CN1418901A - Carboxy polylactic acid contained composition and preparation process thereof - Google Patents
Carboxy polylactic acid contained composition and preparation process thereof Download PDFInfo
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- CN1418901A CN1418901A CN 02155474 CN02155474A CN1418901A CN 1418901 A CN1418901 A CN 1418901A CN 02155474 CN02155474 CN 02155474 CN 02155474 A CN02155474 A CN 02155474A CN 1418901 A CN1418901 A CN 1418901A
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- lactic acid
- alcohol
- acid
- carboxyl
- copolymer
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Abstract
The carboxyl-contained lactic acid copolymer is one or lactic acid and natural polycarboxylic hydroxy acid. It is made up by means of direct condensation of the lactic acid and natural polycarboxyl hdyroxy acid under the action of self-catalysis of lactic acid. In the presence of DCC and DMAP the obtained copolymer can be reacted with hydrophilic macromolecular monobasis alcohol or dibasic alcohol to obtain correspondent segmented copolymer; and the composite is a polymer blend of carboxyl-contained lactic acid copolymer and one or 2-3 kinds of polylactic acid, polyethylene glycol, polyvinyl alcohol, polyhydrox butyric acid, polyhydroxy butyric acid-hydroxypentoic acid, poly epsilon-caprolactam, starch and cellulose. Said invention product possesses good biological compatibility, and has wide regulation range of hydrophilic property.
Description
Technical field
The present invention relates to biological degradation class medical material, relate to contain carboxyl poly(lactic acid) constituent and preparation method thereof in more detail.
Background technology
Poly(lactic acid) is a kind of have good biocompatibility and biodegradable polymkeric substance, can be used as the material of medical operation suture thread and preparations such as injection microcapsule, microballoon and implants through the FDA approval.In recent years, the relevant research that poly(lactic acid) is applied to aspects such as bone internal fixation material, medicament slow release preparation and tissue engineering bracket material has all obtained certain achievement.
The final product that poly(lactic acid) is degraded in human body as bio-medical material is carbonic acid gas and water, and intermediate product is a lactic acid.Lactic acid is to cause body fluid acidifying essential substance.Because the body fluid acidifying, immunizing power is suppressed and infringement and health risk.In addition, as medical material, poly(lactic acid) is a hydrophobic polymer, and its degradation rate is difficult to regulation and control, studies focus greatly so relevant study on the modification to poly(lactic acid) becomes one of this field.Studying more method of modifying is activation and the modification that copolymerization, blend reach the surface of being undertaken by physical adsorption.And this wherein to study relatively what concentrate mainly be copolymerization, by reactive mode and introduce the second monomeric position and can be divided into random, grafting and block copolymerization.Graft copolymerization polymkeric substance commonly used mostly is some natural polymers greatly, as starch, Mierocrystalline cellulose etc. [1. by an outstanding person, Zhu Changying, Jiao Jingliang, Shen Xin, the synthetic and biodegradability research of starch/DL-rac-Lactide graft copolymer, the polymer journal, 2000,6:746-750.2.Ohya?Y，Maruhashi?S，Ouchi?T.Graft?Polymerization?of?L-Lactide?on?pullulan?through?the?TrimethylsiylProtection?method?and?Degradation?of?the?Graft?Copolymers，Macromolecules?1998，31(14)：4662-4665。3.Ohya?Y，Mamhashi?S，Ouchi?T.Preparation?of?Poly(lacticacid)-grafted?Amylose?through?the?Trimethylsilyl?Protection?Method?and?itsBiodegradation，Macromol.Chem.Phys.，1998，199(9)：2017-2022]。And the commonplace monomer that block copolymerization is used comprises oxyacetic acid, the alcohol acid of amino acid and other type [1.Jorres V, Keul H, Hocker H.Aminolysis of α-Amino Acid Salts:First Step in the Synthesis ofOptically Active 2,5-Morpholinediones, Macromol.Chem.Phys., 1998,199:825-8332.Schmidt P, Keul H, Hocker H.Copolymerization of 2,2-DimethyltrimethyleneCarbonate and L-lactide, Macromolecules, 1996,29:3674-3680.3.Vert?M，lenz?R?W.Preparation?and?Properties?of?Poly-β-malic?Acid：A?Functional?Polyester?of?PotentialBiomedical?Importance，Polymer?Preprints，1979，20：608-611]。And copolymerization process commonly used mainly concentrates on the method for ring-opening polymerization.This method is long because of synthetic route, synthesis yield is low, molecular weight of product is low and chain structure is wayward etc., and shortcoming causes its modification narrow range.
