CN107445937A - A kind of method for preparing medical lactide - Google Patents
A kind of method for preparing medical lactide Download PDFInfo
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- CN107445937A CN107445937A CN201610380998.1A CN201610380998A CN107445937A CN 107445937 A CN107445937 A CN 107445937A CN 201610380998 A CN201610380998 A CN 201610380998A CN 107445937 A CN107445937 A CN 107445937A
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- Prior art keywords
- lactic acid
- lactide
- catalyst
- reaction
- added
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/12—1,4-Dioxanes; Hydrogenated 1,4-dioxanes not condensed with other rings
Abstract
The present invention relates to a kind of method for preparing medical lactide, including：Catalyst is added in lactic acid and high boiling solvent carries out polycondensation reaction so that lactic acid generates lact-acid oligomer；Catalyst is added in the lact-acid oligomer of generation, depolymerization reaction is carried out, obtains medical lactide.Method provided by the invention, high boiling solvent is added in polycondensation process, reaction system is not reduced in depolymerization because of the distillation of lactide and become sticky, be not easy to steam, be carbonized, turn yellow, ensure that the stabilization and product quality of production process, and the variability of physical index；And yield is higher, operation is simple, not dangerous, and the production time is short, beneficial to industrialized production, has very high economic value.
Description
Technical field
The present invention relates to the preparation field of high-molecular compound, in particular it relates to a kind of method for preparing medical lactide.
Background technology
Medical lactide is the important source material of synthesis of medical PLA, and medical poly-lactic acid material is as 21 century novel green
Material has extensive prospect in terms of bio-medical material.PLA is nontoxic, nonirritant, have excellent biocompatibility,
Bioabsorbable and biodegradability, also there is high mechanical strength, stable chemical performance and easy processing, Ke Yizuo
For biomedical material, the slow-released carrier as medicine, Srgery grafting material.
And in the synthesis technique of medical PLA, the purity of lactide is extremely important, to make poly-lactic acid in high molecular weight,
High-purity lactide must be selected.The method that existing patent typically uses ring-opening polymerisation, high temperature high vacuum cracking lactic acid oligomers
Prepare lactide.
Such as Chinese patent application 200310107684.7（Publication No. CN 1616450A）One kind is disclosed to add at twice
The method of catalyst preparation lactide, its preparation process are：
1st, lactic acid and catalyst Z nO are pressed 135 ~ 165:1 ratio is added in container and heated, and temperature reaches 100 DEG C and vacuumized,
Slowly heating increases vacuum in 2 ~ 2.5 hours；
2nd, when temperature reaches 135 ~ 155 DEG C, ZnO and La are added2O3, two mixed catalyst mass ratioes are 3 ~ 5:1, it is lactic acid
The 1/300 ~ 250/1 of quality:1；
3rd, vacuum maintains 30 ~ 60min in 0.03 ~ 0.04MPa, sloughs moisture, and no water changes receiving flask when distilling；
4th, heat up 170 ~ 190 DEG C, increase 0.09 ~ 0.10MPa of vacuum, receptive liquid, it is lactide crystal to be cooled to room temperature.
Chinese patent application 200810064553.8（Publication No. CN 101585827A）Disclose one kind and use D, L- breasts
Sour normal pressure dehydration, catalyst decompression dehydration generate lact-acid oligomer, then oligomer Pintsch process generation D, the method for L- lactides,
Its preparation process is：
1st, D, 145 DEG C of normal pressure zeolite dehydrations of Pfansteihl；
2nd, lact-acid oligomer adds catalyst（ZnO）1.5wt% depressurizes 150 DEG C of boiling 2 ~ 3h dehydrations；
170 ~ 250 DEG C of Pintsch process of lact-acid oligomer, it is evaporated under reduced pressure under -0.095Mpa vacuum systems, obtains lactide.
And above patented method has the following disadvantages：
1st, the lactide obtained is light yellow or yellow；
2nd, reactant gradually tails off with the distillation of lactide and sticky, carbonization occurs, and causes to be not easy to distill, and yield reduces；
3rd, the lactide of distillation early stage and the lactide of later stage distillation are unstable on physical index, and variability is bigger.
In the method for existing ring-opening polymerisation generation lactide, the patent on dehydration, polycondensation and depolymerization three-step reaction
Technology is as follows：
Chinese patent application 200510094947.4（Publication No. CN 1951933A）Disclose a kind of polymerization under atmospheric pressure high temperature inert
Gas takes reaction product out of, cooling obtains the method for lactide, and its preparation process is：
1st, L lactic acid carries out dehydration under 150 ~ 180 DEG C of vacuum 5000pa ~ 8000pa, obtains lact-acid oligomer；
2nd, 150 ~ 250 DEG C of synthesis under normal pressure of lact-acid oligomer；
3rd, gasification lactide is taken out of by 200 ~ 500 DEG C of inert gases, lactide is collected in then cooling.
