CN106977739A - A kind of polyacrylic acid gathers（Lactide glycolide）The preparation method of graft copolymer micella - Google Patents

A kind of polyacrylic acid gathers（Lactide glycolide）The preparation method of graft copolymer micella Download PDF

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Publication number
CN106977739A
CN106977739A CN201710376604.XA CN201710376604A CN106977739A CN 106977739 A CN106977739 A CN 106977739A CN 201710376604 A CN201710376604 A CN 201710376604A CN 106977739 A CN106977739 A CN 106977739A
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poly
graft copolymer
preparation
lactide coglycolide
acrylic acid
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朱国全
林治涛
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Shandong University of Technology
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Shandong University of Technology
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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
    • 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
    • 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
    • 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

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
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  • Polyesters Or Polycarbonates (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention discloses a kind of polyacrylic acid and gathered（Lactide glycolide）The preparation method of graft copolymer micella, its preparation method uses following steps：1）Polyacrylic acid is added in dry reactor, it is hydroxy-end capped poly-（Lactide glycolide）Monododecyl ether, solvent and condensing agent, reaction obtain polyacrylic acid and gathered（Lactide glycolide）Graft copolymer；2）Graft copolymer and solvent are added in dry reactor, dissolving obtains graft copolymer stoste；3）Stoste is added in bag filter, is put 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