Summary of the invention
The object of the present invention is to provide a series of carboxyl lactide acid polymer and constituents thereof of containing.
The present invention also aims to provide a kind of preparation method who contains the polylactic acid-based constituent of carboxyl.Poly(lactic acid) is carried out modification, and the preparation hydrophilic/hydrophobic is adjustable, does not cause inflammatory reaction, and the degradation rate of material can be regulated and with the biological degradation medical material that is complementary of growth velocity of tissue.
Contain following listed two or more following structural unit on the molecular chain that contains the carboxyl lactic acid copolymer among the present invention:
Wherein Z is-OH ,-COOH ,-NH
2, m, n=0～8,
Its composition is the blend that contains a kind of in carboxyl lactic acid copolymer and poly(lactic acid), polyoxyethylene glycol, polyvinyl alcohol, polyhydroxybutyrate, polyhydroxybutyrate-hydroxypentanoic acid, poly-epsilon-caprolactone, starch and the Mierocrystalline cellulose or 2～3 kinds.The mass ratio that wherein contains the carboxyl lactic acid copolymer is 0.5～99.9%, is preferably 10～50%.
The preparation that contains the carboxyl lactic acid copolymer among the present invention is with lactic acid and natural many carboxyls alcohol acid, under the self-catalysis of lactic acid, in 120～180 ℃ of temperature, under pressure 20～760mmHg condition, and carry out polyreaction preparation with feeding intake of lactic acid and many carboxyls alcohol acid mol ratio 800～5: 1, the multipolymer that gained contains carboxyl lactic acid copolymer and wetting ability macromolecule dihydric alcohol then is in the presence of DCC and DMAP, and with mol ratio 10～0.1: 1 feeds intake carries out condensation reaction and prepare.
Used natural many carboxyls alcohol acid is selected from citric acid, oxysuccinic acid, tartrate among the present invention; Wetting ability macromolecule dihydric alcohol or monohydroxy-alcohol are selected from polyoxyethylene glycol, PEP-101, four Hydrogen furans polyether Glycols.
The mol ratio of lactic acid and natural many carboxyls alcohol acid is 100～10: 1 among the present invention; The mol ratio of lactic acid and wetting ability macromolecular alcohol is 2～0.5: 1.
Among the present invention, the preparation method who contains carboxyl lactic acid analog copolymer is:
Lactic acid, many carboxyls alcohol acid are added in the reactor, under the nitrogen protection, be heated to 120 ℃; normal pressure reacted 1～4 hour down, slowly was decompressed to 20mmHg, continued reaction 3～5 hours; system is continued to be decompressed to 1～2mmHg, and temperature rises to 150～180 ℃, continues reaction 3～5 hours.Polymkeric substance is dissolved with chloroform, ether sedimentation, vacuum-drying, product is a white fiber shape solid.
The present invention compared with prior art has following advantage:
1, by melt-polycondensation, make and contain carboxyl lactic acid analog copolymer, preparation section is simple, and condition is easy to control, by the adjusting of several comonomer consumptions, the degradation rate of gained multipolymer, hydrophilic/hydrophobic is regulated in a big way.
2, have better biocompatibility, wetting ability is strong, helps adhesion, growth and the breeding of cell.
3, by containing blend such as carboxyl lactic acid analog copolymer and other polymkeric substance such as poly(lactic acid), polyoxyethylene glycol, starch, can make the degradable biological medical material of high comprehensive performance.
4, eliminated the bacillary and sterility reaction that traditional material exists.
Below by embodiment the present invention is further described below.
Embodiment one
PLCA's is synthetic: a certain amount of 88%L-lactic acid (LA) was mixed with citric acid (CA) in 24: 1 in molar ratio, in 150 ℃ of following synthesis under normal pressure 2h, 1.3 * 10
4Pa is reaction 2h down, and 4.0 * 10
3Pa is reaction 4h down, obtains yellow thick L-lactic acid and citric acid oligopolymer.Then add the SnCl of quality for this oligopolymer 0.4%
22H
2O is heated to 150 ℃, progressively is decompressed to 1.06 * 10
3Pa, reaction 8h.After above-mentioned product is cooled to room temperature, with acetone solution, water precipitation, and with behind a large amount of deionized water repetitive scrubbings, filtration under diminished pressure, under 40 ℃ in vacuum drying oven dry 48h, obtain yellow powder shape product P LCA at last.Its
[COOH]=1.52 * 10
-3Mol/g, Tg=47.4 ℃, Tm=130.16 ℃, its degradation rate is obviously faster than PLLA.
