CN102702488A - Preparation method for polylactic acid - Google Patents
Preparation method for polylactic acid Download PDFInfo
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- CN102702488A CN102702488A CN2012101867039A CN201210186703A CN102702488A CN 102702488 A CN102702488 A CN 102702488A CN 2012101867039 A CN2012101867039 A CN 2012101867039A CN 201210186703 A CN201210186703 A CN 201210186703A CN 102702488 A CN102702488 A CN 102702488A
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Abstract
The invention relates to a preparation method for polylactic acid, according to the method, lactide is used as a monomer, and polylactic acid is obtained via a polymerization catalyzed by dibatyl magnesium. By the adoption of the dibatyl magnesium as a catalyst of open-loop polymerization of the lactide, no toxic metal is remained in the prepared polylactic acid, and a minute quantity of organic solvent is used during the preparation process, so that the environmental problem caused by using a large number of solvent is avoided. The output of the polylactic acid prepared according to the method is high, the optic purity is remarkable, the viscosity is controllable, and the prepared polylactic acid is extremely suitable for a raw material of a degradable bone nail which is fixed in a catagma.
Description
Technical field
The present invention relates to the preparation field of POLYACTIC ACID, be specifically related to a kind of method that under dibutylmagnesium catalysis, prepares POLYACTIC ACID by rac-Lactide.
Background technology
POLYACTIC ACID (PLA) is a kind of the have good biocompatibility and synthesized polymer material of biological degradability, also is a kind of Biodegradable material of complete natural circulation type.Nontoxic, the nonirritant of POLYACTIC ACID; Has good biocompatibility; Therefore the macromolecular material that biodegradable absorption, intensity are high, plasticity-is strong, be convenient to machine-shaping has broad application prospects at medical fields such as orthopaedics immobilization material, operating suture, wound dressings, ophthalmology embedded material, pharmaceutical carriers.
As far back as the 1950's, the researchist has just begun the research for the synthetic and application of PLA.Synthesize high-molecular weight, had the D or the L type PLA of opticity to the beginning of the seventies, and tentatively be used for aspects such as pharmaceutical prepn and surgery.In recent years; Along with PLA and multipolymer thereof in fracture, the fix product development and the performance requriements of aspects such as material, engineering material of bone tissue and pharmaceutical controlled release formulation; In the preparation of HMW PLA and have specific composition and the research of the aspect such as synthetic of structure, degradation speed is controlled, degraded back heavy metal free is residual, harmless PLA and multipolymer, demonstrate vast potential for future development.
POLYACTIC ACID can be made by rac-Lactide (Lactide) ring-opening polymerization; The catalyzer that uses mainly contains protonic acid, organo-aluminium compound, pink salt class etc.; Use at present more and be known as catalytic efficiency (best be stannous octoate (Kricheldorf H R, et al, Polylactones 48.SnOct
2-initiated polymerization of lactide:A mechanistic study, Macromolecules, 2000,33,702.), its reaction scheme is following:
But in above-mentioned polymerization process, can't the tin element in the catalyzer thoroughly be removed from the synthetic polymkeric substance, cause residual inevitably heavy metal compound in the polymkeric substance, and medical research show; Stannous octoate has cytotoxicity (Schwarch G, et al, Ring opening polymerization of D; L-lactide in the presence of zinc metal and zinc lactate.Polym.Int; 1998,46,177.; Saunders I K, et al, Polylactones; 39.Zn lactate-catalyzed copolymerization of L-lactide with glycolide or ε-caprolactone, Macromol.Chem.Phys, 1998; 199; 1081.), this makes and uses this type material to bring the hidden danger of insecurity as pharmaceutical material, particularly longer-term (taking the carrier of medicine, the property implanted medical material etc. for a long time) this type of material.
Therefore, adopt hypotoxicity metal-complexing catalyst rac-Lactide ring-opening polymerization becoming rac-Lactide synthetic one big focus.
