CN109988291A - Poly (glycolide-co-lactide) copolymer ultrasonic synthetic method - Google Patents
Poly (glycolide-co-lactide) copolymer ultrasonic synthetic method Download PDFInfo
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- CN109988291A CN109988291A CN201910244772.2A CN201910244772A CN109988291A CN 109988291 A CN109988291 A CN 109988291A CN 201910244772 A CN201910244772 A CN 201910244772A CN 109988291 A CN109988291 A CN 109988291A
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- lactide
- glycolide
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- 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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
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- 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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/78—Preparation processes
Abstract
The invention discloses a kind of poly (glycolide-co-lactide) copolymer ultrasonic synthetic methods, are mixed in proportion using glycolide raw material and lactide raw material, using following synthesis step: 1) glycolide lactide being added in reaction kettle；2) inert gas is passed through into reaction kettle；3) melting of glycolide lactide is warming up in reaction kettle；4) 137 DEG C -142 DEG C are heated in reaction kettle；5) liquefactent in reaction kettle is transferred to ultrasonic reactor and carries out ultrasonic reaction；6) end-capping reagent is added into ultrasonic reactor and carries out end capping reaction, continue to be kept for temperature 0.5 hour；7) it is cooled to 160 DEG C -170 DEG C in ultrasonic reactor, while being vacuumized in ultrasonic reactor；8) it takes out ultrasonic reactor interpolymer and poly (glycolide-co-lactide) polymer beads is made.The present invention polymerize poly (glycolide-co-lactide) copolymer obtained with ultrasonic method, and polymer purity is high；Product favorable reproducibility, operation is controllable, is conducive to product post-forming process, is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to bio-medical material manufacturing technology fields, more particularly, to a kind of poly (glycolide-co-lactide) copolymer
Ultrasonic synthetic method.
Background technique
Poly (glycolide-co-lactide) copolymer (i.e. Vicryl Rapide, abbreviation PGLA) is that a kind of human body is absorbable
Aliphatic high polymer has been widely used in medical domain with the biocompatibility that its is excellent.PGLA can absorb operation stitching
Line has been widely used as second generation medical absorbable suture.Research is found by changing glycolide and lactide
Component ratio, can effectively adjust degradation rate, and ring-opening polymerisation is to obtain commonly using for high molecular weight Vicryl Rapide
Method.
In recent years, PGLA medical absorbable suture is widely used to medical market.But Chinese Medical Device Manufacturers produce
Manufacturer purchases PGLA (Vicryl Rapide) from offshore company.And domestic production manufacturer is because PGLA (hand over by glycolide third
Ester copolymer) product quality stability problem and can not be commercially produced.
Chinese patent (publication number CN1738846A) causes lactide, second is handed over using trifluoromethayl sulfonic acid ester as catalyst
The ring-opening polymerisation of ester prepares lactide-co-glycolide.Chinese patent (publication number CN 1934161A) is handed over by strong acidic ion
Change the lactide of resin polymerization catalyst and (total) oligomeric additive composition, (total) oligomeric catalyst system preparation of glycolide open loop
Lactide-co-glycolide.For Chinese patent (publication number CN 101343354A) using stannous octoate as catalyst, silicone oil is to stablize
Agent prepares Vicryl Rapide.But polymer still has as universality is not strong, severe reaction conditions, and product is not easy point
The defects of from purifying, being at high cost, the most key, polymerization product thermal stability is poor, is not amenable to secondary operation, such as injection molding,
The high temperature and pressure of the techniques such as melting spinning influences, the fast decoupled under high-temperature high-pressure state, is difficult to answer in actual process production
With this is also the basic reason that Vicryl Rapide cannot domesticize always.
Summary of the invention
The present invention, which is to provide for one kind, has the good security performance of bio-compatible high, can carry out post-forming process, meet
The poly (glycolide-co-lactide) copolymer (PGLA) of PGLA medical absorbable suture items quality index is catalyzed using ultrasonic method object
Polyglycolide polymers ultrasonic synthetic method.
