CN105315444B - The purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer - Google Patents
The purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer Download PDFInfo
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Abstract
The invention discloses a kind of purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer, it is to dissolve poly glycol monomethyl ether polylactic acid amphiphilic block copolymer water aqueous solution is made, obtained aqueous solution carries out strong acid cation exchange resin column chromatography and uses, water elution, gained eluent filtering with microporous membrane is degerming, freeze-drying, up to the poly glycol monomethyl ether polylactic acid amphiphilic block copolymer of purifying；The purification process can reduce the Theil indices of poly glycol monomethyl ether polylactic acid amphiphilic block copolymer；Improve its physical behavior, improve dissolubility；The redissolution stability using it as polymer micelle lyophilized formulations made of auxiliary material can be improved；Microorganism can also be removed, it is ensured that microorganism is not exceeded.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, is related to a kind of purification process of pharmaceutic adjuvant.
Background technology
Hydrophobic drug increases the routine techniques hand that medicine water solubility is field of pharmaceutical preparations with surface active agent solubilization
Section, as docetaxel can use polyoxyethylene sorbitan monoleate solubilising.But the solubilization method there are high allergy incidence and preparation stability compared with
The shortcomings of poor.Oleic acid as contained in polyoxyethylene sorbitan monoleate has certain anaphylaxis, patient use with more west made of it he
Generally require to carry out desensitization process before match rule agent；And when docetaxel injection and infusion, physiological saline is preferably selected, is matched somebody with somebody
It should use in 120min after good, if with 5% glucose solution compatibility, should be used in 60min.
The security and tumour passive targeting of polymer micelle become a kind of novel targeted delivery system, anti-swollen
There is preferable application prospect in knurl medicine.It is more demanding to heavy metal and microorganism etc. but polymer micelle is ejection preparation.
Polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (mPEG-PDLLA) is at home and abroad to obtain extensive concern in recent years
A kind of new material, it is with amphipathic, critical micelle concentration (CMC) is low, micella particle diameter is small, can hide reticuloendothelial system
(RES) the advantages that phagocytosis, good biocompatibility, larger degradable and drugloading rate, have commodity Genexol-PM in Korea Spro at present
State lists, while Genexol-PM has been enter into III phase clinical researches in the U.S..Polyethylene glycol monomethyl ether-polylactic acid is amphipathic embedding
The existing preparation method of section copolymer is to react poly glycol monomethyl ether, lactide under stannous octoate catalysis poly- second two is made
Alcohol monomethyl ether-polylactic acid amphiphilic block copolymer crude product, then recrystallized with dichloromethane-ether, room temperature in vacuo drying, obtains
Polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product.The preparation method has the following disadvantages：1) tin contains in product
Amount is higher；2) product is white clumpy solid, and particle diameter difference is big, and dissolving is slow in a solvent；3) with polymer made of the product
Micelle freeze-drying preparation redissolution stability is poor, and medicine is separated out from micella quickly, it is difficult to meets the requirement of clinical practice；4) recrystallize
Solvent ether is inflammable explosive article, causes the product to be difficult to be protected in clean GMP Workshop Productions, control of microorganisms,
It is difficult to the preparation for being directly used in freeze-drying preparation for injection.It is amphipathic therefore, it is necessary to study a kind of polyethylene glycol monomethyl ether-polylactic acid
The purification process of block copolymer, so that the above problem is preferably solved.
The content of the invention
In view of this, it is an object of the invention to provide a kind of injection polyethylene glycol monomethyl ether-polylactic acid is amphipathic embedding
The purification process of section copolymer, can reduce the content of tin in product；Improve its physical behavior, improve dissolubility；It can improve
Redissolution stability using it as polymer micelle lyophilized formulations made of auxiliary material；Microorganism can also be removed, it is ensured that microorganism is not
It is exceeded.
Through research, the present invention provides following technical solution：
The purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer, comprises the following steps：Will
Polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer water, which dissolves, is made aqueous solution, and obtained aqueous solution carries out highly acid
Cation exchange resin column chromatography, is eluted with water, and gained eluent filtering with microporous membrane is degerming, freeze-drying, up to purifying
Polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer.
Further, the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer is by poly glycol monomethyl ether, third
Lactide reacts under stannous octoate catalysis is made polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer crude product, and gained is thick
Product are made with dichloromethane-ether mixed solvent recrystallization again.
