CN100427524C - Process for preparing nontoxic poly lactic acid by direct condensation polymerization of lactic acid - Google Patents
Process for preparing nontoxic poly lactic acid by direct condensation polymerization of lactic acid Download PDFInfo
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- CN100427524C CN100427524C CNB200510042859XA CN200510042859A CN100427524C CN 100427524 C CN100427524 C CN 100427524C CN B200510042859X A CNB200510042859X A CN B200510042859XA CN 200510042859 A CN200510042859 A CN 200510042859A CN 100427524 C CN100427524 C CN 100427524C
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- lactic acid
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Abstract
The present invention provides a method for preparing polylactic acid by melt polycondensation on lactic acid as raw material. After lactic acid is dried and dehydrated, the polycondensation reaction is carried out on the lactic acid under the condition that the temperature is from 100 DEG C to 200 DEG C and the vacuum degree is from 0.1 mmHg to 100 mmHg. Thereby, the polylactic acid is obtained. The present invention does not use any solvent and catalyst, and therefore, the reaction process has no catalyst residue and solvent residue. The present invention can be widely used for the medical domain. The present invention uses the lactic acid as the raw material. Therefore, the cost is low, the productive rate is high, and the molecular weight of the prepared polylactic acid is high. The present invention has simple technology and convenient operation and is favorable to industrial production.
Description
Technical field
The invention belongs to technical field of polymer materials, relate to a kind of preparation method of poly(lactic acid), relate in particular to a kind of method of utilizing the directly synthetic nontoxic medicinal poly(lactic acid) of melt-polycondensation.
Background technology
Poly(lactic acid) (PLA) is a kind of nontoxic, biodegradable polymkeric substance, has excellent biological compatibility.The eventual degradation product of poly(lactic acid) is H
2O and CO
2, intermediate product lactic acid also is normal carbohydrate metabolism product in the body, so can not assemble at vitals.Along with the application of PLA and multipolymer particularly in the continuous expansion of biomedical engineering field, research synthetic to it and that use is deep day by day.The method of synthesizing polylactic acid mainly contains the ring-opening polymerization of rac-Lactide and the direct condensation of lactic acid at present.
Though adopt the ring-opening polymerization of rac-Lactide can obtain high molecular weight polylactic acid, price height low owing to its productive rate and rac-Lactide makes holding at high price of poly(lactic acid), thereby has limited its widespread use.And the direct condensation of poly(lactic acid) is the method for an economy.Because the monomer lactic acid of synthesizing polylactic acid is that inexhaustible farm crop---corn, paddy, potato, Ipomoea batatas etc. are produced as raw material constantly to regenerate on the earth, this just lays a solid foundation for the directly synthetic of poly(lactic acid).In the research of direct method synthesizing polylactic acid, using maximum is solution polymerization, and the polylactic acid molecule amount that this method obtains is higher, but dissolvent residual is arranged, and productive rate is not high yet.In the application of reality, its purposes difference of the poly(lactic acid) of different molecular weight.The poly(lactic acid) that is used for delivery system, molecular weight are between 4000-10000, because the degraded in vivo of the poly(lactic acid) of this molecular weight meets the needs of drug release.Poly(lactic acid) can be divided into two kinds of situations as the carrier of controlled-release pharmaceutical formulation: the one, make pharmaceutical capsule, allowing medicine quantitatively continue to discharge keeps Plasma Concentration steady relatively, reduce medicining times, reduce some medicines simultaneously and concentrate absorption stomach pungency and toxic side effect; The 2nd, be used for the miniature coating film of medicine, zymin, biological products microballon, microballoon as capsule film material, with the steady release of more effective control drug dose.For medicinal poly(lactic acid), what pay close attention to most is not molecular weight, but its toxicity.Given this, the present invention attempts carrying out without catalyzer the direct condensation of poly(lactic acid).
Summary of the invention
The purpose of this invention is to provide a kind of method of utilizing the synthetic nontoxic medicinal poly(lactic acid) of lactic acid direct condensation.
The present invention utilizes the method for the synthetic nontoxic medicinal poly(lactic acid) of lactic acid polycondensation, comprises following processing step:
1. lactic acid is carried out drying treatment: in lactic acid, add molecular sieve drying more than 24 hours.
2. dehydration: with the lactic acid of drying treatment at temperature 30-120 ℃, under the vacuum tightness 10-200mmHg decompression dehydration 2-8 hour.More excellent temperature for removing water is 70-90 ℃, and vacuum tightness is 50-100mmHg, dewaters with this understanding, and dewatering speed is fast, can make lactic acid do not taken away again, the productive rate height.
3. polycondensation: in temperature is 100-200 ℃, and vacuum tightness is under the condition of 0.1-100mmHg, and polycondensation 6-50 hour must polycondensate.More excellent condensation temperature is 120-180 ℃, and vacuum tightness is 10-80mmHg, and with this understanding, polyreaction can be carried out smoothly, can prevent the poly(lactic acid) depolymerization again.