To achieve the goals above, the invention adopts the following technical scheme: poly (glycolide-co-lactide) copolymer ultrasound synthesizes
Method is mixed in proportion using glycolide raw material and lactide raw material, and the poly (glycolide-co-lactide) copolymer is closed using following
At step: 1) mixing glycolide raw material and lactide raw material and be added in reaction kettle；2) it is passed through inert gas into reaction kettle, sets
Swap out air in reaction kettle, and inert gas shielding environment is formed in reaction kettle；3) be warming up in reaction kettle glycolide raw material and
Lactide raw material melts；4) it is heated to 137 DEG C -142 DEG C in reaction kettle, and continues 3 hours；5) liquefactent in reaction kettle is transferred to
Ultrasonic reactor carries out ultrasonic reaction, while 180 DEG C -220 DEG C is heated in ultrasonic reactor, and continue 1 hour；6) Xiang Chaosheng
End-capping reagent is added in reactor and carries out end capping reaction, continues to be kept for temperature 0.5 hour；7) be cooled in ultrasonic reactor 160 DEG C-
170 DEG C, while being vacuumized in ultrasonic reactor, it is kept for vacuum 0.5 hour；8) it after being cooled to room temperature in ultrasonic reactor, takes out
Poly (glycolide-co-lactide) copolymer pellet is made in ultrasonic reactor interpolymer.This programme is adopted in glycolide, lactide polymerization
Polymerization is rapidly promoted with ultrasonic method, shortens polymerization time；After reaction, also with ultrasonic method unreacted small molecule second
Lactide, lactide, dimer and end-capping reagent remove under the conditions of sonic vacuum, avoid be added in this reaction it is various active
Metal and various initiator secondary pollution products；Using ultrasonic method, the molecular weight ratio higher molecule of general catalysis method can be made
Amount, because of the reaction later period, with the increase of molecular weight, macromolecular movement is more difficult, and to aggregate into bigger molecule certainly will need
Energy that will be bigger, and ultrasonic method just makes up the deficiency of catalyst method, because of the reaction later period, micro catalyst is polymerizeing
Body is fixed, and the effect for accelerating reaction is not had；Increase a small amount of end-capping reagent in reaction process to block the end of polymer, it will
The terminal carboxyl group of polymer is replaced as hydroxyl, increases the thermal stability of polymer；After reaction, it is handed over by decompression vaporization second
Ester, lactide and oligomer, then vacuumize, these impurity can be reduced, achieve the effect that purified polymer.
Preferably, the lactide raw material is at least one of L- lactide, D- lactide, DL- lactide.
Preferably, the ratio that the glycolide raw material and lactide raw material mixes in proportion is 0.1:1-4:1.
Preferably, inert gas is argon gas or nitrogen in the step 2), it is passed through inert gas 5 into reaction kettle and divides
Clock is to displace air in reaction kettle.
Preferably, the end-capping reagent used in the step 6) for Isosorbide-5-Nitrae butanediol, ethylene glycol, pentanediol, lauryl alcohol,
At least one of hexadecanol, octadecyl alcolol.
Preferably, the relative degree of vacuum of the vacuum used in the step 7) is -100KPa.
Preferably, clear water is added into ultrasonic reactor, and open ultrasonic progress after heating up after the completion of the step 8)
Cleaning.After this programme has reacted discharging in ultrasonic reactor, proper amount of clear water is added in ultrasonic reactor, in ultrasound after heating
Middle Rapid Cleaning reactor, cleans up, because excess reactant should not stay in reactor, residue is stayed in reactor,
Lower batch materials are reacted to form cross reaction, reaction stability can be seriously affected.
The invention has the following beneficial effects: polymerize Vicryl Rapide obtained, molecule measurer with ultrasonic method
There are better controllability, narrow molecular weight distribution；Polymer is without the impurity such as catalyst, initiator, purity is high；Preparation is simple, has
Conducive to reaction kettle cleaning, product favorable reproducibility, operation is controllable, is particularly suitable for that quality is required to stablize very high biomedicine field,
Product thermal stability is good, is conducive to post-forming process, is suitable for large-scale industrial production.
