CN105315444A - Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer for injection - Google Patents
Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer for injection Download PDFInfo
- Publication number
- CN105315444A CN105315444A CN201410339428.9A CN201410339428A CN105315444A CN 105315444 A CN105315444 A CN 105315444A CN 201410339428 A CN201410339428 A CN 201410339428A CN 105315444 A CN105315444 A CN 105315444A
- Authority
- CN
- China
- Prior art keywords
- pla
- mpeg
- block polymer
- amphipathic nature
- nature block
- 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.)
- Granted
Links
Abstract
The invention discloses a purification method of a polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer for injection. The purification method comprises the following steps: dissolving polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer by water to prepare a water solution, making the water solution go through a strong acid cation exchange resin column to carry out chromatography, eluting the column by water, then filtering the eluent by a microporous filter membrane, sterilizing the eluent, freeze-drying the eluent so as to obtain purified polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer. The provided purification method can reduced the content of tin in polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer, and can improve the physical properties and solubility of the segmented copolymer. Moreover, the re-dissolution stability of a polymer micelle freeze-dried preparation, whose auxiliary material is the segmented copolymer, can be improved, the microbes can also be eliminated, and the microbes in the segmented copolymer will not exceed the standard.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, relate to a kind of purification process of pharmaceutical excipient.
Background technology
It is the routine techniques means of field of pharmaceutical preparations that hydrophobic drug increases medicine water-soluble with surface active agent solubilization, as docetaxel can use Polysorbate 80 solubilising.But the shortcoming such as this solubilizing method exists high irritated incidence and preparation stability is poor.Oleic acid as contained in Polysorbate 80 has certain supersensitivity, and patient goes to toward needing to carry out desensitization process in use with its docetaxel injecta made; And when docetaxel injection and infusion, preferably select physiological saline, should use in 120min after preparing, if with 5% glucose solution compatibility, then should use in 60min.
The security of polymer micelle and tumour passive targeting become a kind of novel targeted drug delivery system, have good application prospect in antitumour drug.But polymer micelle is injection formulations, heavy metal and microorganism etc. require higher.MPEG-PLA amphipathic nature block polymer (mPEG-PDLLA) is a kind of novel material obtaining extensive concern in recent years at home and abroad, its have amphipathic, micelle-forming concentration (CMC) is low, micella particle diameter is little, can hide the engulfing of reticuloendothelial system (RES), good biocompatibility, degradable and the advantage such as drug loading is larger, existing commodity Genexol-PM is in Korean market at present, and Genexol-PM has entered III phase clinical study in the U.S. simultaneously.Poly glycol monomethyl ether, rac-Lactide are reacted obtained MPEG-PLA amphipathic nature block polymer crude product by the existing preparation method of MPEG-PLA amphipathic nature block polymer under stannous octoate catalysis, use dichloromethane-ether recrystallization again, room temperature in vacuo is dry, obtains MPEG-PLA amphipathic nature block polymer product.There is following shortcoming in this preparation method: 1) in product, Theil indices is higher; 2) product is white clumpy solid, and particle diameter difference is large, dissolves slow in a solvent; 3) with the polymer micelle freeze-dried preparation redissolution poor stability that this product is made, medicine is very fast separates out from micella, is difficult to the requirement meeting clinical application; 4) recrystallization solvent ether is inflammable explosive article, and cause this product to be difficult in clean GMP Workshop Production, microbiological manipulation can not be protected, and is difficult to the preparation being directly used in freeze-drying preparation for injection.Therefore, need the purification process studying a kind of MPEG-PLA amphipathic nature block polymer, solved preferably to make the problems referred to above.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of purification process of injection MPEG-PLA amphipathic nature block polymer, the content of tin in product can be reduced; Improve its physical behavior, improve solvability; Can improve with the redissolution stability of its polymer micelle freeze-dried preparation made for auxiliary material; Can also microorganism be removed, guarantee that microorganism does not exceed standard.
After deliberation, the invention provides following technical scheme:
The purification process of injection MPEG-PLA amphipathic nature block polymer, comprise the following steps: MPEG-PLA amphipathic nature block polymer water dissolution is obtained the aqueous solution, obtained aqueous solution carries out strong acid cation exchange resin column chromatography, wash with water, gained elutriant filtering with microporous membrane is degerming, lyophilize, obtains the MPEG-PLA amphipathic nature block polymer of purifying.