MAGNESIUM METAL 99 and compound thereof, though as the too late stannous octoate of catalyst activity, magnesium can be participated in the metabolic processes of human body, is the metal of one type of totally nontoxic.Magnesium is the positively charged ion that interior the 4th of body, cell interior second enrich; It is the indispensable important nutritive element of human body; Nerve, muscle, bone and heart function are had material impact, and visible magnesium has good security basis (Staiger MP Pietak AM.Huadmai J.et al.Magnesium and its alloys as orthopedic biomaterials:a review.Biomaterials.2006:27 (9): 1728～1734.) as bio-medical material.
Publication number is the method that the patent of CN 101367921 discloses a kind of amino acid catalytic synthesis of polylactic acid with lactide opened loop.It is with the amino acid of nontoxic, no metal, the needed by human body catalyzer as the rac-Lactide ring-opening polymerization, has avoided the use metal catalyst, and it is residual that the POLYACTIC ACID of preparation does not have metallic compound.Concrete grammar is to adopt the mass polymerization mode, is catalyzer with amino acid, is monomer with the rac-Lactide, and the two mixture is 140～200 ℃ in temperature of reaction, under the vacuum protection condition, reacts 24～96 hours, and rac-Lactide generation ring-opening polymerization generates POLYACTIC ACID.It is residual to use the resulting POLYACTIC ACID of this method not have metallic compound, and productive rate >=90%, and product is suitable to medicine controlled release carrier and tissue engineering material.Though the nontoxic no metal residual of the product of this method gained, required temperature of reaction is too high, has consumed lot of energy in the time of batch process, does not meet the demand of environmental protection low-carbon (LC).
Publication number is the preparation method that the Chinese patent of CN 1450097A provides a kind of gathering (L-lactic acid); In L-lactic acid, add zinc lactate-tosic acid composite catalyst; Polycondensation is 6～36 hours under 150～200 ℃, 0.06～1.96Kpa condition; It is 10,000～80,000 that product gathers (L-lactic acid) weight-average molecular weight.Publication number is that the Chinese patent of CN 1702091A provides a kind of method of utilizing the lactic acid direct condensation to prepare nontoxic POLYACTIC ACID; D with drying treatment; It is 100～200 ℃ in temperature behind the L-lactic acid decompression dehydration; Vacuum tightness is polycondensation 6～50 hours under the condition of 0.1～100mmHg, and polycondensation phase adopts sectional heating method, heats up 10～30 ℃ in per 3～5 hours.Product polylactic acid molecule amount is 2,000～50,000.Though above-mentioned two kinds of methods all compare the environmental protection low-carbon (LC) in theory, prepared polylactic acid molecule amount is less relatively, does not meet the HMW requirement of fracture internal fixing with the adsorbable bone nail.
Publication number is the problem that acvator that the patent of US 101755010A discloses a kind of synthetic activation rac-Lactide catalyst for polymerization (like stannous octoate etc.) solves tin content overproof in the gained POLYACTIC ACID product: the polymkeric substance or the multipolymer that contain side acid groups and side ester group through employing; Employing contains the PLA resin of acid; Or adopt and to have per at least one acid groups of 250 atomic mass units and to have side lactic acid or the polymkeric substance of POLYACTIC ACID group or multipolymer are handled, the resin that will the contain the polymeric lactic acid units for example metal catalyst residue in the polylactide deactivates.Though this method can effectively be controlled the product heavy metal content, has complex operation, need the drawback of repeated experiments operation.
Publication number is that the patent of JP 102300904A discloses a kind of method that is used to make POLYACTIC ACID, and said method comprises that use is by general formula (1): R
1 nAlX
3-n(1) [wherein n representes 1 to 3 integer; R
1Can represent to have the straight or branched alkyl of 1 to 10 carbon atom identical or different and separately; X can represent halogen atom or Wasserstoffatoms identical or different and separately; And Al representes the aluminium atom] alkylaluminium cpd of expression carries out the step of lactic acid ring-opening polymerization as ring-opening polymerization catalyst.Its temperature of reaction is 100～200 ℃.But its catalyzer that mainly uses is the compound of aluminium, and the improper use of aluminium also can produce some spinoffs.Document announcement is arranged: aluminium salt possibly cause brain injury, causes serious memory loss, and this is the distinctive symptom of degenerative brain disorder.