The patented method has the following disadvantages：
1st, reactant tails off with the distillation of lactide and sticky, carbonization occurs, and causes to be not easy to distill, yield reduces；
2nd, operation and the dangerous property of recovery of high-temperature gas are heated.
Chinese patent application 200810080194.5（Publication No. CN 101434594A）Disclose a kind of mixed solvent method
The method for preparing lactide, its preparation process are：
1st, D/L- lactic acid carries out dehydration at 120 DEG C；
2nd, heat up 160 DEG C, add 0.7 ~ 0.8% catalyst, add low boiling point solvent 10 ~ 20%；
3rd, heat up 220 DEG C, add 0.7 ~ 0.8% catalyst, be evaporated under reduced pressure, produce lactic acid oligomer；
4th, heating decompression lactic acid oligomer, in 160 ~ 200 DEG C, 600 ~ 760mmHg of vacuum, material becomes brown or black by dark yellow
Color, start to crack；Temperature is reacted 2 ~ 3 hours to 250 ~ 280 DEG C, adds high boiling solvent 15 ~ 25%, is evaporated under reduced pressure 4 hours, is obtained
To lactide.
The patented method has the following disadvantages：
1st, lactide color is more yellow；
2nd, process is complicated, and the production time is long, can not large-scale production.
Therefore, if the preparation method for the lactide that prior art relevant issues are overcome at one can be developed, for the neck
Field technique is most important.
The content of the invention
In order to solve the problems, such as that prior art is present, it is an object of the invention to provide a kind of side for preparing medical lactide
Method.
The present invention relates to a kind of method for preparing medical lactide, including：Catalyst is added in lactic acid and higher boiling is molten
Agent carries out polycondensation reaction so that lactic acid generates lact-acid oligomer；Catalyst is added in the lact-acid oligomer of generation, it is anti-to carry out depolymerization
Should, obtain medical lactide.
Wherein, the high boiling solvent is：Diethyl phthalate, silicone oil, hexadecanol or octadecyl alcolol.It is preferred that adjacent benzene two
Formic acid diethylester；
Wherein, the weight of lactic acid and high boiling solvent ratio is 0.5 ~ 2:1；
Wherein, the catalyst added in lactic acid is：Stannous octoate, stannous sulfate, tin octoate or lactic acid tin；
Wherein, lactic acid and the weight ratio that catalyst is added in lactic acid are 800 ~ 1200：1；
Wherein, the process of polycondensation reaction includes pre-polymerization and eventually poly- reaction；
Wherein, through prepolymerization reaction 3 ~ 5 hours under conditions of 150 ~ 200 DEG C and 110 ~ 25Kpa；In 160 ~ 190 DEG C and 20 ~ 5Kpa
Under conditions of through poly- reaction 1.5 ~ 2.5 hours eventually；
Wherein, lactic acid and the weight ratio that catalyst is added in lact-acid oligomer are 600 ~ 700:1, preferably 667:1；
Wherein, medical lactide is obtained through depolymerization reaction, distillation under conditions of 200 ~ 250 DEG C and 10 ~ 3Kpa.It is preferred that 220
DEG C and 3Kpa under conditions of carry out depolymerization reaction；
Wherein, this method is before polycondensation reaction is carried out, in addition to：Dehydration is carried out to lactic acid；
Wherein, the process of dehydration includes：Under conditions of 90 ~ 150 DEG C and 200 ~ 300Kpa, condensation dehydration 2 ~ 4 hours.It is excellent
The condition is selected to be：It is dehydrated 3 hours under 120 DEG C and 200 ~ 250Kpa；
This area can be used conventional for the dehydration of the present invention or disclosed method, can also use the above-mentioned method of the present invention；Afterwards
Person cause the present invention prior art has been done it is improved on the basis of, whole structure is more excellent, and the purpose of dehydration is in order to rear
Face polymerization is more complete；
Method provided by the invention, it is improved on the basis of method of the existing cyclopolymerization into lactide, then in polycondensation process
Add high boiling solvent, be reaction system will not be reduced in depolymerization because of the distillation of lactide and become sticky, be not easy to steam,
Carbonization, turn yellow, ensure that the stabilization and product quality of production process, and the variability of physical index.Obtained lactide exists
Advantageous on material purity and the required accuracy, if subsequently recrystallizing again, number can be seldom.And yield is higher, operation letter
Single, not dangerous, the production time is short, beneficial to industrialized production, has very high economic value.