Specific embodiment
Poly (glycolide-co-lactide) copolymer ultrasonic synthetic method, is mixed in proportion using glycolide raw material and lactide raw material
It closes, poly (glycolide-co-lactide) copolymer uses following synthesis step: 1) glycolide raw material and lactide raw material being mixed and are added instead
It answers in kettle；2) it is passed through inert gas into reaction kettle, displaces air in reaction kettle, forms inert gas shielding in reaction kettle
Environment；3) it is warming up to glycolide raw material in reaction kettle and lactide raw material melts；4) 137 DEG C -142 DEG C are heated in reaction kettle,
And continue 3 hours；5) liquefactent in reaction kettle is transferred to ultrasonic reactor and carries out ultrasonic reaction, while heating in ultrasonic reactor
To 180 DEG C -220 DEG C, and continue 1 hour；6) end-capping reagent is added into ultrasonic reactor and carries out end capping reaction, continue to keep temperature
0.5 hour；7) it is cooled to 160 DEG C -170 DEG C in ultrasonic reactor, while being vacuumized in ultrasonic reactor, keeps vacuum 0.5 small
When；8) it after being cooled to room temperature in ultrasonic reactor, takes out ultrasonic reactor interpolymer and poly (glycolide-co-lactide) copolymer is made；
Lactide raw material is at least one of L- lactide, D- lactide, DL- lactide；
The ratio that glycolide raw material and lactide raw material mix in proportion is 0.1:1-4:1；
Inert gas is argon gas or nitrogen in step 2), inert gas is passed through into reaction kettle 5 minutes to displace reaction
Air in kettle；
The end-capping reagent used in step 6) is in Isosorbide-5-Nitrae butanediol, ethylene glycol, pentanediol, lauryl alcohol, hexadecanol, octadecyl alcolol
At least one；
The relative degree of vacuum of the vacuum used in step 7) is -100KPa；
After the completion of step 8), clear water is added into ultrasonic reactor, and open ultrasound after heating up and cleaned.
Specific implementation process is embodiment 1, weigh 1000g glycolide, 1000g lactide be added 3L reaction kettle in, in kettle
It is inside passed through high purity argon 5 minutes, displaces air in kettle, form inert gas shielding environment.It is rapidly heated to glycolide, third
Lactide dissolution is transferred to ultrasonic reactor, opens ultrasonic reaction after being heated to 140 DEG C of reactions 3 hours, is continuously heating to 180 DEG C of reactions
After 1 hour, a small amount of 1,4-butanediol is added to be blocked, end capping reaction 0.5 hour.Reaction is finished, and reduces temperature to 160 DEG C, is taken out true
Empty (- 100KPa) 0.5 hour, it is cooling, polymer is taken out, particle is made.
Embodiment 2, weigh 1000g glycolide, 1000g lactide be added 3L reaction kettle in, high-purity argon is passed through in kettle
Gas 5 minutes, air in kettle is displaced, forms inert gas shielding environment.It is rapidly heated to glycolide, lactide dissolution, heating
After being reacted 3 hours to 140 DEG C, it is transferred to ultrasonic reactor, opens ultrasonic reaction, after being continuously heating to 190 DEG C of reactions 1 hour, added few
Amount 1,4-butanediol is blocked, and end capping reaction 0.5 hour.Reaction is finished, and is reduced temperature to 170 DEG C, is vacuumized (- 100KPa)
It is 0.5 hour, cooling, polymer is taken out, particle is made.
Embodiment 3, weigh 1000g glycolide, 1000g lactide be added 3L reaction kettle in, high-purity argon is passed through in kettle
Gas 5 minutes, air in kettle is displaced, forms inert gas shielding environment.It is rapidly heated to glycolide, lactide dissolution, heating
After being reacted 3 hours to 140 DEG C, it is transferred to ultrasonic reactor, opens ultrasonic reaction, after being continuously heating to 200 DEG C of reactions 1 hour, added few
Amount 1,4-butanediol is blocked, and end capping reaction 0.5 hour.Reaction is finished, and is reduced temperature to 170 DEG C, is vacuumized (- 100KPa)
It is 0.5 hour, cooling, polymer is taken out, particle is made.
Embodiment 4, weigh 1000g glycolide, 1000g lactide be added 3L reaction kettle in, high-purity argon is passed through in kettle
Gas 5 minutes, air in kettle is displaced, forms inert gas shielding environment.It is rapidly heated to glycolide, lactide dissolution, heating
After being reacted 3 hours to 140 DEG C, it is transferred to ultrasonic reactor, opens ultrasonic reaction, after being continuously heating to 210 DEG C of reactions 1 hour, added few
Amount 1,4-butanediol is blocked, and end capping reaction 0.5 hour.Reaction is finished, and is reduced temperature to 170 DEG C, is vacuumized (- 100KPa)
It is 0.5 hour, cooling, polymer is taken out, particle is made.
Embodiment 5, weigh 1000g glycolide, 1000g lactide be added 3L reaction kettle in, high-purity argon is passed through in kettle
Gas 5 minutes, air in kettle is displaced, forms inert gas shielding environment.It is rapidly heated to glycolide, lactide dissolution, heating
After being reacted 3 hours to 140 DEG C, it is transferred to ultrasonic reactor, opens ultrasonic reaction, after being continuously heating to 220 DEG C of reactions 1 hour, added few
Amount 1,4-butanediol is blocked, and end capping reaction 0.5 hour.Reaction is finished, and is reduced temperature to 170 DEG C, is vacuumized (- 100KPa)
It is 0.5 hour, cooling, polymer is taken out, particle is made.