Publication number is that the patent of JP 200554010 discloses in the presence of catalyzer; The method of POLYACTIC ACID is made in the ring-opening polymerization of the rac-Lactide solution through 30wt% in the methylene dichloride, and institute's metal catalyst is A) condenses and the B that can obtain from the thermal response of aluminium alkoxide, silicon halide and SULPHOSUCCINIC ACID ESTER) have a C
1To C
4The trialkylaluminium of alkyl and/or the mixture of dialkylaluminum chloride.This method can be made the HMW PDDLA that can be used as biodegradable polymkeric substance.Yet the reaction times of this method reaches a couple of days, this means that catalytic activity is insufficient.
Therefore, need to seek a kind of rac-Lactide polymerization and use effective catalyst, make product have that low heavy metal is residual, production energy consumption is lower, human body had multiple advantage such as cytotoxicity.
Summary of the invention
Prepare big, the unsuitable medical technological deficiency of products obtained therefrom of catalyst toxicity in the process for overcoming existing POLYACTIC ACID, the purpose of this invention is to provide a kind of preparation method of POLYACTIC ACID.
POLYACTIC ACID preparation method provided by the invention is a monomer with the rac-Lactide, under the catalysis of dibutylmagnesium (dibutylmagnesium), carries out polyreaction and makes.
Said rac-Lactide is an optically pure L-rac-Lactide (L-lactide).
Said polyreaction adds initiator and causes; Said initiator is preferably lauryl alcohol or terepthaloyl moietie.
In the above-mentioned polyreaction, the mol ratio of rac-Lactide, initiator, dibutylmagnesium is 3000～10000: 1～5: 1～40.
The temperature of reaction of said polyreaction is 100～150 ℃; Reaction times is 24～48 hours.
Said polyreaction is carried out said polyreaction under the protection of rare gas element; Said rare gas element is preferably helium, argon gas or nitrogen.
Said preparation method also comprises the last handling process of POLYACTIC ACID, and step is following: after said polyreaction finishes, adopt the unreacted lactide monomer of organic solvent flush away, residual polymkeric substance promptly got said POLYACTIC ACID in 24～72 hours 20～40 ℃ of following vacuum-dryings.
Said organic solvent is one or more in methylene dichloride, trichloromethane, ETHYLE ACETATE, ethanol, methyl alcohol, sherwood oil, the tetracol phenixin, preferred methylene dichloride.
Adopt the POLYACTIC ACID of method preparation provided by the invention, the viscosity maximum can reach 5.0dl/g, and corresponding weight-average molecular weight can reach 500,000～600,000, and it is residual not have toxic metal, to human non-toxic, can be used as the raw material of medical bone immobilizing material.
Technical scheme of the present invention is catalyzer with the dibutylmagnesium, is the raw material monomer synthesizing polylactic acid with the rac-Lactide.The catalyzer dibutylmagnesium has advantages of high catalytic activity, under 100-150 ℃, normal pressure, can accomplish the ring-opening polymerization of rac-Lactide, obtains the suitable POLYACTIC ACID of MWD.Compared with prior art, technology of the present invention is simple, and is easy to operate, and product yield is high, and when adopting the optical purity raw material, polymerisate racemization can not take place.Preparing method of the present invention is applicable to that limiting viscosity is POLYACTIC ACID synthetic of 0.8～5.0dl/g (weight-average molecular weight is about 80,000～600,000).
POLYACTIC ACID preparation method provided by the invention has the following advantages:
The present invention nontoxic to contain, to human body the dibutylmagnesium of friendly mg ion do not have the toxic metal element residual in the POLYACTIC ACID of preparation as the catalyzer of rac-Lactide ring-opening polymerization.
2. only use a spot of organic solvent in the preparation process of technical scheme of the present invention, avoid a large amount of solvents to use and cause environmental problem.