Embodiment two
The preparation of hydroxyl-terminated polylactic acid: with 100g L-lactic acid (88% aqueous solution) and a certain amount of 1, the 6-hexylene glycol mixes, 150 ℃ of following synthesis under normal pressure 2h, 1.3 * 10
4Pa is reaction 2h down, and 4.0 * 10
3Pa is reaction 4h down, gets light yellow thick oligopolymer.Adding quality is the SnCl of this oligopolymer 0.4%
22H
2O is at 160 ℃, 1.06 * 10
3React 8h under the condition of Pa.
In acetone, with a large amount of distilled water product that settles out, behind the filtration under diminished pressure, dry 48h gets the white powder solid in 40 ℃ of following vacuum drying ovens then with cooled above-mentioned reactants dissolved.
Embodiment three
The preparation of PLCA-PEG segmented copolymer: PLCA and the equimolar PEG of 1mmol are dissolved in the 70ml methylene dichloride, add the catalyzer DMAP of 0.25mmol and the coupling agent DCC of 5mmol, induction stirring 24h under the normal temperature.Elimination byproduct of reaction DCU, filtrate is poured in the excessive ether after concentrating.Behind the filtration under diminished pressure, products therefrom is placed vacuum drying oven, Air drying 48h gets light brown pulverulent solids.Mw=7600, Tg=20.6 ℃, with the contact angle of water be 45 °, water-intake rate is 151%, tensile strength is 8.33MPa, elongation at break is 7.6%.
Embodiment four
The preparation of PLLA/PLCA co-mixing system:
PLLA and PLCA are dissolved in the chloroform in 1: 1 ratio and make film forming liquid, its concentration is controlled at 10g polymkeric substance/100 solvents.Film forming liquid is cast in the tetrafluoroethylene mould of 12cm * 12cm, behind the dry 24h of normal temperature and pressure, 5 * 10
4Dry 12h under the Pa, 1 * 10
4Pa continues down to take out after the dry 12h constant weight, and the mean thickness of measuring film is about 0.14mm, is cut into to put into moisture eliminator behind the small pieces of 10mm * 20mm and preserve.Tg=52.7 ℃, Tm=145.2 ℃, with the contact angle of water be 52 °, water-intake rate is 130%, the purer poly(lactic acid) of degradation rate is fast, and is slow than lactic acid-citric acid multipolymer.
Embodiment five
PLLA, PEG and different PLCA are dissolved in the chloroform in 59.5: 25.5: 15 ratio and make film forming liquid, its concentration is controlled at 10g polymkeric substance/100ml solvent.Film forming liquid is cast in the tetrafluoroethylene mould of 12cm * 12cm, behind the dry 24h of normal temperature and pressure, 5 * 10
4Dry 12h under the Pa, 27Pa continue down to take out after the dry 12h constant weight, and the mean thickness of measuring film is about 0.14mm, are cut into to put into moisture eliminator behind the small pieces of 10mm * 20mm and preserve.Tg=15.8 ℃, Tm
1=61.54 ℃, Tm
2=149.47 ℃, with the contact angle of water be 63 °, tensile strength is 11.6MPa.
Embodiment six
Adding PVA and solvent in the there-necked flask of 250ml are heated with stirring to 100 ~ 140 ℃ and make the PVA dissolving, are cooled to then about 120 ℃ to add PLLA, controlled temperature is no more than 120 ℃ and makes the PLLA dissolving, be cooled to 40 ℃, add PLCA, treat that it all dissolves the back filtration under diminished pressure and promptly makes film forming liquid.Film forming liquid is poured in the tetrafluoroethylene mould, under 45 ℃, allowed its solvent evaporates 7 days, 45 ℃ of following 2 weeks of vacuum-drying.The thickness of film is about 0.07mm.PLLA/PVA/PLCA=18/72/10, tensile strength is 25MPa (doing), 18.5MPa (wetting), elongation at break are 150%, water-intake rate is 520%, with the contact angle of water be 85 °, degradation rate is formed different because of system.