Further, described MPEG-PLA amphipathic nature block polymer poly glycol monomethyl ether, rac-Lactide is reacted under stannous octoate catalysis obtained MPEG-PLA amphipathic nature block polymer crude product, and gained crude product obtains with dichloromethane-ether mixed solvent recrystallization again.
Further, the molecular-weight average of described MPEG-PLA amphipathic nature block polymer is 3000 ~ 6000.
Further, in described MPEG-PLA amphipathic nature block polymer, the molecular-weight average of hydrophilic block poly glycol monomethyl ether is 2000, and the molecular-weight average of hydrophobic block poly(lactic acid) is 1000-4000.
Further, the concentration of the described MPEG-PLA amphipathic nature block polymer aqueous solution is 0.01 ~ 1g/ml.
Further, the concentration of the described MPEG-PLA amphipathic nature block polymer aqueous solution is 0.1 ~ 0.2g/ml.
Further, described storng-acid cation exchange resin is before use through pre-treatment, and described pre-treatment is that storng-acid cation exchange resin is first used water backwash, removing mechanical impurity, again by certain acid, alkaline solution removing solvend, finally transfer storng-acid cation exchange resin to Hydrogen; The amount ratio of described MPEG-PLA amphipathic nature block polymer and pretreated storng-acid cation exchange resin is 1g:1 ~ 100ml.
Further, the amount ratio of described MPEG-PLA amphipathic nature block polymer and pretreated storng-acid cation exchange resin is 1g:15 ~ 100ml.
The pre-treatment of storng-acid cation exchange resin can be carried out according to standard method (National Standard of the People's Republic of China, ion exchange resin pretreatment process, GB/T5476-2013).
Further, the aperture of described millipore filtration is 0.22 μm.
Further, described lyophilize is carried out in the A level clean area that Good Manufacturing Practice and Quality Control of Drug (GMP) version in 2010 specifies.
Beneficial effect of the present invention is: the purification process that the invention provides a kind of injection MPEG-PLA amphipathic nature block polymer, can reduce the content of tin in product; Improve its physical behavior, improve solvability; Can improve with the redissolution stability of its polymer micelle freeze-dried preparation made for auxiliary material; Can also microorganism be removed, guarantee that microorganism does not exceed standard.
Embodiment
In order to make object of the present invention, technical scheme and beneficial effect clearly, will be described in detail the preferred embodiments of the present invention below.The experimental technique of unreceipted actual conditions in preferred embodiment, usually conveniently condition, or carry out according to the condition that reagent manufacturer advises.
In embodiment, storng-acid cation exchange resin used is the D72 large hole strong acid styrene system cation exchange resin that Tianjin Nankai Hecheng S&T Co., Ltd. produces, according to standard method (National Standard of the People's Republic of China before using, ion exchange resin pretreatment process, GB/T5476-2013) carry out pre-treatment.
Embodiment 1, prepare MPEG-PLA amphipathic nature block polymer (molecular-weight average 4000)
Poly glycol monomethyl ether (molecular weight 2000) and rac-Lactide are greater than 0.095MPa in vacuum tightness, temperature is vacuum-drying 12 hours under the condition of 40 DEG C, for subsequent use; Take poly glycol monomethyl ether (molecular weight 2000) 30g, rac-Lactide 30g and stannous octoate 0.15ml joins in reaction flask, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 hours; After completion of the reaction, be cooled to room temperature, obtain MPEG-PLA amphipathic nature block polymer crude product, crude product is used dichloromethane-ether recrystallization, filter product in room temperature in vacuo drying 72 hours, obtain MPEG-PLA amphipathic nature block polymer product (white clumpy solid) 52g.
Embodiment 2, prepare MPEG-PLA amphipathic nature block polymer (molecular-weight average 3000)
Poly glycol monomethyl ether (molecular weight 2000) and rac-Lactide are greater than 0.095MPa in vacuum tightness, temperature is vacuum-drying 12 hours under the condition of 40 DEG C, for subsequent use; Take poly glycol monomethyl ether (molecular weight 2000) 30g, rac-Lactide 15g and stannous octoate 0.15ml joins in reaction flask, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 hours; After completion of the reaction, be cooled to room temperature, obtain MPEG-PLA amphipathic nature block polymer crude product, crude product is used dichloromethane-ether recrystallization, filter product in room temperature in vacuo drying 72 hours, obtain MPEG-PLA amphipathic nature block polymer product (white clumpy solid) 39g.