3. resulting POLYACTIC ACID can keep good optical purity, and molecular weight ranges is wide and controlled, and is very suitable to the raw material of fracture internal fixing with the degradable nail.
4. preparation method provided by the invention is easy and simple to handle, reaction conditions is gentle, yield is higher.
Embodiment
Following examples are used to explain the present invention, but are not used for limiting scope of the present invention.
Embodiment 1
The 20g optical purity of in reaction kettle, packing into is pressed monomer: catalyzer then greater than 99% L-rac-Lactide: initiator=5000: 1: 40 (mol ratio) adds dibutylmagnesium 0.0038g, lauryl alcohol 0.207g.Reaction kettle is vacuumized, use the nitrogen replacement repetitive operation then three times, close reaction kettle under the vacuum, reaction kettle is slowly heated again, 110 ℃ were reacted 48 hours under steady temperature.Behind the stopped reaction, reaction kettle is cooled to room temperature, adds unreacted monomer in the washed with dichloromethane still.At last polymkeric substance is placed vacuum drying oven,, obtain white translucent solid 30 ℃ of following vacuum-dryings 48 hours, productive rate 95%, optical purity is greater than 99%.Polymer viscosity is about 0.8dl/g (ASTM D2857-95).
Embodiment 2
The 20g optical purity of in reaction kettle, packing into is pressed monomer: catalyzer then greater than 99% L-rac-Lactide: initiator=5000: 1: 6 (mol ratio) adds dibutylmagnesium 0.0038g, lauryl alcohol 0.0309g.Reaction kettle is vacuumized, use the nitrogen replacement repetitive operation then three times, close anti-still under the vacuum, again reaction kettle is slowly heated, reacted 48 hours down for 130 ℃ in steady temperature.Behind the stopped reaction, reaction kettle is cooled to room temperature, adds unreacted monomer in the trichloromethane washing still.At last polymkeric substance is placed vacuum drying oven,, obtain white solid 30 ℃ of vacuum-dryings 48 hours, productive rate 92%, optical purity is greater than 99%.Polymer viscosity is 3.2dl/g (ASTM D2857-95).
Embodiment 3
In reaction kettle, pack into the rac-Lactide of 20g, press monomer then: catalyzer: initiator=5000: 1: 2 (mol ratio) adds dibutylmagnesium 0.0038g, lauryl alcohol 0.0103g.Reaction kettle is vacuumized, use the nitrogen replacement repetitive operation then three times, close reactor drum under the vacuum, reaction kettle is slowly heated again, 120 ℃ were reacted 48 hours under steady temperature.Behind the stopped reaction, reaction kettle is cooled to room temperature, adds unreacted monomer in the washed with dichloromethane still then.At last polymkeric substance is placed vacuum drying oven, 30 ℃ of vacuum-dryings 48 hours, obtain faint yellow solid, productive rate 92%, polymer viscosity are 5.0dl/g (ASTMD2857-95).
Comparative Examples
With the rac-Lactide charging capacity identical, according to the prepared POLYACTIC ACID of Chinese patent CN 101367921 with embodiment 1.
The 20 gram rac-Lactides of in reaction kettle, packing into, press monomer: catalyzer=100: 1 (mol ratio) adds l-arginine 0.242g.Reaction kettle is vacuumized, use the nitrogen replacement repetitive operation then three times, close reaction kettle under the vacuum, reaction kettle is slowly heated, reacted 48 hours down for 160 ℃ in steady temperature.Behind the stopped reaction, reaction kettle is cooled to room temperature, adds acetone solution still interpolymer then.Adding deionized water then comes out polymer precipitation.The filtering water places vacuum drying oven with deposition at last, 40 ℃ of dryings 48 hours, obtains the white powder solid, productive rate 87%.Polymer viscosity is 1.1dl/g.
Though, the present invention has been done detailed description in the preceding text with general explanation and specific embodiments, on basis of the present invention, can to some modifications of do or improvement, this will be apparent to those skilled in the art.Therefore, these modifications or the improvement on the basis of not departing from spirit of the present invention, made all belong to the scope that requirement of the present invention is protected.
