CN101343354B

CN101343354B - Poly-lactide, poly-glycolide and preparation for copolymer of the same

Info

Publication number: CN101343354B
Application number: CN2008100321967A
Authority: CN
Inventors: 胡权
Original assignee: Individual
Current assignee: Individual
Priority date: 2008-08-29
Filing date: 2008-08-29
Publication date: 2011-05-04
Anticipated expiration: 2028-08-29
Also published as: CN101343354A

Abstract

The invention discloses a preparation method for poly-lactide acid, polyglycolide and copolymer of the poly-lactide acid and the polyglycolide, which adopts the steps that arbitrary one of lactide or glycolide or the mixture thereof is considered as a monomer, suspending agent and catalyzer are added into the monomer, then the agitation is performed, and the granular product is polymerized. The suspending agent is alkane with the boiling point of higher than 90 DEG C, and the polymerizing temperature is higher than the melting point of the monomer but less than the boiling point of the suspending agent. The preparation method of the invention can be applied in the industrialized large-scale production, effectively solving the problems existing in the prior art that the heat emission of the materials is difficult during the preparation process, and the dissolution is time-consuming, the cost of melting granulating or crushing granulating is high, and the investment of the equipment is large during the late processing process. The product polymerized by utilizing the method has the advantages that the molecular weight is high, the purity is high, the product directly presents a granular shape, the re-granulation operation is not required, the process is simple, and both the equipment investment and the labor cost are very low.

Description

The preparation method of polylactide, poly-glycollide and this two multipolymer

Technical field

The present invention relates to the preparation method of a kind of polylactide, poly-glycollide and polylactide and poly-glycolide copolymer.

Background technology

Poly(lactic acid), polyglycolic acid and multipolymer thereof are the degradable medical materials of consumption maximum in the market.Their production method mainly is mass polymerization.Mass polymerization can make product pure in theory, molecular weight height, but mass polymerization heat radiation difficulty, cause the product at reactor middle part to darken easily, molecular weight reduces, and because polymerization temperature between 130 ℃ to 180 ℃, is lower than the melt temperature of polymkeric substance, so cause its aftertreatment very difficult, generally be after adopting polymerization to finish, in small-scale preparation earlier with (as trichloromethane, acetone etc.) after the dissolution with solvents, and then adding precipitation agent (as ethanol, water etc.) precipitates.Process is very time-consuming, and solvent consumption is very huge.And because polymerization itself is exactly a thermopositive reaction, even if darken in the middle of also can observing system with the macro preparation polymkeric substance of 100 grams, existing degraded to a certain degree takes place.And in mass preparation, product polymerization latter temperature will be raised to more than the melt temperature, extrudes again, and granulation, facility investment are very huge, and too high temperature of reaction makes partial polymer degrade simultaneously, and it is pure also to be not easy to prepare product, has the high-molecular weight product.Therefore it is very high producing polylactide, poly-glycollide and this two multipolymer cost with the method for present this mass polymerization.Synthesize poly-glycollide and polylactide in order to address this problem people's suspension polymerization that begins one's study.This polymerization process normally is dispersed in monomer in the silicone oil medium, and by the little liquid pearl that mechanical stirring obtains suspending, liquid pearl size can also add stablizer and come the maintenance system stable in tens microns and hundreds of micrometer range.Polyreaction is to cause by being dissolved in monomeric catalyzer, in each liquid pearl, all carrying out a bulk polymerization, thus this reaction process can be considered at one time with identical reaction conditions under carried out a series of bulk polymerization.Because the existence of dispersion medium is arranged, so the polymerization system heat transfer property is better.But people make suspension agent with silicone oil, and the silicone oil ratio is easier to suction, and thickness, be difficult to guarantee the purity of own component on the one hand in the industrial production, handle very difficult in the silicone oil thickness in the polymerization middle and later periods on the other hand, cause up to the present can't being prepared into high molecular weight polymers, more can not carry out suitability for industrialized production with this method with suspension polymerization.

Summary of the invention

The object of the present invention is to provide that a kind of production cost is low, the product purity high molecular is high and the preparation method of polylactide, poly-glycollide and this two multipolymer that can scale operation.

The preparation method of this polylactide provided by the invention, poly-glycollide and this two multipolymer is: in these three kinds of materials of mixture of rac-Lactide or glycollide or rac-Lactide and glycollide any one is considered as monomer, in described monomer, add suspension agent, catalyzer, stir then, heat up, aggregate into granulated product, described suspension agent is a boiling point greater than 90 ℃ alkane, polymerization temperature greater than the monomer fusing point less than the suspension agent boiling point.

The existing relatively mass polymerization technology of preparation method of the present invention has solved the problem of the heat radiation difficulty of material in preparation and the dissolving in the last handling process is time-consuming, melt pelletization or pulverize the big problem of cost height, facility investment that granulation brings.And the molecular weight product high purity that polymerize is high and directly in pelletized form, do not need granulation again, and equipment also only needs reactor, stirrer, warming-up device, so technology and equipment are all fairly simple, and facility investment and cost of labor are all very low.Existing relatively suspension polymerization technique, biggest advantage of the present invention is the product purity high molecular height of producing, and can realize industrial sector production, this is because the suspension agent that the present invention adopts is a high boiling alkane, the single purity height of its component, purifying easily, viscosity is low removes easily, therefore can produce high-quality product, the technology simple device is also simple in addition, therefore can carry out large-scale industrialization production.