Further, the average molecular weight of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer for 3000~
6000。
Further, the poly- second two of hydrophilic block in the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer
The average molecular weight of alcohol monomethyl ether is 2000, and the average molecular weight of hydrophobic block polylactic acid is 1000-4000.
Further, the concentration of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer aqueous solution for 0.01~
1g/ml。
Further, the concentration of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer aqueous solution for 0.1~
0.2g/ml。
Further, for the storng-acid cation exchange resin before use by pretreatment, the pretreatment is by strong acid
Property cation exchange resin first use water backwash, remove mechanical admixture, then soluble matter is removed by certain acid, aqueous slkali, finally
Storng-acid cation exchange resin is switched into Hydrogen；The polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer with it is pre-
The amount ratio of storng-acid cation exchange resin after processing is 1g:1~100ml.
Further, the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer and pretreated highly acid
The amount ratio of cation exchange resin is 1g:15~100ml.
The pretreatment of storng-acid cation exchange resin can according to standard method (National Standard of the People's Republic of China, from
Sub-exchange resin preprocess method, GB/T5476-2013) carry out.
Further, the aperture of the miillpore filter is 0.22 μm.
Further, the freeze-drying is in A grades of clean areas as defined in pharmaceutical production quality management practices (GMP) version in 2010
Middle progress.
The beneficial effects of the present invention are：The present invention provides a kind of injection polyethylene glycol monomethyl ether-polylactic acid amphiphilic
The purification process of property block copolymer, can reduce the content of tin in product；Improve its physical behavior, improve dissolubility；Can be with
Improve the redissolution stability using it as polymer micelle lyophilized formulations made of auxiliary material；Microorganism can also be removed, it is ensured that micro- life
Thing is not exceeded.
Embodiment
In order to make the purpose of the present invention, technical solution and beneficial effect clearer, below by the preferred reality of the present invention
Example is applied to be described in detail.The experimental method of actual conditions is not specified in preferred embodiment, usually according to normal condition, or presses
Carried out according to the condition proposed by reagent manufacturer.
Storng-acid cation exchange resin used is big for the D72 of Tianjin Nankai Hecheng S＆T Co., Ltd.'s production in embodiment
Hole strongly acidic styrene type cation exchange resin, using preceding according to standard method (National Standard of the People's Republic of China, ion
Exchanger resin preprocess method, GB/T5476-2013) pre-processed.
Embodiment 1, prepare polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 4000)
By poly glycol monomethyl ether (molecular weight 2000) and lactide vacuum is more than 0.095MPa, temperature is 40 DEG C
Under the conditions of vacuum drying 12 it is small when, it is spare；Weigh poly glycol monomethyl ether (molecular weight 2000) 30g, lactide 30g and octanoic acid is sub-
Tin 0.15ml is added in reaction bulb, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 it is small when；After completion of the reaction, it is cold
But to room temperature, polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer crude product is obtained, by crude product dichloromethane-ether weight
Crystallization, filtration product obtain polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product when room temperature in vacuo drying 72 is small
(white clumpy solid) 52g.
Embodiment 2, prepare polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 3000)
By poly glycol monomethyl ether (molecular weight 2000) and lactide vacuum is more than 0.095MPa, temperature is 40 DEG C
Under the conditions of vacuum drying 12 it is small when, it is spare；Weigh poly glycol monomethyl ether (molecular weight 2000) 30g, lactide 15g and octanoic acid is sub-
Tin 0.15ml is added in reaction bulb, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 it is small when；After completion of the reaction, it is cold
But to room temperature, polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer crude product is obtained, by crude product dichloromethane-ether weight
Crystallization, filtration product obtain polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product when room temperature in vacuo drying 72 is small
(white clumpy solid) 39g.
Embodiment 3:Prepare polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 6000)
By poly glycol monomethyl ether (molecular weight 2000) and lactide vacuum is more than 0.095MPa, temperature is 40 DEG C
Under the conditions of vacuum drying 12 it is small when, it is spare；Weigh poly glycol monomethyl ether (molecular weight 2000) 20g, lactide 40g and octanoic acid is sub-
Tin 0.15ml is added in reaction bulb, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 it is small when；After completion of the reaction, it is cold
But to room temperature, polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer crude product is obtained, by crude product dichloromethane-ether weight
Crystallization, filtration product obtain polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product when room temperature in vacuo drying 72 is small
(white clumpy solid) 42g.