A kind of poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella Method
Technical field
The present invention relates to a kind of poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, 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.It is poly-（Lactide coglycolide）（The weight ratio of lactide and glycolide is 90/ 10）It is the biomaterial with excellent biocompatibility and biodegradability, has good hydrophobicity, in medicine It is widely used.Will be poly-（Lactide coglycolide）Segment is grafted to poly acrylic acid-poly resulting on polyacrylic acid strand （Lactide coglycolide）Graft copolymer has amphipathic, and micella can be self-assembly of in selective solvent, is a kind of new The pharmaceutical carrier of type, has 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 of simple to operate and effect（Lactide-second is handed over Ester）The preparation method of graft copolymer micella.Its technical scheme is：
A kind of poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, it is characterised in that：Copolymer The molecular weight of middle polyacrylic acid segment is 51000~61000, is gathered（Lactide coglycolide）The molecular weight of segment be 2300~ 2400；Its preparation method uses following steps：
1）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer：In dry reactor add polyacrylic acid, Hydroxy-end capped is poly-（Lactide coglycolide）Under monododecyl ether, solvent and condensing agent, inert atmosphere, stirred in 27~33 DEG C Mix reaction 2~3 days, terminating reaction by filtering, dialysis, is dried, obtains object；
2）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer stoste：Polypropylene is added in dry reactor Acid-poly-（Lactide coglycolide）Graft copolymer and solvent, in 46~52 DEG C of stirring and dissolvings 40~60 minutes, obtain object；
3）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella：At room temperature, stoste is added into bag filter In, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 8 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 described poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, step 1） In, gather（Lactide coglycolide）Monododecyl ether is using poly-（D, L- lactide coglycolide）Monododecyl ether（Lactide Weight ratio with glycolide is 90/10）, gather（Lactide coglycolide）The mol ratio of monododecyl ether and polyacrylic acid is 15 ~25:1.
A kind of described poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, 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 1.08~1.8:1, solvent uses dimethyl sulfoxide (DMSO), reactant Solution concentration is 5~15 g/100 ml.
A kind of described poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, step 2） In, solvent uses dimethyl sulfoxide (DMSO), and original liquid concentration is 1~1.5 mg/ml.
A kind of described poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, 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 0.1~0.3 mg/ml.
Compared with prior art, its advantage is the present invention：
1st, described a kind of poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, it is anti-using esterification The means that should be combined with dialysis, it is simple to operate, be easy to grasp；
2nd, described a kind of poly acrylic acid-poly（Lactide coglycolide）Graft copolymer micella is a kind of new pharmaceutical carrier.
Embodiment
Embodiment 1
1）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer
14.6 grams of polyacrylic acid are added in dry reactor（Molecular weight is 51000）, 12.1 grams it is hydroxy-end capped poly-（Third hands over Ester-glycolide）Monododecyl ether（Molecular weight is 2300）, 267 milliliters of dimethyl sulfoxide (DMSO)s are added, 0.076 gram is addedN, N’Under-dicyclohexylcarbodiimide, inert atmosphere, in 27 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, Obtain object；
2）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer stoste
120 milligrams of poly acrylic acid-polies are added in dry reactor（Lactide coglycolide）Graft copolymer, 100 milliliters of diformazans Base sulfoxide, in 46 DEG C of stirring and dissolvings 40 minutes, obtains object；
3）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella
At room temperature, by 1 milliliter of poly acrylic acid-poly（Lactide coglycolide）Graft copolymer stoste adds the dialysis of 5 milliliters of capacity In bag（Molecular cut off is 3500）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 8 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）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer
15.7 grams of polyacrylic acid are added in dry reactor（Molecular weight is 55000）, 12.5 grams it is hydroxy-end capped poly-（Third hands over Ester-glycolide）Monododecyl ether（Molecular weight is 2300）, 282 milliliters of dimethyl sulfoxide (DMSO)s are added, 0.046 gram is addedN, N’Under-DIC, inert atmosphere, in 30 DEG C of stirring reactions 2 days, terminating reaction by filtering, dialysis, was dried, Obtain object；
2）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer stoste
130 milligrams of poly acrylic acid-polies are added in dry reactor（Lactide coglycolide）Graft copolymer, 100 milliliters of diformazans Base sulfoxide, in 49 DEG C of stirring and dissolvings 50 minutes, obtains object；
3）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella
At room temperature, by 1 milliliter of poly acrylic acid-poly（Lactide coglycolide）Graft copolymer stoste adds the dialysis of 6 milliliters of capacity In bag（Molecular cut off is 4000）, put it into 500 milliliters of beakers for filling distilled water, every displacement in 8 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）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer
17 grams of polyacrylic acid are added in dry reactor（Molecular weight is 61000）, 12.6 grams it is hydroxy-end capped poly-（Lactide- Glycolide）Monododecyl ether（Molecular weight is 2400）, 296 ml dimethyl sulfoxide (DMSO)s are added, 0.066 gram of 3- ethyls -1- is added （3- dimethylaminopropyls）Under carbodiimide, inert atmosphere, in 33 DEG C of stirring reactions 3 days, terminating reaction, by filtering, dialysis, dry It is dry, obtain object；
2）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer stoste
140 milligrams of poly acrylic acid-polies are added in dry reactor（Lactide coglycolide）Graft copolymer, 100 milliliters of diformazans Base sulfoxide, in 52 DEG C of stirring and dissolvings 60 minutes, obtains object；
3）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella
At room temperature, by 1 milliliter of poly acrylic acid-poly（Lactide coglycolide）Graft copolymer stoste adds 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 8 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 poly acrylic acid-poly（Lactide coglycolide）The preparation method of graft copolymer micella, it is characterised in that：Copolymerization The molecular weight of polyacrylic acid segment is 51000~61000 in thing, is gathered（Lactide coglycolide）The molecular weight of segment be 2300~ 2400；Its preparation method uses following steps：
1）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer：In dry reactor add polyacrylic acid, Hydroxy-end capped is poly-（Lactide coglycolide）Under monododecyl ether, solvent and condensing agent, inert atmosphere, stirred in 27~33 DEG C Mix reaction 2~3 days, terminating reaction by filtering, dialysis, is dried, obtains object；
2）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer stoste：Polypropylene is added in dry reactor Acid-poly-（Lactide coglycolide）Graft copolymer and solvent, in 46~52 DEG C of stirring and dissolvings 40~60 minutes, obtain object；
3）Poly acrylic acid-poly（Lactide coglycolide）The preparation of graft copolymer micella：At room temperature, stoste is added into bag filter In, put it into 500 milliliters of beakers for filling selective solvent, every displacement in 8 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 poly acrylic acid-poly according to claim 1（Lactide coglycolide）The preparation side of graft copolymer micella Method, it is characterised in that：Step 1）In, gather（Lactide coglycolide）Monododecyl ether is using poly-（D, L- lactide coglycolide） Monododecyl ether（The weight ratio of lactide and glycolide is 90/10）, gather（Lactide coglycolide）Monododecyl ether is with gathering The mol ratio of acrylic acid is 15~25:1.
3. a kind of poly acrylic acid-poly according to claim 1（Lactide coglycolide）The preparation of graft copolymer micella 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 1.08~1.8:1, it is molten Agent uses dimethyl sulfoxide (DMSO), and reactant solution concentration is 5~15 g/100 ml.
4. a kind of poly acrylic acid-poly according to claim 1（Lactide coglycolide）The preparation side of graft copolymer micella 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 poly acrylic acid-poly according to claim 1（Lactide coglycolide）The preparation side of graft copolymer micella 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 0.1~0.3 mg/ml.
CN201710376604.XA 2017-05-25 2017-05-25 A kind of polyacrylic acid gathers（Lactide glycolide）The preparation method of graft copolymer micella Withdrawn CN106977739A (en)

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