Embodiment

Suspension agent employing high boiling alkane is that boiling point is higher than 90 ℃ alkane in the inventive method, and suspension agent and monomeric mass ratio are 5: 1-1: 1.Catalyzer can use any, as present custom catalysts: tin-containing catalyst stannous octoate etc. arranged, anionic catalyst has trialkylaluminium and their some mixtures, such as triisobutyl aluminium, triisobutyl aluminium-water, triisobutyl aluminium-water-phosphoric acid compound systems etc. also have some new highly active organometallic compounds, the grade of organo-transition metal compound can make the polymerization of rac-Lactide rapider, and molecular weight is higher.Catalyzer and monomeric mol ratio are generally 1: 100-1: choose arbitrarily in 10000 scopes.Monomer, catalyzer, suspension agent mixed to stir heat, make monomer generation polymerization, less than the suspension agent boiling point, the polymeric time is in 1 hour-24 hours scopes greater than the monomer fusing point for polymerization temperature.Several embodiment of the lab scale that below to be the contriver carry out preparation method of the present invention:

Embodiment 1

Equipment: magnetic stirring apparatus, there-necked flask.

With stirrer, 50 gram DL rac-Lactides (monomer), 100 milliliters of nonanes, join volume and be in 250 milliliters the there-necked flask, there-necked flask is carried out oil bath heats, be warmed up to 130 ℃ earlier, intensification limit, limit leads to nitrogen, eliminating system air, when rac-Lactide in the system melts fully, add the silicone oil (playing stabilizer function) of the inferior tin of octoate catalyst and 0.5 milliliter, the mol ratio of catalyzer and rac-Lactide is 6/10000ths, be warmed up between 145 ℃ to 150 ℃, regulate rotating speed to 500rpm, reacted 6 hours, stop to heat, continue to stir until being cooled to room temperature (adhesion of particle in the time of can preventing at high temperature), with the liquid elimination, promptly obtain particle diameter 2 millimeters to colourless between 0.2 tip of a hair, transparent polylactide (poly(lactic acid)) particle.Dry back uses trichloromethane as solvent, measures molecular weight in 25 ℃, according to formula:

[η]＝2.21×10 ^-4M _V ^0.77

Calculating viscosity-average molecular weight is 80,000.

Embodiment 2:

With stirrer, 75 gram L rac-Lactides, 150 milliliters of nonanes, joining volume is that oil bath is heated in 250 milliliters of there-necked flasks, is warmed up to 110 ℃ earlier, intensification limit, limit leads to nitrogen, air in the removal system all melts to rac-Lactide as far as possible, and adding monomer catalyst molar ratio is 10/10000ths stannous octoate, 0.5 milliliter silicone oil is as suspension stabilizer, be warmed up between 140 ℃ to 150 ℃, regulate stirring velocity, reacted 7 hours to 500rpm.In order to prevent particle adhesion at high temperature,, the system that obtains is filtered equally, obtain the water white transparency particle of particle diameter between 3 millimeters to 0.2 millimeter continuing rapid cool to room temperature under the basis of stirring.After the drying, use trichloromethane, measure molecular weight in 25 ℃ as solvent, according to formula:

[η]＝5.45×10 ^-4M _V ^0.73

Calculating viscosity-average molecular weight is about 60,000.

Embodiment 3:

With stirrer, 50 gram DL rac-Lactides, 25 gram glycollide, 75 milliliters of nonanes, join volume and be in 250 milliliters the there-necked flask, adding the monomer catalyst molar ratio is centesimal catalyzer, according to the operation polyase 13 of the foregoing description identical with the front hour, reaction finishes postcooling filters, and promptly obtains water white polylactic acid poly ethanol copolymer particle.

Embodiment 4:

With stirrer, 75 gram DL rac-Lactides, 150 milliliters of nonanes, join volume and be in 250 milliliters the there-necked flask, add the monomer catalyst molar ratio and be ten thousand/ catalyzer, according to the operation polymerization of the foregoing description identical with the front 24 hours, reaction finishes postcooling filtered, and promptly obtains water white poly(lactic acid) particle.

Embodiment 5:

Stir and adopt mechanical stirring, there-necked flask is fixed, add 150 gram glycollide, 250 milliliters of nonanes are warmed up to earlier about 100 ℃, limit intensification degree, the limit leads to nitrogen, glycollide is all melted, stirring-head is fixed between two liquid levels, adding monomer catalyst molar ratio is 10/10000ths stannous octoate, regulate stirring velocity to 400rpm, between 140 ℃ to 150 ℃ of temperature, to react after 8 hours, cooling obtains particle diameter at 2 millimeters to 0.1 millimeter water white transparency particles.

Embodiment 6:

Stir and adopt mechanical stirring, and there-necked flask fixed, add 75 gram DL rac-Lactides, add 375 milliliters of decane, be warmed up to 130 ℃ earlier, the limit heating, the limit leads to nitrogen, after rac-Lactide is all melted, adding monomer and catalyst molar ratio are 14/10000ths stannous octoate, regulate stirring velocity to 600rpm, in polymerization between 150 ℃ to 155 ℃ of the temperature 10 hours, cooling obtained the water white transparency particle of particle diameter between 1.5 to 0.1 millimeters.

Claims

1. the copolymer method of a polylactide or poly-glycollide or polylactide and poly-glycollide, it is characterized in that: in these three kinds of materials of mixture of rac-Lactide or glycollide or rac-Lactide and glycollide any one is considered as monomer, in described monomer, add suspension agent, the inferior tin of octoate catalyst, stir then, heat up, aggregate into granulated product, described suspension agent is a boiling point greater than 90 ℃ alkane, polymerization temperature greater than the monomer fusing point less than the suspension agent boiling point, by mass ratio, described suspension agent is 5 with monomeric ratio: 1-1: 1, and inferior tin of described octoate catalyst and monomeric mol ratio are 1: 100-1: 10000.

2. preparation method according to claim 1 is characterized in that polymerization time is 1-24 hour.