Embodiment 3: prepare MPEG-PLA amphipathic nature block polymer (molecular-weight average 6000)
Poly glycol monomethyl ether (molecular weight 2000) and rac-Lactide are greater than 0.095MPa in vacuum tightness, temperature is vacuum-drying 12 hours under the condition of 40 DEG C, for subsequent use; Take poly glycol monomethyl ether (molecular weight 2000) 20g, rac-Lactide 40g and stannous octoate 0.15ml joins in reaction flask, repeatedly inflated with nitrogen, vacuumize, then be warming up to 140 DEG C reaction 6 hours; After completion of the reaction, be cooled to room temperature, obtain MPEG-PLA amphipathic nature block polymer crude product, crude product is used dichloromethane-ether recrystallization, filter product in room temperature in vacuo drying 72 hours, obtain MPEG-PLA amphipathic nature block polymer product (white clumpy solid) 42g.
Embodiment 4, purifying MPEG-PLA amphipathic nature block polymer (molecular-weight average 4000)
MPEG-PLA amphipathic nature block polymer product (molecular-weight average 4000) 10g obtained for embodiment 1 is dissolved in deionized water 50ml, obtained aqueous solution is by being equipped with the chromatography column of 1000ml storng-acid cation exchange resin (through pre-treatment), use deionized water wash-out, gained elutriant aperture is the filtering with microporous membrane of 0.22 μm, filtrate lyophilize, obtains the MPEG-PLA amphipathic nature block polymer product of purifying.
Get the MPEG-PLA amphipathic nature block polymer product of above-mentioned purifying, 1) visual inspection outward appearance, before purifying, product is white clumpy solid, and after purifying, product is homogeneous white loose sprills; 2) use aas determination product Theil indices, result shows, and before purifying, product Theil indices is 148.7mg/kg; After purifying, product Theil indices is less than 10mg/kg; 3) product after purifying is dissolved in 500ml0.9% aseptic sodium chloride solution, after membrane-filter procedure process, checks by Chinese Pharmacopoeia version in 2010 two annex Ⅺ H Sterility Tests, conform with the regulations.
Embodiment 5, purifying MPEG-PLA amphipathic nature block polymer (molecular-weight average 3000)
MPEG-PLA amphipathic nature block polymer product (molecular-weight average 3000) 10g obtained for embodiment 2 is dissolved in deionized water 100ml, obtained aqueous solution is by being equipped with the chromatography column of 150ml storng-acid cation exchange resin (through pre-treatment), use deionized water wash-out, gained elutriant aperture is the filtering with microporous membrane of 0.22 μm, filtrate lyophilize, obtains the MPEG-PLA amphipathic nature block polymer product of purifying.
Get the MPEG-PLA amphipathic nature block polymer product of above-mentioned purifying, 1) visual inspection outward appearance, before purifying, product is white clumpy solid, and after purifying, product is homogeneous white loose sprills; 2) use aas determination product Theil indices, result shows, and before purifying, product Theil indices is 230.4mg/kg; After purifying, product Theil indices is less than 10mg/kg; 3) product after purifying is dissolved in 500ml0.9% aseptic sodium chloride solution, after membrane-filter procedure process, checks by Chinese Pharmacopoeia version in 2010 two annex Ⅺ H Sterility Tests, conform with the regulations.
Embodiment 6, purifying MPEG-PLA amphipathic nature block polymer (molecular-weight average 6000)
MPEG-PLA amphipathic nature block polymer product (molecular-weight average 6000) 10g obtained for embodiment 3 is dissolved in deionized water 100ml, obtained aqueous solution is by being equipped with the chromatography column of 400ml storng-acid cation exchange resin (through pre-treatment), use deionized water wash-out, gained elutriant aperture is the filtering with microporous membrane of 0.22 μm, filtrate lyophilize, obtains the MPEG-PLA amphipathic nature block polymer product of purifying.