Embodiment 4, purifying polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 4000)
By polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product (average molecular weight made from embodiment 1
4000) 10g is dissolved in deionized water 50ml, and obtained aqueous solution is by the way that equipped with 1000ml storng-acid cation exchange resins, (warp is pre-
Processing) chromatographic column, be washed with deionized water de-, gained eluent aperture is 0.22 μm of filtering with microporous membrane, filtrate freezing
It is dry, obtain the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of purifying.
Take the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of above-mentioned purifying, 1) appearance is visually observed,
Product is white clumpy solid before purification, and product is homogeneous white loose sprills after purification；2) surveyed using atomic absorption method
Fixed output quota product Theil indices, the results show that product Theil indices are 148.7mg/kg before purification；Product Theil indices are less than 10mg/ after purification
kg；3) product after purification is dissolved in 500ml0.9% aseptic sodium chloride solutions, after being handled with membrane-filter procedure, by China
Two annex of pharmacopeia version in 2010, Ⅺ H Sterility Tests are checked, meet regulation.
Embodiment 5, purifying polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 3000)
By polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product (average molecular weight made from embodiment 2
3000) 10g is dissolved in deionized water 100ml, and obtained aqueous solution is by the way that equipped with 150ml storng-acid cation exchange resins, (warp is pre-
Processing) chromatographic column, be washed with deionized water de-, gained eluent aperture is 0.22 μm of filtering with microporous membrane, filtrate freezing
It is dry, obtain the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of purifying.
Take the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of above-mentioned purifying, 1) appearance is visually observed,
Product is white clumpy solid before purification, and product is homogeneous white loose sprills after purification；2) surveyed using atomic absorption method
Fixed output quota product Theil indices, the results show that product Theil indices are 230.4mg/kg before purification；Product Theil indices are less than 10mg/ after purification
kg；3) product after purification is dissolved in 500ml0.9% aseptic sodium chloride solutions, after being handled with membrane-filter procedure, by China
Two annex of pharmacopeia version in 2010, Ⅺ H Sterility Tests are checked, meet regulation.
Embodiment 6, purifying polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (average molecular weight 6000)
By polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product (average molecular weight made from embodiment 3
6000) 10g is dissolved in deionized water 100ml, and obtained aqueous solution is by the way that equipped with 400ml storng-acid cation exchange resins, (warp is pre-
Processing) chromatographic column, be washed with deionized water de-, gained eluent aperture is 0.22 μm of filtering with microporous membrane, filtrate freezing
It is dry, obtain the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of purifying.
Take the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product of above-mentioned purifying, 1) appearance is visually observed,
Product is white clumpy solid before purification, and product is homogeneous white loose sprills after purification；2) surveyed using atomic absorption method
Fixed output quota product Theil indices, the results show that the Theil indices of product are 180.6mg/kg before purification；The Theil indices of product are less than after purification
10mg/kg；3) product after purification is dissolved in 500ml0.9% aseptic sodium chloride solutions, after being handled with membrane-filter procedure,
Checked by two annex of Chinese Pharmacopoeia version in 2010, Ⅺ H Sterility Tests, meet regulation.
Embodiment 7, prepare docetaxel-polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (mass ratio 1:6)
Polymer micelle lyophilized formulations (hereinafter referred to as preparation 001)
Polyethylene glycol monomethyl ether-polylactic acid amphiphilic block made from docetaxel 1g and embodiment 1 is weighed respectively
Produce product 6g, adds methanol 200ml, and 25-30 DEG C of temperature control makes polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer complete
Dissolving；Rotary evaporation removes methanol under conditions of temperature is 30-35 DEG C, vacuum is 0.096MPa again, obtains docetaxel
The polymer gel formed with polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer；Again into resulting polymers gel
Add water 100ml, 30-35 DEG C of formation docetaxel polymer micelle aqueous solution of temperature control, with the miillpore filter mistake that aperture is 0.22 μm
Bacterium is filtered out, it is filling by every bottle of 2ml, freezing drying protective agent is put into after half-dozen plug, freeze-dried 48h obtains polymer micelle and freezes
Dry preparation.