Sectional heating method is adopted in polycondensation, promptly every 3-5 hour intensification 10-30 ℃, to improve the molecular weight and the productive rate of poly(lactic acid).
4. acetone solution is used in gained polycondensate cooling back, use ethanol sedimentation again, obtain the poly(lactic acid) that molecular weight is 2000-50000 20-70 ℃ of vacuum-drying then.
The gained polycondensate with acetone solution after, can use ethanol sedimentation earlier, use the distilled water reprecipitation again, carry out vacuum-drying at last.
Described lactic raw material is D, L-lactic acid.
The present invention compared with prior art has the following advantages:
1, the present invention utilizes the lactic acid direct condensation to be prepared into poly(lactic acid), need not any solvent and catalyzer, so catalyst-free is residual, no solvent residue, nontoxic, can be widely used in medical field.
2, the present invention with lactic acid is raw material, and is with low cost, the productive rate height, and the polylactic acid molecule amount of preparation is higher.
3, technology of the present invention is simple, easy to operate, helps suitability for industrialized production.
Embodiment
Every 3-5 hour intensification 10-30 ℃.
Embodiment 1: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 30 ℃, vacuum tightness is to stir dehydration 8 hours under the 200mmHg condition; Temperature-gradient method (per 3 hours heat up 10 ℃) is to 100 ℃, in vacuum tightness be under the condition of 0.1mmHg polymerization 6-8 hour polycondensate; Acetone solution is used earlier in gained polycondensate cooling back, use ethanol sedimentation again, use the distilled water reprecipitation then, to get the 38g viscosity-average molecular weight be 2000 poly(lactic acid) in vacuum-drying under last 20 ℃ of conditions.
Embodiment 2: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 40 ℃, vacuum tightness is to stir dehydration 6 hours under the 150mmHg condition; Temperature-gradient method (per 3 hours heat up 20 ℃) is to 120 ℃, in vacuum tightness be under the condition of 1.0mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 30 ℃ of conditions vacuum-drying to get the 40g viscosity-average molecular weight be 2500 poly(lactic acid).
Embodiment 3: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 50 ℃, vacuum tightness is to stir dehydration 5 hours under the 100mmHg condition; Temperature-gradient method (per 3 hours heat up 30 ℃) is to 130 ℃, in vacuum tightness be under the condition of 50mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 36 ℃ of conditions vacuum-drying to get the 39g viscosity-average molecular weight be 2800 poly(lactic acid).
Embodiment 4: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 60 ℃, vacuum tightness is to stir dehydration 4 hours under the 90mmHg condition; Temperature-gradient method (per 4 hours heat up 10 ℃) is to 140 ℃, in vacuum tightness be under the condition of 10mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 36 ℃ of conditions vacuum-drying to get the 41g viscosity-average molecular weight be 3200 poly(lactic acid).
Embodiment 5: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 70 ℃, vacuum tightness is to stir dehydration 3 hours under the 80mmHg condition; Temperature-gradient method (per 4 hours heat up 20 ℃) is to 150 ℃, in vacuum tightness be under the condition of 20mmHg polymerization 6-8 hour polycondensate; Acetone solution is used earlier in gained polycondensate cooling back, use ethanol sedimentation again, use the distilled water reprecipitation then, to get the 36g viscosity-average molecular weight be 4000 poly(lactic acid) in vacuum-drying under last 40 ℃ of conditions.
Embodiment 6: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 80 ℃, vacuum tightness is to stir dehydration 2 hours under the 70mmHg condition; Temperature-gradient method (per 4 hours heat up 30 ℃) is to 160 ℃, in vacuum tightness be under the condition of 30mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 36 ℃ of conditions vacuum-drying to get the 38g viscosity-average molecular weight be 7000 poly(lactic acid).
Embodiment 7: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 90 ℃, vacuum tightness is to stir dehydration 2 hours under the 60mmHg condition; Temperature-gradient method (per 5 hours heat up 10 ℃) is to 170 ℃, in vacuum tightness be under the condition of 40mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 36 ℃ of conditions vacuum-drying to get the 42g viscosity-average molecular weight be 10000 poly(lactic acid).
Embodiment 8: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 100 ℃, vacuum tightness is to stir dehydration 2 hours under the 50mmHg condition; Temperature-gradient method (per 5 hours heat up 20 ℃) is to 180 ℃, in vacuum tightness be under the condition of 50mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 50 ℃ of conditions vacuum-drying to get the 41g viscosity-average molecular weight be 50000 poly(lactic acid).
Embodiment 9: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 110 ℃, vacuum tightness is to stir dehydration 2 hours under the 30mmHg condition; Temperature-gradient method (per 5 hours heat up 30 ℃) is to 190 ℃, in vacuum tightness be under the condition of 60mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 60 ℃ of conditions vacuum-drying to get the 33g viscosity-average molecular weight be 8000 poly(lactic acid).