Get the MPEG-PLA amphipathic nature block polymer product of above-mentioned purifying, 1) visual inspection outward appearance, before purifying, product is white clumpy solid, and after purifying, product is homogeneous white loose sprills; 2) use aas determination product Theil indices, result shows, and before purifying, the Theil indices of product is 180.6mg/kg; After purifying, the Theil indices of product is less than 10mg/kg; 3) product after purifying is dissolved in 500ml0.9% aseptic sodium chloride solution, after membrane-filter procedure process, checks by Chinese Pharmacopoeia version in 2010 two annex Ⅺ H Sterility Tests, conform with the regulations.
Embodiment 7, prepare docetaxel-MPEG-PLA amphipathic nature block polymer (mass ratio 1:6) polymer micelle freeze-dried preparation (hereinafter referred to as preparation 001)
Take docetaxel 1g and the obtained MPEG-PLA amphipathic nature block polymer product 6g of embodiment 1 respectively, add methyl alcohol 200ml, temperature control 25-30 DEG C makes MPEG-PLA amphipathic nature block polymer dissolve completely; Again temperature be 30-35 DEG C, vacuum tightness rotates evaporative removal methyl alcohol under being the condition of 0.096MPa, obtains the polymer gel that docetaxel and MPEG-PLA amphipathic nature block polymer are formed; Add water 100ml again in resulting polymers gel; temperature control 30-35 DEG C forms the docetaxel polymer micelle aqueous solution; be that the filtering with microporous membrane of 0.22 μm is degerming with aperture; filling by every bottle of 2ml; put into freezing drying protective agent after half-dozen plug, obtain polymer micelle freeze-dried preparation through lyophilize 48h.
Find in experimentation, the MPEG-PLA amphipathic nature block polymer product that embodiment 1 obtains about 1h in methyl alcohol dissolves complete.
Embodiment 8, prepare docetaxel-MPEG-PLA amphipathic nature block polymer (mass ratio 1:6) polymer micelle freeze-dried preparation (hereinafter referred to as preparation 002)
Take the MPEG-PLA amphipathic nature block polymer product 6g of docetaxel 1g and the obtained purifying of embodiment 4 respectively, add methyl alcohol 200ml, temperature control 25-30 DEG C makes MPEG-PLA amphipathic nature block polymer dissolve completely; Again temperature be 30-35 DEG C, vacuum tightness rotates evaporative removal methyl alcohol under being the condition of 0.096MPa, obtains the polymer gel that docetaxel and MPEG-PLA amphipathic nature block polymer are formed; Add water 100ml again in resulting polymers gel; temperature control 30-35 DEG C forms the docetaxel polymer micelle aqueous solution; be that the filtering with microporous membrane of 0.22 μm is degerming with aperture; filling by every bottle of 2ml; put into freezing drying protective agent after half-dozen plug, obtain polymer micelle freeze-dried preparation through lyophilize 48h.
Find in experimentation, MPEG-PLA amphipathic nature block polymer product about 10min in methyl alcohol of the purifying that embodiment 4 is obtained dissolves complete, illustrates to have better solvability by the MPEG-PLA amphipathic nature block polymer product of the inventive method purifying.
The redissolution study on the stability of embodiment 9, preparation 001 and preparation 002
The preparation 001 that Example 7 is obtained and the preparations 002 that enforcement 8 obtains, carry out redissolution study on the stability respectively.The results are shown in Table 1 and table 2, preparation 001 redissolves rear 0.5h and occurs micro-white suspension thing, illustrates that micellar structure is destroyed; And preparation 002 redissolves rear 4h and just occurs micro-white suspension thing, illustrate and better to redissolve stability for polymer micelle freeze-dried preparation that auxiliary material is obtained has with the MPEG-PLA amphipathic nature block polymer of purifying.
Table 1 polymer micelle freeze-dried preparation redissolution study on the stability result 1
Table 2 polymer micelle freeze-dried preparation redissolution study on the stability result 2
Embodiment 10, prepare Disoprofol-MPEG-PLA amphipathic nature block polymer (mass ratio 1:10) polymer micelle freeze-dried preparation (hereinafter referred to as preparation 003)
Take Disoprofol 1g and the obtained MPEG-PLA amphipathic nature block polymer product 10g of embodiment 2 respectively, add methyl alcohol 200ml, temperature control 25-30 DEG C makes MPEG-PLA amphipathic nature block polymer dissolve completely; Again temperature be 30-35 DEG C, vacuum tightness rotates evaporative removal methyl alcohol under being the condition of 0.096MPa, obtains the polymer gel that Disoprofol and MPEG-PLA amphipathic nature block polymer are formed; Add water 100ml again in resulting polymers gel; temperature control 30-35 DEG C forms the docetaxel polymer micelle aqueous solution; be that the filtering with microporous membrane of 0.22 μm is degerming with aperture; filling by every bottle of 2ml; put into freezing drying protective agent after half-dozen plug, obtain polymer micelle freeze-dried preparation through lyophilize 48h.