Claims (7)
1. a kind of poly (glycolide-co-lactide) copolymer ultrasonic synthetic method, which is characterized in that use glycolide raw material and lactide
Raw material mixes in proportion, and the poly (glycolide-co-lactide) copolymer uses following synthesis step: 1) handing over glycolide raw material and third
The mixing of ester raw material is added in reaction kettle；2) it is passed through inert gas into reaction kettle, air in reaction kettle is displaced, in reaction kettle
Form inert gas shielding environment；3) it is warming up to glycolide raw material in reaction kettle and lactide raw material melts；4) add in reaction kettle
Heat continues 3 hours to 137 DEG C -142 DEG C；5) liquefactent in reaction kettle is transferred to ultrasonic reactor and carries out ultrasonic reaction, simultaneously
It is heated to 180 DEG C -220 DEG C in ultrasonic reactor, and continues 1 hour；6) end-capping reagent is added into ultrasonic reactor to be blocked
Reaction continues to be kept for temperature 0.5 hour；7) it is cooled to 160 DEG C -170 DEG C in ultrasonic reactor, while being taken out in ultrasonic reactor true
Sky is kept for vacuum 0.5 hour；8) it after being cooled to room temperature in ultrasonic reactor, takes out ultrasonic reactor interpolymer and poly- second is made
Lactide lactide copolymer.
2. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that described third is handed over
Ester raw material is at least one of L- lactide, D- lactide, DL- lactide.
3. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that the second is handed over
The ratio that ester raw material and lactide raw material mix in proportion is 0.1:1-4:1.
4. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that the step
2) inert gas is argon gas or nitrogen in, inert gas is passed through into reaction kettle 5 minutes to displace air in reaction kettle.
5. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that the step
6) end-capping reagent used in is at least one of ethylene glycol, pentanediol, lauryl alcohol, hexadecanol, octadecyl alcolol.
6. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that the step
7) relative degree of vacuum of the vacuum used in is -100KPa.
7. poly (glycolide-co-lactide) copolymer ultrasonic synthetic method according to claim 1, characterized in that the step
8) after the completion of, clear water is added into ultrasonic reactor, and open ultrasound after heating up and cleaned.
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| CN201910244772.2A CN109988291A (en) | 2019-03-28 | 2019-03-28 | Poly (glycolide-co-lactide) copolymer ultrasonic synthetic method |
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| CN201910244772.2A CN109988291A (en) | 2019-03-28 | 2019-03-28 | Poly (glycolide-co-lactide) copolymer ultrasonic synthetic method |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101445595A (en) * | 2008-12-26 | 2009-06-03 | 上海新上化高分子材料有限公司 | Poly glycolide lactide (PGLA), preparation method and application thereof |
| CN102219889A (en) * | 2004-03-18 | 2011-10-19 | 株式会社吴羽 | Process for producing aliphatic polyester reduced in residual cyclic ester content |
| RU2637923C1 (en) * | 2016-11-30 | 2017-12-08 | Общество с ограниченной ответственностью "Медин-Н" | Method of producing (co) polymer of glycolide and/or lactide for production of absorbable surgical products |
-
2019
- 2019-03-28 CN CN201910244772.2A patent/CN109988291A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102219889A (en) * | 2004-03-18 | 2011-10-19 | 株式会社吴羽 | Process for producing aliphatic polyester reduced in residual cyclic ester content |
| CN101445595A (en) * | 2008-12-26 | 2009-06-03 | 上海新上化高分子材料有限公司 | Poly glycolide lactide (PGLA), preparation method and application thereof |
| RU2637923C1 (en) * | 2016-11-30 | 2017-12-08 | Общество с ограниченной ответственностью "Медин-Н" | Method of producing (co) polymer of glycolide and/or lactide for production of absorbable surgical products |
Non-Patent Citations (2)
| Title |
|---|
| GARETH J. PRICE: "The effect of high-intensity ultrasound on the ring-opening polymerisation of cyclic lactones", 《EUROPEAN POLYMER JOURNAL》 * |
| S. J. STOESSEL: "The Use of Ultrasound to Initiate Ring-Opening Polymerization", 《JOURNAL OF APPLIED POLYMER SCIENCE》 * |
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