CN106977740A - A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella - Google Patents
A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella Download PDFInfo
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- CN106977740A CN106977740A CN201710376605.4A CN201710376605A CN106977740A CN 106977740 A CN106977740 A CN 106977740A CN 201710376605 A CN201710376605 A CN 201710376605A CN 106977740 A CN106977740 A CN 106977740A
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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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- 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
- A61K9/10—Dispersions; Emulsions
- 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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- 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
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
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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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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/07—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media from polymer solutions
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- 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
- C08G2230/00—Compositions for preparing biodegradable polymers
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- 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 polylactic acid graft copolymer micella, and its preparation method uses following steps：1）Polyacrylic acid, hydroxy-end capped PLA monododecyl ether, solvent and condensing agent are added in dry reactor, reaction obtains polyacrylic acid polylactic acid graft copolymer；2）Polyacrylic acid polylactic acid graft copolymer and solvent are added in dry reactor, dissolving obtains polyacrylic acid polylactic acid graft copolymer stoste；3）Stoste is added in bag filter, put it into the beaker for filling selective solvent, 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 preparation method of poly acrylic acid-poly lactic acid graft copolymer micella, belong to biodegradable high
Molecular material preparing technical field.
Background technology
Polyacrylic acid is a kind of biomaterial with good biocompatibility and biodegradability, with excellent
Hydrophily, in medicine extensive application.It is poly-（D,L）Lactic acid is with excellent biocompatibility and biodegradable
The biomaterial of property, with good hydrophobicity, is widely used in medicine.Polylactic acid chain segment is grafted to polypropylene
On acid molecule chain obtained by poly acrylic acid-poly lactic acid graft copolymer have it is amphipathic, can be from group in selective solvent
Dress forms micella, is a kind of new pharmaceutical carrier, 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 lactic acid graft copolymer of simple to operate and effect
The preparation method of micella.Its technical scheme is：
A kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella, it is characterised in that：Polyacrylic acid chain in copolymer
The molecular weight of section is 52000~61000, and the molecular weight of polylactic acid chain segment is 2100~2400；Its preparation method uses following step
Suddenly：
1）The preparation of poly acrylic acid-poly lactic acid graft copolymer：Polyacrylic acid is added in dry reactor, it is hydroxy-end capped poly-
Under lactic acid monododecyl ether, solvent and condensing agent, inert atmosphere, in 28~33 DEG C of stirring reactions 2~3 days, terminating reaction was led to
Filter, dialyse, dry, obtain object；
2）The preparation of poly acrylic acid-poly lactic acid graft copolymer stoste：Poly acrylic acid-poly lactic acid is added in dry reactor to connect
Graft copolymer and solvent, in 47~52 DEG C of stirring and dissolvings 40~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly lactic acid graft copolymer micella：At room temperature, stoste is added in bag filter, put it into
In 500 milliliters of beakers for filling selective solvent, every displacement in 8 hours once, replace 3~4 times, solution display is blue in bag filter
Light, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent, obtain object.
A kind of preparation method of described poly acrylic acid-poly lactic acid graft copolymer micella, step 1）In, PLA list ten
Dialkyl ether is using poly-（D, Pfansteihl）The mol ratio of monododecyl ether, PLA monododecyl ether and polyacrylic acid is 15
~25:1.
A kind of preparation method of described poly acrylic acid-poly lactic acid graft copolymer micella, step 1）In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- DIC or 3- ethyls -1-（3- dimethylaminopropyls）Carbodiimide,
The mol ratio of condensing agent and polyacrylic acid is 1.07~1.9:1, solvent uses dimethyl sulfoxide (DMSO), and reactant solution concentration is 5~
15 g/100 ml。
A kind of preparation method of described poly acrylic acid-poly lactic acid graft copolymer micella, step 2）In, solvent uses two
Methyl sulfoxide, original liquid concentration is 1~1.5 mg/ml.
A kind of preparation method of described poly acrylic acid-poly lactic acid graft copolymer micella, step 3）In, bag filter capacity
For 5~10 ml, bag filter molecular cut off is 3500~4500, and selective solvent uses 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 lactic acid graft copolymer micella, using esterification and dialysis
The means being combined, it is simple to operate, be easy to grasp；
2nd, a kind of described poly acrylic acid-poly lactic acid graft copolymer micella is a kind of new pharmaceutical carrier.