Find in experimentation, the MPEG-PLA amphipathic nature block polymer product that embodiment 2 obtains about 1h in methyl alcohol dissolves complete.
Embodiment 11, prepare Disoprofol-MPEG-PLA amphipathic nature block polymer (mass ratio 1:10) polymer micelle freeze-dried preparation (hereinafter referred to as preparation 004)
Take the MPEG-PLA amphipathic nature block polymer product 10g of Disoprofol 1g and the obtained purifying of embodiment 5 respectively, add methyl alcohol 200ml, temperature control 25-30 DEG C makes MPEG-PLA amphipathic nature block polymer dissolve completely; Again temperature be 30-35 DEG C, vacuum tightness rotates evaporative removal methyl alcohol under being the condition of 0.096MPa, obtains the polymer gel that Disoprofol and MPEG-PLA amphipathic nature block polymer are formed; Add water 100ml again in resulting polymers gel; temperature control 30-35 DEG C forms the docetaxel polymer micelle aqueous solution; be that the filtering with microporous membrane of 0.22 μm is degerming with aperture; filling by every bottle of 2ml; put into freezing drying protective agent after half-dozen plug, obtain polymer micelle freeze-dried preparation through lyophilize 48h.
Find in experimentation, MPEG-PLA amphipathic nature block polymer product about 10min in methyl alcohol of the purifying that embodiment 5 is obtained dissolves completely, illustrates to have better solvability by the MPEG-PLA amphipathic nature block polymer product of the inventive method purifying.
The redissolution study on the stability of embodiment 12, preparation 003 and preparation 004
The preparation 003 that Example 10 is obtained and the preparations 004 that enforcement 11 obtains, carry out redissolution study on the stability respectively.The results are shown in Table 3 and table 4, preparation 003 redissolves rear 0.5h and occurs micro-white suspension thing, illustrates that micellar structure is destroyed; And preparation 004 redissolves rear 6h and just occurs micro-white suspension thing, illustrate and better to redissolve stability for polymer micelle freeze-dried preparation that auxiliary material is obtained has with the MPEG-PLA amphipathic nature block polymer of purifying.
Table 3 polymer micelle freeze-dried preparation redissolution study on the stability result 1
Table 4 polymer micelle freeze-dried preparation redissolution study on the stability result 2
What finally illustrate is, above preferred embodiment is only in order to illustrate technical scheme of the present invention and unrestricted, although by above preferred embodiment to invention has been detailed description, but those skilled in the art are to be understood that, various change can be made to it in the form and details, and not depart from claims of the present invention limited range.
Claims (10)
1. the purification process of injection MPEG-PLA amphipathic nature block polymer, it is characterized in that, comprise the following steps: MPEG-PLA amphipathic nature block polymer water dissolution is obtained the aqueous solution, obtained aqueous solution carries out strong acid cation exchange resin column chromatography, wash with water, gained elutriant filtering with microporous membrane is degerming, lyophilize, obtains the MPEG-PLA amphipathic nature block polymer of purifying.
2. the purification process of injection MPEG-PLA amphipathic nature block polymer as claimed in claim 1, it is characterized in that, described MPEG-PLA amphipathic nature block polymer poly glycol monomethyl ether, rac-Lactide is reacted under stannous octoate catalysis obtained MPEG-PLA amphipathic nature block polymer crude product, and gained crude product obtains with dichloromethane-ether mixed solvent recrystallization again.
3. the purification process of injection MPEG-PLA amphipathic nature block polymer as claimed in claim 2, it is characterized in that, the molecular-weight average of described MPEG-PLA amphipathic nature block polymer is 3000 ~ 6000.