Embodiment 10: be furnished with to 250ml that to add 50ml purity in the three neck round-bottomed flasks of thermometer, water trap be 80% the D through molecular sieve drying, and L-lactic acid, at 120 ℃, vacuum tightness is to stir dehydration 2 hours under the 10mmHg condition; Temperature-gradient method (per 3 hours heat up 30 ℃) is to 200 ℃, in vacuum tightness be under the condition of 100mmHg polymerization 6-8 hour polycondensate; Acetone solution use earlier in gained polycondensate cooling back, uses ethanol sedimentation again, use the distilled water reprecipitation then, at last under 70 ℃ of conditions vacuum-drying to get the 31g viscosity-average molecular weight be 7000 poly(lactic acid).
Claims (5)
1, a kind of method of utilizing the lactic acid direct condensation to prepare nontoxic poly(lactic acid) may further comprise the steps:
1. lactic acid is carried out drying treatment:, add molecular sieve drying in the L-lactic acid more than 24 hours at D;
2. dehydration: with the lactic acid of drying treatment at temperature 30-120 ℃, under the vacuum tightness 10-200mmHg decompression dehydration 2-8 hour;
3. polycondensation: in temperature is 100-200 ℃, and vacuum tightness is under the condition of 0.1-100mmHg, polycondensation 6-50 hour polycondensate;
4. acetone solution is used in gained polycondensate cooling back, use ethanol sedimentation again, then 20-70 ℃ of vacuum-drying.
2, prepare the method for nontoxic poly(lactic acid) according to the described lactic acid direct condensation of claim 1, it is characterized in that: the 2. described dehydration temperaturre of step is 70-90 ℃, and vacuum tightness is 50-100mmHg.
3, prepare the method for nontoxic poly(lactic acid) according to the described lactic acid direct condensation of claim 1, it is characterized in that: the step 3. temperature of described polycondensation is 120-180 ℃, and vacuum tightness is 10-80mmHg.
4, prepare the method for nontoxic poly(lactic acid) according to the described lactic acid direct condensation of claim 1, it is characterized in that: sectional heating method is adopted in the 3. described polycondensation of step, every 3-5 hour intensification 10-30 ℃.
5, the method for preparing nontoxic poly(lactic acid) according to claim 1,2,3,4 described any lactic acid direct condensation, it is characterized in that: step 4. in the gained polycondensate with acetone solution after, use earlier ethanol sedimentation, use the distilled water reprecipitation again, carry out vacuum-drying at last and obtain the poly(lactic acid) that molecular weight is 2000-50000.
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| CNB200510042859XA CN100427524C (en) | 2005-06-22 | 2005-06-22 | Process for preparing nontoxic poly lactic acid by direct condensation polymerization of lactic acid |
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| CN100427524C true CN100427524C (en) | 2008-10-22 |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101240061B (en) * | 2008-02-22 | 2010-11-10 | 华南农业大学 | Method for synthesizing polyracemic lactic acid for carrying medicament |
| CN101831071B (en) * | 2010-05-15 | 2012-05-23 | 西北师范大学 | Degradable poly (lactic acid-glutamic acid) crosslinking microgel, preparation and application thereof |
| CN102838858B (en) * | 2012-09-21 | 2014-12-24 | 上海同杰良生物材料有限公司 | Polylactic acid nucleating agent, preparation method and application thereof |
| CN106867273B (en) * | 2017-02-20 | 2019-05-03 | 宣城亚邦化工有限公司 | Modification phthalocyanine blue pigment and preparation method thereof for the coloring of polylactic acid system |
| CN110972753A (en) * | 2020-01-10 | 2020-04-10 | 湖南文理学院 | Agricultural light conversion spray liquid and preparation method thereof |
| CN113501943B (en) * | 2021-08-03 | 2023-04-18 | 上海丽珠制药有限公司 | Method for preparing polylactic acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1298892A (en) * | 1999-12-09 | 2001-06-13 | 浙江大学 | Process for preparing biodegradable polylactate material by direct polycondensation of lactic acid |
| JP2003335850A (en) * | 2002-05-17 | 2003-11-28 | J Corporation:Kk | Method of manufacturing biodegradable plastic and apparatus for it |
| CN1616515A (en) * | 2004-10-18 | 2005-05-18 | 上海氯碱化工股份有限公司 | Process for preparing high molecular weight poly lactic acid by fusion polycondensation-solid phase polymerization |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1298892A (en) * | 1999-12-09 | 2001-06-13 | 浙江大学 | Process for preparing biodegradable polylactate material by direct polycondensation of lactic acid |
| JP2003335850A (en) * | 2002-05-17 | 2003-11-28 | J Corporation:Kk | Method of manufacturing biodegradable plastic and apparatus for it |
| CN1616515A (en) * | 2004-10-18 | 2005-05-18 | 上海氯碱化工股份有限公司 | Process for preparing high molecular weight poly lactic acid by fusion polycondensation-solid phase polymerization |
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