CN1231516C - Process for preparing poly-(L-lactic acid) - Google Patents
Process for preparing poly-(L-lactic acid) Download PDFInfo
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- CN1231516C CN1231516C CN 03113231 CN03113231A CN1231516C CN 1231516 C CN1231516 C CN 1231516C CN 03113231 CN03113231 CN 03113231 CN 03113231 A CN03113231 A CN 03113231A CN 1231516 C CN1231516 C CN 1231516C
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- lactic acid
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Abstract
The present invention relates to a method for preparing poly-(L-lactic acid). The method comprises: adding a zinc lactate-p-toluenesulfonic acid composite catalyst into the L-lactic acid; carrying out polycondensation reaction for 6 to 36 hours under the condition of 150 to 200 DEG C and 0.06 to 1.96 Kpa; discharging materials and cooling after ending the reaction to obtain a crude product with the appearance in a colorless transparent resin state. After the crude product is refined and dried, a finished product with 10000 to 80000 of weight average molecular weight is obtained to completely satisfy the requirements of medical auxiliary materials, particularly auxiliary materials for slowing, controlling and releasing a pharmaceutical preparation. The present invention has at least 90% of yield and simple process.
Description
One, technical field
The present invention relates to a kind of preparation method of medical macromolecular materials, the preparation method of specifically a kind of poly-(L-lactic acid).
Two, background technology
Early stage synthesizing polylactic acid, how to make catalyzer with zinc oxide, zinc chloride, tin, stannic oxide, white arsenic etc., adopt DL, L, D-lactic acid direct condensation, the resulting polymers molecular weight is lower, be generally less than 10000, bad mechanical strength (Kulkorni, R.K., et al, Arch.Surg., 1966,93,839).In order to improve the molecular weight of poly(lactic acid), the main at present two-step approach that adopts prepares rac-Lactide with lactic acid earlier, is raw material again with the rac-Lactide, adopts ring-opening polymerization method to prepare poly(lactic acid).Catalyzer is used stannous octoate (D.K.Gilding and A.M.Reed.Polymer, 1979,20:1459 more; Spinu M, Jackson C.J., macromol Sci Pure Appl Chem, 1996, A33 (10): 1497; Kricheldorf H.R., Kreiser S.I., Polymer, 1993,36 (6): 1253; D.W.Grijpma, A.J.Nijenhuis., Polymer, 1990,31:2201), tindichloride, tin tetrachloride, tin tetrabromide (Kricheldrof H.R., et al, Eur.Polymer, J., 1989,25 (6), 585), aluminum isopropylate (KricheldrofH.R., Beerl M., Macromolecules, 1988,21:286; Dubois P., Jacobs C., Macromolecules, 1991,24:2266), bimetal oxo bridge alkyl oxide [(n-C
4H
9O)
2AlO]
2Zn (Feng X.D., Polymer, 1985,189), the initiator system (FP, 7829978,1978) of containing metal zinc, rare earth class initiator system (HajimeYasuda 17 (1):, Eiji Ihara, Macromol.Chem.Phys.1995,196 (8): 2417) etc.This preparation method's operational path is long, equipment requirements is high, be that the transformation efficiency of benchmark is low, solvent-oil ratio is big, energy consumption is high, cost is high with monomer lactic acid.
In recent years along with the exploitation and the use of effective catalyst, adopt direct condensation to prepare at present existing many patents of poly(lactic acid) and bibliographical information, Moon S I, Lee C W, Miyamoto M, et al.[J] .Polymer Science, Part A:Polymer Chemical, reported used SnCl at 2000,38 (9): 1673
22H
2After O and tosic acid were compound, catalytic efficiency was apparently higher than using single catalysts such as zinc oxide, white arsenic, ferric oxide, aluminium sesquioxide, titanium dioxide, stannic oxide, tindichloride, tosic acid.Wang Chaoyang, Zhao Yaoming .[J such as Wang Jun] the functional polymer journal, it is 4100 low-molecular-weight PDLLA that 2002,15 (4), 377 reports use the racemic lactic acid zinc catalysts to prepare viscosity-average molecular weight.Wang Chaoyang, Zhao Yaoming .[J such as Mai Hangzhen] synthon, 2002,31 (2): 11 report use racemic lactic acid zinc and taurine composite catalyst prepare PDLLA and have certain effect.This preparation method's operational path is short, equipment requirements is not high, but synthetic polylactic acid molecule amount is not high.
