
2. a kind of poly acrylic acid-poly y-PTMC dual graft copolymerization according to claim 1
The preparation method of thing micella, it is characterised in that：Step 1）In, poly (lactic acid-glycolic acid) monododecyl ether is using poly-（D, Pfansteihl）
Glycolic monododecyl ether（The weight ratio of lactic acid and glycolic is 90/10）, poly (lactic acid-glycolic acid) monododecyl ether is with gathering
The mol ratio of acrylic acid is 15~25:1, the mol ratio of PTMC list undecyl ether and polyacrylic acid for 15~
25:1。
3. a kind of poly acrylic acid-poly y-PTMC dual graft according to claim 1 is total to
The preparation method of polymers micella, it is characterised in that：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
1.07~1.8:1, solvent uses dimethyl sulfoxide (DMSO), and reactant solution concentration is 5~15 g/100 ml.
4. a kind of poly acrylic acid-poly y-PTMC dual graft copolymerization according to claim 1
The preparation method of thing micella, 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 y-PTMC dual graft copolymerization according to claim 1
The preparation method of thing micella, 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 0.1~0.4 mg/ml.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376615.8A CN107043459A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710376615.8A CN107043459A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle |
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| CN201710376615.8A Withdrawn CN107043459A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) PTMC dual graft copolymer micelle |
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