CN102875779A - Process method for synthesizing medical biodegradable polylactic acid by performing polycondensation on lactic acid through catalysis of 1,5,7-triazabicyclo[4.4.0]decane-5-ene (TBD) - Google Patents
Process method for synthesizing medical biodegradable polylactic acid by performing polycondensation on lactic acid through catalysis of 1,5,7-triazabicyclo[4.4.0]decane-5-ene (TBD) Download PDFInfo
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229920000747 poly(lactic acid) Polymers 0.000 title claims abstract description 37
- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 31
- 239000004310 lactic acid Substances 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 17
- 239000004626 polylactic acid Substances 0.000 title claims abstract description 10
- 238000006068 polycondensation reaction Methods 0.000 title claims abstract description 9
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 7
- FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 title abstract description 4
- 230000002194 synthesizing effect Effects 0.000 title abstract description 3
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000000178 monomer Substances 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 3
- -1 poly(lactic acid) Polymers 0.000 claims description 58
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 54
- 238000006243 chemical reaction Methods 0.000 claims description 46
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 29
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 29
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 24
- 241001024099 Olla Species 0.000 claims description 16
- 229910052786 argon Inorganic materials 0.000 claims description 12
- 238000006297 dehydration reaction Methods 0.000 claims description 12
- 239000007789 gas Substances 0.000 claims description 12
- 238000010792 warming Methods 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 4
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 238000012662 bulk polymerization Methods 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 231100000331 toxic Toxicity 0.000 abstract description 6
- 230000002588 toxic effect Effects 0.000 abstract description 6
- 239000002184 metal Substances 0.000 abstract description 5
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 2
- 230000003013 cytotoxicity Effects 0.000 abstract description 2
- 238000009826 distribution Methods 0.000 abstract description 2
- 238000012643 polycondensation polymerization Methods 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 239000012974 tin catalyst Substances 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 239000000126 substance Substances 0.000 description 12
- 230000003292 diminished effect Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 238000003672 processing method Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
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- Polyesters Or Polycarbonates (AREA)
- Medicinal Preparation (AREA)
- Biological Depolymerization Polymers (AREA)
Abstract
The invention discloses a method for synthesizing medical biodegradable polylactic acid by directly performing polycondensation on lactic acid through catalysis of 1,5,7-triazabicyclo[4.4.0]decane-5-ene (TBD). According to the method, the polylactic acid product which is high in biosecurity is obtained by taking the TBD as a catalyst, and an industrial grade lactic acid aqueous solution of which the mass content is 90 percent as monomers, and by solvent-free (body) and two-stage condensation polymerization. According to the method, a tin catalyst which has cytotoxicity is eliminated, and the used catalyst has biocompatibility and biosecurity; the synthesized polylactic acid does not contain any metal and other toxic component and is suitable for medical and medicinal fields; the environment-friendly biodegradable polylactic acid is synthesized by an environment-friendly process (in which any reagent is not used and any toxic product is not generated) by using the environment-friendly catalyst; the polymerization reaction is convenient to realize and practicable; raw materials are low in cost, and the industrial production is easy to realize; and the synthesized product is narrow in molecular weight distribution, and the molecular weight can be regulated from 1.0*10<4> to 4.0*10<4>.
Description
Technical field:
The invention belongs to drug degradation material technology field, relate to the synthetic processing method with height biological safety poly(lactic acid) of bicyclo guanidine catalysis lactic acid.
Background technology:
In recent years, medicine and biomedical development are swift and violent, and the degradable material demand that can be applied to the bioactive bracket material in controlled release and target medicine carrier, hard tissue repairing material, the bioengineered tissue is sharply increased.Biodegradable polylactic acid has good biocompatibility, can improve drug effect, reduce the toxic side effect of dosage and medicine etc. as pharmaceutical carrier, makes it obtain many important application at pharmaceutical science and biomedical aspect.The main employing of at present commercialization poly(lactic acid) production stannous octoate open loop polycondensation method is synthetic and Sold Stannous Chloride Catalyzes acid through direct polycondensation by lactic method is synthetic.But during as pharmaceutical carrier, require not contain in the polymkeric substance any toxic metal and virose other compositions of tool.More than two kinds of methods can reach pharmaceutical carrier desired molecule amount (1.0 * 10
4~4.0 * 10
4) requirement, but used Heavy Metal, Sn saline catalyst is difficult to remove from polymkeric substance, studies have shown that stannous octoate and tin protochloride have cytotoxicity, attract wide attention with the security of the synthetic engineering materials of tin class catalyzer, make its application at pharmaceutical field obtain restriction.Thereby exploitation is efficient, non-toxic catalyst is present research emphasis for the synthetic of poly(lactic acid).
Summary of the invention:
The objective of the invention is to solve the poly(lactic acid) that adopts tin class catalyzer to synthesize, be used for having potential security hidden trouble on the human medicine carrier, provide a kind of nontoxic, be that the direct catalysis lactic acid polymerizes of catalyzer generates the processing method with height biological safety medical biodegradable poly(lactic acid) without the bicyclo guanidine compound of metal.