Found in experimentation, polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product made from embodiment 1
About 1h dissolvings in methyl alcohol finish.
Embodiment 8, prepare docetaxel-polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (mass ratio 1:6)
Polymer micelle lyophilized formulations (hereinafter referred to as preparation 002)
The polyethylene glycol monomethyl ether-polylactic acid for weighing docetaxel 1g and the obtained purifying of embodiment 4 respectively is amphipathic embedding
Section copolymer product 6g, adds methanol 200ml, and 25-30 DEG C of temperature control makes polyethylene glycol monomethyl ether-polylactic acid amphiphilic block
Thing is completely dissolved；Rotary evaporation removes methanol under conditions of temperature is 30-35 DEG C, vacuum is 0.096MPa again, obtains more
The polymer gel that Xi Tasai is formed with polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer；Again to resulting polymers
In gel plus water 100ml, 30-35 DEG C of temperature control form docetaxel polymer micelle aqueous solution, with the micropore that aperture is 0.22 μm
Membrane filtration is degerming, filling by every bottle of 2ml, and freezing drying protective agent is put into after half-dozen plug, and freeze-dried 48h obtains polymer
Micelle freeze-drying preparation.
Found in experimentation, the polyethylene glycol monomethyl ether-polylactic acid amphiphilic block of the obtained purifying of embodiment 4
About 10min dissolvings finish produce product in methyl alcohol, illustrate the polyethylene glycol monomethyl ether-polylactic acid amphiphilic purified by the method for the present invention
Property block copolymer product has more preferable dissolubility.
The redissolution study on the stability of embodiment 9, preparation 001 and preparation 002
Preparation 002 made from preparation 001 made from Example 7 and implementation 8, carries out redissolution study on the stability respectively.Knot
Fruit sees Tables 1 and 2, and micro white suspension thing occurs in 0.5h after the redissolution of preparation 001, illustrates that micellar structure is destroyed；And preparation
Just there is micro white suspension thing in 4h after 002 redissolution, illustrates to be total to the amphipathic block of the polyethylene glycol monomethyl ether-polylactic acid of purifying
Polymers has for polymer micelle lyophilized formulations made from auxiliary material preferably redissolves stability.
1 polymer micelle lyophilized formulations of table redissolve study on the stability result 1
2 polymer micelle lyophilized formulations of table redissolve study on the stability result 2
Embodiment 10, prepare Propofol-polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (mass ratio 1:10)
Polymer micelle lyophilized formulations (hereinafter referred to as preparation 003)
Polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer made from Propofol 1g and embodiment 2 is weighed respectively
Product 10g, adds methanol 200ml, and 25-30 DEG C of temperature control makes polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer complete
Dissolving；Again under conditions of temperature is 30-35 DEG C, vacuum is 0.096MPa rotary evaporation remove methanol, obtain Propofol with
The polymer gel that polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer is formed；Add again into resulting polymers gel
Water 100ml, 30-35 DEG C of formation docetaxel polymer micelle aqueous solution of temperature control, with the filtering with microporous membrane that aperture is 0.22 μm
It is degerming, it is filling by every bottle of 2ml, freezing drying protective agent is put into after half-dozen plug, freeze-dried 48h obtains polymer micelle and freezes
Preparation.
Found in experimentation, polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer product made from embodiment 2
About 1h dissolvings in methyl alcohol finish.
Embodiment 11, prepare Propofol-polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer (mass ratio 1:10)
Polymer micelle lyophilized formulations (hereinafter referred to as preparation 004)
Propofol 1g and the amphipathic block of polyethylene glycol monomethyl ether-polylactic acid of the obtained purifying of embodiment 5 are weighed respectively
Copolymer product 10g, adds methanol 200ml, and 25-30 DEG C of temperature control makes polyethylene glycol monomethyl ether-polylactic acid amphiphilic block
Thing is completely dissolved；Rotary evaporation removes methanol under conditions of temperature is 30-35 DEG C, vacuum is 0.096MPa again, obtains third
Moor the polymer gel that phenol is formed with polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer；Coagulated again to resulting polymers
In glue plus water 100ml, 30-35 DEG C of temperature control form docetaxel polymer micelle aqueous solution, are filtered with the micropore that aperture is 0.22 μm
Membrane filtration is degerming, filling by every bottle of 2ml, and freezing drying protective agent is put into after half-dozen plug, and freeze-dried 48h obtains polymer latex
Beam lyophilized formulations.