4. the purification process of injection MPEG-PLA amphipathic nature block polymer as claimed in claim 3, it is characterized in that, in described MPEG-PLA amphipathic nature block polymer, the molecular-weight average of hydrophilic block poly glycol monomethyl ether is 2000, and the molecular-weight average of hydrophobic block poly(lactic acid) is 1000-4000.
5. the purification process of the injection MPEG-PLA amphipathic nature block polymer as described in any one of Claims 1-4, it is characterized in that, the concentration of the described MPEG-PLA amphipathic nature block polymer aqueous solution is 0.01 ~ 1g/ml.
6. the purification process of injection MPEG-PLA amphipathic nature block polymer as claimed in claim 5, it is characterized in that, the concentration of the described MPEG-PLA amphipathic nature block polymer aqueous solution is 0.1 ~ 0.2g/ml.
7. the purification process of the injection MPEG-PLA amphipathic nature block polymer as described in any one of Claims 1-4, it is characterized in that, described storng-acid cation exchange resin is before use through pre-treatment, described pre-treatment is that storng-acid cation exchange resin is first used water backwash, removing mechanical impurity, again by certain acid, alkaline solution removing solvend, finally transfer storng-acid cation exchange resin to Hydrogen; The amount ratio of described MPEG-PLA amphipathic nature block polymer and pretreated storng-acid cation exchange resin is 1g:1 ~ 100ml.
8. the purification process of injection MPEG-PLA amphipathic nature block polymer as claimed in claim 7, it is characterized in that, the amount ratio of described MPEG-PLA amphipathic nature block polymer and pretreated storng-acid cation exchange resin is 1g:15 ~ 100ml.
9. the purification process of the injection MPEG-PLA amphipathic nature block polymer as described in any one of Claims 1-4, is characterized in that, the aperture of described millipore filtration is 0.22 μm.
10. the purification process of the injection MPEG-PLA amphipathic nature block polymer as described in any one of Claims 1-4, is characterized in that, described lyophilize is carried out in the A level clean area that Good Manufacturing Practice and Quality Control of Drug version in 2010 specifies.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410339428.9A CN105315444B (en) | 2014-07-16 | 2014-07-16 | The purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410339428.9A CN105315444B (en) | 2014-07-16 | 2014-07-16 | The purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105315444A true CN105315444A (en) | 2016-02-10 |
| CN105315444B CN105315444B (en) | 2018-04-17 |
Family
ID=55243825
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410339428.9A Active CN105315444B (en) | 2014-07-16 | 2014-07-16 | The purification process of injection poly glycol monomethyl ether polylactic acid amphiphilic block copolymer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105315444B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602833A (en) * | 2017-09-22 | 2018-01-19 | 上海景峰制药有限公司 | A kind of preparation method and purification process of PDLLA PEG PDLLA triblock copolymers |
| CN112807486A (en) * | 2021-02-09 | 2021-05-18 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| 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 |
| WO2023083265A1 (en) * | 2021-11-10 | 2023-05-19 | 北京渼颜空间生物医药有限公司 | Polyethylene glycol monomethyl ether-polylactic acid copolymer, and preparation method therefor and use thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101875703A (en) * | 2010-05-28 | 2010-11-03 | 砀山宇宁生物科技有限公司 | Method for extracting pectin and synephrine by utilizing peels and marc |
| US20130233827A1 (en) * | 2012-03-09 | 2013-09-12 | Az Electronic Materials (Luxembourg) S.A.R.L. | Methods and materials for removing metals in block copolymers |
| CN103601878A (en) * | 2013-11-25 | 2014-02-26 | 沈阳药科大学 | High-stability polyethylene glycol-polyester polymer and application thereof |
| CN103690512A (en) * | 2013-12-24 | 2014-04-02 | 浙江尖峰药业有限公司 | Deoxidized podophyllotoxin polymer micelle freeze-drying preparation |
| CN103768013A (en) * | 2014-01-17 | 2014-05-07 | 丽珠医药集团股份有限公司 | Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier |
-
2014