The present invention develop first a kind of utilize nontoxic, be catalyzer without organic guanidine compound (bicyclo guanidine) of metal, the lactic acid aqueous solution of mass content 90% is monomer, through the novel process of the synthetic height of body condensation polymerization method biological safety poly(lactic acid).
Used in the present invention nontoxic, without the organic guanidine compound of metal---bicyclo guanidine, its chemistry is by name: 1,5,7-three azabicyclics [4.4.0] last of the ten Heavenly stems-5-alkene (1,5,7-Triazabicyclo[4.4.0] dec-5-ene, english abbreviation is: TBD), its molecular structural formula is as follows:
The synthetic processing method with height biological safety, degradable poly lactic acid of bicyclo guanidine catalysis acid through direct polycondensation by lactic provided by the invention is, utilize organic guanidine compound (bicyclo guanidine) as catalyzer, mass content is that 90% lactic acid aqueous solution is monomer, through the synthetic height of mass polymerization biological safety poly(lactic acid), specifically comprise:
Synthetic route:
Synthesis step:
1st, lactic acid oligomer OLLA's is synthetic
Take the technical grade mass content as 90% lactic acid aqueous solution as monomer, the lactic acid oligomer OLLA of composite number average molecular weight Mn 400 ~ 600 at first, synthesis condition: in reactor, add lactic acid, repeat to vacuumize applying argon gas operation three times after; Under 200Torr, be heated to 100 ~ 120 ℃, dehydration 1h; Reactor is decompressed to 100Torr continues reaction 1h at 130 ~ 150 ℃; Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ~ 170 ℃.
2nd, poly(lactic acid) PLLA's is synthetic
Go on foot synthetic lactic acid oligomer OLLA as raw material, take the commercialization bicyclo guanidine as catalyzer take the 1st, control bicyclo guanidine and lactic acid mass ratio are 1:300 ~ 1:6500, under decompression and certain temperature, carry out the body melt phase polycondensation, the synthetic medicinal poly(lactic acid) of height biological safety that obtains, synthesis condition: in reactor, add the catalyzer bicyclo guanidine, reactor is decompressed to 10Torr, is warming up to 180 ~ 230 ℃ of reaction 10 ~ 20h, obtain poly(lactic acid) PLLA.
The polylactic acid molecule amount that the inventive method is synthesized is 1.0 * 10
4~ 4.0 * 10
4, molecular weight distributing index (PDI) is 1.7-2.0.
Advantage of the present invention and beneficial effect:
1. catalyst system therefor has high degree of biocompatibility, biological safety;
2. institute's synthesizing polylactic acid does not contain any metal and other toxic components, therefore is suitable for the carrier of controlled release and targeted drug;
3. adopt green catalyst and friendly process (do not use any solvent, generate without toxic products), synthetic green (height biological safety) biological degradability poly(lactic acid);
4. institute's sintetics narrow molecular weight distribution, molecular weight can be implemented in 1.0 * 10
4~ 4.0 * 10
4Scope is controlled.
5. react the used time short (10 ~ 20h);
6. polymerization technology is easy, and raw materials cost is cheap, is easy to industrializing implementation.
Embodiment:
Embodiment 1
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 100 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr, at 130 ℃ of lower reaction 1h that continue.Then reactor is decompressed to 30Torr and continues reaction 1h at 160 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 240mg to reactor, reactor is decompressed to 10Torr, be warming up to 180 ℃ of reaction 10h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 75.6%, polymericular weight 1.5 * 10
4, PDI 1.87.
Embodiment 2
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize applying argon gas operation three times.Under 200Torr, be heated to 110 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 130 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 240mg to reactor, reactor is decompressed to 10Torr, be warming up to 190 ℃ of reaction 16h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 73.1%, polymericular weight 2.3 * 10
4, PDI 1.70.
Embodiment 3
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 120 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 130 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 120mg to reactor, reactor is decompressed to 10Torr, be warming up to 200 ℃ of reaction 20h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 70.1%, polymericular weight 3.6 * 10
4, PDI 1.90.
Embodiment 4
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 110 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 140 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 120mg to reactor, reactor is decompressed to 10Torr, be warming up to 210 ℃ of reaction 13h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 69.2%, polymericular weight 4.0 * 10
4, PDI 1.85.
Embodiment 5
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize applying argon gas operation three times.Under 200Torr, be heated to 100 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 150 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 72mg to reactor, reactor is decompressed to 10Torr, be warming up to 220 ℃ of reaction 10h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 67.4%, polymericular weight 2.9 * 10
4, PDI 2.00.
Embodiment 6
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize applying argon gas operation three times.Under 200Torr, be heated to 120 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 140 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 160 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 136mg to reactor, reactor is decompressed to 10Torr, be warming up to 220 ℃ of reaction 15h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 48.5%, polymericular weight 3.4 * 10
4, PDI 1.85.
Embodiment 7
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 100 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 140 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 170 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 72mg to reactor, reactor is decompressed to 10Torr, be warming up to 230 ℃ of reaction 16h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 66.3%, polymericular weight 3.9 * 10
4, PDI 1.78.