Found in experimentation, the polyethylene glycol monomethyl ether-polylactic acid amphiphilic block of the obtained purifying of embodiment 5
About 10min dissolvings are complete in methyl alcohol for produce product, illustrate the polyethylene glycol monomethyl ether-polylactic acid amphiphilic purified by the method for the present invention
Property block copolymer product has more preferable dissolubility.
The redissolution study on the stability of embodiment 12, preparation 003 and preparation 004
Preparation 004 made from preparation 003 made from Example 10 and implementation 11, carries out redissolution study on the stability respectively.
3 and table 4 are the results are shown in Table, micro white suspension thing occurs in 0.5h after preparation 003 redissolves, and illustrates that micellar structure is destroyed；And make
Just there is micro white suspension thing in 6h after agent 004 is redissolved, and illustrates with the amphipathic block of the polyethylene glycol monomethyl ether-polylactic acid of purifying
Copolymer has for polymer micelle lyophilized formulations made from auxiliary material preferably redissolves stability.
3 polymer micelle lyophilized formulations of table redissolve study on the stability result 1
4 polymer micelle lyophilized formulations of table redissolve study on the stability result 2
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although logical
Cross above preferred embodiment the present invention is described in detail, however, those skilled in the art should understand that, can be
Various changes are made to it in form and in details, without departing from claims of the present invention limited range.
Claims (8)
1. the purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer, it is characterised in that including with
Lower step：By polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer with water dissolve be made aqueous solution, obtained aqueous solution into
Row strong acid cation exchange resin column chromatographs, and is eluted with water, and gained eluent filtering with microporous membrane is degerming, freeze-drying,
Up to the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer of purifying；The storng-acid cation exchange resin makes
With preceding by pre-processing, the pretreatment is that storng-acid cation exchange resin is first used water backwash, removes mechanical admixture, then lead to
Certain acid, aqueous slkali removing soluble matter are crossed, storng-acid cation exchange resin is finally switched into Hydrogen；The polyethyleneglycol
Methyl ether-polylactic acid amphiphilic block copolymer and the amount ratio of pretreated storng-acid cation exchange resin are 1g:15~
100ml；In the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer of the purifying, Theil indices are less than 10ppm.
2. the purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer as claimed in claim 1,
It is characterized in that, the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer is by poly glycol monomethyl ether, lactide
Reacted under stannous octoate catalysis and polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer crude product is made, gained crude product is again
It is made with dichloromethane-ether mixed solvent recrystallization.
3. the purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer as claimed in claim 2,
It is characterized in that, the average molecular weight of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer is 3000~6000.
4. the purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer as claimed in claim 3,
It is characterized in that, hydrophilic block polyethyleneglycol first in the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer
The average molecular weight of ether is 2000, and the average molecular weight of hydrophobic block polylactic acid is 1000-4000.
5. such as Claims 1-4 any one of them injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer
Purification process, it is characterised in that the concentration of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer aqueous solution is
0.01~1g/ml.
6. the purification process of injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer as claimed in claim 5,
It is characterized in that, the concentration of the polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer aqueous solution is 0.1~0.2g/
ml。
7. such as Claims 1-4 any one of them injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer
Purification process, it is characterised in that the aperture of the miillpore filter is 0.22 μm.
8. such as Claims 1-4 any one of them injection polyethylene glycol monomethyl ether-polylactic acid amphipathic nature block polymer
Purification process, it is characterised in that the freeze-drying is in A grades of clean areas as defined in pharmaceutical production quality management practices version in 2010
Middle progress.
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| CN112972761A (en) * | 2021-02-09 | 2021-06-18 | 长春圣博玛生物材料有限公司 | Injectable filler and injection |
| CN112807486B (en) * | 2021-02-09 | 2024-03-26 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| WO2023082634A1 (en) * | 2021-11-10 | 2023-05-19 | 渼颜空间(河北)生物科技有限公司 | Biodegradable copolymer, and preparation method therefor and use thereof |
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