Claims (5)
1. one kind contains carboxyl lactic acid copolymer and composition thereof, it is characterized in that: contain the A and the B that contain on the molecular chain of carboxyl lactic acid copolymer in the following structural unit, or A and B and C,
Wherein Z is-OH ,-COOH ,-NH
2, m, n=0～8,
Its composition is the blend that contains a kind of in carboxyl lactic acid copolymer and poly(lactic acid), polyoxyethylene glycol, polyvinyl alcohol, polyhydroxybutyrate, poly-(hydroxybutyric acid-hydroxypentanoic acid), poly-epsilon-caprolactone, starch and the Mierocrystalline cellulose or 2～3 kinds, and the mass ratio that wherein contains the carboxyl lactic acid copolymer is 0.5～99.9%.
2. by the described composition that contains the carboxyl lactic acid copolymer of claim 1, it is characterized in that: the mass ratio that contains the carboxyl lactic acid copolymer in the blend is 10～50%.
3. one kind prepares the described method that contains the carboxyl lactic acid copolymer of claim 1, it is characterized in that: with lactic acid and natural many carboxyls alcohol acid, under the self-catalysis of lactic acid, in 120～180 ℃ of temperature, under pressure 20～760mmHg condition, and carry out polyreaction preparation with feeding intake of lactic acid and many carboxyls alcohol acid mol ratio 800～5: 1, the multipolymer that gained contains carboxyl lactic acid copolymer and wetting ability macromolecule dihydric alcohol or monohydroxy-alcohol then is in the presence of dicyclohexyl carbodiimide (DCC) and Dimethylamino pyridine (DMAP), and with mol ratio 10～0.1: 1 feeds intake carries out condensation reaction and prepare.
4. contain the method for carboxyl lactic acid copolymer by the described preparation of claim 3, it is characterized in that: natural many carboxyls alcohol acid is selected from citric acid, oxysuccinic acid, tartrate; Wetting ability macromolecule dihydric alcohol or monohydroxy-alcohol are selected from polyoxyethylene glycol, PEP-101, four Hydrogen furans polyether Glycols.
5. contain the method for carboxyl lactic acid copolymer by the described preparation of claim 3, it is characterized in that: the mol ratio of lactic acid and natural many carboxyls alcohol acid is 100～10: 1; The mol ratio of lactic acid and wetting ability macromolecular alcohol is 2～0.5: 1.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100372881C (en) * | 2006-08-10 | 2008-03-05 | 同济大学 | Preparation method of full biodegradation polyester copolymer |
| CN100384936C (en) * | 2005-12-08 | 2008-04-30 | 上海林达塑胶化工有限公司 | Method for preparing composite biodegradable master batch |
| CN100406498C (en) * | 2006-03-09 | 2008-07-30 | 四川大学 | Blend material of vinol/polylactic acid graft copolymer and starch, their prepn. and application |
| CN100558795C (en) * | 2006-09-07 | 2009-11-11 | 同济大学 | The preparation method of biodegradation polylactic acid based multicomponent block polymer |
| CN104098774A (en) * | 2013-04-15 | 2014-10-15 | 江南大学 | Preparation method of magnetic-response star-type segmented copolymer nano-micelle as drug carrier |
| CN111905147A (en) * | 2020-08-17 | 2020-11-10 | 刘小雄 | Injection material for beauty and plastic and injection method thereof |
| CN115926122A (en) * | 2022-12-23 | 2023-04-07 | 浙江海正生物材料股份有限公司 | Method for preparing polylactic acid-polyvinyl alcohol graft copolymer |
-
2002
- 2002-12-16 CN CN 02155474 patent/CN1418901A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100384936C (en) * | 2005-12-08 | 2008-04-30 | 上海林达塑胶化工有限公司 | Method for preparing composite biodegradable master batch |
| CN100406498C (en) * | 2006-03-09 | 2008-07-30 | 四川大学 | Blend material of vinol/polylactic acid graft copolymer and starch, their prepn. and application |
| CN100372881C (en) * | 2006-08-10 | 2008-03-05 | 同济大学 | Preparation method of full biodegradation polyester copolymer |
| CN100558795C (en) * | 2006-09-07 | 2009-11-11 | 同济大学 | The preparation method of biodegradation polylactic acid based multicomponent block polymer |
| CN104098774A (en) * | 2013-04-15 | 2014-10-15 | 江南大学 | Preparation method of magnetic-response star-type segmented copolymer nano-micelle as drug carrier |
| CN111905147A (en) * | 2020-08-17 | 2020-11-10 | 刘小雄 | Injection material for beauty and plastic and injection method thereof |
| CN115926122A (en) * | 2022-12-23 | 2023-04-07 | 浙江海正生物材料股份有限公司 | Method for preparing polylactic acid-polyvinyl alcohol graft copolymer |
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