Embodiment 8
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 110 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 150 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 160 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 36mg to reactor, reactor is decompressed to 10Torr, be warming up to 200 ℃ of reaction 15h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 74.6%, polymericular weight 2.4 * 10
4, PDI 1.92.
Embodiment 9
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize applying argon gas operation three times.Under 200Torr, be heated to 120 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 150 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 36mg to reactor, reactor is decompressed to 10Torr, be warming up to 200 ℃ of reaction 16h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 71.3%, polymericular weight 3.2 * 10
4, PDI 1.75.
Embodiment 10
Pack in the reactor Pfansteihl (mass content 90%) of 80g repeats to vacuumize-applying argon gas operation three times.Under 200Torr, be heated to 120 ℃, dehydration reaction 1h.Then reactor is decompressed to 100Torr and continues reaction 1h at 150 ℃.Then reactor is decompressed to 30Torr and continues reaction 1h at 170 ℃, obtain lactic acid oligomer OLLA.
Add catalyzer bicyclo guanidine 11.1mg to reactor, reactor is decompressed to 10Torr, be warming up to 210 ℃ of reaction 20h.Behind the stopped reaction, reactor is chilled to room temperature, with the polymkeric substance acetone solution, then pours in 0 ℃ the ethanol, filtration under diminished pressure, solid is dry 36h under 50 ℃ and vacuum, obtains white solid, i.e. height biological safety medicinal poly(lactic acid), productive rate 68.4%, polymericular weight 4.0 * 10
4, PDI 1.91.
Claims (2)
1. the method for a bicyclo guanidine catalysis acid through direct polycondensation by lactic synthesis of medical biodegradable poly(lactic acid), it is characterized in that the method utilizes the organic guanidine catalyst of biological safety, lactic acid is monomer, synthesizes through bulk polymerization to have height biological safety poly(lactic acid), specifically comprises:
Synthetic route:
Synthesis step:
1st, lactic acid oligomer OLLA's is synthetic
Take the technical grade mass content as 90% lactic acid aqueous solution as monomer, the lactic acid oligomer OLLA of composite number average molecular weight Mn 400 ~ 600 at first, synthesis condition: in reactor, add lactic acid, repeat to vacuumize applying argon gas operation three times after; Be to be heated to 100 ~ 120 ℃ under the 200Torr in vacuum, dehydration 1h; Reactor is decompressed to 100Torr continues reaction 1h at 130 ~ 150 ℃; Then reactor is decompressed to 30Torr and continues reaction 1h at 150 ~ 170 ℃;
2nd, poly(lactic acid) PLLA's is synthetic
Go on foot synthetic lactic acid oligomer OLLA as raw material, take the commercialization bicyclo guanidine as catalyzer take the 1st, control bicyclo guanidine and lactic acid mass ratio are 1:300 ~ 1:6500, under decompression and certain temperature, carry out the body melt phase polycondensation, the synthetic medicinal poly(lactic acid) of height biological safety that obtains, synthesis condition: in reactor, add the catalyzer bicyclo guanidine, reactor is decompressed to 10Torr, is warming up to 180 ~ 230 ℃ of reaction 10 ~ 20h, obtain poly(lactic acid) PLLA.
2. method according to claim 1, the polylactic acid molecule amount that it is characterized in that adopting the method for organic guanidine catalyzing and condensing polymerization to be synthesized in 10-20h is 1.0 * 10
4~ 4.0 * 10
4, molecular weight distributing index (PDI) is 1.7 ~ 2.0.
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CN104725616A (en) * | 2015-04-13 | 2015-06-24 | 南京大学 | Novel process for using organic guanidine catalysis melt-solid polycondensation to synthesize poly (butylene adipate-co-terephthalate) |
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 |
CN112094407A (en) * | 2020-09-27 | 2020-12-18 | 江南大学 | Biguanide group covalent organic framework material and preparation method and application thereof |
CN114685772A (en) * | 2022-04-20 | 2022-07-01 | 深圳光华伟业股份有限公司 | Novel biomedical polylactic acid synthesis method |
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Cited By (7)
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CN104725616A (en) * | 2015-04-13 | 2015-06-24 | 南京大学 | Novel process for using organic guanidine catalysis melt-solid polycondensation to synthesize poly (butylene adipate-co-terephthalate) |
CN104725616B (en) * | 2015-04-13 | 2017-01-11 | 南京大学 | Novel process for using organic guanidine catalysis melt-solid polycondensation to synthesize poly (butylene adipate-co-terephthalate) |
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 |
CN104892916B (en) * | 2015-06-11 | 2017-01-11 | 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 |
CN112094407A (en) * | 2020-09-27 | 2020-12-18 | 江南大学 | Biguanide group covalent organic framework material and preparation method and application thereof |
CN112094407B (en) * | 2020-09-27 | 2021-10-08 | 江南大学 | Biguanide group covalent organic framework material and preparation method and application thereof |
CN114685772A (en) * | 2022-04-20 | 2022-07-01 | 深圳光华伟业股份有限公司 | Novel biomedical polylactic acid synthesis method |
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