Embodiment
Embodiment 1
1）The preparation of poly acrylic acid-poly lactic acid graft copolymer
14.1 grams of polyacrylic acid are added in dry reactor（Molecular weight is 52000）, 10.7 grams of hydroxy-end capped PLA lists
Lauryl ether（Molecular weight is 2100）, 248 milliliters of dimethyl sulfoxide (DMSO)s are added, 0.072 gram is addedN,N’- dicyclohexyl carbon two
Under imines, inert atmosphere, in 28 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid graft copolymer stoste
120 milligrams of poly acrylic acid-poly lactic acid graft copolymers, 100 milliliters of dimethyl sulfoxide (DMSO)s are added in dry reactor, in 47
DEG C stirring and dissolving 40 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid graft copolymer micella
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid graft copolymer stoste is added in the bag filter of 5 milliliters of capacity（Retention point
Son amount is 3500）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 8 hours once, replace 3 times, dialysis
Solution shows blue light in bag, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to scale with distilled water, obtains mesh
Mark thing.
Embodiment 2
1）The preparation of poly acrylic acid-poly lactic acid graft copolymer
15.1 grams of polyacrylic acid are added in dry reactor（Molecular weight is 55000）, 11.2 grams of hydroxy-end capped PLA lists ten
Dialkyl ether（Molecular weight is 2200）, 263 milliliters of dimethyl sulfoxide (DMSO)s are added, 0.045 gram is addedN,N’- diisopropyl carbon two
Under imines, 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 lactic acid graft copolymer stoste
130 milligrams of poly acrylic acid-poly lactic acid graft copolymers, 100 milliliters of dimethyl sulfoxide (DMSO)s are added in dry reactor, in 49
DEG C stirring and dissolving 50 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid graft copolymer micella
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid graft copolymer stoste is added in the bag filter of 6 milliliters of capacity（Retention point
Son amount is 4000）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 8 hours once, replace 4 times, dialysis
Solution shows blue light in bag, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to scale with distilled water, obtains mesh
Mark thing.
Embodiment 3
1）The preparation of poly acrylic acid-poly lactic acid graft copolymer
17.2 grams of polyacrylic acid are added in dry reactor（Molecular weight is 61000）, 12.3 grams of hydroxy-end capped PLA lists ten
Dialkyl ether（Molecular weight is 2400）, 295 ml dimethyl sulfoxide (DMSO)s are added, 0.066 gram of 3- ethyls -1- is added（3- diformazans ammonia third
Base）Under carbodiimide, inert atmosphere, in 33 DEG C of stirring reactions 3 days, terminating reaction by filtering, dialysis, was dried, obtains target
Thing；
2）The preparation of poly acrylic acid-poly lactic acid graft copolymer stoste
140 milligrams of poly acrylic acid-poly lactic acid graft copolymers, 100 milliliters of dimethyl sulfoxide (DMSO)s are added in dry reactor, in 52
DEG C stirring and dissolving 60 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid graft copolymer micella
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid graft copolymer stoste is added in the bag filter of 7 milliliters of capacity（Retention point
Son amount is 4500）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 8 hours once, replace 3 times, dialysis
Solution shows blue light in bag, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to scale with distilled water, obtains mesh
Mark thing.
Claims (5)
1. a kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella, it is characterised in that：Polyacrylic acid in copolymer
The molecular weight of segment is 52000~61000, and the molecular weight of polylactic acid chain segment is 2100~2400；Its preparation method is using following
Step：
1）The preparation of poly acrylic acid-poly lactic acid graft copolymer：Polyacrylic acid is added in dry reactor, it is hydroxy-end capped poly-
Under lactic acid monododecyl ether, solvent and condensing agent, inert atmosphere, in 28~33 DEG C of stirring reactions 2~3 days, terminating reaction was led to
Filter, dialyse, dry, obtain object；
2）The preparation of poly acrylic acid-poly lactic acid graft copolymer stoste：Poly acrylic acid-poly lactic acid is added in dry reactor to connect
Graft copolymer and solvent, in 47~52 DEG C of stirring and dissolvings 40~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly lactic acid graft copolymer micella：At room temperature, stoste is added in bag filter, put it into
In 500 milliliters of beakers for filling selective solvent, every displacement in 8 hours once, replace 3~4 times, solution display is blue in bag filter
Light, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent, obtain object.
2. a kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella according to claim 1, its feature exists
In：Step 1）In, PLA monododecyl ether is using poly-（D, Pfansteihl）Monododecyl ether, PLA monododecyl ether
Mol ratio with polyacrylic acid is 15~25:1.
3. a kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella according to claim 1, its feature
It is：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 1.07~1.9:1, solvent uses dimethyl
Sulfoxide, reactant solution concentration is 5~15 g/100 ml.
4. a kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella according to claim 1, its feature exists
In：Step 2）In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
5. a kind of preparation method of poly acrylic acid-poly lactic acid graft copolymer micella according to claim 1, its feature exists
In：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.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376605.4A CN106977740A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376605.4A CN106977740A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella |
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| CN106977740A true CN106977740A (en) | 2017-07-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710376605.4A Withdrawn CN106977740A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella |
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| CN (1) | CN106977740A (en) |
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2017
- 2017-05-25 CN CN201710376605.4A patent/CN106977740A/en not_active Withdrawn
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Application publication date: 20170725 |