Embodiment
Normal pressure in the present invention refers to 0.1Mpa.
Embodiment 1
50kgL- lactic acid is added in a kettle, the air in replacement reaction kettle；Medium is heated as oil, oil temperature is raised to 120 DEG C,
200Kpa slowly is evacuated to, condensation dehydration, water gradually stops after 3 hours；After logical nitrogen to normal pressure draining, 50g antimony oxides are added
With diethyl phthalate 25kg；Oil temperature is warming up to 170 DEG C, continues slowly to be evacuated to 30Kpa, reacts 4 hours；Now
The preliminary combination water sloughed between lactic acid, by after the dehydrating polycondensation of intermolecular hydroxyl and carboxyl, making lactic acid molecules start to polymerize；
Then lead to after nitrogen to normal pressure draining and change heating medium into water, temperature control continues to be evacuated to 20Kpa, backflow 2 at 175 DEG C
Hour, generate lact-acid oligomer；The last inert nitrogen gas that is passed through in a kettle discharges caused steaming in course of reaction to normal pressure
Distilled water, 75g stannous octoates are added in obtained lact-acid oligomer, heating medium is oil, in 220 DEG C of oil temperature, is evacuated to 3Kpa
Under distill out lactide liquid, the liquid is collected into the storage tank protected with 75 DEG C of water temperatures, discharge separate out after cooling again
Sediment, i.e. product L- lactides, white lenticular, it can be used as medical.
Embodiment 2
With embodiment 1, except that raw material adds 50kgD, Pfansteihl, D, L- lactides, in white is prepared in other conditions
Color lenticular.
Embodiment 3
Other conditions are with embodiment 1, except that it is 1 to add weight ratio:1 Pfansteihl and diethyl phthalate, system
It is standby to obtain L- lactides, white lenticular.
Embodiment 4
Other conditions are with embodiment 1, except that it is 1 to add weight ratio:2 D-ALPHA-Hydroxypropionic acid and diethyl phthalate, system
It is standby to obtain D- lactides, white lenticular.
Claims (6)
1. a kind of method for preparing medical lactide, including：Catalyst is added in lactic acid and high boiling solvent progress polycondensation is anti-
Should so that lactic acid generates lact-acid oligomer；Add catalyst in the lact-acid oligomer of generation, carry out depolymerization reaction, be applied third
Lactide：
The high boiling solvent is：Diethyl phthalate, silicone oil, hexadecanol or octadecyl alcolol；
The weight of lactic acid and high boiling solvent ratio is 0.5 ~ 2:1；
The catalyst added in lactic acid is：Stannous octoate, stannous sulfate, tin octoate or lactic acid tin.
2. according to the method for claim 1, it is characterised in that lactic acid is with the weight ratio that catalyst is added in lactic acid
800~1200：1.
3. method according to claim 1 or 2, it is characterised in that the process of polycondensation reaction includes pre-polymerization and eventually poly- reaction；
Through prepolymerization reaction 3 ~ 5 hours under conditions of 150 ~ 200 DEG C and 110 ~ 25Kpa；Under conditions of 160 ~ 190 DEG C and 20 ~ 5Kpa
Through poly- reaction 1.5 ~ 2.5 hours eventually.
4. according to the method for claim 1, it is characterised in that lactic acid and the weight that catalyst is added in lact-acid oligomer
Than for 600 ~ 700:1.
5. according to the method for claim 1, it is characterised in that anti-through depolymerization under conditions of 200 ~ 250 DEG C and 10 ~ 3Kpa
Should, distillation obtains medical lactide.
6. according to the method described in claim 1,2,4 or 5, it is characterised in that this method is also wrapped before polycondensation reaction is carried out
Include：Dehydration is carried out to lactic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610380998.1A CN107445937A (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing medical lactide |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610380998.1A CN107445937A (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing medical lactide |
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| Publication Number | Publication Date |
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| CN107445937A true CN107445937A (en) | 2017-12-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610380998.1A Pending CN107445937A (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing medical lactide |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113603671A (en) * | 2021-08-13 | 2021-11-05 | 山东谷雨春生物科技有限公司 | Method for improving yield of lactide |
| CN113651794A (en) * | 2021-09-15 | 2021-11-16 | 珠海格力新材料有限公司 | Lactide synthesis method |
-
2016
- 2016-06-01 CN CN201610380998.1A patent/CN107445937A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113603671A (en) * | 2021-08-13 | 2021-11-05 | 山东谷雨春生物科技有限公司 | Method for improving yield of lactide |
| CN113651794A (en) * | 2021-09-15 | 2021-11-16 | 珠海格力新材料有限公司 | Lactide synthesis method |
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Application publication date: 20171208 |