As medical macromolecular materials, the auxiliary material of particularly slow, controlled-release pharmaceutical formulation needs the poly(lactic acid) of weight-average molecular weight 〉=10000.The present invention improves existing processes, carries out polycondensation with L-lactic acid, and selects new composite catalyst and corresponding technological conditions, makes the medical macromolecular materials poly-(L-lactic acid) of weight-average molecular weight 10000～80000.
Three, summary of the invention
The present invention is that the L-lactic acid monomer is when catalyzer exists, under 150～200 ℃, 0.06～1.96Kpa condition, reacted 6～36 hours, the cooling back is refining, removes the catalyzer in the crude product, unreacted monomer and oligopolymer, and drying obtains poly-(the L-lactic acid) of weight-average molecular weight 10000～80000.
Described catalyzer is the composite catalyst that D-lactic acid zinc (I) and tosic acid (II) constitute, and zinc lactate is nontoxic, harmless to human body, is the human body zinc enhancer of routine use.After refining, remove D-lactic acid zinc and tosic acid in the crude product.The mol ratio of catalyst I and II is 1: 0.1～4; The consumption of composite catalyst and monomeric mol ratio are 1: 100～4000.
This technology is reduced to single step reaction with existing two-step reaction, can obtain weight-average molecular weight and be 10000～80000 poly-(L-lactic acid), yield 〉=90%.Reaction finishes promptly to get crude product after the blowing cooling, and outward appearance is the colourless transparent resin shape.Crude product gathers (L-lactic acid) and is white in color Powderedly through refining, dry back, can be used as medical accessory.
Four, embodiment
By the following examples, the present invention is done to describe further.
Embodiment 1:
In being equipped with the 500ml there-necked flask of agitator, distillation column, condenser, thermometer and vacuum distillation apparatus, drop into 424g L-lactic acid (concentration 85.0%), 10.8207g D-lactic acid zinc, 0.6917g tosic acid, under evenly stirring, slowly heat up decompression dehydration.When temperature was raised to 180 ℃, 0.12KPa reduced pressure.Kept this state 6 hours, after material poured out cooling, can obtain being close to poly-(L-lactic acid) crude product of colourless transparent resin shape, after the pulverizing, water, dehydrated alcohol stepwise solvent extraction are removed catalyzer, monomer and the oligopolymer in the crude product, drying gets poly-(L-lactic acid) 264.2g of finished product, is 91.6% of theoretical yield, and recording weight-average molecular weight by GPC is 13860.
Embodiment 2:
Experimental installation is identical with embodiment 1 with experiment condition, only uses 1.5871g D-lactic acid zinc, 0.5073g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 15 hours, must gather (L-lactic acid) 267.6g, is 92.8% of theoretical yield, and recording weight-average molecular weight through GPC is 57680.
Embodiment 3:
Experimental installation is identical with embodiment 1 with experiment condition, with 0.5952g D-lactic acid zinc, 0.3804g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 24 hours, must gather (L-lactic acid) 268.2g, is 93.0% of theoretical yield, and recording weight-average molecular weight through GPC is 79820.
Embodiment 4:
Experimental installation is identical with embodiment 1 with reaction conditions, with 0.3174g D-lactic acid zinc, 0.3044g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 30 hours, must gather (L-lactic acid) 265.7g, is 92.1% of theoretical yield, and recording weight-average molecular weight through GPC is 68940.
Embodiment 5:
Experimental installation is identical with embodiment 1 with reaction conditions, with 0.1988g D-lactic acid zinc, 0.2537g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 30 hours, must gather (L-lactic acid) 264.8g, is 91.8% of theoretical yield, and recording weight-average molecular weight through GPC is 52410.
Embodiment 6:
Experimental installation is identical with embodiment 1 with reaction conditions, with 0.0992g D-lactic acid zinc, 0.1902g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 36 hours, must gather (L-lactic acid) 261.3g, is 90.6% of theoretical yield, and recording weight-average molecular weight through GPC is 43250.
Embodiment 7:
Experimental installation is identical with embodiment 1 with reaction conditions, with 0.0595g D-lactic acid zinc, 0.1427g tosic acid.When temperature is raised to 180 ℃ of post polymerization times is 36 hours, must gather (L-lactic acid) 259.8g, is 90.1% of theoretical yield, and recording weight-average molecular weight through GPC is 37940.
Claims (2)
1. the preparation method of a kind poly-(L-lactic acid), it is characterized in that: the composite catalyst that uses during the polycondensation of monomer L-lactic acid is D-lactic acid zinc-tosic acid, and the mol ratio of D-lactic acid zinc and tosic acid is 1: 0.1～4.
2. preparation method according to claim 1 is characterized in that: the consumption of composite catalyst and monomeric mol ratio are 1: 100～4000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03113231 CN1231516C (en) | 2003-04-18 | 2003-04-18 | Process for preparing poly-(L-lactic acid) |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 03113231 CN1231516C (en) | 2003-04-18 | 2003-04-18 | Process for preparing poly-(L-lactic acid) |
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| CN1450097A CN1450097A (en) | 2003-10-22 |
| CN1231516C true CN1231516C (en) | 2005-12-14 |
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| CN 03113231 Expired - Lifetime CN1231516C (en) | 2003-04-18 | 2003-04-18 | Process for preparing poly-(L-lactic acid) |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102241816B (en) * | 2010-05-14 | 2014-03-05 | 东丽纤维研究所（中国）有限公司 | Polylactic acid composition containing monosulfonic acid compound and preparation method thereof |
| CN102532501B (en) * | 2010-12-29 | 2014-07-09 | 安徽生建可降解聚乳酸新材料有限公司 | Refining method for poly(L-lactic acid) and poly(L-lactic acid-glycolic acid) |
| CN102786670A (en) * | 2012-08-10 | 2012-11-21 | 九江学院 | Polylactic acid as well as synthesis and preparation method thereof |
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Assignee: Wuhu Zhong Ren Pharmaceutical Co.,Ltd. Assignor: ANHUI ZHONGREN TECHNOLOGY CO.,LTD. Contract fulfillment period: 2008.8.8 to 2023.4.17 Contract record no.: 2008320000120 Denomination of invention: Poly (lactic acid) preparation method Granted publication date: 20051214 License type: exclusive license Record date: 20080908 |
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Free format text: EXCLUSIVE LICENCE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.8.8 TO 2023.4.17 Name of requester: WU HU ZHONGREN PHARMACEUTICAL CO., LTD. Effective date: 20080908 |
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Assignee: WUHU SIMCERE ZHONGREN PHARMACEUTICAL Co.,Ltd. Assignor: ANHUI ZHONGREN TECHNOLOGY CO.,LTD. Contract fulfillment period: 2008.11.20 to 2023.4.17 Contract record no.: 2008320001128 Denomination of invention: Poly (lactic acid) preparation method Granted publication date: 20051214 License type: exclusive license Record date: 20081211 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.11.20 TO 2023.4.17; CHANGE OF CONTRACT Name of requester: WUHU XIANSHENGZHONGREN PHARMACEUTICAL CO., LTD. Effective date: 20081211 |
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Effective date of registration: 20101108 Address after: Dalian Lu, Baohe Industrial District of Hefei City, Anhui Province, No. 16 230051 Patentee after: Anhui Fengyuan people Pharmaceutical Co.,Ltd. Address before: 230009 Tunxi Road, Anhui, China, No. 193, No. Patentee before: ANHUI ZHONGREN TECHNOLOGY CO.,LTD. |
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Effective date of registration: 20170103 Address after: 230088 Anhui Hefei Lake Road No. 1429 Patentee after: HEFEI ZHONGREN TECHNOLOGY CO.,LTD. Address before: Dalian Lu, Baohe Industrial District of Hefei City, Anhui Province, No. 16 230051 Patentee before: Anhui Fengyuan people Pharmaceutical Co.,Ltd. |
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