Claims (10)
1. the preparation method of a POLYACTIC ACID is characterized in that, is monomer with the rac-Lactide, under the catalysis of dibutylmagnesium, carries out polyreaction and makes.
2. preparation method according to claim 1 is characterized in that, said rac-Lactide is the L-rac-Lactide.
3. preparation method according to claim 1 is characterized in that, said polyreaction adds initiator and causes.
4. preparation method according to claim 3 is characterized in that, said initiator is lauryl alcohol or terepthaloyl moietie.
5. preparation method according to claim 4 is characterized in that, the mol ratio of said rac-Lactide, initiator, dibutylmagnesium is 3000～10000: 1～5: 1～40.
6. according to each described preparation method of claim 1-5, it is characterized in that the temperature of reaction of said polyreaction is 100～150 ℃, the reaction times is 24～48 hours.
7. preparation method according to claim 6 is characterized in that said polyreaction is carried out under the protection of rare gas element.
8. preparation method according to claim 7 is characterized in that, said rare gas element is helium, argon gas or nitrogen.
9. according to each described preparation method of claim 1-8; It is characterized in that; Said preparation method also comprises: after said polyreaction finishes; Adopt the unreacted lactide monomer of organic solvent flush away, residual polymkeric substance promptly got said POLYACTIC ACID in 24～72 hours 20～40 ℃ of following vacuum-dryings.
10. preparation method according to claim 9 is characterized in that, said organic solvent is one or more in methylene dichloride, trichloromethane, ETHYLE ACETATE, ethanol, methyl alcohol, sherwood oil, the tetracol phenixin.
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| CN2012101867039A CN102702488A (en) | 2012-06-07 | 2012-06-07 | Preparation method for polylactic acid |
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| CN2012101867039A CN102702488A (en) | 2012-06-07 | 2012-06-07 | Preparation method for polylactic acid |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892916A (en) * | 2015-06-11 | 2015-09-09 | 南京大学 | Technology for controlled synthesis of polylactic acid through lactide activity ring-opening polymerization under catalytic action of organic guanidine-nontoxic alcohol |
| CN111499844A (en) * | 2018-03-08 | 2020-08-07 | 深圳市立心科学有限公司 | Medical polylactic acid and preparation method thereof |
| CN117089051A (en) * | 2023-10-20 | 2023-11-21 | 山东谷雨春生物科技有限公司 | Method for synthesizing high molecular weight polylactic acid by solution polymerization method |
-
2012
- 2012-06-07 CN CN2012101867039A patent/CN102702488A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| HANS R. KRICHELDFORF ET AL.: "Polylactones: 32. High-molecular-weight polylactides by ring-opening polymerization with dibutylmagnesium or butylmagnesium chloride", 《POLYMER》 * |
| 魏志勇: "生物可降解脂肪族聚酯的制备、表征与性能研究", 《中国博士学位论文全文数据库（工程科技I辑）》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892916A (en) * | 2015-06-11 | 2015-09-09 | 南京大学 | Technology for controlled synthesis of polylactic acid through lactide activity ring-opening polymerization under catalytic action of organic guanidine-nontoxic alcohol |
| CN111499844A (en) * | 2018-03-08 | 2020-08-07 | 深圳市立心科学有限公司 | Medical polylactic acid and preparation method thereof |
| CN111499844B (en) * | 2018-03-08 | 2022-12-09 | 深圳市立心科学有限公司 | Medical polylactic acid and preparation method thereof |
| CN117089051A (en) * | 2023-10-20 | 2023-11-21 | 山东谷雨春生物科技有限公司 | Method for synthesizing high molecular weight polylactic acid by solution polymerization method |
| CN117089051B (en) * | 2023-10-20 | 2024-01-26 | 山东谷雨春生物科技有限公司 | Method for synthesizing high molecular weight polylactic acid by solution polymerization method |
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Application publication date: 20121003 |