- 2014-07-16 CN CN201410339428.9A patent/CN105315444B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101875703A (en) * | 2010-05-28 | 2010-11-03 | 砀山宇宁生物科技有限公司 | Method for extracting pectin and synephrine by utilizing peels and marc |
| US20130233827A1 (en) * | 2012-03-09 | 2013-09-12 | Az Electronic Materials (Luxembourg) S.A.R.L. | Methods and materials for removing metals in block copolymers |
| CN103601878A (en) * | 2013-11-25 | 2014-02-26 | 沈阳药科大学 | High-stability polyethylene glycol-polyester polymer and application thereof |
| CN103690512A (en) * | 2013-12-24 | 2014-04-02 | 浙江尖峰药业有限公司 | Deoxidized podophyllotoxin polymer micelle freeze-drying preparation |
| CN103768013A (en) * | 2014-01-17 | 2014-05-07 | 丽珠医药集团股份有限公司 | Paclitaxel polymer micelle by using refined amphiphilic block copolymer as carrier |
Non-Patent Citations (2)
| Title |
|---|
| 余琼等: "《生物制药工艺学》", 31 March 2011, 高等教育出版社 * |
| 吴仁芳等: "《电厂化学》", 30 September 2010, 中国电力出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602833A (en) * | 2017-09-22 | 2018-01-19 | 上海景峰制药有限公司 | A kind of preparation method and purification process of PDLLA PEG PDLLA triblock copolymers |
| CN112807486A (en) * | 2021-02-09 | 2021-05-18 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| 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 |
| WO2023083265A1 (en) * | 2021-11-10 | 2023-05-19 | 北京渼颜空间生物医药有限公司 | Polyethylene glycol monomethyl ether-polylactic acid copolymer, and preparation method therefor and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105315444B (en) | 2018-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6147427B2 (en) | Preparation method of lyophilized formulation of nanopolymer micelle of docetaxel | |
| Zhang et al. | Pharmacokinetics, biodistribution, efficacy and safety of N-octyl-O-sulfate chitosan micelles loaded with paclitaxel | |
| CN102125547B (en) | Pharmaceutical composition containing gambogic acid medicament and preparation method thereof | |
| CN102133199B (en) | Doxofylline lyophilized preparation for injection and preparation method thereof | |
| US20190008775A1 (en) | Method for Preparing Modified Sodium Alginate Embolization Microsphere | |
| CN105315444A (en) | Purification method of polyethylene glycol monomethyl ether-polylactic acid amphiphilic segmented copolymer for injection | |
| CN103610649B (en) | Medicament microsphere and preparation method thereof | |
| Kumar et al. | Formulation and evaluation of itraconazole niosomal gel | |
| CN101391098B (en) | Apitoxin liposome preparation and preparation method thereof | |
| CN102935066A (en) | Irinotecan liposome preparation and preparation method thereof | |
| SG188393A1 (en) | 5ALPHA-ANDROSTANE (ALKYL)-3ß,5,6ß-TRIOL INJECTION AND PREPARATION METHOD THEREFOR | |
| CN102406941A (en) | Nanometer insoluble active component containing modified polyegline and preparation method thereof | |
| CN104352442A (en) | Mifepristone chitosan sustained release microspheres and preparation method thereof | |
| CN106995528A (en) | A kind of process for purification of mPEG-PDLLA | |
| CN110251487B (en) | Preparation method and application of alcohol soluble protein nanoparticles for improving drug-loading rate and oral bioavailability of docetaxel | |
| WO2023083265A1 (en) | Polyethylene glycol monomethyl ether-polylactic acid copolymer, and preparation method therefor and use thereof | |
| CN107184566B (en) | Pharmaceutical composition containing lutein, preparation method and preparation thereof | |
| CN102631678A (en) | Triblock polymer carrier containing polyarginine as well as preparation method and application thereof | |
| CN110812335B (en) | Silk fibroin micro-nano particle sustained-release preparation loaded with hydrophobic drug and preparation method thereof | |
| CN105287402A (en) | Docetaxel polymer micelle freeze-dried preparation and special solvent composition | |
| CN109438302B (en) | Acid/reductive degradation amphiphilic compound and preparation method and application thereof | |
| CN103690556B (en) | A kind of hydroxy camptothecin long cyclic liposome | |
| CN101791410B (en) | Preparation and application of conjugate of anti-infective medicament and polysaccharide and medicinal composition thereof | |
| CN102319222A (en) | Decitabine freeze-dried preparation and preparation method thereof | |
| CN102552185B (en) | 9-nitrocamptothecin mixed micelle freeze-dried powder injection and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |