CN107043458A - A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle - Google Patents
A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle Download PDFInfo
- Publication number
- CN107043458A CN107043458A CN201710376614.3A CN201710376614A CN107043458A CN 107043458 A CN107043458 A CN 107043458A CN 201710376614 A CN201710376614 A CN 201710376614A CN 107043458 A CN107043458 A CN 107043458A
- Authority
- CN
- China
- Prior art keywords
- graft copolymer
- poly
- preparation
- dual graft
- acid
- 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.)
- Withdrawn
Links
Classifications
-
- 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
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
- C08G2230/00—Compositions for preparing biodegradable polymers
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Polymers & Plastics (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Polyesters Or Polycarbonates (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
Abstract
The present invention discloses a kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle, using following methods：1）Polyacrylic acid, hydroxy-end capped PLA monododecyl ether, hydroxy-end capped polycaprolactone list undecyl ether, solvent and condensing agent are added in dry reactor, reaction obtains polyacrylic acid polylactic acid poly caprolactone dual graft copolymer；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 preparation method of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, 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.It is poly-（D,L）Lactic acid and polycaprolactone be with excellent biocompatibility and
The biomaterial of biodegradability, has preferable hydrophobicity, is widely used in medicine.By polylactic acid chain segment, gather
Poly acrylic acid-poly lactic acid-polycaprolactone dual graft caprolactone segment is grafted on polyacrylic acid strand simultaneously obtained by is total to
Polymers has amphipathic, and micella can be self-assembly of in selective solvent, is a kind of new pharmaceutical carrier, in medicine and pharmacology
Field has broad application prospects.
The content of the invention
It is an object of the invention to provide a kind of preferable poly acrylic acid-poly lactic acid-polycaprolactone of simple to operate and effect
The preparation method of dual graft copolymer micelle.Its technical scheme is：
A kind of preparation method of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, it is characterised in that：Copolymer
The molecular weight of middle polyacrylic acid segment is 54000~63000, and the molecular weight of polylactic acid chain segment is 2200~2400, polycaprolactone
The molecular weight of segment is 2200~2400；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer：In dry reactor add polyacrylic acid,
Hydroxy-end capped PLA monododecyl ether, hydroxy-end capped polycaprolactone list undecyl ether, solvent and condensing agent, inertia
Under atmosphere, in 28~32 DEG C of stirring reactions 2~3 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste：Polypropylene is added in dry reactor
Acid-PLA-polycaprolactone dual graft copolymer and solvent, in 48~52 DEG C of stirring and dissolvings 50~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle：At room temperature, stoste is added into bag filter
In, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 7 hours once, replace 3~4 times, bag filter
Middle solution shows blue light, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent, obtain target
Thing.
A kind of preparation method of described poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, step 1）
In, PLA monododecyl ether is using poly-（D, Pfansteihl）Monododecyl ether, PLA monododecyl ether and polypropylene
The mol ratio of acid is 15~25:1, the mol ratio of polycaprolactone list undecyl ether and polyacrylic acid is 15~25:1.
A kind of preparation method of described poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, step 1）
In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- DIC or 3- ethyls -1-（3- diformazan ammonia
Propyl group）The mol ratio of carbodiimide, condensing agent and polyacrylic acid is 1.07~1.9:1, solvent uses dimethyl sulfoxide (DMSO), reactant
Solution concentration is 5~15 g/100 ml.
A kind of preparation method of described poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, step 2）
In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
A kind of preparation method of described poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, step 3）
In, bag filter capacity is 5~10 ml, and bag filter molecular cut off is 3500~4500, and selective solvent uses distilled water, molten
Liquid concentration is 0.1~0.4 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-polycaprolactone dual graft copolymer micelle, it is poly- using one kind
The means that compound is combined with the esterification and dialysis that two kinds of different polymeric monomers are carried out simultaneously, it is simple to operate, be easy to grasp；
2nd, a kind of described poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle is a kind of new pharmaceutical carrier.
Embodiment
Embodiment 1
1）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer
15.5 grams of polyacrylic acid are added in dry reactor（Molecular weight is 54000）, 11.7 grams of hydroxy-end capped PLA lists
Lauryl ether（Molecular weight is 2200）With 11.7 grams of hydroxy-end capped polycaprolactone list undecyl ethers（Molecular weight is 2200）,
390 ml dimethyl sulfoxide (DMSO)s are added, 0.075 gram is addedN,N’Under-dicyclohexylcarbodiimide, inert atmosphere, in 28 DEG C of stirrings
Reaction 2 days, terminating reaction by filtering, dialysis, is dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste
130 milligrams of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymers, 100 milliliters of diformazans are added in dry reactor
Base sulfoxide, in 48 DEG C of stirring and dissolvings 50 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste is added to the dialysis of 6 milliliters of capacity
In bag（Molecular cut off is 3500）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 7 hours once, put
Change 3 times, solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to distilled water
Scale, obtains object.
Embodiment 2
1）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone 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 lists
Lauryl ether（Molecular weight is 2300）With 12.2 grams of hydroxy-end capped polycaprolactone list undecyl ethers（Molecular weight is 2300）,
398 ml dimethyl sulfoxide (DMSO)s are added, 0.044 gram is addedN,N’Under-DIC, inert atmosphere, in 30 DEG C of stirrings
Reaction 2 days, terminating reaction by filtering, dialysis, is dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste
140 milligrams of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymers, 100 milliliters of diformazans are added in dry reactor
Base sulfoxide, in 50 DEG C of stirring and dissolvings 55 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste is added to the dialysis of 7 milliliters of capacity
In bag（Molecular cut off is 4000）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 7 hours once, put
Change 4 times, solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to distilled water
Scale, obtains object.
Embodiment 3
1）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer
17.6 grams of polyacrylic acid are added in dry reactor（Molecular weight is 63000）, 12.6 grams of hydroxy-end capped PLA lists
Lauryl ether（Molecular weight is 2400）With 12.6 grams of hydroxy-end capped polycaprolactone list undecyl ethers（Molecular weight is 2400）,
428 ml dimethyl sulfoxide (DMSO)s are added, 0.066 gram of 3- ethyls -1- is added（3- dimethylaminopropyls）Under carbodiimide, inert atmosphere,
In 32 DEG C of stirring reactions 3 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste
145 milligrams of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymers, 100 milliliters of diformazans are added in dry reactor
Base sulfoxide, in 52 DEG C of stirring and dissolvings 60 minutes, obtains object；
3）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle
At room temperature, 1 milliliter of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste is added to the dialysis of 8 milliliters of capacity
In bag（Molecular cut off is 4500）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 7 hours once, put
Change 3 times, solution shows blue light in bag filter, is then poured into in graduated 10 milliliters of volumetric flasks, is adjusted to distilled water
Scale, obtains object.
Claims (5)
1. a kind of preparation method of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle, it is characterised in that：Copolymerization
The molecular weight of polyacrylic acid segment is 54000~63000 in thing, and the molecular weight of polylactic acid chain segment is 2200~2400, is gathered in oneself
The molecular weight of ester segment is 2200~2400；Its preparation method is as follows：
1）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer：In dry reactor add polyacrylic acid,
Hydroxy-end capped PLA monododecyl ether, hydroxy-end capped polycaprolactone list undecyl ether, solvent and condensing agent, inertia
Under atmosphere, in 28~32 DEG C of stirring reactions 2~3 days, terminating reaction by filtering, dialysis, was dried, obtains object；
2）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer stoste：Polypropylene is added in dry reactor
Acid-PLA-polycaprolactone dual graft copolymer and solvent, in 48~52 DEG C of stirring and dissolvings 50~60 minutes, obtain object；
3）The preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle：At room temperature, stoste is added into bag filter
In, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 7 hours once, replace 3~4 times, bag filter
Middle solution shows blue light, is then poured into in graduated volumetric flask, scale is adjusted to selective solvent, obtain target
Thing.
2. a kind of preparation side of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle according to claim 1
Method, it is characterised in that：Step 1）In, PLA monododecyl ether is using poly-（D, Pfansteihl）Monododecyl ether, PLA
The mol ratio of monododecyl ether and polyacrylic acid is 15~25:1, mole of polycaprolactone list undecyl ether and polyacrylic acid
Than for 15~25:1.
3. a kind of preparation of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle according to claim 1
Method, it is characterised in that：Step 1）In, condensing agent is usedN,N’- dicyclohexylcarbodiimide,N,N’- diisopropyl carbon two is sub-
Amine or 3- ethyls -1-（3- dimethylaminopropyls）The mol ratio of carbodiimide, condensing agent and polyacrylic acid is 1.07~1.9:1, it is molten
Agent uses dimethyl sulfoxide (DMSO), and reactant solution concentration is 5~15 g/100 ml.
4. a kind of preparation side of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle according to claim 1
Method, 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 preparation side of poly acrylic acid-poly lactic acid-polycaprolactone dual graft copolymer micelle according to claim 1
Method, it is characterised in that：Step 3）In, bag filter capacity is 5~10 ml, and bag filter molecular cut off is 3500~4500, selection
Property solvent use distilled water, solution concentration is 0.1~0.4 mg/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376614.3A CN107043458A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710376614.3A CN107043458A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107043458A true CN107043458A (en) | 2017-08-15 |
Family
ID=59547060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710376614.3A Withdrawn CN107043458A (en) | 2017-05-25 | 2017-05-25 | A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107043458A (en) |
-
2017
- 2017-05-25 CN CN201710376614.3A patent/CN107043458A/en not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105622963A (en) | Preparation method for polyvinyl alcohol-poly (p-dioxanone)-poly lactic acid-glycolic acid double-grafted copolymer micellae | |
| CN105754110A (en) | Preparation method of a polyvinyl alcohol-polycaprolactone-poly lactic acid-glycolic acid dual-grafted copolymer micelle | |
| CN107043458A (en) | A kind of preparation method of polyacrylic acid polylactic acid poly caprolactone dual graft copolymer micelle | |
| CN107118362A (en) | A kind of preparation method of polyacrylic acid polycaprolactone MPEGPLA copolymer micelles | |
| CN106986996A (en) | A kind of polyacrylic acid polycaprolactone gathers（Lactide glycolide）The preparation method of copolymer micelle | |
| CN106977743A (en) | A kind of preparation method of polyacrylic acid polycaprolactone MPEGPLA dual graft copolymer micelles | |
| CN107118364A (en) | A kind of preparation method of polyacrylic acid PTMC copolymer of poly lactic acid micella | |
| CN107011520A (en) | A kind of preparation method of polyacrylic acid polylactic acid poly Lanthanum Isopropoxide dual graft copolymer micelle | |
| CN107011519A (en) | A kind of method for preparing polyacrylic acid polycaprolactone PTMC copolymer of poly lactic acid micella | |
| CN106977739A (en) | A kind of polyacrylic acid gathers（Lactide glycolide）The preparation method of graft copolymer micella | |
| CN107057075A (en) | A kind of preparation method of polyacrylic acid poly (lactic acid-glycolic acid) polycaprolactone dual graft copolymer micelle | |
| CN106986999A (en) | A kind of method for preparing polyacrylic acid PTMC MPEGPLA copolymer micelles | |
| CN106977729A (en) | A kind of method for preparing polyacrylic acid PPDO MPEGPLA copolymer micelles | |
| CN107011517A (en) | A kind of preparation method of polyacrylic acid polylactic acid poly trimethylene carbonate dual graft copolymer micelle | |
| CN106986995A (en) | A kind of preparation method of polyacrylic acid PPDO copolymer of poly lactic acid micella | |
| CN106977737A (en) | A kind of preparation method of polyacrylic acid polycaprolactone PTMC copolymer of poly lactic acid micella | |
| CN107118366A (en) | A kind of preparation method of polyacrylic acid PTMC graft copolymer micella | |
| CN107057073A (en) | A kind of method for preparing polyacrylic acid PPDO copolymer of poly lactic acid micella | |
| CN106977733A (en) | A kind of method for preparing polyacrylic acid PTMC copolymer of poly lactic acid micella | |
| CN106986997A (en) | A kind of method for preparing polyacrylic acid polycaprolactone copolymer of poly lactic acid micella | |
| CN106977740A (en) | A kind of preparation method of polyacrylic acid polylactic acid graft copolymer micella | |
| CN107033362A (en) | A kind of method for preparing polyacrylic acid polycaprolactone PTMC copolymer micelle | |
| CN107118363A (en) | A kind of preparation method of polyacrylic acid polycaprolactone copolymer of poly lactic acid micella | |
| CN106977734A (en) | One kind prepares polyacrylic acid polycaprolactone and gathered（Lactide glycolide）The method of copolymer micelle | |
| CN106987000A (en) | A kind of preparation method of polyacrylic acid polycaprolactone PPDO copolymer micelle |
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 | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20170815 |
|
| WW01 | Invention patent application withdrawn after publication |